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Objective: To establish the frequency of evolution in CT appearance from an initial scan to a subsequent scan within 12 h and the prognostic significance of such deterioration. Methods: All patients who presented to Department of Neurosurgery, Liaquat National Hospital and Medical College with traumatic brain injury and received their CT scan within the first 4 h of injury were included in the study. Indications for repeat CT scan were: any deterioration in neurological status after the initial scan, potentially deteriorating lesion on initial scan with or without worsening neurology, worsening neurological status after the initial CT scan findings, or no neurological improvement after initial management in patients with normal CT scan with significant head injury. This compiled with the data of 107 patients. Results: There were 67 males and 40 females. The cause of trauma of the 70% patients was road traffic accident. In 11 patients, the lesion evolved towards resorption while 32 patients had no significant changes in the subsequent CT scan. Sixty four patients showed an increase in the size of the lesion and 65.6% of them were required surgical intervention subsequently. Conclusions: In case where the initial CT scan performed within 4 h of significant head injury was not correlated with the patient's neurology, it should be repeated within 12 h.

Bacterial citrate lyase activity has been demonstrated in various eukaryotes, bacteria and archaea, underscoring their importance in energy metabolism of the cell. While the bacterial citrate lyase comprises of three different subunits, M. tuberculosis genome lacks CitD and CitF subunits of citrate lyase complex but encodes for 2 homologs of CitE subunits, Rv2498c and Rv3075c. Using temperature sensitive mycobacteriophages, we were able to generate both single and double citE mutant strains of M. tuberculosis. The survival experiments revealed increased susceptibility of the double mutant strain to oxidative stress in comparison to the parental strain. Also, simultaneous deletion of both citE1 and citE2 in M. tuberculosis genome resulted in impairment of intracellular replication in macrophages. The double mutant strain displayed reduced growth in lungs and spleens of guinea pigs. This is the first study demonstrating that M. tuberculosis critically requires CitE subunits of citrate lyase for pathogenesis. Taken together, these findings position these enzymes as potential targets for development of anti-tubercular small molecules.

Underwater Wireless Sensor Networks (UWSNs) are promising and emerging frameworks having a wide range of applications. The underwater sensor deployment is beneficial; however, some factors limit the performance of the network, i.e., less reliability, high end-to-end delay and maximum energy dissipation. The provisioning of the aforementioned factors has become a challenging task for the research community. In UWSNs, battery consumption is inevitable and has a direct impact on the performance of the network. Most of the time energy dissipates due to the creation of void holes and imbalanced network deployment. In this work, two routing protocols are proposed to avoid the void hole and extra energy dissipation problems which, due to which lifespan of the network increases. To show the efficacy of the proposed routing schemes, they are compared with the state of the art protocols. Simulation results show that the proposed schemes outperform the counterparts.

Objective: Suicide accounts for substantial mortality in low-resourced settings and contributes to nearly 20% of maternal deaths. In Asia, interpersonal conflict is a salient factor that contributes to suicidal thoughts and actions, yet limited research has been done to explore the type and timing of such conflicts and a woman's accompanying social support. Identifying such risk factors can inform improved efforts to identify who to target for psychosocial interventions., Methods: Using the Bachpan Cohort study of mothers in Pakistan ( n  = 1154), we examined the prevalence and interpersonal influences on SI within the past two weeks of pregnancy and then at 3, 6, and 24 months after birth. Using hierarchical mixed effects models, we explored the separate and combined associations of interpersonal factors [e.g., social support, interpersonal conflict, isolation, and past year intimate partner violence (IPV)] on SI at each timepoint., Results: SI prevalence was highest in pregnancy (12.2%) and dropped to 5% throughout two years postpartum. The interpersonal conflict was independently associated with increased odds of SI in pregnancy and 24 months postpartum. IPV was associated with increased SI in pregnancy and 24 months postpartum. Isolation was not associated with SI at any timepoint. Perceived social support remained a robust independent factor associated with reduced SI at all timepoints., Conclusion: In addition to screening and deploying interventions for perinatal women with depression, targeting interventions for those who also experience interpersonal conflict, including intimate partner violence, may significantly reduce suicidal thoughts and related sequelae. Social support is a viable and potentially powerful target to reduce the burden of suicide among women.HIGHLIGHTSSuicidal ideation prevalence was higher in pregnancy compared to postpartum.Perceived social support was independently associated with reduced suicidal ideation.Interventions addressing suicide must attend to women's family and social context.

Background: The COVID-19 pandemic is an epidemiological and psychological crisis; what it does to the body is quite well known by now, and more research is underway, but the syndemic impact of COVID-19 and mental health on underlying chronic illnesses among the general population is not completely understood., Methods: We carried out a literature review to identify the potential impact of COVID-19 and related mental health issues on underlying comorbidities that could affect the overall health of the population., Results: Many available studies have highlighted the impact of COVID-19 on mental health only, but how complex their interaction is in patients with comorbidities and COVID-19, the absolute risks, and how they connect with the interrelated risks in the general population, remain unknown. The COVID-19 pandemic can be recognized as a syndemic due to; synergistic interactions among different diseases and other health conditions, increasing overall illness burden, emergence, spread, and interactions between infectious zoonotic diseases leading to new infectious zoonotic diseases; this is together with social and health interactions leading to increased risks in vulnerable populations and exacerbating clustering of multiple diseases., Conclusion: There is a need to develop evidence to support appropriate and effective interventions for the overall improvement of health and psychosocial wellbeing of at-risk populations during this pandemic. The syndemic framework is an important framework that can be used to investigate and examine the potential benefits and impact of codesigning COVID-19/non-communicable diseases (NCDs)/mental health programming services which can tackle these epidemics concurrently.

Lithium-ion batteries (LIBs) continue to dominate the battery market with their efficient energy storage abilities and their ongoing development. However, at high charge/discharge C-rates their electrochemical performance decreases significantly. To improve the power density properties of LIBs, it is important to form a uniform electron transfer network in the cathode electrode via the addition of conductive additives. Carbon nanotubes (CNTs) with high crystallinity, high electrical conductivity, and high aspect ratio properties have gathered significant interest as cathode electrode conductive additives. However, due to the high aggregational properties of CNTs, it is difficult to form a uniform network for electron transfer within the electrode. In this study, to help fabricate electrodes with well-dispersed CNTs, various electrodes were prepared by controlling (i) the mixing order of the conductive material, binder, and active material, and (ii) the sonication process of the CNTs/NMP solution before the electrode slurry preparation. When the binder was mixed with a well sonicated CNTs/NMP solution, the CNTs uniformly adsorbed to the then added cathode material of LiNi0.6Co0.2Mn0.2O2 and were well-dispersed to form a flowing uniform network. This electrode fabrication process achieved > 98.74% capacity retention after 50 cycles at 5C via suppressed polarization at high current densities and a more reversible H1-M phase transition of the active material. Our study presents a novel design benchmark for the fabricating of electrodes applying well-dispersed CNTs, which can facilitate the application of LIBs in high current density applications.

There is a dearth of evidence synthesis on the prevalence of anxiety among university students even though the risk of psychological disorders among this population is quite high. We conducted a quantitative systematic review to estimate the global prevalence of anxiety among university students during the COVID-19 pandemic. A systematic search for cross-sectional studies on PubMed, Scopus, and PsycINFO, using PRISMA guidelines, was conducted from September 2020 to February 2021. A total of 36 studies were included, using a random-effects model to calculate the pooled proportion of anxiety. A meta-analysis of the prevalence estimate of anxiety yielded a summary prevalence of 41% (95% CI = 0.34-0.49), with statistically significant evidence of between-study heterogeneity (Q = 80801.97, I 2 = 100%, p ≤ 0.0001). A subgroup analysis reported anxiety prevalence in Asia as 33% (95% CI:0.25-0.43), the prevalence of anxiety in Europe as 51% (95% CI: 0.44-0.59), and the highest prevalence of anxiety in the USA as 56% (95% CI: 0.44-0.67). A subgroup gender-based analysis reported the prevalence of anxiety in females as 43% (95% CI:0.29-0.58) compared to males with an anxiety prevalence of 39% (95% CI:0.29-0.50). University students seem to have a high prevalence of anxiety, indicating an increased mental health burden during this pandemic.

Background: Machine learning (ML) offers vigorous statistical and probabilistic techniques that can successfully predict certain clinical conditions using large volumes of data. A review of ML and big data research analytics in maternal depression is pertinent and timely, given the rapid technological developments in recent years., Objective: This study aims to synthesize the literature on ML and big data analytics for maternal mental health, particularly the prediction of postpartum depression (PPD)., Methods: We used a scoping review methodology using the Arksey and O'Malley framework to rapidly map research activity in ML for predicting PPD. Two independent researchers searched PsycINFO, PubMed, IEEE Xplore, and the ACM Digital Library in September 2020 to identify relevant publications in the past 12 years. Data were extracted from the articles' ML model, data type, and study results., Results: A total of 14 studies were identified. All studies reported the use of supervised learning techniques to predict PPD. Support vector machine and random forest were the most commonly used algorithms in addition to Naive Bayes, regression, artificial neural network, decision trees, and XGBoost (Extreme Gradient Boosting). There was considerable heterogeneity in the best-performing ML algorithm across the selected studies. The area under the receiver operating characteristic curve values reported for different algorithms were support vector machine (range 0.78-0.86), random forest method (0.88), XGBoost (0.80), and logistic regression (0.93)., Conclusions: ML algorithms can analyze larger data sets and perform more advanced computations, which can significantly improve the detection of PPD at an early stage. Further clinical research collaborations are required to fine-tune ML algorithms for prediction and treatment. ML might become part of evidence-based practice in addition to clinical knowledge and existing research evidence., (©Kiran Saqib, Amber Fozia Khan, Zahid Ahmad Butt. Originally published in JMIR Mental Health (https://mental.jmir.org), 24.11.2021.)

Background: Depression is one of the most prevalent, yet unrecognized but treatable mental disorders in low and middle income countries (LMICs). In such locations, screening tools that are easy-to-administer, valid, and reliable are needed to assist in detecting symptoms of depression. The Patient Health Questionnaire (PHQ-9) is one of the most widely used depression screeners. However, its applicability to community-based settings of Pakistan is limited by the lack of studies examining its validity and reliability in such settings. The current study aimed to demonstrate the criterion-related validity and internal reliability of the Urdu version of the PHQ-9 in a sample of community-based pregnant women in Pakistan compared to a diagnostic clinical interview, the Structured Clinical Interview for DSM disorders (SCID), using data from a depression treatment cluster randomized trial in rural Pakistan., Methods: Pregnant women in a rural, low income sub-district in Pakistan were approached between October 2014 and February 2016 and, after providing informed consent, screened for depression using the Urdu version of the PHQ-9, with a cutoff of ≥10 used to indicate significant depressive symptoms. Following the PHQ-9, the diagnostic module for current major depressive episode of the SCID was administered. We examined the psychometric properties of PHQ-9 compared to SCID as a gold standard, using sensitivity, specificity, and negative and positive predictive value to measure the criterion-related validity of the PHQ-9 as an indicator of symptoms of depression. We computed area under the receiver operating characteristic curve to determine diagnostic accuracy, and used Cronbach's alpha to assess internal reliability., Results: A total of 1,731 women in their third trimester of pregnancy were assessed for major depressive disorder. Of these women, 572 (33%) met the cutoff for significant depressive symptoms on PHQ-9, and 454 (26%) were assessed positive for depression using the SCID. The sensitivity and specificity of PHQ-9 at a cutoff of ≥10 was 94.7% and 88.9%, respectively. The positive and negative predictive values were 75.2% and 97.9%, respectively; and the area under the curve was 0.959. Internal reliability, as measured by Cronbach's alpha, was 0.844., Discussion: Valid and reliable screening tools to assist in detecting symptoms of depressive disorder are needed in low income settings where depressive disorders are highly prevalent. The Urdu version of the PHQ-9 has not been previously validated against a well-known assessment of depression in a community setting among pregnant women in Pakistan. This study demonstrates that the Urdu version of the PHQ-9 has acceptable criterion-related validity and reliability for screening for depressive symptoms in Pakistan among community-based pregnant women; and when the recommended cut-off score of ≥10 is used it can also serve as an accurate screening tool for major depressive disorder., Competing Interests: The authors declare there are no competing interests.

Glucocorticoids (GC) are implicated in the development of metabolic syndrome, and patients with GC excess share many clinical features, such as central obesity and glucose intolerance. In patients with obesity or type 2 diabetes, systemic GC concentrations seem to be invariably normal. Tissue GC concentrations determined by the hypothalamic-pituitary-adrenal (HPA) axis and local cortisol (corticosterone in mice) regeneration from cortisone (11-dehydrocorticosterone in mice) by the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme, principally expressed in the liver. Transgenic mice have demonstrated the importance of 11β-HSD1 in mediating aspects of the metabolic syndrome, as well as HPA axis control. In order to address the primacy of hepatic 11β-HSD1 in regulating metabolism and the HPA axis, we have generated liver-specific 11β-HSD1 knockout (LKO) mice, assessed biomarkers of GC metabolism, and examined responses to high-fat feeding. LKO mice were able to regenerate cortisol from cortisone to 40% of control and had no discernible difference in a urinary metabolite marker of 11β-HSD1 activity. Although circulating corticosterone was unaltered, adrenal size was increased, indicative of chronic HPA stimulation. There was a mild improvement in glucose tolerance but with insulin sensitivity largely unaffected. Adiposity and body weight were unaffected as were aspects of hepatic lipid homeostasis, triglyceride accumulation, and serum lipids. Additionally, no changes in the expression of genes involved in glucose or lipid homeostasis were observed. Liver-specific deletion of 11β-HSD1 reduces corticosterone regeneration and may be important for setting aspects of HPA axis tone, without impacting upon urinary steroid metabolite profile. These discordant data have significant implications for the use of these biomarkers of 11β-HSD1 activity in clinical studies. The paucity of metabolic abnormalities in LKO points to important compensatory effects by HPA activation and to a crucial role of extrahepatic 11β-HSD1 expression, highlighting the contribution of cross talk between GC target tissues in determining metabolic phenotype.

Mammalian cells contain different phospholipase D enzymes (PLDs) whose distinct physiological roles are poorly understood and whose products have not been characterized. The development of porcine aortic endothelial (PAE) cell lines able to overexpress PLD-1b or -2a under the control of an inducible promoter has enabled us to characterize both the substrate specificity and the phosphatidic acid (PtdOH) product of these enzymes under controlled conditions. Liquid chromatography-MS analysis showed that PLD1b- and PLD2a-transfected PAE cells, as well as COS7 and Rat1 cells, generate similar PtdOH and, in the presence of butan-1-ol, phosphatidylbutanol (PtdBut) profiles, enriched in mono- and di-unsaturated species, in particular 16:0/18:1. Although PtdBut mass increased, the species profile did not change in cells stimulated with ATP or PMA. Overexpression of PLD made little difference to basal or stimulated PtdBut formation, indicating that activity is tightly regulated in vivo and that factors other than just PLD protein levels limit hydrolytic function. In vitro assays using PLD-enriched lysates showed that the enzyme could utilize both phosphatidylcholine and, much less efficiently, phosphatidylethanolamine, with slight selectivity towards mono- and di-unsaturated species. Phosphatidylinositol was not a substrate. Thus PLD1b and PLD2a hydrolyse a structurally similar substrate pool to generate an identical PtdOH product enriched in mono- and di-unsaturated species that we propose to function as the intracellular messenger forms of this lipid.

Cell adhesion is fundamental to establishing and maintaining the discrete tissues in multicellular organisms. Adhesion must be sufficiently strong to preserve tissue architecture, whilst having the capacity to readily dissociate to permit fundamental processes, such as wound repair, to occur. However, very little is known about the signalling mechanisms involved in temporary down-regulation of cell adhesion to facilitate such processes. Cadherins are the principal mediators of cell-cell adhesion in a wide variety of tissues and species and form multi-protein complexes with cytosolic and cytoskeletal proteins to express their full adhesive capacity. In the present study we report that the p85 subunit of phosphoinositide 3-kinase (PI 3-kinase) is associated with the cadherin-based adhesion complex in human epithelial cells. The interaction of p85 with the complex is via beta-catenin. We also show that the interaction of p85 and beta-catenin is direct, involves the N-terminal Src homology domain 2 of p85 and is regulated by tyrosine phosphorylation. These data suggest that PI 3-kinase may play a role in the functional regulation of the cadherin-based adhesion complex.

Phosphoinositides are localized in various intracellular compartments and can regulate a number of intracellular functions, such as cytoskeletal dynamics and membrane trafficking. Phospholipase Ds (PLDs) are regulated enzymes that hydrolyse phosphatidylcholine (PtdCho) to generate the putative second messenger phosphatidic acid (PtdOH). In vitro, PLDs have an absolute requirement for higher phosphorylated inositides, such as phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P(2)]. Whether this lipid is able to regulate the activity of PLD in vivo is contentious. To examine this hypothesis we studied the relationship between PLD and an enzyme critical for the intracellular synthesis of PtdIns(4,5)P(2): phosphatidylinositol 4-phosphate 5-kinase alpha (Type Ialpha PIPkinase). We find that both PLD1 and PLD2 interact with the Type Ialpha PIPkinase and that PLD2 activity in vivo can be regulated solely by the expression of this lipid kinase. Moreover, PLD2 is able to recruit the Type Ialpha PIPkinase to its intracellular location. We show that the physiological requirement of PLD enzymes for PtdIns(4,5)P(2) is critical and that PLD2 activity can be regulated solely by the levels of this key intracellular lipid.

The signalling pathway leading, for example, to actin cytoskeletal reorganisation, secretion or superoxide generation involves phospholipase D (PLD)-catalysed hydrolysis of phosphatidylcholine to generate phosphatidic acid, which appears to mediate the messenger functions of this pathway. Two PLD genes (PLD1 and PLD2) with similar domain structures have been doned and progress has been made in identifying the protein regulators of PLD1 activation, for example Arf and Rho family members. The activities of both PLD isoforms are dependent on phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) and our sequence analysis suggested the presence of a pleckstrin homology (PH) domain in PLD1, although its absence has also been daimed. Investigation of the inositide dependence showed that a bis-phosphorylated lipid with a vicinal pair of phosphates was required for PLD1 activity. Furthermore, PLD1 bound specifically and with high affinity to lipid surfaces containing PI(4,5)P2 independently of the substrate phosphatidylcholine, suggesting a key role for the PH domain in PLD function. Importantly, a glutathione-S-transferase (GST) fusion protein comprising GST and the PH domain of PLD1 (GST-PLD1-PH) also bound specifically to supported lipid monolayers containing PI(4,5)P2. Point mutations within the PLD1 PH domain inhibited enzyme activity, whereas deletion of the domain both inhibited enzyme activity and disrupted normal PLD1 localisation. Thus, the functional PH domain regulates PLD by mediating its interaction with polyphosphoinositide-containing membranes; this might also induce a conformational change, thereby regulating catalytic activity.

Phospholipase D (PLD) activity has been shown to be GTP-dependent both in vivo and in vitro. One protein that confers GTP sensitivity to PLD activity in vitro is the low-molecular-mass G-protein ADP-ribosylation factor (Arf). However, members of the Rho family and protein kinase C (PKC) have also been reported to activate PLD in various cell systems. We have characterized the stimulation of PLD in HL60 cell membranes by these proteins. The results demonstrate that a considerable proportion of HL60 PLD activity is located in a detergent-insoluble fraction of the cell membrane that is unlikely to be a caveolae-like domain, but is probably cytoskeletal. This PLD activity required the presence of Arf1, a Rho-family member and PKC for efficient catalysis of the lipid substrate, suggesting that the activity represents PLD1. We show that recombinant human PLD1b is regulated in a similar manner to HL60-membrane PLD, and that PKCalpha and PKCdelta are equally effective PLD activators. Therefore maximum PLD activity requires Arf, a Rho-family member and PKC, emphasizing the high degree of regulation of this enzyme.

Phospholipase D has been implicated as an important enzyme in a range of cellular responses, including regulated secretion and the formation of secretory vesicles, cell proliferation and control of cell morphology. As insulin treatment of adipocytes has been shown to stimulate a phosphatidylcholine-specific phospholipase D and also modulates membrane trafficking, we wished to determine which isoform(s) of phospholipase D were present within adipocytes, to identify their subcellular distribution, and examine how this distribution may change in response to insulin. Using RT-PCR, 3T3-L1 adipocytes were found to express two isoforms of phospholipase D, specifically PLD1b and PLD2a. Using isoform-specific antibodies, PLD1 and PLD2 were found to be present predominantly in intracellular membranes, unlike the situation reported in other cells. Detailed analysis of the intracellular localisation of PLD1 and PLD2 revealed that these isoforms are differentially localised within adipocytes, implying functionally distinct roles for PLD activity in distinct subcellular compartments., (Copyright 1999 Academic Press.)

Phospholipase D (PLD) activity has been implicated in the regulation of membrane trafficking [1,2], superoxide generation and cytoskeletal remodelling [3,4]. Several PLD genes have now been identified and it is probable that different isoforms regulate distinct functions. Defining the subcellular localisation of each isoform would facilitate understanding of their roles. Previous PLD localisation studies have been based largely on enzyme activity measurements, which cannot distinguish between isoforms [2,5]. We have cloned the cDNAs encoding human PLD1a and PLD1b from an HL60 cell cDNA library and expressed them as catalytically active fusion proteins with green fluorescent protein (GFP) in COS-1 cells and RBL-2H3 cells, a mast cell model which degranulates upon cross-linking of the high-affinity immunoglobulin E (IgE) receptor. In unstimulated cells, GFP-PLD1b colocalised with secretory granule and lysosomal markers; it was not found at the plasma membrane or nucleus and did not colocalise with markers for the Golgi. Stimulation or RBL-2H3 cells through IgE receptor cross-linking caused plasma membrane recruitment of GFP-PLD1b. Inhibition of IgE-receptor-stimulated, PLD-catalysed phosphatidate formation suppressed secretion of granule and lysosomal contents, but did not affect translocation of GFP-PLD1b. These experiments suggest that PLD1 plays a role in regulated exocytosis rather than endoplasmic reticulum (ER) to Golgi membrane transport.

Phospholipase D catalyses the hydrolysis of phosphatidylcholine to generate phosphatidate. The regulation of PLD activity is complex involving a number of small GTP binding proteins, but in particular Arf and Rho, phosphatidylinositol 4,5-bisphosphate and protein kinase C. The cDNA for PLD1 has recently been cloned and shows homology to the yeast and plant genes but only within four domains. Domains I and IV each contain a putative catalytic triad. PLD activity has been detected in plasma membranes, Golgi membranes and in nuclear membranes; it is unclear if different isoenzymes are responsible for this variation, or if the PLDs are differently regulated. The product of PLD activity, PA, appears to be a messenger molecule regulating the actin cytoskeleton and maybe playing a role in the control of membrane traffic and secretion.

We have subcloned the coding sequence for the Escherichia coli lysA gene coding for diaminopimelic acid decarboxylase (DAP decarboxylase) into a eukaryotic expression vector based on the SV40 early promoter. The activities of a series of constructs with different lengths of non-coding DNA at the 5' and 3' ends of the coding region have been compared by measuring the synthesis of lysine from diaminopimelic acid (DAP) in mouse 3T3 cells. A short non-coding sequence at the 3' end reduced the expression of enzyme activity. Stable lines of 3T3 cells have been produced by co-transfection of the chimeric gene with a plasmid coding for G-418 resistance. Cells were grown in medium containing G-418 and resistant clones were screened for an ability to synthesise lysine from DAP. [3H]Lysine produced from [3H]DAP was incorporated into cell proteins. An enzyme extract from a cell line which had incorporated two copies of the gene synthesised 0.082 nmol of lysine/min per mg protein. In the intact cell the rate of lysine synthesis is limited by the uptake of DAP which is taken up at only 5% of the rate of lysine. lysA has a potential as a reporter gene in studies of gene expression in mammalian cells.