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Objectively measuring animal behavior is key to understanding the neural circuits underlying pain. Recent progress in machine vision has presented us with unprecedented scope in behavioral analysis. Here, we apply DeeplabCut (DLC) to dissect mouse behavior on the thermal-plate test — a commonly used paradigm to ascertain supraspinal contributions to noxious thermal sensation and pain hypersensitivity. We determine the signature characteristics of the pattern of mouse movement and posture in 3D in response to a range of temperatures from innocuous to noxious on the thermal-plate test. Next, we test how acute chemical and chronic inflammatory injuries sensitize mouse behaviors. Repeated exposure to noxious temperatures on the thermal-plate can induce learning, and in this study, we design a novel assay and formulate an analytical pipeline that will facilitate the dissection of plasticity mechanisms in pain circuits in the brain. Last, we record and test how activating Tacr1 expressing PBN neurons — a population responsive to sustained noxious stimuli-affects mouse behavior on the thermal plate test. Taken together, we demonstrate that by tracking a single body part of a mouse, we can reveal the behavioral signatures of mice exposed to noxious surface temperatures, report the alterations of the same when injured, and determine if a molecularly and anatomically defined pain responsive circuit plays a role in the reflexive hypersensitivity to thermal pain.

Stress is a powerful modulator of pain. Specifically, acute stress due to physical restraint facilitates stress-induced analgesia (SIA). However, where, and how acute stress and pain pathways interface in the brain must be better understood. Here, we describe how the lateral septum (LS), a forebrain limbic nucleus, facilitates SIA through its downstream targets in the lateral hypothalamus (LH). We show that the LS→LH circuitry is sufficient to drive analgesia and is required for SIA. Further, we reveal that the LS→LH pathway is opioid-dependent and modulates pain through the pro-nociceptive neurons in the rostral ventromedial medulla (RVM). Remarkably, we found that the LS neurons are inhibitory, are recruited specifically when the mice struggle to escape under restraint, and, in turn, inhibit excitatory LH neurons. As a result, the RVM neurons downstream of LH are disengaged when the mice try to escape, thus suppressing nociception. Next, our data indicate that the efforts to escape are communicated by the lateral periaqueductal gray (lPAG) to the LS and activation of the upstream lPAG→LS circuit phenocopies LS→LH activation and results in analgesia. Thus, we have revealed a polysynaptic pathway that can transform escape behavior in mice under restraint to acute stress and resultant analgesia.

Background:Endoscopic retrograde cholangiopancreatography (ERCP), often require sedation during the procedure. The most commonly used drugs for this purpose are midazolam and propofol, which are used as sedative and hypnotic agents with minimal analgesic potential. Aims & objectives:Effects of Sedoanalgesia with Midazolam/ ketamine long with Dexmedetomidine nfusion & Rescue propofol alliquotes regimes on hemodynamic and respiratory variables& recovery profile in patients undergoing ERCP. Methods:In this Retrospective observational study adult patients of ASA gradel- lll were enrolled after taking inform consent from patient & their relatives. Premedication was given in form of inj.Midazolam 0.02 mg/kg iv in Group l,.inj ketamine 0.5 mg/kg iv was given in group ll. Inj.Dexmedetomidine ( bolus dose of 1 μg/kg over 10 min) followed by 0.5μg/kg/hour as maintenance in both the groups.intermittent Intravenous Propofol alliquotes was used for maintain BIS 70-80 in both groups. Amount of propofol used during procedure was notified.. Hemodynamic and respiratory variables, recovery time and adverse events weremonitored & recorded. Results:The hemodynamic and respiratory variables were similar in both groups. Total propofol consumption was significantly lower in the group ll. (205+/-80 mg vs.155+/-20 mg p < 0.001). The recovery period was shorter in group ll (time to achieve the Aldrete score 9 was 9.0 ±2.2 vs. , 6.2+/-1.1min p < 0.001).Adverse events were comparable between the two groups. Conclusion:Ketamine-Dexmedetomidinecombination with propofol may be a safe and useful alternative for sedation for ERCP patients.

BACKGROUND: Half of India´s three million TB patients are treated in the largely unregulated private sector, where quality of care is often poor. Private provider interface agencies (PPIAs) seek to improve private sector quality of care, which can be measured in terms of case fatality and recurrence rates.METHODS: We conducted a retrospective cohort survey of 4,000 private sector patients managed by the PATH PPIA between 2014 and 2017. We estimated treatment and post-treatment case-fatality ratios (CFRs) and recurrence rates. We used Cox proportional hazards models to identify predictors of fatality and recurrence. Patient loss to follow-up was adjusted for using selection weighting.RESULTS: The treatment CFR was 7.1% (95% CI 6.0–8.2). At 24 months post-treatment, the CFR was 2.4% (95% CI 1.7–3.0) and the recurrence rate was 1.9% (95% CI 1.3–2.5). Treatment fatality was associated with age (HR 1.02, 95% CI 1.02–1.03), clinical diagnosis (HR 0.61, 95% CI 0.45–0.84), treatment duration (HR 0.09, 95% CI 0.06–0.10) and adherence. Post-treatment fatality was associated with treatment duration (HR 0.87, 95% CI 0.79–0.91) and adherence.CONCLUSIONS: We found a moderate treatment phase CFR among PPIA-managed private sector patient with low rates of post-treatment fatality and recurrence. Routine monitoring of patient outcomes after treatment would strengthen PPIAs and inform future post TB interventions.

Summary Background Pathology and laboratory medicine diagnostics and diagnostic imaging are crucial to achieving universal health coverage. We analysed Service Provision Assessments (SPAs) from ten low-income and middle-income countries to benchmark diagnostic availability. Methods Diagnostic availabilities were determined for Bangladesh, Haiti, Malawi, Namibia, Nepal, Kenya, Rwanda, Senegal, Tanzania, and Uganda, with multiple timepoints for Haiti, Kenya, Senegal, and Tanzania. A smaller set of diagnostics were included in the analysis for primary care facilities compared with those expected at hospitals, with 16 evaluated in total. Surveys spanned 2004–18, including 8512 surveyed facilities. Country-specific facility types were mapped to basic primary care, advanced primary care, or hospital tiers. We calculated percentages of facilities offering each diagnostic, accounting for facility weights, stratifying by tier, and for some analyses, region. The tier-level estimate of diagnostic availability was defined as the median of all diagnostic-specific availabilities at each tier, and country-level estimates were the median of all diagnostic-specific availabilities of each of the tiers. Associations of country-level diagnostic availability with country income as well as (within-country) region-level availability with region-specific population densities were determined by multivariable linear regression, controlling for appropriate covariates including tier. Findings Median availability of diagnostics was 19·1% in basic primary care facilities, 49·2% in advanced primary care facilities, and 68·4% in hospitals. Availability varied considerably between diagnostics, ranging from 1·2% (ultrasound) to 76·7% (malaria) in primary care (basic and advanced) and from 6·1% (CT scan) to 91·6% (malaria) in hospitals. Availability also varied between countries, from 14·9% (Bangladesh) to 89·6% (Namibia). Availability correlated positively with log(income) at both primary care tiers but not the hospital tier, and positively with region-specific population density at the basic primary care tier only. Interpretation Major gaps in diagnostic availability exist in many low-income and middle-income countries, particularly in primary care facilities. These results can serve as a benchmark to gauge progress towards implementing guidelines such as the WHO Essential Diagnostics List and Priority Medical Devices initiatives. Funding Bill & Melinda Gates Foundation.

Purpose: Radiology global outreach programs have increased in recent years but progressed more slowly than other specialties. Establishing radiology services is increasingly recognized as a priority in resource-limited settings. Myanmar has a tremendous disease burden that is treatable with interventional radiology (IR) techniques, and aims to grow and effectively integrate this service into its public healthcare sector. Through collaborations between Asia Pacific Society of Cardiovascular and Interventional Radiology (APSCVIR) and Myanmar Radiological Society (MRS), the field of IR has grown exponentially over recent years. This study aims to provide a Myanmar national IR report on the current trends and future challenges. Methods and materials: Descriptive variables across five domains (facility and equipment, workforce, supplies, infrastructure, and casemix) from the four public sector hospitals with IR capability were obtained between 2016-2019. The four hospitals were Yangon General Hospital (YGH), Yangon Specialty Hospital (YSH), Mandalay General Hospital (MGH), and Defense Services General Hospital (DSGH). Data were analyzed to demonstrate progress in IR and the differing casemix. Results: There are currently four IR-capable hospitals and nine interventional radiologists across Myanmar’s public healthcare sector. IR case volumes tripled from 514 cases in 2016 to more than 1,500 cases in 2019. The three most common procedures performed were trans-arterial chemoembolization (TACE, 63%), bronchial arterial embolization (BAE, 7.7%), and drainages (7.7%). Significant challenges to the growth and adoption of IR services span the domains of infrastructure, equipment and supplies, workforce, and IR awareness, among other clinical specialties. Conclusion: Myanmar’s healthcare priorities, coupled with international radiological outreach programs, have led to rapid growth of IR. The exponential growth in case volumes is promising for Myanmar and other developing countries. But to widen the scope of practice and integrate the service within local clinical workflows, a holistic effort that addresses multiple domains is needed in the future.

The COVID-19 pandemic has had a devastating impact on global health for almost two years, resulting in nearly 200 million cases and over 4 million deaths worldwide. Despite a range of non-invasive public health measures, (i.e. physical distancing, and masks) vaccines have been one of the more critical and effective interventions to slow the pandemic. Produced at record-breaking speeds, the highly efficacious mRNA vaccines represented hope for many. Including global health organizations who have called for strategies to maximize vaccine equity since their conception. While many high-income countries (HICs) agreed to prioritize global vaccine equity; in truth, individual health outweighed community health. The reality of HICs vaccine purchasing behaviors and distribution have exposed a different agenda - one that aligns with a neoliberal emphasis on individuals and profits at the expense of global good. This commentary questions the efficacy of global health agreements and the commitment from wealthy countries to address global health inequities through a one health framework. Ultimately, concluding that the path to global vaccine equity will require a commitment to global good. Vaccine nationalism and lack of equitable global health policy continues to fuel a never-ending health crisis. HICs must be held accountable for the lack of commitment to global health equity.

The goal of the study is to examine the effectiveness of using an incentivized “test/retest” scenario to improve participants’ performance during stressful situations. The study makes use of an electroencephalography (EEG) machine to detect participants’ stress levels during a one-minute typing test. The typing test administered was a standard, “story-typing” test. A total of 23 student participants were randomly divided into two cohorts: the control cohort and the experimental cohort. Participants were asked to complete a preliminary questionnaire self-assessing their ability to handle stressful situations. Both cohorts were then asked to complete the typing test (hereafter referred to as T1) and fill out an Emotional Stress Reaction Questionnaire (ESRQ), indicating their emotions during the typing test. The participants were then asked to complete the typing test and accompanying ESRQ a second time (hereafter referred to as T2). However, prior to the second test, the participants in the experimental cohort were told that the participant that shows the most improvement in their typing speed (measured in words per minute) will receive a $100 gift card. This stimulus is used to increase the already stressful situation for the experimental cohort and examine whether participants’ brain activity changes when the “retest” is incentivized. Each participant’s EEG data and heartrate were measured through the duration of the experiment and t-tests and regression analyses were used to determine if a statistically significant difference existed between cohorts (control vs. experimental) or within cohorts (T1 vs. T2). The results show that there were no significant changes in brain activity, emotions, or typing performance for the control group of participants (no reward offered). However, the experimental group showed an increase in EEG sensor activity; specifically, the sensors that control vision and emotion. Interestingly, the participant’s performance was found to be correlated to their emotional responses, rather than their EEG sensor data. Additionally, the experimental groups’ positive emotions were increased for the second typing test, which is incentivized. The findings lay a foundation for design settings scenarios where preparatory practices can be incorporated.

Maintenance of cellular proteostasis is vital for post-mitotic cells like neurons to sustain normal physiological function and homeostasis, defects in which are established hallmarks of several age-related conditions like AD, PD, HD, and ALS. The Spatio-temporal accumulation of aggregated proteins in the form of inclusion bodies/plaques is one of the major characteristics of many neurodegenerative diseases, including Huntington’s disease (HD). Toxic accumulation of HUNTINGTIN (HTT) aggregates in neurons bring about the aberrant phenotypes of HD, including severe motor dysfunction, dementia, and cognitive impairment at the organismal level, in an age-dependent manner. In several cellular and animal models, aggrephagy induction has been shown to clear aggregate-prone proteins like HTT and ameliorate disease pathology by conferring neuroprotection. In this study, we used the mouse model of HD, R6/2, to understand the pathogenicity of mHTT aggregates, primarily focusing on autophagy dysfunction. We report that basal autophagy is not altered in R6/2 mice, whilst being functional at a steady-state level in neurons. Moreover, we tested the efficacy of a known autophagy modulator, Nilotinib (Tasigna™), presently in clinical trials for PD, and HD, in curbing mHTT aggregate growth and their potential clearance, which was ineffective in both inducing autophagy and rescuing the pathological phenotypes in R6/2 mice.

Background: The effectiveness of immunotherapies for non-small-cell lung cancer under real-world clinical settings remains uncertain. Materials & methods: Systematic searches of PubMed, EMBASE and Web of Science were conducted. Random-effects models were used to estimate pooled median overall survival and progression-free survival estimates. Results: 36 studies of nivolumab were included for narrative synthesis and 11 of these studies were included for meta-analysis. Age, sex, histology and prior lines of treatment did not affect survival outcomes, while Eastern Cooperative Oncology Group Performance Status and brain metastasis were inversely associated with survival. In the meta-analysis, nivolumab was associated with 9.6 months (95% CI: 8.4–10.9) of overall survival and 2.6 months (95% CI: 1.6–3.6) of progression-free survival. Conclusion: Very-low-certainty evidence suggested the real-world effectiveness of nivolumab was consistent with those observed in the clinical trials.

Background: Primary caesarean section is defined as caesarean section to be performed in women who have not had previous caesarean delivery. The increase in the rates of primary caesarean section is not only due to increased caesarean section in nulligravida but also due to upward rise in caesarean section rates in parous women. Through this study we aimed to examine the frequency and the indications of primary caesarean section in nulliparous and multiparous women.Methods: A prospective study was carried out in the OBGY department of smt. SCL Hospital, NHL municipal medical college from April 2020 to April 2021. All multiparous women with previous normal vaginal delivery who underwent caesarean section this time were included in this study. Patients with previous caesarean section

Background: Referral is a coordinated movement of healthcare seekers through the health system to reach a high level of care in a small and often fatal window of time. Even physiological processes like pregnancy and childbirth are not free of complications. The purpose of this study is to understand maternal and foetal outcome in caesarean sections in referred cases.Methods: A prospective study was carried out in the OBGY department of SMT.SCL HOSPITAL, NHL Municipal medical college from April 2020 to April 2021. All referred antenatal and intranatal patients to our tertiary care centre with >20 weeks of gestation who underwent caesarean section with referral note.Results: A total 64% patients were referred from community health center. 63.5% patients were referred due to lack of high-risk management services. 211 patients underwent caesarean section while 69 patients had normal vaginal delivery. Difficulty in delivery of the baby was encountered in 53% of cases due to deep engagement of the fetal head. Major cause of admission in NICU was sepsis (38.6%) followed by prematurity (23.8%).Conclusions: Cesarean section is one of the quickest and most efficient method in the delivery of the baby and thus should in considered in patients in critical situations .The millennium development goals defined by united nation includes one goal (MDG 5) towards improving maternal health which still remains a challenge. Thus, improving knowledge of women regarding good antenatal care and strengthening referral services will play a big role in this.

Senior Capstone Design courses offer two major types of projects: industry sponsored projects and non-industry sponsored projects. Previous studies show changes in student motivation based on the type of project they select. However, the quantitative data analysis fails to capture the reasoning behind the student’s inclination towards a certain type of project in the beginning of the selection phase. Also, little is known about the personal experiences of the student working on the team and project they choose. This paper addresses the gap in the examination of student motivation based on the type of projects they select. This paper outlines a coding scheme developed to analyze the qualitative interview data gathered during an open-floor style exit interview with all of the senior design teams. The thirty minute exit interviews were conducted at the end of the semester to capture their experiences and reflections about the course. A coding manual is generated which highlights the codes observed frequently among the teams. Themes are developed highlighting the important phases of the course. The objective is to develop a coding scheme for senior capstone design courses which would serve as a guide to the educators to determine various factors that influence student motivation and improve the senior design experience for all students.

In a multifaceted course such as senior capstone design, it is integral to ensure students are receiving a value adding experience. In most universities across the United States, senior capstone design is a multiple semester sequence where design is heavily emphasized and students are encouraged to test their skills, both technical and nontechnical, by solving and implementing solutions to real industry problems. Given the nature of design courses, the takeaways are not things that can be measured solely through the use of a letter grade. Rather, an in-depth reflective interview must be performed to fully comprehend what students received from the course. In this study, an In-Depth Interview Protocol was developed to understand the effectiveness of engineering design courses and improve design education as a whole. This paper outlines the phases that contribute towards the development of an effective interview protocol for implementation in senior capstone design curriculum. The formulation and considerations are outlined with respect to design curriculum and student success. This protocol will be utilized to perform a Reflection Interview for each senior design project team at the end of the spring 2019 semester. The assignment is not graded and is inquisitive on the students’ perceptions of motivation during their time at Florida Tech. The qualitative data gathered will be eligible for further studies and analysis.

PURPOSE Increasing noncommunicable disease burden in sub-Saharan Africa requires the urgent scale-up of pathology and laboratory medicine (PALM) services. To identify service gaps at the district level, we studied geographic variation in the correlation between travel time to health facilities and population density. METHODS We linked geospatial data for Tanzania from multiple sources. Facility locations were extracted from a comprehensive facility list in Africa. Data on geographic factors, demographics, and roads were collected from government and nonprofit databases. We classified facilities assuming increasing PALM service readiness by level: dispensaries, health centers, district hospitals, and regional/referral hospitals. We input these data into the AccessMod 5 algorithm to estimate travel time across Tanzania with 1-km resolution for each PALM classification. We then calculated district-level averages of population and travel time for each PALM category. Associations between these variables were estimated using a bivariable local indicator of spatial autocorrelation, specifying immediate contiguity neighborhood definition. Spatial analysis was restricted to 172 contiguous districts (islands not included). Significance tests were two sided, with an α of .05. RESULTS Analysis included 5,342 dispensaries, 667 health centers, 185 district hospitals, and 34 regional/referral hospitals. Maps revealed clusters of estimated travel time in excess of 6 hours in less populated western and southern districts. More districts reported an average travel time of less than 1 hour to the nearest dispensary (69%) than to regional/referral hospitals (16%). Bivariable local indicators of spatial autocorrelation revealed few significant clusters of spatial correlations; however, significant correlations between low population density and longer travel times in neighboring districts were obtained for 13%, 16%, 15%, and 13% of districts for dispensaries, health centers, district hospitals, and regional/referral hospitals, respectively. CONCLUSION Limited variability of district-level spatial correlations suggests somewhat equitable geographic allocation of PALM services in Tanzania, with small areas of low population density and long travel times that demand additional intervention. Limitations include a lack of ascertainment of specific PALM services.

SYNGAP1, a Synaptic Ras-GTPase activating protein, regulates synapse maturation during a critical developmental window. Heterozygous mutation in SYNGAP1 (SYNGAP1-/+) has been shown to cause Intellectual Disability (ID) in children. Recent studies have provided evidence for altered neuronal protein synthesis in a mouse model of Syngap1-/+. However, the molecular mechanism behind the same is unclear. Here, we report the reduced expression of a known translation regulator, FMRP, during a specific developmental period in Syngap1-/+ mice. Our results demonstrate that FMRP interacts with and regulates the translation of Syngap1 mRNA. We further show reduced Fmr1 translation leads to decreased FMRP level during development in Syngap1-/+ which results in an increase in Syngap1 translation. These developmental changes are reflected in the altered response of eEF2 phosphorylation downstream of NMDA Receptor (NMDAR)-mediated signaling. In this study, we propose a cross-talk between FMRP and SYNGAP1 mediated signaling which can also explain the compensatory effect of impaired signaling observed in Syngap1-/+ mice.

The long half-life and stability of human serum albumin (HSA) make it an attractive candidate for fusion to short-lived therapeutic proteins. Albuferon (Human Genome Sciences [HGS], Inc., Rockville, MD) beta is a novel recombinant protein derived from a gene fusion of interferon-beta (IFN-beta ) and HSA. In vitro, Albuferon beta displays antiviral and antiproliferative activities and triggers the IFN-stimulated response element (ISRE) signal transduction pathway. Array analysis of 5694 independent genes in Daudi-treated cells revealed that Albuferon beta and IFN-beta induce the expression of an identical set of 30 genes, including 9 previously not identified. In rhesus monkeys administered a dose of 50 microg/kg intravenously (i.v.) or subcutaneously (s.c.) or 300 microg/kg s.c., Albuferon beta demonstrated favorable pharmacokinetic properties. Subcutaneous bioavailability was 87%, plasma clearance at 4.7-5.7 ml/h/kg was approximately 140-fold lower than that of IFN-beta, and the terminal half-life was 36-40 h compared with 8 h for IFN-beta. Importantly, Albuferon beta induced sustained increases in serum neopterin levels and 2',5' mRNA expression. At a molar dose equivalent to one-half the dose of IFN-beta, Albuferon beta elicited comparable neopterin responses and significantly higher 2',5'-OAS mRNA levels in rhesus monkeys. The enhanced in vivo pharmacologic properties of IFN-beta when fused to serum albumin suggest a clinical opportunity for improved IFN-beta therapy.

After assuming office as President, Donald Trump on the third day authorized drones strikes in Yemen. Consequently, as per U.S. Central Command (CENTCOM), five suspected member of al Qaeda were killed in central Yemen. Recently U.S. drone strikes killed two more suspected members in Abyan and other two provinces of Southern Yemen. As per, Pentagon “somewhere over 30 strikes” were carried out against al Qaeda in the Arabian Peninsula (AQAP) in two days. With the escalation of conflict in Yemen, drone strikes are likely to soar under Trump. Does this imply that Trump is following the footsteps of Obama in regard to US policy on drones and their utility in military operations?

IFN-kappa is a recently identified type I IFN that exhibits both structural and functional homology with the other type I IFN subclasses. In this study, we have investigated the effect of IFN-kappa on cells of the innate immune system by comparing cytokine release following treatment of human cells with either IFN-kappa or two recombinant IFN subtypes, IFN-beta and IFN-alpha2a. Although IFN-alpha2a failed to stimulate monocyte cytokine secretion, IFN-kappa, like IFN-beta, induced the release of several cytokines from both monocytes and dendritic cells, without the requirement of a costimulatory signal. IFN-kappa was particularly effective in inhibiting inducible IL-12 release from monocytes. Unlike IFN-beta, IFN-kappa did not induce release of IFN-gamma by PBL. Expression of the IFN-kappa mRNA was observed in resting dendritic cells and monocytes, and it was up-regulated by IFN-gamma stimulation in monocytes, while IFN-beta mRNA was minimally detectable under the same conditions. Monocyte and dendritic cell expression of IFN-kappa was also confirmed in vivo in chronic lesions of psoriasis vulgaris and atopic dermatitis. Finally, biosensor-based binding kinetic analysis revealed that IFN-kappa, like IFN-beta, binds strongly to heparin (K(d): 2.1 nM), suggesting that the cytokine can be retained close to the local site of production. The pattern of cytokines induced by IFN-kappa in monocytes, coupled with the unique induction of IFN-kappa mRNA by IFN-gamma, indicates a potential role for IFN-kappa in the regulation of immune cell functions.