Blockage of KHSRP-NLRP3 by MCC950 Can Reverse the Effect of Manganese-Induced Neuroinflammation in N2a Cells and Rat Brain.

Manganese neurotoxicity has been reported to cause a neurodegenerative disease known as parkinsonism. Previous reports have shown that the expression of the KH-type splicing regulatory protein (KHSRP), a nucleic acid-binding protein, and NLRP3 is increased upon Mn exposure. However, the relation between these two during Mn toxicity has not been fully deduced. The mouse neuroblastoma (N2a) and SD rats are treated with LPS and MnCl2 to evaluate the expression of KHSRP and NLRP3. Further, the effect of the NLRP3 inhibitor MCC950 is checked on the expression of NLRP3, KHSRP and pro-inflammatory markers (TNFα, IL-18 and IL-1ß) as well as the caspase-1 enzyme. Our results demonstrated an increment in NLRP3 and KHSRP expression post-MnCl2 exposure in N2a cells and rat brain, while on the other hand with LPS exposure only NLRP3 expression levels were elevated and KHSRP was found to be unaffected. An increased expression of KHSRP, NLRP3, pro-inflammatory markers and the caspase-1 enzyme was observed to be inhibited with MCC950 treatment in MnCl2-exposed cells and rats. Manganese exposure induces NLRP3 and KHSRP expression to induce neuroinflammation, suggesting a correlation between both which functions in toxicity-related pathways. Furthermore, MCC950 treatment reversed the role of KHSRP from anti-inflammatory to pro-inflammatory.

Responding to the Psychological Needs of Health-Care Workers During the COVID-19 Pandemic: Case Study from the Medical College of Wisconsin.

With the advent of the novel coronavirus (COVID-19) pandemic, health-care workers have been faced with an inordinately high level of trauma as frontline providers. The Medical College of Wisconsin (MCW) partnered with affiliate hospitals and community partners to mobilize a matrix of available support and interventions to deliver psychological services to reach all levels of health-care providers in timely, accessible formats. While virtual peer support groups were the most utilized resource among the support group options, other opportunities also provided unique benefits to learners whose education had been disrupted by the pandemic. Mental health must be prioritized for health-care workers in the event of future public health crises. Lessons learned from this pandemic indicate that it is critical to involve learners early on in the process in order to meet their educational needs and to increase access to evidence-based care.

HeadUp: A Low-Cost Solution for Tracking Head Movement of Children with Cerebral Palsy Using IMU.

Cerebral palsy (CP) is a common reason for human motor ability limitations caused before birth, through infancy or early childhood. Poor head control is one of the most important problems in children with level IV CP and level V CP, which can affect many aspects of children's lives. The current visual assessment method for measuring head control ability and cervical range of motion (CROM) lacks accuracy and reliability. In this paper, a HeadUp system that is based on a low-cost, 9-axis, inertial measurement unit (IMU) is proposed to capture and evaluate the head control ability for children with CP. The proposed system wirelessly measures CROM in frontal, sagittal, and transverse planes during ordinary life activities. The system is designed to provide real-time, bidirectional communication with an Euler-based, sensor fusion algorithm (SFA) to estimate the head orientation and its control ability tracking. The experimental results for the proposed SFA show high accuracy in noise reduction with faster system response. The system is clinically tested on five typically developing children and five children with CP (age range: 2-5 years). The proposed HeadUp system can be implemented as a head control trainer in an entertaining way to motivate the child with CP to keep their head up.

A Prospective Randomised Controlled Study Comparing Ultrasonic Dissector with Electrocautery for Axillary Dissection in Patients of Carcinoma Breast.

BACKGROUND: Axillary dissection is one of the important components of modified radical mastectomy (MRM). The present study was conducted to compare surgical outcomes by using monopolar electrocautery and ultrasonic dissector for axillary dissection in MRM. METHODS: A parallel randomised controlled single blinded study was conducted with a sample size of 70 patients who were randomised into two groups. One group underwent MRM using ultrasonic dissector (Group A) and the other one using electrocautery (Group B). Intra- and post-operative outcomes were compared. RESULTS: Group A had an average operating time of 30.86 min, which was statistically less than that of Group B. The mean mop count and the daily drain output in Group A were less as compared to Group B and the differences were statistically significant. Drain was removed early in Group A as compared to Group B. However, post-operative pain scores and seroma formation were not statistically significant among the two groups. CONCLUSION: Ultrasonic dissector group had significantly lesser intra-operative bleeding, operating time and post-operative drain output when compared to electrocautery group. However, the two groups had no significant difference in post-operative pain scores and seroma formation.

Surgical Triage of Breast Disorders During the COVID-19 Pandemic: An Indian Perspective.

Breast complaints are a very common cause of healthcare visits in the female population. They range in severity from benign to malignant, and treatment options vary from simple observation to mastectomy. As healthcare facilities are overburdened with coronavirus disease 2019 (COVID-19) patients, properly triaging patients diagnosed with breast disorders is necessary for the optimal use of limited resources in developing countries. We are proposing a concise triage system for timely intervention among patients with breast disorders during the havoc of the COVID-19 pandemic.

Three-dimensional culture of buffalo granulosa cells in hanging drop mimics the preovulatory follicle stage.

Granulosa cell (GC) culture models mimicking the intrafollicular environment are limited. Such models have a great potential in reproductive toxicity studies. The buffalo, a monovulatory species like humans, could be a better model than polyovulatory rodents. Therefore, we targeted the development and characterization of three-dimensional (3D) culture systems for buffalo GCs. The GCs from small ovarian follicles (SF) maintained the CYP19 gene expression for 144 hr in a 2D culture system. Hence, GCs from SF were cultured directly in 3D using hanging drop and Poly-([2-hydroxyethyl methacrylate]) (polyHEMA) methods in the DMEM media containing 1 ng/ml FSH and 10 ng/ml IGF-1 for 144 hr. The expression profile of nine GC-specific transcripts; CYP19, TNFAIP6, AMH, PTI, NR4A1, FSHR, RUNX, LHR, and COX2/PTGS2; revealed that 3D-spheroids developed in hanging drop method maintained the GC phenotype of preovulatory follicles. Therefore, hanging drop method is a best method for culturing GCs to mimic the intrafollicular environment.

Buffalo (Bubalus bubalis) SCNT embryos produced from somatic cells isolated from frozen-thawed semen: effect of trichostatin A on the in vitro and in vivo developmental potential, quality and epigenetic status.

This study examined the effects of trichostatin A (TSA) treatment of reconstructed buffalo embryos, produced by hand-made cloning using somatic cells isolated from over a decade old frozen-thawed semen, on their in vitro and in vivo developmental competence, quality and epigenetic status. Following treatment of reconstructed embryos with TSA (0, 50 or 75 nM) for 10 h prior to culture, the cleavage (100.0 ± 0, 94.5 ± 2.3 and 96.1 ± 1.2%, respectively) and blastocyst rate (50.6 ± 2.3, 48.4 ± 2.7 and 48.1 ± 2.6%, respectively), total cell number (275 ± 17.4, 289 ± 30.1 and 317 ± 24.2, respectively) and apoptotic index (5.6 ± 0.7, 3.4 ± 0.9 and 4.5 ± 1.4, respectively) were not significantly different among the three groups. However, TSA treatment increased (P < 0.05) the global level of H4K5ac and decreased (P < 0.05) that of H3K27me3 in blastocysts whereas the global level of H3K18ac was not affected significantly. Transfer of embryos treated with 75 nM TSA (n = 10) to recipients resulted in two pregnancies (20%), one out of which was aborted in the second and the other in the third trimester whereas transfer of control embryos (n = 20) or those treated with 50 nM TSA (n = 12) did not result in any pregnancy. In conclusion, these results suggest that TSA treatment of cloned buffalo embryos produced using somatic cells isolated from frozen-thawed semen improved their epigenetic status but not the in vitro developmental potential and offspring rate.

Unicentric Castleman Disease: An Unusual Cause of An Isolated Neck Mass.

Castleman disease (CD) is a rare lymphoproliferative disorder of unknown aetiology. It manifests in two distinct clinical presentations: unicentric and multicentric. Unicentric CD is rare and may present as an isolated neck mass. A 22-year-old man presented with a 6-month history of right neck swelling that occupied the posterior triangle of the right neck region. After surgical exploration, a solitary, well defined, and hyper vascular mass was excise. A histopathological examination confirmed the lesion as CD, hyaline-vascular variant. CD of the neck is a diagnosis that is usually not taken into consideration while evaluating neck masses due to its rarity and unassuming presentation. It should be keep in the differential diagnosis of neck masses as the clinical and radiological features evade a firm diagnosis. The treatment of unicentric CD is complete surgical excision, which cures the patient.

Utilization of Mental Health Services by Medical College of Wisconsin Trainees.

INTRODUCTION: The goal of this study is to describe the change in utilization of mental health services by trainees at a private medical college in Wisconsin after specific interventions were instituted by the administration. METHODS: Multiphase interventions designed to increase access to care were instituted at the student behavioral health clinic. These interventions were based on the findings of online wellness surveys distributed to the Medical College of Wisconsin during the 2016-2017 school year. The authors collected annual utilization reports of student use of mental health services at the Medical College of Wisconsin and plotted them along a timeline of specific administrative interventions. RESULTS: Since the 2016-2017 academic year, medical students have used an average of 1274 mental health service visits per year compared to 637 visits annually during the academic years 2010-2011 through 2015-2016. The number of mental health visits increased significantly during 2016-2017 versus the average number of visits in previous years (P < 001; Cohen's d = 4.39). DISCUSSION: Similar to results shown worldwide, medical students in Wisconsin experience diminished mental health relative to their nonmedical peers. Recommendations have been made to provide additional administrative support to provide increased mental health resources to medical trainees. The findings in this report imply that incorporation of recommendations from the stakeholder medical trainees may be a key feature in the successful design and implementation of these supports.

An uncommon case of a fleeting rash from Western Rajasthan.

A 35 year old farmer presented with an erythematous serpiginous rash on dorsal aspect of left foot with intense pruritus and a feeling of something moving slowly in the rash. The photo of the rash is presented below and the case is discussed further.

Effects of glial cell line-derived neurotrophic factor, fibroblast growth factor 2 and epidermal growth factor on proliferation and the expression of some genes in buffalo (Bubalus bubalis) spermatogonial cells.

The present study evaluated the effects of glial cell line-derived neurotrophic factor (GDNF), fibroblast growth factor (FGF) 2 and epidermal growth factor (EGF) on proliferation and the expression of some genes in spermatogonial cells. Spermatogonial cells were isolated from prepubertal buffalo testes and enriched by double enzyme treatment, filtration through 80- and 60-µm nylon mesh filters, differential plating on lectin-coated dishes and Percoll density gradient centrifugation. Cells were then cultured on a buffalo Sertoli cell feeder layer and formed colonies within 15-18 days. The colonies were found to predominantly contain undifferentiated Type A spermatogonia because they bound Dolichos biflorus agglutinin and did not express c-kit. The colonies expressed alkaline phosphatase, NANOG, octamer-binding transcription factor (OCT)-4 and tumour rejection antigen (TRA)-1-60. Cells were subcultured for 15 days, with or without growth factor supplementation. After 15 days, colony area and the relative mRNA abundance of PLZF were higher (P<0.05) following supplementation with 40 ng mL⁻¹ GDNF + 10 ng mL⁻¹ EGF + 10 ng mL⁻¹ FGF2 than with the same concentrations of GDNF alone or GDNF plus either EGF or FGF2. Expression of TAF4B was higher (P<0.05) in the presence of FGF2, whereas the expression of THY1 was not affected by growth factor supplementation. In the Sertoli cell feeder layer, EGF and FGF2 decreased (P<0.05), whereas GDNF increased (P<0.05), the relative mRNA abundance of ETV5 compared with control. In conclusion, an in vitro culture system that incorporates various growth factors was developed for the short-term culture of buffalo spermatogonia.

Galactose decorated PLGA nanoparticles for hepatic delivery of acyclovir.

The present study explores prospective of surface tailored nanoparticles for targeted delivery of acyclovir along with the interception of minimal side effects. Acyclovir loaded plain and galactosylated poly lectic co glycolic acid (PLGA) nanoparticles were efficiently prepared and characterized by Fourier transform infrared spectroscopy, scanning electron microscopy (SEM), size, polydispersity index, zeta potential, and entrapment efficiency. The formulations were evaluated for in vitro drug release and hemolysis. Further, biodistribution study and fluorescent microscopic studies were carried out to determine the targeting potential of formulations. SEM revealed smooth morphology and spherical shape of the nanoparticles. In vitro, the galactosylated nanoparticles were found to be least hemolytic and exhibited a sustained release pattern. In vivo studies exhibited an augmented bioavailability, increased residence time and enhanced delivery of acyclovir to the liver upon galactosylation. It may therefore be concluded that galactose conjugated PLGA nanoparticles can be used suitably as vehicles for delivery of bioactives specifically to the hepatic tissues and may be thus exploited in the effective management of various liver disorders.

Withdrawal-Emergent Dyskinesia Related to Benztropine: A Case Report.

INTRODUCTION: Benztropine is an anticholinergic drug used as a therapy for Parkinson's disease and treatment for extrapyramidal side effects. While tardive dyskinesia is an involuntary movement disorder that often occurs gradually after long-term use of medications, it does not commonly present acutely. CASE PRESENTATION: A 31-year-old White woman experiencing psychosis presented with spontaneous, acute-onset dyskinesia induced with the withdrawal of benztropine. She had been followed in our academic outpatient clinic for medication management and intermittent psychotherapy. DISCUSSION: The pathophysiology of tardive dyskinesia is not fully understood, but several hypotheses exist, including the involvement of changes in basal ganglia neuronal systems. To our knowledge, this is the first case report to document acute-onset dyskinesia associated with the withdrawal of benztropine. CONCLUSION: his case report, which describes an atypical response to discontinuing benztropine, might offer the scientific community potential clues to better understand the pathophysiology of tardive dyskinesia.

Assessing Variability in Reporting Severity of the Same Symptom (Fatigue) in the Context of Different Psychiatric Syndromes.

Objective The objective of this study is to examine the variability in the self-reported fatigue symptom severity in major depressive disorder (MDD) compared to generalized anxiety disorder (GAD). Methods A retrospective chart review was conducted of 100 patients evaluated for fatigue using depression and anxiety questionnaires. The study examined whether ratings of fatigue varied based on whether fatigue was being rated by the patient in the context of MDD vs. when fatigue was being rated by the same patient in the context of GAD. A related-sample Wilcoxon signed-rank test and Mann-Whitney U test were used to compare the median differences between depression and anxiety fatigue scores. The significance level used was 0.05. Results This study found a statistically significant difference in the median difference of the paired depression fatigue and anxiety fatigue scores (depression score - anxiety score) regardless of the order of administration (Wilcoxon signed-rank test statistic = 135.500, p-value =.008, N = 100 paired scores). Conclusion The study's conclusions show that although the symptom of fatigue is listed in the Diagnostic Statistical Manual 5 (DSM-5) criteria for MDD as well as GAD, it may be perceived by patients differently based on the context of the syndrome. This emphasizes the importance of considering the context of symptom reporting in patients with MDD and GAD to improve diagnostic methodologies and treatment strategies.

Double-liposome-based dual-drug delivery system as vectors for effective management of peptic ulcer.

The aim of the present investigation was to prepare and evaluate a vesicular dual-drug delivery system for effective management of the mucosal ulcer. Inner encapsulating and double liposomes were prepared by the glass-bead and reverse-phase evaporation methods, respectively. The formulation consisted of inner liposomes bearing ranitidine bismuth citrate (RBC) and outer liposomes encapsulating amoxicillin trihydrate (AMOX). The optimized inner liposomes and double liposomes were extensively characterized for vesicle size, morphology, zeta potential, vesicles count, entrapment efficiency, and in vitro drug release. In vitro, the double liposomes demonstrated a sustained release of AMOX and RBC of 93.6 ± 1.9 and 84.1 ± 0.9%, respectively, at the end of 144 hours. Ex vivo studies were conducted on Helicobacter pylori (ATCC26695) bacterial cell lines. Double liposomes showed a more enhanced percent H. pylori growth inhibition than the plain drug combination. Further, in vivo studies illustrated enhanced antisecretory and ulcer-protective activity of double liposomes, as compared to the plain drug combination. Microscopic studies also supported the ulcer-protective action of the formulation. Thus, it may be concluded that double liposomes are instrumental in reducing gastric secretions and targeting ulcer sites with the interception of minimal side effects, thus suggesting their potential in ulcer therapy.

Role of intra-abdominal pressure measurement in patients with acute abdomen requiring exploratory laparotomy.

<b>Introduction:</b> Acute abdomen is one of the most common surgical emergencies faced by a surgeon. Monitoring Intra-Abdominal Pressure (IAP) in patients with acute abdomen referred for exploratory laparotomy may help guide the need for early intervention. </br></br> <b>Aim:</b> This study was performed to determine whether preoperative IAP had any significant association with organ failure as assessed using SOFA score. Furthermore, effect of IAP on patient outcome in terms of hospital stay, mortality was also evaluated. </br></br> <b>Materials and methods:</b> 60 patients above 18 years of age presenting with acute abdomen requiring exploratory laparotomy were included in this prospective observational study from November 2013 until March 2015. IAP and SOFA scores were calculated at the time of admission. The outcome of patients was assessed in terms of hospital stay, morbidity and mortality. The correlation between IAP and SOFA scores was also assessed to determine the risk of organ failure. The inferences were drawn with the use of SPSS v22.0 statistical software. ANOVA, Chi-square and Student's t-test were used in the analysis. </br></br> <b> Results:</b> There was a positive correlation between SOFA score and IAP; and this correlation was found to be statistically significant with Pearson's correlation coefficient being 0.6247 and significance levels being <0.0001. Both hospital stay and mortality positively correlated with the degree of IAP. </br></br> <b> Conclusions:</b> IAP should be routinely measured in patients with acute abdomen requiring exploratory laparotomy. Patients with preoperatively raised IAP should be referred for emergency surgery as soon as possible for better outcome.

Overview of follicle stimulating hormone and its receptors in reproduction and in stem cells and cancer stem cells.

Follicle stimulating hormone (FSH) and its receptor (FSHR) have been reported to be responsible for several physiological functions and cancers. The responsiveness of stem cells and cancer stem cells towards the FSH-FSHR system make the function of FSH and its receptors more interesting in the context of cancer biology. This review is comprised of comprehensive information on FSH-FSHR signaling in normal physiology, gonadal stem cells, cancer cells, and potential options of utilizing FSH-FSHR system as an anti-cancer therapeutic target.

Effect of Mastectomy Flap Fixation on Post-operative Fluid Drainage and Seroma Formation in Breast Cancer Patients A Double-blinded Randomised Control Trial.

<b> Introduction:</b> Post-operative seroma formation is one of the most common complications following modified radical mastectomy (MRM). Quilting is a technique where the mastectomy flaps are sutured to the underlying chest wall muscles with sutures, obliterating the dead space. The authors hypothesised that post-mastectomy dead space obliteration by intermittent mastectomy flap fixation leads to decreased drain output and seroma formation. </br></br> <b> Material and methods: </b> A double-blinded randomised control trial with two arms was conducted from November 2019 to March 2021 in our institute located in India. Patients with non metastatic breast carcinoma planned for MRM were randomly categorised into two groups of 35 patients each. In the test group, each flap was fixed to the underlying muscle using four intermittent 3-0 polyglactin sutures, which was followed by skin closure, and only skin closure was done in the control group. </br></br> <b>Results:</b> The test and control groups did not differ significantly with respect to demographic and tumour characteristics. The average drain output of the test group (155.43 ml) was significantly less than of the control group (206.29 ml). The overall incidence of seroma formation is lower in the test group (5.7%) when compared to the control group (28.6%). The duration of hospital stay in the test group (4.63 days) was significantly shorter when compared to the control group (6.66 days). There was no significant increase in the overall operating time or complications like surgical site infection or skin dimpling due to flap fixation. </br></br> <b>Conclusions:</b> Fixation of MRM flaps is associated with better post-operative outcomes related to drain output and seroma formation without a significant increase in other morbidities or usage of resources.