Distinct inflammatory markers in primary and secondary dengue infection: can cytokines CXCL5, CXCL9, and CCL17 act as surrogate markers?

Dengue fever poses a significant global health threat, with symptoms including dengue hemorrhagic fever and dengue shock syndrome. Each year, India experiences fatal dengue outbreaks with severe manifestations. The primary cause of severe inflammatory responses in dengue is a cytokine storm. Individuals with a secondary dengue infection of a different serotype face an increased risk of complications due to antibody-dependent enhancement. Therefore, it is crucial to identify potential risk factors and biomarkers for effective disease management. In the current study, we assessed the prevalence of dengue infection in and around Aligarh, India, and explored the role of cytokines, including CXCL5, CXCL9, and CCL17, in primary and secondary dengue infections, correlating them with various clinical indices. Among 1,500 suspected cases, 367 tested positive for dengue using Real-Time PCR and ELISA. In secondary dengue infections, the serum levels of CXCL5, CXCL9, and CCL17 were significantly higher than in primary infections (P < 0.05). Dengue virus (DENV)-2 showed the highest concentrations of CXCL5 and CCL17, whereas DENV-1 showed the highest concentrations of CXCL9. Early detection of these cytokines could serve as potential biomarkers for diagnosing severe dengue, and downregulation of these cytokines may prove beneficial for the treatment of severe dengue infections.

Amelioration of tableting properties and dissolution rate of naproxen co-grinded with nicotinamide: preparation and characterization of co-grinded mixture.

OBJECTIVE AND SIGNIFICANCE: Reducing the dimensions, when other additives are present, shows potential as a method to improve the dissolution and solubility of biopharmaceutical classification system class II drugs that have poor solubility. In this investigation, the process involved grinding naproxen with nicotinamide with the aim of improving solubility and the rate of dissolution. METHODS: Naproxen was subjected to co-milling with urea, dimethylurea, and nicotinamide using a planetary ball mill for a duration of 90 min, maintaining a 1:1 molar ratio for the excipients (screening studies). The co-milled combinations, naproxen in its pure milled form, and a physical mixture were subjected to analysis using X-ray powder diffraction (XRPD), scanning electron microscopy (SEM), and solubility assessment. The mixture displaying the highest solubility (naproxen-nicotinamide) was chosen for further investigation, involving testing for intrinsic dissolution rate (IDR) and Fourier-transform infrared spectroscopy (FTIR) after co-milling for both 90 and 480 min. RESULTS AND CONCLUSION: The co-milled combination, denoted as S-3b and consisting of the most substantial ratio of nicotinamide to naproxen at 1:3, subjected to 480 min of milling, exhibited a remarkable 45-fold increase in solubility and a 9-fold increase in IDR. XRPD analysis of the co-milled samples demonstrated no amorphization, while SEM images portrayed the aggregates of naproxen with nicotinamide. FTIR outcomes negate the presence of any chemical interactions between the components. The co-milled sample exhibiting the highest solubility and IDR was used to create a tablet, which was then subjected to comprehensive evaluation for standard attributes. The results revealed improved compressibility and dissolution properties.

Insight into the seroepidemiology and dynamics of circulating serotypes of dengue virus over a 4 year period in western Uttar Pradesh, India.

An important public health problem in India is dengue infection, with every year seeing an increase in cases of dengue fever. Dengue affects all individuals irrespective of their gender and age, although the infection rate is higher among males and younger people. Despite low severity in general, dengue virus can cause severe health conditions in some individuals. Genetic characterization of circulating endemic dengue virus (DENV) serotypes plays a significant role in providing epidemiological knowledge and subsequent vaccine development. In the present study, over a 4 year period, we assessed DENV transmission dynamics in major regions of western Uttar Pradesh in North India. ELISA tests were used to diagnose dengue, and PCRs were used to determine the circulating serotype. We found that dengue infection peaks after the rainy season and affects all sexes and ages. A total of 1277 individuals were found positive for dengue; among them, 61.7 % were male and 38.3 % were female. DEN-1 was found in 23.12 %, DEN-2 in 45 %, DEN-3 in 29.06 % and DEN-4 in 1.5 % of the dengue-infected individuals. All four DENV serotypes were circulating in the study area, and DENV serotype-2 (DEN-2) was the most prevalent serotype.

Antimicrobial Resistance and Genomic Characterization of Six New Sequence Types in Multidrug-Resistant Pseudomonas aeruginosa Clinical Isolates from Pakistan.

Pseudomonas aeruginosa (P. aeruginosa) is a major bacterial pathogen associated with a variety of infections with high mortality rates. Most of the clinical P. aeruginosa isolates belong to a limited number of genetic subgroups characterized by multiple housekeeping genes' sequences (usually 5-7) through the Multi-Locus Sequence Typing (MLST) scheme. The emergence and dissemination of novel multidrug-resistant (MDR) sequence types (ST) in P. aeruginosa pose serious clinical concerns. We performed whole-genome sequencing on a cohort (n = 160) of MDR P. aeruginosa isolates collected from a tertiary care hospital lab in Pakistan and found six isolates belonging to six unique MLST allelic profiles. The genomes were submitted to the PubMLST database and new ST numbers (ST3493, ST3494, ST3472, ST3489, ST3491, and ST3492) were assigned to the respective allele combinations. MLST and core-genome-based phylogenetic analysis confirmed the divergence of these isolates and positioned them in separate branches. Analysis of the resistome of the new STs isolates revealed the presence of genes blaOXA-50, blaPAO, blaPDC, blaVIM-2, aph(3')-IIb, aac(6')-II, aac(3)-Id, fosA, catB7, dfrB2, crpP, merP and a number of missense and frame-shift mutations in chromosomal genes conferring resistance to various antipseudomonal antibiotics. The exoS, exoT, pvdE, rhlI, rhlR, lasA, lasB, lasI, and lasR genes were the most prevalent virulence-related genes among the new ST isolates. The different genotypic features revealed the adaptation of these new clones to a variety of infections by various mutations in genes affecting antimicrobial resistance, quorum sensing and biofilm formation. Close monitoring of these antibiotic-resistant pathogens and surveillance mechanisms needs to be adopted to reduce their spread to the healthcare facilities of Pakistan. We believe that these strains can be used as reference strains for future comparative analysis of isolates belonging to the same STs.

Antibiotic-mediated expression analysis of Shiga toxin 1 and 2 in multi-drug-resistant Shiga toxigenic Escherichia coli.

Shiga toxin-producing Escherichia coli (STEC) is an important foodborne pathogens, known to cause enteric infections especially diarrhea, mainly attributed to Shiga toxins (Stxs). The use of certain antibiotics for treating this infection is controversial, owing to an increased risk for producing Stxs (Stx 1 and Stx 2). Increased antibiotic resistance is also thought to be involved in the pathogenesis of STEC diseases. The purpose of this study was to analyze the effects of antibiotics on induction of Stx 1 and Stx 2 in clinical STEC isolates and to investigate the relationships between increased resistance and Stx production. Fifteen clinical isolates were treated with sub minimum inhibitory concentrations (Sub MIC) of clinically used antibiotics (ciprofloxacin, fosfomycin, tigecycline, and meropenem), and the changes in expression levels of stx1 and stx2 genes were estimated using qRT-PCR. The expressions of Shiga toxins were found to be increased up to 6.5- and eightfold under ciprofloxacin and tigecycline Sub MIC, respectively. Fosfomycin had weak induction effect of up to twofold, whereas meropenem had the weakest influence on such expression. Resistant isolates were found to be more prone to increased expression of toxins.

Glucose Transporter 1 Overexpression in Oral Squamous Cell Carcinoma.

OBJECTIVE: To determine association of immunohistochemical over expression of GLUT 1 (Glucose transporter 1) in oral squamous cell carcinoma (SCC) with histopathological grade and smoking. STUDY DESIGN: Descriptive cross-sectional study. PLACE AND DURATION OF STUDY: Pathology Department, King Edward Medical University (KEMU), Lahore, from January 2018 to July 2018. METHODOLOGY: Paraffin blocks of diagnosed cases of oral SCC presenting at Pathology Department, KEMU, were selected for immunostain GLUT 1. Tumor was graded by WHO 2010 grading. Immunoreactive score (IRS) was calculated for GLUT 1, by multiplying proportion and intensity score of stain. Data was analysed by SPSS 21. Chi-square test was used to measure correlation between GLUT 1 staining, smoking and grade of tumor. P<0.005 was taken as significant. RESULTS: A total of 60 biopsies were included in the study. GLUT 1 was positive in 52 (86.6%) and negative in 8 (13.3%) biopsies. When differentiation of tumor was compared with GLUT 1 positivity with the help of Chi-square test p<0.001 and 95% CI, out of 52 positive biopsies 32 (61.5%) were well, 18 (34.6%) were moderately and 2 (3.8%) were poorly differentiated. GLUT 1 was positive in 43 (82.7%) and only 9 (17.31%) of non-smokers. GLUT 1 was negative in 7 (87.5%) smokers and positive in only 1 (12.5%) of smokers. CONCLUSION: GLUT 1 is positive diffusely in oral SCC with higher expression in lower grades of tumor. As the tumor loses squamous differentiation, it also loses GLUT 1 receptors and thus expression. Smoking has no significant relation with tumor differentiation or GLUT 1 expression.

Draft Genome Sequence of a bla NDM-1- and bla PME-1-Harboring Pseudomonas aeruginosa Clinical Isolate from Pakistan.

We performed Illumina whole-genome sequencing on a carbapenem-resistant Pseudomonas aeruginosa strain isolated from a cystic fibrosis patient with chronic airway colonization. The draft genome comprises 6,770,411 bp, including the carbapenemase bla NDM-1 and the extended-spectrum beta-lactamase bla PME-1 This isolate harbors 3 prophages, 14 antibiotic resistance genes, and 257 virulence genes.

Unusual case of hemidiaphragmatic paralysis secondary to cervical herpes zoster.

Hemidiaphragmatic paralysis is usually caused by surgery, malignancy or trauma and rarely by viral infections. Herpes zoster (shingles) results in varied neurological complications, but peripheral motor involvement or diaphragmatic paralysis is rare. We report the case of an 87-year-old male who presented with worsening breathlessness soon after an episode of shingles, affecting his right neck and upper chest. He had no alarm symptoms, history of trauma or malignancy. Skin lesions resolved after a few weeks, but his breathing did not improve. Chest X-ray revealed a new finding of elevated right hemidiaphragm; diaphragmatic ultrasound confirmed paradoxical cranial movement of right hemidiaphragm on sniff testing. CT scan showed no lung mass and complete collapse of right lower lobe due to elevated right hemidiaphragm. Patient has required no treatment and is under regular follow-up with the ventilation clinic.

Feasibility of physiologist-led stress echocardiography for the assessment of coronary artery disease.

BACKGROUND: Physiologist-led stress echocardiography (PLSE) services provide potential for expansion of SE services and increased productivity for cardiologists. There are however no published data on the feasibility of PLSE. We sought to assess the feasibility, safety and robustness of PLSE and cardiologist-led stress echocardiography (CLSE) for coronary artery disease (CAD) assessment. METHODS: Retrospective analysis of 898 patients undergoing PLSE or CLSE for CAD assessment using exercise or dobutamine stress over 24 months. PLSE involved 2 cardiac physiologists (exercise) or 1 physiologist plus 1 cardiac nurse (dobutamine). A cardiology registrar was present in the echocardiography department during PLSE in case of medical complications. CLSE involved 1 physiologist and 1 trainee cardiologist who analysed the study and reviewed findings with an imaging cardiologist. Sixteen-segment wall motion scoring (WMS, WMSI) analysis was performed. Feasibility (stressor, image quality, proportion of completed studies, agreement with imaging cardiologist analysis) and safety (complication rate) were compared for PLSE and CLSE. RESULTS: The majority of studies were CLSE (56.2%) and used dobutamine (68.7%). PLSE more commonly used exercise (69.2%). Overall, 96% of studies were successfully completed (>14 diagnostic segments in 98%, P = 0.899 PLSE vs CLSE). Commencement of PLSE was associated with an increase in annual SE's performed for CAD assessment. Complication rates were comparably very low for PLSE and CLSE (0.8% vs 1.8%, P = 0.187). There was excellent agreement between PLSE and CLSE WMS interpretation of 480 myocardial segments at rest (κ = 0.87) and stress (κ = 0.70) and WMSI (ICCs and Pearson's r >0.90, zero Bland-Altman mean bias). CONCLUSION: This to our knowledge is the first study of the feasibility of PLSE. PLSE performed by well-trained physiologists is feasible and safe in contemporary practice. PLSE and CLSE interpretation of stress echocardiography for CAD agree very closely.