Knowledge, attitude and practices regarding dengue and its vector among medical practitioners in Malakand region, Pakistan

Abstract Dengue fever (DF) is increasingly recognized as one of the worlds major mosquito borne diseases and causes significant morbidity and mortality in tropical and subtropical countries. Dengue fever is endemic in most part of Pakistan and continues to be a public health concern. Knowledge, attitude and practices can play an important role in management of the disease. Current study was aimed to determine the level of knowledge, attitude and practices regarding dengue fever among health practitioners, to study the level of knowledge and attitude with preventive practices for dengue fever. A cross sectional study was carried out in medical practitioners of the four districts of Malakand region during October to November 2019. A pre-structured questionnaire was used to collect data from medical practitioners. Data was analyzed using Graph Pad version 5. Significant value was considered when less than 0.05 (at 95% confidence of interval). The results revealed that most of participants have seen dengue vector (62%), the media being the most quoted source of information. Nearly 81.2% participants were aware from transmission of dengue fever is by mosquito bite. Practices based upon preventive measures were found to be predominantly focused towards prevention of mosquito bites rather than elimination of breeding places. Although the knowledge regarding DF and mosquito control measure was quite high among the medical practitioners but this knowledge was not put into practice. Further studies are required to aware the people about dengue and its vector in order to get prevention and control.

Resumo A dengue (DF) é cada vez mais reconhecida como uma das principais doenças transmitidas por mosquitos do mundo e causa significativa morbidade e mortalidade em países tropicais e subtropicais. A dengue é endêmica na maior parte do Paquistão e continua a ser um problema de saúde pública. Conhecimento, atitude e práticas podem desempenhar papel importante no manejo da doença. O presente estudo teve como objetivo determinar o nível de conhecimento, atitude e práticas em relação à dengue entre os profissionais de saúde, para estudar o nível de conhecimento e atitude com as práticas preventivas da dengue. Um estudo transversal foi realizado com médicos dos quatro distritos da região de Malakand de outubro a novembro de 2019. Um questionário pré-estruturado foi usado para coletar dados de médicos. Os dados foram analisados no Graph Pad versão 5. Valor significativo foi considerado quando menor que 0,05 (com intervalo de confiança de 95%). Os resultados revelaram que a maioria dos participantes já viu o vetor da dengue (62%), sendo a mídia a fonte de informação mais citada. Quase 81,2% dos participantes sabiam que a transmissão da dengue é por picada de mosquito. Constatou-se que as práticas baseadas em medidas preventivas se concentravam predominantemente na prevenção de picadas de mosquitos, e não na eliminação de criadouros. Embora o conhecimento sobre DF e medidas de controle de mosquitos fosse bastante elevado entre os médicos, esse conhecimento não foi colocado em prática. Mais estudos são necessários para conscientizar a população sobre a dengue e seu vetor, a fim de se obter prevenção e controle.

Knowledge, attitude and practices regarding dengue and its vector among medical practitioners in Malakand region, Pakistan.

Dengue fever (DF) is increasingly recognized as one of the world's major mosquito borne diseases and causes significant morbidity and mortality in tropical and subtropical countries. Dengue fever is endemic in most part of Pakistan and continues to be a public health concern. Knowledge, attitude and practices can play an important role in management of the disease. Current study was aimed to determine the level of knowledge, attitude and practices regarding dengue fever among health practitioners, to study the level of knowledge and attitude with preventive practices for dengue fever. A cross sectional study was carried out in medical practitioners of the four districts of Malakand region during October to November 2019. A pre-structured questionnaire was used to collect data from medical practitioners. Data was analyzed using Graph Pad version 5. Significant value was considered when less than 0.05 (at 95% confidence of interval). The results revealed that most of participants have seen dengue vector (62%), the media being the most quoted source of information. Nearly 81.2% participants were aware from transmission of dengue fever is by mosquito bite. Practices based upon preventive measures were found to be predominantly focused towards prevention of mosquito bites rather than elimination of breeding places. Although the knowledge regarding DF and mosquito control measure was quite high among the medical practitioners but this knowledge was not put into practice. Further studies are required to aware the people about dengue and its vector in order to get prevention and control.

Pseudomonas aeruginosa infection in augmented care: the molecular ecology and transmission dynamics in four large UK hospitals.

BACKGROUND: Pseudomonas aeruginosa is a common opportunistic pathogen and molecular typing in outbreaks has linked patient acquisition to contaminated hospital water systems. AIM: To elucidate the role of P. aeruginosa transmission rates in non-outbreak augmented care settings in the UK. METHODS: Over a 16-week period, all water outlets in augmented care units of four hospitals were sampled for P. aeruginosa and clinical isolates were collected. Outlet and clinical P. aeruginosa isolates underwent whole-genome sequencing (WGS), which with epidemiological data identified acquisition from water as definite (level 1), probable (level 2), possible (level 3), and no evidence (level 4). FINDINGS: Outlets were positive in each hospital on all three occasions: W (16%), X (2.5%), Y (0.9%) and Z (2%); and there were 51 persistently positive outlets in total. WGS identified likely transmission (at levels 1, 2 and 3) from outlets to patients in three hospitals for P. aeruginosa positive patients: W (63%), X (54.5%) and Z (26%). According to the criteria (intimate epidemiological link and no phylogenetic distance), approximately 5% of patients in the study 'definitely' acquired their P. aeruginosa from their water outlets in the intensive care unit. This study found extensive evidence of transmission from the outlet to the patients particularly in the newest hospital (W), which had the highest rate of positive outlets. CONCLUSIONS: The overall findings suggest that water outlets are the most likely source of P. aeruginosa nosocomial infections in some settings, and that widespread introduction of control measures would have a substantial impact on infections.

Analysis of single nucleotide polymorphisms implicate mTOR signalling in the development of new-onset diabetes after transplantation.

INTRODUCTION: Despite excellent first year outcomes in kidney transplantation, there remain significant long-term complications related to new-onset diabetes after transplantation (NODAT). The purpose of this study was to validate the findings of previous investigations of candidate gene variants in patients undergoing a protocolised, contemporary immunosuppression regimen, using detailed serial biochemical testing to identify NODAT development. METHODS: One hundred twelve live and deceased donor renal transplant recipients were prospectively followed-up for NODAT onset, biochemical testing at days 7, 90, and 365 after transplantation. Sixty-eight patients were included after exclusion for non-white ethnicity and pre-transplant diabetes. Literature review to identify candidate gene variants was undertaken as described previously. RESULTS: Over 25% of patients developed NODAT. In an adjusted model for age, sex, BMI, and BMI change over 12 months, five out of the studied 37 single nucleotide polymorphisms (SNPs) were significantly associated with NODAT: rs16936667:PRDM14 OR 10.57;95% CI 1.8-63.0;p = 0.01, rs1801282:PPARG OR 8.5; 95% CI 1.4-52.7; p = 0.02, rs8192678:PPARGC1A OR 0.26; 95% CI 0.08-0.91; p = 0.03, rs2144908:HNF4A OR 7.0; 95% CI 1.1-45.0;p = 0.04 and rs2340721:ATF6 OR 0.21; 95%CI 0.04-1.0; p = 0.05. CONCLUSION: This study represents a replication study of candidate SNPs associated with developing NODAT and implicates mTOR as the central regulator via altered insulin sensitivity, pancreatic ß cell, and mitochondrial survival and dysfunction as evidenced by the five SNPs. GENERAL SIGNIFICANCE: 1)Highlights the importance of careful biochemical phenotyping with oral glucose tolerance tests to diagnose NODAT in reducing time to diagnosis and missed cases.2)This alters potential genotype:phenotype association.3)The replication study generates the hypothesis that mTOR signalling pathway may be involved in NODAT development.

Cytomegalovirus-Associated CD4(+) CD28(null) Cells in NKG2D-Dependent Glomerular Endothelial Injury and Kidney Allograft Dysfunction.

Emerging data suggest that expansion of a circulating population of atypical, cytotoxic CD4(+) T cells lacking costimulatory CD28 (CD4(+) CD28(null) cells) is associated with latent cytomegalovirus (CMV) infection. The purpose of the current study was to increase the understanding of the relevance of these cells in 100 unselected kidney transplant recipients followed prospectively for a median of 54 months. Multicolor flow cytometry of peripheral blood mononuclear cells before transplantation and serially posttransplantation was undertaken. CD4(+) CD28(null) cells were found predominantly in CMV-seropositive patients and expanded in the posttransplantation period. These cells were predominantly effector-memory phenotype and expressed markers of endothelial homing (CX3CR1) and cytotoxicity (NKG2D and perforin). Isolated CD4(+) CD27(-) CD28(null) cells proliferated in response to peripheral blood mononuclear cells previously exposed to CMV-derived (but not HLA-derived) antigens and following such priming incubation with glomerular endothelium resulted in signs of endothelial damage and apoptosis (release of fractalkine and von Willebrand factor; increased caspase 3 expression). This effect was mitigated by NKG2D-blocking antibody. Increased CD4(+) CD28(null) cell frequencies were associated with delayed graft function and lower estimated glomerular filtration rate at end follow-up. This study suggests an important role for this atypical cytotoxic CD4(+) CD28(null) cell subset in kidney transplantation and points to strategies that may minimize the impact on clinical outcomes.

Transitional B lymphocytes are associated with protection from kidney allograft rejection: a prospective study.

Recent cross-sectional studies suggest an important role for transitional B lymphocytes (CD19 + CD24hiCD38hi) in promoting transplant tolerance, and protecting from late antibody-mediated rejection (ABMR). However, prospective studies are lacking. This study enrolled 73 de novo transplant recipients, and collected serial clinical, immunological and biochemical information over 48 ± 6 months. Cell phenotyping was conducted immediately prior to transplantation, and then on five occasions during the first year posttransplantation. When modeled as a time-dependent covariate, transitional B cell frequencies (but not total B cells or "regulatory" T cells) were associated with protection from acute rejection (any Banff grade; HR: 0.60; 95% CI: 0.37-0.95; p = 0.03). No association between transitional B cell proportions and either de novo donor-specific or nondonor-specific antibody (dnDSA; dnNDSA) formation was evident, although preserved transitional B cell proportions were associated with reduced rejection rates in those patients developing dnDSA. Three episodes of ABMR occurred, all in the context of nonadherence, and all associated with in vitro anti-HLA T cell responses in an ELISPOT assay (p = 0.008 versus antibody-positive patients not experiencing ABMR). This prospective study supports the potential relevance of transitional ("regulatory") B cells as a biomarker and therapeutic intervention in transplantation, and highlights relationships between humoral immunity, cellular immunity and nonadherence.

Fewer adverse events after reoperative parathyroidectomy associated with initial minimally invasive parathyroidectomy.

BACKGROUND: This study compared reoperative complication rates after initial minimally invasive parathyroidectomy and standard cervical exploration. METHODS: Records from patients who underwent 1 reoperative parathyroidectomy at a single institution (1998 to 2012) were retrospectively reviewed. RESULTS: Seventy-seven patients were included; 74% underwent initial standard cervical exploration. Preoperative and operative characteristics were similar between groups; 74% underwent focused, unilateral reoperation. A significantly higher rate of postoperative complications occurred in the initial standard cervical exploration group (42% vs 15%, P = .03) that could not be explained by differences in the rates of symptomatic hypocalcemia (P = .5). The type of prior parathyroidectomy was significantly associated with postoperative complications (odds ratio 4.1, 95% confidence interval 1.1 to 15.7, P = .04). In a multivariable logistic regression model that included body mass index, type of operation (for initial and reoperation), and initial operation performed prereferral as covariates, type of prior parathyroidectomy remained a significant predictor of postoperative complications. CONCLUSION: Higher rates of postoperative sequelae after initial standard cervical exploration should be considered before performing routine 4-gland exploration.

The importance of Rho-associated kinase-induced Ca2+ sensitization as a component of electromechanical and pharmacomechanical coupling in rat ureteric smooth muscle.

Ureteric peristalsis, which occurs via alternating contraction and relaxation of ureteric smooth muscle, ensures the unidirectional flow of urine from the kidney to the bladder. Understanding of the molecular mechanisms underlying ureteric excitation-contraction coupling, however, is limited. To address these knowledge deficits, and in particular to test the hypothesis that Ca2+ sensitization via activation of the RhoA/Rho-associated kinase (ROK) pathway plays an important role in ureteric smooth muscle contraction, we carried out a thorough characterization of the electrical activity, Ca2+ signaling, MYPT1 (myosin targeting subunit of myosin light chain phosphatase, MLCP) and myosin regulatory light chain (LC20) phosphorylation, and force responses to membrane depolarization induced by KCl (electromechanical coupling) and carbachol (CCh) (pharmacomechanical coupling). The effects of ROK inhibition on these parameters were investigated. We conclude that the tonic, but not the phasic component of KCl- or CCh-induced ureteric smooth muscle contraction is highly dependent on ROK-catalyzed phosphorylation of MYPT1 at T855, leading to inhibition of MLCP and increased LC20 phosphorylation.

Rho-kinase inhibition and electromechanical coupling in rat and guinea-pig ureter smooth muscle: Ca2+-dependent and -independent mechanisms.

Recent data have shown Ca(2+)-dependent activation of Rho-kinase by sustained depolarization of arterial smooth muscle. Visceral smooth muscles, however, contract phasically in response to action potentials and it is unclear whether Ca(2+)-dependent or -independent Rho-kinase activation occurs. We have therefore investigated this, under physiologically relevant conditions, in intact ureter. Action potentials, ionic currents, Ca(2+) transients, myosin light chain (MLC) phosphorylation and phasic contraction evoked by action potentials in guinea-pig and rat ureter were investigated. In rat, but not guinea-pig ureter, three Rho-kinase inhibitors, Y-27632, HA-1077 and H-1152, significantly decreased phasic contractions and Ca(2+) transients. Voltage- and current-clamp data showed that Rho-kinase inhibition reduced the plateau component of the action potential, inhibited Ca(2+)-channels and, indirectly, Ca(2+)-activated Cl(-) channels. The Ca(2+) channel agonist Bay K8644 could reverse these effects. The K(+) channel blocker TEA could also reverse the inhibitory effect of Y-27632 on the action potential and Ca(2+) transient. Ca(2+) transients and inward current, activated by carbachol-induced sarcoplasmic reticulum Ca(2+)release, were not affected by Rho-kinase inhibition. Rho-kinase inhibition produced a Ca(2+)-independent increase in the relaxation rate of contraction, associated with acceleration of MLC dephosphorylation, which was sensitive to calyculin A. These data show for the first time that: (1) Rho-kinase has major effects on Ca(2+) signalling associated with the action potential, (2) this effect is species dependent and (3) Rho-kinase controls relaxation of phasic contraction of myogenic origin. Thus Rho-kinase can modulate phasic smooth muscle in the absence of agonist, and the mechanisms are both Ca(2+)-dependent, involving ion channels, and Ca(2+)-independent, involving MLC phosphorylation activity.

The synaptic glycoprotein neuroplastin is involved in long-term potentiation at hippocampal CA1 synapses.

Neuroplastin-65 and -55 (previously known as gp65 and gp55) are glycoproteins of the Ig superfamily that are enriched in rat forebrain synaptic membrane preparations. Whereas the two-Ig domain isoform neuroplastin-55 is expressed in many tissues, the three-Ig domain isoform neuroplastin-65 is brain-specific and enriched in postsynaptic density (PSD) protein preparations. Here, we have assessed the function of neuroplastin in long-term synaptic plasticity. Immunocytochemical studies with neuroplastin-65-specific antibodies differentially stain distinct synaptic neuropil regions of the rat hippocampus with most prominent immunoreactivity in the CA1 region and the proximal molecular layer of the dentate gyrus. Kainate-induced seizures cause a significant enhancement of neuroplastin-65 association with PSDs. Similarly, long-term potentiation (LTP) of CA1 synapses in hippocampal slices enhanced the association of neuroplastin-65 with a detergent-insoluble PSD-enriched protein fraction. Several antibodies against the neuroplastins, including one specific for neuroplastin-65, inhibited the maintenance of LTP. A similar effect was observed when recombinant fusion protein containing the three extracellular Ig domains of neuroplastin-65 was applied to hippocampal slices before LTP induction. Microsphere binding experiments using neuroplastin-F(c) chimeric proteins show that constructs containing Ig1-3 or Ig1 domains, but not Ig2-3 domains mediate homophilic adhesion. These data suggest that neuroplastin plays an essential role in implementing long-term changes in synaptic activity, possibly by means of a homophilic adhesion mechanism.

Diet-induced enhancement of naloxone sensitivity is independent of changes in body weight.

Intake of palatable solutions can enhance the anorectic potency of opioid antagonists. This experiment examined the relative contributions of orosensory experience and body weight gain to the enhanced anorectic potency of naloxone (0.125, 0.25, 0.5, and 1.0 mg/kg i.p.). Four groups of male hooded Lister rats (Charles River) were maintained on separate feeding regimes for 3 months. S-ADLIB rats were nondeprived with free access to lab chow and 20% (w/v) sucrose solution. S-RESTRICT rats received limited sucrose (50 ml/day) and chow (15 g/day) access, yoking their body weights to ADLIB rats receiving free access to lab chow only. RESTRICT rats received approx. 15 g of chow/day to maintain their body weights at 90% of the ADLIB rats. Fifteen-minute sucrose intake tests revealed marked differences between naloxone sensitivity of chronic sucrose drinkers and sucrose-naive groups. Intakes of S-ADLIB and S-RESTRICT were suppressed at all doses (max suppression >60%). In comparison to animals given sucrose, ADLIB and RESTRICT animals were significantly less sensitive (maximum suppression = 35%). Naloxone potency was independent of body weight differences. The data demonstrate that overconsumption of palatable ingesta, and not diet-induced weight gain, is sufficient to enhance antagonist potency. The study confirms that orosensory stimulation can induce plasticity in opioid systems, supporting an important role for opioids in intake regulation and general reward processes.