Response to the Letter to the Editor on “The Effectiveness of Technology-Supported Exercise Therapy for Low Back Pain: A Systematic Review”

No abstract available

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A Risk Scoring System for the Prediction of Functional Deterioration, Institutionalization, and Mortality Among Medicare Beneficiaries

Objective We sought to develop a risk scoring system for predicting functional deterioration, institutionalization, and mortality. Identifying predictors of poor health outcomes informs clinical decision-making, service provision, and policy development to address the needs of persons at greatest risk for poor health outcomes. Design This is a cohort study with 21,257 community-dwelling Medicare beneficiaries 65 yrs and older who participated in the 2001–2008 Medicare Current Beneficiary Survey.  Derivation of the model was conducted in 60% of the sample and validated in the remaining 40%. Multinomial logistic regression model generated β coefficients, which were used to create a risk scoring system. Our outcome was instrumental activity of daily living stage transitions (stable/improved function and functional deterioration), institutionalization, or mortality for 2 yrs of follow-up. Results A total of 18 factors were identified for functional deterioration (P

https://ift.tt/2POBujH

Rehabilitation for Cancer Survivors: How We Can Reduce the Healthcare Service Inequality in Low- and Middle-Income Countries

Cancer diagnosis often substantially affects patient's physical, psychological, and emotional status. Most patients with cancer experience declining of energy, activity levels, social-cultural participation, and relationships. In addition, cancer progression and adverse effects of aggressive cancer treatment often cause debilitating pain, fatigue, weakness, joint stiffness, depression, emotional instability, limited mobility, poor nutritional status, skin breakdown, bowel dysfunction, swallowing difficulty, and lymphedema leading into functional impairment and disability that can be addressed through rehabilitation care. Comprehensive care models by involving cancer rehabilitation have resulted in significant improvement of patient's quality of life. Although cancer rehabilitation has been implemented in many high-income countries, it is either not yet or suboptimally delivered in most low- and middle-income countries. In this review, we discussed gaps regarding cancer rehabilitation services and identified opportunities to improve quality of cancer care in developing countries. Future collaborations among international organizations and stakeholders of health care delivery systems are required to initiate and improve high-quality cancer rehabilitation in the developing countries.

https://ift.tt/2xpJWPy

Clinical Improvements Are Not Explained by Changes in Tendon Structure on Ultrasound Tissue Characterization After an Exercise Program for Patellar Tendinopathy

Objectives The aim of this study was to investigate the effects of a 4-wk in-season exercise program of isometric or isotonic exercises on tendon structure and dimensions as quantified by ultrasound tissue characterization (UTC). Design This was a randomized clinical trial. Volleyball and basketball players (16–31 yrs, n = 29) with clinically diagnosed patellar tendinopathy were randomized to a 4-wk isometric or isotonic exercise program. The programs were designed to decrease patellar tendon pain. A baseline and 4-wk UTC scan was used to evaluate change in tendon structure. Results No significant change in tendon structure or dimensions on UTC was detected after the exercise program despite patellar tendinopathy symptoms improving. The percentage and mean cross-sectional area of aligned fibrillar structure (echo types I + II) (Z = −0.414, P = 0.679) as well as disorganized structure (echo types III + IV) (Z = −0.370, P = 0.711) did not change over the 4-wk exercise program. Change in tendon structure and dimensions on UTC did not differ significantly between the groups. Conclusion Structural properties and dimensions of the patellar tendon on UTC did not change after a 4-wk isometric or isotonic exercise program for athletes with patellar tendinopathy in-season, despite an improvement in symptoms. It seems that structural improvements are not required for a positive clinical outcome.

https://ift.tt/2PItWiu

Efficacy of Bedside Respiratory Muscle Training in Patients With Stroke: A Randomized Controlled Trial

Objective Inspiratory and expiratory muscles are important for effective respiratory function. This study aimed to investigate the efficacy of bedside respiratory muscle training on pulmonary function and stroke-related disabilities in stroke rehabilitation. Design Patients with stroke (N = 40) in a rehabilitation unit were randomly assigned to either the intervention group (n1 = 20) or the control group (n2 = 20). Both groups participated in a conventional stroke rehabilitation program. During the study period, the intervention group received bedside respiratory muscle training twice a day for 3 wks. The respiratory muscle training consisted of (1) a breath stacking exercise, (2) inspiratory muscle training, and (3) expiratory muscle training. The primary outcomes were measures of pulmonary function: forced vital capacity, forced expiratory volume in 1 sec, and peak flow. Secondary outcomes were stroke-related disabilities assessed using the National Institutes of Health Stroke Scale, Modified Barthel Index, Berg Balance Scale, Fugl-Meyer Assessment, the Korean Mini-Mental State Examination, and pneumonia incidence. Results Pulmonary function was significantly improved in the intervention group after 3 wks of respiratory muscle training (P

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Association of Activities of Daily Living With Load During Step Ascent Motion in Nursing Home–Residing Elderly Individuals: An Observational Study

Objective This study aimed to examine the association of independence in activities of daily living with the loads during step ascent motion and other motor functions in 32 nursing home–residing elderly individuals. Design Independence in activities of daily living was assessed by using the Functional Independence Measure. The loads at the upper (i.e., pulling up) and lower (i.e., pushing up) levels during the step ascent task was measured on a step ascent platform. Hip extensor, knee extensor, plantar flexor muscle, and quadriceps setting strengths; lower extremity agility using the stepping test; and hip and knee joint pain severities were measured. One-legged stance and functional reach distance for balance and maximal walking speed, timed up-and-go time, five-chair-stand time, and step ascent time were also measured to assess mobility. Results Stepwise regression analysis revealed that the load at pushing up during step ascent motion and timed up-and-go time were significant and independent determinants of Functional Independence Measure score. Functional Independence Measure score decreased with decreased load at pushing up and increased timed up-and-go time. Conclusions The study results suggest that depending on task specificity, both one step up task's push-up peak load during step ascent motion and timed up-and-go can partially explain activities of daily living's Functional Independence Measure score in nursing home–residing elderly individuals. Lower extremity muscle strength, agility, pain, or balance measures did not add to the prediction.

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Effect of Polydeoxyribonucleotide Injection in a Patient With Carpal Tunnel Syndrome

Ultrasound-guided corticosteroid injection into the carpal tunnel is widely performed for the management of carpal tunnel syndrome. However, this injection may worsen the condition in patients with type 2 diabetes mellitus. Polydeoxyribonucleotide was recently recognized as a substitute for corticosteroid because of its anti-inflammatory effects. A 41-yr-old woman with type 2 diabetes mellitus was admitted to our rehabilitation clinic with a 1-mo history of numbness and tingling in her right hand and first three fingers tips. She declined corticosteroid treatment because of a previous episode of uncontrolled blood glucose levels after corticosteroid injection. Therefore, ultrasound-guided polydeoxyribonucleotide injections into the carpal tunnel were carried out. At the 6-mo follow-up, the patient demonstrated an improvement in the carpal tunnel syndrome symptoms without any complications. Thus, polydeoxyribonucleotide injections into the carpal tunnel can be an alternative to corticosteroid injections for carpal tunnel syndrome if there are limitations because of adverse effects of the latter.

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Femoral Artery Blood Flow and Microcirculatory Perfusion During Acute, Low-Level Functional Electrical Stimulation in Spinal Cord Injury

Objective Functional electrical stimulation (FES) may help to reduce the risk of developing macrovascular and microvascular complications in people with spinal cord injury. Low-intensity FES has significant clinical potential because this can be applied continuously throughout the day. This study examines the acute effects of low-intensity FES using wearable clothing garment on vascular blood flow and oxygen consumption in people with spinal cord injury. Design This was a cross-sectional observation study. Methods Eight participants with a motor complete spinal cord injury received four 3-min unilateral FES to the gluteal and hamstring muscles. Skin and deep femoral artery blood flow and oxygen consumption were measured at baseline and during each bout of stimulation. Results Femoral artery blood flow increased by 18.1% with the application of FES (P = 0.02). Moreover, femoral artery blood flow increased further during each subsequent block of FES (P = 0.004). Skin perfusion did not change during an individual block of stimulation (P = 0.66). Skin perfusion progressively increased with each subsequent bout (P 0.05). Conclusion Low-intensity FES acutely increased blood flow during stimulation, with a progressive increase across subsequent FES bouts. These observations suggest that continuous, low-intensity FES may represent a practical and effective strategy to improve perfusion and reduce the risk of vascular complications.

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The Power of Doppler in the Popliteal Fossa: Sonographic Diagnosis of a Fibular Nerve Neurofibroma in a Patient With Posterior Knee Swelling

No abstract available

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Evidence of the Homeostatic Regulation With the Combination of Transcranial Direct Current Stimulation and Physical Activity

Background Transcranial direct current stimulation (tDCS) can optimize beneficial effects induced by motor practice in patients with neurological disorders. However, possibly because of homeostatic regulation, the conditioning effects of tDCS are often imprecise and variable, limiting its therapeutic application. Objective The aim of the study was to explore the magnitude and direction of the after effects induced by physical activity (PA) on tDCS-preconditioned cortical excitability (CE). Design First, a crossover experiment was performed with 12 subjects to determine whether a single session of low-, moderate-, and high-intensity PA on a treadmill modulates the motor CE measured by transcranial magnetic stimulation. In a second crossover experiment, we investigated long-lasting changes (until 90 mins) of the effects induced by PA (with intensities defined by the first experiment) on motor CE after the subject had been preconditioned by tDCS (using different polarities). Results and Conclusions In experiment 1, we found that high- and moderate-intensity PA modulate the CE. Experiment 2 demonstrated that preconditioning the CE using tDCS homeostatically changes the direction and magnitude of after effects induced by subsequent PA plasticity caused by motor activity. In conclusion, the results suggest that the direction of after effects induced by the combination of physical exercise with tDCS on the CE is regulated within a physiologically defined range.

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Evidence-Based Physiatry: Clinical Practice Guideline Noninvasive Treatments for Low Back Pain

No abstract available

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Two-Year Longitudinal Changes in Lower Limb Strength and Its Relation to Loss in Function in a Large Cohort of Patients With Duchenne Muscular Dystrophy

Objective The main objective of this study was to examine the effect of disease on strength in two functionally important lower limb muscles for a period of 2 yrs in children with Duchene muscular dystrophy. Design Seventy-seven Duchene muscular dystrophy children participated in this study. Plantar flexors, knee extensors, strength, and performance on timed tests (6-min walk, 4-stairs, 10-m walk, supine-up) were assessed yearly for 2 yrs. Multivariate normal regression was used to assess changes in strength over time in the Duchene muscular dystrophy group. Spearman correlations were computed to examine relationship between strength and function. Results Normalized plantar flexor and knee extensor strength showed a significant decrease (P

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Successful First Gait of a Child With Hip-Disarticulation Prosthesis

An infant boy underwent hip disarticulation for infantile fibrosarcoma immediately after birth. His rehabilitation began when he was 4 mos old and involved training with his left (residual) leg. He could stand with support at 12 mos. His initial prosthesis fitting was performed at the age of 13 mos. He could stand and walk with support at 15 mos of age and could walk with no additional support and go up and down stairs at 2 yrs. A single-axis prosthetic knee joint was introduced at the age of 2 yrs 3 mos. His first gait using a hip prosthesis was successful, and his prosthesis was replaced at appropriate intervals with no major problems. The authors believe that the key to achieving a successful prosthetic gait in children is good communication among the medical team, which should comprise an orthopedic doctor, rehabilitation doctor, nurse, physical therapist, prosthetist/orthotist, and the patient's parents.

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Corticosteroid Injections Into Lumbar Facet Joints: A Prospective, Randomized, Double-Blind Placebo-Controlled Trial

Background Corticosteroid injections into the intra-articular zygapophysial (z-joints) are frequently used to treat this cause of low back pain. No studies have been done on the efficacy of intra-articular corticosteroids in those with z-joint pain confirmed by dual comparative medial branch blocks. Objective The aim of the study was to determine whether an injection of a corticosteroid into lumbar z-joints is effective in reducing pain and the need for radiofrequency neurotomy. Methods This is a double-blind, prospective, randomized, placebo-controlled trial. The study was conducted in Academic Medical Center. Twenty-eight subjects with z-joint pain confirmed by medial branch blocks were included in the study. Subjects with confirmed z-joint pain via dual comparative medial branch block were randomized to receive either intra-articular corticosteroid (triamcinolone 20 mg) or saline via fluoroscopic guided injection. Results No statistically significant difference in the need for radiofrequency neurotomy (radiofrequency neurotomy) between the groups, with 75% (95% confidence interval = 50.5%–99.5%) of the saline group vs. 91% (95% confidence interval = 62.3%–100%) of the corticosteroid group receiving radiofrequency neurotomy. There is no difference in mean time to radiofrequency neurotomy between saline (6.1 wks) and corticosteroid (6.5 wks) groups. There is a need for radiofrequency neurotomy. Conclusions Corticosteroid injections into the lumbar z-joints were not effective in reducing the need for radiofrequency neurotomy of the medial branches in those with z-joint pain confirmed by dual comparative medial branch blocks.

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Exercise Therapy for Low Back Pain: A Systematic Review

No abstract available

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Cost-Effectiveness Analysis of Routine Venous Doppler Ultrasound for Diagnosis of Deep Venous Thrombosis at Admission to Inpatient Rehabilitation

Objective The aims of the study were to identify whether timing of venous thromboembolism diagnosis is associated with differences in patient outcomes and to perform a cost-effectiveness analysis of routine venous Doppler ultrasound at admission to inpatient rehabilitation, taking into account costs associated with prolonged inpatient rehabilitation length of stay, and development of pulmonary embolism. Design This was a retrospective cohort study of 2312 consecutive patient discharges from a single inpatient rehabilitation facility for an 18-mo period. Cost-effectiveness model was built using TreeAge Healthcare Pro. The base case was constructed using probabilities and inpatient rehabilitation length of stay identified from retrospective analysis. Cost of Doppler ultrasound was obtained through the literature, and daily inpatient rehabilitation cost was obtained from the study institution. Results Venous thromboembolism was diagnosed in 6.6% of patients. Asymptomatic patients diagnosed with venous thromboembolism on screening Doppler ultrasound had shorter inpatient rehabilitation length of stay (P = 0.045) and lower rate of pulmonary embolism (P

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An Uncommon Cause of Upper Limb Pain: Cervical Perineural (Tarlov) Cyst Chain

No abstract available

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Delirium Screening and Management in Inpatient Rehabilitation Facilities

Delirium is an acute and fluctuating disturbance in cognition attention and awareness that is often a reflection of abnormal physiological condition of an individual. Delirium is highly prevalent among an older population and is associated with high mortality, poor medical and functional outcomes, and high healthcare cost. Delirium often has iatrogenic triggers, and it has been recognized as a quality indicator of healthcare organizations. Despite its high prevalence and significance, more than 50% of the delirium cases are underrecognized by healthcare professionals and remained untreated. Most patients in inpatient rehabilitation facilities are older adults with multiple risk factors for delirium including operation, intensive care stay, multiple co-morbidities, and impaired mobility. Early detection, intervention, and primary prevention of delirium will allow patients to avoid additional morbidities and reach their maximum functional potential during their rehabilitation stay. After the systematic implementation of delirium screening in our inpatient rehabilitation facility, we found that 10.3% of patients were screened positive for delirium at admission. This review discusses the systematic implementation of screening and intervention for delirium as well as the epidemiology of delirium to increase the awareness and guide clinical practice for clinicians in inpatient rehabilitation facilities.

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Ultrasound-Guided Injection of Botulinum Toxin for Cricopharyngeal Dysphagia

No abstract available

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An Ethnography of Breastaurant Masculinity: Themes of Objectification, Sexual Conquest, Male Control, and Masculine Toughness in a Sexually Objectifying Restaurant

Abstract

The present study is based on a 2-year participant-observer ethnography of a group of men in a "breastaurant" to characterize the unique masculinity features that environment evokes. Currently, whereas some research examines sexually objectifying restaurant environments regarding their impacts upon women in those spaces, no known scholarly attention has been given to men and masculinities in these environments. Through thematic analysis of table dialogue supplemented by brief unstructured interviews, I identify four major and one minor theme of "breastaurant masculinity" as distinctive to that environment. These include sexual objectification, sexual conquest, male control of women, masculine toughness, and (as a minor theme) rationalizations for why men frequent breastaurants. Following recent trends in masculinities research, my study interprets the breastaurant as a type of male preserve that erects a local pastiche hegemony in which these themes gain protected status. It also theorizes that the unique interactive environment of the breastaurant between (mostly) male patrons and attractive female servers who provide heterosexual aesthetic labor to the patrons, primarily in the form of ersatz sexual availability, produces these masculinity features. Given their current rapid expansion and popularity within masculine subcultures, the breastaurant therefore becomes an important site for critical masculinities research. Practice implications are discussed for management and counseling professionals who aim to improve outcomes in social and professional situations for both women and men.

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Cutaneous angioleiomyoma of the auricle: a painless variant of a painful tumour

Cutaneous angioleiomyomas (ALMs) are uncommon benign tumours of the skin which derive from the smooth muscle layer of dermal blood vessels. They usually present as tender nodules in the fifth or sixth decade of life, predominantly in the legs of females. These tumours rarely present on the head and neck, especially the ear. Head and neck ALMs differ from their more common leg counterparts in that they are painless. Additionally, they do not manifest with a female predominance. Herein, a new case of a painless auricular ALM in a 63-year-old man is reported.

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Genitalia self-mutilation commanded by hallucinations: a psychointensive case of Klingsor syndrome

Description 

One of the world's rarest cases recorded up to date stands a case of hallucination influenced genitalia self-mutilation (GSM). There are just 13 cases recorded on PubMed till date. What and who is Klingsor? It was derived from the name of a character in Parsifal (a German opera) who had engaged in the act of self-castration for gaining entry into the prestige brotherhood of the Knights of the Holy Grail. In one of the first recorded cases in 1990, the author argued that the term 'Klingsor' be applied to all cases of GSM to patients of psychotic illness and not just religious conflicts.1 Some literatures call this syndrome as Skoptic syndrome.

Various surveys done by psychologists found psychosis beneath the cases of men carrying out autocastration. One of the most famous cases documented of Thomas Corbett, the man behind the assassination of John Wilkes Booth and...

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Primary intratracheal schwannoma resected during bronchoscopy using argon plasma coagulation

A 63-year-old man presented with intermittent, progressively worsening dyspnoea associated with cough and blood-tinged sputum. Initial work-up showed left axis deviation on ECG, chest X-ray with an elevated left hemidiaphragm and a non-contrast CT chest that showed a multilobulated mass in the proximal trachea. Bronchoscopy showed a whitish-appearing lesion, which was then sampled and partially resected with pathology showing a schwannoma with no malignant cells. He felt partial relief post procedure; however, he presented a month later with similar symptoms of dyspnoea and a repeat CT scan showed enlargement of the mass in the same location. The patient underwent another flexible bronchoscopy and resection with argon plasma coagulation (APC)/electrocautery snare. APC/electrocautery is an effective interventional bronchoscopy technique that can be used to resect endoluminal lesions or extraluminal lesions that have infiltrated into the airway using flexible/rigid bronchoscopy. It is more cost-effective, safe, works well with vascular lesions and achieves excellent haemostasis as compared with Nd:YAG lasers.

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A rare cause of ascites in a renal transplant recipient

Thirty-five-year-old man, underwent renal transplantation 4 years back and was doing well. He now presented with complaints of ascites with engorged neck veins and dyspnoea on exertion for last 6 months. Examination showed elevated jugular venous pressure with two prominent descents, high pitched diastolic heart sound (pericardial knock). Echocardiography showed characteristic features of thickened pericardium, septal bounce, expiratory flow reversal in hepatic veins and phasic variation of mitral inflow, suggestive of constrictive pericarditis. The patient was started on empirical antitubercular therapy and diuretics. The patient symptomatically improved, but in view of persisting constrictive physiology he was planned for pericardiectomy.

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Dental management of a patient with 22q11.2 deletion syndrome (22q11.2DS)

22q11.2 deletion syndrome (22q11.2DS) is one of the most common microdeletion syndromes, with an incidence of approximately 1/2000–1/4000 live births; it is thought to be mainly attributable to a de novo deletion. The clinical phenotype of this syndrome is highly variable. Certain craniofacial and oral features are common to most patients with 22q11.2DS, including a high prevalence of dental caries; abnormalities of tooth shape, eruption and number; and enamel defects such as hypomineralisation and hypoplasia. This report focuses on the dental features and management of an 8-year-old boy with 22q11.2DS. Dental treatments were carried out under general anaesthesia. In summary, facial dysmorphism and common dental manifestations are typically noticeable in patients with this syndrome. Therefore, dentists need to be aware of the dental features of this condition in order to refer them to the adequate specialists. Cooperation among and experience with different specialties are mandatory to improve quality of life for patients with 22q11.2DS.

https://ift.tt/2QGUH88

Mid-ventricular takotsubo cardiomyopathy triggered by major depressive disorder after abortion

Description 

A 28-year-old gravida 7 para 5 woman presented from an outlying facility with non-radiating, crushing, severe left-sided chest pain. She was initially treated for a non-ST elevation myocardial infarction with ECG evidence of T wave inversions in leads II, III, aVF, V5, V6 and an abnormal troponin level at 0.56 ng/mL. Accordingly, left heart catheterisation was performed emergently and revealed normal coronary arteries without any obstruction (figure 1). Left ventriculography showed mid-ventricular hypokinesis with hyperdynamic apical and basal wall contraction, consistent with a mid-ventricular takotsubo cardiomyopathy (TCM) (video 1). The ejection fraction was estimated at 30%–35%.

Figure 1

Coronary angiogram showing normal coronary arteries. (A) Left anterior oblique 30 view. (B) Right anterior oblique 10 cranial 40 view. (C) Left anterior oblique 45 caudal 25 view.

Video 1

Left ventriculogram.

Medical history was significant for an elective abortion...

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A case of young diabetes and parasuicide

Wolfram syndrome is a rare monogenic cause of juvenile onset diabetes mellitus. It is a non-autoimmune, insulin-deficient state with concurrent or consequent optic atrophy. Here we depict the case of a 16-year-old young girl afflicted with this condition, who presented with parasuicide on a background of depressive disorder. The aetiology of this presentation was attributable to multiple physical ailments and a genetic predisposition conferred by the disease-causing mutation for which she tested positive. She was managed with intensive insulin therapy and specific psychotherapy. Her case highlights the importance of recognising and addressing these comorbidities associated with Wolfram syndrome, so as to curtail disastrous consequences.

https://ift.tt/2QHv4nQ

Subperiosteal haematoma of the orbit secondary to frontal sinusitis

Reported is the case of a 79-year-old woman initially diagnosed with periorbital abscess on the background of a recent upper respiratory tract infection. Unexpectedly, intraoperative findings were that of a haematoma rather than an abscess. Subperiosteal orbital haematoma (SOH) is an extremely rare complication of rhinosinusitis. In contrast to the more common periorbital abscess, it is seldom listed as a complication of sinusitis. A review of reported cases suggests an older patient demographic are affected by SOH in contrast to periorbital abscess which typically affects paediatric patients. Given current demographic trends toward an older patient population with multiple comorbidities, failure to consider SOH as a differential will have important implications on preoperative workup, perioperative care and final outcome for patients. We present this case as a reminder of a rare but important complication of a common disease.

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Custom 3D-printed finger proximal phalanx as salvage of limb function after aggressive recurrence of giant cell tumour

Giant cell tumours (GCT) of the finger phalanges are extremely rare but have a high rate of recurrence. This report details the case of a GCT of the proximal phalanx of the fourth finger in a 64-year-old man. The patient was initially subjected to systemic neoadjuvant denosumab treatment, and subsequent aggressive curettage, sparing of the articular joints, local cryotherapy and autologous intercalary fibular bone graft. Finger function after surgery was considered satisfactory, despite limited proximal interphalangeal (PIP) joint motion. Aggressive local GCT recurrence was noted at the 32-month follow-up, with entire articular and diaphyseal phalangeal destruction. The patient refused amputation and, after analysing several reconstruction options, he was treated by entire en bloc resection and reconstruction employing a 3D-printed custom titanium implant. At the 24-month follow-up, the patient is free of disease and pain, and has a stable finger, good metacarpal–phalangeal joint motion, fusion of the PIP joint, a good Musculoskeletal Tumour Society score, and functional ability.

https://ift.tt/2QMO98e

Suspicious breast pseudocalcifications

Description 

We present a follow-up case of an invasive right ductal breast carcinoma in a 72-year-old woman.

A follow-up mammography study (figure 1) performed 1 year after right lumpectomy (wide local excision) shows postsurgical changes in the right breast and reveals 'de novo' coarse/amorphous microcalcifications in the left breast axis. Some of these calcifications show radiolucent centre, and can only be depicted in the craniocaudal mammographic images, raising concern for hypothetic cutaneous location, although presenting suspicious features.

Figure 1

Mammographic images showing postlumpectomy (wide local excision) changes in the right upper outer quadrant and coarse and amorphous calcifications in the left breast. Blue square shows the magnification of the calcifications, revealing some calcifications with radiolucent centre.

Cancer biomarkers and clinical status were unremarkable.

An ultrasound (US) evaluation was further advised. The patient was told not to apply any cream, lotion or deodorant on...

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Severe pulmonary hypertension associated with hepatic arteriovenous malformation in a patient with hereditary haemorrhagic telangiectasia

We report a case of 46-year-old Asian woman with a history of recurrent epistaxis who presented with dyspnoea on exertion. Physical examination revealed mucocutaneous telangiectasias and signs of heart failure. Further evaluation showed huge hepatic arteriovenous malformation and severe pulmonary hypertension. This case demonstrates an uncommon manifestation of hereditary haemorrhagic telangiectasia presented with severe pulmonary hypertension.

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Primary peritoneal hepatoid adenocarcinoma: a diagnostic and therapeutic conundrum in patients with gastrointestinal bleeding

Description 

A 50-year-old man with a history of iron-deficiency anaemia and fatty liver disease presented to the emergency department complaining of black tarry stools with associated weakness and shortness of breath for 1 week. At presentation, contrast-enhanced CT revealed multiple hypervascular masses in the abdomen and pelvis with the largest lesion located in the right lower quadrant, abutting the right psoas muscle (figure 1). Laboratory evaluation demonstrated a haemoglobin level of 5.5 g/dL (normal, 13.5–17.5 g/dL). Upper endoscopy showed a mass, which was making an extrinsic impression into the stomach (figure 2). Colonoscopy was unremarkable for abnormalities. Endoscopic ultrasound-guided fine-needle aspiration (FNA) of the lesion adjacent to the stomach was performed using a 22-gauge needle (Expect Slimline; Boston Scientific, Natick, Massachusetts, USA). The FNA was positive for metastatic carcinoma with hepatic features. Furthermore, capsule endoscopy identified blood clots surrounding the multiple, small intestinal masses. These lesions were...

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Endogenous bacterial endophthalmitis and subretinal abscess complicating diabetic ketoacidosis

Description 

A 26-year-old Lithuanian man with type 1 diabetes, diagnosed at aged 14, presented to the emergency department with shortness of breath as well as left flank pain. The patient was taking a basal-bolus (Actrapid/Lantus) regimen of insulin and had no other medical conditions. The patient was found to be in diabetic ketoacidosis (blood glucose level 21 mmol/L, pH 7.10) and diagnosed with chest sepsis based on bilateral consolidation on a chest X-ray. The patient was admitted to the high dependency unit and treated empirically with intravenous flucloxacillin and ceftriaxone. Blood cultures grew a fully sensitive Staphylococcus aureus. The patient's flank pain failed to improve and on day 3 of admission CT of the abdomen and pelvis demonstrated a left 4.9 cm intermedius muscle abscess (figure 1). There were additional small focal collections in the left psoas, right psoas and right erector spinae muscle. Radiologically guided aspiration of the left intermedius...

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MRI SPACE sequence confirmation of occluded MCA M2 dissection stump masquerading as a ruptured MCA aneurysm

Intracranial vascular pathologies often have overlapping clinical presentations. Dissected vessel occlusions and bifurcation aneurysms can appear similar on pretherapeutic imaging. The medical management of these two entities is drastically different. The patient is a 51-year-old man who presented with severe, sudden-onset headache. Initial presentation was consistent with a ruptured middle cerebral artery (MCA) aneurysm and surgical clipping was recommended. However, further review of radiographic findings could not definitively differentiate an aneurysmal origin of the symptoms as opposed to intracranial dissection followed by occlusion of the M2 branch of the MCA. MRI sampling perfection with application optimised contrasts using different flip angle evolution (SPACE) was performed and showed thin flow signalling distal to the dissected vessel stump confirming the diagnosis. Accurate diagnosis is a crucial step in directing treatment for intracranial vascular lesions. MRI SPACE is a simple tool in the diagnostic armamentarium to adequately direct treatment and avoid the potential for unnecessary interventions.

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Paediatric massage for treatment of acute diarrhoea in children: a meta-analysis

Massage therapy has been used by many traditional Chinese medicine physicians to treat acute diarrhoea in children. Since no relevant systematic reviews assessed the clinical effectiveness or the risk of massa...

https://ift.tt/2xoaS2p

Marathons and myasthenia gravis: a case report

The cardinal symptoms of auto-immune myasthenia gravis are fatigue and weakness. Endurance events such as marathon running would seem incompatible with this chronic disease. Many patients stop sport altogether...

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View point: gaps in the current guidelines for the prevention of Methicillin-resistant Staphylococcus aureus surgical site infections

The authors advocate the addition of two preventative strategies to the current United State's guidelines for the prevention of surgical site infections. It is known that Staphylococcus aureus, including Methicil...

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Whole-Genome Multi-omic Study of Survival in Patients with Glioblastoma Multiforme

Glioblastoma multiforme (GBM) has been recognized as the most lethal type of malignant brain tumor. Despite efforts of the medical and research community, patients' survival remains extremely low. Multi-omic profiles (including DNA sequence, methylation and gene expression) provide rich information about the tumor. These profiles are likely to reveal processes that may be predictive of patient survival. However, the integration of multi-omic profiles, which are high dimensional and heterogeneous in nature, poses great challenges. The goal of this work was to develop models for prediction of survival of GBM patients that can integrate clinical information and multi-omic profiles, using multi-layered Bayesian regressions. We apply the methodology to data from GBM patients from The Cancer Genome Atlas (TCGA, n=501) to evaluate whether integrating multi-omic profiles (SNP-genotypes, methylation and gene expression) with clinical information (demographics as well as treatments) leads to an improved ability to predict patient survival. The proposed Bayesian models were used to estimate the proportion of variance explained by clinical covariates and omics and to evaluate prediction accuracy in cross validation (using the area under the Receiver Operating Characteristic curve, AUC). Among clinical and demographic covariates, age (AUC=0.664) and the use of temozolomide (AUC=0.606) were the most predictive of survival. Among omics, methylation (AUC=0.623) and gene expression (AUC=0.593) were more predictive than either SNP (AUC=0.539) or CNV (AUC=0.547). While there was a clear association between age and methylation, the integration of age, the use of temozolomide, and either gene expression or methylation led to a substantial increase in AUC in cross-validaton (AUC=0.718). Finally, among the genes whose methylation was higher in aging brains, we observed a higher enrichment of these genes being also differentially methylated in cancer.

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Targeting Toll-Like Receptors for Cancer Therapy

Abstract

The immune system encompasses a broad array of defense mechanisms against foreign threats, including invading pathogens and transformed neoplastic cells. Toll-like receptors (TLRs) are critically involved in innate immunity, serving as pattern recognition receptors whose stimulation leads to additional innate and adaptive immune responses. Malignant cells exploit the natural immunomodulatory functions of TLRs, expressed mainly by infiltrating immune cells but also aberrantly by tumor cells, to foster their survival, invasion, and evasion of anti-tumor immune responses. An extensive body of research has demonstrated context-specific roles for TLR activation in different malignancies, promoting disease progression in certain instances while limiting cancer growth in others. Despite these conflicting roles, TLR agonists have established therapeutic benefits as anti-cancer agents that activate immune cells in the tumor microenvironment and facilitate the expression of cytokines that allow for infiltration of anti-tumor lymphocytes and the suppression of oncogenic signaling pathways. This review focuses on the clinical application of TLR agonists for cancer treatment. We also highlight agents that are undergoing development in clinical trials, including investigations of TLR agonists in combination with other immunotherapies.

https://ift.tt/2MMvy8Q

234 Feasibly Mitigating Provider Terror: Introducing a High-Fidelity, Tissue-Based Task Trainer for the Deliberate Practice of Emergent Hysterotomies

Simulation has become a standard pedagogy for training emergency medicine providers by offering the opportunity to deliberately practice procedural skills and prepare for low frequency, life-threatening clinical events. Resuscitative hysterotomy is perhaps the most daunting and infrequently performed procedure in the emergency department (ED). Given the paucity of clinical exposure to this intervention, resuscitative hysterotomy is an ideal candidate for simulation-mediated deliberate practice. To date, there are only a few resuscitative hysterotomy task-trainers available for training; further complicated by costly components and maintenance fees.

https://ift.tt/2OAMeC6

233 The Use of High-Fidelity Simulation to Identify Potential Protocol Violations and Latent Risk Threats During Standardized Protocol Training in a Large, Multicenter Study

High-fidelity simulation (HF-SIM) has been used extensively in medical education and quality improvement; however, its role in protocol training for large clinical research trials is not well described. We sought to utilize HF-SIM for protocol training for a large multicenter clinical trial in order to standardize training and identify potential protocol violations (PPVs) or study-related latent risk threats (LRTs) prior to enrolling patients in the Hyperbaric Oxygen Brain Injury Treatment (HOBIT) Trial.

https://ift.tt/2NRX75h

337 Characteristics of Prior Emergency Departments Visits Associated With Subsequent Opioid Overdose

Drug overdose was the leading cause of injury death in 2013, causing approximately 2.5 million emergency department (ED) visits in 2011. Several studies have reported epidemiological data from ED databases of opioid overdoses on a national or statewide level. Here we identified clinical and demographic information of opioid overdose patients from 2 medical centers in Staten Island, to better identify this population within the ED. Through the identification of high-risk clinical and demographic characteristic of abuse, intervention can potentially be instituted.

https://ift.tt/2ODdrE3

1 A Randomized Trial Comparing the Combination of Intravenous Lidocaine and Ketorolac to Either Analgesics Alone for Emergency Department Patients With Acute Renal Colic

NSAID's (IV ketorolac) and opioids (morphine) constitutes the mainstay of treatment of renal colic either alone or in combinations. Despite their synergism and analgesic superiority when administered together, both classes of these medications possess a set of unfavorable side effects that limit their use. Emerging data of the use of IV lidocaine for patients with renal colic demonstrated good analgesic efficacy and safety profile. However, none of the trials directly compared lidocaine to ketorolac or the combination of both as viable options in patients unable to tolerate or to have serious contraindications to opioids.

https://ift.tt/2NRX4q7

3 Magnetocardiography Using a Novel Analysis System (Cardioflux) in the Evaluation of Emergency Department Observation Unit Chest Pain Patients

Magnetocardiography (MCG), a non-invasive diagnostic modality that measures the magnetic field arising from the electrical activity of the heart cycle, has been found to be superior to ECG in detection of myocardial ischemia in patients with acute chest pain. The objective of this pilot study is to evaluate MCG using Cardioflux (MCG-CF), a novel MCG analysis system, in the workup of ED observation unit (EDOU) chest pain patients by comparing MCG-CF with stress testing (ST) and/or coronary angiography (CA) to identify myocardial ischemia.

https://ift.tt/2NRQXlL

2 Ketamine Versus Midazolam for Out-of-Hospital Agitation: A Prospective Study

Controversy exists regarding the ideal sedation protocol for agitated patients in the out-of-hospital environment. We hypothesized a ketamine-based tiered dosing protocol would be superior to a midazolam-based tiered dosing protocol for out-of-hospital agitation.

https://ift.tt/2NRX2P1

273 Prevalence of Hepatitis C and Needle/Syringe Sharing in Emergency Department Opioid Overdose Patients

In the midst of the devastating opioid epidemic, drug overdose deaths are at an all-time high. Drug overdose is now the leading injury-associated cause of death in the United States. In 2017, 403 accidental drug overdose cases were identified in Marion County, Indiana, which represents a 17% increase from 2016. ED visits due to opioid overdose increased from 1,856 in 2011 to 2,977 in 2015 and 8,297 in 2016 in Indiana. Along with the dramatic increase in overdose deaths, Hepatitis C virus (HCV) infection rates have spiked, creating an epidemic within an epidemic.

https://ift.tt/2ODdmAf

305 The Significance of Neuroimaging in Evaluating Patients Presenting With Dizziness to the Emergency Department

The aim of the study is to determine the usefulness of computed tomography (CT) and magnetic resonance imaging (MRI) in the evaluation of patients with dizziness in the emergency department (ED) focusing mainly on CT findings as the CT scan is the first line management in the ED and to determine the signs and symptoms that potentially predict the presence of acute abnormalities on the CT head evaluation

https://ift.tt/2OAMelA

241 Impact of Specialized Geriatric Care Coordination Within a Senior Emergency Care Unit

As the general population ages, the elderly represent a high-risk subset of emergency department (ED) patients; the multiple medical comorbidities and physical deconditioning associated with aging often complicate an inpatient admission following an acute injury. The University of California San Diego (UCSD) Health Center debuted a senior emergency care unit (SECU) in January, 2017 with a multi-disciplinary team to identify candidates for and coordinate out-of-hospital treatment plans and dispositions.

https://ift.tt/2OAJmVS

4 Impact of High Sensitivity Troponins of Discharge Rates of Patients Presenting to the Emergency Department With Chest Pain

High sensitivity troponins have recently been introduced into clinical care in the US. Data from outside the US shows that more patients can be safely discharged from the ED. There have been no prior studies of the clinical impact of transition to high sensitivity troponin in the US. Our hypothesis was that transitioning from a 4th generation to a 5th generation high sensitivity troponin assay would increase the ED discharge rate and shorten ED length of stay for admitted patients.

https://ift.tt/2NQOZCi

321 Severe Metabolic Acidosis Was Associated With Unfavorable Neurological Outcome in Patients With Out-of-Hospital Cardiac Arrest

Metabolic acidosis is observed in 98% of patients with Out-of-hospital cardiac arrest (OHCA). The longer the no-flow or low-flow duration, the more severe the acidosis is in these patients. This study aim to demonstrate the blood pH on arrival at emergency department (ED) could be an independent predictor of neurological prognosis in patients with OHCA.

https://ift.tt/2OAJkgI

5 Reporting Persons With Mental Health Issues: Prospective Study on Gun Control Innovation

The recent school shootings in Parkland, FRL and Santa Fe, TX has revived debate about early flagging of people who exhibit behavior or symptomology associated with violent behavior. People flagged as at risk may be reported to third-parties such as psychiatrists and law enforcement and may temporarily or permanently become ineligible to possess firearms. Different groups of people including teachers, therapists or counselors, family physicians, and emergency physicians could be part of an assessment system to flag individuals.

https://ift.tt/2NRWZmj

289 Impact of a Visible Stopwatch on Time That Patients Spend in the Trauma Bay During Resuscitation

This study implemented a stopwatch visible to all providers during trauma resuscitation to assess whether this decreased time spent in the trauma bay.

https://ift.tt/2OBEcJk

6 Prognostic Value of qSOFA, SIRS and News in the Emergency Department for Predicting 7-Day Mortality: A Prospective Study

Sepsis is the primary cause of death from infection worldwide. In 2016, Sepsis-3, a new clinical concept termed "quick Sepsis-Related Organ Failure Assessment" (qSOFA) was introduced to identify high-risk patients with suspected infection (outside of critical care settings). The present study aimed to validate qSOFA for use in a university hospital emergency department in Hong Kong. Furthermore, we compared the prognostic value of qSOFA and the previous Systemic Inflammatory Response Syndrome (SIRS) criteria, along with a widely used early warning score, the National Early Warning Score (NEWS).

https://ift.tt/2NQa6Vj

257 A Clinical Decision Rule to Screen Out Thoracolumbar Injury in the Emergency Department

Thoracolumbar (TL) injury is a common finding in the multi-trauma patient. However, the incidence and pattern of TL injury in milder trauma patients, typically seen in the average emergency department setting, is unclear. The aim of this study is to develop a clinical decision rule (CDR) to evaluate the TL-spine in non-severe blunt trauma patients and avoid dedicated imaging in low-risk cases. Ideally the rule would be both sensitive and simple to use.

https://ift.tt/2OA3OWN

7 Performance of Single Versus Double Site Intraosseous Blood Transfusion Strategies in a Swine [Sus Scrofa] Model of Hemorrhagic Shock

1. Discuss and clarify the utility of intraosseous blood transfusions for treating hypovolemic battlefield injuries in military out-of-hospital settings

https://ift.tt/2NQa4Nb

345 Impact of Emergency Department Blood Pressure on Stroke Severity

To evaluate the association of systolic blood pressure (sBP) in the emergency department (ED) with ED stroke severity in patients with acute ischemic stroke (AIS)

https://ift.tt/2Ow0mfQ

8 A Double-Blind, Placebo-Controlled Trial of Lofexidine for Opioid Withdrawal Syndrome

Treatment of opioid overdose in the emergency department is a commonplace event and may serve as an opportunity for patients to transition into long-term treatment of opioid use disorder. However, abrupt opioid cessation results in a severe opioid withdrawal syndrome (OWS) that may motivate patients to use opioids (Rx or illicit) rather than seek further treatment. Lofexidine (LFX) is an alpha2-adrenergic receptor agonist that counteracts the noradrenergic hyperactivity underlying OWS. LFX has been evaluated for treatment of OWS after abrupt withdrawal of short-acting opioids.

https://ift.tt/2NQa281

329 Using Digital Health to Enhance Medical Screening Exam in the Emergency Department

Surges in patient arrivals put stress on emergency department (ED) resources contributing to increased time-to-provider, increased walk-outs and decreased patient satisfaction. A medical screening exam (MSE) performed by a Provider-in-Triage (PIT) has been shown to both aid in early identification of seriously ill patients as well as those with non-critical illness. PIT assessments are frequently encumbered by interruptions as the provider navigates through the physical space of the ED. Research suggests that so-called "task switching" causes disruption in the primary task and may contribute to error.

https://ift.tt/2OCth1S

9 Banyan BT Blood Test Predicts Absence of Intracranial Injuries After Mild Traumatic Brain Injury: Results of the Pivotal ALERT-TBI Multicenter Study

To validate a blood test combining ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP), at pre-determined cut-off values, to predict traumatic intracranial injuries on head CT scan acutely after mild traumatic brain injury (TBI).

https://ift.tt/2NRWQiL

Intertumoral Heterogeneity in SCLC Is Influenced by the Cell Type of Origin [Research Articles]

The extent to which early events shape tumor evolution is largely uncharacterized, even though a better understanding of these early events may help identify key vulnerabilities in advanced tumors. Here, using genetically defined mouse models of small cell lung cancer (SCLC), we uncovered distinct metastatic programs attributable to the cell type of origin. In one model, tumors gain metastatic ability through amplification of the transcription factor NFIB and a widespread increase in chromatin accessibility, whereas in the other model, tumors become metastatic in the absence of NFIB-driven chromatin alterations. Gene-expression and chromatin accessibility analyses identify distinct mechanisms as well as markers predictive of metastatic progression in both groups. Underlying the difference between the two programs was the cell type of origin of the tumors, with NFIB-independent metastases arising from mature neuroendocrine cells. Our findings underscore the importance of the identity of cell type of origin in influencing tumor evolution and metastatic mechanisms.

SIGNIFICANCE: We show that SCLC can arise from different cell types of origin, which profoundly influences the eventual genetic and epigenetic changes that enable metastatic progression. Understanding intertumoral heterogeneity in SCLC, and across cancer types, may illuminate mechanisms of tumor progression and uncover how the cell type of origin affects tumor evolution. Cancer Discov; 8(10); 1–16. ©2018 AACR.

See related commentary by Pozo et al., p. 1216.

https://ift.tt/2piFs91

Functional silencing of HSD17B2 in prostate cancer promotes disease progression

Purpose: Steroidogenic enzymes are essential for prostate cancer development. Enzymes inactivating potent androgens were not investigated thoroughly, which leads to limited interfere strategies for prostate cancer therapy. Here we characterized the clinical relevance, significance and regulation mechanism of enzyme HSD17B2 in prostate cancer development. Experimental Design: HSD17B2 expression was detected with patient specimens and prostate cancer cell lines. Function of HSD17B2 in steroidogenesis, AR signaling and tumor growth was investigated with prostate cancer cell lines and xenograft model. DNA methylation and mRNA alternative splicing were investigated to unveil the mechanisms of HSD17B2 regulation. Results: HSD17B2 expression was reduced as prostate cancer progresses. 17βHSD2 decreased potent androgen production by converting testosterone (T) or dihydrotestosterone (DHT) to their upstream precursors. HSD17B2 overexpression suppressed androgen-induced cell proliferation and xenograft growth. Multiple mechanisms were involved in HSD17B2 functional silencing including DNA methylation, androgen stimulation and mRNA alternative splicing. DNA methylation and T stimulation decreased HSD17B2 mRNA or protein level respectively. Two new catalytic-deficient isoforms, generated by alternative splicing, bound to wild type 17βHSD2 and promoted its degradation. Splicing factors SRSF1 and SRSF5 participated in the generation of new isoforms. Conclusion: Our findings provide evidence of the clinical relevance, significance and regulation of HSD17B2 in prostate cancer progression, which might provide new strategies for clinical management by targeting the functional silencing mechanisms of HSD17B2.

https://ift.tt/2NVw5dg

A PET Imaging Strategy for Interrogating Target Engagement and Oncogene Status in Pancreatic Cancer

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is one of the most deadly cancers with a 5-year survival rate of less than 10%. Physicians often rely on biopsy or CT to guide treatment decisions, but these techniques fail to reliably measure the actions of therapeutic agents in PDAC. KRAS mutations are present in >90% of PDAC and are connected to many signaling pathways through its oncogenic cascade, including extracellular regulated kinase (ERK) and MYC. A key downstream event of MYC is transferrin receptor (TfR), which has been identified as a biomarker for cancer therapeutics and imaging. Experimental Design: In this study, we aimed to test if zirconium-89 transferrin ([⁸⁹Zr]Zr-Tf) could measure changes in MYC depending on KRAS status of PDAC, and assess target engagement of anti-MYC and anti-ERK targeted therapies. Results: Mice bearing iKras*p53* tumors showed significantly higher (P< 0.05) uptake of [⁸⁹Zr]Zr-Tf in mice withdrawn from inducible oncogenic KRAS. A therapy study with JQ1 showed a statistically significant decrease (P< 0.05) of [⁸⁹Zr]Zr-Tf uptake in drug vs. vehicle-treated mice bearing Capan-2 and Suit-2 xenografts. IHC analysis of resected PDAC tumors reflects the data observed via PET imaging and radiotracer biodistribution. Conclusions: Our study demonstrates that [⁸⁹Zr]Zr-Tf is a valuable tool to noninvasively assess oncogene status and target engagement of small molecule inhibitors downstream of oncogenic KRAS, allowing a quantitative assessment of drug delivery.

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Landscape of EGFR -dependent and -independent resistance mechanisms to osimertinib and continuation therapy post-progression in EGFR-mutant NSCLC

Purpose: Osimertinib was initially approved for T790M positive NSCLC and, more recently, for first-line treatment of EGFR-mutant NSCLC. However, resistance mechanisms to osimertinib have been incompletely described. Experimental Design: Using cohorts from MD Anderson Lung Cancer Moonshot GEMINI and Moffitt Cancer Center Lung Cancer databases, we collected clinical data for patients treated with osimertinib. Molecular profiling analysis was performed at the time of progression in a subset of the patients. Results: In the 118 patients treated with osimertinib, 42 had molecular profiling at progression. T790M was preserved in 21 (50%) patients and lost in 21 (50%). EGFR C797 and L792 (26%) mutations were the most common resistance mechanism and were observed exclusively in T790M-preserved cases. MET amplification was the second most common alteration (14%). Recurrent alterations were observed in 22 genes/pathways, including PIK3CA, FGFR, and RET. Preclinical studies confirmed MET, PIK3CA, and epithelial-to-mesenchymal transition (EMT) as potential resistance drivers. Alterations of cell cycle genes were associated with shorter median PFS (4.4 vs 8.8 months, p=0.01). In 76 patients with progression, osimertinib was continued in 47 cases with a median second progression-free survival (PFS2) was of 12.6 months; 21 patients received local consolidation radiation with median PFS of 15.5 months. Continuation of osimertinib beyond progression was associated with a longer overall survival compared to discontinuation (OS 11.2 vs 6.1 months, p=0.02). Conclusions: Osimertinib resistance is associated with diverse, predominantly EGFR-independent genomic alterations. Continuation of osimertinib post-progression, alone or in conjunction with radiotherapy, may provide prolonged clinical benefit in selected patients.

https://ift.tt/2NUv4Cn

Preclinical evaluation of the Hsp70 peptide tracer TPP-PEG24-DFO[89Zr] for tumor-specific PET/CT imaging

High precision in vivo PET/CT imaging of solid tumors improves diagnostic credibility and clinical outcome of patients. An epitope of the oligomerization domain of Hsp70 is exclusively exposed on the membrane of a large variety of tumor types, but not on normal cells, and thus provides a universal tumor-specific target. Here we developed a novel PET tracer TPP-PEG24-DFO[89Zr] based on the tumor cell penetrating peptide probe TPP, which specifically recognizes membrane Hsp70 (mHsp70) on tumor cells. The implemented PEG24 moiety supported tracer stability and improved biodistribution characteristics in vivo. The KD of the tracer ranged in the low nanomolar range (18.9±11.3nM). Fluorescein-isothiocyanate (FITC)-labeled derivatives TPP-[FITC] and TPP-PEG24-[FITC] revealed comparable and specific binding to mHsp70-positive 4T1, 4T1+, a derivative of the 4T1 cell line sorted for high Hsp70 expression, and CT26 tumor cells, but not to mHsp70-negative normal fibroblasts. The rapid internalization kinetics of mHsp70 into the cytosol and the favorable biodistribution of the peptide-based tracer TPP-PEG24-DFO[89Zr] in vivo enabled a tumor-specific accumulation with a high tumor-to-background contrast and renal body clearance. The tumor-specific enrichment of the tracer in 4T1+ (6.2±1.1%ID/g), 4T1 (4.3±0.7%ID/g) and CT26 (2.6±0.6%ID/g) mouse tumors with very high, high and intermediate mHsp70 densities, respectively, reflected mHsp70 expression profiles of the different tumor types, whereas, benign mHsp70-negative fibroblastic hyperplasia showed no tracer accumulation (0.2±0.03%ID/g). The ability of our chemically optimized peptide-based tracer TPP-PEG24-DFO[89Zr] to detect mHsp70 in vivo suggests its broad applicability in targeting and imaging with high specificity for any tumor type that exhibits surface expression of Hsp70.

https://ift.tt/2OBd0KH

Comprehensive phenotypic characterization of human invasive lobular carcinoma cell lines in 2D and 3D cultures

Invasive lobular carcinoma (ILC) is the second most common subtype of breast cancer following invasive ductal carcinoma (IDC) and characterized by the loss of E-cadherin-mediated adherens junctions. Despite displaying unique histological and clinical features, ILC still remains a chronically understudied disease, with limited knowledge gleaned from available laboratory research models. Here we report a comprehensive 2D and 3D phenotypic characterization of four estrogen receptor-positive human ILC cell lines: MDA-MB-134, SUM44, MDA-MB-330 and BCK4. Compared to the IDC cell lines MCF7, T47D and MDA-MB-231, ultra-low attachment culture conditions revealed remarkable anchorage-independence unique to ILC cells, a feature not evident in soft agar gels. 3D Collagen I and Matrigel culture indicated a generally loose morphology for ILC cell lines, which exhibited differing preferences for adhesion to ECM proteins in 2D. Furthermore, ILC cells were limited in their ability to migrate and invade in wound-scratch and transwell assays, with the exception of haptotaxis to Collagen I. Transcriptional comparison of these cell lines confirmed the decreased cell proliferation and E-cadherin-mediated intercellular junctions in ILC while uncovering the induction of novel pathways related to cyclic nucleotide phosphodiesterase activity, ion channels, drug metabolism and alternative cell adhesion molecules such as N-cadherin, some of which were differentially regulated in ILC versus IDC tumors. Altogether, these studies provide an invaluable resource for the breast cancer research community and facilitate further functional discoveries towards understanding ILC, identifying novel drug targets, and ultimately improving the outcome of patients with ILC.

https://ift.tt/2NVvVma

FDA Ad Campaign Hopes to Halt E-Cigarette Use Among Teens

TUESDAY, Sept. 18, 2018 -- The U.S. Food and Drug Administration on Tuesday launched a new ad campaign aimed at curbing rampant e-cigarette use among American teens. The new program, called "The Real Cost" Youth E-Cigarette Prevention Campaign, is...

https://ift.tt/2NnVBIS

Socioeconomic Status Lower Among U.S. Sexual Minorities

TUESDAY, Sept. 18, 2018 -- Sexual minorities, especially females, are of lower socioeconomic status (SES) than their heterosexual counterparts, according to a study published online Sept. 6 in the Journal of Epidemiology & Community...

https://ift.tt/2DaZb4c

Sport Specialization Tied to Pediatric Overuse Injury

TUESDAY, Sept. 18, 2018 -- Sport specialization in children and adolescents is associated with an increased risk of overuse musculoskeletal injuries, according to a review published in the September issue of Pediatrics. David R. Bell, Ph.D., from...

https://ift.tt/2NpxQjo

U.S. Senate Passes Opioids Bill

TUESDAY, Sept. 18, 2018 -- The Senate on Monday passed on a 99-1 vote legislation aimed at curbing the nation's ongoing opioid addiction crisis. The comprehensive bipartisan package earmarks billions of dollars to prevent cross-border opioid...

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Active Choice Intervention Tied to Increase in Flu Shot Rates

TUESDAY, Sept. 18, 2018 -- An active choice intervention is associated with an increase in influenza vaccination rates, according to a study published online Sept. 14 in JAMA Network Open. Rebecca H. Kim, M.D., M.P.H., from the University of...

https://ift.tt/2DaZ3Sg

Screening Potential Probiotic Characteristics of Lactobacillus brevis Strains In Vitro and Intervention Effect on Type I Diabetes In Vivo

Diabetes has become the third most serious threat to human health, after cancer and cardiovascular disease. Notably, Lactobacillus brevis is the most common species of LAB that produces γ-aminobutyric acid (GABA). The aim of this study is to clarify the effect of time, strain types, antibiotic concentrations, different levels of pH, and intestinal juices in aerobic or anaerobic conditions and the effect of interactions between these factors on the potential properties of KLDS 1.0727 and KLDS 1.0373, furthermore, antagonistic activity against foodborne pathogens. Moreover, another aim is to study the capability of KLDS 1.0727 and KLDS 1.0373 strains as gad gene carriers to express GABA that reduce the risk of type 1 diabetes in C57BL/6 mice as diabetic models. The obtained results exhibited the surprising tolerance of Lactobacillus brevis strains in vitro digestion models mimicking the conditions of the gastrointestinal tract, further, large antagonistic activity against foodborne pathogeneses. In vivo results displayed the significant effect on glucose level reduction, blood plasma, and histological assays of mice organs. As recommended, the use of Lactobacillus brevis strains should be widely shared in the market as a natural source of GABA in pharmaceutical and food applications.

https://ift.tt/2piTBDh

Polymorphisms in the Chicken Growth Differentiation Factor 9 Gene Associated with Reproductive Traits

The aim of the study was to investigate GDF9 gene polymorphisms and their association with reproductive traits in chicken using DNA sequencing. A total of 279 Dongxiang blue-shelled (DX) chickens and 232 Luhua (LH) chickens were used for validation. We detected 15 single nucleotide polymorphisms (SNPs): nine SNPs were previously unreported in chicken, two were missense mutations, and only three exhibited significant associations with reproductive traits. G.17156387C>T was significantly associated with age at first egg (AFE) and weight of first egg (WFE) in both breeds. Birds carrying the CC genotype exhibited higher AFE and WFE values than those with the TT genotype. The SNP g.17156427A>G exhibited an association with egg weight at 300 days of age (EWTA) in DX but not in LH chickens. The SNP g.17156703A>C affected the AFE and EN (total number of eggs at 300 days of age) in DX chickens. In addition, certain diplotypes significantly affected AFE, BWTA (body weight at 300 days of age), and EN in both breeds. RT-PCR results showed that the GDF9 gene was highly expressed in stroma with cortical follicles (STR) and prehierarchal follicles. These results provided further evidence that the GDF9 gene is involved in determining reproductive traits in chicken.

https://ift.tt/2D6i2gV

Virological failure among adolescents on ART, Harare City, 2017- a case-control study

Zimbabwe is on track towards achieving viral suppression among adults (87%). However, adolescents have only achieved 44% by 2016. In Harare city, 57% of adolescents had attained viral suppression after 12 mont...

https://ift.tt/2NlK3pB

Trichosporon inkin meningitis in Northeast Brazil: first case report and review of the literature

Trichosporon species may colonize the skin, respiratory tract and gastrointestinal tract of human beings. The yeast is recognized as etiological agent of white piedra, a superficial mycosis. Nevertheless, immunoc...

https://ift.tt/2Dj6aZc

Catecholamine-Induced Cardiomyopathy in Pheochromocytoma: How to Manage a Rare Complication in a Rare Disease?

Horm Metab Res
DOI: 10.1055/a-0669-9556

Pheochromocytomas and paragangliomas (PHEOs) are rare neuroendocrine tumors. Clinical manifestations include different cardiovascular signs and symptoms, which are related to excessive secretion of catecholamines. Catecholamine-induced cardiomyopathy in PHEO (CICMPP) is a rare but dreaded complication of PHEO. Once patient is diagnosed with this condition, the prognosis is worse and a surgical risk is much higher than expected. This article focuses on how catecholamines affect the heart and the pathophysiologic mechanism of CICMPP. The cardiovascular responses to catecholamine depend mostly on which catecholamine is released as well as the amount of catecholamine that is released. The acute release of norepinephrine and epinephrine from PHEO increases heart rate, systemic vascular resistance, myocardial contractility, and reduces venous compliance. The excessive adrenergic stimulation by catecholamine results in severe vasoconstriction and coronary vasospasm, myocardial ischemia, and subsequently damage, and necrosis. Chronically elevated catecholamine levels lead to significant desensitization of cardiac β-adrenoceptors. The increased levels of the enzyme β-adrenoceptors kinase (βARK) in the heart seems to mediate these biochemical and physiological changes that are consistently correlated with attenuated responsiveness to catecholamine stimulation. Through these mechanisms different types of cardiomyopathy (CMP) can be formed. This review discusses extensively the 3 types of cardiomyopathies that can be present in a PHEO patient. It also provides the clinical presentation and diagnostic and therapeutic algorithm in managing patients with CICMPP.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Evaluation of the nutrient content of yogurts: a comprehensive survey of yogurt products in the major UK supermarkets

Objectives

To comprehensively survey the sugar and nutrient contents of yogurt products available in UK supermarkets, in particular those marketed to children.

Design

A cross-sectional survey of yogurt products available in the UK's supermarkets in November 2016.

Methods

Data were collected from five major online UK supermarkets and a process flow strategy was used to place yogurts into eight categories: children's, dairy alternatives, dessert, drinks, fruit, flavoured, natural/Greek style and organic. A comprehensive database of product information for 921 unique products was created and analysed.

Results

The total sugar, fat, protein, calcium and energy contents were highly variable across categories, and the ranges were extremely broad. Although lower than the dessert category, the medians (range) of the total sugar content of children's (10.8 g/100 g (4.8–14.5)), fruit (11.9 g/100 g (4.6–21.3)), flavoured (12.0 g/100 g (0.1–18.8)) and organic (13.1 g/100 g (3.8–16.9)) yogurt products were all well above 10 g/100 g, and represented >45% of total energy. Only two out of 101 children's yogurt and fromage frais products surveyed qualified as low sugar (≤5 g/100 g). Natural/Greek yogurts had dramatically lower sugar contents (5.0 g/100 g (1.6, 9.5), largely lactose) than all other categories. While low-fat (<3 g/100 g) products had less sugar and energy than higher fat yogurts, nonetheless 55% (285 of 518 low-fat yogurts) contained between 10 and 20 g sugar/100 g. Within the children's category, fromage frais had higher protein (5.3 g/100 g (3.3, 8.6) vs 3.2 (2.8, 7.1); p<0.0001) and calcium contents (150 mg/100 g (90, 240) vs 130.5 mg/100 g (114, 258); p=0.0015) than yogurts.

Conclusions

While there is good evidence that yogurt can be beneficial to health, products on the market vary widely in total sugars. Fewer than 9%, and only 2% of the children's, products surveyed were low enough in sugar to earn 'green' in UK front of the pack labelling. Reformulation for the reduction of free sugars in yogurts is warranted.

https://ift.tt/2QElzpj

Annular pancreas: endoscopic and pancreatographic findings from a tertiary referral ERCP center

Annular pancreas is a congenital anomaly where pancreatic tissue encircles the duodenum. Current knowledge of endoscopic findings of annular pancreas is limited to small case series. The aim of this study is to describe the endoscopic and pancreatographic findings of patients with annular pancreas at a large tertiary care ERCP center.

https://ift.tt/2D9u3lO

Quality assurance of colonoscopy within the Dutch national colorectal cancer screening program

Colorectal cancer (CRC) screening is capable of reducing CRC-related morbidity and mortality. Colonoscopy is the reference standard to detect CRC, also providing the opportunity to detect and resect its precursor lesions; colorectal polyps. Therefore, colonoscopy is either used as a primary screening tool or as a subsequent procedure after a positive triage test in screening programs based on non-invasive stool testing or sigmoidoscopy. However, in both settings, colonoscopy is not fully protective for the occurrence of post-colonoscopy CRCs (PCCRCs).

https://ift.tt/2pk3YXx

Analysis of Mid-esophageal Biopsies Increases Sensitivity of Detection of Eosinophilic Esophagitis

https://ift.tt/2pjdaes

Small Bowel Ulcers from Cryocrystalglobulinemia

https://ift.tt/2DladEn

Microbiome 101: Studying, Analyzing, and Interpreting Gut Microbiome Data for Clinicians

Advances in technical capabilities for reading out complex human microbiomes are leading to an explosion of microbiome research, leading in turn to intense interest among clinicians in applying these techniques to their patients. In this review, we discuss the content of the human microbiome, including inter- and intra-subject variability, considerations of study design including important confounding factors, and different methods in the laboratory and on the computer to read out the microbiome and its resulting gene products and metabolites.

https://ift.tt/2pkYgEO

Switchable inteins for conditional protein splicing

Journal Name: Biological Chemistry
Issue: Ahead of print


https://ift.tt/2xv8xBY

Single-Cell RNA Sequencing of the Adult Mouse Kidney: From Molecular Cataloging of Cell Types to Disease-Associated Predictions

Single-cell transcriptomic analyses have emerged as a powerful tool in dissecting cell diversity and function within complex biological systems.1 As high-throughput approaches have evolved,2-4 the field has moved toward large data sets comprising thousands of cells or nuclei.5-8 In a recent report in Science from the Suszták laboratory, Park et al9 describe single-cell RNA sequencing (scRNAseq) analyses of 57,979 cells from the kidneys of 7 adult male mice. Analyses of these data by computational approaches and follow-up studies in vivo led the authors to 3 key conclusions: (1) the work constitutes a comprehensive cell atlas for the mouse kidney and identifies novel cell types; (2) kidney disease–associated genes highlight specific cell types, thus pinpointing the cellular origin of each disease; and (3) in the collecting system, there is a rare cell type that shares features of both intercalated (ICs) and principal cells (PCs), which can transition into either cell type depending on activity of the Notch cell-signaling pathway.

https://ift.tt/2xvJhvr

Nephrotic Syndrome With Mutations in NPHS2: The Role of R229Q and Implications for Genetic Counseling

Mutations in the NPHS2 gene, which encodes the podocyte slit diaphragm protein podocin, cause autosomal recessive steroid-resistant nephrotic syndrome (Online Mendelian Inheritance in Man [OMIM] #600995). Basic research and clinical studies have provided important insights about genotype-phenotype correlations. This knowledge allows personalized genetic (risk) counseling and should lead to changes in the advice given to patients. A patient who carries the R229Q variant (which has a high allele frequency of 3.7% in the European population) in combination with a pathogenic variant in exon 7 or 8 is at high risk for developing nephrotic syndrome that may not manifest before adulthood, whereas a patient with 2 pathogenic variants will develop congenital or childhood-onset nephrotic syndrome.

https://ift.tt/2QGBZxm

MIF Matters: The Macrophage Migration Inhibitory Factor and Kidney Injury

Acute kidney injury (AKI) is a common complication of cardiac surgery involving cardiopulmonary bypass. There are nearly 2 million cardiac surgeries annually worldwide, with AKI incidence rates between 5% and 42%.1 AKI in the setting of cardiac surgery has been associated with longer hospital stays and increased mortality risk. The relationship between cardiac surgery and AKI in humans has served as a natural experiment; cardiac surgery is common and often used for biomarker discovery, yet our understanding of the mechanism of AKI following it has been evolving.

https://ift.tt/2xsqh0I

Salary and Resources Provided to Junior Faculty in Radiation Oncology

Adequate resource allocation is essential for junior radiation oncology faculty to navigate the road to academic advancement. We surveyed junior academic radiation oncologists in the US and Canada using a pre-tested questionnaire evaluating: time, space, staff, start-up resources, and compensation. Our findings suggest perceived needs for protected time and personnel support.

https://ift.tt/2NPFbZf

FDA takes important steps to encourage appropriate and rational prescribing of opioids through final approval of new safety measures governing the use of immediate-release opioid analgesic medications

September 18, 2018 -- Today, the U.S. Food and Drug Administration took new steps as part of its broader efforts to address the opioid crisis by approving the final Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS). This new plan...

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New influenza surveillance tool supports communities

LAKEVILLE, Minn. — ImageTrend announces influenza tracking using Continuum® software in preparation for the upcoming flu season1. As each incident report is posted by EMS care providers, Continuum automatically begins to monitor the aggregate data for developing trends or surges in influenza-like symptoms. Sudden spikes or increased concentration of incidents can trigger...

https://ift.tt/2MLIaNu

Preventing Childhood Obesity Through a Mindfulness-Based Parent Stress Intervention: A Randomized Pilot Study

To assess the feasibility of engaging stressed, low-income parents with obesity in a novel mindfulness-based parent stress intervention aimed at decreasing the risk of early childhood obesity.

https://ift.tt/2xjEYE4

Simultaneous Cryosectioning of Multiple Rodent Brains

Here, we present a protocol to freeze and section brain tissue from multiple animals as a timesaving alternative to processing single brains. This reduces staining variability during immunohistochemistry and reduces time cryosectioning and imaging.

https://ift.tt/2OB68Nt

Research Analysis: Key takeaways from PART and Airways-2 Trials

Comparing endotracheal, laryngeal tube and supraglottic airway device intubation during out of hospital cardiac arrest

https://ift.tt/2DaxU22

PCR documentation for non-transporting first responders

Including clear, complete documentation in your patient care report is a critical component of patient care

https://ift.tt/2plAOqF

Negative Additive Manufacturing of Complex Shaped Boron Carbides

A method called negative additive manufacturing is used to produce near fully dense complex shaped boron carbide parts of various length scales. This technique is possible via the formulation of a novel suspension involving resorcinol-formaldehyde as a unique gelling agent that leaves behind a homogenous carbon sintering aid after pyrolysis.

https://ift.tt/2xuoyrD

Identification, Histological Characterization, and Dissection of Mouse Prostate Lobes for In Vitro 3D Spheroid Culture Models

Genetically engineered mice are useful models for investigating prostate cancer mechanisms. Here we present a protocol to identify and dissect prostate lobes from a mouse urogenital system, differentiate them based on histology, and isolate and culture the primary prostate cells in vitro as spheroids for downstream analyses.

https://ift.tt/2xnJyRA

Synthesis and Characterization of Placental Chondroitin Sulfate A (plCSA)-Targeting Lipid-Polymer Nanoparticles

Here, we present a protocol for the synthesis of placental chondroitin sulfate A binding peptide (plCSA-BP)-conjugated lipid-polymer nanoparticles via single-step sonication and bioconjugate techniques. These particles constitute a novel tool for the targeted delivery of therapeutics to most human tumors and placental trophoblasts to treat cancers and placental disorders.

https://ift.tt/2xy1yrE

Scribes Improve Physician Workflow, Patient Interaction

TUESDAY, Sept. 18, 2018 -- Use of medical scribes is associated with decreased physician documentation burden, improved work efficiency, and improved patient interactions, according to a study published online Sept. 17 in JAMA Internal...

https://ift.tt/2PK3IfC

Incident Contrast Sensitivity Common in Middle-Aged Adults

TUESDAY, Sept. 18, 2018 -- The risk of incident contrast sensitivity (CS) impairment is increased with factors such as cadmium exposure and older age, according to a study published online Sept. 13 in JAMA Ophthalmology. Adam J. Paulsen, from the...

https://ift.tt/2xgK4kv

Drug Prices Increase More Than Expected After Shortages

TUESDAY, Sept. 18, 2018 -- Prices for drugs under shortage increase more than twice as quickly as expected in the absence of a shortage, according to a research letter published online Sept. 18 in the Annals of Internal Medicine. Inmaculada...

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2006 to 2015 Saw Increase in Severe Maternal Morbidity

TUESDAY, Sept. 18, 2018 -- From 2006 to 2015, the proportion of women experiencing severe maternal morbidity increased 45 percent, according to a statistical brief published by the Agency for Healthcare Research and Quality. Kathryn R. Fingar,...

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Many Middle, High Schoolers Report E-Cigarette Cannabis Use

TUESDAY, Sept. 18, 2018 -- Nearly one in 11 U.S. middle and high school students used cannabis in electronic cigarettes (e-cigarettes) in 2016, according to a research letter published online Sept. 17 in JAMA Pediatrics. Katrina F. Trivers, Ph.D.,...

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Review: Treatments for Primary Basal Cell Carcinoma Compared

TUESDAY, Sept. 18, 2018 -- For patients with primary basal cell carcinoma (BCC), estimated recurrence rates are similarly low for excision, Mohs surgery, curettage and diathermy, and external-beam radiation, according to a review and meta-analysis...

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Compliance With Requirement to Report Results on EUCTR Is Poor

TUESDAY, Sept. 18, 2018 -- Half of trials on the European Union Clinical Trials Register (EUCTR) are non-compliant with the European Commission's requirement that all trials post results to the registry within 12 month of completion, according to a...

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Tips for Advising Patients Living in Highly Polluted Settings

TUESDAY, Sept. 18, 2018 -- Clinicians advising families living overseas in highly polluted settings should understand their patients' concerns and have a network of resources to draw upon for guidance, according to an article published in the Aug. 1...

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Tafamidis Treats Transthyretin Amyloid Cardiomyopathy

TUESDAY, Sept. 18, 2018 -- In patients with transthyretin amyloid cardiomyopathy, treatment with tafamidis reduces all-cause mortality and cardiovascular-related hospitalizations versus placebo, according to a study published in the Sept. 13 issue...

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Ranolazine Doesn't Cut VT, VF, Death in High-Risk ICD Patients

TUESDAY, Sept. 18, 2018 -- For high-risk patients with implantable cardioverter-defibrillators (ICDs), ranolazine does not significantly reduce the risk of ventricular tachycardia (VT) or ventricular fibrillation (VF) requiring appropriate ICD...

https://ift.tt/2PKH72a

Olfactory Context Dependent Memory: Direct Presentation of Odorants

The use of an olfactometer for directly presenting odorants opens exciting opportunities for researchers of olfactory memory. The current paper discusses issues related to this methodology as related to a previously published experiment on olfactory context dependent memory.

https://ift.tt/2xk4Cs6

'Boden Food Plate': Novel Interactive Web-based Method for the Assessment of Dietary Intake

The 'Boden Food Plate' is an electronic food diary designed to be an interactive and fun method to collect dietary intake using visual depictions. The purpose of this study was to validate the web-based application against a traditional three-day estimated food diary method.

https://ift.tt/2xu4964

What you missed at the 2018 Pinnacle Leadership Forum

Pinnacle program co-chair, Jay Fitch, recounts the highlights from this year's leadership forum

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Antipruritic effect of bezafibrate and serum autotaxin measures in patients with primary biliary cholangitis

It was with great interest that we read the recent guidelines from the British Society of Gastroenterology on the treatment and management of primary biliary cholangitis (PBC).1 The authors propose a pragmatic drug approach to treat cholestatic pruritus with cholestyramine as first-line and rifampicin as second-line use, followed by naltrexone, sertraline or gabapentin as third-line options, although with concerns regarding tolerability and adverse events.

Pruritus is a characteristic, potentially agonising symptom of PBC that remains poorly cared.2 New drug options are definitively needed to relieve patients of this symptom. Bezafibrate, a pan-agonist of peroxisome proliferator-activated receptors, has been suggested to reduce itch intensity in patients with PBC.3 This beneficial effect has recently been confirmed in a placebo-controlled phase III trial Bezafibrate in Combination with Ursodeoxycholic Acid in PBC (BEZURSO).4 The mechanisms by which bezafibrate improves pruritus in PBC remain unknown. As the lysophospholipase...

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ARID1A, a SWI/SNF subunit, is critical to acinar cell homeostasis and regeneration and is a barrier to transformation and epithelial-mesenchymal transition in the pancreas

Objective

Here, we evaluate the contribution of AT-rich interaction domain-containing protein 1A (ARID1A), the most frequently mutated member of the SWItch/sucrose non-fermentable (SWI/SNF) complex, in pancreatic homeostasis and pancreatic ductal adenocarcinoma (PDAC) pathogenesis using mouse models.

Design

Mice with a targeted deletion of Arid1a in the pancreas by itself and in the context of two common genetic alterations in PDAC, Kras and p53, were followed longitudinally. Pancreases were examined and analysed for proliferation, response to injury and tumourigenesis. Cancer cell lines derived from these models were analysed for clonogenic, migratory, invasive and transcriptomic changes.

Results

Arid1a deletion in the pancreas results in progressive acinar-to-ductal metaplasia (ADM), loss of acinar mass, diminished acinar regeneration in response to injury and ductal cell expansion. Mutant Kras cooperates with homozygous deletion of Arid1a, leading to intraductal papillary mucinous neoplasm (IPMN). Arid1a loss in the context of mutant Kras and p53 leads to shorter tumour latency, with the resulting tumours being poorly differentiated. Cancer cell lines derived from Arid1a-mutant tumours are more mesenchymal, migratory, invasive and capable of anchorage-independent growth; gene expression analysis showed activation of epithelial-mesenchymal transition (EMT) and stem cell identity pathways that are partially dependent on Arid1a loss for dysregulation.

Conclusions

ARID1A plays a key role in pancreatic acinar homeostasis and response to injury. Furthermore, ARID1A restrains oncogenic KRAS-driven formation of premalignant proliferative IPMN. Arid1a-deficient PDACs are poorly differentiated and have mesenchymal features conferring migratory/invasive and stem-like properties.

https://ift.tt/2D4QHvs

Prevalence and burden of hepatitis D virus infection in the global population: a systematic review and meta-analysis

Objective

Hepatitis D virus (HDV) is a defective virus that completes its life cycle only with hepatitis B virus (HBV). The HBV with HDV super-infection has been considered as one of the most severe forms of the chronic viral hepatitis. However, there is a scarcity of data on the global burden of HDV infection.

Design

We searched PubMed, Embase, Cochrane Library and China Knowledge Resource Integrated databases from 1 January 1977 to 31 December 2016. We included studies with a minimum sample size of 50 patients. Our study analysed data from a total of 40 million individuals to estimate the prevalence of HDV by using Der-Simonian Laird random-effects model. The data were further categorised according to risk factors.

Results

From a total of 2717 initially identified studies, only 182 articles from 61 countries and regions met the final inclusion criteria. The overall prevalence of HDV was 0.98% (95% CI 0.61 to 1.42). In HBsAg-positive population, HDV pooled prevalence was 14.57% (95% CI 12.93 to 16.27): Seroprevalence was 10.58% (95% CI 9.14 to 12.11) in mixed population without risk factors of intravenous drug use (IVDU) and high-risk sexual behaviour (HRSB). It was 37.57% (95% CI 29.30 to 46.20) in the IVDU population and 17.01% (95% CI 10.69 to 24.34) in HRSB population.

Conclusion

We found that approximately 10.58% HBsAg carriers (without IVDU and HRSB) were coinfected with HDV, which is twofold of what has been estimated before. We also noted a substantially higher HDV prevalence in the IVDU and HRSB population. Our study highlights the need for increased focus on the routine HDV screening and rigorous implementation of HBV vaccine programme.

https://ift.tt/2NoWNvq

Changes in neuromuscular structure and functions of human colon during ageing are region-dependent

Objective

To determine if human colonic neuromuscular functions decline with increasing age.

Design

Looking for non-specific changes in neuromuscular function, a standard burst of electrical field stimulation (EFS) was used to evoke neuronally mediated (cholinergic/nitrergic) contractions/relaxations in ex vivomuscle strips of human ascending and descending colon, aged 35–91 years (macroscopically normal tissue; 239 patients undergoing cancer resection). Then, to understand mechanisms of change, numbers and phenotype of myenteric neurons (30 306 neurons stained with different markers), densities of intramuscular nerve fibres (51 patients in total) and pathways involved in functional changes were systematically investigated (by immunohistochemistry and use of pharmacological tools) in elderly (≥70 years) and adult (35–60 years) groups.

Results

With increasing age, EFS was more likely to evoke muscle relaxation in ascending colon instead of contraction (linear regression: n=109, slope 0.49%±0.21%/year, 95% CI), generally uninfluenced by comorbidity or use of medications. Similar changes were absent in descending colon. In the elderly, overall numbers of myenteric and neuronal nitric oxide synthase-immunoreactive neurons and intramuscular nerve densities were unchanged in ascending and descending colon, compared with adults. In elderly ascending, not descending, colon numbers of cell bodies exhibiting choline acetyltransferase immunoreactivity increased compared with adults (5.0±0.6 vs 2.4±0.3 neurons/mm myenteric plexus, p=0.04). Cholinergically mediated contractions were smaller in elderly ascending colon compared with adults (2.1±0.4 and 4.1±1.1 g-tension/g-tissue during EFS; n=25/14; p=0.04); there were no changes in nitrergic function or in ability of the muscle to contract/relax. Similar changes were absent in descending colon.

Conclusion

In ascending not descending colon, ageing impairs cholinergic function.

https://ift.tt/2D4QuZc

Virtual reality in GI endoscopy: intuitive zoom for improving diagnostics and training

Message

Among the many areas which may benefit from virtual reality (VR), GI endoscopy could be an important one. We developed a system to magnify the endoscopic image on forward movement of the endoscopists head to zoom into areas of interest during real-time endoscopy, called intuitive zoom. We could show that VR could be conveniently incorporated into daily endoscopic work when it comes to closely examining operator-defined regions of interest. Additionally, applied light intensity-derived three-dimensional (3D)reconstruction of the intestinal mucosa was used to better assess lesions such as polyps using the Paris classification. These new techniques might improve routine endoscopic diagnosis and therapy and open a new world of endoscopic training.

In more detailStudy background

Flexible endoscopy is performed using a two-dimensional (2D) image of the working area. Although this is regarded as a standard since 1970,1 new technologies allowing for stereoscopic vision thus improving visual spacial perception emerge....

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What Is Stress? A Systems Perspective

Synopsis

The term "stress" is used to capture important phenomena at multiple levels of biological organization, but finding a general and rigorous definition of the concept has proven challenging. Current models in the behavioral literature emphasize the cognitive aspects of stress, which is said to occur when threats to the organism are perceived as uncontrollable and/or unpredictable. Here we adopt the perspective of systems biology and take a step toward a general definition of stress by unpacking the concept in light of control theory. Our goal is to clarify the concept so as to facilitate integrative research and formal analysis. We argue that stress occurs when a biological control system detects a failure to control a fitness-critical variable, which may be either internal or external to the organism. Biological control systems typically include both feedback (reactive, compensatory) and feedforward (predictive, anticipatory) components; their interplay accounts for the complex phenomenology of stress in living organisms. The simple and abstract definition we propose applies to animals, plants, and single cells, highlighting connections across levels of organization. In the final section of the paper we explore some extensions of our approach and suggest directions for future research. Specifically, we discuss the classic concepts of conditioning and hormesis and review relevant work on cellular stress responses; show how control theory suggests the existence of fundamental trade-offs in the design of stress responses; and point to potential insights into the effects of novel environmental conditions, including those resulting from anthropogenic change.

https://ift.tt/2xtHczU

CRISPR/Cas9 Gene Editing to Make Conditional Mutants of Human Malaria Parasite P. falciparum

We describe a method for generating glmS-based conditional knockdown mutants in Plasmodium falciparum using CRISPR/Cas9 genome editing.

https://ift.tt/2xCThmH

Multidisciplinary treatment for locally advanced breast cancer with internal mammary lymph node metastasis in an elderly patient

Abstract

Internal mammary lymph node (IMLN) metastasis is one of the important prognostic indicators in breast cancer. However, the management for IMLN metastasis is not established. The dissection for IMLN metastasis is not recommended in the National Comprehensive Cancer Network guidelines version3. 2015. Furthermore, radiotherapy including IMLN region and biopsy have attendant risks and hence should be performed with caution. Here, we describe our experience of multidisciplinary treatment for locally advanced breast cancer with IMLN metastasis in an elderly patient. Core-needle biopsy of the breast tumor histologically diagnosed the tumor as estrogen receptor positive, progesterone receptor positive, human epidermal growth factor receptor-2 negative, and high Ki-67 labeling index. IMLN swelling was detected by ultrasonography and breast cancer metastasis was diagnosed by fine-needle aspiration cytology. The patient underwent mastectomy and axillary lymph node dissection, followed by postmastectomy radiation therapy. Systemic therapy using tegafur plus uracil (UFT®; Taiho Pharmaceutical Co., Ltd, Tokyo, Japan) and letrozole was beneficial treatment for disease control.

https://ift.tt/2xsGC6z

Correction to: Daphnane diterpenes inhibit the metastatic potential of B16F10 murine melanoma cells in vitro and in vivo

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https://ift.tt/2OzPCx6

An adaptive combination constrained proportionate normalized maximum correntropy criterion algorithm for sparse channel estimations

An adaptive combination constrained proportionate normalized maximum correntropy criterion (ACC-PNMCC) algorithm is proposed for sparse multi-path channel estimation under mixed Gaussian noise environment. The...

https://ift.tt/2xxI1rI

Editorial: Deep life, kia ora!

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Steep redox gradient and biogeochemical cycling driven by deeply sourced fluids and gases in a terrestrial mud volcano

ABSTRACT

Mud volcanoes provide an accessible channel through which deep subsurface environments can be observed. The manner in which deeply sourced materials shape biogeochemical processes and microbial communities in such geological features remains largely unknown. This study characterized redox transitions, biogeochemical fluxes and microbial communities for samples collected from a methane-rich mud volcano in southwestern Taiwan. Our results indicated that oxygen penetration was confined within the upper 4 mm of fluids/muds and counteracted by the oxidation of pyrite, dissolved sulfide, methane and organic matter at various degrees. Beneath the oxic zone, anaerobic sulfur oxidation, sulfate reduction, anaerobic methanotrophy and methanogenesis were compartmentalized into different depths in the pool periphery, forming a metabolic network that efficiently cycles methane and sulfur. Community members affiliated with various Proteobacteria capable of aerobic oxidation of sulfur, methane and methyl compounds were more abundant in the anoxic zone with diminished sulfate and high methane. These findings suggest either the requirement of alternative electron acceptors or a persistent population that once flourished in the oxic zone. Overall, this study demonstrates the distribution pattern for a suite of oxidative and reductive metabolic reactions along a steep redox gradient imposed by deep fluids in a mud volcano ecosystem.

https://ift.tt/2NUtiB4

Selection of Bradyrhizobium or Ensifer symbionts by the native Indian caesalpinioid legume Chamaecrista pumila depends on soil pH and other edaphic and climatic factors

ABSTRACT

Nodules of Chamaecrista pumila growing in several locations in India were sampled for anatomical studies and for characterization of their rhizobial microsymbionts. Regardless of their region of origin, the nodules were indeterminate with their bacteroids contained within symbiosomes which were surrounded by pectin. More than 150 strains were isolated from alkaline soils from the Thar Desert (Rajasthan), wet-acidic soils of Shillong (Meghalaya), and from trap experiments using soils from four other states with different agro-ecological regions. Molecular phylogenetic analysis based on five housekeeping (rrs, recA, glnII, dnaK andatpD) and two symbiotic (nodA and nifH) genes was performed for selected strains. Chamaecrista pumila was shown to be nodulated by niche-specific diverse strains of either Ensifer or Bradyrhizobium in alkaline (Thar Desert) to neutral (Tamil Nadu) soils and only Bradyrhizobium strains in acidic (Shillong) soils. Concatenated core gene phylogenies showed four novel Ensifer-MLSA types and nine Bradyrhizobium-MLSA types. Genetically diverse Ensifer strains harbored similar sym genes which were novel. In contrast, significant symbiotic diversity was observed in the Bradyrhizobium strains. The C. pumila strains cross-nodulated Vigna radiata and some wild papilionoid and mimosoid legumes. It is suggested that soil pH and moisture level played important roles in structuring the C. pumila microsymbiont community.

https://ift.tt/2D4HPpE

Fecal indicator bacteria and zoonotic pathogens in marine snow and California mussels (Mytilus californianus)

ABSTRACT

Pollution of nearshore waters with disease-causing microorganisms impacts ecosystems health through illness and deaths in people and wildlife, as well as negative socioeconomic consequences of impaired marine resources. Insight on pathogen ecology in coastal habitats is crucial for accurately mitigating inputs and impacts of microbial pollution. Three objectives were addressed to (i) compare fecal pollution in proximity to (a) freshwater runoff, and (b) endemic marine wildlife; (ii) evaluate presence and magnitude of fecal microorganisms in marine snow and mussels and (iii) determine if pathogens in mussels and FIB levels in seawater or mussels are correlated. Sampling during the wet season, proximity to freshwater, and FIB levels in mussel homogenates (but not seawater) were associated with pathogen presence in mussels. Pathogens and FIB were enriched in aggregate-rich fractions, further supporting an important role of marine snow in pathogen transmission. The lack of association between FIB in surrounding waters and presence of pathogens in mussels calls into question current regulations for insuring safe seafood to consumers in the United States, and alternative monitoring approaches such as direct testing for select pathogens should be further evaluated.

https://ift.tt/2NNKWGP

Volatile phenols are produced by strains of Dekkera bruxellensis under Brazilian fuel ethanol industry-like conditions

Abstract

Dekkera bruxellensis is a spoilage yeast in wine and fuel ethanol fermentations able to produce volatile phenols from hydroxycinnamic acids by the action of the enzymes cinnamate decarboxylase (CD) and vinyphenol reductase (VR) in wine. However, there is no information about this ability in the bioethanol industry. This work evaluated CD and VR activities and 4-ethylphenol production from p-coumaric acid by three strains of D. bruxellensis and PE-2, an industrial Saccharomyces cerevisiae strain. Single and multiple-cycle batch fermentations in molasses and sugarcane juice were carried out. D. bruxellensis strains showed similar CD activity but differences in VR activity. No production of 4-ethylphenol by S. cerevisiae in any fermentation system or media was observed. The concentrations of 4-ethylphenol peaked during active growth of D. bruxellensis in single-cycle fermentation but they were lower than in multiple-cycle fermentation. Higher concentrations were observed in molasses with molar conversion (p-coumaric acid to 4-ethylphenol) ranging from 45–85%. As the first report on 4-ethylphenol production in sugarcane musts by D. bruxellensis in industry-like conditions, it opens up a new avenue to investigate its effect on the viability and fermentative capacity of S. cerevisiae as well as to understand the interaction between the yeasts in the bioethanol industry.

https://ift.tt/2MKUvBw