Search

According to (Coetzee and Pauw 2013), the retention of capable staff of nursing is crucial for leaders of nursing because of identifying the consequences of shortage in nursing staff. However, the skills and ability of leaders affect reactions to the situations (Coetzee and Pauw 2013). The deficiency of nursing staff relies on many components of the delivery of healthcare. There is a negative influence on the nursing staff's high turnover on patients, finance, and outcomes of hospitals (Mxenge, Dywill, et al., 2014; Langove and Isha, 2017). Recruiting and training of nursing have a monetary impact which is evaded by a good number of healthcare corporations. The standard cost of substituting a nurse is estimated in the USA from 42,000 USD to 64,000 USD (Galati and Moessner 2013). Zhang, Jiang et al. (2017) stated that the organization of healthcare is always changing and the global turnover of nurses is high. According to the Economic Survey of Pakistan (2012), there is an unavailability of 60,000 staff of nursing in Pakistan (Rehman, Jingdong, et al. 2019). Also, Pakistan is one of the 57 countries that have a severe deficiency of nursing staff under the standard of WHO to provide needed healthcare (McGuire 2016). Therefore, organizations of healthcare consistently struggle to retain nursing staff to deal with the issues of nursing scarcity (Ponte and Sturgeon 2014). This research study would provide a more effective understanding of the backgrounds of turnover of employees if job complexity, the volume of job information that a person holds at the selection time, and the scenario of the labor market were carefully considered. For this reason, these issues are taken as research limitations and more study need to be done to address these problems (Lu Lu, Lu, Gursoy, & Neale, 2016; Shaozhuang Ma, Silva, Callan, & Trigo, 2016; Mamoona Rasheed, Iqbal, & Mustafa, 2018) Various earlier researches on productive workplace atmosphere which has focused on several positive results such as performance, employees' well-being, and behavior of organizational citizenship (Lonsdale, 2016; Zhang, Gong, et al., 2017; Evans and Dobrosielska 2019). Keywords: Emotional intelligence, Organizational Commitments, Turnover Intention, Pakistani Healthcare Sector

Despite advances in surgical technique and postoperative care, long-term survival of children born with hypoplastic left heart syndrome (HLHS) remains limited, with cardiac transplantation as the only alternative for patients with failing single ventricle circulations. Maintenance of systemic right ventricular function is crucial for long-term survival, and interventions that improve ventricular function and avoid or defer transplantation in patients with HLHS are urgently needed. We hypothesize that the young myocardium of the HLHS patient is responsive to the biological cues delivered by bone marrow-derived mesenchymal stem cells (MSCs) to improve and preserve right ventricle function. The ELPIS trial (Allogeneic Human MEsenchymal Stem Cell Injection in Patients with Hypoplastic Left Heart Syndrome: An Open Label Pilot Study) is a phase I/IIb trial designed to test whether MSC injection will be both safe and feasible by monitoring the first 10 HLHS patients for new major adverse cardiac events. If our toxicity stopping rule is not activated, we will proceed to the phase IIb component of our study where we will test our efficacy hypothesis that MSC injection improves cardiac function compared with surgery alone. Twenty patients will be enrolled in a randomized phase II trial with a uniform allocation to MSC injection versus standard surgical care (no injection). The 2 trial arms will be compared with respect to improvement of right ventricular function, tricuspid valve annulus size, and regurgitation determined by cardiac magnetic resonance and reduced mortality, morbidity, and need for transplantation. This study will establish the safety and feasibility of allogeneic mesenchymal stem cell injection in HLHS patients and provide important insights in the emerging field of stem cell-based therapy for congenital heart disease patients.

Background Aging frailty, characterized by decreased physical and immunological functioning, is associated with stem cell depletion. Human allogeneic mesenchymal stem cells (allo-hMSCs) exert immunomodulatory effects and promote tissue repair. Methods This is a randomized, double-blinded, dose-finding study of intravenous allo-hMSCs (100 or 200-million [M]) vs placebo delivered to patients (n = 30, mean age 75.5 ± 7.3) with frailty. The primary endpoint was incidence of treatment-emergent serious adverse events (TE-SAEs) at 1-month postinfusion. Secondary endpoints included physical performance, patient-reported outcomes, and immune markers of frailty measured at 6 months postinfusion. Results No therapy-related TE-SAEs occurred at 1 month. Physical performance improved preferentially in the 100M-group; immunologic improvement occurred in both the 100M- and 200M-groups. The 6-minute walk test, short physical performance exam, and forced expiratory volume in 1 second improved in the 100M-group (p = .01), not in the 200M- or placebo groups. The female sexual quality of life questionnaire improved in the 100M-group (p = .03). Serum TNF-α levels decreased in the 100M-group (p = .03). B cell intracellular TNF-α improved in both the 100M- (p < .0001) and 200M-groups (p = .002) as well as between groups compared to placebo (p = .003 and p = .039, respectively). Early and late activated T-cells were also reduced by MSC therapy. Conclusion Intravenous allo-hMSCs were safe in individuals with aging frailty. Treated groups had remarkable improvements in physical performance measures and inflammatory biomarkers, both of which characterize the frailty syndrome. Given the excellent safety and efficacy profiles demonstrated in this study, larger clinical trials are warranted to establish the efficacy of hMSCs in this multisystem disorder. Clinical Trial Registration www.clinicaltrials.gov: CRATUS (#NCT02065245).

Rationale: Intracoronary infusion of bone marrow (BM) mononuclear cells after acute myocardial infarction (AMI) has led to limited improvement in left ventricular function. Although experimental AMI models have implicated cytokine-related impairment of progenitor cell function, this response has not been investigated in humans. Objective: To test the hypothesis that peripheral blood (PB) cytokines predict BM endothelial progenitor cell colony outgrowth and cardiac function after AMI. Methods and Results: BM and PB samples were collected from 87 participants 14 to 21 days after AMI and BM from healthy donors was used as a reference. Correlations between cytokine concentrations and cell phenotypes, cell functions, and post-AMI cardiac function were determined. PB interleukin-6 (IL-6) negatively correlated with endothelial colony–forming cell colony maximum in the BM of patients with AMI (estimate±SE, −0.13±0.05; P =0.007). BM from healthy individuals showed a dose-dependent decrease in endothelial colony–forming cell colony outgrowth in the presence of exogenous IL-1β or IL-6 ( P P P =0.002) in BM, and mesenchymal stromal cell colony maximum in PB (estimate±SE, 0.02±0.005; P Conclusions: Two weeks after AMI, increased PB platelet-derived growth factor BB glycoprotein was associated with increased BM function, whereas increased IL-6 was associated with BM impairment. Validation studies confirmed inflammatory cytokine impairment of BM that could be reversed by blocking IL-1R or IL-6R. Together, these studies suggest that blocking IL-1 or IL-6 receptors may improve the regenerative capacity of BM cells after AMI. Clinical Trial Registrations: URL: http://www.clinicaltrials.gov . Unique identifier: NCT00684060.

Background Despite Food and Drug Administration approval of 2 new drugs for idiopathic pulmonary fibrosis (IPF), curative therapies remain elusive and mortality remains high. Preclinical and clinical data support the safety of human mesenchymal stem cells as a potential novel therapy for this fatal condition. The Allogeneic Human Cells (hMSC) in patients with Idiopathic Pulmonary Fibrosis via Intravenous Delivery (AETHER) trial was the first study designed to evaluate the safety of a single infusion of bone marrow–derived mesenchymal stem cells in patients with idiopathic pulmonary fibrosis. Methods Nine patients with mild to moderate IPF were sequentially assigned to 1 of 3 cohorts and dosed with a single IV infusion of 20, 100, or 200 × 10 6 human bone marrow–derived mesenchymal stem cells per infusion from young, unrelated, men. All baseline patient data were reviewed by a multidisciplinary study team to ensure accurate diagnosis. The primary end point was the incidence (at week 4 postinfusion) of treatment-emergent serious adverse events, defined as the composite of death, nonfatal pulmonary embolism, stroke, hospitalization for worsening dyspnea, and clinically significant laboratory test abnormalities. Safety was assessed until week 60 and additionally 28 days thereafter. Secondary efficacy end points were exploratory and measured disease progression. Results No treatment-emergent serious adverse events were reported. Two nontreatment-related deaths occurred because of progression of IPF (disease worsening and/or acute exacerbation). By 60 weeks postinfusion, there was a 3.0% mean decline in % predicted FVC and 5.4% mean decline in % predicted diffusing capacity of the lungs for carbon monoxide. Conclusions Data from this trial support the safety of a single infusion of human mesenchymal stem cells in patients with mild-moderate IPF. Trial Registry ClinicalTrials.gov; No.: NCT02013700; URL: www.clinicaltrials.gov.

Background: Recent preclinical studies of stroke recovery have explored the possibility of utilizing exosomes (ES) instead of complete cells as therapeutic agents. ES are endosomal origin small-membrane vesicles with a size of 40 to 100nm in diameter, secreted from many types of cells including mesenchymal stem cells (MSCs). ES-encapsulated transfer of miRNAs promotes neurite remodeling and functional recovery of stroke in rats. The optimal route of delivery of ES in stroke is not established. While a few studies have shown efficacy of intra-venous exosomes administration for stroke, there is one study exploring intra-arterial exosome therapy (IAX) with single dose of 100ug exosomes. We propose intra-arterial delivery of exosomes in a dose escalation study to establish safety and early efficacy. Methods: Female ovariectomized Sprague-Dawley rats were exposed to MCAo for 90 min. Rats were treated with IAX (10, 50 and 100ug/0.5mL), IAMSCs (1x10 5 cells/0.5mL) or IA phosphate-buffered saline (IAPBS) at 1 day (1D) after MCAo. To test neurological and motor function, the standardized neurobehavioral test battery and the rotarod test were performed. The mean duration (in seconds) on the device was recorded from 3 rotarod measurements. The rats were tested at pre-surgery, 7, 15 and 30 days post-MCAo. Results: There was no neurological worsening or mortality post IA exosome delivery at any dose tier. The Neurological deficit score of IAX 10ug treatment group at POD 7, 15 and 30, and IAX 50ug treatment at POD 15 were significantly improved in comparison to IA PBS. IAX 10ug treatment group showed trend of improvement in motor coordination compared to the IA PBS/MSC/higher doses of exosome treatment groups. Conclusions: The Neurological deficit scores of IAX 10ug treatment group were significantly improved in comparison to IA PBS. Lower dose than previously published might be most effective, and noninferior to IA-MSCs.

Background: Despite the efficacy of thrombectomy for large vessel occlusion acute ischemic stroke (AIS) , ~50% of patients have significant residual deficits. Pre-clinical data on intra-arterially (IA) administered mesenchymal stem cells (MSCs) in stroke are promising and this approach is attractive for clinical application. While there is a concern for micro-occlusion with IA delivery due to the large size of MSCs, a dose of 1 x 10 5 MSCs given 24-48 hr in a rodent reperfusion middle cerebral artery occlusion (rMCAo) model has been shown to be safe and effective. As per STAIR recommendations, we performed a dose-escalation (DE) study of IA-MSCs in a large animal stroke model. Methods: An endovascular canine rMCAo model using retractable platinum coil for 60-120 min was established. At 48 hr post-rMCAo, allogeniec canine MSCs were delivered using a 0.0165” microcatheter in the ipsilateral upper cervical internal carotid artery in escalating doses (based on proportion of rodent to canine total cerebral blood volume). Serial MRIs and neurological deficit scoring (NDS) were performed over 30 days. Animals were euthanized at 15-30 d post-rMCAo and brains were harvested. Results: Female canines (n=13), age 12-36 months, weighing 22-26 kg received IA MSCs ranging from 5-80 x 10 6 (M). At doses of 5-40 M IA-MSCs no neurological worsening was observed. Serial NDS and stroke volume on MRI showed no increase post-IA-MSCs and actually showed progressive reduction. A higher numerical reduction was seen in the 10-40 M groups compared to 5 M. However, in the one canine receiving 80 M IA-MSCs, there was significant worsening of the MCA-area infarction and NDS due to microembolization at this higher dose. Gross examinations and histopathology of brain tissue were consistent with ischemia. The brain of a canine receiving 80 M cells showed differentially aged areas of necrosis supporting two ischemic events. Neuroblasts, doublecortin-positive cells, and neovascularization were observed in canine brains suggesting regenerative mechanisms. Conclusions: These data suggest that IA-MSCs are safe in a large animal model up to 40 M IA-MSCs and is the maximum tolerated dose in this DE study. Furthermore, our data suggests that up to 40 M IA-MSCs may be promising in exploring efficacy in AIS.

Mitochondrial diseases are a group of clinically and genetically heterogeneous disorders driven by oxidative phosphorylation dysfunction of the mitochondrial respiratory chain which due to pathogenic mutations of mitochondrial DNA (mtDNA) or nuclear DNA (nDNA). Recent progress in molecular genetics and biochemical methodologies has provided a better understanding of the etiology and pathogenesis of mitochondrial diseases, and this has expanded the clinical spectrum of this conditions. But the treatment of mitochondrial diseases is largely symptomatic and thus does not significantly change the course of the disease. Few clinical trials have led to the design of drugs aiming at enhancing mitochondrial function or reversing the consequences of mitochondrial dysfunction which are now used in the clinical treatment of mitochondrial diseases. Several other drugs are currently being evaluated for clinical management of patients with mitochondrial diseases. In this review, the current status of treatments for mitochondrial diseases is described systematically, and newer potential treatment strategies for mitochondrial diseases are also discussed.

Alveolar echinococcosis (AE) is a zoonotic parasitic diseases caused by a cestode parasite known as Echinococcus multilocularis. The parasite has a wildlife cycle with definitive hosts (foxes) and small mammals as intermediate hosts (rodents) while humans are the accidental hosts. Parasite infection pressure relation to time of the year and age dependent infection pressure for parasite abundance also depend on the urbanization. The aim of current work is forecasting the thresholds via the computational analysis of the disease spread which is a useful approach since it can help to design the experimental settings with better planning and efficiency. Network analysis when interlinked with the computational techniques provides better insight into the spatial and temporal heterogeneities. In the present study, a mathematical framework that describes the transmission dynamics and control measures of E. multilocularis in foxes is documented. We used treatment of foxes with baits for the prevention of the E. multilocularis infection. A novel approach of networking, called Petri net (PN), based on density dependent differential equations, is utilized during this research. The accurate description of the transmission of the parasite and the effect of drug on it is provided to the readers in this article. The transitions, which are difficult to analyse theoretically, are presented with the aid of the discrete approach of networking. A discrete mathematical framework can prove to be an accurate and robust tool to analyse and control the parasite dynamics.

Introduction Cystic echinococcosis (CE) is a parasitic zoonotic disease caused by the larval stage of Echinococcus granulosus tapeworms. It has a worldwide geographic distribution and can threaten the livestock industry and human health in endemic areas, including Pakistan. CE prevalence is high in Pakistan due to lack of local knowledge about disease transmission and a lack of control measures. The Pakistan province of Baluchistan shares a border with Iran and Afghanistan and is largely agricultural. However, little is known about E. granulosus transmission in this region. Methods Information on surgically confirmed cases of CE in Baluchistan Province was obtained through evaluation of paraffin fixed cyst samples and patient records obtained from three local hospitals for the years 2011–2018. Results A total of 22 paraffin fixed samples were collected during the study period. The majority of cysts were obtained from the liver (9/22; 40.9%), with anatomical location not available for two of the cysts. Demographic information was available for 18 cases. Females made up 61.1% (11/18) of the cases. The largest numbers of cases were found in the 31–40 years age group (5/18; 22.7%). Discussion This study shows that Echinococcus spp. parasites are circulating in the study area. In order to control the disease, a comprehensive regional surveillance and control program is needed.

Introduction: The present study was conducted to investigate prevalence of intestinal parasites and the risk factors related to socio-demographic characteristics of patients admitted in pathology ward, General Hospital, Gujranwala. Methodology: 318 stool samples were collected from patients and examined under light microscope by using wet mount technique. While socio-demographic information was collected in the form of a questionnaire. Results: The results showed seven (n = 7) species of intestinal parasites were prevalent in stool samples of patients. Among them, four (n = 4) were helminth and three (n = 3) were protozoan parasites causing single and mixed infections. Overall prevalence of intestinal parasites was 78.3% (n = 249/318) considering both male and female patients. Highest prevalence was recorded for A. lumbricoides (n = 125, 39.3%) followed by H. nana (n = 10, 3.1%), S. stercoralis and T. saginata (n = 6, 1.9%). Among protozoan parasites, higher prevalence was recorded in G. lamblia (n = 23, 7.2%) followed by E. histolytica (n = 21, 6.6%). Among single infections, the most prevalent parasite was A. lumbricoides and less prevalent parasites were S. stercoralis and T. saginata. The factors that had significant effect (p < 0.05) on prevalence of parasitic species were contaminated water, food, soil, and surrounding environment. Conclusions: The present study determined that the parasite helminth (A. lumbricoides, H. nana, S. stercoralis, T. saginata) and protozoan (G. lamblia and E. histolytica) are common that pose an important public health concern in Pakistan.

Objectives To evaluate the existing status of human milk banks in India with reference to infrastructure, human resources, funding mechanisms, operating procedures and quality assurance. Methods A pretested questionnaire was administered to 16 out of 22 human milk banks across India, operational for more than one year prior to commencing the study. Results 11 (69%) milk banks were in government or charitable hospitals; only 2 (12.5%) were established with government funding. 8 (50%) had a dedicated technician and only 1(6%) had more than five lactation counsellors. Milk was collected predominantly from mothers of sick babies and in postnatal care wards followed by pediatric outpatient departments, camps, satellite centers, and homes. 10 (63%) reported gaps between donor milk demand and supply. 12 (75%) used shaker water bath pasteurizer and cooled the milk manually without monitoring temperature, and 4 (25%) pooled milk under the laminar airflow. 10 (63%) tracked donor to recipient and almost all did not collect data on early initiation, exclusive breastfeeding or human milk feeding. Conclusions Our study reports the gaps of milk banking practices in India, which need to be addressed for strengthening them. Gaps include suboptimal financial support from the government, shortage of key human resources, processes and data gaps, and demand supply gap of donor human milk.

Background More than 20% of patients with cirrhosis do not receive semi-annual hepatocellular carcinoma (HCC) surveillance as recommended. Few studies have evaluated the effects of patient-level factors on surveillance receipt. Methods We administered a telephone survey to a large cohort of patients with cirrhosis from 3 health systems (a tertiary care referral center, a safety-net health system, and Veterans Affairs) to characterize patient knowledge, attitudes, and perceived barriers of HCC surveillance. Multinomial logistic regression was performed to identify factors associated with HCC surveillance receipt (semi-annual and annual vs none) during the 12-month period preceding survey administration. Results Of 2871 patients approached, 1020 (35.5%) completed the survey. Patients had high levels of concern about developing HCC and high levels of knowledge about HCC. However, patients had knowledge deficits, including believing surveillance was unnecessary when physical examination and laboratory results were normal. Nearly half of patients reported barriers to surveillance, including costs (28.9%), difficulty scheduling (24.1%), and transportation (17.8%). In the year before the survey, 745 patients (73.1%) received 1 or more surveillance examination; 281 received on-schedule, semi-annual surveillance and 464 received annual surveillance. Semi-annual HCC surveillance (vs none) was significantly associated with receipt of hepatology subspecialty care (odds ratio, 30.1; 95% CI, 17.5–51.8) and inversely associated with patient-reported barriers (odds ratio, 0.62; 95% CI, 0.41–0.94). Patterns of associations comparing annual vs no surveillance were similar although the magnitude of effects were reduced. Conclusions Patient-reported barriers such as knowledge deficits, costs, difficulty scheduling, and transportation are significantly associated with less frequent receipt of HCC surveillance, indicating a need for patient-centered interventions, such as patient navigation.

Background Although human mesenchymal stem cells (hMSCs) have been tested in ischemic cardiomyopathy, few studies exist in chronic nonischemic dilated cardiomyopathy (NIDCM). Objectives The authors conducted a randomized comparison of safety and efficacy of autologous (auto) versus allogeneic (allo) bone marrow-derived hMSCs in NIDCM. Methods Thirty-seven patients were randomized to either allo- or auto-hMSCs in a 1:1 ratio. Patients were recruited between December 2011 and July 2015 at the University of Miami Hospital. Patients received hMSCs (100 million) by transendocardial stem cell injection in 10 left ventricular sites. Treated patients were evaluated at baseline, 30 days, and 3-, 6-, and 12-months for safety (serious adverse events [SAE]), and efficacy endpoints: ejection fraction, Minnesota Living with Heart Failure Questionnaire, 6-min walk test, major adverse cardiac events, and immune biomarkers. Results There were no 30-day treatment-emergent SAEs. Twelve-month SAE incidence was 28.2% with allo-hMSCs versus 63.5% with auto-hMSCs (p = 0.1004 for the comparison). One allo-hMSC patient developed an elevated (>80) donor-specific calculated panel reactive antibody level. The ejection fraction increased in allo-hMSC patients by 8.0 percentage points (p = 0.004) compared with 5.4 with auto-hMSCs (p = 0.116; allo vs. auto p = 0.4887). The 6-min walk test increased with allo-hMSCs by 37.0 m (p = 0.04), but not auto-hMSCs at 7.3 m (p = 0.71; auto vs. allo p = 0.0168). MLHFQ score decreased in allo-hMSC (p = 0.0022) and auto-hMSC patients (p = 0.463; auto vs. allo p = 0.172). The major adverse cardiac event rate was lower, too, in the allo group (p = 0.0186 vs. auto). Tumor necrosis factor-α decreased (p = 0.0001 for each), to a greater extent with allo-hMSCs versus auto-hMSCs at 6 months (p = 0.05). Conclusions These findings demonstrated safety and clinically meaningful efficacy of allo-hMSC versus auto-hMSC in NIDCM patients. Pivotal trials of allo-hMSCs are warranted based on these results. (Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis in Dilated Cardiomyopathy [PoseidonDCM]; NCT01392625)

Rationale: Culture-expanded cells originating from cardiac tissue that express the cell surface receptor cKit are undergoing clinical testing as a cell source for heart failure and congenital heart disease. Although accumulating data support that mesenchymal stem cells (MSCs) enhance the efficacy of cardiac cKit + cells (CSCs), the underlying mechanism for this synergistic effect remains incompletely understood. Objective: To test the hypothesis that MSCs stimulate endogenous CSCs to proliferate, migrate, and differentiate via the SDF1/CXCR4 and stem cell factor/cKit pathways. Methods and Results: Using genetic lineage-tracing approaches, we show that in the postnatal murine heart, cKit + cells proliferate, migrate, and form cardiomyocytes, but not endothelial cells. CSCs exhibit marked chemotactic and proliferative responses when cocultured with MSCs but not with cardiac stromal cells. Antagonism of the CXCR4 pathway with AMD3100 (an SDF1/CXCR4 antagonist) inhibited MSC-induced CSC chemotaxis but stimulated CSC cardiomyogenesis ( P P Conclusions: Together these findings show that MSCs exhibit profound, yet differential, effects on CSC migration, proliferation, and differentiation and suggest a mechanism underlying the improved cardiac regeneration associated with combination therapy using CSCs and MSCs. These findings have important therapeutic implications for cell-based therapy strategies that use mixtures of CSCs and MSCs.

Previous studies of fine motor control have focused on the ability of participants to match their grip force production to a visually provided template. We investigated differences exhibited in pinch force control during variable force production templates, including sine-, sawtooth-, and square-wave templates. Our results indicate that increased force requirements are associated with increased error rates and a noisier frequency spectrum, consistent with previous studies. Our results also indicate that visual feedback, in the form of template shape, directly affect pinch force production features and motor unit firing patterns, despite the use of consistent baseline force requirements, amplitude changes, and visual signal frequency. This suggests that CNS modulation of motor unit responses can be triggered by basic changes in visual feedback unrelated to force requirements. The potential implications of error compensation based on this study due to aging are also discussed.

The popularity of cell therapy as a viable strategy for the research and development of regenerative medicine continues to rise.1 Completed clinical trials have transplanted patient or donor derived cell products as biological packages of potent proregenerative, antifibrotic, and tissue-rejuvenating factors and have fostered the development of new treatments for previously incurable diseases.1,2 However, as a biological agent, cell products are inherently variable because of donor differences, processing techniques, and artificial in vitro laboratory culturing with animal or human products.3 This variability alters the quality and regenerative potency of a cell product and ultimately the clinical outcome. In response, cell-processing protocols must be designed to optimize cell preparation, cell transplantation, and quality assurance for each cell product. Potency assay development and the identification of cell potency biomarkers has become a critical component of current standards for the analysis and enhancement of cell products. Article, see p 255 Mesenchymal stem cells (MSCs) are a leading cell product candidate for the treatment of multiple inflammatory, degenerative, and chronic diseases. Commonly derived from the bone marrow, adipose, and cord tissue, MSCs are easily isolated and can be expanded in large numbers. In addition to direct tissue integration, transplanted MSCs have several paracrine and signaling effects on the tissue. MSCs secrete many beneficial cytokines and cellular compounds (microRNAs and micro vesicles exosomes) that produce immunomodulatory, anti-inflammatory, antifibrotic, promigratory, and proproliferative effects. It is argued that the regenerative potential of MSCs cannot be replaced with a cocktail of …

Recent outbreaks of Cutaneous Leishmaniasis (CL) in Waziristan make the disease a public health concern in Khyber Pakhtunkhwa (KPK) province, Pakistan. The awareness and behavior of local community towards the disease is an important factor towards effective control and management of CL in endemic areas of Pakistan. A cross-sectional community based survey was piloted in new emerging district of North Waziristan Agency (KPK province), Pakistan from August 2019- February 2020. The study aimed to examine the Knowledge, Attitude and Practices (KAP) of the local community members regarding CL. The results revealed that majority of the participants were male. Only 48.2% participants have knowledge about CL and the respondents had a moderate knowledge of CL vector and the disease. Few of the respondents were aware that CL is caused by sand flies, their breeding place, biting time, transmission of CL and control measures. Skin infection and sand-flies were the main disease symptoms and disease vector were known to some of the respondents. Most of the respondents showed positive attitude towards disease seriousness and believed that the disease could be cured and can be treated through modern medicines. Admission to hospitals, cleanliness and use of bed nets were the treatment measures for the disease in suspected patients, whereas some believed that the use of bed nets could be helpful in preventing the leishmaniasis. Moderate knowledge of the CL and its transmission in the study area emphasize the need to initiate health education and awareness campaigns to reduce the disease risk and burden in this highly endemic area in near future.

Mitochondrial diseases are a group of clinically and genetically heterogeneous disorders driven by oxidative phosphorylation dysfunction of the mitochondrial respiratory chain which due to pathogenic mutations of mitochondrial DNA (mtDNA) or nuclear DNA (nDNA). Recent progress in molecular genetics and biochemical methodologies has provided a better understanding of the etiology and pathogenesis of mitochondrial diseases, and this has expanded the clinical spectrum of this conditions. But the treatment of mitochondrial diseases is largely symptomatic and thus does not significantly change the course of the disease. Few clinical trials have led to the design of drugs aiming at enhancing mitochondrial function or reversing the consequences of mitochondrial dysfunction which are now used in the clinical treatment of mitochondrial diseases. Several other drugs are currently being evaluated for clinical management of patients with mitochondrial diseases. In this review, the current status of treatments for mitochondrial diseases is described systematically, and newer potential treatment strategies for mitochondrial diseases are also discussed.

Cystic echinococcosis (CE) is a zoonotic parasitic disease that can result in human and animal health problems globally. Although the disease is known to be endemic in Asia and the Middle East, there are few epidemiological studies on CE in Pakistan. The purpose of the present study was to identify the Echinococcus granulosus sensu lato species and genotypes contributing to human CE cases in the Khyber Pakhtunkhwa (KPK) province of Pakistan. A total of fifty-six formalin fixed paraffin embedded (FFPE) CE cyst samples of human origin were collected from the Pathology Department, Rehman Medical Institute (RMI), KPK for the years 2012-2017. Cyst samples came from the liver (26/56; 46.4%), lungs (3/56; 5.3%), spleen (3/56; 5.3%), pelvis (1/56; 1.8%), breast (1/56; 1.8%), and thigh (1/56; 1.8%). The organ location for 21 of the cysts was not recorded. World Health Organization-Informal Working Group on Echinococcosis (WHO-IWGE) ultrasound-based cyst staging was available for 17 of the 26 (65.4%) hepatic cysts. Five of these cysts (29.4%) were CE3 (transitional), nine (52.9%) were CE4 (inactive), and three (17.6%) were CE5 (inactive). Most of the cysts were obtained from CE patients that were ethnically Afghan Pashtuns (44/56; 78.6%), while 12.5% (7/56) were from patients that were Pakistani Pashtuns. The majority (41/56; 73.2%) of patients reported having close interactions with dogs. Using 12SrRNA primers, 33 cyst samples were identified as being caused by E. granulosus sensu stricto (s.s.). Mitochondrially encoded cytochrome C oxidase 1 (mt-CO1) was evaluated for the remaining 23 samples. PCR product was obtained from six of these 23 samples. Of these six samples, one was identified as Echinococcus canadensis (G6/7). Haplotype analysis showed high haplotype and low nucleotide diversity for the mt-CO1 gene. There were 26 polymorphic sites for the mt-CO1 sequence, of which 65.3% (17/26) were parsimony informative. The E. canadensis mt-CO1 haplotype network consisted of 11 haplotypes, with a main central haplotype. In conclusion, it appears that E. granulosus s.s. and E. canadensis (G6/7) are circulating in the northwestern region of Pakistan. Further molecular epidemiological studies are needed to explore the local genetic diversity of the parasite.

The outbreak of novel coronavirus (COVID-19) is a public health emergency that had caused disastrous results in more than 100 countries. The ability to detect disease outbreaks in the early stages is a key component of efficient disease control and prevention. With the increased availability of electronic health-care data and spatial analysis techniques, there is great potential to develop algorithms to enable more effective disease surveillance. The research focuses to develop a transparent user-friendly method to simulate the outbreak data. The paper describes the GIS tools to identify and define the field of investigation which requires consideration of the strengths and limitations of data collection instruments, facility of locational data collection, accuracy of locational data, and pertinent attributes for understanding disease risk. Using such information, it is quite easy for authorities to locate the highly effected area and take appropriate actions in that particular areas. However, GIS techniques, resources, and methods can be used in Pakistan for more effective investigation of vulnerable geographical locations., Graphical abstract Unlabelled Image, Highlights • The outbreak of 2019 novel coronavirus disease (COVID-19) is a public health emergency of international concern. • The ability to detect disease outbreaks in their early stages is a key component of efficient disease control and prevention. • The research focuses to develop a transparent user-friendly method to simulate spatial-temporal disease outbreak data. • GIS techniques, resources, and methods can be used in Pakistan for more effective investigation of disease. • Using such information, it is quite easy for authorities to locate the highly effected area and take appropriate actions in that particular areas.

Human cystic echinococcosis (CE) is an important zoonotic parasitic disease. It is one of the NTDs having strong roots in Pakistan. There are limited studies on the prevalence of CE in Pakistan. A retrospective study was conducted to determine the geographical distribution of human CE in Punjab (Lahore, Multan, and Faisalabad) and Sindh (Karachi and Hyderabad) provinces of Pakistan. Clinical records of infected patients from nine major hospitals were retrieved from 2008 to 2018. A total of 188 surgically confirmed cases were included from selected hospitals during the study period, which showed the annual frequency of 18.8 cases/year. The number of reported cases was higher in Sindh province (67.55%) compared to Punjab (32.45%). Total number of CE cases/city was higher in Karachi (47.34%) compared to Hyderabad city (20.21%), while in Punjab province, this frequency was higher in Lahore (25%) followed by Multan (5.32%) and Faisalabad (2.13%). Out of total 188 patients, 73 (38.83%) were males and 115 (61.7%) were females. In surveyed hospitals, high burden of infection was reported in young adults (21–30 years; 29.79%) followed by 21.81% and 17.02% in 31–40 and 41–50 age groups, respectively. Data retrieved from the hospital record of diagnosed cases of CE showed liver (36.17%, n = 68) as the most affected organ followed by lungs (26.06%, n = 49). In this survey, some unusual sites of cyst formation were also observed. Current study is a step forward towards filling the gap of knowledge for prevalence and regional distribution of hydatidosis in Pakistan reporting the CE cases in humans for the first time in Multan and Faisalabad.

Introduction Rabies is one of the most neglected tropical diseases in numerous regions of the world. Annually, 60,000 deaths have been reported, mostly in Asia and Africa. Dogs are responsible for approximately 99% of human deaths due to rabies. Consequently, incidences of canine bites are increased yet rabies continues to remain a neglected disease in Pakistan. The objective of the study was to investigate the Knowledge, Attitude and Practices (KAP) for rabies, among the participants from urban and rural population of Rawalpindi and Islamabad, Pakistan. Methods Data was collected by conducting household based cross-sectional survey over a period of 5 months (from January 2018 to May 2018). Quantitative data was collected in the form of questionnaires to investigate awareness and knowledge of rabies among the participants. The questionnaire compromised of socio-demographic features and degree of KAP with respect to rabies management and control. Results A total sample size of 434 participants responded in the study. Among them, 89.4% were found to have heard about rabies, 38.7% have no knowledge of signs and symptoms, 93.3% knew that infected dogs are the major cause of spreading rabies and 77.6% considered that the vaccination of animals is important for prevention of rabies. However, only 39.8% actively seek medical treatment at a hospital if bitten by a dog. From the 434 participants 61 reported dog bites, of which 68.8% (42/61) were male and 49.1% (30/61) belonged to age group of 6–25 years. Conclusion This study concludes that respondents have relatively limited knowledge, inconsistent attitude and poor practices towards rabies prevention and control. There is a high need of imparting knowledge to the population from multidisciplinary programs for effective management and prevention of rabies.

Theileriosis is a widespread and economically important disease of small ruminants in Pakistan. Ruminants are the intermediate hosts in the lifecycle of Theileria spp., with ticks of the family Ixodidae being the definitive hosts. To better understand the distribution and prevalence of theileriosis in Pakistan, a molecular survey was performed in small ruminants from the Lower Dir district of the Khyber Pakhtunkhwa province. A total of 200 healthy sheep and goats were screened from Maidan, Samar Bagh and Munda districts of district Dir Lower, Pakistan during December (2017) to April (2018). DNA samples were screened through nested PCR using universal primers. The amplified 492–498 bp amplicon was subjected to RLB analysis which was based on the hypervariable of the 18S rRNA gene to test for the presence of genotypes of Theileria in blood samples. A phylogeny was constructed to determine the species of Theileria genotypes. Nested PCR results indicated 53.5% prevalence of one or more Theileria genotypes in the blood of the host animal. From RLB assay, 27 animals (13.5%) showed infection with only a single species of Theileria while 80 animals (40%) showed coinfection by multiple Theileria spp. Based on the 18S rRNA phylogeny, the unknown genotype is of the species Theileria luwenshuni and is closely related to Chinese isolates. The present finding is the first report on molecular diagnosis of Theileria luwenshuni in small ruminants in Pakistan.

Known interventions like breastfeeding and kangaroo mother care (KMC) can avert a large share of infant deaths. Mother Baby Friendly Initiative Plus (MBFI+) is an integrated approach to ensure exclusive human milk diet through promotion of breastfeeding, KMC, and provision of donor human milk (DHM) to vulnerable neonates lacking mothers' own milk.Qualitative research was conducted among 56 service recipients including mothers and key influencers and 9 service providers to understand their knowledge, perceptions, and practices on breastfeeding, KMC, DHM, and human milk banks (HMBs) in 2 facilities in India, one with and another without an operational HMB. This article presents the findings on breastfeeding and KMC.Nearly all mothers mentioned that antenatal visits lacked information on breastfeeding. Most were unaware of the recommended duration of exclusive breastfeeding. Most parents knew about the benefits of breast milk and colostrum. Limited staff and privacy in facilities resulted in inadequate breastfeeding and milk expression support to mothers, who found feeding of preterm and low-birth-weight babies challenging. Mothers shared challenges in breastfeeding at home, such as low family support and privacy and burden of household chores. Only those mothers who practiced KMC were aware of its benefits. Few service providers and recipients were comfortable with the practice of wet nursing in the absence of breastfeeding.MBFI+ is a promising approach to strengthen breastfeeding and KMC. Quality counseling on breastfeeding and milk expression from antenatal period, increasing awareness and training on KMC for mothers, improving infrastructure, addressing staff shortage, and building capacities of hospital staff on MBFI+ are needed.

Scaling-up human milk banks (HMBs) is a promising solution for saving vulnerable newborns. Exploring perceptions and practices on donor human milk (DHM) and HMBs is essential to strengthen and scale-up an integrated HMB system resting on a model called the "Mother Baby Friendly Initiative Plus" (MBFI+), which includes promoting breastfeeding, encouraging kangaroo mother care, and providing safe DHM to vulnerable babies without access to mother's own milk.A qualitative research was conducted among 56 service recipients including mothers and key influencers and 9 service providers to understand their perceptions and practices on DHM and HMBs.Service providers opined that DHM is safe and lifesaving for vulnerable babies. Challenges shared were limited supply of DHM because of low awareness on milk donation, shortage of trained staff, and risk of milk contamination. They stated that although most mothers were comfortable in donating milk, few were reluctant to donate milk as they feared shortage of milk for their own babies, or milk expression may cause weakness. Recipient mothers accepted use of DHM as per facility norms but had concerns about donor mothers' health and hygiene and measures for ensuring milk safety. Most grandmothers were resistant toward donating or receiving DHM for their grandchildren. Many fathers were comfortable with donating once they knew it is lifesaving and did not compromise supply for their babies. Service providers shared opportunities for scale-up, like improving awareness and infrastructure, lactation counseling by skilled personnel, supportive hospital environment, and establishing HMBs in every city and district.Human milk banking should be strengthened as part of the MBFI+ model. For this, behavior change communication targeted at mothers and influencers about breastfeeding and HMB from the antenatal period, capacity-building among service providers, and government ownership is necessary.

OBJECTIVEIn cell transplantation trials for spinal cord injury (SCI), quantifiable imaging criteria that serve as inclusion criteria are important in trial design. The authors’ institutional experience has demonstrated an overall high rate of screen failures. The authors examined the causes for trial exclusion in a phase I, open-lab clinical trial examining the role of autologous Schwann cell intramedullary transplantation. Specifically, they reviewed the imaging characteristics in people with chronic SCI that excluded applicants from the trial, as this was a common cause of screening failures in their study.METHODSThe authors reviewed MRI records from 152 people with chronic (> 1 year) SCI who volunteered for intralesional Schwann cell transplantation but were deemed ineligible by prospectively defined criteria. Rostral-caudal injury lesion length was measured along the long axis of the spinal cord in the sagittal plane on T2-weighted MRI. Other lesion characteristics, specifically those pertaining to lesion cavity structure resulting in trial exclusion, were recorded.RESULTSImaging records from 152 potential participants with chronic SCI were reviewed, 42 with thoracic-level SCI and 110 with cervical-level SCI. Twenty-three individuals (55%) with thoracic SCI and 70 (64%) with cervical SCI were not enrolled in the trial based on imaging characteristics. For potential participants with thoracic injuries who did not meet the screening criteria for enrollment, the average rostral-caudal sagittal lesion length was 50 mm (SD 41 mm). In applicants with cervical injuries who did not meet the screening criteria for enrollment, the average sagittal lesion length was 34 mm (SD 21 mm).CONCLUSIONSWhile screening people with SCI for participation in a cell transplantation clinical trial, lesion length or volume can exclude potential subjects who appear appropriate candidates based on neurological eligibility criteria. In planning future cell-based therapy trials, the limitations incurred by lesion size should be considered early due to the screening burden and impact on candidate selection.

Introduction: An increased prevalence of cardiovascular disease has been found in women of child bearing age which varies between 0.3-3.5%. Heart diseases are the most significant non obstetrical causes of maternal deaths accounting for as much as 20.5% of all cases. Heart disease in pregnancy is a high risk condition with increased risk of maternal and foetal morbidity and mortality; hence it mandates a multidisciplinary approach. Aim: To find out prevalence, spectrum of disorder and outcome in pregnancy with heart disease in a tertiary care centre in North Eastern India. Materials and Methods: In this prospective hospital based, time bound study all pregnant women or puerperia with heart disease during the study period were followed up throughout pregnancy and their feto-maternal outcomes were compared with equal number of women without heart disease. Based on the symptoms all the patients were classified according to New York Heart Association (NYHA) functional classification. Patients were evaluated for development of any cardiac complication, obstetrical complication, and perinatal outcomes. Statistical analysis was performed using the SPSS software package (version 16.0). Results: Total number of pregnant women with heart disease was 55 and prevalence of heart disease in pregnant women admitted during the study period was found to be 2.32%. Congenital heart disease was the most common encountered type 49.09% followed by Rheumatic Heart Disease (RHD) 41.82%. Cardiac complications were present in 18% women and most common complication was congestive cardiac failure (80%). Preterm delivery was significantly higher among the cases (25%). Instrumental deliveries were higher among the cases (23.06% vs. 7.6%). The foetal outcome (live birth) was significantly better in controls. Low birth weight was higher among the cases (34.61% babies among cases and 12.73% babies among controls). Out of all maternal deaths, 10.34% were attributed to cardiac cause. All three mothers who died belonged to NYHA Class 4 and were anaemic. Conclusion: There is a significant shift in trends of spectrum of heart disease with congenital emerging as predominant lesion. This signifies an important change in the trends and spectrum of cardiac disease in our institute with lower incidence of RHD. With better health facilities, pregnant women with congenital heart disease will continue to rise and hence expertise in management of such conditions is imperative in times to come.

This study investigated the occurrence of four non-steroidal anti-inflammatory drugs (NSAIDs) and four benzodiazepines/anti-depressants (ADs) in municipal wastewater in Mardan city, Pakistan, and in River Kabul and River Indus receiving untreated sewage. Liquid chromatography with a triple quadrupole tandem mass spectrometry (LC-MS/MS) was used for the analysis of paracetamol, diclofenac, ibuprofen, and codeine (NSAIDs) and diazepam, bromazepam, lorazepam, and temazepam (ADs). Except codeine and lorazepam, all the target compounds were observed in sewage and surface water in various concentrations. In sewage, paracetamol was found at the higher end (32.4 μg/L) of the reported ranges in literature for other countries. Results of river samples showed that the target compounds were usually lower in concentration than the respective EC50 values for aquatic organisms. However, the levels for paracetamol and ibuprofen were critical depicting the consequence of untreated disposal. Environmental risk assessment by estimating the risk quotient (RQ) as the ratio of measured environmental concentration and predicted no-effect concentration showed medium to high (RQ > 1 and 0.1

Iron deficiency is one of the commonest nutritional deficiencies among women of child bearing age, in both the developed and developing world. Iron deficiency anaemia is potentially preventable as well as treatable with the use of various iron preparations. Of all the injectable iron formulations Ferric Carboxy Maltose (FCM) has best efficacy and safety profile, however, rare adverse events can occur which should always be borne in mind. The index case is a 30-year-old women G4P2L2A1 attended casualty with bleeding per vaginum. Suction and evacuation was done for incomplete abortion. Patient received FCM after two weeks for moderate anaemia. She developed anaphylactic shock within five minutes of starting the drug. Patient was managed symptomatically with inotropes and blood transfusion. She recovered fully and was discharged well. Reports of severe anaphylactic reactions with the use of FCM are less but not absent thus, judicious and cautious use of the preparation is warranted.

Pakistan is a developing country existing geographically at a pivoted location between two of the world’s largest pollution emitting countries (China and India) which adds to the severity of environmental issues faced by the country. These concerns include air pollution, climate change, and extreme weather situations prevailing in Pakistan. This increasing air pollution is deteriorating the health, threatening the food security and adding up its share to the already existing global warming. The initial step in devising a wide ranging, multifaceted, economically feasible, and sustainable solution to deal with the severity of this issue is the quantification of the air pollution and greenhouse gas emission in Pakistan. The GAINS model is one of the most comprehensive tools, dealing with the air pollutants and greenhouse gases covered by the Kyoto Protocol. This study has utilized this model to analyze the source-based anthropogenic emissions of air pollutants (NH3 and SO2), volatile organic compounds (VOCs), and greenhouse gases (CH4 and CO2), their impacts and abatement cost, for the duration of 1990–2030, in the Khyber Pakhtunkhwa and Balochistan regions of Pakistan. An overall increasing trend was observed during 1990–2030 for (a) air pollutants: NH3 (223.52–568.87kT/Y); SO2 (50.52–332.95kT/Y), (b) VOCs (121.76–246.81kT/Y), and (c) greenhouse gases: CO2 (7.83–62.45MT/Y) and CH4 (1120-2314kT/Y). The emission inventories created for all greenhouse gases together estimated the increase of 42.37 to 138.57 MTCO2eq. for greenhouse gases over the time duration of 1990–2030.

Rationale: Autologous bone marrow mesenchymal stem cells (MSCs) and c-kit + cardiac progenitor cells (CPCs) are 2 promising cell types being evaluated for patients with heart failure (HF) secondary to ischemic cardiomyopathy. No information is available in humans about the relative efficacy of MSCs and CPCs and whether their combination is more efficacious than either cell type alone. Objective: CONCERT-HF (Combination of Mesenchymal and c-kit + Cardiac Stem Cells As Regenerative Therapy for Heart Failure) is a phase II trial aimed at elucidating these issues by assessing the feasibility, safety, and efficacy of transendocardial administration of autologous MSCs and CPCs, alone and in combination, in patients with HF caused by chronic ischemic cardiomyopathy (coronary artery disease and old myocardial infarction). Methods and Results: Using a randomized, double-blinded, placebo-controlled, multicenter, multitreatment, and adaptive design, CONCERT-HF examines whether administration of MSCs alone, CPCs alone, or MSCs+CPCs in this population alleviates left ventricular remodeling and dysfunction, reduces scar size, improves quality of life, or augments functional capacity. The 4-arm design enables comparisons of MSCs alone with CPCs alone and with their combination. CONCERT-HF consists of 162 patients, 18 in a safety lead-in phase (stage 1) and 144 in the main trial (stage 2). Stage 1 is complete, and stage 2 is currently randomizing patients from 7 centers across the United States. Conclusions: CONCERT-HF will provide important insights into the potential therapeutic utility of MSCs and CPCs, given alone and in combination, for patients with HF secondary to ischemic cardiomyopathy. Clinical Trial Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT02501811.