Glucuronoxylomannan intranasal challenge prior to Cryptococcus neoformans pulmonary infection enhances cerebral cryptococcosis in rodents.

The encapsulated fungus Cryptococcus neoformans is the most common cause of fungal meningitis, with the highest rate of disease in patients with AIDS or immunosuppression. This microbe enters the human body via inhalation of infectious particles. C. neoformans capsular polysaccharide, in which the major component is glucuronoxylomannan (GXM), extensively accumulates in tissues and compromises host immune responses. C. neoformans travels from the lungs to the bloodstream and crosses to the brain via transcytosis, paracytosis, or inside of phagocytes using a "Trojan horse" mechanism. The fungus causes life-threatening meningoencephalitis with high mortality rates. Hence, we investigated the impact of intranasal exogenous GXM administration on C. neoformans infection in C57BL/6 mice. GXM enhances cryptococcal pulmonary infection and facilitates fungal systemic dissemination and brain invasion. Pre-challenge of GXM results in detection of the polysaccharide in lungs, serum, and surprisingly brain, the latter likely reached through the nasal cavity. GXM significantly alters endothelial cell tight junction protein expression in vivo, suggesting significant implications for the C. neoformans mechanisms of brain invasion. Using a microtiter transwell system, we showed that GXM disrupts the trans-endothelial electrical resistance, weakening human brain endothelial cell monolayers co-cultured with pericytes, supportive cells of blood vessels/capillaries found in the blood-brain barrier (BBB) to promote C. neoformans BBB penetration. Our findings should be considered in the development of therapeutics to combat the devastating complications of cryptococcosis that results in an estimated ~200,000 deaths worldwide each year.

Health status of tribes of Uttar Pradesh with special reference to health-seeking behaviour of uncharted Tharu tribe: A mapping review.

Background & objectives: The tribal population in India is considered as one of the vulnerable groups with respect to their achievements in health and other developmental issues. In this context, this mapping review attempted to understand the health profile of the Tharu tribal community residing in the northern State of Uttar Pradesh, India through literature mining. Tharu tribe is one of the indigenous groups living in the Terai plain on the Indo-Nepal border. In 1967, this tribe was documented as a Scheduled Tribe by the Government of India. The present review aimed to map the health-seeking behaviour of the Tharu population and review other factors pertaining to their health such as socioeconomic, developmental, employment, education, etc. Methods: Online data search was carried out on PubMed and Google Scholar using search terms 'Tharu' AND 'India'. In addition, official reports avaibale in public domain and grey literature was also searched. Results: Twenty seven studies including reviews, articles, books/book chapters were evaluated along with 13 reports (including reports from government organizations and grey literature) were retrieved and analyzed. Of the 27 published reports, 16 were found relevant to Tharu tribe in India. A total of 29 (16 articles + 13 reports ) were included in this review. Interpretation & Conclusions: This mapping review highights the health seeking behaviour of the Tharu tribe in India that can help inform future interventions to improve the health status of the Tharu tribe as well as other aspects of their development.

Estimates of the burden of human rabies deaths and animal bites in India, 2022-23: a community-based cross-sectional survey and probability decision-tree modelling study.

BACKGROUND: Reliable and recent data of human rabies deaths and animal bites are not available in India, where a third of global cases occur. Since there is a global target of eliminating dog-mediated human rabies by 2030, understanding whether the country is on track is essential. We aimed to estimate the animal-bite burden and the number of human rabies deaths in India. METHODS: We conducted a community-based nationwide cross-sectional survey with a multistage cluster-sampling design from March 2, 2022 to Aug 26, 2023, covering 60 districts in 15 Indian states. The head of the household or an adult family member was interviewed to collect information about animal-bite history in family members, receipt of anti-rabies vaccination (ARV), and death following animal bite in the family. Annual animal-bite incidence along with 95% CIs were estimated after applying the sampling weights and adjusting for clustering. We estimated annual human rabies deaths using a decision-tree probability model with parameters from the community survey and laboratory data on rabies positivity among suspected rabid dogs. FINDINGS: Of the 337 808 individuals residing in the 78 807 households surveyed, 2052 gave a history of animal bite, mostly (1576 [76·8%]) due to dogs in the past 1 year. The weighted and adjusted annual incidence of animal bite was 6·6 (95% CI 5·7-7·6) per 1000 population, translating into 9·1 million bites nationally. Annual dog-bite incidence was 5·6 (4·8-6·6) per 1000. Among people who had been bitten by a dog, 323 (20·5%) did not receive ARV, and 1043 (66·2%) received at least three doses. Nearly half (615 [49·1%]) of the 1253 individuals who received one dose did not complete their full course of vaccination. We estimated 5726 (95% uncertainty interval 3967-7350) human rabies deaths occurring annually in India. INTERPRETATION: Although there was a substantial decline in human rabies deaths over the past two decades, to eliminate dog-mediated human rabies by 2030, India needs to fast-track its actions by adopting a focused one-health approach. Integrating human and animal surveillance, ensuring timely administration of full course of post-exposure prophylaxis, and accelerating dog vaccination across the country are crucial steps towards this goal. FUNDING: Indian Council of Medical Research.

Ureteral Stone Mimicking Metastasis - Planar Bone Scan When Single-photon Emission Computed Tomography/Computed Tomography Is a Necessity.

In this case, we demonstrated a ureteric stone that resembled bone metastasis. Because bone-seeking radiopharmaceuticals are excreted into the urine by the kidneys, normal kidneys and bladder are well visualized on skeletal scintigraphs leading to incidental detection of urinary tract abnormalities. Bone tracer uptake related to ureteral stones has been reported [Figure 1] several times before. We present a right ureteral stone mimicking abnormal focal sacral uptake on planar scan in a patient with rectal cancer. This case emphasizes the importance of using single-photon emission computed tomography/computed tomography to determine the cause of abnormal uptake on a planar scan.

Incidentally Detected Metachronous Malignancy in Patients of Papillary Carcinoma of Thyroid Posthigh-Dose Radioiodine Therapy.

Thyroid cancer is one of the most common endocrine cancers. The most common histological subtypes are papillary and follicular variants; these are "differentiated thyroid cancers" and are associated with an excellent prognosis. The exact mechanism of thyroid cancer is not known. Several genetic alterations and environmental factors are found to be associated with this cancer. Patients with differentiated thyroid cancer are treated with postoperative radioactive iodine (RAI) therapy to ablate residual thyroid tissue and metastatic micro-foci. It is thought that after RAI, there is an increased risk of secondary malignancies such as lung, renal, and stomach cancer and lymphomas. However, the risk of secondary malignancy is not clear. They may be associated with genetic syndromes, environmental factors, and radiation exposure. The secondary malignancy may be detected incidentally during follow-up or present with signs and symptoms of that malignancy. There is no direct association between second malignancy and radiation exposure in I-131 therapies. We present a case series of five patients treated with high doses of I-131 for the remnant. The patients developed metachronous malignancies later in life.

Facilitators and barriers to the uptake of COVID-19 vaccine precaution dose among adult population: qualitative analysis across six different states of India.

Introduction: India launched the COVID-19 vaccination drive on 16th January 2021 by vaccinating the adult population above 18 years of age. This was followed by the introduction of an additional precaution dose. As on 18th October 2022, 1,02,66,96,808 (1.02 Billion) first dose and 94, 95, 39,516 (949 Million) second doses of COVID-19 vaccine were administered. However, when compared to the uptake of the primary doses, the precaution dose uptake lagged behind with only 21,75, 12,721 (217 million) doses administered. Even though, the uptake of the primary doses remained optimal, irrespective of different interventions by the Government of India, the uptake of the precaution dose remained poor. In this context, the Ministry of Health & Family Welfare wanted to understand the facilitators and Barriers for precaution dose uptake among adults so that future immunization campaigns could address these issues. Methods: An exploratory qualitative study was conducted to assess the facilitators and barriers for COVID-19 precaution dose uptake at community level across 6 different states in India. From each of the states, two districts with the highest and lowest rates of COVID-19 vaccine precaution dose uptake were selected. In each of these districts, 2 block Primary Healthcare Centres (PHCs), one with high and one with low uptake were identified. Within these block PHCs, a PHC field area with high and low precaution dose uptakes was identified. From the identified sites a minimum of four IDIs, four FGDs were conducted among the community members. KIIs of the State Immunization Officers, District Immunisation Officers, PHC Medical Officers, healthcare workers like Accredited Social Health Activist/Auxiliary Nurse Midwife were also conducted. The data was audio recorded and it was transcribed, translated and analysed using framework approach. Results: It was observed that rise in COVID-19 cases prompted the community to take the precaution dose, this along with the cost of hospitalization and the number of productive days being lost as a result of being infected resulted in vaccine uptake. The fear of non-availability of COVID-19 vaccines latter on also prompted people for vaccine uptake. While the barriers were, poor accessibility to vaccination centers, long hours of travel, poor road connectivity and lack of transportation facilities. However, the most prominent barriers observed across all study sites was that a sense of pandemic fatigue and complacency had developed both among the providers as well as the beneficiaries. Other barriers include differences in vaccination schedules and longer duration between the primary doses of some vaccines. Media was identified to be both a barrier and facilitator for Covid-19 Precaution dose uptake. Even though media played an important role in disseminating information in the beginning of the campaign, it was soon followed by the circulation of both misinformation and disinformation. Discussion: The study identified that dissemination of accurate information and community involvement at each stage of planning and implementation are crucial for the success of any campaign. Efforts should be constantly made to address and re-invent strategies that will be most suitable for the needs of the community. Therefore, in order to ensure successful vaccination campaigns, it is crucial that along with political will it is also important to have a decentralized approach with inter-sectoral coordination with different stakeholders such as healthcare workers, community members and the different departments such as the local self-governments, education department, law & order department etc. These lessons learnt from COVID-19 vaccination campaigns must not be forgotten and must be applied in future vaccination campaigns and while framing public health policies.

Extensive Pleural Involvement in Pediatric T-Cell Lymphoblastic Lymphoma.

Lymphoblastic lymphoma (LBL) is the common non-Hodgkin lymphoma in childhood and adolescence. T-cell LBL (T-LBL) usually manifests with an anterior mediastinal mass and disseminated disease. We present a 12-year-old girl with progressive neck swelling and dyspnea for 1 year. Fluorodeoxyglucose positron-emission tomography/computed tomography done for pretreatment staging unveiled hypermetabolic lymph nodes on both sides of the diaphragm with splenic and bone marrow involvement. Apart from these, there was the extensive involvement of the left pleura. Biopsy and immunohistochemistry revealed T-LBL. The extensive secondary pleural involvement in pediatric T-LBL is rarely seen and needs to be reported.

Utility of F-18 Fluorodeoxyglucose Positron Emission Tomography - Computed Tomography in Primary Thyroid Lymphoma.

Primary thyroid lymphoma (PTL) is an uncommon malignancy. The majority of PTLs are non-Hodgkin's lymphoma. Fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT) is the state-of-the-art imaging in lymphoma and plays a pivotal role in staging, follow-up, and treatment decisions. There is good evidence that it performs well in a wide variety of nodal and extranodal lymphomas (ENL). However, the data are scarce on its usefulness in rare ENL. Herein, we describe four cases of PTLs and a brief review of the literature. FDG PET/CT was performed at baseline to assess the disease status and response to treatment. This case series highlights the varied appearance of PTL and response to treatment. It establishes the importance of FDG PET/CT in the personalized management of PTL.

F-18 Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in a Case of Subcutaneous T-cell Lymphoma Presenting as Breast Mass and Panniculitis-Like Features: A Rare Entity.

Subcutaneous panniculitis-like T-cell lymphoma (SPTCL) is an unusual subtype of cutaneous lymphoma and clinically appears as erythematous, subcutaneous infiltrates, and recurrent papulonodules. It is defined as a rare cytotoxic a/b T-cell lymphoma characterized by primary involvement of subcutaneous tissue-mimicking panniculitis and a predominant CD3+/CD4/CD8+ phenotype in (2005) the World Health Organization-European Organization for Research and Treatment of Cancer classification for cutaneous lymphomas. On metabolic imaging, these lesions are invariably fluorodeoxyglucose (FDG) avid. SPTCL which presents as a breast mass is a rare entity. Here, we present a case of SPTCL presents as FDG avid breast mass and subcutaneous nodules.

Health Seeking Behaviour and Healthcare Utilization in a Rural Cohort of North India.

BACKGROUND: The healthcare infrastructure of a country determines the health-seeking behaviour of the population. In developing countries such as India, there is a great disparity in the distribution of healthcare institutions across urban and rural areas with disadvantages for people living in rural areas. OBJECTIVES: Our objectives were to study the health-seeking behavior and factors associated with the use of formal healthcare among the Gorakhpur Health and Demographic Surveillance System (GHDSS) cohort of North India. METHODS: The study was conducted in 28 villages from two rural blocks in the Gorakhpur district of eastern Uttar Pradesh, North India. Structured questionnaires were used to collect the data with regard to demographics, health-seeking behaviour and healthcare utilization. An adjusted odds ratio with 95% confidence interval was used to report the factors associated with the utilization of healthcare. RESULTS: Out of 120,306 individuals surveyed, 19,240 (16%) individuals reported having any health problem in the last 15 days. Of them, 90% sought healthcare for their health needs. The formal healthcare utilization was 79%. The use of public health facilities was very low (37%) with most of the people seeking treatment from private healthcare (63%). Females, people with a higher level of education (graduate and above), and those belonging to rich and middle tercile were more likely to use formal healthcare services. Among different ailments, respiratory problems, gastrointestinal problems, and musculoskeletal problems were associated with decreased use of formal healthcare. CONCLUSION: About four in five individuals surveyed who had health problems sought treatments from formal healthcare with three in five preferring private institutions to public healthcare facilities due to a perceived higher level of treatment quality and nearby availability. There is an urgent need to re-establish community trust among public healthcare facilities with a focus on delivering on-site health care and enhancing the quality of services offered by public healthcare institutions.

Surface Modification of Bioresorbable Phosphate Glasses for Controlled Protein Adsorption.

The traditional silicate bioactive glasses exhibit poor thermal processability, which inhibits fiber drawing or sintering into scaffolds. The composition of the silicate glasses has been modified to enable hot processing. However, the hot forming ability is generally at the expense of bioactivity. Metaphosphate glasses, on the other hand, possess excellent thermal processability, congruent dissolution, and a tailorable degradation rate. However, due to the layer-by-layer dissolution mechanism, cells do not attach to the material surface. Furthermore, the congruent dissolution leads to a low density of OH groups forming on the glass surface, limiting the adsorption of proteins. It is well regarded that the initial step of protein adsorption is critical as the cells interact with this protein layer, rather than the biomaterial itself. In this paper, we explore the possibility of improving protein adsorption on the surface of phosphate glasses through a variety of surface treatments, such as washing the glass surface in acidic (pH 5), neutral, and basic (pH 9) buffer solutions followed or not by a treatment with (3-aminopropyl)triethoxysilane (APTS). The impact of these surface treatments on the surface chemistry (contact angle, ζ-potential) and glass structure (FTIR) was assessed. In this manuscript, we demonstrate that understanding of the material surface chemistry enables to selectively improve the adsorption of albumin and fibronectin (used as model proteins). Furthermore, in this study, well-known silicate bioactive glasses (i.e., S53P4 and 13-93) were used as controls. While surface treatments clearly improved proteins adsorption on the surface of both silicate and phosphate glasses, it is of interest to note that protein adsorption on phosphate glasses was drastically improved to reach similar protein grafting ability to the silicate bioactive glasses. Overall, this study demonstrates that the limited cell/phosphate glass biological response can easily be overcome through deep understanding and control of the glass surface chemistry.

In-vitro dissolution characteristics and human adipose stem cell response to novel borophosphate glasses.

The main drawbacks of traditional silicate bioactive glasses are their narrow hot forming domain and noncongruent dissolution. In this article, we report on new borophosphate glasses [xMn Om + (100 - x) (47.5P2 O5 + 2.5B2 O3 + 10Na2 O + 20CaO + 20SrO)], Mn Om being CuO, Ag2 O, and CeO2 , having high thermal processability, hence suitable for fiber drawing and sintering into scaffolds. Furthermore, the glasses dissolve congruently in simulated body fluid (SBF) and TRIS buffer solution, eventually leading to the precipitation of a reactive layer. Human adipose stem cells (hASC) were cultured in media enriched with glass extract at different dilutions, to investigate the optimal ion concentration for cell survival. Cells grew in all the extracts, except in the undiluted Cu-doped glass extract. At dilution 1:10, the lactate dehydrogenase (LDH) activity and cell proliferation were comparable to the control, while at 1:100, the cells proliferated faster than the control. Thus, the reference (undoped), Ag and Ce-doped glasses were found to be suitable for cell viability and proliferation. Cytotoxicity assessments using the LDH assay indeed revealed the high cytotoxicity of the Cu extract. This raises questions about the use of Cu in bioactive glasses and its optimal concentration as a dopant.

Wood-based nanocellulose and bioactive glass modified gelatin-alginate bioinks for 3D bioprinting of bone cells.

A challenge in the extrusion-based bioprinting is to find a bioink with optimal biological and physicochemical properties. The aim of this study was to evaluate the influence of wood-based cellulose nanofibrils (CNF) and bioactive glass (BaG) on the rheological properties of gelatin-alginate bioinks and the initial responses of bone cells embedded in these inks. CNF modulated the flow behavior of the hydrogels, thus improving their printability. Chemical characterization by SEM-EDX and ion release analysis confirmed the reactivity of the BaG in the hydrogels. The cytocompatibility of the hydrogels was shown to be good, as evidenced by the viability of human osteoblast-like cells (Saos-2) in cast hydrogels. For bioprinting, 4-layer structures were printed from cell-containing gels and crosslinked with CaCl2. Viability, proliferation and alkaline phosphatase activity (ALP) were monitored over 14 d. In the BaG-free gels, Saos-2 cells remained viable, but in the presence of BaG the viability and proliferation decreased in correlation with the increased viscosity. Still, there was a constant increase in the ALP activity in all the hydrogels. Further bioprinting experiments were conducted using human bone marrow-derived mesenchymal stem cells (hBMSCs), a clinically relevant cell type. Interestingly, hBMSCs tolerated the printing process better than Saos-2 cells and the ALP indicated BaG-stimulated early osteogenic commitment. The addition of CNF and BaG to gelatin-alginate bioinks holds great potential for bone tissue engineering applications.

The effect of S53P4-based borosilicate glasses and glass dissolution products on the osteogenic commitment of human adipose stem cells.

Despite the good performance of silicate bioactive glasses in bone regeneration, there is considerable potential to enhance their properties by chemical modifications. In this study, S53P4-based borosilicate glasses were synthesized and their dissolution profile was studied in simulated body fluid by assessing pH change, ion release and conversion to hydroxyapatite. The viability, proliferation, attachment, osteogenesis and endothelial marker expression of human adipose stem cells (hASCs) was evaluated upon direct culture on glass discs and in the extract medium. This is the first study evaluating cell behavior in response to borosilicate glasses based on S53P4 (commercially available as BonAlive®). Replacing silicate with borate in S53P4 increased the glass reactivity. Despite the good viability of hASCs under all conditions, direct culture of cells on borosilicate discs and in undiluted extract medium reduced cell proliferation. This was accompanied with changes in cell morphology. Regarding osteogenic commitment, alkaline phosphatase activity was significantly reduced by the borosilicate glass discs and extracts, whereas the expression of osteogenic markers RUNX2a, OSTERIX, DLX5 and OSTEOPONTIN was upregulated. There was also a borosilicate glass-induced increase in osteocalcin protein production. Moreover, osteogenic supplements containing borosilicate extracts significantly increased the mineral production in comparison to the osteogenic medium control. Interestingly, borosilicate glasses stimulated the expression of endothelial markers vWF and PECAM-1. To conclude, our results reveal that despite reducing hASC proliferation, S53P4-based borosilicate glasses and their dissolution products stimulate osteogenic commitment and upregulate endothelial markers, thus supporting their further evaluation for regenerative medicine.