The one with the rumour: COVID-19-related conversations on Pakistani Twitter.

OBJECTIVES: The COVID-19 pandemic has been a massive crisis exacerbated by the spread of misinformation on social media. Twitter is a highly popular microblogging platform in Pakistan, and the large population there lacks digital literacy, making them vulnerable to various forms of online and digital propaganda. This study aims to analyse the content of COVID-19-related tweets from Pakistan. STUDY DESIGN: The current study is a content analysis of COVID-19-related tweets in Pakistani Twitter during the early stages of the pandemic, with a particular emphasis on misinformation, political content, health-related content, risk framing, and rumours. METHODS: The Twitter data were obtained and anonymised by a third party for this study. The selected tweets were manually coded, and the following thematic tweet categories were identified: Science, Data, Pseudoscience, Healthcare, Conspiracies, Policies and Politics, Humour, and Pandemic life. RESULTS AND CONCLUSIONS: Results indicated that the Policies and Politics category contained the majority of tweets (46.3%). Most science-based tweets focussed on nonpharmaceutical interventions (68.8%). As anticipated, the categories of Pseudoscience and Conspiracies were found to contain the most misinformation. Additionally, the number of likes and retweets for different tweet categories were compared, and no significant differences were found.

Effects of wastewater type on stability and operating conditions control strategy in relation to the formation of aerobic granular sludge - a review.

Currently, research trends on aerobic granular sludge (AGS) have integrated the operating conditions of extracellular polymeric substances (EPS) towards the stability of AGS systems in various types of wastewater with different physical and biochemical characteristics. More attention is given to the stability of the AGS system for real site applications. Although recent studies have reported comprehensively the mechanism of AGS formation and stability in relation to other intermolecular interactions such as microbial distribution, shock loading and toxicity, standard operating condition control strategies for different types of wastewater have not yet been discussed. Thus, the dimensional multi-layer structural model of AGS is discussed comprehensively in the first part of this review paper, focusing on diameter size, thickness variability of each layer and diffusion factor. This can assist in facilitating the interrelation between disposition and stability of AGS structure to correspond to the changes in wastewater types, which is the main objective and novelty of this review.

Synergic effects of cancer stem cells markers, CD44 and embryonic stem cell transcription factor Nanog, on bladder cancer prognosis.

Background: Therapy that targets cancer stem cells has the potential to eradicate cancer and prevent tumour recurrence. Therefore, we hypothesized the combined prognostic significance of stem cell markers CD44 (prevalent in basal layer of urothelial carcinoma) and Nanog (embryonic stem cell transcription factor) in bladder cancer.Material and Methods: CD44 and Nanog expression were determined by immunohistochemistry in 112 bladder cancer cases of which 79 were non-muscle invasive and 33 muscle invasive.Results: A significant correlation was found between CD44 and Nanog expression (r = 0.41, p < 0.001). The bladder cancer patients with high CD44 and Nanog expression had poor recurrence-free survival and poor overall survival (all p < 0.01). Multivariate Cox regression analysis identified lymph node positivity (hazard ratio; HR 3.81, 95% confidence interval; CI 1.66-8.75), CD44 (HR/95%CI 7.03 [3.04-16.22]) and Nanog (HR/95%CI 2.89 [1.23-6.77]) as independent prognostic biomarkers for recurrence-free survival, whilst a combined index of CD44 and Nanog expression (high expression group; HR/95%CI 25.45 [6.71-96.50] for recurrence-free survival) and lymph node positivity (HR/95%CI 3.68 [1.63-8.33] for recurrence-free survival) were independent prognostic biomarkers for recurrence-free survival and overall survival (all p < 0.001).Conclusions: A combined index of CD44 and Nanog expression is a promising prognostic predictor of recurrence-free survival and overall survival in bladder cancer. It may help identification of patients who will benefit from intensive treatment.

Are interventions to increase the uptake of screening for cardiovascular disease risk factors effective? A systematic review and meta-analysis.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death globally. However, many individuals are unaware of their CVD risk factors. The objective of this systematic review is to determine the effectiveness of existing intervention strategies to increase uptake of CVD risk factors screening. METHODS: A systematic search was conducted through Pubmed, CINAHL, EMBASE and Cochrane Central Register of Controlled Trials. Additional articles were located through cross-checking of the references list and bibliography citations of the included studies and previous review papers. We included intervention studies with controlled or baseline comparison groups that were conducted in primary care practices or the community, targeted at adult populations (randomized controlled trials, non-randomized trials with controlled groups and pre- and post-intervention studies). The interventions were targeted either at individuals, communities, health care professionals or the health-care system. The main outcome of interest was the relative risk (RR) of screening uptake rates due to the intervention. RESULTS: We included 21 studies in the meta-analysis. The risk of bias for randomization was low to medium in the randomized controlled trials, except for one, and high in the non-randomized trials. Two analyses were performed; optimistic (using the highest effect sizes) and pessimistic (using the lowest effect sizes). Overall, interventions were shown to increase the uptake of screening for CVD risk factors (RR 1.443; 95% CI 1.264 to 1.648 for pessimistic analysis and RR 1.680; 95% CI 1.420 to 1.988 for optimistic analysis). Effective interventions that increased screening participation included: use of physician reminders (RR ranged between 1.392; 95% CI 1.192 to 1.625, and 1.471; 95% CI 1.304 to 1.660), use of dedicated personnel (RR ranged between 1.510; 95% CI 1.014 to 2.247, and 2.536; 95% CI 1.297 to 4.960) and provision of financial incentives for screening (RR 1.462; 95% CI 1.068 to 2.000). Meta-regression analysis showed that the effect of CVD risk factors screening uptake was not associated with study design, types of population nor types of interventions. CONCLUSIONS: Interventions using physician reminders, using dedicated personnel to deliver screening, and provision of financial incentives were found to be effective in increasing CVD risk factors screening uptake.

Percutaneously inserted long-term central venous catheters in pigs of different sizes.

Pigs are used for long-term biomedical experiments requiring repeated injections, infusions and collections of blood samples. Thus, it is necessary for vascular catheters to be indwelling to avoid undue stress to the animals and the use of restraints. We propose a refined model of percutaneous insertion of long-term central venous catheters to minimize the surgical trauma and postoperative complications associated with catheter insertion. Different sizes of needles (18 Ga versus 21 Ga) for initial puncture of the veins were compared. In conventional pigs weighing less than 30 kg, catheter insertion may be facilitated by using a microintroducer set with a 21 Ga needle. In pigs weighing 50 kg, a standard 18 Ga needle may be preferable.

Morphological and comparative genomic analyses of pathogenic and non-pathogenic Fusarium solani isolated from Dalbergia sissoo.

Sissoo or shisham (Dalbergia sissoo Roxb.) is one of the finest wood of South Asia. Fusarium solani is a causal organism of sissoo wilt, decline, or dieback. It is also a potential causal organism associated with other valuable tree species. Thirty-eight Fusarium isolates including 24 F. solani and 14 Fusarium sp., were obtained in 2005 from different geographical locations in India. All 38 (18 pathogenic and 20 non-pathogenic) isolates were characterized for genomic analysis, growth behaviour, pigmentation and sensitivity to carbendazim. Based on growth pattern, growth rate, pigmentation and sensitivity to carbendazim, all 38 isolates showed a wide range of variability, but no correlation with pathogenicity or geographical distribution. Three techniques were used for comparative genomic analysis: random amplified polymorphic DNA (RAPD); inter simple sequence repeats (ISSR); and simple sequence repeats (SSR). A total of 90 primers targeting different genome regions resulted a total of 1159 loci with an average of 12.88 loci per primer. These primers showed high genomic variability among the isolates. The maximum loci (14.64) per primer were obtained with RAPD. The total variation of the first five principal components for RAPD, ISSR, SSR and combined analysis were estimated as 47.42, 48.21, 46.30 and 46.78 %, respectively. Among the molecular markers, highest Pearson correlation value (r = 0.957) was recorded with combination of RAPD and SSR followed by RAPD and ISSR (r = 0.952), and SSR and ISSR (r = 0.942). The combination of these markers would be similarly effective as single marker system i.e. RAPD, ISSR and SSR. Based on polymorphic information content (PIC = 0.619) and highest coefficient (r = 0.995), RAPD was found to be the most efficient marker system compared to ISSR and SSR. This study will assist in understanding the population biology of wilt causing phytopathogen, F. solani, and in assisting with integrated disease management measures.

Cardioversion in late pregnancy: a case report.

About 1% of all pregnancies are complicated by maternal cardiac diseases. Among the various cardiac pathologies complicating pregnancy, arrhythmias are the most common. Most of them are diagnosed for the first time during pregnancy. Tachyarrhythmias are the commonest form of arrhythmias reported during pregnancy. Risk factors for this are the presence of organic heart disease, various hormonal and hemodynamic changes during pregnancy. Fortunately most of these arrhythmias are benign and require no intervention. Treatment options must take into consideration hemodynamic status of mother, gestational age and the possible teratogenic effect of medications on the fetus. We are hereby reporting a case of successful electrical cardioversion performed in a woman at 37th week of gestation due to resistant symptomatic atrial fibrillation.

Characterization and biocontrol potential of entomopathogenic fungus, Beauveria bassiana isolates against Spilarctia obliqua.

Beauveria bassiana is a known natural enemy of a number of insect pests of crop plants. In order to screen different isolates of any given entomopathogens molecular markers provide a means for constructing the molecular phylogeny, diversity and link to virulent phenotypes. Eight isolates of B. bossiona isolated from different insect hosts and from different location at Pantnagar (Uttrakhand) were characterized by PCR-based RAPD markers. Bioassays were conducted by using first, second and third instar larvae of Spilarctia oblique in order to categorize the isolates based on virulence. The isolates were arbitrarily rated as more virulent, moderately virulent and less virulent based on the speed of killing. A wide range of variation in virulence was observed and the isolates of same insect origin and location showed differences in their aggressiveness. No correlation was found between the pathogenicity of the isolates and the relatedness of the original insect host. The pathogenicity against first, second and third instar larva of Spilarctia obliqua did not reveal any relatedness with the clustering pattern.

PCR-Based Identification and Characterization of Fusarium sp. Associated with Mango Malformation.

Mango malformation is the most serious disease of mango causing considerable damage to the mango orchards worldwide. It is a major threat for mango cultivation in north Indian belt. In recent years, Fusarium sp. is finding wide acceptability in scientific community as a causal agent of this disease. However, little information is known about the variability in Fusarium isolates from malformed mango tissues. Therefore, the major objective of present study was the identification and analysis of genetic diversity among Fusarium isolates collected from malformed mango tissues. Two texon selective primers, ITS-Fu-f and ITS-Fu-r, were used for quick identification of Fusarium spp. The fungal genomic DNA was extracted from using CTAB method and was utilized as template for PCR amplification. Total 224 bands were amplified by 18 RAPD primers at an average of 12.44 bands per primer. The size of the obtained amplicons ranged from 0.264 kb (minimum) to 3.624 kb (maximum). Data scored from 25 isolates of Fusarium sp. with 18 RAPD primers were used to generate similarity coefficients. The similarity coefficient ranged from 0.17 to 0.945. Based on DNA fingerprints, all isolates were categorized into two major clusters. This study indicated a wide variability among different isolates of Fusarium.

High-risk behaviours among juvenile prison inmates in Pakistan.

OBJECTIVES: To assess the sexual- and drug-use-related risk behaviours of male juvenile detainees in Karachi, Pakistan. DESIGN: Cross-sectional study. METHODS: A cross-sectional study was conducted of prison inmates aged 15-21 years in Karachi Juvenile Prison in 2002. In total, 321 inmates were interviewed about sexual orientation and behaviours, and knowledge about human immunodeficiency virus (HIV) and sexually transmitted infections (STIs). Urine specimens were collected and tested for Chlamydia trachomatis and Neisseria gonorrhoeae using ligase chain reaction. RESULTS: A substantial proportion (n=111, 34.6%) of the participants were sexually active. Sixty-two (19%) and 67 (21%) had had sex with a male or female before incarceration, respectively. Twenty-seven (8.4%) participants had an STI, and 50% of the 109 sexually active participants had had multiple sexual partners. Use of addictive substances was associated with sexual activity. The mean knowledge score computed from the sum of 16 items was 4.7, with a median of 2.9. A large proportion (40%) of participants knew about condoms, but very few (3.4%) had ever used one. The mean+/-standard deviation risk score from nine items was 2.4+/-1.7. On the basis of behavioural and biological markers, 117 (36.4%) participants had high-risk behaviour. In multivariate logistic regression analysis, knowledge, risk perception and age were predictive of higher risk. CONCLUSIONS: HIV risk behaviours are common among adolescent inmates. Although inmates do have knowledge about modes of transmission and condom use, the use of condoms is significantly low. Interventions are needed for behavioural change among this group.

Knowledge of female genital mutilation among healthcare professionals.

The World Health Organisation estimates that 2 million women undergo some form of female genital mutilation (FGM) annually. Because of increasing migration, clinicians in the UK are increasingly exposed to women who have suffered FGM. Recognising this trend, the RCOG has set standards for guidance of health professionals caring for women with FGM. As yet, no study has assessed levels of knowledge of FGM among relevant health professionals. An anonymous structured questionnaire based on the Royal College of Obstetricians and Gynaecologists' standards was circulated among staff at a University Teaching Hospital. A total of 45 participants completed the questionnaire. Only 40% were familiar with the regulations in the FGM Act of 2003; 58% were unable to list the different categories of FGM; 47% incorrectly thought that caesarean section is the best way of managing FGM if vaginal examination is not possible in the first stage of labour and 54% chose anterior episiotomy as the treatment of choice during the second stage. Our study found that there were significant gaps both in theoretical knowledge and practice.

Phosphorylation of calsenilin at Ser63 regulates its cleavage by caspase-3.

Calsenilin is a member of the neuronal calcium sensor (NCS) family of proteins that interacts with the presenilins. Calsenilin has been found to act as a Kv4alpha channel interactor and as a transcriptional repressor. We have recently shown that calsenilin can be cleaved by caspase-3 and that its cleavage separates the conserved calcium-binding domain from the variable N-terminal domain. Here, we demonstrate that calsenilin can be phosphorylated by casein kinase I and that its phosphorylation can be regulated by intracellular calcium. In addition, phosphorylated calsenilin is a substrate for serine/threonine protein phosphatase (PP) 1 and/or 2A. Phosphorylation within the N-terminal domain at Ser63, the major phosphorylation site of calsenilin, inhibits cleavage of the molecule by caspase-3. Given that the N-terminal domain of calsenilin is not conserved in the larger NCS family including other KChIP/CALP proteins, phosphorylation of calsenilin may regulate a functional role that is unique to this member of the superfamily.

Oestrogen receptor transcripts associated with cervical human papillomavirus infection.

OBJECTIVE: Studies have been inconsistent in establishing sex steroids as a risk factor for human papillomavirus (HPV) infections. This study was designed to determine whether cervical oestrogen receptors (as measured by oestrogen receptor transcripts) at the cervix would be associated with cervical HPV infections. METHODS: In 175 women, ages 14-44, we tested for the presence of HPV DNA and oestrogen receptors transcripts at the cervix during routine pelvic examinations. All subjects completed a self administered questionnaire regarding sexual and menstrual histories. RESULTS: 40% of the women (n=70) tested positive for HPV at the cervix. Of those women testing positive for HPV, 99% had detectable levels of Oestrogen receptors transcripts (n=69/70). HPV cervical infections were independently associated with presence of Oestrogen receptors transcripts (OR=39.8, CI=4.4, 361.1) and greater numbers of sexual partners (OR=1.1, CI=1.01, 1.18). CONCLUSION: Women who expressed higher levels of oestrogen receptors transcripts were significantly more likely to have cervical HPV infection. These results demonstrate that Oestrogen receptors may play an important part in cervical HPV infections.

Biochemical and immunocytochemical characterization of calsenilin in mouse brain.

Mutations in the presenilin 1 and 2 genes cause the majority of early onset familial forms of Alzheimer's disease. Here we describe the biochemical and immunohistochemical characterization of calsenilin, a novel calcium binding protein that we have previously shown to interact with presenilins 1 and 2, in mouse brain. The co-immunoprecipitation of endogenous calsenilin and presenilin 1 demonstrates that these proteins are physiologic binding partners. Although calsenilin has been predicted to be a soluble protein, we have found that the majority of it is tightly associated with the cytoplasmic face of intracellular membranes and that it can only be dissociated using harsh treatments such as urea. In addition, we have demonstrated that calsenilin is a developmentally regulated protein that is mainly present in the brain, where it localizes to both the hippocampus and cerebellum. Calsenilin staining co-localized with the somatodendritic marker microtubule-associated protein-2 primarily in the granular cell layer of the cerebellum, indicating that calsenilin expression is primarily neuronal. In primary cultured neurons, calsenilin immunoreactivity was observed in cell bodies as well as in some neuronal processes. Co-localization experiments using specific axonal and dendritic markers indicate that these processes were mainly axonal in nature, although a smaller subset of dendrites also appears to contain calsenilin. In summary, we have established that calsenilin and presenilin 1 can interact at physiologic levels, and that calsenilin is a developmentally regulated protein that is expressed primarily in the cerebellum and hippocampus. Although calsenilin is a soluble protein, it is tightly associated with the membrane. Finally, the expression pattern of calsenilin, which is similar to that of the presenilin(s), suggests that the common locations of these two proteins provide an opportunity for physical interaction in vivo.

Calsenilin enhances apoptosis by altering endoplasmic reticulum calcium signaling.

Calsenilin (also called DREAM and KChIP3), a member of the neuronal calcium sensor family, was isolated in a yeast two-hybrid screen using an apoptotic domain of presenilin 2 as bait. Calsenilin is a cytoplasmic protein, but interacts with the COOH-termini of both presenilin 1 and presenilin 2 at the endoplasmic reticulum and the Golgi apparatus. In this study, we have investigated calsenilin's effect on apoptosis. In stable neuroglioma cell lines, we observed that calsenilin enhances apoptosis in response to serum withdrawal or thapsigargin. Consistent with these observations, caspase and apparently calpain activities were increased during apoptosis in calsenilin-overexpressing cells. Moreover, using calcium imaging we were able to show that cells treated with thapsigargin released more calcium from intracellular stores when calsenilin was overexpressed. Taken together, these data suggest that calsenilin causes cells to be more susceptible to apoptotic triggers, possibly by altering calcium dynamics.

Identification and characterization of a sodium/calcium exchanger, NCX-1, in osteoclasts and its role in bone resorption.

We provide the first demonstration for a Na+/Ca2+ exchanger, NCX-1, in the osteoclast. We speculate that by using Na+ exchange, NCX-1 couples H+ extrusion with Ca2+ fluxes during bone resorption. Microspectrofluorimetry of fura-2-loaded osteoclasts revealed a rapid and sustained, but reversible, cytosolic Ca2+ elevation upon Na+ withdrawal. This elevation was abolished by the cytosolic introduction (by gentle permeabilization) of a highly specific Na+/Ca2+ exchange inhibitor peptide, XIP, but not its inactive analogue, sXIP. Confocal microscopy revealed intense plasma membrane immunofluorescence with an isoform-specific monoclonal anti-NCX-1 antibody applied to gently permeabilized osteoclasts. Electrophysiological studies using excised outside-in membrane patches showed a low-conductance, Na+-selective, dichlorobenzamil-sensitive, amiloride-insensitive channel that we tentatively assigned as being an NCX. Finally, to examine for physiological relevance, an osteoclast resorption (pit) assay was performed. There was a dramatic reduction of bone resorption following NCX-1 inhibition by dichlorobenzamil and XIP (but not with S-XIP). Together, the results suggest that a functional NCX, likely NCX-1, is involved in the regulation of osteoclast cytosolic Ca2+ and bone resorption.

Calsenilin is a substrate for caspase-3 that preferentially interacts with the familial Alzheimer's disease-associated C-terminal fragment of presenilin 2.

Calsenilin is a member of the recoverin family of neuronal calcium-binding proteins that we have previously shown to interact with presenilin 1 (PS1) and presenilin 2 (PS2) holoproteins. The expression of calsenilin can regulate the levels of a proteolytic product of PS2 (Buxbaum, J. D., Choi, E. K., Luo, Y., Lilliehook, C., Crowley, A. C., Merriam, D. E., and Wasco, W. (1998) Nat. Med. 4, 1177-1181) and reverse the presenilin-mediated enhancement of calcium signaling (Leissring, M. A., Yamasaki, T. R., Wasco, W., Buxbaum, J. D., Parker, I., and LaFerla, F. M. (2000) Proc. Natl. Acad. Sci. U. S. A. 97, 8590-8593). Here, we have used cultured mammalian cells that transiently or stably express calsenilin to extend the characterization of calsenilin and of the calsenilin-PS2 interaction. We have found that calsenilin has the ability to interact with endogenous 25-kDa C-terminal fragment (CTF) that is a product of regulated endoproteolytic cleavage of PS2 and that the presence of the N141I PS2 mutation does not significantly alter the interaction of calsenilin with PS2. Interestingly, when the 25-kDa PS2 CTF and the 20-kDa PS2 CTF are both present, calsenilin preferentially interacts with the 20-kDa CTF. Increases in the 20-kDa fragment are associated with the presence of familial Alzheimer's disease-associated mutations (Kim, T., Pettingell, W. H., Jung, Y., Kovacs, D. M., and Tanzi, R. E. (1997) Science 277, 373-376). However, the finding that the production of the 20-kDa fragment is regulated by the phosphorylation of PS2 (Walter, J., Schindzielorz, A., Grunberg, J., and Haass, C. (1999) Proc. Natl. Acad. Sci. U. S. A. 96, 1391-1396) suggests that it is a regulated physiological event that also occurs in the absence of the familial Alzheimer's disease-associated mutations in PS2. Finally, we have demonstrated that calsenilin is a substrate for caspase-3, and we have used site-directed mutagenesis to map the caspase-3 cleavage site to a region that is proximal to the calcium binding domain of calsenilin.

Comparison of thiopentone sodium and propofol for electro convulsive therapy (ECT).

OBJECTIVE: For safe conduct of electro convulsive therapy (ECT), general anaesthesia is administered to the patients. In this study we compared thiopentone sodium and propofol as induction agents for ECT. PATIENTS AND METHODS: Twenty five patients each undergoing at least 2 sessions of ECT at the psychiatry department were included in the study. Each patient either received thiopentone or propofol for induction of sleep in a randomized manner. Drugs were evaluated regarding their effects on ECT induced haemodynamic changes (Blood pressure, Heart rate), seizure duration related to the procedure and recovery from sleep. Any side effects during the procedure and recovery were also noted. RESULTS: Propofol offered a superior haemodynamic stability during the procedure and a quick recovery from sleep. CONCLUSION: Propofol was found to be a better induction agent for ECT compared to thiopentone sodium.

Outbreak of Crimean-Congo haemorrhagic fever in Quetta, Pakistan: contact tracing and risk assessment.

In December 1994 in a private hospital in Quetta, Pakistan, 3 health-workers contracted Crimean-Congo haemorrhagic fever (CCHF) after surgery on a bleeding patient who later died. We conducted a retrospective study to determine transmission risks among contacts. Fifty contacts gave blood for antibody tests and answered questions about exposure. Two of four people exposed percutaneously and one of five with cutaneous exposure contracted CCHE The person with cutaneous exposure was a surgeon who tore his glove during surgery and noted blood on his hand but no cut. There were no anti-CCHF antibodies or CCHF cases among persons whose skin came into contact with body fluids other than blood (0/4), who had skin-to-skin contact (0/16) with patients or were physically close to them (0/21). Three index case relatives reported that although 10 family members had cutaneous exposure, none developed CCHF. The family refused blood tests. CCHF transmission in resource-constrained settings can be limited by focusing on avoiding health worker contact with blood.