Oral manifestations of disseminated histoplasmosis are rare but can present in immunocompromised individuals. We report a case of disseminated Histoplasmosis presenting with presumed oral involvement and pneumonia in a seropositive HIV individual. A 32-year-old male with HIV presented to the emergency department for a two-week history of abdominal pain and a tongue ulcer in the setting of significant weight loss, blood-tinged sputum, and non-adherence with antiretroviral therapy for three years.
View Article and Find Full Text PDFIt is very rare to see fungal arthritis and pyomyositis in immunocompetent patients. Here, we report a case of Scedosporium infection in an immunocompetent patient with interesting 18F-FDG PET/CT and 68Ga-NOTA UBI PET/CT findings.
View Article and Find Full Text PDFThe profile of hypercalcaemia in hospitalized patients in India seems to be changing. However, studies evaluating the profile of hypercalcaemia in hospitalized settings in India are extremely limited. This prospective study aims to evaluate the clinical and biochemical profile of hospitalized patients with hypercalcaemia from a tertiary care centre in north India.
View Article and Find Full Text PDFAs next-generation sequencing technologies produce deeper genome coverages at lower costs, there is a critical need for reliable computational host DNA removal in metagenomic data. We find that insufficient host filtration using prior human genome references can introduce false sex biases and inadvertently permit flow-through of host-specific DNA during bioinformatic analyses, which could be exploited for individual identification. To address these issues, we introduce and benchmark three host filtration methods of varying throughput, with concomitant applications across low biomass samples such as skin and high microbial biomass datasets including fecal samples.
View Article and Find Full Text PDFInhibiting the immune checkpoint (ICP) PD-1 based on PD-L1 expression status has revolutionized the treatment of various cancers, yet its efficacy in anaplastic thyroid carcinoma (ATC) remains limited. The therapeutic response depends upon multiple factors, particularly the conduciveness of the tumor's immune milieu. This study comprehensively evaluated and classified ATC's immune microenvironment (IME) to elucidate the factors behind suboptimal response to anti-PD therapy.
View Article and Find Full Text PDFPrimary hyperparathyroidism is mostly caused by parathyroid adenoma(s) which are generally localized using routine imaging modalities such as neck ultrasonography and Tc-SestaMIBI scintigraphy. However, these can miss ectopic parathyroid adenomas due to their limited sensitivities. These ectopic lesions can later lead to failure of surgical excision and necessitate the need for a re-exploration.
View Article and Find Full Text PDFTelomeres are repetitive nucleoprotein complexes at chromosomal termini essential for maintaining genome stability. Telomeric RNA, or TERRA, is a previously presumed long noncoding RNA of heterogeneous lengths that contributes to end-capping structure and function, and facilitates telomeric recombination in tumors that maintain telomere length via the telomerase-independent Alternative Lengthening of Telomeres (ALT) pathway. Here, we investigated TERRA in the radiation-induced DNA damage response (DDR) across astronauts, high-altitude climbers, healthy donors, and cellular models.
View Article and Find Full Text PDFMaintenance of astronaut health during spaceflight will require monitoring and potentially modulating their microbiomes. However, documenting microbial shifts during spaceflight has been difficult due to mission constraints that lead to limited sampling and profiling. Here we executed a six-month longitudinal study to quantify the high-resolution human microbiome response to three days in orbit for four individuals.
View Article and Find Full Text PDFIt is now widely recognised that the environment in space activates a diverse set of genes involved in regulating fundamental cellular pathways. This includes the activation of genes associated with blood homoeostasis and erythropoiesis, with a particular emphasis on those involved in globin chain production. Haemoglobin biology provides an intriguing model for studying space omics, as it has been extensively explored at multiple -omic levels, spanning DNA, RNA, and protein analyses, in both experimental and clinical contexts.
View Article and Find Full Text PDFThe SpaceX Inspiration4 mission provided a unique opportunity to study the impact of spaceflight on the human body. Biospecimen samples were collected from four crew members longitudinally before (Launch: L-92, L-44, L-3 days), during (Flight Day: FD1, FD2, FD3), and after (Return: R + 1, R + 45, R + 82, R + 194 days) spaceflight, spanning a total of 289 days across 2021-2022. The collection process included venous whole blood, capillary dried blood spot cards, saliva, urine, stool, body swabs, capsule swabs, SpaceX Dragon capsule HEPA filter, and skin biopsies.
View Article and Find Full Text PDFThe advent of civilian spaceflight challenges scientists to precisely describe the effects of spaceflight on human physiology, particularly at the molecular and cellular level. Newer, nanopore-based sequencing technologies can quantitatively map changes in chemical structure and expression at single molecule resolution across entire isoforms. We perform long-read, direct RNA nanopore sequencing, as well as Ultima high-coverage RNA-sequencing, of whole blood sampled longitudinally from four SpaceX Inspiration4 astronauts at seven timepoints, spanning pre-flight, day of return, and post-flight recovery.
View Article and Find Full Text PDFSpaceflight can change metabolic, immunological, and biological homeostasis and cause skin rashes and irritation, yet the molecular basis remains unclear. To investigate the impact of short-duration spaceflight on the skin, we conducted skin biopsies on the Inspiration4 crew members before (L-44) and after (R + 1) flight. Leveraging multi-omics assays including GeoMx™ Digital Spatial Profiler, single-cell RNA/ATAC-seq, and metagenomics/metatranscriptomics, we assessed spatial gene expressions and associated microbial and immune changes across 95 skin regions in four compartments: outer epidermis, inner epidermis, outer dermis, and vasculature.
View Article and Find Full Text PDFAs spaceflight becomes more common with commercial crews, blood-based measures of crew health can guide both astronaut biomedicine and countermeasures. By profiling plasma proteins, metabolites, and extracellular vesicles/particles (EVPs) from the SpaceX Inspiration4 crew, we generated "spaceflight secretome profiles," which showed significant differences in coagulation, oxidative stress, and brain-enriched proteins. While >93% of differentially abundant proteins (DAPs) in vesicles and metabolites recovered within six months, the majority (73%) of plasma DAPs were still perturbed post-flight.
View Article and Find Full Text PDFSpaceflight induces molecular, cellular and physiological shifts in astronauts and poses myriad biomedical challenges to the human body, which are becoming increasingly relevant as more humans venture into space. Yet current frameworks for aerospace medicine are nascent and lag far behind advancements in precision medicine on Earth, underscoring the need for rapid development of space medicine databases, tools and protocols. Here we present the Space Omics and Medical Atlas (SOMA), an integrated data and sample repository for clinical, cellular and multi-omic research profiles from a diverse range of missions, including the NASA Twins Study, JAXA CFE study, SpaceX Inspiration4 crew, Axiom and Polaris.
View Article and Find Full Text PDFHuman spaceflight has historically been managed by government agencies, such as in the NASA Twins Study, but new commercial spaceflight opportunities have opened spaceflight to a broader population. In 2021, the SpaceX Inspiration4 mission launched the first all-civilian crew to low Earth orbit, which included the youngest American astronaut (aged 29), new in-flight experimental technologies (handheld ultrasound imaging, smartwatch wearables and immune profiling), ocular alignment measurements and new protocols for in-depth, multi-omic molecular and cellular profiling. Here we report the primary findings from the 3-day spaceflight mission, which induced a broad range of physiological and stress responses, neurovestibular changes indexed by ocular misalignment, and altered neurocognitive functioning, some of which match those of long-term spaceflight, but almost all of which did not differ from baseline (pre-flight) after return to Earth.
View Article and Find Full Text PDFVon Hippel-Lindau disease is a rare multisystem disorder that shows autosomal dominant inheritance. It is a cancer syndrome that is characterized by the development of a variety of benign and malignant tumors-CNS hemangioblastomas, retinal angiomas, endolymphatic sac tumors, renal cysts and tumors, pancreatic cysts and tumors, adrenal pheochromocytomas, and epididymal cystadenomas. Here we present the 68 Ga-labeled DOTANOC scans of 2 siblings who show an interesting spectrum of findings consistent with Von Hippel-Lindau disease.
View Article and Find Full Text PDFTertiary hyperparathyroidism (THPT) is characterized by over secretion of parathyroid hormone caused by long-standing secondary hyperparathyroidism. THPT can affect the bones as well as cause extraskeletal calcifications. The bony lesions often mimic multiple skeletal metastases or multiple myeloma.
View Article and Find Full Text PDFVery few imaging techniques can demonstrate the presence of . Technitium-99m Ethambutol scintigraphy is one of them, although literature on the utility of this technique is scarce. We describe a patient with iliopsoas abscess showing increased uptake on Tc-99 m ethambutol scintigraphy which was later confirmed to be tubercular by the microbiological analysis of pus.
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