Abstract Introduction Canal wall down (CWD) mastoidectomy has many drawbacks, including chronic otorrhea not responding to medications, granulations, dizziness on exposure to cold or hot water, and tendency of debris accumulation in the mastoid cavity, demanding periodic cleaning. Many of these problems can be solved by reconstruction of the posterior meatal wall (PMW). Objectives To assess the results of PMW reconstruction after CWD mastoidectomy for cholesteatoma using titanium mesh and platelet-rich plasma (PRP) mixed with bone pate. Methods This study was conducted with 20 patients that have atticoantral chronic suppurative otitis media. All cases were subjected to CWD mastoid surgery with complete elimination of the disease and reconstruction of the PMW by titanium mesh and the mixture of PRP with bone pate. All patients were exposed to a full preoperative evaluation and full postoperative assessment of the complications, the appearance of the external auditory canal contour, and the hearing gain expressed by the change of the air bone gap postoperatively. Results The PMW reconstructed by titanium mesh and the mixture of PRP with bone pate showed a smooth contour. During the follow-up of 12 to 36 months, the postoperative appearance of the external auditory canal contour was found to be smooth without hidden pouches, irregularities or stenosis in all cases. No granulation, foreign body reaction, or extrusion and/or displacement of the titanium mesh were registered. No facial palsy or recurrent cholesteatoma was reported. Conclusion The surgical reconstruction of the PMW using PRP, bone pate and titanium mesh after CWD mastoidectomy appears to be reliable without considerable complications, giving a smooth appearance to the PMW.
https://ift.tt/2zrvGJE
Δευτέρα 9 Ιουλίου 2018
Platelet-Rich Plasma in Reconstruction of Posterior Meatal Wall after Canal Wall Down Mastoidectomy
Development and Administration of Chronic Suppurative Otitis Media Questionnaire-12 (COMQ-12) and Chronic Otitis Media Outcome Test-15 (COMOT-15) in Kannada
Abstract Introduction It is essential to determine the quality of life among individuals with chronic suppurative otitis media (CSOM). However, there is limited literature on healthrelated quality of life measurements in Kannada-speaking individuals with CSOM. Objectives The present study attempted to translate and validate Chronic Suppurative Otitis Media Questionnaire-12 (COMQ-12) and Chronic Otitis Media Outcome Test- 15 (COMOT-15) in Kannada. Method The English questionnaires were translated and back-translated, and they were later verified for content validity. The developed questionnaires were then administered to 100 individuals with CSOM for further validation. Results The results of the study showed that the translated questionnaires have good internal consistency for measuring quality of life among individuals with CSOM. The study also showed that Kannada-speaking individuals with CSOM show significant impairment in their health-related quality of life measures. Conclusions The impairments weremore related to ear symptoms and psychological issues. However, test-retest reliability of the developed questionnaire and its further validation are essential. Thus, these questionnaires attempt to understand the problems of the individuals with CSOM from the patients' perspective and help clinicians provide the appropriate management.
https://ift.tt/2m86m1W
Pitch-Matching Accuracy and Temporal Auditory Processing
Abstract Introduction Pitch-matching refers to the ability to vocally reproduce an acoustic model in a corresponding tone to the presented sound. This ability, which is dependent on pitch perception ability, can vary among individuals, and some are not able to sing in the correct tune or discriminate differences between tones. Objective To correlate pitch-matching accuracy and auditory processing in individuals without musical training. Methods A Pitch-Matching Test (vocal reproduction of synthesized and human voice sounds) and two commercially available tests of auditory temporal processing (the Pitch Pattern Sequence Test and the Random Gap DetectionTest) were administered to all participants. A total of 62 college students of both genders, aged between 18 and 35 years old, were divided into 2 groups, according to their performances in the Pitch- Matching Test (the accurate match group and the inaccurate match group). Results In the Pitch-Matching Test, both groups achieved better results when reproducing vocalized sounds. The accurate match group achieved a significantly higher pitch pattern sequence test performance. In the Random Gap Detection Test analysis, there were no differences between the two groups. The Pearson's chi-squared test showed a direct correlation between the Pitch-Matching Test and the Pitch Pattern Sequence Test. Conclusion The findings of this study suggest the existence of a significant relationship between temporal auditory processing and pitch-matching, through which accurate pitch-matching individuals perform better in the Pitch Pattern Sequence Test. Inaccurate pitch-matching individuals may be skilled at discriminating pitch, despite their poor performance in the Pitch-Matching Test.
https://ift.tt/2zqKtEn
Short-Term Audiological Results of Diode Laser in Comparison with Manual Perforation in Stapes Surgery
Abstract Introduction Diode laser is a new alternative in stapes surgery for otosclerosis. The present study is the first to compare the short-term results of the surgery performed using diode laser to those obtained through the conventional fenestration technique. Objective To use audiometry to establish a comparative analysis between the functional results obtained through surgery for otosclerosis using diode laser and the conventional technique. Method Audiometric evaluation of 12 patients submitted to stapes surgery for otosclerosis, using diode laser or conventional fenestration by needle and drills, between 2014 and 2015. Each group was composed of 6 patients. Pre and postoperative measures were compared for three months in both groups. The speech recognition threshold, the air and bone conduction threshold, as well as the gap between them at 500 Hz, 1 KHz, 2 KHz and 4 KHz were measured. Results Significant difference in bone conduction and SRT was observed when compared post- and preoperative results in the diode group. However diode and conventional technique groups presented significant differences in air conduction and air-bone gap, suggesting that both can provide functional improvement. Conclusion Laser stapedotomy is a safe technique with good results. Both laser surgery and the conventional technique have improved the hearing of patients with a discreet advantage for the diode laser. Further prospective and randomized clinical trials are required to disclose all possible benefits of the stapes surgery using diode laser.
https://ift.tt/2m4udiT
The Impact of Deep Brain Stimulation on the Quality of Life and Swallowing in Individuals with Parkinson’s Disease
Abstract Introduction Deep brain stimulation (DBS) is an established treatment for Parkinson's disease (PD). However, there is little evidence regarding the effect of DBS on dysphagia. Objective To assess the swallowing and quality of life of individuals with PD before and after DBS surgery. Methods Our sample consisted of people who had undergone DBS surgery in a referral hospital in the state of Rio Grande do Sul, Brazil. The inclusion criteria were a diagnosis of PD and having undergone DBS surgery. A cognitive screening, through a questionnaire about depression and quality of life, was conducted. Evaluations of each patient's swallowing were performed before and after surgery. The assessment consisted of anamnesis, clinical assessment, the Functional Oral Intake Scale, clinical evaluation of swallowing, and the Hoehn and Yahr scale. Results The sample included 10 individuals, all male, with a mean age of 57.3 years (±4.7), a mean disease duration of 13.0 years (±2.4), and mean level education of 8.1 years (±4.0). In the clinical evaluation of the swallowing, a significant improvement after DBS was not observed. However, little changes in the signs and symptoms of dysphagia that had a positive impact on the quality of life were observed. Furthermore, there was no relation between the patients' motor subtype and swallowing pre- and post-DBS. Conclusion There was an improvement in the quality of life of the patients after DBS. However, the improvement in the clinical signs and symptoms of dysphagia did not cause an overall improvement in the swallowing function.
https://ift.tt/2zrVkhu
Comparative Study Between Peristomal Patches in Patients with Definitive Tracheostomy
Abstract Introduction To prevent or diminish pulmonary problems in laryngectomized patients, continuous use of a heat and moisture exchanger (HME) is recommended. Therefore, automatic speaking valves are also often combined with an HME to enable hands-free speech. In order to keep these devices in place, most commonly, peristomal patches are used. Objective This prospective clinical 2 x 2 crossover study aims at assessing the added value of a new patch for HME application, the Provox StabiliBase OptiDerm (SBO). The device combines the stable and conical base of the Provox StabiliBase with the skinfriendlier hydrocolloid Provox OptiDerm (OD) patch. Methods Thirty-two laryngectomized patients were included in this multicenter study. Participants were asked to compare SBO to OD, and to the patch they normally use. The primary outcome measure was patient preference. Results Overall, 60% of the participants had preference for their normally used patch, 23% preferred the SBO and 17% indicated no preference. When comparing the SBO to the OD, 43% preferred the SBO, 40% the OD and 17% had no preference. Conclusion Most patients preferred their normally used patch and SBO was favored by a subgroup. Provox StabiliBase OptiDerm seems to be a valuable addition to the existing patches and further increases patients' options for HME application.
https://ift.tt/2m4u9Qb
Frequency of Cervical Nodal Metastasis in Early- Stage Squamous Cell Carcinoma of the Tongue
Abstract Introduction Oral cavity carcinoma is an aggressive tumor, with the tongue being one of the most common subsites of involvement. Surgery is a gold standardmethod of dealing with advanced-stage tumors. However, for early-stage carcinomas of the tongue, the management remains controversial. Several studies have indicated that early-stage cancers have a high chance of occult cervical node metastasis, which, if left untreated, can greatly affect the prognosis. Certain parameters can help identify patients with occult cervical node metastases, and can avoid unnecessary neck dissection in node negative patients. Tumor thickness is one such objective parameter. Objective To estimate the frequency of cervical lymph node metastasis in patients with early-stage, node-negative (N0) squamous cell carcinoma of the tongue. Methods In-patient hospital data was reviewed from January 2013 until March 2014, and 78 patients who underwent primary resection of the tumor and neck dissection for biopsy-proven, early stage squamous cell carcinoma of the tongue were included. Data such as tumor thickness, tumor differentiation and presence of occult nodal metastasis in the surgical specimen were gathered from the histopathology reports. The frequency of subclinical cervical lymph node metastasis in patients with early-stage squamous cell carcinoma of the tongue was estimated. Results A total of 69% of the patients with tumor thicknesses > 5 mm had tumor metastases in the neck nodes, while 100% of the patients with tumor thicknesses < 5 mm had no neck nodal metastasis. Conclusion A tumor thickness > 5 mm is significantly associated with subclinical metastasis, and prophylactic neck dissection is warranted in such cases.
https://ift.tt/2N3JADF
Dynamic Slow Motion Video Endoscopy as an Adjunct to Impedance Audiometry in the Assessment of Eustachian Tube Function
Abstract Introduction Eustachian tube (ET) dysfunction plays an important role not only in the pathophysiology of various middle ear disorders, but also in predicting the outcome of the treatment. As there is no single test that assesses both the anatomic and physiological functions of the ET, a combination of tympanometry and dynamic slow motion video endoscopy may improve the sensitivity of ET function assessment. Objective To find out if there is any correlation between dynamic slow motion nasal video endoscopy and impedance audiometry in assessing ET function in patients with middle ear diseases. Methods Ours was a descriptive study performed with 106 patients attending the Ear, Nose and Throat (ENT) Outpatient Department of a tertiary care center in South India with features suggestive ofmiddle ear disease. All patients underwent impedance audiometry and dynamic slow motion nasal video endoscopy, and were graded based on the severity of the ET pathology. Results A total of 47 out of 97 patients with abnormal endoscopy findings also had abnormal impedance audiometry. The correlation was greater among the patients with higher grades of ET dysfunction. The endoscopy findings of 106 cases, when correlated with middle ear manometry, revealed that 56 cases showed complete agreement, and 50 cases showed disagreement. The nasal endoscopy results, when correlated with middle ear manometry studies by using McNemar's chi-squared (χ2) test, showed a significant association between the 2 tests (p = 0.017). Conclusion There is a significant alteration in middle ear pressure as the severity of the ET tube dysfunction increases. Impedance audiometry and nasal endoscopy provide a better measure of ET function.
https://ift.tt/2KNfVSw
ENT Foreign Bodies: An Experience
Abstract Introduction Ear, nose and throat (ENT) foreign bodies (FBs) are common occurrences, particularly among children. The proper recognition, study, and management of FBs are required to prevent complications. Their consequences are greatly variable, from mild disturbances that may not require hospitalization up to life-threatening complications. Objective To analyze the clinical spectrum of ENT FBs, the methods of removal, the outcomes and complications as seen in a tertiary referral hospital. Methods This hospital-based cross-sectional retrospective study was performed from July 2014 to June 2016. Patients with any type of ENT FBs, regardless of age, were included in the study; data was collected from 1,013 patients (572 males and 440 females) with a mean age of 12.5 years. Results Foreign bodies represented a large category among ENT emergencies (30%). Children were affected more frequently, particularly ≤ 6 years old. Swallowed FBs were themost common (53.6%), followed by aural FBs (24.68%), nasal FBs (19%), and inhaled FBs (2.6%). A total of 54.69% of ENT s were removed under general anesthesia (GA). Conclusion Foreign bodies (FB) in the ears, nose or throat are a common occurrence in otorhinolaryngology (ENT) emergency services. Children are the most affected age group. The commonest site of FB lodgment is in the throat. Ear, nose and throat FBs need to be properly managed to avoid complications.
https://ift.tt/2N1kdCs
The Role of the Level of Interleukin-33 in the Therapeutic Outcomes of Immunotherapy in Patients with Allergic Rhinitis
Abstract Introduction Allergic rhinitis (AR) affects up to 40% of the population and results in nasal itching, congestion, sneezing, and clear rhinorrhea. Objectives This study aimed to evaluate the changes in the clinical symptoms and in the level of serum interleukin (IL)-33 before and after pollen immunotherapy (IT) in patients with AR. Methods The total symptomscore and the levels of total immunoglobulin E (IgE) and IL-33 were determined in the serum of 10 non-allergic healthy controls and 45 patients with AR who were equally divided into 3 groups: GI (patients did not receive IT), GII (patients had received IT for 6 months) and GIII (patients had received IT for 2 years). Results There was a significantly higher concentration of IgE and IL-33 in the serum of patients with AR than in that of non-allergic patients. Furthermore, serum level of IL-33 decreased significantly after pollen IT. But, there was no significant reduction in the serum level of IL-33 between GII and GIII patients. Conclusion Our results show a clinical improvement associated with a decrease in serum level of IL-33 after pollen IT.
https://ift.tt/2KI5bEU
Assessment of Pulmonary Function before and after Sinus Surgery in Lung Transplant Recipients
Abstract Introduction The association between sinus and lung diseases is well known. However, there are scarce studies regarding the effects of sinus surgery on pulmonary function in lung transplant recipients. The present study describes our experience with sinus surgery in lung transplant recipients with chronic rhinosinusitis. Objectives To assess the impact of sinus surgery for chronic rhinosinusitis on pulmonary function and on inpatient hospitalization days due to lower respiratory tract infection in lung transplant recipients. Methods A retrospective study conducted between 2006 and 2012 on a sample of lung transplant recipients undergoing sinus surgery for chronic rhinosinusitis. Pulmonary function, measured by forced vital capacity (FVC) and forced expiratory volume in the first second (FEV1), as well as inpatient hospitalization days due to lower respiratory tract infection, were compared 6 months before and 6 months after sinus surgery. Results The FEV1 values increased significantly, and the inpatient hospitalization days due to bronchopneumonia decreased significantly 6 months after sinus surgery. The preoperative and postoperative median FEV1 values were 2.35 and 2.68 respectively (p = 0.0056). The median number of inpatient hospitalization days due to bronchopneumonia 6 months before and 6 months after surgery were 32.82 and 5.41 respectively (p = 0.0013). Conclusion In this sample of lung transplant recipients with chronic rhinosinusitis, sinus surgery led to an improvement in pulmonary function and a decrease in inpatient hospitalization days due to bronchopneumonia.
https://ift.tt/2N3O4dw
An Analysis of Anatomic Variations of the Sphenoid Sinus and Its Relationship to the Internal Carotid Artery
Abstract Introduction The sphenoid sinus (SS) has a high variability; its anatomical relations and variationsmust be well understood prior to the expanded endoscopic surgery (EES) at the skull base via the endonasal transsphenoidal approach. A feared complication is injury to the internal carotid artery (ICA). Objective To evaluate the anatomic variations of the SS and its relationship to the ICA using computed tomography (CT). Methods Cross-sectional retrospective study. Analysis of 90 patients' CT scans on axial, coronal and sagittal planes with 1 mm slices, evaluating lateral and posterior extensions of pneumatization of the SS, deviation of the sphenoid septum, presence of septations and their relationship to the parasellar and paraclival segments of the internal carotid artery (psICA and pcICA, respectively). Results The association between the protrusions of the psICA and the pcICA was statistically significant (p < 0.001), as was the association between the lateral extension of pneumatization of the SS and the protrusion of the psICA (p = 0.014). The presence of the posterior extension of pneumatization of the SS and protrusion of the pcICA occurred in 46% of the cases. Deviation of the sphenoid septum in the direction of the pcICA was present in 14% and dehiscence of the pcICA was seen in 3.6% of the cases. Conclusion Using the CT scan to recognize the type of extensions of pneumatization of the SS, the deviation of the sphenoid septum, and the presence of septations is beneficial to identify accurately the ICA and to reduce the risk of injury to it.
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Unusual Presentation of Differentiated Thyroid Cancer Metastasis
Abstract Introduction The rates of thyroid cancers are on a rise, especially well-differentiated thyroid cancers. This could be partly due to newer diagnostic modalities, like highresolution ultrasound, that can pick up smaller lesions. Differentiated thyroid cancers with distantmetastases are not common, and even rarer is the initial presentation with complaints not related to the neck. Objectives The objective of this series was to study and report the unusual cases of patients with differentiated thyroid cancer with distant metastasis. There is a lack of data in the literature on these cases, and due to the rarity of such metastases, no definite treatment protocol has been defined. Methods A retrospective chart review of 1,200 cases of thyroid surgeries was performed. A total of 10 cases of well-differentiated thyroid cancer on the final histopathology exam that had initially presented with usual complaints to departments other than the Otolaryngology Department were identified. Results A total of 6 patients had papillary carcinoma, whereas 4 patients had follicular carcinoma on final the histopathology exam. Two patients presented with iliac crest lesions, 2 with vertebral lesions one each with parapharyngeal mass, supraclavicular mass, labia majora swelling and bleeding, lung, rib and neck of femur lesion. Conclusion There are still no specific guidelines on how to address these patients with differentiated thyroid cancer with distant metastasis (except for the cases of bone and lung lesions) and on which treatment should be offered in case of recurrence. More studies on the subject are required.
https://ift.tt/2MZ6lJ1
The Effects of Experimental Intratympanic Steroid Administration on Organ of Corti Type 1 Spiral Ganglion
Abstract Introduction It is unclear how effective is the intratympanic (IT) steroid treatment on organ of Corti type 1 spiral ganglion, its optimal dosage and frequency of administration. The effect of dexamethasone on cochlear functions in individuals with a normal hearing ability is also unknown. Objective The aim of this study was to evaluate, at the electrophysiological and ultrastructural levels, the effect of IT dexamethasone administration in guinea pigs with normal hearing on organ of Corti type 1 spiral ganglion. Methods A total of 20 guinea pigs (n = 40 ears) whose hearing was detected to be normal by electrophysiological tests were included in the study and randomly divided into 6 groups. Four groups were considered study groups, while 2 groups were considered control groups. Dexamethasone was administered intratympanically in doses of 2 mg/mL and 4 mg/mL in the guinea pigs in the study groups. The animals in the control groups received physiological saline in equal doses as the study groups. All interventions were performed under general anesthesia, and the electrophysiological tests were repeated following the IT injections. Results No statistically significant differences were found among the groups when the IT injections were evaluated in terms of the electrophysiological measurements (p > 0.05). The ultrastructural evaluation showed a cellular mitochondrial increase in the spiral ganglions of the cochlea in the groups in which dexamethasone was administered in a dose of 4 mg/mL. Conclusion According to the findings of this study, it can be suggested that the IT injection of dexamethasone is safe, and when applied in a dose of 4mg/mL, it increases metabolic activity at the cellular level.
https://ift.tt/2KJK1Gy
Polysomnography Applied to Patients with Tinnitus: A Review
Abstract Introduction Tinnitus has been defined as an "auditory phantom perception," meaning that tinnitus results from an abnormal activity within the nervous system, in the absence of any internal or external acoustic stimulation. About 10 to 15% of the adult population is affected by tinnitus, and a relevant percentage of tinnitus sufferers experience symptoms severe enough to significantly affect quality of life, including sleep disturbances, work impairment, and, in some cases, psychiatric distress. The selfrated complaints about tinnitus focus on emotional distress, auditory perceptual difficulties, and sleep disturbances. Objectives To evaluate the works that show sleep disorders in patients with tinnitus, and sleep disorders assessed by polysomnography. Data Synthesis We found four studies with polysomnography to assess sleep disorders in patients with tinnitus. The first study evaluated 80 patients who were military personnel without major psychiatric disturbances, and their tinnitus was associated with noise-induced permanent hearing. The second study was a prospective, case-control, nonrandomized study of 18 patients affected by chronic tinnituswho were compared with a homogeneous control group consisting of 15 healthy subjects. The last work evaluated questionnaires mailed to patients before their initial appointment at the Oregon Health Sciences University Tinnitus Clinic between 1994 and 1997. These questionnaires requested information pertaining to insomnia, tinnitus severity, and loudness. Follow-up questionnaires were mailed to 350 patients 1 to 4 years (mean 5 ± 2.3 years) after their initial appointment at the clinic. Conclusion There are few studies with polysomnography for the evaluation of patients with sleep disorders caused by tinnitus. This shows the need for more studies on this subject.
https://ift.tt/2N1RbCF
Comparison of Bite Force with Locking Plates versus Non-Locking Plates in the Treatment of Mandibular Fractures: A Meta-Analysis
Abstract Introduction Mandibular fractures represent a high percentage of all facial fractures, and the bite force is a fundamental parameter to measure the actual mandibular function and, subsequently, the masticatory efficiency and quality of life. Objectives The purpose of the present systematic review was to verify if there is any difference in the bite forces of patients with mandibular fractures fixed by locking or non-locking plates, testing the null hypothesis of no difference in this parameter. Data Synthesis A systematic review of the literature was conducted using four databases (PubMed, Virtual Health Library,Web of Science and Science Direct) without restrictions as to publication date or language. We found 3,039 abstracts, and selected 4 articles for this review. Conclusion The overall results show better performance in bite force for the locking plates when compared with the non-locking plates in the incisor region (mean deviation [MD]: 1.18; 95% confidence interval [95%CI]: 0.13-2.23), right molar region (MD: 4.71; 95%CI: 0.63-8.79) and left molar region (MD: 10.34; 95%CI: 4.55-16.13). Although the results of this study indicated a better bite force result with the locking plates, there is still no sufficient evidence to support this information safely.
https://ift.tt/2m60BS7
Intratympanic Gentamicin for Intractable Ménière’s Disease - A Review and Analysis of Audiovestibular Impact
Abstract Introduction Intratympanic gentamicin regulates the symptoms in most patients with incapacitating Ménière's disease. The treatment protocols have changed over the years from medical labyrinthectomy to preservation of vestibular function. Objectives This study aims to review the audiovestibular response related to the effect of the drug in controlling vertigo. Data Synthesis Articles were identified by means of a search in the PubMed database using the key words Meniere and intratympanic or transtympanic gentamicin. Total 144 articles were reviewed after excluding those that were technical reports, those based on experimental animal studies, those that focused on outcomes other than vertigo (tinnitus or aural fullness), those with delivery methods other than tympanic membrane injection, and those with bilateral cases. If there was more than one article by the same author(s) or institution, only the most recent one matching the aforementioned criteria and those that were not overlapping were included. Conclusion Titration methods or multiple injections on a daily basis can be preferred if the patients have profound or non-serviceable hearing, since these methods have significant incidence of hearing loss. Treatment protocols with a frequency of injection not shorter than once a week, or those with injections on a monthly basis as "needed" provide the same level of vertigo control with better preservation of hearing. Caloric testing is not an ideal tool to analyze the correlation between vertigo control and the effect of gentamicin as compared with gain asymmetry of the vestibulo-ocular reflex. Vestibular-evoked myogenic potentials and the head thrust test are more reliable than other vestibular tests for the follow-up of patients undergoing gentamicin treatment.
https://ift.tt/2zmvE5W
Educational Analytics: A New Frontier for Gamification?
https://ift.tt/2m60xBR
Evaluating a Blended Online Learning Model Among Undergraduate Nursing Students: A Quantitative Study
https://ift.tt/2zmvyeA
Use of Communication Tools for Mechanically Ventilated Patients in the Intensive Care Unit
https://ift.tt/2m60sOz
Leveraging MIMO-OFDM radio signals for device-free occupancy inference: system design and experiments
In device-free radio frequency (RF) body occupancy inference systems, RF signals encode information (e.g., body location, posture, activity) about moving targets (not instrumented) that alter the radio propaga...
https://ift.tt/2NFrMQj
An unusual case of mycobacterium tuberculous coronary arteritis and thrombosis resulting in acute myocardial infarction
Abstract
Tuberculosis (TB) is a prevalent infection worldwide and an endemic infection in Singapore. The most common presentation is that of pulmonary tuberculosis. Extra pulmonary tuberculosis usually involves the lymph nodes, pleura, central nervous system, or abdominal cavity. Involvement of the heart is rare (0.14–2% of TB cases), and when it is involved, it tends to be in the pericardium or myocardium. Here, a rare case of sudden death due to tuberculous coronary arteritis with tuberculous coronary thrombosis resulting in acute myocardial infarction is presented.
https://ift.tt/2zpPYTU
Cancers, Vol. 10, Pages 228: NGAL is Downregulated in Oral Squamous Cell Carcinoma and Leads to Increased Survival, Proliferation, Migration and Chemoresistance
Cancers, Vol. 10, Pages 228: NGAL is Downregulated in Oral Squamous Cell Carcinoma and Leads to Increased Survival, Proliferation, Migration and Chemoresistance
Cancers doi: 10.3390/cancers10070228
Authors: Javadi Monisha Nand Kishor Roy Ganesan Padmavathi Kishore Banik Devivasha Bordoloi Amrita Devi Khwairakpam Frank Arfuso Arunachalam Chinnathambi Tahani Awad Alahmadi Sulaiman Ali Alharbi Gautam Sethi Alan Prem Kumar Ajaikumar B. Kunnumakkara
Oral cancer is a major public health burden worldwide. The lack of biomarkers for early diagnosis has increased the difficulty in managing this disease. Recent studies have reported that neutrophil gelatinase-associated lipocalin (NGAL), a secreted glycoprotein, is upregulated in various tumors. In our study, we found that NGAL was significantly downregulated in primary malignant and metastatic tissues of oral cancer in comparison to normal tissues. The downregulation of NGAL was strongly correlated with both degree of differentiation and stage (I–IV); it can also serve as a prognostic biomarker for oral cancer. Additionally, tobacco carcinogens were found to be involved in the downregulation of NGAL. Mechanistic studies revealed that knockdown of NGAL increased oral cancer cell proliferation, survival, and migration; it also induced resistance against cisplatin. Silencing of NGAL activated mammalian target of rapamycin (mTOR)signaling and reduced autophagy by the liver kinase B1 (LKB1)-activated protein kinase (AMPK)-p53-Redd1 signaling axis. Moreover, cyclin-D1, Bcl-2, and matrix metalloproteinase-9 (MMP-9) were upregulated, and caspase-9 was downregulated, suggesting that silencing of NGAL increases oral cancer cell proliferation, survival, and migration. Thus, from our study, it is evident that downregulation of NGAL activates the mTOR pathway and helps in the progression of oral cancer.
https://ift.tt/2KJnYQv
Eighteen-year-old man with autism, obsessive compulsive disorder and a SHANK2 variant presents with severe anorexia that responds to high-dose fluoxetine
The SHANK2 gene codes for a protein involved in organising the postsynaptic density and disruptions have been associated with autism spectrum disorders (ASDs). ASDs are frequently comorbid with intellectual disability and anxiety disorders and emerging evidence suggests potentially common aetiologies. Here, we report the case of an 18-year-old man with ASD who presented with severe anorexia due to fear of food contamination, food avoidance and stereotypies attributable to underlying obsessive compulsive disorder (OCD). The patient was found to be heterozygous for c.2518C>T (p.Pro840Ser), a likely damaging coding variant in the proline rich region of SHANK2. Interestingly, the patient's disordered eating behaviour began to improve only after high-dose fluoxetine was initiated to target OCD symptoms. Overall, this case highlights the utility of molecular genetic testing in clinical psychiatry and provides an example of how genetic information can inform clinicians in the treatment of complex neuropsychiatric syndromes.
https://ift.tt/2KWIzA4
Quizartinib Bests Chemo for FLT3-Mutant AML [News in Brief]
Targeted agent extends survival for patients with relapsed or refractory disease.
https://ift.tt/2MYESqT
Therapeutic targeting of the pre-metastatic stage in human brain metastasis
Brain metastases (BM) result from the spread of primary tumors to the brain and are a leading cause of cancer mortality in adults. Secondary tissue colonization remains the main bottleneck in metastatic development, yet this "pre-metastatic" stage of the metastatic cascade, when primary tumor cells cross the blood-brain barrier and seed the brain before initiating a secondary tumor, remains poorly characterized. Current studies rely on specimens from fully developed macro-metastases to identify therapeutic options in cancer treatment, overlooking the potentially more treatable "pre-metastatic" phase when colonizing cancer cells could be targeted before they initiate the secondary brain tumor. Here we use our established brain metastasis initiating cell (BMIC) models and gene expression analyses to characterize pre-metastasis in human lung-to-brain metastases. Pre-metastatic BMIC engaged invasive and epithelial developmental mechanisms while simultaneously impeding proliferation and apoptosis. We identified the dopamine agonist Apomorphine to be a potential pre-metastasis-targeting drug. In vivo treatment with Apomorphine prevented BM formation, potentially by targeting pre-metastasis-associated genes KIF16B, SEPW1, and TESK2. Low expression of these genes was associated with poor survival of lung adenocarcinoma patients. These results illuminate the cellular and molecular dynamics of pre-metastasis, which is subclinical and currently impossible to identify or interrogate in human patients with BM. These data present several novel therapeutic targets and associated pathways to prevent BM initiation.
https://ift.tt/2KVAXOa
SMAD4 suppresses WNT-driven de-differentiation and oncogenesis in the differentiated gut epithelium
The cell-of-origin of colon cancer is typically thought to be the resident somatic stem cells, which are immortal and escape the continual cellular turnover characteristic of the intestinal epithelium. However, recent studies have identified certain conditions in which differentiated cells can acquire stem-like properties and give rise to tumors. Defining the origins of tumors will inform cancer prevention efforts as well as cancer therapies, as cancers with distinct origins often respond differently to treatments. We report here a new condition in which tumors arise from the differentiated intestinal epithelium. Inactivation of the differentiation-promoting transcription factor SMAD4 in the intestinal epithelium was surprisingly well-tolerated in the short term. However, after several months, adenomas developed with characteristics of activated WNT signaling. Simultaneous loss of SMAD4 and activation of the WNT pathway led to de-differentiation and rapid adenoma formation in differentiated tissue. Transcriptional profiling revealed acquisition of stem cell characteristics, and co-labeling indicated that cells expressing differentiated enterocyte markers entered the cell cycle and re-expressed stem cell genes upon simultaneous loss of SMAD4 and activation of the WNT pathway. These results indicate that SMAD4 functions to maintain differentiated enterocytes in the presence of oncogenic WNT signaling, thus preventing de-differentiation and tumor formation in the differentiated intestinal epithelium.
https://ift.tt/2L6ISF1
Dichotomous associations of liver pathology with hepatocellular carcinoma morphology in Middle Africa: the situation in Cameroon
This study evaluates the occurrence of the various morphological subtypes of hepatocellular carcinoma (HCC) and their connections with some risk factors in Cameroonian patients. The database of the 360 liver b...
https://ift.tt/2L2Tng9
Determinants of low birth weight among neonates born in Amhara Regional State Referral Hospitals of Ethiopia: unmatched case control study
This study was conducted to identify the determinants of low birth weight among infants born in Amhara Regional State Referral Hospitals of Ethiopia.
https://ift.tt/2L0qpKw
Maize Genomes to Fields: 2014 and 2015 field season genotype, phenotype, environment, and inbred ear image datasets
Crop improvement relies on analysis of phenotypic, genotypic, and environmental data. Given large, well-integrated, multi-year datasets, diverse queries can be made: Which lines perform best in hot, dry enviro...
https://ift.tt/2KTNT73
Determinants of burnout syndrome among nursing students in Cameroon: cross-sectional study
Burnout syndrome defined as a state of emotional exhaustion and disengagement; which could reduce optimal healthcare delivery, is relatively common amongst healthcare trainees. We sought to assess the determin...
https://ift.tt/2L43rC7
Prevalence and risk factors of gastro-esophageal reflux disease among undergraduate medical students from a southern Indian medical school: a cross-sectional study
Gastro-esophageal reflux disease (GERD) affects all age groups, and various lifestyle as well as psychological factors are recognized as risk factors for GERD. Undergraduate medical students are exposed to lif...
https://ift.tt/2KT2rnF
Emerging Targeted Therapy for Tumors with NTRK Fusion Proteins
The oncogenesis-promoting role of chromosomal rearrangements for several hematological and solid malignancies is well recognized. However, identifying targetable, actionable, and druggable chromosomal rearrangements remains a challenge. Targeting gene fusions and chromosomal rearrangements is an effective strategy in treating gene rearrangement-driven tumors. The NTRK (Neurotrophic Tyrosine Receptor Kinase) gene family encodes three tropomyosin-related kinase (TRK) receptors that preserve central and peripheral nervous system development and function. NTRK genes, similar to other genes, are subject to alterations, including fusions. Preclinical studies have demonstrated that Trk fusion proteins promote oncogenesis by mediating constitutive cell proliferation and survival. Several clinical trials have estimated the safety and efficacy of TRK fusion kinase receptor inhibitors and have demonstrated encouraging antitumor activity in patients with NTRK-rearranged malignancies. Specifically, larotrectinib and entrectinib have emerged as potent, safe, and promising TRK inhibitors. Herein, we discuss the potential oncogenic characteristics of TRK fusion proteins in various malignancies and highlight ongoing clinical trials of kinase inhibitors targeting them.
https://ift.tt/2m5A9YP
P127. Nerve ultrasound in children with ulnar neuropathy associated with supracondylar humerus fracture
Assessing nerve traumas in children is challenging. Electrodiagnostic studies are often not tolerated. We tested if ultrasound examination in children with recent supracondylar humerus fracture and ulnar nerve pathology was well tolerated and whether it was helpful in assessing the nerve trauma.
https://ift.tt/2m4cQyD
P73. A new cognitive diagnostic marker to distinguish between Subjective Cognitive Decline, mild cognitive impairment and healthy adults?
Patients with Subjective Cognitive Decline (SCD) have an increased risk of Alzheimer's diseases (AD) pathology while their performance in usual cognitive tests is normal. The goal of the present study was to assess whether another cognitive test, late verbal recall, can distinguish between SCD, mild cognitive impairment (MCI) and no cognitive impairment (healthy controls, HC).We used a late recall method which has so far only been applied in epilepsy patients (Witt et al., 2012). After being screened with the CERAD test battery (Morris et al., 1989; Mirra et al., 1991) patients from our memory clinic were called 24 h later and asked whether they still remembered words of the list they had to learn the day before.
https://ift.tt/2m3bEvv
P72. Agonists and antagonists of specific serotonergic subreceptors and combined GABAA agonists and NMDA antagonists as a possible treatment of Alzheimers disease
In Alzheimer's disease, neurotransmitter alterations, for example acetylcholine deficiency and a surplus of the excitotoxic glutamate have been described and are associated with cognitive impairment. An interaction between acetylcholine deficiency and beta-amyloid formation has also been reported. Neurotransmitter imbalances between noradrenaline, dopamine and 5-HT on the one hand, and acetylcholine, GABA and glutamate on the other hand have been reported in the temporal cortex and hippocampus. Since serotonin plays an important role in cognitive processes a question arises, whether agonists or antagonists at specific serotonergic subreceptors, for example 5-HT4 or 5-HT7 agonists or 5-HT6 antagonists, can improve cognitive functions.
https://ift.tt/2zokNYX
P77. Prognosis of cognitive decline in Parkinsons disease: a combined marker of quantitative EEG and clinical variables improves prediction
Models have been constructed to estimate individual risk for global cognitive impairment in Parkinson's disease (PD) using a small set of clinical predictor variables (age at disease onset, sex, education, MMSE, motor impairment, depression) (Liu et al., 2017). The prediction algorithm accurately forecast cognitive decline with a predefined cut-off score. Slowing of the electroencephalogram (EEG) is frequent in PD and as it is a predictive biomarker for dementia in PD (PDD), it is likely that adding information about EEG frequency might increase predictive accuracy of cognitive decline.
https://ift.tt/2ulKm7c
1. The development of propagated discharge and behavioural arrest in hippocampal and amygdala kindled seizures
Patients with focal temporal lobe seizures often experience transient episodes of impaired awareness with behavioural arrest, but the precise mechanism remains unknown. The Blumenfeld hypothesis attributes these deficits to a loss of cholinergic input to the cortex. This is presumed to result from increased activation of inhibitory regions that suppress subcortical arousal, giving rise to slow wave activity. To investigate this hypothesis – and more specifically, to characterize the relationship between propagated discharge, cortical slow waves and behavioural arrest – we performed kindling studies in rats.
https://ift.tt/2m3bvbr
P106. Anodal tDCS over the left sensorimotor area improves motor symptoms and modulates corticocortical coherence in Parkinson’s disease
Network activity in the beta range is correlated with motor symptoms in Parkinson's disease (PD). Anodal transcranial direct current stimulation (atDCS) over the sensorimotor area modulates cortical excitability and may alleviate motor symptoms in PD. In this study, we aimed to explore the effect of atDCS over the left sensorimotor area on clinical motor outcome, right hand fine motor performance and cortical motor network connectivity.In this double-blind randomized sham-controlled combined EEG and tDCS study, we investigated ten pharmacologically treated idiopathic PD patients after overnight withdrawal of dopaminergic medication and eleven healthy controls during an isometric precision grip task of the right hand before and after stimulation.
https://ift.tt/2zq29QD
2. The anticonvulsant effects of intravenous 5a-dihydroprogesterone on amygdala-kindled seizures in rats
5a-dihydroprogesterone (DHP), the first metabolite of progesterone and the precursor of allopregnanolone, has anticonvulsant properties. Past studies have reported the suppression of amygdala-kindled seizures by DHP administered via the subcutaneous route. We now demonstrate strong anticonvulsant effects of DHP administered intravenously (IV) via the jugular vein.
https://ift.tt/2m5yum3
P17. Impaired auditory attention in adolescents with developmental dyslexia
Developmental dyslexia (DD) refers to the pathological impairment in the acquisition of reading and/or writing skills that is not accounted for by biological age, intelligence or inadequate schooling (WHO, 2011). It is hypothesized that DD relies, at least in part, on the impaired ability to shift attention to relevant information (Hari and Renvall, 2001). On a neurophysiological level, attention is represented by alpha oscillations (about 8–12 Hz). In adults with DD, recent studies showed altered alpha oscillations during the processing of auditory and visual stimuli (Dhar et al., 2010) but also in resting state (Papagiannopoulou and Lagopoulos, 2016).
https://ift.tt/2ug8Kas
3. The effect of environmental enrichment on GBL-induced Infantile Spasm-like seizures in Ts65Dn mice
Infantile spasms (IS) is the most common and severe form of epilepsy that occurs in infants between four and twelve months of age. Symptoms of IS include sporadic flexion and/or extension in all limbs and torso, multifocal spike discharges and manifestation of cognitive and psychomotor impairments later on in development. A strong correlation between Down Syndrome (DS) and IS was reported in recent research. It has also been shown that environmental enrichment was able to reduce the severity of atypical absence epilepsy, which is observed after IS in some patients, in a rat model.
https://ift.tt/2m4fmFd
P119. Activity-dependent plasticity of the endolymphatic space in vestibular migraine – A single case study
A new reasonable and dependable distinguishing criterion in the difficult clinical differentiation between Vestibular Migraine (VM) and Menière's Disease (MD) might be the proof of an endolymphatic hydrops (ELH) via gadolinium-enhanced magnetic resonance imaging of the inner ear (iMRI) Lempert et al.. However, so far published studies are inconclusive and sparse. This single case study clinically documents the volume of the endolymphatic space (ELS) in a VM patient longitudinally over 12 months during an attack-free period (T1), shortly after an VM attack (T2), and three attack-free months later (T3).
https://ift.tt/2ukkDw3
4. Suppression of hippocampal kindling seizures by lorazepam and levetiracetam
Benzodiazepine GABA enhancers and levetiracetam are known to be effective in suppression of kindling seizures, but the effects of these antiepileptic drugs on regional after discharges adjacent to the kindling sits are largely unknown. We explored this issue in a mouse model of hippocampal kindling and compared the effects of lorazepam and levetiracetam on hippocampal and piriform after discharges as the piriform cortex is thought to play a critical role in genesis of kindling seizures.
https://ift.tt/2m3bnst
P95. Immunmodulatory effects of intrathecal administration of triamcinolone in experimental autoimmune neuritis model in lewis rats
We studied the immunmodulatory effects of triamcinolone applied intrathecally in the animal model of experimental autoimmune neuritis (EAN) in Lewis rats.
https://ift.tt/2zqh5hx
5. Prospective pre-emptive EEG study prior to west syndrome
Since the original description of hypsarrhythmia by visual inspection as a "chaotic" and disorganized pattern in 1954, we have continued this clinical practice of EEG interpretation with solely visual inspection until the present day. The description of hypsarrhythmia as "chaotic" [Gibbs EL, Fleming MM, Gibbs FA. Pediatrics 1954;13(1):66–73], was challenged by van Putten and Stam 17 years ago [IEEE Eng Med Biol Mag. 2001;20(5):72–9]. We are now conducting the first prospective study in newborn babies with risk factors for infantile spasms.
https://ift.tt/2m6whHj
P13. Semi-automatic, machine-learning based segmentation of peripheral nerves for quantitative morphometry: Comparison of low- and high-resolution MR neurography
Current state-of-the-art to diagnose peripheral neuropathy are neurological examination and electrodiagnostic studies. However, deeply situated nerves and plexus remain difficult to assess using these techniques, hence magnetic resonance neurography (MRN) emerged as a complementary method. MRN remains a qualitative approach and quantification, in terms of extraction of imaging biomarkers is needed to facilitate diagnosis and for follow-up examinations. Towards a multi-parametric quantitative imaging approach, accurate nerve segmentation needs to be performed first.
https://ift.tt/2uk4t5M
6. Continuous spike-waves of slow-wave sleep in 20 year old woman with epilepsy and autism
A 20 yo RH woman, followed for 16 years by the same neurologist (PAH), had seizure onset at 1.5 years: afebrile CPSz secondarily generalised with automatisms, duration 5 min, recurrent every 2–4 weeks. Initial treatment consisted of PHT 5 mg/kg/day, then CBZ 30 mg/kg + VPA 18 mg/kg/day with improvement. PMHx: SGA 2.7 kg at birth, 7–8 h labour, "R. leg bent" at birth, in India. FHx negative Szs. Initial development "normal": walked 12 months, words at 18 months (Gujerati), ESL at 4 years (JK, Can.).
https://ift.tt/2m4ZJxl
7. Frequency and etiology of status epilepticus in pediatric patient of KAUH, Kingdom of Saudi Arabia
Status epilepticus (SE) is a condition of continuous seizure which persists more than 30 min or two or more seizures without full recovery. Any seizure that lasts more than 5 min needs to be considered as a case of SE for successful management of the condition. SE poses serious threat to life in children and requires immediate medical attention because continuous seizures not only damage the brain but also hinders the development of brain in later stages.
https://ift.tt/2maIivr
P123. Ginkgo biloba extract EGb 761 improves vestibular compensation after unilateral labyrinthectomy in the rat and modulates hippocampal and cerebellar networks
Investigation of the efficacy and mode of action of the Ginkgo biloba extract EGb 761 in a rat model of unilateral labyrinthectomy (UL).
https://ift.tt/2zqgOv1
8. The impact of comorbidity on seizure severity in elderly patients
To evaluate the effect of the presence of comorbidities on the severity of seizures among elderly patients in Saudi Arabia KFSH&RC.
https://ift.tt/2maIcnz
P112. Modulatory effects of anodal transcranial direct current stimulation on fronto-striatal gain control of the interplay between selective attention and perception
Carrying conversations in public spaces with a plethora of competing sensory inputs demands flexible interactions between attention and perception for selectively processing goal-relevant information. We postulate that the fronto-striatal network plays a key role in regulating this interaction. However, to date the underlying gain control mechanisms are not yet well understood. Neuronal gain control can be fine-tuned by membrane potential regulated changes in neuronal excitability. Anodal transcranial current stimulation (atDCS) has been shown to cause a depolarization of resting membrane potentials, which increases neuronal excitability.
https://ift.tt/2zqgIDF
Effect of cumulative intravenous voriconazole dose on renal function in hematological patients [PublishAheadOfPrint]
The intravenous voriconazole (VRC) is formulated by the incorporation of sulfobutylether-β-cyclodextrin (SBECD), which may accumulate to adversely affect renal function. However, the effect of long-term use of intravenous VRC on renal function is unclear. Our retrospective data confirmed that worsening of renal function was significantly associated with cumulative dose of intravenous VRC (≥ 400mg/kg), suggesting that a higher cumulative dose of intravenous VRC was a risk factor for renal dysfunction.
https://ift.tt/2zn3M1j
ROLE OF ASCORBIC ACID AS SUPPORTING IN THE THERAPEUTIC OF CHAGAS DISEASE: BENEFITS IN THE ASSOCIATION WITH LOW DOSE OF BENZNIDAZOLE [PublishAheadOfPrint]
The acute phase of Chagas disease (CD) is characterized by high parasitic proliferation and intense inflammation, exacerbating the generation of reactive oxygen and nitrogen species (ROS and RNS, respectively). These reactive molecules are also increased by the metabolism of the nitroheterocyclic compounds Benznidazole (BZ) and Nifurtimox, the only drugs available for the treatment of CD. This oxidative environment, associated with the intracellular multiplication of Trypanosoma cruzi, leads to tissue destruction, triggering the pathogenic process. Both drugs have limited efficacy and serious side effects, which demonstrates the need to seek alternative therapies. Due to the difficulty in developing new drugs, reviewing therapeutic regimens appears advantageous and the use of BZ in low doses associated with antioxidants, as ascorbic acid (AA), would be a valid alternative to attenuate oxidative stress. In our in vivo studies, mice receiving the combination AA(7.14mg/kg/day)+BZ10(10mg/kg/day) showed a reduction in parasitemia more effective than those receiving BZ or AA alone. The combined treatment was effective in decreasing intracellular ROS and lipid peroxidation in cardiac tissue. Histological and PCR analyzes showed that AA also reduced the cardiac parasitism. However, the greatest benefit was seen in AA+BZ10 group since cardiac inflammation was significantly reduced. In addition, the combined therapy prevented the hepatic damage induced by the infection. Our findings suggest that AA associated with a low dose of BZ may improve the trypanocidal activity and attenuate the toxic effects of BZ. The decrease in oxidative damage and inflammation observed in mice treated with AA+BZ10 could result in increased cardioprotection.
https://ift.tt/2m3P8m4
Echinocandin treatment of Candida albicans biofilms enhances neutrophil extracellular trap (NET) formation. [PublishAheadOfPrint]
The nosocomial pathogen Candida albicans forms biofilms on medical devices that persist in the face of antifungals and host defenses. Echinocandins, the most effective anti-biofilm drugs, have recently been shown to augment the activity of neutrophils against biofilms through an unknown mechanism. Here we show that treatment of C. albicans biofilms with sub-inhibitory concentrations of echinocandins promotes the formation of neutrophil extracellular traps (NETs), structures of DNA, histones, and antimicrobial proteins with antifungal activity.
https://ift.tt/2uiG14N
Synergy between circular bacteriocin AS-48 and ethambutol against Mycobacterium tuberculosis [PublishAheadOfPrint]
The increasing incidence of multi-drug resistant Mycobacterium tuberculosis and the very few drugs available for treatment is promoting the discovery and development of new molecules that could help in the control of this disease. Bacteriocin AS-48 is an antibacterial peptide produced by Enterococcus faecalis, active against several Gram-positive bacteria. We have found that AS-48 was active against Mycobacterium tuberculosis, including H37Rv and other reference and clinical strains, and also against some non-tuberculous clinical mycobacterial species. The combination of AS-48 with either lysozyme or with ethambutol (commonly used in the treatment of drug susceptible tuberculosis) increased the antituberculosis action of AS-48, showing a synergic interaction. Under these conditions, AS-48 exhibits a MIC close to some of the first-line antituberculosis agents. The inhibitory activity of AS-48 and its synergistic combination with ethambutol was also observed on M. tuberculosis infected macrophages.
Finally, AS-48 did not show any cytotoxicity against THP-1, MHS and J774.2 macrophage cell lines, at concentrations close to its MIC. In summary, bacteriocin AS-48 has an interesting antimycobacterial activity in vitro and low cytotoxicity, so further studies in vivo will contribute to its development as a potential additional drug for antituberculosis therapy.
https://ift.tt/2m3Si9r
Malaria Prophylaxis Using Naphthoquine-Azithromycin Combination: Randomized, Double-Blind, Placebo-Controlled Studies to Assess Safety and Protective Efficacy in Southeast Asia [PublishAheadOfPrint]
New prophylactic drugs against malaria infections are urgently needed. We conducted randomized, double-blind, placebo-controlled, phase 2 trials of a new antimalarial drug combination, naphthoquine-azithromycin (NQAZ), to determine its safety and protective efficacy in a low-endemicity area of Southeast Asia. In the first trial, 127 healthy volunteers were randomized to receive two single-doses of either 400 mg of NQAZ (200 mg of each drug), 800 mg of NQAZ (400 mg of each drug), or placebo on day 0 and day 30. Weekly follow-ups were performed for two months, and physical and clinical laboratory exams were done during the second and eighth week. Both drug regimens were well tolerated without any serious adverse events. Four adverse events (transient and slight elevation of serum transaminase concentrations) were found only in the two drug-treated groups and thus might be drug-related. In the second trial, 353 volunteer villagers were randomized into the same three groups as in the first trial, and malaria infections were followed for a month. For the intention-to-treat analysis, both regimens offered greater than 90% prophylactic efficacies against all malaria infections. When the analysis was done according to parasite species, 400 mg and 800 mg NQAZ provided 81.63 and 90.59% prophylactic efficacies, respectively, against Plasmodium falciparum infections, whereas both offered 100% prophylactic efficacy against Plasmodium vivax and Plasmodium ovale. These trials showed that NQAZ had a good safety profile and monthly single doses of 400 mg or 800 mg for adults offered excellent prophylaxis against malaria infections, especially the two relapsing species.
https://ift.tt/2zlYaEM
Efficiency of Target Larvicides is Conditioned by ABC-Mediated Transport in the Zoonotic Nematode Anisakis pegreffii [PublishAheadOfPrint]
Anisakiasis is among the most significant emerging food-borne parasitoses contracted through consumption of thermally unprocessed seafood harbouring infective Anisakis spp. larvae. The efficacy of the currently applied anthelminthic therapy in humans and in model organisms has not proven sufficient, so alternative solutions employing natural compounds combined with chemical inhibitors should be explored. By testing toxicity of the natural monoterpenes nerolidol and farnesol, and conventional anthelminthics abamectin and levamisole, in the presence/absence of MK-571 and Valspodar that inhibit the ABC transporter proteins Multidrug Resistance Protein (MRP-like) and P-glycoprotein (P-gp), we determined the preliminary traits of Anisakis detoxifying mechanisms. We found that Anisakis P-gp and MRP-like transporters have a role in the efflux of the tested compounds, which could be useful in the design of novel anthelminthic strategies. Expectedly, transporter activation and efflux fluctuated over time; they were synchronously active very early post-exposure, while the activity of one transporter dominated over the other in a time-dependent manner. MRP-like transporters dominated in the efflux of farnesol and P-gp dominated in efflux of nerolidol, while both were active in effluxing levamisole. The highest toxicity was exerted by abamectin, a P-gp inhibitor per se, also eliciting the highest oxidative stress in treated Anisakis larvae. We suggest that ß-tubulin, observed for the first time as a core element in Anisakis cuticle, might represent an important target for the tested compounds.
https://ift.tt/2m6FGym
Repurposing strategy of atorvastatin against Trypanosoma cruzi: in vitro monotherapy and combined therapy with benznidazole exhibits synergistic trypanocidal activity [PublishAheadOfPrint]
Statins are inhibitors of cholesterol synthesis but other biological properties, like antimicrobial effects, have been assigned leading to the designation of their pleiotropic aspect. Our goal was investigate the activity and selectivity of atorvastatin (AVA) against T. cruzi using in vitro models aiming more effective and safer therapeutic options through drug repurposing proposals under monotherapy and in combination with benznidazole (BZ). Phenotypic screening used different strains (Tulahuen (DTU VI) and Y (DTU II)) and forms (intracellular forms, bloodstream and tissue-derived trypomastigotes) of the parasite. While assaying Tulahuen strain, AVA is more active against intracellular amastigotes (SI=3). Also, against another parasite DTU (Y strain), this statin was more active (2.1-fold) and selective (2.4-fold) against bloodstream trypomastigotes (SI=51) than upon the intracellular forms (SI=20). The cytomorphological approach using phalloidin–TRITC permitted to verify that AVA did not induced cell density reduction and CC maintained their typical cytoarchitecture. Combinatory approaches using fixed-ratio methods showed that AVA and BZ gave synergistic interactions against both trypomastigotes and intracellular forms (mean FICIs = 0.46 ± 0.12 and 0.48 ± 0.03 respectively). In this sense, the repurposing strategy of AVA, especially in combination with BZ leading to a synergic effect, encourages future studies in order to identify novel therapeutic protocols for Chagas disease treatment.
https://ift.tt/2zn3x6p
Pharmacokinetics of ciprofloxacin in children with complicated urinary tract infection: results of a multicenter population pharmacokinetic study. [PublishAheadOfPrint]
Resistance rates for ciprofloxacin, which is labeled for treating complicated urinary tract infections in children, are rapidly rising. As there is limited knowledge on developmental pharmacology of ciprofloxacin, the primary aim of this study was to develop a population pharmacokinetic model for ciprofloxacin in children treated for complicated urinary tract infections. Children to whom ciprofloxacin was prescribed, intravenous (10-15 mg/kg body weight every 12 h) or per os (15-20 mg/kg every 12 h), were enrolled. 108 Serum and 119 urine samples were obtained during 10 intravenous and 13 oral courses of ciprofloxacin in 22 patients (age range 0.31 – 15.51 years). A one-compartment model best described our data. Fat free mass and glomerular filtration rate (estimated by a formula using cystatin C and creatinine), standardized for body surface area, were significant covariates for ciprofloxacin clearance. In our population, ciprofloxacin clearance is 0.16 – 0.43 L/h/kg of body weight, volume of distribution 0.06 – 2.88 L/kg, and bioavailability 59.6%. All of our patients had a clinical cure of their infection. Based on target attainment simulations across doses, all children reached the pharmacodynamic target for Enterobacteriaceae, but on average only 53% for Pseudomonas aeruginosa, and 3% for Staphylococcus aureus, at the 15 mg/kg oral dose. For treating urinary tract infections caused by Pseudomonas aeruginosa, oral doses should be at least 20 mg/kg. Furthermore, in our population, fat free mass and kidney function should be considered as they prove to be significant covariates for ciprofloxacin clearance and hence, exposure.
https://ift.tt/2m6sPfP
Bioequivalence of a Fixed-Dose Combination Tablet of the Complete 2-Drug Regimen Dolutegravir and Rilpivirine for the Treatment of HIV-1 Infection [PublishAheadOfPrint]
Background: A complete 2-drug regimen of dolutegravir 50 mg and rilpivirine 25 mg was approved to treat HIV-1 infection in virologically suppressed patients after demonstrating acceptable efficacy and tolerability. This study investigated the bioequivalence and pharmacokinetics of the fixed-dose combination tablet compared with separate tablets. Secondary endpoints were tolerability and safety of the fixed-dose combination tablet.
Methods: In this open-label, randomized-sequence, 2-way crossover trial, single doses of the fixed-dose combination tablet (test) and the combination of separate tablets (reference) were administered to healthy adults after a moderate-fat meal, with a 21-day washout between treatments. Pharmacokinetic samples were collected through 12 days after dosing. The primary endpoints were area under the plasma concentration-time curve (AUC) and maximum concentration of drug (Cmax). The study employed a prespecified sample-size re-estimation based on a blinded midpoint review of Cmax variability to update the enrollment size to achieve statistical power.
Results: Of 118 participants enrolled, 113 received both treatments and underwent pharmacokinetic assessment. The 90% confidence intervals for the geometric least squares means ratios for AUC0-, AUC0-t, and Cmax (test vs reference) were within the bioequivalence range of 0.80 to 1.25 for both drugs, indicating bioequivalence. In this study, a single dose of either treatment was well tolerated overall, with 4% (n=5) and 3% (n=3) of participants reporting adverse events considered related to the test and reference treatments, respectively.
Conclusions: The dolutegravir/rilpivirine fixed-dose combination tablet is bioequivalent to a combination of separate tablets and no new safety signals emerged.
https://ift.tt/2zo8SdE
Efficacy of short-course antibiotic treatments for community-acquired pneumonia in adults: A systematic review and meta-analysis [PublishAheadOfPrint]
Background: The duration of therapy for community-acquired pneumonia (CAP) remains undefined. We sought to investigate whether short-course antibiotic treatment for CAP is associated with favorable clinical outcomes in adult patients.
Methods: We systematically searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov for studies comparing the effectiveness and safety between treatment regimens administered for ≤6 days and ≥7 days. We defined treatment for ≤6 days as "short-course" and treatment for ≥7 days as "long-course".
Results: Twenty-one clinical trials (4861 clinically evaluable patients) were included and 19 out of 21 trials were randomized. Clinical cure was similar between the compared groups [4069 patients, RR= 0.99 (95% CI, 0.97-1.01)], irrespective of patient setting (outpatient/inpatient) [RR= 0.98, (95% CI, 0.96-1.00)/RR= 1.00, (95% CI, 0.92-1.09), respectively] or severity of pneumonia [RR= 1.05, (95% CI, 0.96-1.14)]. Also, relapses were similar between short and long-course treatment groups [1923 patients, RR= 0.67 (95% CI, 0.30-1.46)]. Short-course treatment was associated with fewer serious adverse events [1923 patients, RR= 0.73 (95% CI, 0.55-0.97)] and, importantly, resulted in lower mortality compared to long-course treatment [2802 patients, RR= 0.52 (95% CI, 0.33-0.82)].
Conclusion: In CAP, short-course antibiotic treatment (≤6 days) is equally effective and potentially superior, in terms of mortality and serious adverse events, compared to longer-course treatment.
https://ift.tt/2uajTKA
In vitro and In vivo characterization of NOSO-502, a novel inhibitor of bacterial translation [PublishAheadOfPrint]
Antibacterial activity screening of a collection of Xenorhabdus strains led to the discovery of the Odilorhabdins, a new antibiotic class with broad-spectrum activity against Gram-positive and Gram-negative pathogens. Odilorhabdins inhibit bacterial translation by a new mechanism of action on ribosomes. A lead-optimization program identified NOSO-502 as a promising candidate. NOSO-502 has MIC values ranging from 0.5 to 4 μg/ml against standard Enterobacteriaceae strains and carbapenem-resistant Enterobacteriaceae (CRE) isolates that produce KPC, AmpC, or OXA enzymes and metallo-β-lactamases. In addition, this compound overcomes multiple chromosome-encoded or plasmid-mediated resistance mechanisms of acquired resistance to colistin. It is effective in mouse systemic infection models against E. coli EN122 (ESBL) or E. coli ATCC BAA-2469 (NDM-1), achieving an ED50 of 3.5 mg/kg and 1-, 2- and 3-log reductions in blood burden at 2.6, 3.8, and 5.9 mg/kg, respectively, in the first model and 100% survival in the second, starting with a dose as low as 4 mg/kg. In a UTI model of E. coli UTI89, urine, bladder and kidney burdens were reduced by 2.39, 1.96, and 1.36 log10 CFU/ml, respectively, after injecting 24 mg/kg. There was no cytotoxicity against HepG2, HK-2, or HRPT cells, no inhibition of hERG-CHO or Nav 1.5 -HEK current, and no increase of micronuclei at 512 μM. NOSO-502, a compound with a new mechanism of action, is active against Enterobacteriaceae, including all classes of CRE, has a low potential for resistance development, shows efficacy in several mouse models, and has a favorable in vitro safety profile.
https://ift.tt/2uimMbK
HIV-1 integrase inhibitors that are broadly effective against drug-resistant mutants [PublishAheadOfPrint]
Integrase strand transfer inhibitors (INSTIs) have emerged as clinically effective therapeutics that inhibit HIV-1 replication by blocking the strand transfer reaction, catalyzed by HIV-1 integrase (IN). Of the three FDA-approved INSTIs, Dolutegravir (DTG) is the least apt to select for resistance. However, recent salvage therapy regimens had low response rates with therapies that included DTG, suggesting that DTG resistance can be selected in patients.
Using a single-round infection assay, we evaluated a collection of our best inhibitors and DTG against a broad panel of INSTI-resistant mutants. Two of the new compounds, 4c and 4d, had superior antiviral profiles against the mutants we tested compared to DTG.
The susceptibility profiles of 4c and 4d suggest that these compounds are candidates for development as INSTIs. Modeling the binding of 4d to HIV-1 IN reinforced the significance of mimicking the DNA substrate in developing compounds that broadly effective in their ability to inhibit HIV-1 INs with mutations in the active site.
https://ift.tt/2u6f3xV
Assessment of the additional value of verapamil to a moxifloxacin and linezolid combination regimen in a murine tuberculosis model. [PublishAheadOfPrint]
Favorable treatment outcome of multidrug resistant tuberculosis (MDR-TB) is only 54% and therefore new drug regimens are urgently needed. In this study, we evaluated the activity of the combination of moxifloxacin and linezolid as a possible new MDR-TB regimen in a murine TB model and the additional value of the efflux-pump inhibitor verapamil to this backbone. BALB/c mice were infected with drug sensitive Mycobacterium tuberculosis and were treated with human-equivalent doses of moxifloxacin (200 mg/kg) and linezolid (100 mg/kg) with or without verapamil (12.5 mg/kg) for 12 weeks. Pharmacokinetic parameters were collected during treatment at steady state. After 12 weeks of treatment, a statistically significant decline in mycobacterial load in the lungs was observed with the moxifloxacin-linezolid regimen with and without verapamil (5.9 and 5.0 Log colony forming units, respectively), but sterilization was not achieved yet. The spleens of all mice were culture-negative after 12 weeks of treatment with both treatment modalities and the addition of verapamil caused a significant reduction in relapse (14/14 positive spleens without versus 9/15 with verapamil, p=0.017).
Concluding, treatment with a combination regimen of moxifloxacin and linezolid showed a strong decline in mycobacterial load in the mice. The addition of verapamil to this backbone had a modest additional effect in terms of reducing mycobacterial load in the lung as well as reducing spleen relapse rate. These results warrant further studies on the role of efflux pump inhibition in improving the efficacy of MDR-TB backbone regimens.
https://ift.tt/2ugUL4j
Multiclonal expansion and high prevalence of {beta}-lactamase-negative high-level ampicillin-resistant Haemophilus influenzae in Japan, and susceptibility to quinolones [PublishAheadOfPrint]
β-lactam-resistant Haemophilus influenzae is a clinical concern. A high prevalence (>40%) of β-lactamase-negative high-level ampicillin-resistant H. influenzae (High-BLNAR) isolates has been reported in Japan. However, the reasons for the expansion are unknown. High-BLNAR possesses an amino acid substitution, either Asn526Lys (group III) or Arg517His (group III-like) in addition to Ser385Thr, in penicillin-binding protein 3 (PBP3). To determine the current prevalence of High-BLNAR and the mechanisms behind their expansion in Japan, their prevalence, PBP3 types, multilocus sequence types, and susceptibilities to quinolones approved in Japan as alternatives were determined.
Sixty percent of H. influenzae clinical isolates (n=62/104) were BLNAR. Among BLNAR, 92% (n=57/62) were High-BLNAR. Most were classified as belonging to group III, which contained many genotypes (11 PBP3 types and 25 sequence types). These results indicate that the expansion of High-BLNAR isolates was multiclonal and still dominant in Japanese clinical setting. One High-BLNAR harbored the novel amino acid substitution Asn526Met in addition to Ser385Thr in PBP3, suggesting a new group (group IV).
No quinolone-resistant H. influenzae isolates were identified. The minimum inhibitory concentrations (MICs) of the quinolones [lsqb]moxifloxacin, garenoxacin, and tosufloxacin[rsqb] were similar to that of levofloxacin, whereas sitafloxacin exhibited a lower MIC. However, we obtained four H. influenzae isolates showing decreased quinolone susceptibility with the amino acid substitution Ser84Leu in GyrA. Three of these were High-BLNAR.
In summary, this study shows that multiclonal High-BLNAR dominates in a Japanese university hospital. Isolates remain sensitive to quinolones, but vigilance is required to prevent the development of fluoroquinolone resistance in High-BLNAR strains.
https://ift.tt/2u3dBwr
Insights into long-term catheter-related infections by multidrug-resistant bacteria: the role of lock-therapy [PublishAheadOfPrint]
Objectives: The management of long-term central venous catheters (LTCVCs) infections by multi-drug resistant (MDR) bacteria in cancer patient is a challenger. The objectives of this study were to analyse outcomes in cancer patients with LTCVC-associated infection, identify risks for unfavourable outcomes and determine the impact of MDR bacteria and antibiotic lock therapy (ALT) in managing such infections.
Methods: We evaluated all LTCVC-associated infections treated between January 2009 and December 2016. Infections were reported in accordance with international guidelines for catheter-related infections. The outcome measures were 30-day-mortality, and treatment failure. We analysed risk factors by Cox forward-stepwise regression.
Results: We identified 296 LTCVC-associated infections, 212 (71.6%) were classified as bloodstream infections (BSIs). The most common agent was Staphylococcus aureus.46 (21.7%) infections were due to multi-drug resistant (MDR) Gram-negative.ALT was used in 62 (29.2%) patients, with a 75.9% success rate. Risk factors identified for failure of the initial treatment were having a high Sequential Organ Failure Assessment (SOFA) score at diagnosis of infection and being in palliative care; introduction of ALT at the start of treatment was identified as a protective factor. Risk factors identified for 30-day-mortality after LTCVC-associated infection were a high SOFA score at diagnosis, infection with MDR bacteria, and palliative care; introduction of ALT at the start of treatment, haematological malignancies, and adherence to an institutional protocol for the management of LTCVC-associated infection were identified as protective factors.
Conclusions: Despite the high incidence of infection with MDR bacteria, ALT improves the outcome of LTCVC-associated infection in cancer patients.
https://ift.tt/2zvVrbA
The Fungal Cyp-51 Inhibitor VT-1129 is Efficacious in an Experimental Model of Cryptococcal Meningitis [PublishAheadOfPrint]
Cryptococcal meningitis is a significant cause of morbidity and mortality in immunocompromised patients. VT-1129 is a novel fungal-specific Cyp51 inhibitor with potent in vitro activity against Cryptococcus species. Our objective was to evaluate the in vivo efficacy VT-1129 against cryptococcal meningitis. Mice were inoculated intracranially with C. neoformans. Oral treatment with VT-1129, fluconazole, or placebo began 1 day later and continued for either 7 or 14 days, and brains and plasma were collected on day 8 or 15, 1 day after therapy ended, and fungal burden was assessed. In the survival study, treatment continued until day 10 or day 28 after which mice were monitored off-therapy until day 30 or day 60, respectively, to assess survival. Fungal burden was also assessed in the survival arm. VT-1129 plasma and brain concentrations were also measured. VT-1129 reached a significant maximal survival benefit (100%) at a dose of 20 mg/kg once daily. VT-1129 at doses of ≥ 0.3 mg/kg/day and each dose of fluconazole significantly reduced brain tissue fungal burden compared to control after both 7 and 14 days of dosing. Fungal burden was also undetectable in most mice treated with dose of ≥ 3 mg/kg/day, even ≥ 20 days after dosing had stopped in the survival arm. In contrast, rebounds in fungal burden were observed with fluconazole. These results are consistent with the VT-1129 concentrations, which remained elevated long after dosing had stopped. These data demonstrate the potential utility of VT-1129 to have a marked impact in the treatment of cryptococcal meningitis.
https://ift.tt/2u6eHr5
Prevalence and molecular characterization of Escherichia coli clinical isolates carrying mcr-1 in a Chinese teaching hospital from 2002 to 2016 [PublishAheadOfPrint]
Colistin will be gradually banned from animal feeds in China and switched to clinical human therapy in the near future (1)....
https://ift.tt/2unxIoy
In Vivo Pharmacodynamic Characterization of a Novel Antibiotic Odilorhabdins, NOSO-502 against Escherichia coli and Klebsiella pneumoniae in a Murine Thigh Infection Model [PublishAheadOfPrint]
NOSO-502 is a novel odilorhabdin antibiotic with potent activity against Enterobacteriaceae. The goal of these studies was to determine which pharmacokinetic/pharmacodynamic (PK/PD) indice and magnitude best correlated with efficacy in the murine thigh infection model. Six E. coli and 6 K. pneumoniae were utilized. MICs were determined using CLSI methods and ranged from 1 to 4 mg/L. A neutropenic murine thigh infection model was utilized for all treatment studies. Single-dose plasma pharmacokinetics were determined in mice after subcutaneous administration of 7.81, 31.25, 125 and 500 mg/kg. Pharmacokinetic studies exhibited peak concentration (Cmax) values of 1.49 to 84.6 mg/L, area under the concentration-time curve (AUC0-) values of 1.94 to 352 mg*h/L, and beta-elimination half-lives of 0.41 to 1.1 h. Dose fractionation studies were performed using total drug doses 7.81 mg/kg to 2000 mg/kg fractionated into q3-, q6-, q12-, or q24-hourly regimens. Nonlinear regression analysis demonstrated AUC/MIC was the PK/PD parameter that best correlated with efficacy (R2 0.86). In subsequent studies, we used the neutropenic murine thigh infection model to determine the magnitude of NOSO-502 AUC/MIC needed for the efficacy against a diverse group of Enterobacteriaceae. Mice were treated with four-fold increasing doses (range 3.91 to 1000 mg/kg) of NOSO-502 every 6 hours. The mean fAUC/MIC magnitudes associated with net stasis and 1-log kill endpoint for K. pneumoniae were 4.22 and 17.7, respectively. The mean fAUC/MIC magnitude associated with net stasis endpoint for E. coli was 10.4. NOSO-502 represents a promising novel, first-in-class odilorhabdin antibiotic with in vivo potency against Enterobacteriaceae.
https://ift.tt/2u3dgtF
Molecular Insights into Functional Differences Between mcr-3- and mcr-1-Mediated Colistin Resistance [PublishAheadOfPrint]
The global emergence of plasmid-mediated colistin resistance genes mcr-1 and mcr-3 has threatened the role of the "last resort" drug colistin in the defense against infections caused by multidrug-resistant Gram-negative bacteria. However, functional differences between these two genes in mediating colistin resistance remains poorly understood. Protein sequence alignment of MCR-3 and MCR-1 was therefore conducted in Clustal Omega to identify sequence divergence. The molecular recognition of lipid A head group phosphatidylethanolamine and MCR-3 enzyme was studied by homology modeling and molecular docking, with the catalytic mechanism of MCR-3 also being explored. Thr277 in MCR-3 was validated as the key amino acid residue responsible for the catalytic reaction using site-directed mutagenesis and was shown to act as a nucleophile. Lipid A modification induced by the MCR-3 and MCR-1 enzymes was confirmed by electrospray ionization time-of-flight mass spectrometry. Far-UV circular dichroism spectra of the MCR-3 and MCR-1 enzymes suggested that MCR-3 was more thermostable than MCR-1, with a melting temperature of 66.19°C compared with 61.14°C for MCR-1. These data provided molecular insight into the functional differences between mcr-3 and mcr-1 in conferring colistin resistance.
https://ift.tt/2zoDbkn
{beta}-lactam dosage regimens in septic patients with augmented renal clearance [PublishAheadOfPrint]
Augmented renal clearance is commonly observed in septic patients and may result in insufficient β-lactam serum concentrations. The aims of this study were to evaluate potential correlations between drug concentrations or total body clearance of β-lactam antibiotics and measured creatinine clearance, and to quantify the need for drug dosage adjustments in septic patients with different levels of augmented renal clearance. We reviewed 256 antibiotic measurements (512 drug concentrations) from a cohort of 215 critically ill patients with a measured creatinine clearance ≥ 120 mL/min, and who received therapeutic drug monitoring of meropenem, cefepime, ceftazidime or piperacillin from October 2009 until December 2014 at Erasme Hospital. Population pharmacokinetic analysis of the data was performed using the Pmetrics software package for R. 55% of drug concentrations showed insufficient β-lactam serum concentrations to treat infections due to Pseudomonas aeruginosa. There were significant, yet weak correlations between measured creatinine clearance and trough concentrations of meropenem (r= -0.21, p=0.01), trough concentrations of piperacillin (r= -0.28, p= 0.0071), concentrations at 50% of the dosage interval (r= -0.41, p <0.0001), and total body clearance of piperacillin (r= 0.39, p= 0.0002). Measured creatinine clearance adequately explained changes in drug concentrations in population pharmacokinetic models for cefepime, ceftazidime, and meropenem, but not for piperacillin. Therefore, specific PK modelling can predict certain β-lactam concentrations based on renal function, but not on absolute values of measured creatinine clearance, easily available for clinicians. Currently, routine therapeutic drug monitoring is required to adjust daily regimens in critically ill patients receiving standard dosing regimens.
https://ift.tt/2u8Plc5
Streptococcus pyogenes-purpura fulminans as an invasive form of group A streptococcal infection
Streptococcus pyogenes is an uncommon pathogen of purpura fulminans, and the pathogenesis of S. pyogenes-purpura fulminans remains unclear because of paucity of cases. We reported a pediatric case of S. pyogenes-...
https://ift.tt/2KIagNE
Protective effects of Liuweiwuling tablets on carbon tetrachloride-induced hepatic fibrosis in rats
Liuweiwuling tablets (LWWL) are an herbal product that exerts remarkable effects on liver protection and aminotransferase levels, and they have been approved by the Chinese State Food and Drug Administration (...
https://ift.tt/2N1XB4H
Resveratrol prevents nanoparticles-induced inflammation and oxidative stress via downregulation of PKC-α and NADPH oxidase in lung epithelial A549 cells
Exposure to carbon black nanoparticles (CBNPs), a well-known industrial production, promotes pulmonary toxicity through inflammation and oxidative stress. Recent studies show that some polyphenols exert their ...
https://ift.tt/2KHzH1G
Deep Learning for Detection of Focal Epileptiform Discharges from Scalp EEG Recordings
Since the first recording of the human EEG by Hans Berger in 1924 (Berger, 1929), visual assessment by trained experts has remained the gold standard, despite the digital nature of EEG recordings. While visual analysis has proven to be invaluable (Schomer and Lopes da Silva, 2011), it has various limitations, including time-consuming review times, long learning curves, inter-observer variability and the need for specialized personnel (Lodder and van Putten, 2014; Faught, 1993). Visual analysis limits widespread use of long-term ambulatory recordings, although it has been established that this may improve diagnostic sensitivity for detecting interictal discharges (Askamp and van Putten, 2014; Geut et al., 2017).
https://ift.tt/2L70DE8
Womens prepregnancy lipid levels and number of children: a Norwegian prospective population-based cohort study
Objective
To study prepregnancy serum lipid levels and the association with the number of children.
DesignProspective, population-based cohort.
SettingLinked data from the Cohort of Norway and the Medical Birth Registry of Norway.
Participants2645 women giving birth to their first child during 1994–2003 (488 one-child mothers and 2157 women with ≥2 births) and 1677 nulliparous women.
Main outcome measuresORs for no and one lifetime pregnancy (relative to ≥2 pregnancies) obtained by multinomial logistic regression, adjusted for age at examination, education, body mass index (BMI), smoking, time since last meal and oral contraceptive use.
ResultsAssessed in quintiles, higher prepregnant triglyceride (TG) and TG to high-density lipoprotein (TG:HDL-c) ratio levels were associated with increased risk of one lifetime pregnancy compared with having ≥2 children. Compared with the highest quintile, women in the lowest quintile of HDL cholesterol levels had an increased risk of one lifetime pregnancy (OR 1.7, 95% CI 1.2 to 2.4), as were women with the highest low-density lipoprotein (LDL) cholesterol, TG and TG:HDL-c ratio quintiles (compared with the lowest) (OR 1.2, 95% CI 0.8 to 1.7; OR 2.2, 95% CI 1.5 to 3.2; and OR 2.2, 95% CI 1.5 to 3.2, respectively). Similar effects were found in women with BMI≥25 and the highest LDL and total cholesterol levels in risk of lifetime nulliparity.
ConclusionWomen with unfavourable prepregnant lipid profile had higher risk of having no or only one child. These findings substantiate an association between prepregnant serum lipid levels and number of children. Previously observed associations between low parity and increased cardiovascular mortality may in part be due to pre-existing cardiovascular disease lipid risk factors.
https://ift.tt/2NCzXgc
Clinical efficacy of anti-migration features in fully covered self-expandable metallic stents for anastomotic biliary strictures after liver transplantation: comparison of standard and anti-migration stents
Anastomotic biliary strictures (ABSs) are one of the most frequent adverse events that occur after orthotopic liver transplantation (OLT). Multiple plastic stents (MPSs) have been validated for this indication. More recently, fully covered self-expandable metallic stents (FCSEMSs) have been used with positive outcomes, but also have a higher rate of migration, which may limit success. Our primary objective was to compare stent migration rates observed with "standard" FCSEMSs (Std-FCSEMSs) and so-called "anti-migration" FCSEMSs (Am-FCSEMSs), which are newly designed with reversed proximal side flaps.
https://ift.tt/2zpbqbE
Clinical feasibility of single-source dual-spiral 4D dual-energy CT for proton treatment planning within the thoracic region
Single-source dual-spiral dual-energy computed tomography (DECT) provides additional patient information but is prone to motion between the two consecutively acquired CT scans. Here, the clinical applicability of dual-spiral time-resolved DECT (4D-DECT) for proton treatment planning within the thoracic region was evaluated.
https://ift.tt/2KM7DdK
Straight Proximal Humeral Nailing: Risk of Iatrogenic Tendon Injuries with Respect to Different Entry Points in Anatomical Specimens
Publication date: Available online 9 July 2018
Source: Injury
Author(s): A.M. Schwarz, G.M. Hohenberger, S. Euler, A.H. Weiglein, R. Riedl, S. Kuchling, R. Krassnig, M. Plecko
Abstract
Background
The purpose of the study was to evaluate the relationship of implant-related injuries to the adjacent anatomical structures in a newer generation straight proximal humeral nail (PHN) regarding different entry points. The proximity of the proximal lateral locking-screws of the MultiLoc proximal humeral nail (ML PHN) may cause iatrogenic tendon injuries to the lateral edge of the bicipital humeral groove (BG) as reference point for the tendon of the long head of biceps brachii (LBT) as well as the lateral insertion of the infraspinatus tendon (IST).
Materials and Methods
The study comprised n = 40 upper extremities. Nail application was performed through a deltoid approach and supraspinatus tendon (SSP) split with a ML PHN. All tests were performed in three different entry points. First nail (N1) - standard position in line with the humeral shaft axis; second nail (N2) – a more lateral entry point; third alternative (N3) - medial position, centre of the humeral head. After nail placement, each specimen was screened for potential implant-related injuries or worded differently hit rates (HR) to the BG and the IST. The distances to the anatomical structures were measured and statistically interpreted.
Results
The observed iatrogenic IST injury rate was 17.5% (n = 7/40) for N1, 5% (n = 2/40) for N2 and 62.5% (n = 25/40) for N3, which was statistically significantly higher (p < 0.001). Regarding the BG, the evaluated HR was 7.5% (n = 3/40) for both N1 and N2. Only the nail placed in the head centre (N3) showed an iatrogenic injury rate of 20% (n = 8/40) (p < 0.062). No statistically significant association between humeral head size and the HR could be observed (head diameter: IST: p = 0.323, BG: p = 0.621; head circumference: IST: p = 0.167; BG: p = 0.940). For the IST and BG, all distances in nail positions N1 and N2 as well as N2 and N3 differ statistically significant (p < 0.001).
Conclusions
An entry point for nail placement in line or slightly laterally to the humeral shaft axis - but still at the cartilage - should be advocated.
https://ift.tt/2L4nnF3
Imaging-Based Outcomes for 24 Gy in 2 Daily Fractions for Patients with De Novo Spinal Metastases treated with Spine Stereotactic Body Radiotherapy (SBRT)
This study reports mature outcomes for a large cohort of patients with no prior radiation (de novo) treated uniformly with 24 Gy in 2 daily spine SBRT fractions for metastases, which represents the SBRT regimen under evaluation on the ongoing SC-24 phase III randomized trial (NCT02512965). This fractionation is safe and effective in achieving high tumor control rates and the outcomes presented will serve as the benchmark data for SC-24.
https://ift.tt/2KKHgor
Early changes in serial CBCT-measured parotid gland biomarkers predict chronic xerostomia after head and neck radiotherapy
Imaging for head and neck radiotherapy (HNR) normal tissue treatment response typically requires advanced techniques and/or extra sessions, limiting wide adoption and clinical utility. Parotid glands were delineated on daily CBCT images during the course of HNR for 105 patients who had xerostomia grade scored at one year following treatment. CBCT-measured dynamic intensity changes were associated with chronic xerostomia, with improved prediction over dose alone, which may have profound implications for adaptive radiotherapy.
https://ift.tt/2N4qjBV
Long Term Outcomes of a Phase II Trial of Chemotherapy with Consolidative Radiation Therapy for Oligometastatic Non-Small Cell Lung Cancer
Recent data indicate consolidative radiation therapy (CRT) improves progression free survival (PFS) for patients with oligometastatic non-small cell lung cancer (NSCLC). Data regarding long term outcomes are limited.
https://ift.tt/2KI8bRH
From Colorectal Cancer Screening Guidelines to Headlines: Beware!
https://ift.tt/2NE0ie8
Opioid Use Disorder, Stigma, and Transplantation: A Call to Action
https://ift.tt/2NCscac
New Insights Into Optimal Timing of Hepatitis C Virus Treatment for Dialysis Patients Waitlisted for Kidney Transplant
https://ift.tt/2L6U1FO
Cross-sex Hormones and Acute Cardiovascular Events in Transgender Persons A Cohort Study
https://ift.tt/2NAAkIa
Comparative Benefits and Harms of Basal Insulin Analogues for Type 2 Diabetes A Systematic Review and Network Meta-analysis
https://ift.tt/2J7aSH5
Transplanting Hepatitis C Virus–Infected Versus Uninfected Kidneys Into Hepatitis C Virus–Infected Recipients A Cost-Effectiveness Analysis
https://ift.tt/2NE04Uk
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Αλέξανδρος Γ. Σφακιανάκης Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,0030693260717...
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Alimentary Pharmacology &Therapeutics, EarlyView. https://ift.tt/2qECBIJ
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heory of COVID-19 pathogenesis Publication date: November 2020Source: Medical Hypotheses, Volume 144Author(s): Yuichiro J. Suzuki ScienceD...
