Nasopharyngeal carriage of Streptococcus pneumoniae serotypes among sick and healthy children in northern India: A case-control study.

BACKGROUND: Streptococcus pneumoniae is leading bacterial cause of community acquired pneumonia and according to World Health Organization, responsible for 14 % death in children. There is effective vaccine available against Streptococcus pneumoniae. Hence the primary objective was to isolate Streptococcus pneumoniae from nasopharyngeal swabs in children aged 2-59 months with and without community acquired pneumonia and to assess their serotypes. METHODS: This case-control study was conducted in tertiary teaching institutes in northern India. Hospitalized children, aged 2-59 months, with World Health Organization-defined community acquired pneumonia were included as cases. Age matched healthy controls were recruited from immunization clinic. All enrolments were done after written informed parental consent. Nasopharyngeal swabs were taken from both cases and controls, and were cultured on 5 % sheep blood agar with gentamycin plate for growth of Streptococcus pneumoniae and incubated in a jar at 370 for 18-24 hrs. Quellung reaction test was used for serotyping. RESULTS: From March 2017 to December 2022, 2693 children (1910 cases and 783 controls), were recruited. The median age of cases was 7 months and controls 10 months. Almost all the cases had received antibiotics prior to hospitalization. Streptococcus pneumoniae positivity in nasopharyngeal swab was 8.1 % in cases, of which 56.8 % were vaccine serotypes and 23.6 % in controls, of which 37.8 % were vaccine serotypes. Adjusted odds ratio of isolating vaccine serotypes among cases as compared to controls was 1.77 (95 % CI, 1.09-2.88). CONCLUSION: Streptococcus pneumoniae isolation from nasopharyngeal was found to be in lower proportion in cases as compared to control, though colonization with vaccine serotypes was higher in cases as compared to control. Therefore, pneumococcal vaccine coverage must be increased to prevent community acquired pneumonia.

Nasopharyngeal Carriage of Streptococcus pneumoniae Serotypes Among Healthy Children in Northern India.

Streptococcus pneumoniae (SP) infections cause morbidity and mortality among children worldwide. Hence India introduced 13-valent pneumococcal conjugate vaccine (PCV-13) in 2017 in a phased manner. The primary objective of this study was to assess the proportion of healthy children having nasopharyngeal colonization (NP) with SP. Secondary objective was to determine prevalent serotype of SP among the PCV13 vaccinated and non-vaccinated children. This cross-sectional study was conducted in 4 hospitals of Lucknow District, Northern India. Three hundred healthy children (2-59 months) were recruited between July and August 2019 from vaccination-clinics of hospitals. NP specimen was cultured using 5% sheep blood agar plate containing gentamicin. Pneumococcal isolates were identified by optochin sensitivity and bile-solubility tests. Serotyping was done using Quellung Method. Of the 300 healthy children, 56.7% (170/300) were males and 59.3% (181/300) had received at least one dose of PCV13 vaccine. The NP carriage rate of SP among healthy children was 37.7% (113/300). Vaccine serotypes were found in 33.3% (22/66) in PCV vaccinated children and 48.9% (23/47) in non-vaccinated children (p 0.09). Common vaccine serotypes that isolated were: 18C, 19A, 19F, 23F, 3, 4, 6A, 6B, 9 V. Thus more than one-third of healthy children had NP colonization with SP. Adjusting for age, there was a trend for significant reduction in vaccine serotypes in the NP with one doses versus two or more doses (ptrend = 0.04).

Extra credit for disruption: trend of disruption in radiology academic journals.

AIM: To identify the most disruptive publications, which are those that are cited more frequently than their own references, in academic radiology journals and their characteristics, such as the number of authors and relative time to publication. MATERIAL AND METHODS: A comprehensive literature search was undertaken to identify the 100 most disruptive publications in the field of radiology. Subsequently, statistical analysis was applied to establish the distribution of disruptive scores of the isolated publications using a non-parametric probability density function. The relation between disruptive scores and citation counts was then determined, with the aid of a correlation coefficient. Finally, data regarding any significant connection between disruption scores and time of publication, number of authors, and study design were examined. RESULTS: Analysing the top 100 papers in increments of 10-year periods showed no significant difference in the distribution of disruption scores over time. No correlation between an article's citation count and disruption score was established. Additionally, no significant relation between the number of authors/study design and disruption scores was identified. CONCLUSION: The disruption score highlights significant impact elements not entirely accounted for by citation count. Its potential benefit in assessing scientific impact should be contemplated.

Estradiol inhibits HIV-1BaL infection and induces CFL1 expression in peripheral blood mononuclear cells and endocervical mucosa.

An inhibitory effect of estradiol (E2) on HIV-1 infection was suggested by several reports. We previously identified increased gene expression of actin-binding protein cofilin 1 (CFL1) in endocervix in the E2-dominated proliferative phase of the menstrual cycle. Actin cytoskeleton has an integral role in establishing and spreading HIV-1 infection. Herein, we studied in vitro effects of E2 on HIV-1 infection and on CFL1 expression to gain insight into the mechanism of HIV-1 inhibition by E2. E2 dose-dependently inhibited HIV-1BaL infection in peripheral blood mononuclear cells (PBMCs) and endocervix. In PBMCs and endocervix, E2 increased protein expression of total CFL1 and phosphorylated CFL1 (pCFL1) and pCFL1/CFL1 ratios. LIMKi3, a LIM kinase 1 and 2 inhibitor, abrogated the phenotype and restored infection in both PBMCs and endocervix; inhibited E2-induced expression of total CFL1, pCFL1; and decreased pCFL1/CFL1 ratios. Knockdown of CFL1 in PBMCs also abrogated the phenotype and partially restored infection. Additional analysis of soluble mediators revealed decreased concentrations of pro-inflammatory chemokines CXCL10 and CCL5 in infected tissues incubated with E2. Our results suggest a link between E2-mediated anti-HIV-1 activity and expression of CFL1 in PBMCs and endocervical mucosa. The data support exploration of cytoskeletal signaling pathway targets for the development of prevention strategies against HIV-1.

Total annulus excision tympanoplasty - a solution to recurrent myringitis: double blind randomised trial.

OBJECTIVE: In spite of continuous refinements in tympanoplasty techniques, results are variable, and it is not uncommon to see a discharging eardrum even after a good graft uptake. This study aimed to evaluate the efficacy of total annulus excision tympanoplasty in comparison with conventional underlay tympanoplasty. METHOD: This was a double blinded, randomised, controlled trial performed at a tertiary care centre. After inclusion and exclusion criteria were met, 56 patients were enrolled and randomised, and 28 patients were allocated to each group (group A (conventional tympanoplasty) and group B (total annulus excision)). Patients and evaluators were blind to the procedure performed. RESULTS: Patients in group B (total annulus excision) showed better graft uptake and no discharge with better gains in air conduction thresholds (p < 0.05) when compared with group A (conventional tympanoplasty). CONCLUSION: In view of the advantages it offers, total annulus excision tympanoplasty may be preferred over the conventional techniques in patients with central perforations.

Increased tracheostomy rates in head and neck cancer surgery during the COVID-19 pandemic.

Surgical practice during the coronavirus disease 2019 (COVID-19) pandemic has changed significantly, without supporting data. With increasing experience, a dichotomy of practice is emerging, challenging existing consensus guidelines. One such practice is elective tracheostomy. Here, we share our initial experience of head and neck cancer surgery in a COVID-19 tertiary care centre, emphasizing the evolved protocol of perioperative care when compared to pre-COVID-19 times. This was a prospective study of 21 patients with head and neck cancers undergoing surgery during the COVID-19 pandemic, compared to 193 historical controls. Changes in anaesthesia, surgery, and operating room practices were evaluated. A strict protocol was followed. One patient tested positive for COVID-19 preoperatively. There was a significant increase in pre-induction tracheostomies (28.6% vs 6.7%, P=0.005), median hospital stay (10 vs 7 days, P=0.001), and postponements of surgery (57.1% vs 27.5%, P=0.01), along with a significant decrease in flap reconstructions (33.3% vs 59.6%, P=0.03). There was no mortality and no difference in postoperative morbidity. No healthcare personnel became symptomatic for COVID-19 during this period. Tracheostomy is safe during the COVID-19 pandemic and rates have increased. Despite increased rescheduling of surgeries and longer hospital stays, definitive cancer care surgery has not been deferred and maximum patient and healthcare worker safety has been ensured.

Emergence of spatio-temporal variations in chemotherapeutic drug efficacy: in-vitro and in-Silico 3D tumour spheroid studies.

BACKGROUND: The mechanisms of action and efficacy of cisplatin and paclitaxel at cell population level are well studied and documented, however the localized spatio-temporal effects of the drugs are less well understood. We explore the emergence of spatially preferential drug efficacy resulting from variations in mechanisms of cell-drug interactions. METHODS: 3D spheroids of HeLa-C3 cells were treated with drugs, cisplatin and paclitaxel. This was followed by sectioning and staining of the spheroids to track the spatio-temporal apoptotic effects of the drugs. A mechanistic drug-cell interaction model was developed and simulated to analyse the localized efficacy of these drugs. RESULTS: The outcomes of drug actions on a local cell population was dependant on the interactions between cell repair probability, intracellular drug concentration and cell's mitosis phase. In spheroids treated with cisplatin, drug induced apoptosis is found to be scattered throughout the volume of the spheroids. In contrast, effect of paclitaxel is found to be preferentially localized along the periphery of the spheroids. Combinatorial treatments of cisplatin and paclitaxel result in varying levels of cell apoptosis based on the scheduling strategy. CONCLUSIONS: The preferential action of paclitaxel can be attributed to the cell characteristics of the peripheral population. The model simulations and experimental data show that treatments initiated with paclitaxel are more efficacious due to the cascading of spatial effects of the drugs.

Variability of contrast enhancement of pancreas on computed tomography in patients with acute pancreatitis and isolated extrapancreatic necrosis.

BACKGROUND AND STUDY AIM: To evaluate the variability in the enhancement of pancreas on computed tomography (CT) in patients with acute pancreatitis (AP) and isolated extrapancreatic necrosis (EPN) and to investigate whether it affects the extrapancreatic findings and patient outcomes. PATIENTS AND METHODS: This retrospective study comprised of consecutive patients with isolated EPN evaluated between April 2017 and April 2019. A radiologist measured the pancreatic attenuation values (PAV) of head, body, and tail on a contrast enhanced CT. Using a cut-off PAV of 100HU, patients were divided into two groups. The extrapancreatic CT findings and outcome parameters were compared between the two groups. RESULTS: Thirty patients (mean age, 42.13 years, 17 males) with isolated EPN were evaluated. The mean PAV in the head, body, and tail was 83.13 HU (range, 59-161), 84.17 HU (range, 60-160), and 82.23 HU (range, 53-137). The overall mean PAV was 83.12 HU (range, 58-152). There were six patients with overall mean PAV≥100 HU. The group with PAV≥100 HU had a higher number of patients with infected necrosis (66.6% vs. 14.2%, P=0.018). PAV had a significant association with length of hospitalization (P=0.045). CONCLUSION: There is significant variability in the pancreatic enhancement on CT among patients with AP and isolated EPN. Patients with PAV≥100 HU had a significantly longer hospital stay. This, however, may be related to a greater number of patients with infected necrosis in this group.

Comprehensive analysis of mitochondrial DNA based genetic diversity in Indian goats.

Thirty four distinct breeds and many non-descript populations represent the caprine diversity of India. Genetic characterization of breeds is an essential element in designing breeding strategies and preserving genetic diversity. Considering the popularity of mitochondrial DNA for phylogeographical studies, this study involved an extensive analysis of population structure and genetic diversity of 28 defined breeds and 5 lesser known populations representing all four major agro-climatic zones of India using mitochondrial DNA markers. Analysis of hypervariable region 1 of mtDNA control region in 443 goats together with 22 reference sequences, delineated 341 distinct haplotypes belonging to four maternal haplogroups; A, B, C and D, with haplogroup A representing 90% of the individuals. The haplotype and nucleotide diversity indices of Indian goats were 0.998 ± 0.001 and 0.028 ± 0.001, respectively indicating abundant genetic variability. Estimates of population demographic parameters from mismatch analysis suggested a relatively good fit to the model of either spatial or demographic expansion of Indian goats. AMOVA analysis and topology of MJ network suggested lack of phylogeographic structure in domestic goats, which can be attributed to unstructured animal breeding, dwindling pastures and nomadic pastoralism. Genetic differentiation between goats from different agro-ecological regions was in accordance with their geographical propinquity.

Shaping the zebrafish myotome by intertissue friction and active stress.

Organ formation is an inherently biophysical process, requiring large-scale tissue deformations. Yet, understanding how complex organ shape emerges during development remains a major challenge. During zebrafish embryogenesis, large muscle segments, called myotomes, acquire a characteristic chevron morphology, which is believed to aid swimming. Myotome shape can be altered by perturbing muscle cell differentiation or the interaction between myotomes and surrounding tissues during morphogenesis. To disentangle the mechanisms contributing to shape formation of the myotome, we combine single-cell resolution live imaging with quantitative image analysis and theoretical modeling. We find that, soon after segmentation from the presomitic mesoderm, the future myotome spreads across the underlying tissues. The mechanical coupling between the future myotome and the surrounding tissues appears to spatially vary, effectively resulting in spatially heterogeneous friction. Using a vertex model combined with experimental validation, we show that the interplay of tissue spreading and friction is sufficient to drive the initial phase of chevron shape formation. However, local anisotropic stresses, generated during muscle cell differentiation, are necessary to reach the acute angle of the chevron in wild-type embryos. Finally, tissue plasticity is required for formation and maintenance of the chevron shape, which is mediated by orientated cellular rearrangements. Our work sheds light on how a spatiotemporal sequence of local cellular events can have a nonlocal and irreversible mechanical impact at the tissue scale, leading to robust organ shaping.

99mTc-MAG3 diuresis renography in differentiating renal obstruction: Using statistical parameters as new quantifiable indices.

OBJECTIVE: The aim of this study was to research, develop and assess the feasibility of using basic statistical parameters derived from renogram, "mean count value (MeanCV) and "median count value (MedianCV)", as novel indices in the diagnosis of renal obstruction through diuresis renography. SUBJECTS AND METHODS: First, we re-digitalized and normalized 132 renograms from 74 patients in order to derive the MeanCV and MedianCV. To improve the performance of the parameters, we extrapolated renograms by a two-compartmental modeling. After that, the cutoff points for diagnosis using each modified parameter were set and the sensitivity and specificity were calculated in order to determine the best variants of MeanCV and MedianCV that could differentiate renal obstruction status into 3 distinct classes - i) unobstructed, ii) slightly obstructed, and iii) heavily obstructed. RESULTS: The modified MeanCV and MedianCV derived from extended renograms predicted the severity of the renal obstruction. The most appropriate variants of MeanCV and MedianCV were found to be the MeanCV50 and the MedianCV60. The cutoff points of MeanCV50 in separating unobstructed and obstructed classes as well as slightly and heavily obstructed classes were 0.50 and 0.72, respectively. The cutoff points of MedianCV60 in separating unobstructed and obstructed classes as well as slightly and heavily obstructed classes were 0.35 and 0.69, respectively. Notably, MeanCV50 and MedianCV60 were not significantly influenced by either age or gender. CONCLUSIONS: The MeanCV50 and the MedianCV60 derived from a renogram could be incorporated with other quantifiable parameters to form a system that could provide a highly accurate diagnosis of renal obstructions.

Inferior right hepatic vein on routine contrast-enhanced CT of the abdomen: prevalence and correlation with right hepatic vein size.

AIM: To determine the prevalence of the inferior right hepatic vein (IRHV) in patients undergoing routine contrast-enhanced computed tomography (CECT) of the abdomen and to compare it with the size of the right hepatic vein (RHV). MATERIALS AND METHODS: Two hundred and twenty-four consecutive patients who underwent routine CECT abdomen, with adequate venous opacification, were included in the study. The number and diameter of IRHVs and the diameter of the RHV was noted in each case. RESULTS: A total of 214 IRHVs were detected in 126 cases (56.2%) with a mean diameter of 4.15±1.44 mm. The number of IRHVs ranged from one to four (more than one IRHV was present in 39.7% [50/126] of cases). In approximately one-third of cases (46/126), an IRHV ≥5 mm was found. A weak negative correlation was found between size of the RHV and IRHV (Pearson's correlation coefficient -0.222; p=0.01). The RHV was smaller in size in patients with an IRHV (7.34±1.88 mm) than in patients without an IRHV (8.47±1.99 mm) on CECT abdomen. A larger IRHV was associated with a smaller RHV (6.91±2.05 mm). CONCLUSION: The presence of IRHV on routine CECT abdomen is frequent, and it is not uncommon to encounter more than one IRHV. The diameter of the IRHV has a weak negative correlation with the diameter of the RHV, and a smaller RHV is found in patients with an IRHV.

Correlation of Foot Bimalleolar Angle and Ultrasonography in Assessing the Severity of Club Foot in Neonates Treated by the Ponseti Method.

Introduction: Correlation of Pirani score and foot bimalleolar (FBM) angle has been used in few studies but correlation of FBM angle with ultrasonography has never been evaluated so they are being correlated in assessing the severity of clubfoot in neonates treated by Ponseti method. Material and Methods: Thirty-two feet with congenital talipes equinovarus (CTEV) deformity in neonates were prospectively treated by the Ponseti method. FBM angle and ultrasound parameters were measured three times i.e. at the time of initial presentation, at four weeks of treatment and at completion of treatment. The feet were divided according to the Pirani score in groups: one (0-2.0), two (2.5-4) and three (4.5-6). Correlation between FBM angle and ultrasound parameters were evaluated using Pearson correlation/regression. Results: Correlation between FBM angle and ultrasound parameters were statistically significant (p-value < 0.05). Conclusion: Ultrasound has the potential to accurately depict the pathoanatomy in clubfoot. FBM angle and ultrasound are objective methods to assess the severity of clubfoot. FBM angle and ultrasonography correlated in severity of deformity and correction achieved along the course of treatment.

Correlation of Foot Bimalleolar Angle and Ultrasonography in Assessing the Severity of Club Foot in Neonates Treated by the Ponseti Method

@#Introduction: Correlation of Pirani score and foot bimalleolar (FBM) angle has been used in few studies but correlation of FBM angle with ultrasonography has never been evaluated so they are being correlated in assessing the severity of clubfoot in neonates treated by Ponseti method. Material and Methods: Thirty-two feet with congenital talipes equinovarus (CTEV) deformity in neonates were prospectively treated by the Ponseti method. FBM angle and ultrasound parameters were measured three times i.e. at the time of initial presentation, at four weeks of treatment and at completion of treatment. The feet were divided according to the Pirani score in groups: one (0-2.0), two (2.5-4) and three (4.5-6). Correlation between FBM angle and ultrasound parameters were evaluated using Pearson correlation/regression. Results: Correlation between FBM angle and ultrasound parameters were statistically significant (p-value < 0.05). Conclusion: Ultrasound has the potential to accurately depict the pathoanatomy in clubfoot. FBM angle and ultrasound are objective methods to assess the severity of clubfoot. FBM angle and ultrasonography correlated in severity of deformity and correction achieved along the course of treatment.

Evaluation of fever in the immediate post-operative period following shoulder arthroplasty.

AIMS: To determine the incidence and timing of post-operative fevers following shoulder arthroplasty and the resulting investigations performed. PATIENTS AND METHODS: A retrospective review was conducted of all patients undergoing shoulder arthroplasty over a nine-year period. The charts of all patients with a post-operative fever (≥ 38.6°C) were reviewed and the results of all investigations were analysed. RESULTS: A total of 2167 cases (in 1911 patients) were included of whom 92 (4.2%) had a documented fever. Obese cases had a significantly greater risk for fever (relative risk 1.53; 95% confidence interval 1.02 to 2.32; p = 0.041). Investigations were performed in 43/92 cases (46.7%), with a diagnosis being made in six cases (6.6% of the total, two of whom had their diagnosis made post-discharge). CONCLUSION: Around one in 25 cases develop a fever following shoulder arthroplasty; most have no infective aetiology. These patients may be being over-investigated; investigations should be performed in patients with persistent fever or on those with an identifiable source of infection on clinical examination. Cite this article: Bone Joint J 2017;99-B:1515-19.

Comparative outcomes of outpatient and inpatient total shoulder arthroplasty: an analysis of the Medicare dataset.

AIMS: The aim of the present study was to compare the 30- and 90-day re-admission rates and complication rates of outpatient and inpatient total shoulder arthroplasty (TSA). PATIENTS AND METHODS: The United States Medicare Standard Analytical Files database was questioned to identify patients who had undergone outpatient or inpatient TSA between 2005 and 2012. Patient characteristics were compared between the two groups using chi-squared analysis. Multivariate logistic regression analysis was used to control for differences in baseline patient characteristics and to compare the two groups in terms of post-operative complications within 90 days and re-admission within 30 days and 90 days. RESULTS: A total of 123 347 Medicare subscribers underwent TSA between 2005 and 2012; 3493 (2.8%) had the procedure performed as an outpatient. A significantly greater proportion of patients who underwent TSA as inpatients were women, had a history of smoking, and had a greater incidence of medical comorbidity including diabetes, coronary artery disease, congestive heart failure, and chronic kidney disease (p < 0.05 for all). Re-admission rates were significantly higher for inpatients at both 30 days (0.83% versus 0.60%, p = 0.016, odds ratio 1.8) and 90 days (2.87% versus 2.04%, p < 0.001, odds ratio 1.8). Complications, including thromboembolic events (p < 0.001) and surgical site infection (p = 0.002), were significantly higher in inpatients. CONCLUSION: Patients who underwent TSA on an outpatient basis were overall younger and healthier than those who had inpatient surgery, which suggests that patient selection was taking place. After controlling for age, gender, and medical conditions, patients who underwent TSA as outpatients had lower rates of 30- and 90-day re-admission and a lower rate of complications than inpatients. Cite this article: Bone Joint J 2017;99-B:934-8.

Immune deficiency and autoimmunity in patients with CTLA-4 (CD152) mutations.

Immune deficiency disorders are a heterogeneous group of diseases of variable genetic aetiology. While the hallmark of immunodeficiency is susceptibility to infection, it is increasingly clear that autoimmunity is prevalent, suggestive of a more general immune dysregulation in some cases. With the increasing use of genetic technologies, the underlying causes of immune dysregulation are beginning to emerge. Here we provide a review of the heterozygous mutations found in the immune checkpoint protein CTLA-4, identified in cases of common variable immunodeficiency disorders (CVID) with accompanying autoimmunity. Study of these mutations provides insights into the biology of CTLA-4 as well as suggesting approaches for rational treatment of these patients.

Evidence of positive selection and concerted evolution in the rapidly evolving PRDM9 zinc finger domain in goats and sheep.

Meiotic recombination contributes to augmentation of genetic diversity, exclusion of deleterious alleles and proper segregation of chromatids. PRDM9 has been identified as the gene responsible for specifying the location of recombination hotspots during meiosis and is also the only known vertebrate gene associated with reproductive isolation between species. PRDM9 encodes a protein with a highly variable zinc finger (ZF) domain that varies between as well as within species. In the present study, the ZF domain of PRDM9 on chromosome 1 was characterized for the first time in 15 goat breeds and 25 sheep breeds of India. A remarkable variation in the number and sequence of ZF domains was observed. The number of ZF repeats in the ZF array varied from eight to 12 yielding five homozygous and 10 heterozygous genotypes. The number of different ZF domains was 84 and 52 producing 36 and 26 unique alleles in goats and sheep respectively. The posterior mean of dN/dS or omega values were calculated using the codeml tool of pamlx to identify amino acids that are evolving positively in goats and sheep, as positions -1, +3 and +6 in the ZF domain have been reported to experience strong positive selection across different lineages. Our study identified sites -5, -1, +3, +4 and +6 to be experiencing positive selection. Small ruminant zinc fingers were also found to be evolving under concerted evolution. Our results demonstrate the existence of a vast diversity of PRDM9 in goats and sheep, which is in concert with reports in many metazoans.