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Background: Community health workers (CHWs) play a critical role in grassroots healthcare and are essential for achieving the health-related Sustainable Development Goals. While there is a critical shortage of essential health workers in low- and middle-income countries, WHO and international partners have reached a consensus on the need to expand and strengthen CHW programmes as a key element in achieving Universal Health Coverage (UHC). The COVID-19 pandemic has further revealed that emerging health challenges require quick local responses such as those utilizing CHWs. This is the second paper of our 11-paper supplement, "Community health workers at the dawn of a new era". Our objective here is to highlight questions, challenges, and strategies for stakeholders to consider while planning the introduction, expansion, or strengthening of a large-scale CHW programme and the complex array of coordination and partnerships that need to be considered.Methods: The authors draw on the outcomes of discussions during key consultations with various government leaders and experts from across policy, implementation, research, and development organizations in which the authors have engaged in the past decade. These include global consultations on CHWs and global forums on human resources for health (HRH) conferences between 2010 and 2014 (Montreux, Bangkok, Recife, Washington DC). They also build on the authors' direct involvement with the Global Health Workforce Alliance.Results: Weak health systems, poor planning, lack of coordination, and failed partnerships have produced lacklustre CHW programmes in countries. This paper highlights the three issues that are generally agreed as being critical to the long-term effectiveness of national CHW programmes-planning, coordination, and partnerships. Mechanisms are available in many countries such as the UHC2030 (formerly International Health Partnership), country coordinating mechanisms (CCMs), and those focusing on the health workforce such as the national Human Resources for Health Observatory and the Country Coordination and Facilitation (CCF) initiatives introduced by the Global Health Workforce Alliance.Conclusion: It is imperative to integrate CHW initiatives into formal health systems. Multidimensional interventions and multisectoral partnerships are required to holistically address the challenges at national and local levels, thereby ensuring synergy among the actions of partners and stakeholders. In order to establish robust and institutionalized processes, coordination is required to provide a workable platform and conducive environment, engaging all partners and stakeholders to yield tangible results. [ABSTRACT FROM AUTHOR]

Background: A biofeedback-based balance training system can be used to provide the compromised sensory information to subjects in order to retrain their sensorimotor function. In this study, the design and evaluation of the low-cost, intuitive biofeedback system developed at Gyeongsang National University is extended to provide multimodal biofeedback for balance training by utilization of visual and haptic modalities.Methods: The system consists of a smartphone attached to the waist of the subject to provide information about tilt of the torso, a personal computer running a purpose built software to process the smartphone data and provide visual biofeedback to the subject by means of a dedicated monitor and a dedicated Phantom Omni(®) device for haptic biofeedback. For experimental verification of the system, eleven healthy young participants performed balance tasks assuming two distinct postures for 30 s each while acquiring torso tilt. The postures used were the one foot stance and the tandem Romberg stance. For both the postures, the subjects stood on a foam platform which provided a certain amount of ground instability.Results: Post-experiment data analysis was performed using MATLAB(®) to analyze reduction in body sway. Analysis parameters based on the projection of trunk tilt information were calculated in order to ascertain the reduction in body sway and improvements in postural control. Two-way analysis of variance (ANOVA) showed no statistically significant interactions between postures and biofeedback. Post-hoc analysis revealed statistically significant reduction in body sway on provision of biofeedback. Subjects exhibited maximum body sway during no biofeedback trial, followed by either haptic or visual biofeedback and in most of the trials the multimodal biofeedback of visual and haptic together resulted in minimization of body sway, thus indicating that the multimodal biofeedback system worked well to provide significant (p < 0.05) assistance in postural control.Conclusions: A multimodal biofeedback system can offer more customized training methods and hence provide therapists with a comprehensive solution for a diverse array of patients. It is necessary to identify the long-term effects of this novel biofeedback system. In the future, the balance training schemes for individuals with upright balance issues will be studied. [ABSTRACT FROM AUTHOR]

Background: Haptic control is a useful therapeutic option in rehabilitation featuring virtual reality interaction. As with visual and vibrotactile biofeedback, kinesthetic haptic feedback may assist in postural control, and can achieve balance control. Kinesthetic haptic feedback in terms of body sway can be delivered via a commercially available haptic device and can enhance the balance stability of both young healthy subjects and stroke patients. Method: Our system features a waist-attached smartphone, software running on a computer (PC), and a dedicated Phantom Omni® device. Young healthy participants performed balance tasks after assumption of each of four distinct postures for 30 s (one foot on the ground; the Tandem Romberg stance; one foot on foam; and the Tandem Romberg stance on foam) with eyes closed. Patient eyes were not closed and assumption of the Romberg stance (only) was tested during a balance task 25 s in duration. An Android application running continuously on the smartphone sent mediolateral (ML) and anteroposterior (AP) tilt angles to a PC, which generated kinesthetic haptic feedback via Phantom Omni®. A total of 16 subjects, 8 of whom were young healthy and 8 of whom had suffered stroke, participated in the study. Results: Post-experiment data analysis was performed using MATLAB®. Mean Velocity Displacement (MVD), Planar Deviation (PD), Mediolateral Trajectory (MLT) and Anteroposterior Trajectory (APT) parameters were analyzed to measure reduction in body sway. Our kinesthetic haptic feedback system was effective to reduce postural sway in young healthy subjects regardless of posture and the condition of the substrate (the ground) and to improve MVD and PD in stroke patients who assumed the Romberg stance. Analysis of Variance (ANOVA) revealed that kinesthetic haptic feedback significantly reduced body sway in both categories of subjects. Conclusion: Kinesthetic haptic feedback can be implemented using a commercial haptic device and a smartphone. Intuitive balance cues were created using the handle of a haptic device, rendering the approach very simple yet efficient in practice. This novel form of biofeedback will be a useful rehabilitation tool improving the balance of stroke patients. [ABSTRACT FROM AUTHOR]

Background: Integration of kinesthetic and tactile cues for application to post-stroke gait rehabilitation is a novel concept which needs to be explored. The combined provision of haptic cues may result in collective improvement of gait parameters such as symmetry, balance and muscle activation patterns. Our proposed integrated cue system can offer a cost-effective and voluntary gait training experience for rehabilitation of subjects with unilateral hemiparetic stroke.Methods: Ten post-stroke ambulatory subjects participated in a 10 m walking trial while utilizing the haptic cues (either alone or integrated application), at their preferred and increased gait speeds. In the system a haptic cane device (HCD) provided kinesthetic perception and a vibrotactile feedback device (VFD) provided tactile cue on the paretic leg for gait modification. Balance, gait symmetry and muscle activity were analyzed to identify the benefits of utilizing the proposed system.Results: When using kinesthetic cues, either alone or integrated with a tactile cue, an increase in the percentage of non-paretic peak activity in the paretic muscles was observed at the preferred gait speed (vastus medialis obliquus: p <  0.001, partial eta squared (η2) = 0.954; semitendinosus p <  0.001, partial η2 = 0.793) and increased gait speeds (vastus medialis obliquus: p <  0.001, partial η2 = 0.881; semitendinosus p = 0.028, partial η2 = 0.399). While using HCD and VFD (individual and integrated applications), subjects could walk at their preferred and increased gait speeds without disrupting trunk balance in the mediolateral direction. The temporal stance symmetry ratio was improved when using tactile cues, either alone or integrated with a kinesthetic cue, at their preferred gait speed (p <  0.001, partial η2 = 0.702).Conclusions: When combining haptic cues, the subjects walked at their preferred gait speed with increased temporal stance symmetry and paretic muscle activity affecting their balance. Similar improvements were observed at higher gait speeds. The efficacy of the proposed system is influenced by gait speed. Improvements were observed at a 20% increased gait speed, whereas, a plateau effect was observed at a 40% increased gait speed. These results imply that integration of haptic cues may benefit post-stroke gait rehabilitation by inducing simultaneous improvements in gait symmetry and muscle activity. [ABSTRACT FROM AUTHOR]

Background: The Warburg effect is a rare condition in tumor biology, illustrated by significant lactate production in the presence of oxygen. The Warburg effect is associated with very poor prognosis in patients with malignancy. Case presentation: We report a 76-year-old Caucasian woman with double-expressor diffuse large B cell lymphoma who presented with severe lactic acidosis and extreme hypoglycemia with normal mentation. Her lactic acidosis was initially controlled with a bicarbonate infusion, and the patient was started promptly on steroids, followed by chemotherapy, but her clinical course was complicated by tumor lysis syndrome, acute renal failure requiring hemodialysis, and progressive liver failure. She manifested a temporary clinical response to chemotherapy but eventually died of complications. Conclusions: This case demonstrates the importance of prompt recognition of the Warburg effect, aggressive supportive measures, and early initiation of chemotherapy. Future studies are needed to characterize the role of hemodialysis in this setting. [ABSTRACT FROM AUTHOR]

Background: Haptic control is a useful therapeutic option in rehabilitation featuring virtual reality interaction. As with visual and vibrotactile biofeedback, kinesthetic haptic feedback may assist in postural control, and can achieve balance control. Kinesthetic haptic feedback in terms of body sway can be delivered via a commercially available haptic device and can enhance the balance stability of both young healthy subjects and stroke patients.Method: Our system features a waist-attached smartphone, software running on a computer (PC), and a dedicated Phantom Omni® device. Young healthy participants performed balance tasks after assumption of each of four distinct postures for 30 s (one foot on the ground; the Tandem Romberg stance; one foot on foam; and the Tandem Romberg stance on foam) with eyes closed. Patient eyes were not closed and assumption of the Romberg stance (only) was tested during a balance task 25 s in duration. An Android application running continuously on the smartphone sent mediolateral (ML) and anteroposterior (AP) tilt angles to a PC, which generated kinesthetic haptic feedback via Phantom Omni®. A total of 16 subjects, 8 of whom were young healthy and 8 of whom had suffered stroke, participated in the study.Results: Post-experiment data analysis was performed using MATLAB®. Mean Velocity Displacement (MVD), Planar Deviation (PD), Mediolateral Trajectory (MLT) and Anteroposterior Trajectory (APT) parameters were analyzed to measure reduction in body sway. Our kinesthetic haptic feedback system was effective to reduce postural sway in young healthy subjects regardless of posture and the condition of the substrate (the ground) and to improve MVD and PD in stroke patients who assumed the Romberg stance. Analysis of Variance (ANOVA) revealed that kinesthetic haptic feedback significantly reduced body sway in both categories of subjects.Conclusion: Kinesthetic haptic feedback can be implemented using a commercial haptic device and a smartphone. Intuitive balance cues were created using the handle of a haptic device, rendering the approach very simple yet efficient in practice. This novel form of biofeedback will be a useful rehabilitation tool improving the balance of stroke patients. [ABSTRACT FROM AUTHOR]

Background: Echinococcosis has a worldwide geographical distribution with endemic foci on every inhabited continent. Due to the frequent outbreaks in different parts of Pakistan in the recent past, echinococcosis is being described as a neglected tropical disease and is considered one of the most neglected parasitic diseases in the country. In endemic regions, predominantly settings with limited resources, there are high numbers of echinococcosis patients, as these communities do not have access to appropriate treatment. In Pakistan, there are limited reports on echinococcosis. The disease is prevalent in human and livestock, but this has not been sufficiently explored yet. Pakistan is an agricultural country and due to the disease's zoonotic mode of transmission, there is a dire need of future research on it. The present paper is an effort to highlight the importance of echinococcosis in Pakistan. Discussion: There is a dire need for future research on echinococcosis in Pakistan as very few investigations had been carried out on this topic thus far. The prevalence of the disease in neighbouring countries highlights that Pakistan might be at severe risk of this zoonotic infection and further supports the need for more research. In Pakistan, the majority of the population lives in rural areas with limited acess to proper hygienic/sanitary facilities. These conditions favour the outbreak of diseases such as echinococcosis. The limited available data could result in higher outbreaks in the future, and thus cause the already weak healthcare system to overburden. The country has a meagre annual budget for health, which is being spent on known infections such as polio, dengue fever and hepatic viral infections. A proper surveillance system for echinococcosis is required across the country as treatment is usually expensive, complicated and may require extensive surgery and/or prolonged drug therapy. Development of new/novel drugs and other treatment modalities receives very little, if any, attention. Prognostic awareness programmes against this infection involve deworming of the infected animals, improved food inspection and slaughterhouse hygiene, and public education campaigns. Conclusion: Future research on echinococcosis is anticipated to demonstrate whether the epidemiology, diagnosis and recombinant vaccines/antibodies relating to echinococcosis can meet the quality standards (purity, potency, safety and efficacy) defined by the World Health Organization. Research work should be carried out on the epidemiology and serodiagnosis of echinocossis in the different areas of Pakistan, which will be useful for the proper eradication of echinococcosis in this region. The health department should implement awareness-raising campaigns for the general public in order to reduce the burden of disease. [ABSTRACT FROM AUTHOR]

Background: Although deep neural networks (DNNs) are showing state of the art performance in clinical gait analysis, they are considered to be black-box algorithms. In other words, there is a lack of direct understanding of a DNN's ability to identify relevant features, hindering clinical acceptance. Interpretability methods have been developed to ameliorate this concern by providing a way to explain DNN predictions.Methods: This paper proposes the use of an interpretability method to explain DNN decisions for classifying the movement that precedes freezing of gait (FOG), one of the most debilitating symptoms of Parkinson's disease (PD). The proposed two-stage pipeline consists of (1) a convolutional neural network (CNN) to model the reduction of movement present before a FOG episode, and (2) layer-wise relevance propagation (LRP) to visualize the underlying features that the CNN perceives as important to model the pathology. The CNN was trained with the sagittal plane kinematics from a motion capture dataset of fourteen PD patients with FOG. The robustness of the model predictions and learned features was further assessed on fourteen PD patients without FOG and fourteen age-matched healthy controls.Results: The CNN proved highly accurate in modelling the movement that precedes FOG, with 86.8% of the strides being correctly identified. However, the CNN model was unable to model the movement for one of the seven patients that froze during the protocol. The LRP interpretability case study shows that (1) the kinematic features perceived as most relevant by the CNN are the reduced peak knee flexion and the fixed ankle dorsiflexion during the swing phase, (2) very little relevance for FOG is observed in the PD patients without FOG and the healthy control subjects, and (3) the poor predictive performance of one subject is attributed to the patient's unique and severely flexed gait signature.Conclusions: The proposed pipeline can aid clinicians in explaining DNN decisions in clinical gait analysis and aid machine learning practitioners in assessing the generalization of their models by ensuring that the predictions are based on meaningful kinematic features. [ABSTRACT FROM AUTHOR]

Background: Ischemia is the major cause of acute kidney injury (AKI), associated with high mortality and morbidity. Mesenchymal stem cells (MSCs) have multilineage differentiation potential and can be a potent therapeutic option for the cure of AKI. Methods: MSCs were cultured in four groups SNAP (S-nitroso N-acetyl penicillamine), SNAP + Methylene Blue (MB), MB and a control for in vitro analysis. Cultured MSCs were pre-conditioned with either SNAP (100 μM) or MB (1 μM) or both for 6 hours. Renal ischemia was induced in four groups (as in in vitro study) of rats by clamping the left renal padicle for 45 minutes and then different pre-conditioned stem cells were transplanted. Results: We report that pre-conditioning of MSCs with SNAP enhances their proliferation, survival and engraftment in ischemic kidney. Rat MSCs pre-conditioned with SNAP decreased cell apoptosis and increased proliferation and cytoprotective genes’ expression in vitro. Our in vivo data showed enhanced survival and engraftment, proliferation, reduction in fibrosis, significant improvement in renal function and higher expression of pro-survival and pro-angiogenic factors in ischemic renal tissue in SNAP pre-conditioned group of animals. Cytoprotective effects of SNAP pre-conditioning were abrogated by MB, an inhibitor of nitric oxide synthase (NOS) and guanylate cyclase. Conclusion: The results of these studies demonstrate that SNAP pre-conditioning might be useful to enhance therapeutic potential of MSCs in attenuating renal ischemia reperfusion injury. [ABSTRACT FROM AUTHOR]

Background: The significance of investigation for diagnosing and managing thyroid dysfunction in pregnant females has been extensively documented in the medical literature. This study aimed to determine trimester-specific reference ranges for thyroid-stimulating hormones (TSH), free T3 (FT3), and free T4 (FT4) in apparently healthy pregnant women attending tertiary care hospitals in Lahore.Methods: This cross-sectional study was conducted at two tertiary care Hospitals in Lahore, Pakistan. In this multi-centric study, 500 pregnant females were initially enrolled from September 2019 to December 2019 who fulfilled the inclusion criteria. For measurement of serum FT3, FT4, thyroid stimulating hormone (TSH), anti-thyroid peroxidase (anti-TPO), and thyroglobulin antibodies, 5 ml of the blood sample was drawn, under aseptic conditions, from each subject using Maglumi 800 chemiluminescence immunoassay (CLIA) system.Results: Out of 500 subjects, 23 subjects with positive anti-TPO, 19 subjects with anti-TG antibodies, and 12 subjects due to less volume of serum yielded from whole blood (serum less than 3 ml) were excluded from the analysis. Ten samples were hemolyzed and not included in the analysis. A total of 436 samples were examined for analysis. Of the remaining 436 subjects, 133 (30.5%) were from 1st trimester, 153 (35.1%) from 2nd trimester, and 150 (34.4%) from 3rd trimester. As the data were non-normal, the 2.5th, 50th, and 97.5th percentiles were calculated to express each group's results. Trimester specific range of TSH 0.168-4.294, 0.258-4.584 and 0.341-4.625 mIU/mL, FT31.857-4.408, 1.958-4.621 and 2.025-4.821 pmol/L and FT4 8.815-18.006, 8.306-17.341 and 7.402-17.292 pmol/L.Conclusion: In this study, we established a trimester-specific reference range for our local population's thyroid function test. The results of this study have complemented the results of previous studies. [ABSTRACT FROM AUTHOR]

Background: Convalescent plasma(CP) was utilized as potential therapy during COVID-19 pandemic in Pakistan. The study aimed at appraisal of CP transfusion safety and usefulness in COVID pneumonia.Methods: Single arm, MEURI study design of non-randomized open label trial was conducted in five centers. Patients werecategorized as moderately severe, severe, and critical. The primary endpoint was a) improvement in clinical status and change in category of disease severity; secondary endpoint was b) CP ability to halt disease progression to invasive ventilation. CP transfused to hospitalized patients. Statistical tests including median (interquartile ranges), Mann-Whitney U test, Fisher's exact test using SPSS ver. 23, ANOVA and Chi-square test were applied for the analysis of results parameters before and after CP treatment. SOFA score was applied for multiorgan failure in severe and critical cases.Results: A total of 50 adult patients; median age 58.5 years (range: 29-92 years) received CP with infusion titers; median 1:320 U/mL (Interquartile range 1:80-1:320) between April 4 to May 5, 2020. The median time from onset of symptoms to enrollment in trial was 3 to 7 days with shortness of breath and lung infiltration as severity criterion. In 35 (70%) recipients, oxygen saturation improved from 80 to 95% within 72h, with resolution of lung infiltrates. Primary endpoint was achieved in 44 (88%) recipients whereas secondary endpoint was achieved in 42 (84%). No patient experienced severe adverse events. A high SOFA score (> 7) correlated with deaths in severe and critical patients. Eight (16%) patients expired due to comorbidities; cardiac arrest in 2 (4%), multiorgan failure secondary to cytokine storm in 5 (10%) and ventilator associated complications in 1 (2%).Conclusion: CP transfusion can be used as a safe and useful treatment in moderately severe and severe patients.Trial Registration: The trial registration number is NCT04352751  ( https://www.irct.ir/search/result?query=IRCT20200414047072N1 ). Trial Registration date is 28th April 2020. [ABSTRACT FROM AUTHOR]

After publication of the original article [1], we were notified that an author's name has been erroneously spelled. Aamir Ali Khattak should be replaced with Aamer Ali Khattak. [ABSTRACT FROM AUTHOR]

Background: Malaria is the fifth leading cause of death worldwide. Pakistan is considered as a moderate malaria-endemic country but still, 177 million individuals are at risk of malaria. Roughly 60% of Pakistan's population, live in malaria-endemic regions. The present study is based upon the survey of various health care centers in 10 major cities of Northern and Southern Punjab to find out the malarial infection patterns in 2015. The diagnosis, seasonal variations, age and gender-wise distribution of Plasmodium spp. circulating in the study area were also included in the objectives.Methods: The malaria-suspected patients '16075' were enrolled for malaria diagnosis using microscopy, out of which 925 were malaria positive which were processed for molecular analysis using nested PCR. The 18S rRNA genes of Plasmodium species were amplified, sequenced, blast and the phylogenetic tree was constructed based on sequences using online integrated tool MEGA7.Results: The 364 cases recruited from Northern Punjab with the highest incidence in Rawalpindi (25.5%) and lowest in Chakwal (15.9%). From Southern Punjab 561 cases were enlisted Rajanpur (21.4%) maximum and lowest from Multan and Rahim Yar Khan (18%). The slide positivity rate, annual parasite incidence, and annual blood examination rates were 5.7 per 1000 population, 0.1, and 0.2% respectively. The only P. vivax (66.7%), P. falciparum (23.7%) and mixed infection by these two species (9.6%) were diagnosed. The same trend (P. vivax > P. falciparum > mixed infection) in species identification %age was confirmed from molecular analysis. However, the occurrence of malaria was higher in Southern Punjab (5.5%) as compared to the Northern Punjab (4.0%). The overall malaria percentage occurrence of treatment-seeking patients in all recruited cities of Punjab was 4.9%. The age-group of 1-20 and males among genders were more affected by malaria. The comparison of different seasons showed that the malaria infection was at a peak in Summer and post-monsoon.Conclusion: The incidence of malaria was high in the flood infected rural areas of Southern Punjab, Summer, and post-monsoon. The age group (1-20) and gender-wise males were more affected by malaria. [ABSTRACT FROM AUTHOR]

Background: Pyrazinamide (PZA) is an important component of first-line drugs because of its distinctive capability to kill subpopulations of persistent Mycobacterium tuberculosis (MTB). The prodrug (PZA) is converted to its active form, pyrazinoic acid (POA) by MTB pncA-encoded pyrazinamidase (PZase). Mutation in pncA is the most common and primary cause of PZA resistance. The aim of the present study was to explore the molecular characterization of PZA resistance in a Pashtun-dominated region of Khyber Pakhtunkhwa, Pakistan.Methods: We performed drug susceptibility testing (DST) on 753 culture-positive isolates collected from the Provincial Tuberculosis Control Program Khyber Pakhtunkhwa using the BACTEC MGIT 960 PZA method. In addition, the pncA gene was sequenced in PZA-resistant isolates, and PZA susceptibility testing results were used to determine the sensitivity and specificity of pncA gene mutations.Results: A total of 69 isolates were PZA resistant (14.8%). Mutations were investigated in 69 resistant, 26 susceptible and one H37Rv isolates by sequencing. Thirty-six different mutations were identified in PZA-resistant isolates, with fifteen mutations, including 194_203delCCTCGTCGTG and 317_318delTC, that have not been reported in TBDRM and GMTV Databases and previous studies. Mutations Lys96Thr and Ser179Gly were found in the maximum number of isolates (n = 4 each). We did not detect mutations in sensitive isolates, except for the synonymous mutation 195C > T (Ser65Ser). The sensitivity and specificity of the pncA sequencing method were 79.31% (95% CI, 69.29 to 87.25%) and 86.67% (95% CI, 69.28 to 96.24%).Conclusion: Mutations in the pncA gene in circulating isolates of geographically distinct regions, especially in high-burden countries, should be investigated for better control and management of drug-resistant TB. Molecular methods for the investigation of PZA resistance are better than DST. [ABSTRACT FROM AUTHOR]

Background: Nitrogen (N) is a key macronutrient required for plant growth and development. In this study, watermelon plants were grown under hydroponic conditions at 0.2 mM N, 4.5 mM N, and 9 mM N for 14 days. Results: Dry weight and photosynthetic assimilation at low N (0.2 mM) was reduced by 29 and 74% compared with high N (9 mM). The photochemical activity (Fv/Fm) was also reduced from 0.78 at high N to 0.71 at low N. The N concentration in the leaf, stem, and root of watermelon under low N conditions was reduced by 68, 104, and 108%, respectively compared with 9 mM N treatment after 14 days of N treatment. In the leaf tissues of watermelon grown under low N conditions, 9598 genes were differentially expressed, out of which 4533 genes (47.22%) were up-regulated whereas, 5065 genes (52.78%) were down-regulated compared with high N. Similarly in the root tissues, 3956 genes were differentially expressed, out of which 1605 genes were up-regulated (40.57%) and 2351 genes were down-regulated (59.43%), compared with high N. Our results suggest that leaf tissues are more sensitive to N deficiency compared with root tissues. The gene ontology (GO) analysis showed that the availability of N significantly affected 19 biological processes, 8 cell component metabolic pathways, and 3 molecular functions in the leaves; and 13 biological processes, 12 molecular functions, and 5 cell component metabolic pathways in the roots of watermelon. The low affinity nitrate transporters, high affinity nitrate transporters, ammonium transporters, genes related with nitrogen assimilation, and chlorophyll and photosynthesis were expressed differentially in response to low N. Three nitrate transporters (Cla010066, Cla009721, Cla012765) substantially responded to low nitrate supply in the root and leaf tissues. Additionally, a large number of transcription factors (1365) were involved in adaptation to low N availability. The major transcription factor families identified in this study includes MYB, AP2-EREBP, bHLH, C2H2 and NAC. Conclusion: Candidate genes identified in this study for nitrate uptake and transport can be targeted and utilized for further studies in watermelon breeding and improvement programs to improve N uptake and utilization efficiency. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The provision of health and wellness care is undergoing an enormous transformation. A key element of this revolution consists in prioritizing prevention and proactivity based on the analysis of people's conducts and the empowerment of individuals in their self-management. Digital technologies are unquestionably destined to be the main engine of this change, with an increasing number of domain-specific applications and devices commercialized every year; however, there is an apparent lack of frameworks capable of orchestrating and intelligently leveraging, all the data, information and knowledge generated through these systems.Methods: This work presents Mining Minds, a novel framework that builds on the core ideas of the digital health and wellness paradigms to enable the provision of personalized support. Mining Minds embraces some of the most prominent digital technologies, ranging from Big Data and Cloud Computing to Wearables and Internet of Things, as well as modern concepts and methods, such as context-awareness, knowledge bases or analytics, to holistically and continuously investigate on people's lifestyles and provide a variety of smart coaching and support services.Results: This paper comprehensively describes the efficient and rational combination and interoperation of these technologies and methods through Mining Minds, while meeting the essential requirements posed by a framework for personalized health and wellness support. Moreover, this work presents a realization of the key architectural components of Mining Minds, as well as various exemplary user applications and expert tools to illustrate some of the potential services supported by the proposed framework.Conclusions: Mining Minds constitutes an innovative holistic means to inspect human behavior and provide personalized health and wellness support. The principles behind this framework uncover new research ideas and may serve as a reference for similar initiatives. [ABSTRACT FROM AUTHOR]

Background: Foot-and-mouth disease (FMD) is endemic in Pakistan and causes huge economic losses. This work focus on the Landhi Dairy Colony (LDC), located in the suburbs of Karachi. LDC is the largest Buffalo colony in the world, with more than 300,000 animals (around 95% buffaloes and 5% cattle, as well as an unknown number of sheep and goats). Each month from April 2006 to April 2007 we collected mouth-swabs from apparently healthy buffaloes and cattle, applying a convenient sampling based on a two-stage random sampling scheme, in conjunction with participatory information from each selected farm. Furthermore, we also collected epithelium samples from animals with clinical disease, as well as mouth-swabs samples from those farms. In addition, we analysed a total of 180 serum samples randomly collecting 30 samples each month at the local slaughterhouse, from October 2006 to March 2007. Samples have been screened for FMDV by real-time RT-PCR and the partial or full 1D coding region of selected isolates has been sequenced. Serum samples have been analysed by applying serotype-specific antibody ELISA and non-structural proteins (NSP) antibody ELISA. Results: FMDV infection prevalence at aggregate level shows an endemic occurrence of FMDV in the colony, with peaks in August 2006, December 2006 and February 2007 to March 2007. A significant association of prevalence peaks to the rainy seasons, which includes the coldest time of the year and the muslimic Eid-festival, has been demonstrated. Participatory information indicated that 88% of all questioned farmers vaccinate their animals. Analysis of the serum samples showed high levels of antibodies for serotypes O, A, Asia 1 and C. The median endpoint-titre for all tested serotypes, except serotype C, in VNT titration is at a serum dilution of equal or above 1/100. All 180 serum samples collected have been tested for antibodies against the non-structural proteins and all but four have been found positive. Out of the 106 swab-samples from apparently healthy and affected animals positive in real-time RTPCR, we sequenced the partial or full 1D coding region from 58 samples. In addition we sequenced the full 1D coding region of 17 epithelium samples from animals with clinical signs of FMD. From all sequenced samples, swabs and epithelium, 19 belong to the regional PanAsia II lineage of serotype O and 56 to the A/Iran/2005 lineage of serotype A. Conclusion: For an effective and realisable FMD control program in LDC, we suggest to introduce a twice annually mass vaccination of all buffaloes and cattle in the colony. These mass vaccinations should optimally take place shortly before the beginning of the two rainy periods, e.g. in June and September. Those vaccinations should, in our opinion, be in addition to the already individually performed vaccinations of single animals, as the latter usually targets only newly introduced animals. This suggested combination of mass vaccination of all large ruminants with the already performed individually vaccination should provide a continuous high level of herd immunity in the entire colony. Vaccines used for this purpose should contain the matching vaccine strains, i.e. as our results indicate antigens for A/Iran/2005 and the regional type of serotype O (PanAsia II), but also antigens of the, in this world region endemic, Asia 1 lineage should be included. In the long term it will be important to control the vaccine use, so that subclinical FMD will be avoided. [ABSTRACT FROM AUTHOR]

Background: According to the World Reference Laboratory for FMD, a new subtype of FMDV serotype A was detected in Iran in 2005. This subtype was designated A/IRN/2005, and rapidly spread throughout Iran and moved westwards into Saudi Arabia and Turkey where it was initially detected from August 2005 and subsequently caused major disease problems in the spring of 2006. The same subtype reached Jordan in 2007. As part of an ongoing project we have also detected this subtype in Pakistan with the first positive samples detected in April 2006. To characterise this subtype in detail, we have sequenced and analysed the complete coding sequence of three subtype A/IRN/2005 isolates collected in Pakistan in 2006, the complete coding sequence of one subtype A/IRN/2005 isolate collected during the first outbreak in Turkey in 2005 and, in addition, the partial 1D coding sequence derived from 4 epithelium samples and 34 swab-samples from Asian buffaloes or cattle subsequently found to be infected with the A/IRN/2005 subtype. Results: The phylogenies of the genome regions encoding for the structural proteins, displayed, with the exception of 1A, distinct, serotype-specific clustering and an evolutionary relationship of the A/IRN/2005 sublineage with the A22 sublineage. Potential recombination events have been detected in parts of the genome region coding for the non-structural proteins of FMDV. In addition, amino acid substitutions have been detected in the deduced VP1 protein sequence, potentially related to clinical or subclinical outcome of FMD. Indications of differential susceptibility for developing a subclinical course of disease between Asian buffaloes and cattle have been detected. Furthermore, hitherto unknown insertions of 2 amino acids before the second start codon, as well as sublineage specific amino acids have been detected in the genome region encoding for the leader proteinase of A/IRN/2005 sublineage. Conclusion: Our findings indicate that the A/IRN/2005 sublineage has undergone two different paths of evolution for the structural and non-structural genome regions. The structural genome regions have had their evolutionary starting point in the A22 sublineage. It can be assumed that, due to the quasispecies structure of FMDV populations and the error-prone replication process, advantageous mutations in a changed environment have been fixed and lead to the occurrence of the new A/IRN/2005 sublineage. Together with this mechanism, recombination within the non-structural genome regions, potentially modifying the virulence of the virus, may be involved in the success of this new sublineage. The possible origin of this recombinant virus may be a co-infection with Asia1 and a serotype A precursor of the A/IRN/2005 sublineage potentially within Asian Buffaloes, as these appears to relatively easy become infected, but usually without developing clinical disease and consequently showing not a strong acute inflammatory immune response against a second FMDV infection. [ABSTRACT FROM AUTHOR]

Background: Radiation induced secondary cancers are a rare but severe late effect after breast conserving therapy. Intraoperative radiotherapy (IORT) is increasingly used during breast conserving surgery. The purpose of this analysis was to estimate secondary cancer risks after IORT compared to other modalities of breast radiotherapy (APBI - accelerated partial breast irradiation, EBRT - external beam radiotherapy).Methods: Computer-tomography scans of an anthropomorphic phantom were acquired with an INTRABEAM IORT applicator (diameter 4 cm) in the outer quadrant of the breast and transferred via DICOM to the treatment planning system. Ipsilateral breast, contralateral breast, ipsilateral lung, contralateral lung, spine and heart were contoured. An INTRABEAM source (50 kV) was defined with the tip of the drift tube at the center of the spherical applicator. A dose of 20 Gy at 0 mm depth from the applicator surface was prescribed for IORT and 34 Gy (5 days × 2 × 3.4 Gy) at 10 mm depth for APBI. For EBRT a total dose of 50 Gy in 2 Gy fractions was planned using two tangential fields with wedges. The mean and maximal doses, DVHs and volumes receiving more than 0.1 Gy and 4 Gy of organs at risk (OAR) were calculated and compared. The life time risk for secondary cancers was estimated according to NCRP report 116.Results: IORT delivered the lowest maximal doses to contralateral breast (< 0.3 Gy), ipsilateral (1.8 Gy) and contralateral lung (< 0.3 Gy), heart (1 Gy) and spine (< 0.3 Gy). In comparison, maximal doses for APBI were 2-5 times higher. EBRT delivered a maximal dose of 10.4 Gy to the contralateral breast and 53 Gy to the ipsilateral lung. OAR volumes receiving more than 4 Gy were 0% for IORT, < 2% for APBI and up to 10% for EBRT (ipsilateral lung). The estimated risk for secondary cancer in the respective OAR is considerably lower after IORT and/or APBI as compared to EBRT.Conclusions: The calculations for maximal doses and volumes of OAR suggest that the risk of secondary cancer induction after IORT is lower than compared to APBI and EBRT. [ABSTRACT FROM AUTHOR]