Seizure onset zone localization using postictal hypoperfusion detected by arterial spin labelling MRI

Abstract

Neurological dysfunction following epileptic seizures is a well-recognized phenomenon. Several potential mechanisms have been suggested to explain postictal dysfunction, with alteration in cerebral blood flow being one possibility. These vascular disturbances may be long lasting and localized to brain areas involved in seizure generation and propagation, as supported by both animal and human studies. Therefore, measuring perfusion changes in the postictal period may help localize the seizure onset zone. Arterial spin labelling is a non-invasive, rapid and reproducible magnetic resonance imaging technique that measures cerebral perfusion. To this end, we measured postictal perfusion in patients with drug resistant focal epilepsy who were admitted to our seizure-monitoring unit for presurgical evaluation. Twenty-one patients were prospectively recruited and underwent arterial spin labelling scanning within 90 min of a habitual seizure. Patients also underwent a similar scan in the interictal period, after they were seizure-free for at least 24 h. The acquired scans were subtracted to identify the areas of significant postictal hypoperfusion. The location of the maximal hypoperfusion was compared to the presumed seizure onset zone to assess for concordance. Also, the localizing value of this technique was compared to other structural and functional imaging modalities. Postictal perfusion reductions of >15 units (ml/100 g/l) were seen in 15/21 patients (71.4%). In 12/15 (80%) of these patients, the location of the hypoperfusion was partially or fully concordant with the location of the presumed seizure onset zone. This technique compared favourably to other neuroimaging modalities, being similar or superior to structural magnetic resonance imaging in 52% of cases, ictal single-photon emission computed tomography in 60% of cases and interictal positron emission tomography in 71% of cases. Better arterial spin labelling results were obtained in patients in whom the seizure onset zone was discernible based on non-invasive data. Thus, this technique is a safe, non-invasive and relatively inexpensive tool to detect postictal hypoperfusion that may provide useful data to localize the seizure onset zone. This technique may be incorporated into the battery of conventional investigations for presurgical evaluation of patients with drug resistant focal epilepsy.

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False acute kidney injury alert due to model car fuel ingestion

We report a case of accidental ingestion of model car fuel (Optifuel) resulting in an apparent elevation of serum creatinine of 274 µmol/L (3.1 mg/dL) as measured by the Jaffe (alkaline picrate) reaction, which resulted in an acute kidney injury (AKI) stage 3 alert being reported. Optifuel contains nitromethane, which has been reported to interfere in the Jaffe reaction causing falsely high creatinine measurements. The laboratory staff were vigilant about this potential interfering substance so repeated the analysis of the creatinine using an enzymatic method that showed a markedly lower result of 47 µmol/L (0.5 mg/dL). This report highlights the ability of nitromethane to potentially mimic AKI and the importance of being aware of the limitations of biochemical tests to avoid misinterpretation of results and instigating inappropriate treatment.

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Typical carcinoid involving the main carina managed with arterial embolisation, endobronchial resection and ablation, ultimately followed by carinal resection

Bronchial carcinoids are uncommon pulmonary tumours, and the gold standard management is surgical resection. Their management is often complicated by their proximal location and propensity to bleed when manipulated. A 22-year-old man was found to have typical carcinoid tumour involving the carina and surgical resection was considered not feasible. We report our experience with a multimodality approach involving arterial embolisation, with subsequent endobronchial resection and ablation. Residual disease was found and managed with definitive carinal resection.

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Possible congenital dilatation of the pancreatic duct

The main pancreatic duct can become dilated in a number of conditions. We describe a patient with gross dilatation of the main pancreatic duct without evidence of causative underlying pathology suggesting congenital dilatation of the pancreatic duct. A 36-year-old man presented with signs of intestinal obstruction and a history of surgery for congenital pyloric stenosis. Incidental findings on CT showed a massively dilated main pancreatic duct. On MRI there was no duct irregularity or solid mural nodule, making a main duct intraductal papillary mucinous neoplasm unlikely. Endoscopic ultrasound findings were in keeping with those on MRI. Fine needle aspiration revealed a non-viscous fluid with a low carcinoembryonic antigen and high amylase concentration, consistent with normal pancreatic fluid levels rather than a mucinous collection. After 1 year, the cyst remains unchanged. This patient will be kept under surveillance with yearly MRI.

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Retroperitoneal teratoma simulating giant adrenal myelolipoma: a diagnostic puzzle

Teratoma is a germ-cell tumour that is common in para-axial regions. Retroperitoneal teratoma is rare and comprise only about 1% of all teratomas. We present a 21-year-old female who presented with a lump in the abdomen. After radiological investigations, she was diagnosed as case of adrenal myelolipoma which on excision turned out histologically to be retroperitoneal teratoma. Our case highlights the limitation of radiological investigations in preoperative diagnosis of teratoma.

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Acromegaly with hypophosphataemia: McCune-Albright syndrome

A 38-year-old man presented with excessive height gain and progressive enlargement of the extremities since childhood. This was compounded by lower limb deformities over the past 5 years. On examination, his height was 196 cm, he had macroglossia, acral enlargement, seborrhoea, hyperhidrosis—suggesting acrogigantism. He had facial asymmetry, wind-swept deformity of lower limbs and a café-au-lait macule over his trunk. Investigations revealed normal-sized pituitary gland with dysplastic cranial bones. Isotope bone scintigraphy was suggestive of polyostotic fibrous dysplasia. A diagnosis of McCune-Albright syndrome was made and trans-sphenoidal hypophysectomy was undertaken. He had persistent hypophosphataemia. Tubular reabsorption of phosphate adjusted for glomerular filtration rate was low and serum FGF-23 level was high. Ga-DOTATATE scintigraphy showed somatostatin-receptor expression in all the dysplastic lesions. FGF-23 produced by the bony lesions could counteract the phosphate-retaining effect of GH excess resulting in hypophosphataemia, which further worsened following hypophysectomy.

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Simultaneous combined complete tear of radial and ulnar collateral ligaments of thumb in an adolescent

Isolated tear of collateral ligaments of thumb are common but combined injuries of both radial and ulnar collateral ligaments are rare. These cases are reported in athletes involved in high-impact sports. Here, we report a case of a 15-year-old boy with pain at base of the thumb and instability following low-impact sporting activity. On subsequent clinicoradiological assessment, simultaneous combined complete tear of both radial and ulnar collateral ligaments of the thumb was noted. Delayed primary repair of both collateral ligaments was done. This case highlights the rarity of this type of injury in an adolescent and also the use of appropriate clinical tests and imaging modalities for early diagnosis of such injuries. Restoration of joint stability as early as possible either by repair or reconstruction of ligaments needs to be considered to prevent secondary osteoarthritis of metacarpophalangeal joint.

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Auditory Evoked Potential Mismatch Negativity in Normal-Hearing Adults

Abstract Introduction Mismatch Negativity (MMN) corresponds to a response of the central auditory nervous system. Objective The objective of this study is to analyze MMN latencies and amplitudes in normal-hearing adults and compare the results between ears, gender and hand dominance. Methods This is a cross-sectional study. Forty subjects participated, 20 women and 20 men, aged 18 to 29 years and having normal auditory thresholds. A frequency of 1000Hz (standard stimuli) and 2000Hz (deviant stimuli) was used to evoked the MMN. Results Mean latencies in the right ear were 169.4ms and 175.3ms in the left ear, with mean amplitudes of 4.6μV in the right ear and 4.2μV in the left ear. There was no statistically significant difference between ears. The comparison of latencies between genders showed a statistically significant difference for the right ear, being higher in the men than in women. There was no significant statistical difference between ears for both right-handed and left-handed group. However, the results indicated that the latency of the right ear was significantly higher for the left handers than the right handers. We also found a significant result for the latency of the left ear, which was higher for the right handers. Conclusion It was possible to obtain references of values for the MMN. There are no differences in the MMN latencies and amplitudes between the ears. Regarding gender, the male group presented higher latencies in relation to the female group in the right ear. Some results indicate that there is a significant statistical difference of the MMN between right- and left-handed individuals.

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Relation between Ossicular Erosion and Destruction of Facial and Lateral Semicircular Canals in Chronic Otitis Media

Abstract Introduction Chronic otitis media can cause multiple middle ear pathogeneses. The surgeon should be aware of relation between ossicular chain erosion and other destructions because of the possibility of complications. Objective This study aimed to investigate the rates of ossicular erosion in cases of patients with and without facial nerve canal destruction, who had undergone mastoidectomy due to chronic otitis media with or without cholesteatoma. Methods We retrospectively analyzed three hundred twenty-seven patients who had undergone tympanomastoidectomy between April 2008 and February 2014. We documented the types of mastoidectomy (canal wall up, canal wall down, and radical mastoidectomy), erosion of themalleus, incus and stapes, and the destruction of facial and lateral semi-circular canal. Results Out of the 327 patients, 147 were women (44.95%) and 180 were men (55.04%) with a mean age 50.8 ± 13 years (range 8-72 years). 245 of the 327 patients (75.22%) had been operated with the diagnosis of chronic otitis media with cholesteatoma. FNCD was present in 62 of the 327 patients (18.96%) and 49 of these 62 (79.03%) patients had chronic otitis media with cholesteatoma. The correlation between the presence of FNCD with LSCC destruction and stapes erosion in chronic otitis media with cholesteatoma is statistically significant (p < 0.05). Conclusion Although incus is the most common of destructed ossicles in chronic otitis media, facial canal destruction is more closely related to stapes erosion.

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Effectiveness of Low Cut Modified Amplification using Receiver in the Canal Hearing Aid in Individuals with Auditory Neuropathy Spectrum Disorder

Abstract Introduction The studies on hearing aid benefit in individuals with auditory neuropathy spectrum disorder (ANSD) shows limited benefit. Low cut modified amplification is found to be effective in few individuals with ANSD. With advancement in technology, receiver in the canal (RIC) hearing aids have proven to be more effective than traditional behind the ear (BTE) hearing aids. Objective Thus, the present study attempts to determine the effectiveness of low cut modified amplification using RIC and BTE. Method Twenty participants with ANSD were fitted with BTE and RIC using traditional and low cut modified amplification. We divided them into good and poor performers based on unaided speech identification scores (SIS). We then compared aided SIS and aided benefit across conditions in good and poor performers with ANSD across both conditions using BTE and RIC. Results The results of the study showed that the aided performance improved with low cut modified amplification in both BTE and RIC hearing aids. The improvement noticed with low-cut modified fitting with RIC was significant in more than BTE, especially in good performers with ANSD. Conclusion The improved clarity and naturalness of sound with RIC may have led to better aided scores and better acceptance of the hearing aid. Thus, low-cut modified amplification, preferably with RIC, needs to be attempted in fitting individuals with ANSD, especially in those with good unaided SIS in quiet.

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Relationship of Tumor Thickness with Neck Node Metastasis in Buccal Squamous Cell Carcinoma: An Experience at a Tertiary Care Hospital

Abstract Introduction Squamous cell carcinoma is the most common malignancy of the head and neck, with the buccal mucosa being the most common site involved. Early locoregional metastasis is a hallmark of this disease, and early stage tumors may harbor metastatic nodes that are occult. Certain parameters can help identify high-risk patients for whom the pattern of occult nodal metastasis can be predicted. Tumor thickness is one such objective parameter. Objective To determine the relationship of tumor thickness with neck node metastasis in squamous cell carcinoma of the buccal mucosa. Methods A retrospective chart review of 102 patients with biopsy-proven squamous cell carcinoma of the buccal mucosa with N0 Necks was performed. All patients underwent tumor resection with neck dissection, and the tumor thickness was measured. Univariate and multivariate analyses were performed. Results A total of 102 patients, of which 73.53% were males and 26.47% were females. Themean age of the patients was 49.3 ± 11.1 years. It was found that the risk of neck node metastasis in buccal squamous cell carcinoma increases 35.5 times for a tumor thickness ≥ 2 mm, and the risk of neck nodemetastasis in buccal squamous cell carcinoma decreases by 0.58 times for each centimeter decrease in tumor size, while the rate of occult neck lymph node metastasis was found to be 37%. Conclusion We conclude that tumor thickness is significantly related with neck nodal metastasis in buccal squamous cell carcinoma, considering the age of the patient and the size of the tumor.

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Late-term Effects of Surgery on Nasal Functions in Patients who Underwent Total Laryngectomy Surgery

Abstract Introduction There is a common opinion that losing airway functions in total laryngectomy patients cause changes in nasal physiological rates. Studies conducted to review the subject present gaps, especially in terms of objective measurements. Objective We evaluated late-term effects of surgery on nasal functions in patients who underwent total laryngectomy surgery more than two years ago. Methods We included in the study 22 patients who had undergone total laryngectomy, as well as 24 healthy subjects with similar demographic characteristics as the control group. We performed acoustic rhinometry for intranasal volume and cross-sectional area measurements, saccharin test formeasurement of nasalmucociliary clearance, and smell identification test for evaluation of olfactory function in the patient and control groups. We compared and statistically analyzed the data obtained from the groups. Results In our study, although late-term (>2 years) measurements were not statistically significant, we detected more nasal passage patency in the patient group than in the control group. In smell identification test, lower scores were obtained in the patient group. The difference between measurements in both groups was statistically significant. Conclusion We believe that since the upper respiratory tract is disabled due to tracheostomy in patients with total laryngectomy, atrophy occurs in the late term and, consequently, nasal mucociliary clearance is impaired. We also see diminished olfactory function in total laryngectomy patients.

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Impact of Successful Choanal Atresia Repair on the Nasal Mucosa: A Preliminary Study

Abstract Introduction Themain histological features of the nasalmucosa in choanal atresia are distorted cilia, marked increase of mucous submucosal glands associated with marked reduction of goblet cell density, and lymphocytic cellular infiltration. Objective To study the nasal mucosal changes in cases of choanal atresia after successful repair compared with pre-repair mucosal histological features. Methods Tissue samples were taken from the inferior turbinate of 3 patients (1 bilateral and 2 unilateral) who were successfully operated. Then, the biopsies were subjected to histopathological, histochemical and immunohistochemical studies. After that, the results were compared with pre-repair findings in the choanal atresia side and in the normal side. Results Four biopsies (4 repaired choanal atresia sides) of the mucosa of the inferior turbinate revealed that 1 patient (who had a bilateral choanal atresia repaired), after achieving a patent choana for 8 months, had not completely recovered a normal nasal mucosa. The other 2 patients, after 18 and 23 months of achieving a patent choana, showed normal nasal cavities. Conclusion The main histological features of the nasal mucosa in choanal atresia could be reversed by surgery, making the patients regain their choanal patency, with their mucosae changing back to normal gradually with time.

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A Comparative Study between Universal Eclectic Septoplasty Technique and Cottle

Abstract Introduction Since the last century surgical correction of nasal septum deviation has been improved. The Universal Eclectic Technique was recently reported and there are still few studies dedicated to address this surgical approach. Objective The objective of this study is to compare the results of septal deviation correction achieved using the Universal Eclectic Technique (UET) with those obtained through Cottle's Technique. Methods This is a prospective study with two consecutive case series totaling 90 patients (40 women and 50 men), aged between 18 and 55 years. We divided patients into two groups according to the surgical approach. Fifty-three patients underwent septoplasty through Universal Eclectic Technique (UET) and thirty-seven patients were submitted to classical Cottle's septoplasty technique. All patients have answered the Nasal Obstruction Symptom Evaluation Scale (NOSE) questionnaire to assess pre and postoperative nasal obstruction. Results Statistical analysis showed a significantly shorter operating time for the UET group. Nasal edema assessment performed seven days after the surgery showed a prevalence of mild edema in UET group and moderate edema in Cottle's technique group. In regard to complication rates, UET presented a single case of septal hematoma while in Cottle's technique group we observed: 02 cases of severe edemas, 01 case of incapacitating headache, and 01 complaint of nasal pain. Conclusion The Universal Eclectic Technique (UET) has proven to be a safe and effective surgical technique with faster symptomatic improvement, low complication rates, and reduced surgical time when compared with classical Cottle's technique.

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Treatment Challenges of Group A Beta-hemolytic Streptococcal Pharyngo-Tonsillitis

Abstract Introduction Despite its in vitro efficacy, penicillin often fails to eradicate Group A β-hemolytic streptococci (GABHS) from patients with acute and relapsing pharyngotonsillitis (PT). Objective This review of the literature details the causes of penicillin failure to eradicate GABHS PT and the therapeutic modalities to reduce and overcome antimicrobial failure. Data Synthesis The causes of penicillin failure in eradicating GABHS PT include the presence of β lactamase producing bacteria (BLPB) that "protect" GABHS from any penicillin; the absence of bacteria that interfere with the growth of GABHS; coaggregation between GABHS and Moraxella catarrhalis; and the poor penetration of penicillin into the tonsillar tissues and the tonsillo-pharyngeal cells, which allows intracellular GABHS and Staphylococcus aureus to survive. The inadequate intracellular penetration of penicillin can allow intracellular GABHS and S. aureus to persist. In the treatment of acute tonsillitis, the use of cephalosporin can overcome these interactions by eradicating aerobic BLPB (including M. catarrhalis), while preserving the potentially interfering organisms and eliminating GABHS. Conclusion In treatment of recurrent and chronic PT, the administration of clindamycin, or amoxicillin-clavulanic acid, can eradicate both aerobic and anaerobic BLPB, as well as GABHS. The superior intracellular penetration of cephalosporin and clindamycin also enhances their efficacy against intracellular GABHS and S. aureus.

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Methods of Hearing Preservation during Cochlear Implantation

Abstract Introduction Recent advances in surgical techniques and electrode design have made residual hearing preservation during cochlear implantation (CI) possible, achievable, and desirable. Objectives The objective of this study was to review the literature regarding methods used for hearing preservation during CI surgery. Data Synthesis We performed a search in the LILACS, MEDLINE, SciELO, PubMed databases, and Cochrane Library, using the keywords CI, hearing preservation, CI electrode design, and CI soft surgery. We fully read about 15 studies that met the criteria described in "study selection". The studies showed that several factors could contribute to possible cochlear damage during or after CI surgery and must be kept in mind; mechanical damage during electrode insertion, shock waves in the perilymph fluid due to implantation, acoustic trauma due to drilling, loss of perilymph and disruption of inner ear fluid homeostasis, potential bacterial infection, and secondary intracochlear fibrous tissue formation. The desire to preserve residual hearing has led to the development of the soft-surgery protocols with its various components; avoiding entry of blood into the cochlea and the use of hyaluronate seem to be reasonably supported, whereas the use of topical steroids is questionable. The site of entry into the cochlea, electrode design, and the depth of insertion are also important contributing factors. Conclusion Hearing preservation would be useful for CI patients to benefit from the residual low frequency, as well as for the children who could be candidate for future regenerative hair cell therapy.

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Pathophysiology and Diagnosis of Vertebrobasilar Insufficiency: A Review of the Literature

Abstract Introduction Vertebrobasilar insufficiency is defined as transitory ischemia of the vertebrobasilar circulation. Dizziness, vertigo, headaches, vomit, diplopia, blindness, ataxia, imbalance, and weakness in both sides of the body are the most common symptoms. Objective To review the literature regarding the three available diagnostic testing in patients with dizziness complaints secondary to vertebrobasilar insufficiency (VBI): magnetic resonance angiography; transcranial Doppler ultrasound; and vertebrobasilar deprivation testing. Data Synthesis We selected 28 studies that complied with our selection criteria for appraisal. The most frequent cause of the hemodynamic changes leading to VBI is atherosclerosis. The main clinical symptoms are dizziness, vertigo, headaches, vomit, diplopia, blindness, ataxia, imbalance, and weakness in both sides of the body. Even though arteriography is considered the most important exam to diagnose the disease, the inherent risks of this exam should be taken into consideration. The magnetic resonance angiography has been widely studied and is a good method to identify and localize any occlusions and stenosis in both neck and intracranial great vessels. Conclusion Each patient with a suspected diagnosis of VBI should be individually evaluated and treated, taking in consideration the pros and cons of each diagnostic testing and treatment option.

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Adenomatous Tumors of the Middle Ear: A Literature Review

Abstract Introduction Neuroendocrine adenomas of the middle ear (NAME) are uncommon causes of middle ear masses. Mostly limited to case reports and small series, the literature is poor in providing an overall assessment of these tumors. Objective To review the current literature about all aspects of the disease, including its etiology, clinical manifestations, diagnosis, and treatment. Data Synthesis The pathogenesis of adenomatous tumors of the middle ear is not clear yet. One potential explanation is that an undifferentiated pluripotent endodermal stem cell may still be present in the middle ear mucosal surface, and may be the origin of the tumors. It typically appears as a nonspecific retrotympanic mass. The average age of onset for the disease is the fifth decade, and the most common clinical symptom is conductive hearing loss. Malign behavior is rare. There are numerous differential diagnoses of NAME. The final diagnosis depends on microscopic findings. The preoperative evaluation should include the use of computed tomography and magnetic resonance imaging. The adjunctive therapy of middle ear adenomatous tumors with radiotherapy, chemotherapy or somatostatin analogs is generally not recommended. Conclusion There is still much debate on pathogenesis and classification of NAME. Saliba's classification is currently the most complete and preferable one. Aggressive surgical procedure with ossicular chain excision is the gold standard treatment. Followup with physical and radiological exams is mandatory, particularly if the first procedure was conservative, without the removal of the encased ossicles.

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The potential clinical benefits of medicines optimisation through comprehensive geriatric assessment, carried out by secondary care geriatricians, in a general practice care setting in North Staffordshire, UK: a feasibility study

Objectives

To evaluate the feasibility and potential clinical benefits of medicines optimisation through comprehensive geriatric assessment (CGA) of frail patients with multiple conditions, by secondary care geriatricians in a general practice care setting.

Methods

Seven general practitioner (GP) practices in one region of Stoke-on-Trent volunteered to take part. GPs selected patients (n=186) who were local permanent residents, at least 65 years old and on eight or more medications per day. Patients were sent a written invitation outlining the assessment purpose/format. Prior to patient assessments, primary care staff prepared packs detailing patient medical history, recent consultations, current medications, recent laboratory tests and social circumstances. One hour was allocated for the CGA per patient, with one of three geriatricians, to enable sufficient time to explore all relevant aspects. Assessment comprised a full history, thorough clinical examination, assessment of balance and mobility, mental function and information on home environment and support arrangements. After consultation, geriatricians made recommendations regarding further assessments, investigations or medication changes. Geriatricians entered their main findings and recommendations onto a standard template.

Results

In total, 687 recommendations for changes in patients' medication regimens were made for 169 (91%) patients. In 17 (9%) patients there was no recommendation to alter medications. This resulted in an average of four alterations in medication per patient. The predominant changes to medications were to stop medications (34%) or to reduce the dosage (24%). Starting a new medication represented 18% of all the medication changes. Adherence rates to geriatrician medication recommendations were 72% at 6 months and 65% at 12 months.

Conclusions

CGA of older patients with complex needs, by geriatricians in a general practice care setting, is feasible. Our study demonstrated constructive collaboration between GPs and geriatricians from secondary care, suggesting further studies and clinical trials are feasible and have scope to yield beneficial outcomes.

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A national survey exploring oral healthcare service provision across Australian community pharmacies

Objectives

This study investigated pharmacists' and pharmacy assistants' current practices and perspectives with regard to oral healthcare provision across Australian community pharmacies.

Design

Cross-sectional study. A questionnaire for each pharmacist and pharmacy assistant cohort was developed and administered by online or postal means. Pearson's ² test was used to examine relationships between categorical variables.

Participants

Pharmacists and pharmacy assistants working within 2100 randomly selected Australian community pharmacies.

Results

The overall response rate was 58.5% (644/1100) for the pharmacist cohort and 28% (280/1000) for the pharmacy assistant cohort. This represents pharmacy staff responses from 803 community pharmacies across Australia (approximately 14.6%, 803/5500 of community pharmacies nationally). Overall, the majority of pharmacists (80.2%; 516/644) and pharmacy assistants (83.6%; 234/280) reported providing oral health advice/consultations to health consumers up to five times each week. More than half of community pharmacists and pharmacy assistants were involved in identifying signs and symptoms for oral health problems; and the majority believed health consumers were receptive to receiving oral health advice. Additionally, more than 80% of pharmacists and 60% of pharmacy assistants viewed extended oral healthcare roles positively and supported integrating them within their workplace; extended roles include provision of prevention, early intervention and referral to oral healthcare services. The most commonly reported barriers to enhance pharmacy staff involvement in oral healthcare within Australian community pharmacies include lack of knowledge, ongoing training and resources to assist practice.

Conclusion

This study highlights that Australian pharmacists have an important role in oral health and provides evidence supporting the need for growing partnerships/collaborations between pharmacy and dental healthcare professionals and organisations to develop, implement and evaluate evidence-based resources, interventions and services to deliver improved and responsive oral healthcare within Australian communities.

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Non-adherence to immunosuppressants following renal transplantation: a protocol for a systematic review

Introduction

Adherence to immunosuppressant medication is essential for renal transplant recipients. This review aims to summarise what is known about non-adherence, with a view to providing comprehensive evidence to inform strategies aimed at advancing adherent behaviour.

Methods and analysis

A systematic review of quantitative studies that report adherence to immunosuppressants in adult (over 18 years) renal transplant recipients. The review will follow the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines; study quality will be assessed using the Downs and Black checklist. Systematic searches will be completed across relevant databases. Two reviewers will independently extract data using a predefined data extraction form. We will summarise the operationalisation of adherence across studies and use narrative synthesis to identify factors associated with non-adherence. A meta-analysis will be conducted if there is sufficient homogeneity, and available data, across studies to estimate the prevalence of non-adherence in renal transplant recipients. Heterogeneity will be assessed using the I² test. Survival analysis will be conducted to estimate hazard ratios to explore the impact of non-adherence on graft survival, graft failure and patient survival.

Ethics and dissemination

Findings will be published in a peer-reviewed journal and disseminated at conferences for professionals and researchers. Review outcomes will help support clinical practice by highlighting the extent of non-adherence among adults, and in doing so, signpost the need for suitable intervention.

Trial registration number

PROSPERO registration number (CRD42016038751).

http://ift.tt/2fVBuPn

Efficacy and safety of instantaneous wave-free ratio in patients undergoing coronary revascularisation: protocol for a systematic review

Introduction

Effective selection of coronary lesions for revascularisation is pivotal in the management of symptoms and adverse outcomes in patients with coronary artery disease. Recently, instantaneous 'wave-free' ratio (iFR) has been proposed as a new diagnostic index for assessing the severity of coronary stenoses without the need of pharmacological vasodilation. Evidence of the effectiveness of iFR-guided revascularisation is emerging and a systematic review is warranted.

Methods and analysis

This is a protocol for a systematic review of randomised controlled trials and controlled observational studies. Electronic sources including MEDLINE via Ovid, Embase, Cochrane databases and ClinicalTrials.gov will be searched for potentially eligible studies investigating the effects of iFR-guided strategy in patients undergoing coronary revascularisation. Studies will be selected against transparent eligibility criteria and data will be extracted using a prestandardised data collection form by two independent authors. Risk of bias in included studies and overall quality of evidence will be assessed using validated methodological tools. Meta-analysis will be performed using the Review Manager software. Our systematic review will be performed according to the guidance from the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement.

Ethics and dissemination

Ethics approval is not required. Results of the systematic review will be disseminated as conference proceedings and peer-reviewed journal publication.

Trial registration number

This protocol is registered in the International Prospective Register of Systematic Reviews (PROSPERO), registration number CRD42017065460.

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Cross-sector user and provider perceptions on experiences of shared-care clozapine: a qualitative study

Objectives

(1) To explore individual perceptions on experiences of people receiving and/or delivering a shared-care clozapine serviceand (2) to gain an understanding of effectiveness and acceptability of shared-care clozapine.

Design

Interpretative phenomenological analysis guided the delivery and analysis of a semistructured interview and focus group study designed to explore participant experience of shared-care clozapine. Ethical approval 13/EM/0286 was gained in July 2013 from East Midlands—Nottingham 1 REC.

Participants

Eight stakeholder groups from Adult and Forensic Mental Health involved in shared-care clozapine provision delivered in primary care were identified for recruitment from one mental health trust in England (six different groups of healthcare professionals (HCPs), clozapine service users (CSUs) and their carers). To be eligible for recruitment, all potential participants had to be either providing, receiving or the carer of a person receiving clozapine by shared care.

Results

32 HCPs and 6 CSUs were recruited and 14 interviews and 6 participant homogenous focus groups were run. Four shared superordinate themes were identified: Clozapine Process, The Sharing of Care, The Provision of Care and Multi-professional Relationships. Differences between Adult and Forensic engagement in shared care were noted and both HCP and CSU relationships were mapped to the Wish conceptual framework of relationships to provide insight into how shared-care clozapine can provide a mechanism for provision of person-centred care, which was present in the Forensic HCP–CSU but not General Adult HCP–CSU relationship.

Conclusions

The Forensic HCP/CSU relationship demonstrated how cross-sector working through shared-care clozapine can provide a mechanism for provision of person-centred care by enabling a person-centred focus to care delivery which supported CSUs to live as independently as possible. Person-centred care demonstrably improves patient care outcomes and wider implementation of shared-care clozapine could provide greater integration of people with serious mental illness and reduce stigma within the community while improving patient outcomes.

http://ift.tt/2fVZQZw

Canada-DONATE study protocol: a prospective national observational study of the medical management of deceased organ donors

Introduction

Research on the management of deceased organ donors aims to improve the number and quality of transplants and recipient outcomes. In Canada, this research is challenged by regionalisation of donation services within provinces and the geographical, clinical and administrative separation of donation from transplantation services. This study aims to build a national platform for future clinical trials in donor management. Objectives are to engage collaborators at donation hospitals and organ donation organisations (ODOs) across Canada, describe current practices, evaluate the effectiveness of donation-specific interventions and assess the feasibility of future clinical trials.

Methods and analysis

This ongoing prospective observational study of the medical management of deceased organ donors will enrol more than 650 consented potential donors from adult intensive care units at 33 hospital sites across Canada, each participating for 12 months. ODOs ensure enrolment of consecutive eligible participants. Research staff record detailed data about participants, therapies, organ assessments, death declaration procedures and adverse clinical exposures from the time of donation consent to organ recovery. ODOs provide reasons that organs are declined, dates and places of transplantation, and recipient age and sex.

Descriptive analyses will summarise current practices. Effectiveness analyses will examine donation-specific interventions with respect to the number of transplants, using multilevel regression models to account for clustering by donor, hospitals and ODOs. Feasibility analyses will focus on acceptance of the research consent model; participation of academic and community hospitals as well as ODOs; and accessibility of recipient data.

Ethics and dissemination

This study uses a waiver of research consent. Hospitals will receive reports on local practices benchmarked to (1) national practices and (2) national donor management guidelines. We will report findings to donation and transplant collaborators (ie, clinicians, researchers, ODOs) and publish in peer-reviewed journals.

Trial registration number

NCT03114436.

http://ift.tt/2ybADoq

sTLR4/MD-2 complex inhibits colorectal cancer migration and invasiveness in vitro and in vivo by lncRNA H19 down-regulation

Abstract

Long non-coding RNAs (lncRNAs) have multiple functions in gene regulation and during cellular processes. However, the functional roles of lncRNAs in colorectal cancer (CRC) have not yet been well understood. In our previous study, we demonstrated that sTLR4/MD-2 complex can inhibit CRC in vitro and in vivo by targeting LPS. Therefore, the aim of the present study is to investigate the expression of lncRNA H19 in CRC and to evaluate its effect on the inhibition of sTLR4/MD-2 complex. The expression of H19 is measured in 63 CRC tumor tissues and adjacent normal tissues by quantitative real-time PCR (qRT-PCR). The effects of H19 on migration and invasiveness are evaluated by wound healing assay, migration and invasion assays. Results showed that H19 is significantly overexpressed in cancerous tissues and CRC cell lines compared with adjacent normal tissues and a normal human intestinal epithelial cell line. Moreover, H19 overexpression is closely associated with CRC patients. Our in vitro data indicated that knockdown of H19 inhibits the migration and invasiveness of CRC cells. And in vivo sTLR4/MD-2 complex inhibits tumor growth in mice and the expression of H19 is down-regulated. These results suggest that sTLR4/MD-2 complex inhibits CRC migration and invasiveness in vitro and in vivo by lncRNA H19 down-regulation.

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Immune cells and autoantibodies in pulmonary arterial hypertension

Abstract

Analyses of immunity in pulmonary arterial hypertension (PAH) support the notion that maladaptation of the immune response exists. Altered immunity is an increasingly recognized feature of PAH. Indeed, a delicate balance between immunity and tolerance exists and any disturbance may result in chronic inflammation or autoimmunity. This is suggested by infiltration of various immune cells (e.g. macrophages, T and B lymphocytes) in remodeled pulmonary vessels. In addition, several types of autoantibodies directed against antinuclear antigens, endothelial cells (ECs) and fibroblasts have been found in idiopathic and systemic sclerosis-associated PAH. These autoantibodies may play an important role in EC apoptosis and in the expression of cell adhesion molecules. This review article provides an overview of immunity pathways highlighting their potential roles in pulmonary vascular remodeling in PAH and the possibility of future targeted therapy.

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Phelan-McDermid syndrome due to SHANK3 mutation in an intellectually disabled adult male: successful treatment with lithium

For 30 years, Phelan and co-workers described a syndrome characterised by neonatal hypotonia, global developmental delay, strongly impaired speech, sleep disturbances and hyperreactivity to sensory stimuli. This Phelan-McDermid syndrome (PMS), also presenting with symptoms from the autism spectrum and a higher risk of developing seizure disorders, may be caused by a deletion of chromosome 22q13 or by a mutation in the SHANK3 gene. Its core psychopathological phenotype comprises symptoms from the bipolar spectrum for which generally treatment with a mood-stabilising anticonvulsant in combination with an atypical antipsychotic seems to be most effective. In addition to two elsewhere published adolescent patients, we here describe in detail the history of an adult male patient with PMS caused by a SHANK3 mutation in whom successive treatment regimens with antipsychotics and mood-stabilising anticonvulsants were all ineffective. Ultimately, addition of lithium to existing olanzapine therapy led to enduring stabilisation of mood and behaviour.

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Breast pseudoaneurysm arising from core needle biopsy should be left well alone

A 45-year-old woman previously fit and well, developed a pseudoaneurysm of the breast following core needle biopsy. She was ultimately reassured and discharged without further intervention. Pseudoaneurysm is a rare complication of core needle biopsy which, contrary to previously published cases, can be managed conservatively.

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Does public transport use prevent declines in walking speed among older adults living in England? A prospective cohort study

Objectives

Although there is some evidence that public transport use confers public health benefits, the evidence is limited by cross-sectional study designs and health-related confounding factors. This study examines the effect of public transport use on changes in walking speed among older adults living in England, comparing frequent users of public transport to their peers who did not use public transport because of structural barriers (poor public transport infrastructure) or through choice.

Design

Prospective cohort study.

Setting

England, UK.

Participants

Older adults aged ≥60 years eligible for the walking speed test. 6246 individuals at wave 2 (2004–2005); 5909 individuals at wave 3 (2006–2007); 7321 individuals at wave 4 (2008–2009); 7535 individuals at wave 5 (2010–2011) and 7664 individuals at wave 6 (2012–2013) of the English Longitudinal Study of Ageing.

Main outcome measure

The walking speed was estimated from the time taken to walk 2.4 m. Fixed effects models and growth curve models were used to examine the associations between public transport use and walking speed.

Results

Older adults who did not use public transport through choice or because of structural reasons had slower walking speeds (–0.02 m/s (95% CI –0.03 to –0.003) and –0.02 m/s (95% CI –0.03 to –0.01), respectively) and took an extra 0.07 s to walk 2.4 m compared with their peers who used public transport frequently. The age-related trajectories of decline in walking speed were slower for frequent users of public transport compared with non-users.

Conclusions

Frequent use of public transport may prevent age-related decline in physical capability by promoting physical activity and lower limb muscle strength among older adults. The association between public transport use and slower decline in walking speed among older adults is unlikely to be confounded by health-related selection factors. Improving access to good quality public transport could improve the health of older adults.

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Human Metapneumovirus Infection: Pneumonia Risk Factors in Solid Organ Transplantation Patients and CT findings.

Background: Human metapneumovirus (HMPV) is a newly detected pathogen which can cause lower respiratory tract disease. Clinical characteristics, computed tomography (CT) findings, and outcomes of HMPV pneumonia in solid organ transplantation (SOT) patients have not been well demonstrated. Methods: Between January 2010 and February 2016, clinical and imaging findings of 59 patients receiving SOT (types of organ: 37 kidney, 16 liver, 4 heart and 2 pancreas and kidney) who had HMPV infection detected in nasopharyngeal or bronchoalveolar lavage by reverse transcription polymerase chain reaction were retrospectively evaluated. Results: Most (90%) of the patients were detected between March and June. In the 59 SOT patients with upper respiratory tract infection (URI), 29 (49%) progressed to lower respiratory tract disease (LRD) after a median of 7 days (range, 2-31 days). Co-infection was noted in 39% of patients. In Cox proportional hazards analysis, low lymphocyte count ( 10 mg/dL (HR, 2.93, 95% CI, 1.19-7.21, P=0.02) at URI diagnosis were associated with HMPV pneumonia. On CT, HMPV pneumonia presented as bilateral ill-defined centrilobular nodules, consolidation and ground-glass opacities, while lymphadenopathy or effusion is not common. There were no significantly different imaging CT findings between patients with HMPV infection alone and those with co-infection. Conclusions: HMPV pneumonias were detected in nearly half of SOT patients showing URI symptoms with positive HMPV, and low lymphocyte count and high CRP at URI diagnosis were significant factors associated with HMPV pneumonia. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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The Importance in Using Serially Measured TAC Clearance Values, Especially during the Early Posttransplant Period.

No abstract available

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The Authors' Reply.

No abstract available

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Chronic liraglutide administration fails to suppress postprandial glucagon levels in type 1 diabetic islet allograft recipients with graft dysfunction.

No abstract available

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The Role of Computed Tomography Scans in Diaphyseal Femur Fractures Following Gunshot Injuries: A Survey of Orthopaedic Traumatologists

Publication date: Available online 28 September 2017
Source:Injury
Author(s): John S. Hwang, Peter D. Gibson, Kenneth L. Koury, Nicholas Stekas, Michael S. Sirkin, Mark C. Reilly, Mark R. Adams
The objective of this study was to analyze if the addition of CT changed the management of femoral shaft fractures caused by gunshot wounds when compared to those managed with plain radiography alone.MethodsA multiple-choice, single-answer electronic survey was created to compare utility of advanced imaging when treating femur fractures resulting from gunshot injury. A total of ten femoral shaft fracture cause by gunshot injuries were selected for an online survey to be administered to orthopeaedic traumatologists. The survey compared the use the of fixation device and surgical planning before and after the CT scan.ResultsA total of 99 surveys were initiated, of which 82 were completed. For proximal shaft fractures, 37% of experts reported that a CT scan should be ordered based on the radiograph alone, prior to reviewing the CT. After reviewing the CT, 5% of experts reported that they would have performed a "major" change, and 10% reported that they would have performed a "minor" change. 4% of surveyors would have changed their decision regarding ordering a CT. For distal femoral shaft fractures, 42% of experts selected that a CT scan would have been ordered prior to reviewing the CT. After reviewing the CT, 2% would have performed a "major" change, and 8% would have performed a "minor" change in management. 5% of surveyors would have changed their decision regarding ordering a CT.ConclusionOur study demonstrated that CT scans are relatively unlikely to cause major changes in fracture management of gunshot-induced fractures of femoral shaft.



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Corrigendum to “Does early beta-blockade in isolated severe traumatic brain injury reduce the risk of post traumatic depression?” [Injury 48 (2017) 101–105]

Publication date: Available online 28 September 2017
Source:Injury
Author(s): Rebecka Ahl, Gabriel Sjolin, Shahin Mohseni




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Prediction of massive blood transfusion in battlefield trauma: development and validation of the Military Acute Severe Haemorrhage (MASH) score

Publication date: Available online 28 September 2017
Source:Injury
Author(s): Jacqueline V. Mclennan, Kevin C. Mackway-Jones, Jason E. Smith
BackgroundThe predominant cause of preventable trauma death is bleeding, and many of these patients need resuscitation with massive blood transfusion. In resource-constrained environments, early recognition of such patients can improve planning and reduce wastage of blood products. No existing decision rule is sufficiently reliable to predict those patients requiring massive blood transfusion. This study aims to produce a decision rule for use on arrival at hospital for patients sustaining battlefield trauma.MethodsA retrospective database analysis was undertaken using the UK Joint Theatre Trauma Registry to provide a derivation and validation dataset. Regression analysis of potential predictive factors was performed. Predictive factors were analysed through multi-logistic regression analysis to build predictive models; sensitivity and specificity of these models was assessed, and the best fit models were analysed in the validation dataset.ResultsA decision rule was produced using a combination of injury pattern, clinical observations and pre-hospital data. The proposed rule, using a score of 3 or greater, demonstrated a sensitivity of 82.7% and a specificity of 88.8% for prediction of massive blood transfusion, with an AUROC of 0.93 (95% CI 0.91–0.95).ConclusionsWe have produced a decision tool with improved accuracy compared to any previously described tools that can be used to predict blood transfusion requirements in the military deployed hospital environment.



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Effect of Hypothermia on Apoptosis in Traumatic Brain injury and Hemorrhagic Shock Model

Publication date: Available online 28 September 2017
Source:Injury
Author(s): Oğuz EROĞLU, Turgut DENİZ, Prof. Dr. KISA Üçler, Prof. Dr. Pınar ATASOY, Assoc. Prof. Dr. KuzeyAYDINURAZ
IntroductionThe neuroprotective mechanisms of therapeutic hypothermia against trauma-related injury have not been fully understood yet. In this study, we aimed to investigate the effects of therapeutic hypothermia on biochemical and histopathological markers of apoptosis using Traumatic brain injury (TBI) and hemorrhagic shock (HS) model.MethodsA total of 50 male albino-wistar rats were divided into five groups: Group isolated TBI, Group NT (HT+HS+normothermia), Group MH (HT+HS+mild hypothermia), Group MoH (HT+HS+moderate hypothermia) and Group C (control). Neurological deficit scores were assessed at baseline and at 24hours. The rats were, then, sacrificed to collect serum and brain tissue samples. Levels of Caspase-3,6,8, proteoglycan-4 (PG-4), malondialdehyde (MDA), and nitric oxide (NO) were measured in serum and brain tissue samples. Histopathological examination was performed in brain tissue.ResultsThere were significant differences in the serum levels of Caspase-3 between Group NT and Group C (p=0.018). The serum levels of Caspase-6 in Group NT (0.70±0.58) were lower than Group MH (1.39±0.28), although the difference was not statistically significant (p=0.068). There were significant differences in the brain tissue samples for Caspase-3 levels between Group NT and Group C (p=0.049). A significant difference in the Caspase-8 brain tissue levels was also observed between Group NT and Group C (p=0.022). Group NT had significantly higher scores of all the pathological variables (for edema p<0.017; for gliosis p<0.001; for congestion p<0.003, for hemorrhage p<0.011) than Group C.ConclusionOur study results suggest that hypothermia may exert its neuroprotective effects by reducing markers of apoptotic pathway, particularly Caspase-3 on TBI and HS.



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The Effect Of Resuscitation Strategy On The Longitudinal Immuno-inflammatory Response To Blunt Trauma

Publication date: Available online 28 September 2017
Source:Injury
Author(s): Alexander Bonde, Ask Tybjærg Nordestgaard, Rasmus Kirial, Peter Svenningsen, Martin Sillesen
INTRODUCTIONResuscitation strategies following blunt trauma have been linked to immuno-inflammatory complications leading to systemic inflammatory syndrome (SIRS), sepsis and multiple organ failure (MOF). The effect of resuscitation strategy on longitudinal inflammation marker trajectories is, however, unknown. We hypothesized that the effect of resuscitation strategy extends beyond the trauma-related coagulopathy, perhaps affecting the longitudinal immuno-inflammatory response to injury.METHODSWe analyzed data prospectively collected for the Inflammation and Host Response to Injury (Glue Grant) study. Blood sampling for inflammation marker analyses from blunt trauma patients was done on admission days 0, 1, 4, 7, 14, 21 and 28 where applicable.Total volume transfused of packed red blood cells (PRBC), fresh frozen plasma (FFP), platelets (PLT), and crystalloids during the initial 48hours was extracted, along with an analysis for an array of cytokines by Enzyme Linked Immunosorbent Assay (ELISA) technique. A within patient concentration change (WPCC) was calculated to quantify longitudinal alterations in cytokine levels, while controlling for potential confounders. To account for the multiple comparisons performed, p-values obtained from the multivariate regression model were post-hoc corrected by the false detection rate (FDR) q-value.RESULTSNo longitudinal trajectories of inflammatory markers were found to be associated with PRBC- or PLT transfusion. Three proinflammatory cytokines (Il-1β, MIP-1β, and TNFR2) were negatively associated with volume of FFP transfused (q=0.02, q<0.001 and q=0.007 respectively), and one proinflammatory cytokine (MIP-1β) was positively associated with crystalloid infusion (q=0.005).CONCLUSIONSResuscitation strategy employed following blunt trauma has limited association to longitudinal inflammation marker trajectories, with a potential association between the strategy employed and IL-1β, TNFR2, and MIP-1β trajectories, respectively.



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Lower Amputation Rate after Fasciotomy by Straight Midline Incision Technique for a 22,900-Volt Electrical Injury to the Upper Extremities

Publication date: Available online 28 September 2017
Source:Injury
Author(s): Young-Soo Jan, Byung Hoon Lee, Hyun-Soo Park
PurposeThe purpose of this study is to compare the major amputation rate following two different fasciotomy techniques, conventional versus straight midline, in patients with high-voltage arc burn injury by electric currents of 22,900V to the upper extremities.MethodsA retrospective analysis of 230 patients (270 burned upper limbs) who underwent fasciotomy after high-voltage electrical injuries between 1996 and 2007 was performed. The patients were divided into two groups according to the fasciotomy method used. From 1996 to 2002, 158 patients (184 limbs) underwent conventional fasciotomy by Green's volar-ulnar incision (conventional fasciotomy group). From 2003 to 2007, 72 patients (86 limbs) underwent fasciotomy using a straight midline curved incision (midline fasciotomy group). The patients were also divided into two groups based on whether the fasciotomy procedure was performed early or late. Patients who underwent fasciotomies <8h after injury were classified as early, while those who underwent it >8h after injury were classified as late. Major amputation rates were compared between two fasciotomy methods and analyzed following fasciotomy timing.ResultsThe midline fasciotomy group had a significantly lower major amputation rate (33.7%) than the conventional fasciotomy group (59.2%) (p<0.001). A subsequently decreased major amputation rate of 27.8% was observed in the early fasciotomy subgroup of the midline fasciotomy group (p=0.025).ConclusionEarly fasciotomy remarkably reduced the major amputation rate after high-voltage arc injury; in the setting of minimized vascular exposure after fasciotomy, a midline straight incision could ensure that various types of reconstructive microsurgical procedures and primary skin closures can be used to save limbs.



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The experience and understanding of pain management in recently discharged adult trauma patients: A qualitative study

Publication date: Available online 28 September 2017
Source:Injury
Author(s): Helen Goldsmith, Andrea McCloughen, Kate Curtis
IntroductionPain following injury is often intense, prolonged and debilitating. If poorly managed, this acute pain has the potential to delay rehabilitation and lead to chronic pain. Recent quantitative Australian research recommends implementing further information and interventions to improve trauma patient outcomes, however, to ensure effectiveness, exploration of the patient perspective is imperative to ensure the success of future pain management strategies. This study aimed to gain understanding about the experience of pain management using prescribed analgesic regimens of recently discharged adult trauma patients.MethodSemi-structured interviews were used to explore the experiences and understandings of trauma patients in managing pain using prescribed analgesic regimens during the initial post-hospital discharge period. Twelve participants were purposively selected over a 6-month period at a level one trauma outpatient clinic based on questionnaire responses indicating pain related concerns. Qualitative data were thematically analysed.ResultsThe overarching finding was that injuries and inadequate pain management incapacitate the patient at home. Four main themes were developed: injury pain is unique and debilitating; patients are uninformed at hospital discharge; patients have low confidence with pain management at home; and patients make independent decisions about pain management. Patients felt they were not given adequate information at hospital discharge to support them to make effective decisions about their pain management practices at home.ConclusionThere is a need for more inclusive and improved hospital discharge processes that includes patient and family education around pain management following injury. To achieve this, clinician education, support and training is essential.



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Patterns of Vasopressor Utilization During the Resuscitation of Massively Transfused Trauma Patients

Publication date: Available online 27 September 2017
Source:Injury
Author(s): Galinos Barmparas, Navpreet K. Dhillon, Eric JT Smith, Russell Mason, Nicolas Melo, Gretchen M. Thomsen, Daniel R. Margulies, Eric J. Ley
BackgroundThe use of vasopressors (VP) in the resuscitation of massively transfused trauma patients might be considered a marker of inadequate resuscitation. We sought to characterize the utilization of VP in patients receiving massive transfusion and examine the association of their use with mortality.MethodsTrauma patients admitted from January 2011 to October 2016 receiving massive transfusion, defined as 3 units of pRBC within the first hour from admission, were selected for analysis. Demographics, admission vital signs and labs, use of VP, surgical interventions and outcomes were collected. Standard statistical tools were utilized.ResultsOver the 5-year study period, 120 trauma patients met inclusion criteria. The median age was 39 years with 77% being male and 41% sustaining a penetrating injury. Patients who received VP [VP (+)] were more likely to have a lower admission GCS (median 4.5 vs. 14.0, p <0.01) and less likely to have a penetrating injury (31% vs. 54%, p=0.02). The overall mortality was 49% and significantly higher in the VP (+) cohort (60% vs. 34%, AHR: 9.9, adjusted p=0.03). Mortality increased in a stepwise fashion with increasing number of VP utilized, starting at 34% for no VP, to 78% for 3 VP, and 100% for 5 or more. The majority of deaths in the VP (−) group (88%) occurred within one day from admission. For the VP (+) group, 57% of deaths occurred within one day, with the remaining 43% occurring at a later time.ConclusionIn the era of massive transfusion protocols, vasopressors are commonly utilized in exsanguinating trauma patients and their use is associated with a higher mortality risk. Deaths in patients receiving vasopressors are more likely to occur later compared to those in patients who do not receive vasopressors. Further research to characterize the role of these agents in the resuscitation of trauma patients is required.



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Location of atypical femoral fracture can be determined by tensile stress distribution influenced by femoral bowing and neck-shaft angle: a CT-based nonlinear finite element analysis model for the assessment of femoral shaft loading stress

Publication date: Available online 27 September 2017
Source:Injury
Author(s): Yoto Oh, Koji Fujita, Yoshiaki Wakabayashi, Yoshiro Kurosa, Atsushi Okawa
IntroductionLoading stress due to individual variations in femoral morphology is thought to be strongly associated with the pathogenesis of atypical femoral fracture (AFF). In Japan, studies on AFF regarding pathogenesis in the mid-shaft are well-documented and a key factor in the injury is thought to be femoral shaft bowing deformity. Thus, we developed a CT-based finite element analysis (CT/FEA) model to assess distribution of loading stress in the femoral shaft.Patients and MethodsA multicenter prospective study was performed at 12 hospitals in Japan from August 2015 to February 2017. We assembled three study groups—the mid-shaft AFF group (n=12), the subtrochanteric AFF group (n=10), and the control group (n=11)—and analyzed femoral morphology and loading stress in the femoral shaft by nonlinear CT/FEA.ResultsFemoral bowing in the mid-shaft AFF group was significantly greater (lateral bowing, p<0.0001; anterior bowing, p<0.01). Femoral neck-shaft angle in the subtrochanteric AFF group was significantly smaller (p<0.001). On CT/FEA, both the mid-shaft and subtrochanteric AFF group showed maximum tensile stress located adjacent to the fracture site. Quantitatively, there was a correlation between femoral bowing and the ratio of tensile stress, which was calculated between the mid-shaft and subtrochanteric region (lateral bowing, r=0.6373, p<0.0001; anterior bowing, r=−0.5825, p<0.001).ConclusionsCT/FEA demonstrated that tensile stress by loading stress can cause AFF. The location of AFF injury could be determined by individual stress distribution influenced by femoral bowing and neck-shaft angle.



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Research priorities in cancer cachexia: The University of Rochester Cancer Center NCI Community Oncology Research Program Research Base Symposium on Cancer Cachexia and Sarcopenia.

Purpose of review: Cancer cachexia remains understudied and there are no standard treatments available despite the publication of an international consensus definition and the completion of several large phase III intervention trials in the past 6 years. In September 2015, The University of Rochester Cancer Center NCORP Research Base led a Symposium on Cancer Cachexia and Sarcopenia with goals of reviewing the state of the science, identifying knowledge gaps, and formulating research priorities in cancer cachexia through active discussion and consensus. Recent findings: Research priorities that emerged from the discussion included the implementation of morphometrics into clinical decision making, establishing specific diagnostic criteria for the stages of cachexia, expanding patient selection in intervention trials, identifying clinically meaningful trial endpoints, and the investigation of exercise as an intervention for cancer cachexia. Summary: Standardizing how we define and measure cancer cachexia, targeting its complex biologic mechanisms, enrolling patients early in their disease course, and evaluating exercise, either alone or in combination, were proposed as initiatives that may ultimately result in the improved design of cancer cachexia therapeutic trials. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Practical approaches to managing cancer patients with weight loss.

Purpose of review: Poor appetite and weight loss are a source of family conflict, psychological distress, and associated with poor tolerance to chemotherapy, impaired quality of life, and decreased survival. Despite clinicians' concern about the effect of cachexia on their patients, few oncological professional organizations provide guidelines for the treatment of cancer-related weight loss. Recent findings: Recent publications indicate there is an unmet need for addressing cachexia in patients with cancer. Studies also reveal that patients are often consuming inadequate calories and protein. Inadequate oral intake may be mitigated by a multimodal interdisciplinary approach that uses pharmacological and nonpharmacological measures such as exercise and counseling. Other positive clinical outcomes include decreased symptom burden, improved quality of life, and enhanced physical performance. Summary: Experience from specialist cachexia clinics and published literature indicates that simple assessments and interventions can be applied more broadly in clinical practice and that the interdisciplinary multimodal approach is important for achieving successful outcomes. The positive influence of this approach on clinical outcomes also has to be considered in clinical trial design. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Impact of advance care planning on end-of-life management.

Purpose of review: The aim of this review is to critically appraise the recent evidence on different aspects of impact of advance care planning (ACP) in palliative care and to reflect on further implications on practice and research in the future. Recent findings: Evidence about various ACP impacts is rapidly growing and most common outcome measures are still advance directive completion, change in hospital admission rate and patients' and families' views and experiences with ACP. Mainly descriptive studies bring new information of ACP impact for specific groups of patients, their families, settings, countries, contexts, staff and healthcare system as such. It is not yet clear who and when would best conduct ACP, from general practitioners (GPs) to specialists in the hospitals and even lay-navigators for cancer patients; from early ACP conversations to critical ACP in acute events at the end-of-life. The need for ACP impacts high-quality evidence is becoming more urgent because latest future projections are showing higher palliative care needs than previously expected. Summary: Recent studies on various ACP impacts reveal variety of outcomes for different patient groups and settings, and are contributing to a wider picture of ACP situation around the world. However, high-quality evidence on ACP impact is still urgently expected in times of growing need for system-level changes for effective ACP implementation. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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What is next after anamorelin?.

Purpose of review: In spite of its relevance, treatments for the cancer anorexia and cachexia syndrome (CACS) are not available. One of the agents that recently reached phase III clinical trials is anamorelin. Its development, along with that of other agents for this indication, will be reviewed here, with a focus on the gaps in the current knowledge and future directions. Recent findings: In spite of several targets showing promising results in early development, their difficulties obtaining regulatory approval underscore the need to reconsider the current strategies in drug development and the challenges in the field of CACS. Summary: Further research is needed in order to meet the challenges of developing treatments for CACS. Preclinical studies should expand our understanding about key regulators of appetite, muscle, and energy metabolism in this setting using models that can be translated reliably to humans. Clinical research efforts should focus on validating the entry criteria, endpoints, outcomes, and the potential synergistic effects and interaction between different targets, nutrition, and exercise interventions. Clinical meaningfulness and significance should be taken into account in the design of clinical trials. It is essential that all key stakeholders are included in the design of future strategies. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Palliative and end-of-life care for adults with advanced chronic obstructive pulmonary disease: a rapid review focusing on patient and family caregiver perspectives.

Purpose of review: The aim of the review was to explore patient and family caregiver perspectives on key issues for ensuring quality of end-of-life care for people with chronic obstructive pulmonary disease (COPD). The growing evidence on the value of specialist palliative care services demonstrates significant improvements in treatments and provisions; however, much of the literature is generic in nature or centred on people with a cancer diagnosis. In this review, we examine the literature to ascertain the views and needs of patients and carers affected by advanced COPD, a highly debilitating condition that can have a profoundly negative impact on the quality of end-of-life experience. Recent findings: A total of 19 papers were included in the review. The main themes in the literature were Holistic Care, Illness Trajectory and Technology. Summary: Areas of unmet need emphasized across physical, psychosocial and spiritual domains were identified, particularly in relation to appropriate and timely conversations. Positive developments in the care and treatment of advanced COPD include the use of the STIOLTO Respimat inhaler, a brief educative and psychosocial intervention based on cognitive-behavioural therapy, and high-intensity exercise training. There is some evidence regarding the use of technology in end-stage COPD. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Heart rate variability: implications for perioperative anesthesia care.

Purpose of review: Heart rate variability (HRV) is a measure of the balance between both the parasympathetic and sympathetic nervous system and may provide useful information for anesthesia care providers. HRV may offer predictive information about critically ill and operative patients. Further, HRV collection provides real-time information of patient autonomic nervous system status and may allow tailoring of the analgesia for patients in the ICU and operating room. Recent findings: Reduced and abnormal resting HRV predict sudden and nonsudden cardiac death. Recent evidence shows that decreased HRV correlates with worsened outcomes in both trauma patients and patients with sepsis, as well as the risk of developing hypotension after induction of general anesthesia and placement of intrathecal local anesthesia. In addition, HRV appears to provide an accurate assessment of the nociception-analgesia balance in deeply sedated ICU patients and those under general anesthesia. Summary: No study has assessed the prognostic value of preoperative HRV in patients presenting for surgery. Use of HRV for patient risk stratification and intraoperative analgesia management may allow tailored perioperative care and improved outcomes. If intraoperative HRV data leads to decreased perioperative opioid use, opioid-related adverse events, a serious perioperative issue, may be decreased. Clinical Trials Registration: Not applicable Copyright (C) 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Difficult airway management and training: simulation, communication, and feedback.

Purpose of review: Successful and sustainable training and learning of the management of difficult and normal airway is essential for all clinically active anesthesiologists. We emphasize the importance of a continuously updated learning and training environment based on actual knowledge, best available equipment, standardized procedures, and educational theory. Recent findings: In the past, most of the training were based on 'learning by doing' under the supervision of superiors or experienced colleagues. This has been recognized as insufficient and training has evolved to its recent level by structuring it into technical, methodological, and behavioral components. Additionally, a large part of it has been shifted away from learning on patients to simulated scenarios in designated environments. The contents, structure, components, and succession of components have been refined according to the steadily evolving and available instruments. Increasingly, team interaction and behavioral aspects gained more attention and became part of standardized education units that are tailored to the learners' clinical role and level of experience. Summary: We present the details of the Zurich Airway Training and Simulation program, which has been constantly updated to the actual state of knowledge and available equipment. Copyright (C) 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Perioperative management of cardiac rhythm assist devices in ambulatory surgery and nonoperating room anesthesia.

Purpose of review: Patients with cardiac implantable electronic devices (CIEDs) frequently undergo various surgical procedures and in the past perioperative management involved only placing magnet over the device. New programming features, development of implantable cardiac defibrillator (ICD), cardiac resynchronization therapy, and increasing complexity of the operating room equipment have led to new sources of electromagnetic interference (EMI). A comprehensive understanding of the CIED is necessary to provide a timely and optimal care to the patients. Recent findings: Technological advancements and direct implantation of the transvenous implantable cardiac defibrillators into the heart have led to less clear lines between the pacemakers and the ICD. Subcutaneous ICD as well as the leadless transcatheter deployed intracardiac pacemaker development has complicated the issue further. Summary: Rapidly developing technologies and increasing number of patients with these devices coming for noncardiac surgeries necessitate continuous education of the anesthesia team regarding perioperative management of such devices. Copyright (C) 2017 YEAR Wolters Kluwer Health, Inc. All rights reserved.

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Green Teeth in the Primary and Permanent Dentition

A 9-year-old girl was admitted to the oral pathology department presenting green teeth coloration. The patient's medical history noted that after 20 days of birth she was diagnosed with biliary atresia. She underwent surgery to restore the bile flow (hepatoportoenterostomy); however, she had persistent conjugated hyperbilirubinemia. At 3 years of age, she underwent liver transplantation and progressed to a thrombosis of the portal vein and splenomegaly. Medications at presentation included tacrolimus as immunosuppressive agent to prevent organ transplant rejection and prednisone.

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Look Beyond a Strange Smile: A Clue to Renal Disease

A 14-year-old boy presented at the emergency department after having a generalized tonic–clonic seizure associated with severe obtundation of sensorium in the postictal period. Blood pressure was very high (180/100 mm Hg). He had previously suffered from polyuria and polydipsia for an unknown duration. Secondary nocturnal enuresis had been present since 8 years of age, after 5 years of dryness.

http://ift.tt/2wn2c9S

An Impressive, Sudden, and Purpuric Eruption

An afebrile 18-month-old boy, previously healthy, presented with an asymptomatic purpuric eruption for 1 day. Physical examination showed large, purpuric, medallion-shaped blanching patches on the cheeks and auricles, and multiple erythematous, targetoid, and coalescing patches in limbs (Figure, A-D). Apart from a slight rhinitis, the rest of clinical and routine laboratory examinations were unremarkable, including coagulation tests. C-reactive protein was slight elevated (1.5 mg/dL). A diagnosis of acute hemorrhagic edema of infancy was made.

http://ift.tt/2xGsdm0

Recruitment and Retention: Recommendations from the Association of Medical School Pediatric Department Chairs Education Committee and the Council on Medical Student Education in Pediatrics Task Force on Community Preceptors

The traditional model of community-based education for medical students1,2 is under threat.3-5 The Association of American Medical Colleges6 and the Alliance for Clinical Education7 have described the problem and suggested strategies to recruit and retain volunteer community preceptors. The Association of Medical School Pediatric Department Chairs Education Committee and the Council on Medical Student Education in Pediatrics (COMSEP) formed a task force of leaders from both organizations to address preceptor need in pediatrics.

http://ift.tt/2xH87YU

Physical Fitness and Metabolic Syndrome in Children with Repaired Congenital Heart Disease Compared with Healthy Children

To determine whether children who underwent surgery for congenital heart disease (CHD) are as fit as their peers.

http://ift.tt/2wn2ddW

Scalp Lesions in a Pediatric Patient with Hyper IgM Syndrome: Clinical and Histologic Mimicry of Cryptococcus neoformans Infection

We report a case of cutaneous cryptococcosis due to Cryptococcus neoformans in a pediatric patient with hyper IgM syndrome with scalp lesions that resembled tinea capitis on gross examination and mimicked juvenile xanthogranuloma on histologic examination. This case highlights the importance of considering cutaneous cryptococcosis in patients with hyper IgM syndrome.

http://ift.tt/2wn2dKY

Gli1 is a potential cancer stem cell marker and predicts poor prognosis in ductal breast carcinoma

Glioma-associated oncogene homolog 1 (Gli1) maintains the cancer stem cell–like characteristics in various tumors. However, its expression in cancer stem cells (CSC) in ductal breast carcinoma has not been well studied. We aimed to characterize Gli1 as a potential CSC marker and investigate its clinical significance in ductal breast carcinoma. Immunohistochemical staining was used to study the relationship of Gli1 to clinicopathologic features, cell cycle regulation–related genes, and CSC markers.

http://ift.tt/2k74Xul

Phase II neoadjuvant treatment intensification trials in rectal cancer: a systematic review

Multiple phase II trials of neoadjuvant treatment intensification in locally advanced rectal cancer have reported promising efficacy signals but these have not translated into improved cancer outcomes in phase III trials. Improvements in phase II trial design are needed to reduce these false positive signals. This systematic review evaluated the design of phase II trials of neoadjuvant long-course (chemo)radiotherapy treatment intensification in locally advanced rectal cancer.

http://ift.tt/2x0rNVD

A systematic review of normal-tissue complication models relevant to standard fractionation radiation therapy of the head and neck region published after the QUANTEC reports

There has recently been an increasing interest in model-based evaluation and comparison of different treatment options in radiation oncology studies. This is partly driven by the considerable technical advancements in radiation therapy of the last decade, leaving radiation oncologists with a multitude of options to consider. In lieu of randomized trials comparing all of these different treatment options for varying indications, which is unfeasible, treatment evaluations based on normal-tissue complication probability (NTCP) models offer a practical alternative.

http://ift.tt/2yw76lq

The incidence of lymph node metastasis in early gastric cancer according to the expanded criteria in comparison with the absolute criteria of the Japanese Gastric Cancer Association: a systematic review of the literature and meta-analysis

Japanese criteria for curative endoscopic resection of early gastric cancer initially included non-ulcerated, well-differentiated mucosal lesions ≤2 cm in diameter, known as the absolute criteria. Subsequently, these indications were expanded to include larger, ulcerated and undifferentiated mucosal lesions as well as differentiated lesions with slight submucosal invasion (SM1). Whether patients meeting the expanded criteria (Ex) can be safely managed without gastrectomy and lymph node dissection has been controversial.

http://ift.tt/2wmDgza

Gemtuzumab Receives New FDA Approval for Acute Myeloid Leukemia

FDA has approved gemtuzumab ozogamicin (Mylotarg™) for adults with newly diagnosed CD33-positive AML and patients 2 years and older with CD33-positive AML who have experienced a relapse or whose disease has not responded to initial treatment.

http://ift.tt/2xA9NWq

The Knob Supination Task: A Semi-automated Method for Assessing Forelimb Function in Rats

This manuscript describes a semi-automated task that quantifies supination in rats. Rats reach, grasp, and supinate a spherical manipulandum. The rat is rewarded with a pellet if the turn angle exceeds a criterion set by the user. This task increases throughput, sensitivity to injury, and objectivity compared to traditional tasks.

http://ift.tt/2wZB316

Endovascular Graft Systems: Letter to Health Care Providers - Type III Endoleaks Associated with Use

Audience: Risk Manager, Surgery, Cardiology, Radiology [Posted 09/28/2017] ISSUE: The FDA is evaluating recent information regarding Type IIIa and IIIb endoleaks with the use of endovascular graft systems indicated for a procedure known as...

http://ift.tt/2wZDzPU

Sample Preparation for Mass Spectrometry-based Identification of RNA-binding Regions

We describe a protocol to identify RNA-binding proteins and map their RNA-binding regions in live cells using UV-mediated photocrosslinking and mass spectrometry.

http://ift.tt/2hyPiD1

Endovascular Graft Systems: Letter to Health Care Providers - Type III Endoleaks Associated with Use

Audience: Risk Manager, Surgery, Cardiology, Radiology [Posted 09/28/2017] ISSUE: The FDA is evaluating recent information regarding Type IIIa and IIIb endoleaks with the use of endovascular graft systems indicated for a procedure known as...

http://ift.tt/2wZDzPU

Semiautomated Longitudinal Microcomputed Tomography-based Quantitative Structural Analysis of a Nude Rat Osteoporosis-related Vertebral Fracture Model

The goal of this protocol is to generate a nude rat osteoporosis-related vertebral compression fracture model that can be longitudinally evaluated in vivo using a semiautomated microcomputed tomography-based quantitative structural analysis.

http://ift.tt/2wZmXwI

In Vitro Bioluminescence Assay to Characterize Circadian Rhythm in Mammary Epithelial Cells

An in vitro bioluminescence assay to determine cellular circadian rhythm in mammary epithelial cells is presented. This method utilizes mammalian cell reporter plasmids expressing destabilized luciferase under the control of the PERIOD 2 gene promoter. It can be adapted to other cell types to evaluate organ-specific effects on circadian rhythm.

http://ift.tt/2k4rt6S

Application of microscope-based scanning software (Panoptiq) for the interpretation of cervicovaginal cytology specimens

BACKGROUND

Digital pathology increasingly has been gaining the attention of pathologists worldwide. However, the application of digital cytology by Panoptiq (ViewsIQ, Vancouver, Canada) microscope-based scanning software is relatively unexplored. Panoptiq enables the operator to combine low-power panoramic digital images with z-stacks at regions of interest with a significantly smaller image size than that obtained by whole-slide scanning. The current study aimed to evaluate the feasibility of the use of Panoptiq in the digital interpretation of cervicovaginal cytology specimens in comparison with conventional light microscopy.

METHODS

A total of 100 liquid-based cytology slides were selected sequentially. The dotted slides were reviewed and scanned, in which all dotted areas were scanned further by the ×20 objective with z-stacks. The cases were reviewed by 4 pathologists and a cytotechnologist using conventional light microscopy and digital cytology images acquired by Panoptiq and interpreted based on the Bethesda classification system. The washout time was set as 3 weeks. The Cohen kappa coefficient was calculated to measure the agreement between the 2 modalities.

RESULTS

Digital cytology demonstrated an intermodality agreement among 3 observers who had sufficient training in digital pathology at concordance rates between 81% and 90% with kappa values between 0.76 and 0.86, whereas the other 2 observers who did not have sufficient training in digital pathology had lower agreement at a concordance rate of between 56% and 57%, with kappa values between 0.41 and 0.44.

CONCLUSIONS

Panoptiq appears to be feasible for the interpretation of cervicovaginal cytology specimens but requires adequate training in digital pathology. Cancer Cytopathol 2017. © 2017 American Cancer Society.

http://ift.tt/2wYIrcT

Physical Limits on the Precision of Mitotic Spindle Positioning by Microtubule Pushing forces

Tissues are shaped and patterned by mechanical and chemical processes. A key mechanical process is the positioning of the mitotic spindle, which determines the size and location of the daughter cells within the tissue. Recent force and position-fluctuation measurements indicate that pushing forces, mediated by the polymerization of astral microtubules against­ the cell cortex, maintain the mitotic spindle at the cell center in Caenorhabditis elegans embryos. The magnitude of the centering forces suggests that the physical limit on the accuracy and precision of this centering mechanism is determined by the number of pushing microtubules rather than by thermally driven fluctuations. In cells that divide asymmetrically, anti-centering, pulling forces generated by cortically located dyneins, in conjunction with microtubule depolymerization, oppose the pushing forces to drive spindle displacements away from the center. Thus, a balance of centering pushing forces and anti-centering pulling forces localize the mitotic spindles within dividing C. elegans cells.

We discuss microtubule-based mechanisms of the mitotic spindle positioning, a key mechanical process that shapes and patterns tissues. The magnitude of the centering forces indicates that the physical limit on the accuracy and precision of centering is set by the number of contributing microtubules rather than by thermally driven fluctuations.

http://ift.tt/2ftTcZD

The Other Face of an Editor: ADAR1 Functions in Editing-Independent Ways

The RNA editing enzyme ADAR1 seemingly has more functions besides RNA editing. Mouse models lacking ADAR1 and sensors of foreign RNA show that RNA editing by ADAR1 plays a crucial role in the innate immune response. Still, RNA editing alone cannot explain all observed phenotypes. Thus, additional roles for ADAR1 must exist. Binding of ADAR1 to RNA is independent of its RNA editing function. Thus, ADAR1 may compete with other RNA-binding proteins. A very recent manuscript elaborates on this and reports competition of ADAR1 with STAUFEN1, thereby modulating RNA-degradation. ADAR1 is also known to recruit proteins such as DROSHA to nascent transcripts. Still, many open questions remain. For instance, the biological role of the Z-DNA binding domains in ADAR1 is not defined. Moreover, the impact of ADAR1 on the RNA-folding landscape is unclear. In sum, moonlighting functions of ADAR1 may be manifold and have a great impact on the transcriptome.

Adenosine to inosine RNA editing by ADAR1 is mostly known for its role in the innate immune response to help discriminate self from non-self RNA. Here we discuss the other face of ADAR1 that impacts on cellular processes independent of its editing function. These include Staufen-mediated-decay (SMD), mRNA processing, or miRNA maturation.

http://ift.tt/2hygAto

Fused-Ring Acceptors with Asymmetric Side Chains for High-Performance Thick-Film Organic Solar Cells

Abstract

A kind of new fused-ring electron acceptor, IDT-OB, bearing asymmetric side chains, is synthesized for high-efficiency thick-film organic solar cells. The introduction of asymmetric side chains can increase the solubility of acceptor molecules, enable the acceptor molecules to pack closely in a dislocated way, and form favorable phase separation when blended with PBDB-T. As expected, PBDB-T:IDT-OB-based devices exhibit high and balanced hole and electron mobility and give a high power conversion efficiency (PCE) of 10.12%. More importantly, the IDT-OB-based devices are not very sensitive to the film thickness, a PCE of 9.17% can still be obtained even the thickness of active layer is up to 210 nm.

A new fused-ring electron acceptor (IDT-OB), bearing asymmetric side chains, is facilely synthesized for high-efficiency thick-film organic solar cells. The asymmetric structure makes it easier to form ideal phase separation when blended with a polymer donor. Power conversion efficiencies of 10.12% and 8.57% are obtained with the active-layer thicknesses of 130 and 320 nm, respectively.

http://ift.tt/2xAIuLK

Metal-Ion-Modified Black Phosphorus with Enhanced Stability and Transistor Performance

Abstract

Black phosphorus (BP), a burgeoning elemental 2D semiconductor, has aroused increasing scientific and technological interest, especially as a channel material in field-effect transistors (FETs). However, the intrinsic instability of BP causes practical concern and the transistor performance must also be improved. Here, the use of metal-ion modification to enhance both the stability and transistor performance of BP sheets is described. Ag⁺ spontaneously adsorbed on the BP surface via cation–π interactions passivates the lone-pair electrons of P thereby rendering BP more stable in air. Consequently, the Ag⁺-modified BP FET shows greatly enhanced hole mobility from 796 to 1666 cm² V⁻¹ s⁻¹ and ON/OFF ratio from 5.9 × 10⁴ to 2.6 × 10⁶. The mechanisms pertaining to the enhanced stability and transistor performance are discussed and the strategy can be extended to other metal ions such as Fe³⁺, Mg²⁺, and Hg²⁺. Such stable and high-performance BP transistors are crucial to electronic and optoelectronic devices. The stability and semiconducting properties of BP sheets can be enhanced tremendously by this novel strategy.

A simple and effective metal-ion modification strategy based on cation–π interactions is applied to black phosphorus to enhance both its air stability and its transistor performance. Such stable and high-performance black-phosphorus transistors, which are enhanced tremendously by this novel strategy, have large potential in electronic and optoelectronic devices.

http://ift.tt/2xECC1u

Layered-Double-Hydroxide Nanosheets as Efficient Visible-Light-Driven Photocatalysts for Dinitrogen Fixation

Abstract

Semiconductor photocatalysis attracts widespread interest in water splitting, CO₂ reduction, and N₂ fixation. N₂ reduction to NH₃ is essential to the chemical industry and to the Earth's nitrogen cycle. Industrially, NH₃ is synthesized by the Haber–Bosch process under extreme conditions (400–500 °C, 200–250 bar), stimulating research into the development of sustainable technologies for NH₃ production. Herein, this study demonstrates that ultrathin layered-double-hydroxide (LDH) photocatalysts, in particular CuCr-LDH nanosheets, possess remarkable photocatalytic activity for the photoreduction of N₂ to NH₃ in water at 25 °C under visible-light irradiation. The excellent activity can be attributed to the severely distorted structure and compressive strain in the LDH nanosheets, which significantly enhances N₂ chemisorption and thereby promotes NH₃ formation.

Layered-double-hydroxide (LDH) nanosheets are shown to exhibit outstanding visible-light-driven photocatalytic activity for the reduction of N₂ to NH₃ under ambient conditions. Irradiation of CuCr-LDH nanosheets in N₂-saturated water with 500 nm monochromatic light produces NH₃. The excellent activity can be attributed to the severely distorted structure and compressive strain of the LDH nanosheets, promoting NH₃ formation.

http://ift.tt/2xzUDAz

Engineered Ferritin for Magnetogenetic Manipulation of Proteins and Organelles Inside Living Cells

Abstract

Magnetogenetics is emerging as a novel approach for remote-controlled manipulation of cellular functions in tissues and organisms with high spatial and temporal resolution. A critical, still challenging issue for these techniques is to conjugate target proteins with magnetic probes that can satisfy multiple colloidal and biofunctional constraints. Here, semisynthetic magnetic nanoparticles are tailored based on human ferritin coupled to monomeric enhanced green fluorescent protein (mEGFP) for magnetic manipulation of proteins inside living cells. This study demonstrates efficient delivery, intracellular stealth properties, and rapid subcellular targeting of those magnetic nanoparticles via GFP–nanobody interactions. By means of magnetic field gradients, rapid spatial reorganization in the cytosol of proteins captured to the nanoparticle surface is achieved. Moreover, exploiting efficient nanoparticle targeting to intracellular membranes, remote-controlled arrest of mitochondrial dynamics using magnetic fields is demonstrated. The studies establish subcellular control of proteins and organelles with unprecedented spatial and temporal resolution, thus opening new prospects for magnetogenetic applications in fundamental cell biology and nanomedicine.

Magnetic manipulation of intracellular proteins is realized by designing semisynthetic magnetic nanoparticles based on the protein cage ferritin. Demonstrating efficient delivery, intracellular stealth properties, and rapid targeting of organelle structures, the magnetic nanoparticles are applied for the remote manipulation of targeted proteins, as well as for remote-controlled reduction of mitochondrial dynamics.

http://ift.tt/2xFgUue

Solvent-Assisted Micromolding of Biohybrid Hydrogels to Maintain Human Hematopoietic Stem and Progenitor Cells Ex Vivo

Abstract

Array-format cell-culture carriers providing tunable matrix cues are instrumental in current cell biology and bioengineering. A new solvent-assisted demolding approach for the fabrication of microcavity arrays with very small feature sizes down to single-cell level (3 µm) of very soft biohybrid glycosaminoglycan–poly(ethylene glycol) hydrogels (down to a shear modulus of 1 kPa) is reported. It is further shown that independent additional options of localized conjugation of adhesion ligand peptides, presentation of growth factors through complexation to gel-based glycosaminoglycans, and secondary gel deposition for 3D cell embedding enable a versatile customization of the hydrogel microcavity arrays for cell culture studies. As a proof of concept, cell-instructive hydrogel compartment arrays are used to analyze the response of human hematopoietic stem and progenitor cells to defined biomolecular and spatial cues.

A solvent-assisted demolding approach is reported for the fabrication of microcavity arrays from very soft glycosaminoglycan–poly(ethylene glycol) hydrogels with sizes down to the single-cell level. Adhesion ligand conjugation, growth-factor loading, and secondary gel deposition enable a versatile customization, which is demonstrated in experiments with human hematopoietic stem and progenitor cells.

http://ift.tt/2yaRWGj

Selective CO2 Capture and High Proton Conductivity of a Functional Star-of-David Catenane Metal–Organic Framework

Abstract

Network structures based on Star-of-David catenanes with multiple superior functionalities have been so far elusive, although numerous topologically interesting networks are synthesized. Here, a metal–organic framework featuring fused Star-of-David catenanes is reported. Two triangular metallacycles with opposite handedness are triply intertwined forming a Star-of-David catenane. Each catenane fuses with its six neighbors to generate a porous twofold intercatenated gyroid framework. The compound possesses exceptional stability and exhibits multiple functionalities including highly selective CO₂ capture, high proton conductivity, and coexistence of slow magnetic relaxation and long-range ordering.

A metal–organic framework, which represents the rare networks composed of Star-of-David catenanes, is designed. The structural complexity of the unique framework highlights different facets of the same compound. Remarkably, the material shows highly selective CO₂ capture for a molecular-sieving effect, superionic proton conductivity, and coexistence of slow magnetic relaxation and long-range ordering.

http://ift.tt/2yJyxZU

MYC Controls Human Pluripotent Stem Cell Fate Decisions through Regulation of Metabolic Flux

Cliff et al. show that, contrary to prior understanding, a metabolic switch away from glycolysis is not a required step for human pluripotent stem cell differentiation, and that, in fact, differentiation to ectoderm requires maintenance of high glycolytic flux via MYC/MYCN activity, indicating its role as a developmental regulator.

http://ift.tt/2xOfC24

Differentiation of Human Pluripotent Stem Cells into Functional Lung Alveolar Epithelial Cells

Jacob et al. differentiate human pluripotent stem cells (PSCs) into type II alveolar cells (iAEC2s). They find that iAEC2s display many of the functions, transcriptomic features, and surfactant-processing capacities that characterize primary cells. Finally, they derive AEC2s from gene-edited, patient-specific PSCs to model surfactant protein B deficiency in vitro.

http://ift.tt/2fTgpoL

Jak1 Integrates Cytokine Sensing to Regulate Hematopoietic Stem Cell Function and Stress Hematopoiesis

Selective JAK1 inhibition has emerged as a potential strategy for treating autoimmune and hematological diseases. Levine and colleagues show that Jak1 integrates multiple cytokine signals in normal and malignant HSCs to regulate their self-renewal and quiescence, highlighting further potential therapeutic benefits and risks of Jak1 inhibition.

http://ift.tt/2fUrc1S

A large-scale, multi-center serum metabolite biomarkers identification study for the early detection of hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is the third most lethal cancer worldwide. The lack of effective biomarkers for the early detection of HCC results in unsatisfactory curative treatments. Here, metabolite biomarkers were identified and validated for HCC diagnosis. A total of 1448 subjects, mainly including normal controls and patients with chronic hepatitis B virus infection, liver cirrhosis, and HCC were recruited from multi-center in China. Liquid chromatography-mass spectrometry (LC-MS)-based metabolomics methods were used to characterize the subjects' serum metabolic profiles and to screen and validate the HCC biomarkers. A serum metabolite biomarker panel including phenylalanyl-tryptophan and glycocholate, was defined. This panel had a higher diagnostic performance than did α-fetoprotein (AFP) in differentiating HCC from a high-risk population of cirrhosis, such as area under the receiver-operating characteristic curve (AUC) of 0.930, 0.892, 0.807 for panel versus 0.657, 0.725, 0.650 for AFP in the discovery, test and cohort 1 of the validation set, respectively. In the nested case-control study, this panel had high sensitivity (rang 80.0-70.3%) to detect preclinical HCC, and its combination with AFP provided better risk prediction of preclinical HCC before clinical diagnosis. Besides, this panel showed a larger AUC than did AFP (0.866 versus 0.682) to distinguish small-HCC, and 80.6% of the AFP false-negative patients with HCC were correctly diagnosed using this panel in the test set, which was corroborated by the validation set. The specificity and biological relevance of the identified biomarkers were further evaluated using sera from other two cancers and HCC tissue specimens, respectively. Conclusions: The discovered and validated serum metabolite biomarker panel exhibits good diagnostic performance for the early detection of HCC from at-risk populations. This article is protected by copyright. All rights reserved.

http://ift.tt/2fUeNev

Distinct Role of Nuclear Receptor Corepressor 1 Regulated de novo Fatty Acids Synthesis in Liver Regeneration and Hepatocarcinogenesis

Abstract

Means to improve liver regeneration is urgent to be found, but with risks to facilitate the development of tumor. NCoR1 is a co-repressor of nuclear receptors which regulates the expression level of metabolic genes, however, little is known about its potential contribution for liver regeneration and hepatocarcinogenesis. Here, we found liver-specific NCoR1 knock-out(NCoR1^Δhep) dramatically enhances liver regeneration after partial hepatectomy and surprisingly blocks the process of DEN-induced hepatocarcinogenesis. Both RNA-seq and metabolic assay results revealed exclusively improved expression of Fasn and Acc2 in NCoR1^Δhep mice, suggesting the critical role of de novo fatty acids synthesis(FAS) in liver regeneration. Continual enhanced de novo FAS in NCoR1^Δhep mice resulted in overwhelmed ATP and NADPH consumption and increased mitochondrial ROS production, which subsequently attenuated hepatocarcinogenesis through inducing apoptosis of hepatocytes at early stage after DEN administration. Conclusion: NCoR1 functions as a negative modulator for hepatic de novo FAS and mitochondria energy adaptation, playing distinct roles in either regeneration or carcinogenesis. This article is protected by copyright. All rights reserved.

http://ift.tt/2ybiRSa