Rapid expansion of Neisseria gonorrhoeae ST7827 clone in Australia, with variable ceftriaxone phenotype unexplained by genotype.

BACKGROUND: Neisseria gonorrhoeae is identified as a priority pathogen due to its capacity to rapidly develop antimicrobial resistance (AMR). Following the easing of SARS-CoV-2 pandemic travel restrictions across international borders in the state of New South Wales (NSW), Australia, a surge of gonococcal isolates with raised ceftriaxone MIC values were detected. METHODS: All N. gonorrhoeae isolates (n = 150) with increased ceftriaxone MIC values in NSW between 1 January 2021 and July 2022 from males and females from all sites were sequenced. RESULTS: A new emergence and rapid expansion of an N. gonorrhoeae ST7827 clone was documented within NSW, Australia and provides further evidence of the ability of N. gonorrhoeae to undergo sufficient genomic changes and re-emerge as a geographically restricted subclone. Mapping AMR determinants to MIC results did not reveal any genomic pattern that correlated with MIC values. CONCLUSIONS: The rapid dissemination and establishment of this clone at the population level is a new and concerning demonstration of the agility of this pathogen, and underscores concerns about similar incursions and establishment of MDR clones. Moreover, it is notable that in this context the AMR genotype-phenotype correlates remain unclear, which requires further investigation to enable better understanding of genomic aspects of AMR in N. gonorrhoeae.

A quantitative structural analysis of AR-42 derivatives as HDAC1 inhibitors for the identification of promising structural contributors.

Alteration and abnormal epigenetic mechanisms can lead to the aberration of normal biological functions and the occurrence of several diseases. The histone deacetylase (HDAC) family of enzymes is one of the prime regulators of epigenetic functions modifying the histone proteins, and thus, regulating epigenetics directly. HDAC1 is one of those HDACs which have important contributions to cellular epigenetics. The abnormality of HDAC is correlated to the occurrence, progression, and poor prognosis in several disease conditions namely neurodegenerative disorders, cancer cell proliferation, metastasis, chemotherapy resistance, and survival in various cancers. Therefore, the progress of potent and effective HDAC1 inhibitors is one of the prime approaches to combat such diseases. In this study, both regression and classification-based molecular modelling studies were conducted on some AR-42 derivatives as HDAC1 inhibitors to elucidate the crucial structural aspects that are responsible for regulating their biological responses. This study revealed that the molecular polarizability, van der Waals volume, the presence of aromatic rings as well as the higher number of hydrogen bond acceptors might affect prominently their inhibitory activity and might be responsible for proper fitting and interactions at the HDAC1 active site to pertain effective inhibition.

Pre-existing influenza-specific nasal IgA or nasal viral infection does not affect live attenuated influenza vaccine immunogenicity in children.

The United Kingdom has a national immunization programme which includes annual influenza vaccination in school-aged children, using live attenuated influenza vaccine (LAIV). LAIV is given annually, and it is unclear whether repeat administration can affect immunogenicity. Because LAIV is delivered intranasally, pre-existing local antibody might be important. In this study, we analysed banked samples from a study performed during the 2017/18 influenza season to investigate the role of pre-existing influenza-specific nasal immunoglobulin (Ig)A in children aged 6-14 years. Nasopharyngeal swabs were collected prior to LAIV immunization to measure pre-existing IgA levels and test for concurrent upper respiratory tract viral infections (URTI). Oral fluid samples were taken at baseline and 21-28 days after LAIV to measure IgG as a surrogate of immunogenicity. Antibody levels at baseline were compared with a pre-existing data set of LAIV shedding from the same individuals, measured by reverse transcription-polymerase chain reaction. There was detectable nasal IgA specific to all four strains in the vaccine at baseline. However, baseline nasal IgA did not correlate with the fold change in IgG response to the vaccine. Baseline nasal IgA also did not have an impact upon whether vaccine virus RNA was detectable after immunization. There was no difference in fold change of antibody between individuals with and without an URTI at the time of immunization. Overall, we observed no effect of pre-existing influenza-specific nasal antibody levels on immunogenicity, supporting annual immunization with LAIV in children.

Clinicopathological Spectrum of Xanthogranulomatous Pyelonephritis.

Xanthogranulomatous pyelonephritis (XGP) is an uncommon and distinct type of chronic infective pyelonephritis causing destruction of the kidney, severely affecting the renal function. The perinephric adipose tissue and peritoneum is not uncommonly involved. The study was undertaken to decipher the clinicopathologic spectrum of XGP. Forty cases of XGP were diagnosed on histopathology over a period of 13 years (2005-2017). Relevant clinical details and radiological findings were recorded from the case files. Out of a total of 40 cases, 26 were female and 14 were male with a mean age of 39.5 ± 13.6 years. Flank pain was the most common presenting symptom. All the patients had unilateral disease and underwent nephrectomy for a nonfunctional kidney. Gross examination showed enlarged kidney with replacement of cortico-medullary tissue by yellow nodular areas of fatty tissue and dilatation of the pelvicalyceal system. Thirty-six (90%) cases had nephrolithiasis. Histologically, the characteristic feature was the existence of lipid-laden foamy macrophages. Renal parenchymal involvement was diffuse in majority (31, 77.5%). Two (5.0%) of the patients had coexisting carcinoma in the same kidney. Histopathologic examination gives the definitive diagnosis of XGP which relies on the characteristic morphology. Surgical intervention in the form of nephrectomy is the treatment of choice and offers good treatment outcomes.

Coronary Artery Disease Associated Transcription Factor TCF21 Regulates Smooth Muscle Precursor Cells that Contribute to the Fibrous Cap.

TCF21 is a basic helix-loop-helix transcription factor that has recently been implicated as contributing to susceptibility to coronary heart disease based on genome wide association studies. In order to identify transcriptionally regulated target genes in a major disease relevant cell type, we performed siRNA knockdown of TCF21 in in vitro cultured human coronary artery smooth muscle cells and compared the transcriptome of siTCF21 versus siCONTROL treated cells. The raw (FASTQ) as well as processed (BED) data from 3 technical replicates per treatment has been deposited with Gene Expression Omnibus (GSE44461).

Supratentorial glioblastoma multiforme metastasizing to the cervical spinal cord.

Cases of glioblastoma multiforme (GBM) metastasizing to the leptomeninges or the intramedullary spine are rare and their prognosis are relatively poor. We present a case of supratentorial glioblastoma WHO grade IV which was later diagnosed to have cervical intramedullary metastasis 7 months after the primary surgery.

Custom made pressure appliance for presurgical sustained compression of auricular keloid.

Keloid is dermal lesion characterized by nodular fibroblastic proliferation, which is considered an aberration of wound healing process. It is believed to be the confused scar that does not know when to stop growing. Pressure therapy using clips or splints is widely used for the treatment of keloids; however, it is often very difficult to control the amount and direction of pressure applied. Among the most common complications of this therapy is ulceration due to excessive pressure. A case of presurgical size reduction for a large ear keloid with a custom made pressure appliance is presented. This novel design of the appliance allows for better control over the amount and direction of the pressure applied on the scar tissue.

Evaluation of safety and immunogenicity of a live attenuated tetravalent (G1-G4) Bovine-Human Reassortant Rotavirus vaccine (BRV-TV) in healthy Indian adults and infants.

BACKGROUND: Rotavirus infections, prevalent in human populations worldwide are mostly caused by Group A viruses. Live attenuated rotavirus vaccines are highly effective in preventing severe rotavirus gastroenteritis. However, the cost of these vaccines and local availability can be a barrier for widespread adoption in public health programs in developing countries where infants suffer a heavy burden of rotavirus related morbidity and mortality. A phase I/II study was carried out with the long term aim to produce a locally licensed vaccine which is equally safe and immunogenic as compared to available licensed vaccines. METHODS: This study was conducted in two cohorts. In the first cohort, 20 healthy adults were administered a single dose of the rotavirus vaccine (highest antigen concentration planned for infants) or placebo and were followed up for 10 days for safety. Following demonstration of safety in adult volunteers, 100 healthy infants were recruited (cohort 2) and randomly divided into five equal study groups. They were administered three doses of either the investigational rotavirus vaccine (BRV-TV) at one of the three antigen concentrations or Rotateq or Placebo at 6-8, 10-12 and 14-16 weeks of age. All infants were followed up for safety till 28 days after the third dose. Immune response to the vaccine, in terms of seroresponse and geometric mean concentrations, was compared across the five study groups. RESULTS: Increase in anti-rotavirus serum IgA antibodies from baseline, demonstrated higher immune response for all the three antigen concentrations of BRV-TV vaccine and RotaTeq in comparison with the placebo. Sero-response rates for placebo, BRV-TV dose-levels 10(5.0) FFU, 10(5.8) FFU, 10(6.4) FFU, and Rotateq at 28 days post third dose were 11.1%, 27.8%, 41.2%, 83.3%, and 63.2% respectively using the four-fold or more criteria. The BRV-TV vaccine arm corresponding to the highest antigen concentration of 10(6.4) FFU had a higher sero-response rate compared to the active comparator arm (RotaTeq), 28 days post each vaccine dose. The safety profile was comparable across the treatment groups. CONCLUSIONS: Overall, the results showed that all three doses of BRV-TV vaccine were safe, well tolerated and displayed good immunogenicity (dose-response) in healthy Indian infants.

A multicenter prospective hospital-based surveillance to estimate the burden of rotavirus gastroenteritis in children less than five years of age in India.

BACKGROUND: Rotavirus is the leading cause of severe, dehydrating diarrhea in children aged <5 years globally, with an estimated 25 million outpatient visits and 2 million hospitalizations attributable to rotavirus infections each year. The aim of this hospital-based surveillance was to summarize the local epidemiological and virological features of rotavirus and to estimate the disease burden in the population under surveillance in India. METHODS: During the 16 months surveillance period from April 2011 through July 2012, a total of 4711 children under the age of 5 years were admitted with acute diarrhea at 12 medical centers attached to medical schools throughout India. Stool samples were randomly collected from 2051 (43.5%) subjects and were analyzed for rotavirus positivity using commercial enzyme immunoassay kit (Premier Rotaclone Qualitative Elisa) at the respective study centers. Rotavirus positive samples were genotyped for VP7 and VP4 by reverse-transcription polymerase chain reaction (RT-PCR) at a central laboratory. RESULTS: During the study period, maximum number of rotavirus related hospitalizations were reported from December 2011 through February 2012. Out of the 2051 stool samples tested for rotavirus, overall 541 (26.4%) samples were positive for rotavirus VP6 antigen in stool. The highest positivity was observed in the month of December, 2011 (52.5%) and lowest in the month of May, 2011 (10.3%). We found that majority of the rotavirus positive cases (69.7%) were in children <24 months of age. The most common genotypes reported were G1 (38%), G2 (18%), G9 (18%), G12 (9%) and mixed strains (17%). CONCLUSIONS: The results of this study confirm the significant burden of acute rotavirus gastroenteritis as a cause of hospitalizations in under five children in India.

Facial hyperpigmentation: causes and treatment.

By midcentury, the U.S.A. will be more ethnically and racially diverse. Skin of colour will soon constitute nearly one-half of the U.S. population, and a full understanding of skin conditions that affect this group is of great importance. Structural and functional differences in the skin, as well as the influence of cultural practices, produce variances in skin disease and presentation based on skin type. In the skin of colour population, dyschromia is a growing concern, and a top chief complaint when patients present to the physician. A thorough understanding of the aetiology and management strategies of facial hyperpigmentation is of importance in caring for those afflicted and also in the development of new therapies.

Seasonal variations in the water quality, diversity and population ecology of intertidal macrofauna at an industrially influenced coast.

Present communication reports the physico-chemical and biological quality of seawater and status of benthos of a highly industrialized shore of the north-western coastline of India. The coastal area considered for the present study, encircled by a variety of industries, was divided into two sampling sites and monitored for two consecutive years. Results of the water quality suggest that the obtained values of the physical and chemical parameters of seawater were comparable with data reported earlier. However, data obtained in the biological parameters of the seawater showed a declining trend. Results of the intertidal macrofaunal diversity studies revealed that the muddy upper littoral zones were represented by few species of coelenterata, porifera, arthropoda and mollusca. In the rocky-muddy middle littoral zones, gastropods, stars fishes, corallites, crabs, polychetes and tubeworms were present, whereas, predominantly rocky lower littoral zones were comparatively rich in macrofaunal diversity with small patches of coral colonies. However, when the results obtained in the present study was compared with that of earlier reported data, it was clear that the macrofaunal diversity indeed declined considerably over the years. This may be due to habitat destruction and habitat alteration in the coastline caused by increased anthropogenic activities in the area. Seasonal variations in the population density and abundance were observed in most of the faunal groups except in sessile corals and sponges. This may be due to local migration of the faunal groups towards deeper regions of the Gulf, as supported by the analysis of similarity, to avoid influx of freshwater during monsoon, and high temperature during summer and post monsoon seasons. The overall assessment of different parameters of this study revealed that though the physico- chemical characteristics of the seawater did not varied much from the earlier reported status, the biological characteristics of the seawater and intertidal zone was affected possibly by a high degree of anthropogenic pressure.

Leprosy among adolescents in Kolkata, India.

Leprosy, manifesting during adolescence when significant physical and emotional changes are taking place, poses further stress and strain both on the individual and on the family. Based on hospital records, focus group discussions and in-depth interviews, data on 258 adolescent leprosy patients seen at a leprosy referral hospital in Kolkata, India, are presented. The male-female sex ratio was 1.93:1, 56.6% were multibacillary patients and 13.2% had grade 2 disability. At the time of final follow up, 10% of PB and 33% of MB patients had already discontinued treatment. The commonest complication was reaction (14.5%). Adolescents were still dependent on their parents for health matters. Data obtained from questionnaires confirmed the role of social stigma in hiding, delay in starting of MDT and defaulting. Frequent hospital admissions resulted in loss of jobs and disruption of studies and caused psychological disturbances. It is critical to identify and treat adolescent leprosy on a priority basis. Health education and counselling programmes must be more focused and acceptable. Further research is necessary.

Phenotypic differentiation of TGF-beta1-responsive pluripotent premesenchymal prehematopoietic progenitor (P4 stem) cells from murine bone marrow.

On the horizon of modern molecular medicine is the requisite technology to capture multipotent human stem cells that are capable of self-renewal and to direct these stem cells along defined lineages for therapeutic purposes. In this article, we describe the hematopoietic and mesenchymal differentiation potential of a unique population of transforming growth factor-beta1 (TGF-beta1)-responsive stem cells derived from murine bone marrow. Stringent selection of the stem cells was accomplished under low serum conditions by virtue of an inherent survival response to a TGF-beta1-vWF fusion protein that was bound to collagen matrices. The TGF-beta1-responsive stem cells initially exhibited a non-adherent and uniformly blastoid morphology, underwent expansion into colonies upon serum reconstitution, and were capable of overt cytodifferentiation along fibrogenic, osteogenic, chondrogenic, or adipogenic lineages upon growth factor stimulation. Remarkably, these stem cells also underwent rapid expansion in the presence of either hematopoietic stem cell factor (SCF) or interleukin3 (IL-3), and differentiated into myeloid and lymphoid phenotypes upon exposure to the latter. Taken together, these results support the hypothesis that pluripotent premesenchymal prehematopoietic progenitor cells, designated P4 stem cells, are present postnatally in murine bone marrow and, thus, may be summarily isolated for various cell-based experimental therapies.

Effect of climate on the seasonal endocrine profile of native and crossbred sheep under semi-arid conditions.

Thirty-four 2-year-old ewes, of which 17 were native (Chokla) and 17 were Avivastra (Chokla 67.5% x 32.5% Rambouillet) breeds of similar body weights, were selected. Both groups were maintained under the same management conditions with 8 hours daily grazing. In addition to grazing, each ewe received 300 g/day of a concentrate mixture comprising crude protein 20% and 70% total digestible nutrients. The ewes of both breeds were not mated during the study. The daily environmental parameters were recorded throughout the year, consisting of four main seasons, namely rainy, winter, spring and summer. Blood samples were collected into heparinized tubes during the morning hours for seasonal studies via indwelling jugular vein catheters to avoid stress to the animals, but for the diurnal studies the sampling was done twice daily at 07:00 and 17:00 continuously for three days in each season. Cortisol, thyroxine (T4) and triiodothyronine (T3) were estimated in the samples. The T4 and T3 profiles were maximal in the summer, followed by the rainy season in both groups, with no significant differences. However, the cortisol in both the groups was maximal during the spring rather than the summer. No significant differences were found in T3 concentration between morning and afternoon in any season in the native ewes but these animals showed significantly higher levels of T4 in the morning. The opposite was true for the crossbred animals with regard to both the T3 and T4 profiles. Significantly more cortisol was found in the evening than in the morning in both genetic groups in all seasons.

Factors regulating the metastatic potential of benign giant cell tumour of bone--study of an unusual case with short review of literature.

Benign giant cell tumour of bone with metastases to other bones and lungs is extremely rare. Benign metastasising giant cell tumour is distinctly separate from multicentric giant cell tumour, primary and secondary malignant giant cell tumour. Factors regulating the local recurrence and metastatic potential of this benign tumour depend on its aggressiveness which can be better assessed by clinical and radiological parameters rather than the histopathological appearance. A benign giant cell tumour of ischium with metastasis to vertebra and lung over an eleven year period is discussed. Extreme paucity of literature prompted to publish the article. A short review of factors determining the recurrence and metastatic spread of benign giant cell tumour of bone is highlighted.

Multifocal giant cell tumour of bone in a skeletally immature patient--a case report.

Giant cell tumor of bone is usually seen in adults affecting a single bone. Multiple giant cell tumour of bone occurring in skeletally immature patients is extremely rare. Multifocal giant cell tumor of bone in a ten year old boy involving upper end of humerus and tibia is being reported for its extreme paucity in literature.

Molecular mechanism of decreased glutathione content in human immunodeficiency virus type 1 Tat-transgenic mice.

Human immunodeficiency virus (HIV) progressively depletes GSH content in humans. Although the accumulated evidence suggests a role of decreased GSH in the pathogenesis of HIV, significant controversy remains concerning the mechanism of GSH depletion, especially in regard to envisioning appropriate therapeutic strategies to help compensate for such decreased antioxidant capacity. Tat, a transactivator encoded by HIV, is sufficient to cause GSH depletion in vitro and is implicated in AIDS-associated Kaposi's sarcoma and B cell lymphoma. In this study, we report a decrease in GSH biosynthesis with Tat, using HIV-1 Tat transgenic (Tat+) mice. A significant decline in the total intracellular GSH content in liver and erythrocytes of Tat+ mice was accompanied by decreased gamma-glutamylcysteine synthetase regulatory subunit mRNA and protein content, which resulted in an increased sensitivity of gamma-glutamylcysteine synthetase to feedback inhibition by GSH. Further study revealed a significant reduction in the activity of GSH synthetase in liver of Tat+ mice, which was linearly associated with their GSH content. Therefore, Tat appears to decrease GSH in vivo, at least partially, through modulation of GSH biosynthetic enzymes.

Primary malignant giant cell tumour of bone--a study of two cases with short review.

Primary malignant giant cell tumour of bone is extremely rare. It is distinctly separate from benign metastasising giant cell tumour of bone and secondary malignant giant cell tumour which occurs in response to radiotherapy and repeated curettage of benign giant cell tumor. The tumor has high mortality rate. It usually affects lower end of femur and upper end of tibia. Two usually affects lower end of femur and upper end of tibia. Two cases, on involving upper end of tibia and other in vertebra are discussed. Extreme paucity of literature prompted to publish this article. A short review of radiological appearance, histopathological findings and treatment modalities is highlighted.

Epidermal dysplasia and abnormal hair follicles in transgenic mice overexpressing homeobox gene MSX-2.

The homeobox gene Msx-2 is expressed specifically in sites of skin appendage formation. To explore its part in skin morphogenesis, we produced transgenic mice expressing Msx-2 under the control of the cytomegalovirus promoter. The skin of these transgenic mice was flaky, exhibiting desquamation and shorter hairs. Histologic analysis showed thickened epidermis with hyperproliferation, which was restricted to the basal layer. Hyperkeratosis was also evident. A wide zone of suprabasal cells were misaligned and coexpressed keratins 14 and 10. There was reduced expression of integrin beta 1 and DCC in the basal layer. Hair follicles were misaligned with a shrunken matrix region. The dermis showed increased cellularity and empty vacuoles. We suggest that Msx-2 is involved in the growth control of skin and skin appendages.