Detection of Cervical Precancer Using Visual Inspection Method with Acetic Acid.

BACKGROUND: Cervical cancer screening is the priority activity of the government. Visual inspection with Acetic acid (VIA), Pap smear Liquid-based cytology, and HPV DNA testing are different methods of screening. VIA-based screening is the cost-effective method of screening in a resource-constrained setting like in our country as this doesn't require cyto-histological testing, can be performed by trained paramedics too, and is as accurate as a cytological test. The aim is to explore pre-cancer cervical lesions by screening women in the community by visual inspection using acetic-acid. METHODS: Community-based cross-sectional study done at a health camp setting for three months from March to June 2023. The married non-pregnant women of 30-60 years were screened. Descriptive tests as well as sub-group analysis performed by Chi-Square tests. RESULTS: From ten community health camps, 1255 cases were screened and screen positivity was 14.3%. Positive results were proportionately distributed to all parity by 13-19%. Half of the positive results (47.2%) were in the 34-40 age group. There were no significant differences in screen positivity by parity or vaginal discharge. Menopausal women had 7.7% screen positivity. CONCLUSIONS: The prevalence of VIA positivity in the community was found double the previous facility-based prevalence; and there was no significant difference by parity, menopausal status, and vaginal discharge. The positivity was more in 30-45 years of age.

Comparative evaluation of insertion characteristics of PLMA using different techniques in the pediatric age group.

Background and Aims: The laryngeal mask airway ProSeal (PLMA) insertion should be easy, fast, and atraumatic. Most studies have been done on adults who cannot be considered as the reflection of pediatric patients. In this study, we compared the first attempt success rate of three techniques of PLMA insertion: introducer, 90° rotation, and pharyngoscopy technique in the pediatric population. Material and Methods: In this prospective comparative randomized study, a total of 135 patients of American Society of Anesthesiology grade I and II, aged three to eleven years, with normal airways scheduled for elective surgery, were randomly allocated into three groups: introducer, 90° rotation, and pharyngoscopy group. Parameters evaluated were: first attempt insertion success rate, insertion time, ease of insertion score, hemodynamic parameters, oropharyngeal seal pressure, manipulations, PLMA blood staining, postoperative sore throat, and hoarseness. Results: First attempt insertion success rate was higher in the 90° rotation (97.78%) and pharyngoscopy (97.78%) group as compared to the introducer group (93.33%). But the result was not statistically significant. PLMA insertion time was the least in the rotation group, followed by the pharyngoscopy and introducer group (P < 0.0001). Mean arterial pressure and heart rate were significantly raised in the pharyngoscopy versus rotation group and the introducer versus 90° rotation group after PLMA insertion. Oropharyngeal seal pressure was significantly higher in the introducer as compared to the rotation group (P = 0.007). Conclusion: All three techniques had a high first-attempt insertion success rate. As the rotation technique had the best result in insertion time and hemodynamic response, it may be considered a good alternative to pharyngoscopy and introducer technique in pediatric patients of age three to eleven years with a normal airway.

Genetic and functional enrichments associated with Enterococcus faecalis isolated from the urinary tract.

IMPORTANCE: Urinary tract infection (UTI) is a global health issue that imposes a substantial burden on healthcare systems. Women are disproportionately affected by UTI, with >60% of women experiencing at least one UTI in their lifetime. UTIs can recur, particularly in postmenopausal women, leading to diminished quality of life and potentially life-threatening complications. Understanding how pathogens colonize and survive in the urinary tract is necessary to identify new therapeutic targets that are urgently needed due to rising rates of antimicrobial resistance. How Enterococcus faecalis, a bacterium commonly associated with UTI, adapts to the urinary tract remains understudied. Here, we generated a collection of high-quality closed genome assemblies of clinical urinary E. faecalis isolated from the urine of postmenopausal women that we used alongside detailed clinical metadata to perform a robust comparative genomic investigation of genetic factors that may be involved in E. faecalis survival in the urinary tract.

Development of a high-throughput minimum inhibitory concentration (HT-MIC) testing workflow.

The roots of the minimum inhibitory concentration (MIC) determination go back to the early 1900s. Since then, the test has undergone modifications and advancements in an effort to increase its dependability and accuracy. Although biological investigations use an ever-increasing number of samples, complicated processes and human error sometimes result in poor data quality, which makes it challenging to replicate scientific conclusions. Automating manual steps using protocols decipherable by machine can ease procedural difficulties. Originally relying on manual pipetting and human vision to determine the results, modern broth dilution MIC testing procedures have incorporated microplate readers to enhance sample analysis. However, current MIC testing procedures are unable to simultaneously evaluate a large number of samples efficiently. Here, we have created a proof-of-concept workflow using the Opentrons OT-2 robot to enable high-throughput MIC testing. We have further optimized the analysis by incorporating Python programming for MIC assignment to streamline the automation. In this workflow, we performed MIC tests on four different strains, three replicates per strain, and analyzed a total of 1,152 wells. Comparing our workflow to a conventional plate MIC procedure, we find that the HT-MIC method is 800% faster while simultaneously boasting a 100% accuracy. Our high-throughput MIC workflow can be adapted in both academic and clinical settings since it is faster, more efficient, and as accurate than many conventional methods.

Functional and genetic adaptations contributing to Enterococcus faecalis persistence in the female urinary tract.

Enterococcus faecalis is the leading Gram-positive bacterial species implicated in urinary tract infection (UTI). An opportunistic pathogen, E. faecalis is a commensal of the human gastrointestinal tract (GIT) and its presence in the GIT is a predisposing factor for UTI. The mechanisms by which E. faecalis colonizes and survives in the urinary tract (UT) are poorly understood, especially in uncomplicated or recurrent UTI. The UT is distinct from the GIT and is characterized by a sparse nutrient landscape and unique environmental stressors. In this study, we isolated and sequenced a collection of 37 clinical E. faecalis strains from the urine of primarily postmenopausal women. We generated 33 closed genome assemblies and four highly contiguous draft assemblies and conducted a comparative genomics to identify genetic features enriched in urinary E. faecalis with respect to E. faecalis isolated from the human GIT and blood. Phylogenetic analysis revealed high diversity among urinary strains and a closer relatedness between urine and gut isolates than blood isolates. Plasmid replicon (rep) typing further underscored possible UT-GIT interconnection identifying nine shared rep types between urine and gut E. faecalis . Both genotypic and phenotypic analysis of antimicrobial resistance among urinary E. faecalis revealed infrequent resistance to front-line UTI antibiotics nitrofurantoin and fluoroquinolones and no vancomycin resistance. Finally, we identified 19 candidate genes enriched among urinary strains that may play a role in adaptation to the UT. These genes are involved in the core processes of sugar transport, cobalamin import, glucose metabolism, and post-transcriptional regulation of gene expression. IMPORTANCE: Urinary tract infection (UTI) is a global health issue that imposes substantial burden on healthcare systems. Women are disproportionately affected by UTI with >60% of women experiencing at least one UTI in their lifetime. UTIs can recur, particularly in postmenopausal women, leading to diminished quality of life and potentially life-threatening complications. Understanding how pathogens colonize and survive in the urinary tract is necessary to identify new therapeutic targets that are urgently needed due to rising rates of antimicrobial resistance. How Enterococcus faecalis , a bacterium commonly associated with UTI, adapts to the urinary tract remains understudied. Here, we generated a collection of high-quality closed genome assemblies of clinical urinary E. faecalis isolated from the urine of postmenopausal women that we used alongside detailed clinical metadata to perform a robust comparative genomic investigation of genetic factors that may mediate urinary E. faecalis adaptation to the female urinary tract.

Detection of three pandemic causing coronaviruses from non-respiratory samples: systematic review and meta-analysis.

SARS-CoV-2 has posed an unprecedented challenge to the world. Pandemics have been caused previously by viruses of this family like Middle East Respiratory Corona Virus (MERS CoV), Severe Acute Respiratory Syndrome Corona Virus (SARS CoV). Although these viruses are primarily respiratory viruses, but they have been isolated from non-respiratory samples as well. Presently, the detection rate of SARS-CoV-2 RNA from different clinical specimens using Real Time Reverse Transcriptase Polymerized Chain Reaction (qRT-PCR) after onset of symptoms is not yet well established. Therefore, the aim of this systematic review was to establish the profile of detecting SARS-CoV-2, MERS CoV, SARS CoV from different types of clinical specimens other than the respiratory using a standard diagnostic test (qRT-PCR). A total of 3429 non-respiratory specimens were recorded: SARS CoV (total sample-802), MERS CoV (total sample-155), SARS CoV-2 (total sample-2347). Out of all the samples studied high positive rate was seen for saliva with 96.7% (14/14; 95% CI 87.6-100.0%) for SARS CoV and 57.5% (58/250; 95% CI - 1.2 to 116.2%) for SARS CoV-2, while low detection rate in urine samples for SARS CoV-2 with 2.2% (8/318; 95% CI 0.6-3.7%) and 9.6% (12/61; 95% CI - 0.9 to 20.1%) for SARS CoV but there was relatively higher positivity in urine samples for MERS CoV with detection rate of 32.4% (2/38; 95% CI - 37.3 to 102.1%). In Stool sample positivity was 54.9% (396/779; 95% CI 41.0-68.8%), 45.2% (180/430; 95% CI 28.1-62.3%) and 34.7% (4/38; 95% CI - 29.5 to 98.9%) for SARS CoV-2, MERS CoV, and SARS CoV, respectively. In blood sample the positivity was 33.3% (7/21; 95% CI 13.2-53.5%), 23.7% (42/277; 95% CI 10.5-36.9%) and 2.5% (2/81; 95% CI 0.00-5.8%) for MERS CoV, SARS CoV-2 and SARS CoV respectively. SARS-CoV-2 along with previous two pandemic causing viruses from this family, were highly detected stool and saliva. A low positive rate was recorded in blood samples. Viruses were also detected in fluids along with unusual samples like semen and vaginal secretions thus highlighting unique pathogenic potential of SARS-CoV-2.

Enhanced chemotherapeutic toxicity of cyclodextrin templated size-tunable rhodamine 6G nanoGUMBOS.

Nanodrugs have been widely investigated for combating the large number of side effects associated with conventional therapeutics. Several investigations of such nanomedicines have demonstrated the profound role of nanoparticle size in therapeutic efficacy. Herein, we report the role of cyclodextrin (CD)-templating on the size and therapeutic properties of rhodamine 6G (R6G) nanoGUMBOS, i.e. nanomaterials derived from a Group of Uniform Materials Based on Organic Salts (GUMBOS). In these studies, templating of nanoGUMBOS using 2-hydroxypropyl-alpha (2-HP-α), 2-hydroxypropyl beta (2-HP-ß), and gamma (γ) cyclodextrin (CD) led to a significant reduction in size and enhanced uniformity as indicated by transmission electron microscopy (TEM) images. In addition, CD-templated nanoGUMBOS remarkably displayed a three to four fold enhancement in toxicity towards cancer cells as compared to nanoGUMBOS without CD-templates, suggesting a significant improvement in therapeutic efficacy. Correlation between size and toxicity suggests that CD-templated nanoparticles of ∼70 to 80 nm produced optimal toxicity. Even more interesting, all investigated nanoGUMBOS displayed no toxicity toward normal cells under examined conditions. Moreover, these nanoGUMBOS display comparable chemotherapeutic toxicity to the parent dye, [R6G][Cl], while also eliminating toxicity towards normal cells, indicating their strong chemotherapeutic potential. The studies outlined here provide further insight into an approach that may be employed for rapid synthesis of size tunable nanodrugs for enhanced chemotherapeutic efficacy.

Anilino-(2-bromophenyl) acetonitrile: a promising orally effective antileishmanial agent.

Visceral leishmaniasis (VL) or kala-azar is a worldwide disseminated intracellular infection caused by the hemoflagellate protozoan parasites Leishmania donovani. Chemotherapeutic scenario presents a deplorable picture and demands an urgent search for a new and safe anti-VL drugs, preferably active by oral route. In search of new antileishmanial agents, a total of 16 compounds belonging to the anilino-(substituted phenyl)-acetonitrile class were tested in vitro in promastigote/macrophase-amastigote systems and in vivo in L. donvoani/hamster model for their antileishmanial activity. Compound 3, anilino-(2-bromophenyl)-acetonitrile, exhibited most promising activity both in vitro at a concentration of 100 microg/ml (82.33 and 94.36% in promastigote and macrophase-amastigote systems, respectively) and in vivo at a dose of 50 mg/kg for 5 days (82.11 and 80% by i.p. and p.o. routes, respectively), hence this compound was investigated in detail. To maximize its bioavailability, dissolution profile, absorption, the compound was also tested in vivo as its soluble form. But no enhancement in activity was observed. From the results of different parameters for example ED(50) and LD(50) etc. compound 3 appears to be a potent orally effective compound which could further be investigated to establish its potential as a candidate molecule of antileishmanial therapy.

Successful explantation of a ventricular assist device following fulminant influenza type A-associated myocarditis.

We report a case of fulminant myocarditis associated with refractory ventricular fibrillation following influenza A infection. Histologic examination was consistent with myocarditis and serology confirmed the viral etiology. The patient was supported with biventricular assist devices for 20 days during which her refractory ventricular fibrillation resolved spontaneously. This is the first documented case of resolution of prolonged ventricular fibrillation while on a ventricular assist device. This case suggests those patients with fulminant viral myocarditis and refractory ventricular arrhythmias may be supported successfully with ventricular assist devices until myocardial recovery takes place.