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Abstract Background Hematopoietic acute radiation syndrome (H-ARS) occurring after exposure to ionizing radiation damages bone marrow causing cytopenias, increasing susceptibility to infections and death. We and others have shown that cellular therapies like human mesenchymal stromal cells (MSCs), or monocytes/macrophages educated ex-vivo with extracellular vesicles (EVs) from MSCs were effective in a lethal H-ARS mouse model. However, given the complexity of generating cellular therapies and the potential risks of using allogeneic products, development of an “off-the-shelf” cell-free alternative like EVs may have utility in conditions like H-ARS that require rapid deployment of available therapeutics. The purpose of this study was to determine the feasibility of producing MSC-derived EVs at large scale using a bioreactor and assess critical quality control attributes like identity, sterility, and potency in educating monocytes and promoting survival in a lethal H-ARS mouse model. Methods EVs were isolated by ultracentrifugation from unprimed and lipopolysaccharide (LPS)-primed MSCs grown at large scale using a hollow fiber bioreactor and compared to a small scale system using flasks. The physical identity of EVs included a time course assessment of particle diameter, yield, protein content and surface marker profile by flow-cytometry. Comparison of the RNA cargo in EVs was determined by RNA-seq. Capacity of EVs to generate exosome educated monocytes (EEMos) was determined by qPCR and flow cytometry, and potency was assessed in vivo using a lethal ARS model with NSG mice. Results Physical identity of EVs at both scales were similar but yields by volume were up to 38-fold more using a large-scale bioreactor system. RNA-seq indicated that flask EVs showed upregulated let-7 family and miR-143 micro-RNAs. EEMos educated with LPS-EVs at each scale were similar, showing increased gene expression of IL-6, IDO, FGF-2, IL-7, IL-10, and IL-15 and immunophenotyping consistent with a PD-L1 high, CD16 low, and CD86 low cell surface expression. Treatment with LPS-EVs manufactured at both scales were effective in the ARS model, improving survival and clinical scores through improved hematopoietic recovery. EVs from unprimed MSCs were less effective than LPS-EVs, with flask EVs providing some improved survival while bioreactor EVs provide no survival benefit. Conclusions LPS-EVs as an effective treatment for H-ARS can be produced using a scale-up development manufacturing process, representing an attractive off-the-shelf, cell-free therapy.

OBJECTIVE: To identify the risk factors and relationship between type 2 diabetes mellitus and depression. INTRODUCTION: People with type 2 diabetes compared to those without have double the chance to develop depression 1. Diabetes leads to depression or vice versa, remains an unsolved puzzle. Although association between Diabetes and Depression have been declared since many years but there is no definite answer to the chicken and egg dilemma, to make it less complicated a few researchers have labeled the link between the two to be bidirectional2 . Diabetes and depression have become common and the complications they bring along together leave deep psychological and physical imprints on their victims leading to functional limitation, poor quality of life and raised mortality rate. METHODOLOGY: The study was conducted at Ziauddin University Hospital over a period of six months, it is a cross sectional study. Sample size of 100 was taken. A questionnaire was designed that evaluated age, gender, co morbids, occupation, marital status, compliance, education, weight and HbA1c levels of participants. SRQ 20 depression scale was used to diagnose depression. Data was entered and analyzed by version 20 of SPSS. RESULTS: Different demographic and social variables were assessed in this study. 36.5% patients out of the total sample were depressed. The highest number of depressed people was found among elderly participants >60 years of age. 22 males and more than double i.e. 51 females were depressed. Obese patients (BMI>30) were found to have poor glycemic control. Illiteracy contributed to 48% (N=36) of the total depressed. The un-employed had two times more chance to develop depression as compared to participants who were employed. It was noticed that depression prevailed more among diabetic patients belonging to lower socioeconomic class. Marital status was highly significant in causing depression. P value= 0.001. Only 27% (34 out of 126) diabetic patients developed depression in the absence of any complications and 73% remained un depressed. Religious beliefs seemed to play a vital role in reduction of depressive symptoms. CONCLUSION: Research suggests that co-morbid diabetes and depression is not a rare finding. Risk factors must be ruled out and the chances to develop depression should be identified at an earlier stage before complications worsen the condition. No more depression should go un-recognized and hence un treated in type 2 DM patients. KEY WORDS: Depression, type 2 diabetes mellitus, risk factors

Schwann cells are essential for the maintenance and function of motor neurons, axonal networks, and the neuromuscular junction. In amyotrophic lateral sclerosis, where motor neuron function is progressively lost, Schwann cell function may also be impaired. Recently, important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been reported. This case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles, marking, to our knowledge, the first instance of such treatment. An 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral sclerosis. After initial diagnosis, the patient underwent a combination of generic riluzole, sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis, and taurursodiol. The patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron function. We confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired (senescent) and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles, cultured expanded from a cadaver donor improved their growth capacity in vitro. After a period of observation lasting 10 weeks, during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored, the patient received weekly consecutive infusions of 1.54 × 1012 (×2), and then consecutive infusions of 7.5 × 1012 (×6) allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered saline. None of the infusions were associated with adverse events such as infusion reactions (allergic or otherwise) or changes in vital signs. Clinical lab serum neurofilament and cytokine levels measured prior to each infusion varied somewhat without a clear trend. A more sensitive in-house assay suggested possible inflammasome activation during the disease course. A trend for clinical stabilization was observed during the infusion period. Our study provides a novel approach to address impaired Schwann cells and possibly motor neuron function in patients with amyotrophic lateral sclerosis using allogeneic Schwann cell-derived exosomal vesicles. Initial findings suggest that this approach is safe.

Abstract COVID-19 pandemic has increased social media engagement globally. This study examined the correlation between social media use and physical/mental health among university students, considering gender and academic year. Out of 146 responses, 119 were analyzed after excluding participants with pre-existing psychological conditions. Results showed a significant correlation between social media use and mental health for all participants (correlation coefficient = 0.30, p

Objective: To assess the nutritional status of children (up to 2 years of age) visiting the National Institute of Child Health (NICH) Karachi and to determine its association with breastfeeding and complementary feeding practices. Study Design: Cross-Sectional Study. Place and Duration of Study: Outpatient Department, National Institute of Child Health, Karachi Pakistan, from Jan to Jun 2021. Methodology: Children aged 1 to 24 months were included. Demographic information, weight, height, weight for height and grade of malnutrition using WHO criteria were checked and categorized as median, -1S.D, -2S.D, -3SD and -4 SD. Face-to-face interview with the mother was conducted using a semi-structured questionnaire based on WHO Infant and Young Child Feeding guidelines to find out the breastfeeding and complementary feeding practices of the mother. Results: A total of 355 children were enrolled with a mean age of 9.18±5.90 months. Median SD was attained by 65(18.3%) children, 177(49.9%) infants lied within -1SD(mild malnutrition), 77(21.4%) within -2SD(moderate malnutrition) while 36(10.1%) had severe malnutrition including 26(7.3%) within -3SD and 10(2.8%) within -4SD. Exclusive breastfeeding for up to 6 months had a significantly lower frequency of severe malnourishment (p-value

Introduction: The SARS-CoV-2 pandemic has been affecting the health and economic, as well as social, life of the entire globe since the end of 2019. The virus causes COVID-19, with a wide range of symptoms among the infected individuals, from asymptomatic infection to mortality. This, along with a high infection rate, prompted efforts to investigate the potential mechanisms of the different clinical manifestations caused by SARS-CoV-2 among the infected populations. Hypothesis: One of the possible mechanisms that has been reported is the ABO blood system polymorphism. Indeed, one of the major proposed mechanisms is the presence of naturally occurring anti-A antibodies in individuals of groups O and B, which could be partially protective against SARS-CoV-2 virions. Objective and Method: This article aimed to review the published data on the potential effect of the ABO blood group system on the susceptibility to COVID-19 and the disease progression and outcomes. Results: The reviewed data suggest that individuals of blood group A are at a higher risk of infection with SARS-CoV-2 and may develop severe COVID-19 outcomes, whereas blood group O is considered protective against the infection, to some extent. However, some of the available studies seem to have been influenced by unaccounted confounders and biases. Conclusion: Therefore, further appropriately controlled studies are warranted to fully investigate the possible association between the ABO blood groups and COVID-19 susceptibility and severity.

What are the effects of parenting styles on academic performance and how unequal are these effects on secondary school students from different gender and socioeconomic status families constitute the theme of this paper. A cross-sectional and purposive sampling technique was adopted to gather information from a sample of 448 students on a Likert scale. Chi-square, Kendall's Tau-c tests and hierarchical multiple regression analyses were used to determine the extent of the relationship among the variables. Chi-square and Kendall's Tau-c (Tc) test results established that the socioeconomic status of the respondent's family explained variation in children's academic performance due to parenting style; however, no significant difference was observed in the academic performance of students based on gender. Furthermore, hierarchal multiple regression analysis established that the family's socioeconomic status, authoritative parenting, permissive parenting, the interaction of socioeconomic status and authoritative parenting, and the interaction of socioeconomic status and permissive parenting were significant predictors (P

Abstract The Production Assistance for Cellular Therapies (PACT) Program, is funded and supported by the US Department of Health and Human Services’ National Institutes of Health (NIH) National Heart Lung and Blood Institute (NHLBI) to advance development of somatic cell and genetically modified cell therapeutics in the areas of heart, lung, and blood diseases. The program began in 2003, continued under two competitive renewals, and ended June 2021. PACT has supported cell therapy product manufacturing, investigational new drug enabling preclinical studies, and translational services, and has provided regulatory assistance for candidate cell therapy products that may aid in the repair and regeneration of damaged/diseased cells, tissues, and organs. PACT currently supports the development of novel cell therapies through five cell processing facilities. These facilities offer manufacturing processes, analytical development, technology transfer, process scale‐up, and preclinical development expertise necessary to produce cell therapy products that are compliant with Good Laboratory Practices, current Good Manufacturing Practices, and current Good Tissue Practices regulations. The Emmes Company, LLC, serves as the Coordinating Center and assists with the management and coordination of PACT and its application submission and review process. This paper discusses the impact and accomplishments of the PACT program on the cell therapy field and its evolution over the duration of the program. It highlights the work that has been accomplished and provides a foundation to build future programs with similar goals to advance cellular therapeutics in a coordinated and centralized programmatic manner to support unmet medical needs within NHLBI purview.

Peripheral nerve injury (PNI) is found in a relatively large portion of trauma patients. If the injury is severe, such as with the presence of a long segmental gap, PNI can present a challenge for treatment. The current clinical standard of nerve harvest for the repair of long segmental gap PNI can lead to many potential complications. While other methods have been utilized, recent evidence indicates the relevance of cell therapies, particularly through the use of Schwann cells, for the treatment of PNI. Schwann cells (SCs) are integral in the regeneration and restoration of function following PNI. SCs are able to dedifferentiate and proliferate, remove myelin and axonal debris, and are supportive in axonal regeneration. Our laboratory has demonstrated that SCs are effective in the treatment of severe PNI when axon guidance channels are utilized. However, in order for this treatment to be effective, optimal techniques for cellular placement must be used. Thus, here we provide relevant background information, preclinical, and clinical evidence for our method in the treatment of severe PNI through the use of SCs and axon guidance channels.

ObjectiveTo systematically evaluate the literature on the therapeutic use of Schwann cells (SC) in the repair of peripheral nerve injuries.MethodsThe Cochrane Library and PubMed databases were searched using terms [(“peripheral nerve injury” AND “Schwann cell” AND “regeneration”) OR (“peripheral nerve injuries”)]. Studies published from 2008 to 2022 were eligible for inclusion in the present study. Only studies presenting data from in-vivo investigations utilizing SCs in the repair of peripheral nerve injuries qualified for review. Studies attempting repair of a gap of ≥10 mm were included. Lastly, studies needed to have some measure of quantifiable regenerative outcome data such as histomorphometry, immunohistochemical, electrophysiology, or other functional outcomes.ResultsA search of the PubMed and Cochrane databases revealed 328 studies. After screening using the abstracts and methods, 17 studies were found to meet our inclusion criteria. Good SC adherence and survival in conduit tubes across various studies was observed. Improvement in morphological and functional outcomes with the use of SCs in long gap peripheral nerve injuries was observed in nearly all studies.ConclusionBased on contemporary literature, SCs have demonstrated clear potential in the repair of peripheral nerve injury in animal studies. It has yet to be determined which nerve conduit or graft will prove superior for delivery and retention of SCs for nerve regeneration. Recent developments in isolation and culturing techniques will enable further translational utilization of SCs in future clinical trials.

Abstract Background Bone marrow-derived mesenchymal stem cells (BM-MSCs) have shown therapeutic potential in various in vitro and in vivo studies in cutaneous wound healing. Furthermore, there are ubiquitous studies highlighting the pro-regenerative effects of BM-MSC extracellular vesicles (BM-MSC EVs). The similarities and differences in BM-MSC EV cargo among potential healthy donors are not well understood. Variation in EV protein cargo is important to understand, as it may be useful in identifying potential therapeutic applications in clinical trials. We hypothesized that the donors would share both important similarities and differences in cargo relating to cell proliferation, angiogenesis, Wnt signaling, and basement membrane formation—processes shown to be critical for effective cutaneous wound healing. Methods We harvested BM-MSC EVs from four healthy human donors who underwent strict screening for whole bone marrow donation and further Good Manufacturing Practices-grade cell culture expansion for candidate usage in clinical trials. BM-MSC EV protein cargo was determined via mass spectrometry and Proteome Discoverer software. Corresponding proteomic networks were analyzed via the UniProt Consortium and STRING consortium databases. Results More than 3000 proteins were identified in each of the donors, sharing > 600 proteins among all donors. Despite inter-donor variation in protein identities, there were striking similarities in numbers of proteins per biological functional category. In terms of biologic function, the proteins were most associated with transport of ions and proteins, transcription, and the cell cycle, relating to cell proliferation. The donors shared essential cargo relating to angiogenesis, Wnt signaling, and basement membrane formation—essential processes in modulating cutaneous wound repair. Conclusions Healthy donors of BM-MSC EVs contain important similarities and differences among protein cargo that may play important roles in their pro-regenerative functions. Further studies are needed to correlate proteomic signatures to functional outcomes in cutaneous repair.

In this study, we report 2 cases of abnormal systemic artery to left lower lobe (ASALLL) with hemoptysis. In case 1, a 15-year-old boy experienced intermittent hemoptysis for over a year. After diagnosis of ASALLL by chest-enhanced computerized tomography (CT), interventional embolization was performed to treat the abnormal arteries, and the patient was cured and discharged. Case 2 is a 36-year-old man with chest pain and hemoptysis recurring for many years and aggravating for 5 days. ASALLL was diagnosed by chest-enhancement CT examination. After thoracoscopic resection of the left lower lobe, the patient was discharged. These cases show that the clinical manifestations of ASALLL are mainly recurrent hemoptysis symptoms. For patients with hemoptysis, the disease should be found and not limited to symptomatic treatment. Chest-enhanced CT scanning can diagnose ASALLL, and interventional embolization or surgical treatment can be selected for treatment.

Objective: To assess the relevance of urine test (UT), urine culture (UC) and stone culture (SC) for postoperative infections and to investigate the optimal perioperative antibiotic treatment strategy in association with percutaneous nephrolithotomy (PCNL) in patients with renal calculi. Materials and methods: Between September 2016 and September 2018 1,060 patients treated with PCNL were included in the study. The results of UT, UC and SC were reviewed. The details of perioperatively administered antibiotics and postoperative infections were recorded. Results: A positive UT was associated with an increased incidence of infection; this was also the case in patients with negative UC (p < 0.05). There was no significant difference in incidence of infection between patients who were given a single dose of antibiotics compared with those given multiple doses when UC was negative, whether UT was positive or negative (all p > 0.05). The incidence of infection was decreased when pre-operative antibiotics were administered according to the sensitivity pattern based on UC (p < 0.05). This outcome was particularly evident when the treatment duration exceeded 7 days (p < 0.05). A positive SC was associated with increased incidence of infection, even if the patient had a negative UC and UT (p < 0.05). The incidence of infection was significantly decreased when antibiotic treatment was administered based on the results of SC (p < 0.05). Conclusion: Pre-operative prophylaxis with a single-dose antibiotic was sufficient in patients with negative UC, whether UT was positive or negative. Pre-operative treatment with antibiotics according to the bacterial sensitivity pattern should be administered for ≥7 days in patients with positive UC. The postoperative antibiotic treatment strategy should be tailored according to the SC results.

Abstract Background Although major driver gene have been identified, the complex molecular heterogeneity of renal cell cancer (RCC) remains unclear. Therefore, more relevant genes need to be identified to explain the pathogenesis of renal cancer. Methods Microarray datasets GSE781, GSE6344, GSE53000 and GSE68417 were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were identified by employing GEO2R tool, and function enrichment analyses were performed by using DAVID. The protein-protein interaction network (PPI) was constructed and the module analysis was performed using STRING and Cytoscape. Survival analysis was performed using GEPIA. Differential expression was verified in Oncomine. Cell experiments (cell viability assays, transwell migration and invasion assays, wound healing assay, flow cytometry) were utilized to verify the roles of the hub genes on the proliferation of kidney cancer cells (A498 and OSRC-2 cell lines). Results A total of 215 DEGs were identified from four datasets. Six hub gene (SUCLG1, PCK2, GLDC, SLC12A1, ATP1A1, PDHA1) were identified and the overall survival time of patients with RCC were significantly shorter. The expression levels of these six genes were significantly decreased in six RCC cell lines(A498, OSRC-2, 786- O, Caki-1, ACHN, 769-P) compared to 293t cell line. The expression level of both mRNA and protein of these genes were downregulated in RCC samples compared to those in paracancerous normal tissues. Cell viability assays showed that overexpressions of SUCLG1, PCK2, GLDC significantly decreased proliferation of RCC. Transwell migration, invasion, wound healing assay showed overexpression of three genes(SUCLG1, PCK2, GLDC) significantly inhibited the migration, invasion of RCC. Flow cytometry analysis showed that overexpression of three genes(SUCLG1, PCK2, GLDC) induced G1/S/G2 phase arrest of RCC cells. Conclusion Based on our current findings, it is concluded that SUCLG1, PCK2, GLDC may serve as a potential prognostic marker of RCC.

Abstract Background Echinococcosis is a zoonotic parasitic disease causing serious health problems in both humans and animals in different endemic regions across the world. There are two different forms of human echinococcosis: Cystic Echinococcosis (CE) and Alveolar Echinococcosis (AE). CE is caused by the larval stage of Echinococcus granulosus sensu lato and AE by the larval stage of Echinococcus multilocularis. Geographically, CE is universally distributed, while AE is prevalent in the northern hemisphere. Although the disease is endemic in neighboring countries (China, Iran and India) of Pakistan, there are limited reports from that country. Besides, there are no comprehensive data on the genotyping of Echinococcus species in humans based on sequence analysis. This study aimed to detect the presence of human CE and to identify Echinococcus spp. in human isolates through genetic characterization of hydatid cysts in the Punjab Province of Pakistan. Methods Genetic analysis was performed on 38 human hydatid cyst samples collected from patients with echinococcosis using mitochondrial cytochrome c oxidase subunit 1 (cox1), cytochrome b (cytb) and NADH subunit 1 (nad1). Patient data including age, epidemiological history, sex, and location were obtained from hospital records. Results According to the sequence analysis we detected E. granulosus sensu stricto (n = 35), E. canadensis (G6/G7) (n = 2), and E. multilocularis (n = 1). Thus, the majority of the patients (92.1%, 35/38) were infected with E. granulosus s.s. This is the first molecular confirmation of E. canadensis (G6/G7) and E. multilocularis in human subjects from Pakistan. Conclusions These findings suggested that E. granulosus s.s. is the dominant species in humans in Pakistan. In addition, E. canadensis (G6/G7) and E. multilocularis are circulating in the country. Further studies are required to explore the genetic diversity in both humans and livestock.

Aim: The aim of the study was to identify the challenges and problems faced by student nurses and paramedic students during the clinical practice stage of their education.Design: The current study utilized a cross-sectional research design.Methods: A sample of 259 students was selected through convenience sampling, comprising 127 student nurses and 132 paramedic students. An adapted self-administered questionnaire, the Clinical Learning Environment Supervision and Nurse Teacher (CLES+T) evaluation scale was used to collect data, with the permission of the author. Socio-demographic characteristics were shown in the form of frequency and percentages. Findings concerning the evaluation of clinical learning were calculated in the context of descriptive statistical analysis, such as mean and standard deviation. An independent sample t-test was applied to compare the findings.Results: The mean age of respondents was 21.39 years, of whom 60 (61.8%) were male and 99 (32.2%) were female. The highest mean score (3.87 ± 0.77) was awarded to Nursing Care Provided on the Ward, while the lowest mean score was achieved for Supervisory Relationships on the Ward (3.71 ± 0.84).Conclusion: The study showed overall satisfaction with the clinical environment. Male and paramedic students were least satisfied. Considerable improvement is needed in the context of Pedagogical Atmosphere and Supervisory Relationships on the ward.

Objectives: Children’s cognitive and motor development is intertwined with their nutritional status and compromised by an impoverished environment. This study examined a modified Bruininks Oseretsky Test of motor proficiency - Brief Form (BOT2 BF) to evaluate its sensitivity in identifying motor differences secondary to malnutrition and poverty. Methods: Data was drawn from 1058 children who participated in a responsive-stimulation and nutrition intervention in the first two years of life. Outcome measures included motor development assessed via BOT2 BF, child anthropometry (height- and weight-for-age), according to the World Health Organization growth reference charts and household economic and demographic information collected using a family report questionnaire. Results: Mann Whitney U test was significant for malnutrition, socio-economic status and maternal literacy at p< 0.05, for a 6-item motor composite of BOT2 BF. Psychometric properties of the BOT2 BF were robust for this Pakistani cohort. Conclusion: A 6-item motor composite of BOT2 BF is a reliable tool to measure motor performance in Pakistani pre-school children Continuous....

A pandemic brought on by COVID-19 has created a scalable health crisis. The search to help alleviate COVID-19-related complications through therapeutics has become a necessity. Zofin is an investigational, acellular biologic derived from full-term perinatal amniotic fluid that contains extracellular vesicles. Extracellular nanoparticles as such have been studied for their immunomodulatory benefits via cellular therapeutics and, if applied to COVID-19-related inflammation, could benefit patient outcome. Subjects (n = 8) experiencing mild-to-moderate COVID-19 symptoms were treated with the experimental intervention. Complete blood count, complete metabolic panel, inflammatory biomarkers, and absolute lymphocyte counts were recorded prior to and on days 4, 8, 14, 21, and 30 as markers of disease progression. Additionally, chest x-rays were taken of the patients prior to and on days 8 and 30. Patients experienced no serious adverse events. All COVID-19-associated symptoms resolved or became stable with no indication of disease worsening as found by patient and chest x-ray reports. Inflammatory biomarkers (CRP, IL-6, TNF-α) and absolute lymphocyte counts improved throughout the study period. Findings from a proof-of-concept, expanded access trial for COVID-19 patients prove the acellular biologic is safe and potentially effective to prevent disease progression in a high-risk COVID-19 population with mild-to-moderate symptoms.

Hydrocephalus and Posterior Reversible Encephalopathy Syndrome (PRES) are under-diagnosed conditions in peri-partum period. As eclampsia mimics these conditions and it can mislead the clinician to an incorrect diagnosis causing potential morbidity and mortality. A case of a 35 year old pregnant woman with seizures presented that was initially diagnosed as eclampsia but failure to regain consciousness post-delivery led to a multidisciplinary team formation and further investigation through Magnetic Resonance Imaging (MRI) that finally revealed communicating hydrocephalous and PRES. Prompt management was initiated by placing a Ventriculo-Peritoneal (VP) shunt resulting in full neurological recovery afterwards. As per author’s knowledge there has not been a similar case reported as yet.

Background: Non-ischemic dilated cardiomyopathy (NIDCM) responds variably to intramyocardial injection of mesenchymal stem cells (MSCs). We hypothesized that NIDCM genotype may influence responsiveness to MSC therapy and performed genotyping on all patients in the POSEIDON-DCM trial. Methods: POSEIDON-DCM patients (n = 34) underwent genetic sequence analysis and deletion/duplication testing. The results were classified as positive for pathological variants (PV+; n = 8), negative for any variants (V−; n = 6), or as variants of uncertain significance (VUS; n = 20). All outcomes of therapy were analysed for each category of genetic results. Findings: The 3 groups were indistinguishable at baseline with regard to ejection fraction (EF), demographics, medication use, or functional parameters. V− patients had an increase in EF at 12 months: +13.6% (IQR = +7.8%; +20.5%; p = 0.002), compared with VUS (+6.5%; IQR = +0.9%, +11.1%; p = 0.005) and PV+(−5.9%; IQR = −12.7%, +1.0; p = 0.2; p = 0.01 between groups). Six-minute walk distance improved in V- patients, but not in VUS and PV+. V− patients improved MLHFQ, compared to the other 2 groups, which did not improve over time. EPCCFUs increased by 9.7 ± 1.9 in V− (p = 0.009) compared to VUS and PV+ patients. V− patients had one-year survival (100%) compared with VUS (85%) and PV+ (40%; p = 0.015 log-rank). Similarly, MACE rates were lower in V− (0%) than PV+ (61.9%) or VUS (42.2%; p = 0.021 log-rank). Interpretation: Our findings support the concept that the genetic profile of NIDCM patients plays a role in responsiveness to MSC therapy, with V− patients more likely to benefit and the converse for PV+. This observation emphasizes the need for further genetic studies, because of important implications for the management of NIDCM syndromes. Keywords: Precision medicine, Variants of uncertain significance, Positive for pathologic/likely pathologic variant, Dilated cardiomyopathy

Background: The parasitic disease, cystic echinococcosis (CE), is a serious health problem in Pakistan. Risk of disease transmission is increased by economic and political instability, poor living conditions, and limited awareness of hygienic practices. The current study aimed to investigate the community perception and awareness regarding the risk factors of CE in Pakistan, from a One Health perspective.Methods: We conducted a community-based survey involving 454 participants in the major cities of Pakistan. Quantitative data based on knowledge, attitude, and practices (KAP), the One Health concept, risk factors, and community perception of CE among the general population of the major cities of Pakistan were collected. The questions included those related to knowledge, attitude, practices, One Health concept, risk factors, and community perception. The Chi-squared test was applied to determine the associations regarding KAPs across socio-demographic parameters.Results: KAPs had no significant associations with sociodemographic aspects such as age, sex, religion, ethnicity, education, marital status, occupation, or financial status of the participants. The findings indicated a lack of awareness about CE among the participants. Respondents were unaware of the risk factors and the One Health concept of CE. However, the community attitude and perception were positive toward the control of CE.Conclusion: Illiteracy, deficient sanitation systems and lack of awareness are the contributing factors to CE in Pakistan. It is necessary to make the community aware regarding CE and its importance. Increasing this awareness represents an important step toward the eradication and control of CE.

The U.S. Food and Drug Administration (FDA) provides guidance for expanded access to experimental therapies, which in turn plays an important role in the Twenty-first Century Cures Act mandate to advance cell-based therapy. In cases of incurable diseases where there is a lack of alternative treatment options, many patients seek access to cell-based therapies for the possibility of treatment responses demonstrated in clinical trials. Here, we describe the use of the FDA’s expanded access to investigational new drug (IND) to address rare and emergency conditions that include stiff-person syndrome, spinal cord injury, traumatic brain stem injury, complex congenital heart disease, ischemic stroke, and peripheral nerve injury. We have administered both allogeneic bone marrow-derived mesenchymal stem cell (MSC) and autologous Schwann cell (SC) therapy to patients upon emergency request using Single Patient Expanded Access (SPEA) INDs approved by the FDA. In this report, we present our experience with 10 completed SPEA protocols.

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Inclusion of women and minorities in clinical research is critical to fully assess the safety and efficacy of innovative therapies. With inadequate representation of demography, generalizability is impaired since pharmacokinetics and pharmacodynamics differ in these patient populations. This study was designed to analyze the voluntary participation rates of different demographic groups in cell-based therapy clinical trials conducted by the Interdisciplinary Stem Cell Institute (ISCI) at the University of Miami, Miller School of Medicine. ISCI conducted eight clinical trials between 2007 and 2017. The trials enrolled patients with ischemic and non-ischemic cardiomyopathy, idiopathic pulmonary fibrosis (IPF), aging-frailty, and Type-2 Diabetes. Participants received cell-based therapy (n = 218) or placebo (n = 33). Among the 251 participants, 29.5% were Hispanic and 20% were women. The proportion of individuals participating in each trial was compared to that of the respective disease populations attending University of Miami Health System clinics to calculate the participation to prevalence ratio (PPR). Distribution of women accurately reflected the population attending the University of Miami Health System in trials for dilated cardiomyopathy (DCM) and aging-frailty but was under-represented in others. Similarly, Hispanics and whites were accurately represented in three of the five disease fields, with Hispanics under-represented in frailty and diabetes, and whites over-represented in DCM and IPF. Black patients were accurately represented in the diabetes trial but were under-represented in all others. This study provides insight into challenges of achieving representative inclusion in research. Novel community engagement strategies are necessary to improve inclusion of women and under-represented minorities in clinical research of cell-based therapy.

Neurophysiological testing can provide quantitative information about motor, sensory, and autonomic system connectivity following spinal cord injury (SCI). The clinical examination may be insufficiently sensitive and specific to reveal evolving changes in neural circuits after severe injury. Neurophysiologic data may provide otherwise imperceptible circuit information that has rarely been acquired in biologics clinical trials in SCI. We reported a Phase 1 study of autologous purified Schwann cell suspension transplantation into the injury epicenter of participants with complete subacute thoracic SCI, observing no clinical improvements. Here, we report longitudinal electrophysiological assessments conducted during the trial. Six participants underwent neurophysiology screening pre-transplantation with three post-transplantation neurophysiological assessments, focused on the thoracoabdominal region and lower limbs, including MEPs, SSEPs, voluntarily triggered EMG, and changes in GSR. We found several notable signals not detectable by clinical exam. In all six participants, thoracoabdominal motor connectivity was detected below the clinically assigned neurological level defined by sensory preservation. Additionally, small voluntary activations of leg and foot muscles or positive lower extremity MEPs were detected in all participants. Voluntary EMG was most sensitive to detect leg motor function. The recorded MEP amplitudes and latencies indicated a more caudal thoracic level above which amplitude recovery over time was observed. In contrast, further below, amplitudes showed less improvement, and latencies were increased. Intercostal spasms observed with EMG may also indicate this thoracic “motor level.” Galvanic skin testing revealed autonomic dysfunction in the hands above the injury levels. As an open-label study, we can establish no clear link between these observations and cell transplantation. This neurophysiological characterization may be of value to detect therapeutic effects in future controlled studies.

Post-COVID-19 infection symptoms such as mental fog, tachycardia, and extreme fatigue are just a few of the symptoms wreaking havoc on patients’ lives. Patients with long-term symptoms following COVID-19 are being called long haulers. To date, long haulers are receiving little to no guidance from physicians on their lingering COVID-19 symptoms with limited treatment options available. Zofin is an acellular biologic that contains the extracellular vesicle (EV) fraction of human amniotic fluid and is under investigation for use as a COVID-19 therapeutic. We obtained FDA and IRB approval to investigate the therapeutic use of Zofin in a single long hauler patient case experiencing prolonged shortness of breath and respiratory impairment. Administration of the EV product was shown to be safe. Furthermore, demonstrated respiratory improvements through chest X ray images and oxygen saturation measurement. The single patient IND studies were completed without any reported adverse events or safety concerns. Furthermore, these completed studies demonstrate the feasibility and a therapeutic potential of amniotic fluid-derived EVs for COVID-19 long hauler intervention.

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BackgroundClear cell renal cell carcinoma (ccRCC) is the most common subtype of renal cell carcinoma (RCC), which accounts for majority of RCC-related deaths. It is clearly essential to further identify more novel prognostic signatures and therapeutic targets.Material and MethodsWe identified differentially expressed genes (DEGs) between ccRCC and adjacent normal tissues in GEO database using a Robust Rank Aggregation (RRA) method. An mRNA signature (mRNASig) based on DEGs was developed using Cox and LASSO analysis in the TCGA database and validated in the ICGC database. Afterward, the influence of mRNASig mRNAs on the immune microenvironment in ccRCC was explored using comprehensive bioinformatics analysis.ResultsA total of 957 robust DEGs were identified using the RRA method. mRNASig comprised CEP55, IFI44, NCF4, and TCIRG1 and was developed and validated to identify high-risk patients who had poorer prognosis than low-risk patients. A nomogram was also constructed based on mRNASig, AJCC stage, and tumor grade. The mRNASig were closely related to a variety of tumor-infiltrating lymphocytes, especially including CD8+ T cells, activated CD4+ memory T cells, regulatory T cells, activated NK cells, and resting NK cells. The mRNASig were also correlated positively with the expression of CTLA4, LAG3, PDCD1, TIGIT, and HAVCR2.ConclusionWe developed and validated mRNASig to assist clinicians in making personalized treatment decisions. Furthermore, CEP55, IFI44, NCF4, and TCIRG1 may be novel potential targets for future treatment of ccRCC.

BackgroundRecent evidence of significant sex-based differences in the presentation of Type 2 Diabetes Mellitus (DM) and its complications has been found in humans, which may contribute to sex-based differences in reduced functionality and quality of life. Some functionality, such as tactile function of the hands, has significant direct impact on quality of life. The purpose of the current study was to explore the impact of DM and sex on tactile function, with consideration of variability in health state measures.Research design and methodsA case-control single time point observational study from 2012-2020 in an ethnically diverse population-based community setting. The sample consists of 132 adult individuals: 70 independent community dwelling persons with DM (PwDM) and 62 age- and sex-matched controls (42 males and 90 females in total). The Semmes-Weinstein monofilament test was used to evaluate tactile sensation of the hands.ResultsTactile sensation thresholds were adversely impacted by sex, age, degree of handedness, high A1c, diagnosis of DM, and neuropathy. Overall, strongly right-handed older adult males with poorly controlled DM and neuropathy possessed the poorest tactile discrimination thresholds. When self-identified minority status was included in a secondary analysis, DM diagnosis was no longer significant; negative impacts of age, neuropathy, degree of handedness, and high A1c remained significant.ConclusionsThe data indicate significant impacts of male sex, age, degree of handedness, self-identified minority status, and metabolic health on the development of poor tactile sensation. This combination of modifiable and non-modifiable factors are important considerations in the monitoring and treatment of DM complications.

Background: Cystic echinococcosis (CE) is a global zoonotic parasitic disease caused by the larval stage of Echinococcus granulosus and it has been reported from both livestock and humans in Pakistan. The definitive host of E. granulosus is the dog, and the large number of stray dogs in Pakistan contributes to the spread of CE. However, there is little information between stray dogs and CE relation in the country.Methods: During the study, total 123 butcher's shops and abattoirs were included for collection of data relating to the hydatid cyst prevalence in slaughtered animals (sheep, goat, cattle, and buffaloes). The number of animals slaughtered in each butcher's shop during sampling period was also recorded, and the association of the shop environment with dogs was inspected.Results: Data was collected for CE from 123 butcher's shops in Rawalpindi and Islamabad, Pakistan. The slaughtering rate the in the butcher's shops was 2–10 animals/day including sheep/goat/cattle and buffaloes. The overall prevalence of CE in all examined animals was 2.77%. In buffaloes the higher prevalence was recorded as compared to other hosts. The findings showed that lung and liver were most affected organs and majority (59%) of the cysts were fertile in infected animals. The presence of a large number of stray dogs were an important factor in the spread of CE. They were rarely vaccinated, have easy access to infected offal at slaughtering site and had insufficient or inappropriate anthelmintic treatment.Conclusions: The most pressing need is to raise public awareness of this huge problem by considering CE a major ailment and promoting the collection and mapping of epidemiological data. Efficient CE control is required, especially treating dogs with antiparasitic drugs, for which government support and affiliation with the veterinary sector is essential.

Abstract Background Cystic echinococcosis (CE) is a human and animal health problem in many endemic areas worldwide. It is considered a neglected zoonotic disease caused by the larval form (hydatid cyst) of Echinococcus spp. tapeworm. There are limited studies on echinococcosis in Pakistan. Methods A cross-sectional survey was conducted to find out recent knowledge, attitudes and practices on the occurrence of cystic echinococcosis in butchers and dog owners in both urban and rural areas of Rawalpindi/Islamabad regions, Pakistan. The quantitative data was collected in the form of questionnaires to investigate the knowledge and awareness of CE among community members and their routine practices that were behind the factors involved in hydatid cyst infection. The practices and infrastructure of abattoirs/butcher shops and their role in transmission of cystic echinococcosis were also evaluated in the present study. Results The participants involved in the study were dog owners and people who kept animals. A total of 400 people were interviewed and 289 questionnaires were received. The results showed that only 4.1% of people have heard about the disease, and 58.1% were closely associated with dogs. Sixty-three percent of dogs in study area were consuming uncooked organs (e.g. liver, lung, etc.) of slaughtered animals, while 100% of dogs at butcher shops were consuming uncooked organs. Home slaughtering was common in 20.06%. Among butchers, 32.3% had heard about zoonoses and 7.61% knew about CE. The statistical analysis showed that there was highly significant difference (P < 0.05) among most of the practices that were associated with the prevalence of CE. Conclusions It was concluded from the present study that, the knowledge and awareness of CE among people of Rawalpindi/Islamabad were low. Because of dogs and poor knowledge of CE among community members and butchers, the transmission of echinococcosis is facilitated. Therefore, there is urgent need to strengthen awareness and health education among people, as well as proper practices related to the CE not only in the study area, but also in other areas of Pakistan.

INTRODUCTION: Uterine inversion is the collapse of uterine fundus into the endometrial cavity resulting in turning the uterus partially or completely inside out. Uterine inversion during cesarean section is an extremely rare obstetric complication and the exact incidence is not known. CASE DESCRIPTION: We report complete inversion of uterus in 38-year-old female, Gravida 2 Para 1+0, 38+0 weeks gestational age, admitted for elective lower segment cesarean section due to previous 1 scar. Delivery of the baby was uneventful. Complete inversion of uterus through uterine incision was noticed immediately after detachment of placenta. Oxytocin infusion was discontinued immediately, and uterine inversion was reversed manually by exteriorizing uterus and then making a fist and applying force on the fundus. Uterus was closed back in two layers, but it remained relaxed despite, massaging, oxytocin and sublingual misoprostol; therefore, modified B-lynch sutures were applied. This helped the patient to be prevented from any further complications. She was discharged as planned and was stable on follow up visits. CONCLUSION: Uterine inversion was promptly identified and corrected without any major complications.

Make Headway for Echinococcosis: Take along the Ignored Cases

Background: Blood pressure (BP) is obligatorily measured each time a patient visits Emergency room (ER) or is admitted in ICU/CCU. Accuracy of blood pressure measurement in clinical settings is the key to appropriate diagnosis of hypertension in a patient. It remains elusive, however, whether oscillatory automated BP measurement yields lower values than auscultatory manual methods. It has been witnessed that both the devices give different readings of the same patient at one point in time. This study helped to determine the accurate or more reliable of the two devices. Methods: A double-blind randomized clinical cross over trial was carried out at Ziauddin University Hospital from February 2018 to June 2018. Sample of 100 was taken through random sampling. The device used in this study was the Dinamap Procare 100. SPSS 20 was used for data entry and analysis. Results: The mean of difference in systolic manual Blood Pressure (sMBP) and systolic automated Blood Pressure (sABP) was estimated to be 15.62 with a standard deviation of ± 8.57, while the mean of difference in diastolic MBP and ABP was 12.6 with a standard deviation of ± 24.7. Both systolic and diastolic readings were far low by automated devices in comparison to Manual devices. Conclusion: The results of this study suggested that automated method in measurement of BP frequently shows lower BP. This can influence diagnosis of hypertension and management of certain medical conditions.

Background: Endothelial dysfunction, characterized by diminished endothelial progenitor cell (EPC) function and flow-mediated vasodilation (FMD), is a clinically significant feature of heart failure (HF). Mesenchymal stem cells (MSCs), which have pro-angiogenic properties, have the potential to restore endothelial function. Accordingly, we tested the hypothesis that MSCs increase EPC function and restore flow-mediated vasodilation (FMD). Methods: Idiopathic dilated and ischemic cardiomyopathy patients were randomly assigned to receive autologous (n = 7) or allogeneic (n = 15) MSCs. We assessed EPC-colony forming units (EPC-CFUs), FMD, and circulating levels of vascular endothelial growth factor (VEGF) in patients before and three months after MSC transendocardial injection (n = 22) and in healthy controls (n = 10). Findings: EPC-colony forming units (CFUs) were markedly reduced in HF compared to healthy controls (4 ± 3 vs. 25 ± 16 CFUs, P

Insufficient donor nerve graft material in peripheral nerve surgery remains an obstacle for successful long-distance regeneration. Schwann cells (SCs) can be isolated from adult mammalian peripheral nerve biopsies and can be grown in culture and retain their capacity to enhance peripheral nerve regeneration within tubular repair strategies in multiple animal models. Human Schwann cells (hSCs) can be isolated, expanded in number, and retain their ability to promote regeneration and myelinate axons, but have never been tested in a clinical case of peripheral nerve injury. A sural nerve biopsy and peripheral nerve tissue from the traumatized sciatic nerve stumps was obtained after Food and Drug Administration (FDA) and Institutional Review Board (IRB) approval as well as patient consent. The SCs were isolated after enzymatic digestion of the nerve and expanded with the use of heregulin β1 (0.1 μg/ml) and forskolin (15 mM). After two passages the Schwann cell isolates were combined with sural nerve grafts to repair a large sciatic nerve defect (7.5 cm) after a traumatic nerve injury. The sural nerve and the traumatized sciatic nerve ends both served as an excellent source of purified (90% and 97%, respectively) hSCs. Using ultrasound and magnetic resonance imaging (MRI) we were able to determine continuity of the nerve graft repair and the absence of tumor formation. The patient had evidence of proximal sensory recovery and definitive motor recovery distal to the repair in the distribution of the tibial and common peroneal nerve. The patient did experience an improvement in her pain scores over time. The goals of this approach were to determine the safety and clinical feasibility of implementing a new cellular repair strategy. In summary, this approach represents a novel strategy in the treatment of peripheral nerve injury and represents the first reported use of autologous cultured SCs after human peripheral nerve injury.

Mesenchymal stem cells (MSC) improve alveolar and vascular structures in experimental models of bronchopulmonary dysplasia (BPD). Female MSC secrete more anti-inflammatory and pro-angiogenic factors as compared to male MSC. Whether the therapeutic efficacy of MSC in attenuating lung injury in an experimental model of BPD is influenced by the sex of the donor MSC or recipient is unknown. Here we tested the hypothesis that female MSC would have greater lung regenerative properties than male MSC in experimental BPD and this benefit would be more evident in males.To determine whether intra-tracheal (IT) administration of female MSC to neonatal rats with experimental BPD has more beneficial reparative effects as compared to IT male MSC.Newborn Sprague-Dawley rats exposed to normoxia (RA) or hyperoxia (85% O2) from postnatal day (P) 2- P21 were randomly assigned to receive male or female IT bone marrow (BM)-derived green fluorescent protein (GFP+) MSC (1 x 106 cells/50 μl), or Placebo on P7. Pulmonary hypertension (PH), vascular remodeling, alveolarization, and angiogenesis were assessed at P21. PH was determined by measuring right ventricular systolic pressure (RVSP) and pulmonary vascular remodeling was evaluated by quantifying the percentage of muscularized peripheral pulmonary vessels. Alveolarization was evaluated by measuring mean linear intercept (MLI) and radial alveolar count (RAC). Angiogenesis was determined by measuring vascular density. Data are expressed as mean ± SD, and analyzed by ANOVA.There were no significant differences in the RA groups. Exposure to hyperoxia resulted in a decrease in vascular density and RAC, with a significant increase in MLI, RVSP, and the percentage of partially and fully muscularized pulmonary arterioles. Administration of both male and female MSC significantly improved vascular density, alveolarization, RVSP, percent of muscularized vessels and alveolarization. Interestingly, the improvement in PH and vascular remodeling was more robust in the hyperoxic rodents who received MSC from female donors. In keeping with our hypothesis, male animals receiving female MSC, had a greater improvement in vascular remodeling. This was accompanied by a more significant decrease in lung pro-inflammatory markers and a larger increase in anti-inflammatory and pro-angiogenic markers in male rodents that received female MSC. There were no significant differences in MSC engraftment among groups.Female BM-derived MSC have greater therapeutic efficacy than male MSC in reducing neonatal hyperoxia-induced lung inflammation and vascular remodeling. Furthermore, the beneficial effects of female MSC were more pronounced in male animals. Together, these findings suggest that female MSC maybe the most potent BM-derived MSC population for lung repair in severe BPD complicated by PH.

This paper considers how representations of Islam and Vodou have shaped the ways we understand Atlantic history, relations of power, and the symbolic importance of religion as an interpretive category. It emphasizes the Caribbean region’s trope of cosmopolitanism as a key organizing principle in historiography and theory building, arguing that although cosmopolitanism can be a valuable discursive strategy in self-reflexive constructions of identity, the concept marginalizes or elides Islam and leaves ambivalent space for Africa. The paper calls for re-examining how Muslims and Islam are conceptualized as world historical and Caribbean regional phenomena, and how implicit assumptions inform our analytical vocabulary.

Objective: Cystic echinococcosis (CE) is a zoonotic parasitic disease and a neglected infectious disease affecting more than one million people globally. It is caused by the tapeworm parasite of Echinococcus granulosus sensu lato. It is endemic in the neighbours of Pakistan. However, there are limited studies on molecular epidemiology of CE in Pakistan. Methods: Discrimination of Echinococcus species has been done mostly by morphologically and less work has been done by molecular methods in Pakistan. There are limited studies have been conducted to explore the molecular epidemiology of Echinococcus species in human and livestock. In human just retrospective studies have been conducted and there is a serious lack of studies on molecular basis. Results: So far in Pakistan just four studies have been published on genotyping of Echinococcus spp. common sheep strain (G1) and buffalo strain (G3) in livestock (small and large ruminants) and Echinococcus granulosus sensu stricto (G1-G3) in buffaloes, while Echinococcus granulosus sensu stricto (G1-G3), Echinococcus multilocularis, Echinococcus canadensis (G6/7) in human have been reported. Based on these four studies clearly shows that CE is yet neglected in Pakistan. These findings indicate that due to the higher population of sheep and buffaloes, G1 and G3 strains are highly prevalent in human and animals. Association of stray dogs with sheep herds and other livestock at the grazing sites is responsible for the higher prevalence of CE that acts an active role in the transmission of CE while the wild animals and camel are responsible for the less infection. Conclusion: There is dire need of more studies on molecular identification of CE to understand its species diversity and molecular epidemiology in Pakistan. It is an important step toward management of echinococcosis based on One Health Concept.

Cystic echinococcosis (CE) is zoonotic neglected tropical parasitic disease. It is endemic in the some Asian countries like China, Turkey, Iran and India. In Pakistan it is neglected and limited studies have been conducted on epidemiology of CE due to the lack of the fundings. It is not explored yet in Pakistan to estimate incidence and disease burden. In Pakistan recent emergence of CE and its transmission reservoirs are threating to have a higher incidence rate in near future. We are very grateful to Hanian Medical University, China for providing an excellent opportunity under “The Belt and Road Tropical Medical Alliance” which is inspired by the strategy of the “One Belt & One Road Initiative”. This forum will provide direction towards World Health Organization’s call for strengthening tropical disease prevention and research. Taking this opportunity, data on endemicity of CE from Pakistan will be shared in front of scientific community at First International Conference of Tropical Medicine at Hanian Medical University, China. In this way the international cooperation, establishment of research laboratories, collaborative research projects, technology transfer and scientists training will be done under the umbrella of this platform for the screening, control and management of CE in Pakistan. In this international forum of institutions of higher learning, medical institutions, scientific institutions and public health institutions of member countries of “The Belt and Road Tropical Medical Alliance” will not only promote and help the control and management of echinococcosis but also open new directions towards other neglected tropical diseases in Pakistan.

Background: Hydatidosis is a zoonotic parasitic disease and a serious human and animal health problem in many endemic areas of the world. It is caused by the tapeworm parasite of Echinococcus granulosus sensu lato. This parasite is endemic in the neighboring countries like China, Iran and India. There are limited studies on CE in Pakistan. Methods: This study primarily aimed to determine the prevalence of hydatidosis in slaughtered livestocks in Chakwal district (Chakwal, Bhaun, Kallar kahar, Choa saidan shah and Balkasar) from June to December 2015. The livestocks were inspected after slaughtering and the ages, breeds and organ wise prevalence were recorded. Results: A total of 6 095 animals (sheep, goat, buffaloes and cattle) of different genders, ages and breeds were inspected after slaughtering. Overall prevalence was 8.55% (88/1 045) in sheep followed by 8.42% (88/1 045), 6.90% (4/58), 2.99% (138/4 608) in cattle, buffaloes and goats, respectively. Liver wise prevalence was 7.75%, 6.90%, 0.06%, 1.30% in cattle, buffaloes, goats and sheep, respectively while lung wise prevalence was 7.55%, 0.67%, 0.00%, 0.00%, in sheep, cattle, buffaloes and goats, respectively. Male (9.50%) were more infected than female (1.96%) in all hosts. Breed wise prevalence was higher in desi breed of cattle followed by crossbreed and other breeds. In goats, teddhi breed was more infected then beetal while in sheep Afghani breed was more infected than the others. Cattle of 6-9 years groups were more infected than 0-3 and 3-6 years age groups. Buffaloes of the only age group of 6-9 years were infected while in goat and sheep 3-6 years were more infected than 0-3 years. According to the statistical analysis there was a significant difference (P

[First paragraph] Nation Dance: Religion, Identity, and Cultural Difference in the Caribbean. PATRICK TAYLOR (ed.). Bloomington: Indiana University Press, 2001. x +220 pp. (Paper US$ 19.95) Translating Kali 's Feast: The Goddess in Indo-Caribbean Ritual and Fiction. STEPHANOS STEPHANIDES with KARNA SINGH. Amsterdam: Rodopi, 2000. xii + 200 pp. (Paper US$ 19.00) Between Babel and Pentecost: Transnational Pentecostalism in Africa and Latin America. ANDRÉ CORTEN & RUTH MARSHALL-FRATANI (eds.). Bloomington: Indiana University Press, 2001. 270 pp. (Paper US$ 22.95) Encyclopedia of African and African-American Religions. STEPHEN D. GLAZIER (ed.). New York: Routledge, 2001. xx + 452 pp. (Cloth US$ 125.00) As paradigms and perspectives change within and across academie disciplines, certain motifs remain at the crux of our inquiries. Evident in these four new works on African and New World African and South Asian religions are two motifs that have long defined the Caribbean: the relationship between cultural transformation and cultural continuity, and that between cultural diversity and cultural commonality. In approaching religion from such revisionist sites as poststructuralism, diaspora, hybridity, and creolization, however, the works reviewed here attempt to move toward new and more productive ways of thinking about cultures and histories in the Americas. In the process, other questions arise. Particularly, can what are essentially redirected language and methodologies in the spirit of postmodern interventions teil us more about local interpretation, experience, and agency among Caribbean, African American, and African peoples than can more traditional approaches? While it is up to individual readers to decide this for themselves, my own feeling is that it is altogether a good thing that these works still echo long-standing conundrums: the Herskovits/Frazier debate over cultural origins, the tensions of assimilation in "plural societies," and the significance of religion in everyday life. Perhaps one of the most important lessons that research in the Caribbean has for broader arenas of scholarship is that foundational questions are tenacious even in the face of paradigm shifts, yet can always generate new modes of inquiry, defying intellectual closure and neat resolution.

[First paragraph] The Haunting Past: Politics, Economics and Race in Caribbean Life. ALVIN O. THOMPSON. Kingston: Ian Randle, 1997. xvi + 283 pp. (Cloth US$ 70.95, Paper US$ 27.95) Nationalism and Identity: Culture and the Imagination in a Caribbean Diaspora. STEFANO HARNEY. Kingston: University of the West Indies; London: Zed Books, 1996. 216 pp. (Paper J$ 350.00, US$ 10.00, £6.00) Recharting the Caribbean: Land, Law, and Citizenship in the British Virgin Islands. BILL MAURER. Ann Arbor: University of Michigan Press, 1997. xvii + 301 pp. (Cloth US$ 44.50) Building on views espoused by the American Enterprise Institute, columnist George Will solves the dilemma of unequal development among contemporary nation-states in one fell swoop: Western Europe and North America outstripped Latin America and its environs, among other places, for one reason - culture. Much meaning must be unpacked from that word, but the conclusion is: The spread of democracy, free markets, technology, and information is not enough to rescue ... nations, from the consequences of their cultural deficits. Such deficits, although not incurable, are intractable. (Will 1999:64) Another "lesson to be drawn," he says, is that "Government cannot revise culture, wholesale, but government has - it cannot help but have - cultural consequences" (Will 1999:64). Even as we embark on the twenty-first century, we cling to hoary, Age of Imperialism presumptions about the character and role of culture - signaled implicitly with a capital C. Such presumptions fuel statements like the above; governments convey material and moral improvements but these do not take hold in culturally inadequate environments.

While regional heterogeneity in islet distribution has been well studied in rodents, less is known about human pancreatic histology. To fill gaps in our understanding, regional differences in the adult human pancreas were quantitatively analyzed including the pathogenesis of type 2 diabetes (T2D). Cadaveric pancreas specimens were collected from the head, body and tail regions of each donor, including subjects with no history of diabetes or pancreatic diseases (n = 23) as well as patients with T2D (n = 12). The study further included individuals from whom islets were isolated (n = 7) to study islet yield and function in a clinical setting of islet transplantation. The whole pancreatic sections were examined using an innovative large-scale image capture and unbiased detailed quantitative analyses of the characteristics of islets from each individual (architecture, size, shape and distribution). Islet distribution/density is similar between the head and body regions, but is >2-fold higher in the tail region. In contrast to rodents, islet cellular composition and architecture were similar throughout the pancreas and there was no difference in glucose-stimulated insulin secretion in islets isolated from different regions of the pancreas. Further studies revealed preferential loss of large islets in the head region in patients with T2D. The present study has demonstrated distinct characteristics of the human pancreas, which should provide a baseline for the future studies integrating existing research in the field and helping to advance bi-directional research between humans and preclinical models.

[First paragraph] The Cuba Commission Report: A Hidden History of the Chinese in Cuba. The Original English-Language Text of 1876 (Introduction by Denise Helly). Baltimore: Johns Hopkins University Press, 1993. viii + 160 pp. (Paper US$21.95) Indentured Labor, Caribbean Sugar: Chinese and Indian Migrants to the British West Indies, 1838-1918. WALTON LOOK LAI. Baltimore: Johns Hopkins University Press, 1993. xxviii + 370 pp. (Cloth US$ 39.95) The world system formed by European mercantile and industrial capitalism and the history of transcontinental labor migrations from Africa to the Americas have been amply documented. The genesis, evolution, and demise of New World slavery are subjects much scrutinized and debated, particularly since the 1960s. Enjoying a less extensive tradition of historiography are the variously devised alternative labor schemes that came on the heels of emancipation: the colonially-orchestrated efforts to contract free and voluntary workers to take the place of slaves in a system of production theoretically the moral antithesis of that earlier "peculiar institution." Yet scholarship on indentured labor systems has consistently revealed that the "freedom" of immigrant workers was merely nominal, the "voluntary" nature of their commitments arguable, and the indenture projects often only ideally a kinder, gentier form of labor extraction.

An emergency autologous islet transplant after a traumatic Whipple operation and subsequent total pancreatectomy was performed for a 21-year-old patient who was wounded with multiple abdominal gunshot wounds. After Whipple pancreatectomy, the remnant pancreas (63.5 g), along with other damaged organs, was removed by the surgeons at Walter Reed Army Medical Center (WRAMC) and shipped to Diabetes Research Institute (DRI) for islet isolation. The pancreas was preserved in UW solution for 9.25 h prior to islet isolation. Upon arrival, the organ was visually inspected; the pancreatic head was missing, the rest of the pancreas was damaged and full of blood; the tail looked normal. A 16-gauge catheter was inserted into the main duct and directed towards tail of the pancreas after the dissection of main duct in the midbody of the pancreas. The pancreas was distended with collagenase solution (Roche MTF) through the catheter. During 10 min of intraductal delivery of enzyme, the gland was distended uniformly. No leakage of the solution was observed. The pancreas was transferred to a Ricordi chamber for automated mechanical and enzymatic digestion. Islets were purified using a COBE 2991 cell processor. Islet equivalents (IEQ; 221,250) of 40% purity and 90% viability were recovered during the isolation, which were shipped back to WRAMC and infused by intraportal injection into the patient. Immediate islet function was demonstrated by the rapid elevation of serum C peptide followed by insulin independence with near normal oral glucose tolerance test (OGTT) 1 and 2 months later. It is possible to restore near normal glucose tolerance with autologous islet transplantation after total pancreatectomy even with suboptimal number of islets while confirming that islets processed at a remote site are suitable for transplantation.