Serum Galactomannan as a Minimally Invasive Diagnostic Tool for Fungal Skull Base Osteomyelitis.

Multidrug resistant strains and fungi add to treatment conundrums in skull base osteomyelitis (SBO). Deep tissue culture in these patients is challenging due to their advanced age and co-morbidities. Besides, fungal culture positivity is seen only in 60% of invasive aspergillosis. To determine the efficacy of a minimally invasive test-Serum Galactomannan (sGM)-for diagnosing fungal SBO. Prospective observational study. Thirty- three patients, clinically diagnosed with SBO were included in this study. Baseline ESR (Erythrocyte Sedimentation Rate), CRP (C- Reactive Protein), pain score, and sGM were noted for all patients. Antifungal Voriconazole was initiated on patients if the sGM values were more than 0.8. At the 12th week of treatment, all parameters were repeated and compared with the baseline values. A significant reduction was noted in ESR, CRP, and pain scores at the 12th week of treatment compared to the baseline values in patients with raised sGM values who were started on Voriconazole. For a culture-proven fungal skull base osteomyelitis with a cut-off value of sGM > / = 0.8, the obtained sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 81.82, 36.36, 39.13, 80 and 51.52% respectively. At a cut-off value of sGM > / = 01.6, the values of sensitivity/specificity, PPV, NPV and accuracy were 81.82/72.73%, 60%, 88.89% and 75.76%. Culture-negative patients in SBO with sGM value > 0.8 were more likely to be fungal SBO. An sGM cut-off of 1.6 was observed to give maximum accuracy for diagnosing fungal SBO.

Effect of irradiated nonionic surfactant on drug-protein binding.

In this work, the effect of γ-irradiated surfactants on drug-protein binding has been assessed. Irradiated aqueous solutions of Pluronic F-127, Pluronic L-35, Tween 20, and Tween 80 surfactants were used. Gamma irradiation was carried out for three different doses, to these four surfactants viz., 6, 30, and 36 kGy. Two drugs, Ornidazole (ONZ) and Telmisartan (TMS) were used for the binding study. The effect of four irradiated surfactants in the presence of drug - Bovine serum albumin (BSA) protein was analyzed. The drug solutions in methanol-aqueous media were combined with BSA in the initial step. In the next two succeeding steps, drug-BSA interaction in the presence of unirradiated and irradiated surfactants were carried out. The results of drug-BSA due to addition of irradiated and unirradiated surfactants were compared. The interaction processes were assessed through UV Spectroscopy, DLS, zeta potential, turbidity, and docking studies. Improved binding was observed for both the drugs and four surfactants for irradiated surfactants as determined from the binding constant values using UV spectroscopic studies. The DLS measurements demonstrated no general trend of increase or decrease in micellar size with absorbed dose. The binding and change in the size of micelles were observed to be highly drug and surfactant-specific. Among the four surfactants, irradiated Pluronic F-127 showed higher binding affinity. To the best of our knowledge, this is the first report on the effect of γ-irradiated surfactant on drug-BSA interaction. This can be applied to other drug-protein systems to tune their interaction to the required level.Communicated by Ramaswamy H. Sarma.

Genome-informed trophic classification and functional characterization of virulence proteins from the maize tar spot pathogen Phyllachora maydis.

Phyllachora maydis is an ascomycete foliar fungal pathogen and the causal agent of tar spot in maize. Though P. maydis is considered an economically important foliar pathogens of maize, our general knowledge of the trophic lifestyle and functional role of effector proteins from this fungal pathogen remains limited. Here, we utilized a genome-informed approach to predict the trophic lifestyle of P. maydis and functionally characterized a subset of candidate effectors from this fungal pathogen. Leveraging the most recent P. maydis genome annotation and the CATAStrophy pipeline, we show this fungal pathogen encodes a predicted Carbohydrate-active enzymes (CAZymes) repertoire consistent with that of biotrophs. To investigate fungal pathogenicity, we selected 18 candidate effector proteins that were previously shown to be expressed during primary disease development. We assessed whether these putative effectors share predicted structural similarity with other characterized fungal effectors and determined whether any suppress plant immune responses. Using AlphaFold2 and Foldseek, we showed one candidate effector, PM02_g1115, adopts a predicted protein structure similar to that of an effector from Verticillium dahlia. Furthermore, transient expression of candidate effector-fluorescent protein fusions in Nicotiana benthamiana revealed two putative effectors, PM02_g378 and PM02_g2610, accumulated predominantly in the cytosol, and three candidate effectors, PM02_g1115, PM02_g7882, and PM02_g8240 consistently attenuated chitin-mediated reactive oxygen species production. Collectively, these results presented herein provide insights into the predicted trophic lifestyle and putative functions of effectors from P. maydis and will likely stimulate continued research to elucidate the molecular mechanisms used by P. maydis to induce tar spot.

Microplastic contamination in Ashtamudi Lake, India: Insights from a Ramsar wetland.

Estuaries function as temporary storage sites for plastic debris, influencing the distribution of microplastics (MPs) across ecosystems. This research delves into the presence of MPs in the water, sediment, fish, and shellfish of Ashtamudi Lake, a Ramsar wetland with brackish water located on the southwest coast of India. Given the lake's significance in supporting the livelihoods of numerous fishers and acting as a vital source of fishery resources for both local consumption and export, examining the contamination of the system by MPs becomes particularly pertinent. The highest percentage composition of MPs was found in macrofauna at 60.6% (with fish at 19.6% and shellfish at 40.9%), followed by sediment (22.8%) and water (16.7%). The primary types of MPs identified in all samples were fibers (35.6%), fragments (33.3%), and films (28%), with beads being the least represented at 3.03%. ATR-FTIR and Raman spectra analysis identified five polymers from shellfish (polypropylene, polyethylene, polystyrene, nylon, and polyvinyl chloride), five from fish guts (nylon, polypropylene, polyethylene, polyurethane, and polysiloxane), four in sediment (polypropylene, polyethylene, nylon, rayon), and four in water samples (polypropylene, polyethylene, nylon, and polystyrene). SEM-EDAX analysis of MPs obtained from the samples revealed degradation and the presence of inorganic elements such as Na, Mg, Al, Si, S, K, Cl, P, and Ca, as well as heavy metals like Pb, Mo, Rh, Pd, Ti, and Fe. The existence of these plastic polymers and heavy metals in microplastic samples poses a threat to vulnerable biota; people consume contaminated fish and shellfish, underscoring the importance of monitoring MPs in lake water. This investigation of MPs in Ashtamudi Lake highlights the system's susceptibility to plastic pollution and the bioavailability of smaller MPs to aquatic organisms. Identified sources of MPs in the lake include fishing and aquaculture activities, sewage pollution, improper solid waste management in lake watersheds, and unsustainable tourism. Upstream and downstream management interventions are recommended to address MP pollution in Ashtamudi Lake.

Reduced Fascicle Area Demonstrated in Ilioinguinal Nerves Resected from Primary Inguinal Herniorrhaphy Patients as Evidence of Compression Neuropathy.

Methods: 30 male patients with primary inguinal hernias undergoing primary inguinal herniorrhaphy were prospectively recruited for ilioinguinal nerve resection and evaluation. Three samples of the resected ilioinguinal nerve (proximal, canal, and distal) were evaluated using Masson's trichrome stain to measure fascicle and total nerve cross-sectional area and detect changes in collagen. Results: The fascicle cross-sectional area in the canal segment was significantly decreased compared to the proximal control with a large effect size observed (p = 0.016, η2 = 0.16). There was no significant difference in the nerve cross-sectional area between locations, but there was a moderate to large effect size observed between locations (p = 0.165, η2 = 0.105). There was no significant difference in collagen content nor effect size observed between locations (p = 0.99, η2 = 1.503 × 10-4). Interpretation. The decrease in the fascicle cross-sectional area within the inguinal canal further suggests that there is chronic pressure applied by hernia tissue consistent with axon degeneration. Collagen content is uniformly distributed along the length of the nerve. Further studies with larger samples are needed to confirm the observed effect of nerve location on the total nerve cross-sectional area and axon loss.

Optimization of a standardized letter of recommendation for faculty who wish to support candidates applying to surgical training programs.

Letters of recommendation (LORs) play an important role in applicant selection for graduate medical education programs. LORs may be of increasing importance in the evaluation of applicants given the recent change of the USMLE Step 1 to pass/fail scoring and the relative lack of other objective measures by which to differentiate and stratify applicants. Narrative letters of recommendation (NLORs), although widely used, have certain limitations, namely variability in interpretation, introduction of gender/race bias, and performance inflation. Standardized letters of recommendation (SLOR) have been proposed as a potential corrective to these limitations. We conducted a series of semi-structured interviews and focus groups to gather perspectives from letter writers and readers to inform methods for improving information elicited by SLORs from which we collected and analyzed data using the constant comparative method and a process of iterative coding. We applied our findings to the development of a novel SLOR for use in surgical residency program applications and were subsequently invited to help revise existing SLORs for a surgical post-graduate training program.

Surgical journal clubs: Navigating the post-pandemic landscape.

Pandemic-related distancing regulations gave medical educators at our college an opportunity to reimagine and expand our evidenced-based medicine curriculum to an asynchronous, virtual format. We share the experience of course directors, faculty, and students with our new surgical journal club format. Our goal was to support learners' critical appraisal skills of the surgical literature through active learning modalities such as visual abstract generation and audio-synopsis creation. We included surgeons whose practice locations and schedules may preclude participation. The curriculum was applied to our pre-existing community-based journal clubs. The asynchronous, virtual format allowed us to expand these journal clubs to include rural surgeons.

Nanocosmetics and Skin Health: A Comprehensive Review of Nanomaterials in Cosmetic Formulations.

The development of nanocosmetics nanotechnology has ushered in a new age in cosmetic research, completely changing the skincare scene. This abstract investigates the relationship between skincare and nanotechnology, particularly emphasizing the effects of nanocosmetics on skin health. Cosmetics, known as "nanocosmetics," use materials at the nanoscale, typically between 1 and 100 nanometers, to improve the effectiveness and delivery of active chemicals. Nanotechnology in cosmetics allows for the development of sophisticated delivery methods that provide enhanced stability and tailored distribution, including nanoemulsions and nanocapsules. This breakthrough overcomes the constraints of conventional formulations by enabling the entry of active ingredients into the skin's deeper layers. Studies investigating nanocosmetics and skin health were included. This encompassed in vitro studies, animal models, and clinical studies of various designs. Exclusion criteria included studies focusing solely on nanotechnology unrelated to skin health or nanocosmetics and review articles editorials, commentaries, and conference abstracts. Nanocosmetics is a groundbreaking development in skincare that provides creative answers to a range of skin issues. As the area develops, realizing the full potential of nanotechnology in fostering ideal skin health will need sustained research and adherence to safety regulations.

The Link Between Dysregulated Immunometabolism and Vascular Damage: Implications for the Development of Atherosclerosis in Systemic Lupus Erythematosus and Other Rheumatic Diseases.

A bimodal pattern of mortality in systemic lupus erythematosus (SLE) exists. Early-stage deaths are predominantly caused by infection, whereas later-stage deaths are mainly caused by atherosclerotic disease. Further, although SLE-related mortality has reduced considerably in recent years, cardiovascular (CV) events remain one of the leading causes of death in people with SLE. Accelerated atherosclerosis in SLE is attributed to both an increase in traditional CV risk factors and the inflammatory effects of SLE itself. Many of these changes occur within the microenvironment of the vascular-immune interface, the site of atherosclerotic plaque development. Here, an intimate interaction between endothelial cells, vascular smooth muscle cells, and immune cells dictates physiological vs pathological responses to a chronic type 1 interferon environment. Low-density neutrophils (LDNs) have also been implicated in eliciting vasculature-damaging effects at such lesion sites. These changes are thought to be governed by dysfunctional metabolism of immune cells in this niche due at least in part to the chronic induction of type 1 interferons. Understanding these novel pathophysiological mechanisms and metabolic pathways may unveil potential innovative pharmacological targets and therapeutic opportunities for atherosclerosis, as well as shed light on the development of premature atherosclerosis in patients with SLE who develop CV events.

Exploring bacterial diversity in Arctic fjord sediments: a 16S rRNA-based metabarcoding portrait.

The frosty polar environment houses diverse habitats mostly driven by psychrophilic and psychrotolerant microbes. Along with traditional cultivation methods, next-generation sequencing technologies have become common for exploring microbial communities from various extreme environments. Investigations on glaciers, ice sheets, ponds, lakes, etc. have revealed the existence of numerous microorganisms while details of microbial communities in the Arctic fjords remain incomplete. The current study focuses on understanding the bacterial diversity in two Arctic fjord sediments employing the 16S rRNA gene metabarcoding and its comparison with previous studies from various Arctic habitats. The study revealed that Proteobacteria was the dominant phylum from both the fjord samples followed by Bacteroidetes, Planctomycetes, Firmicutes, Actinobacteria, Cyanobacteria, Chloroflexi and Chlamydiae. A significant proportion of unclassified reads derived from bacteria was also detected. Psychrobacter, Pseudomonas, Acinetobacter, Aeromonas, Photobacterium, Flavobacterium, Gramella and Shewanella were the major genera in both the fjord sediments. The above findings were confirmed by the comparative analysis of fjord metadata with the previously reported (secondary metadata) Arctic samples. This study demonstrated the potential of 16S rRNA gene metabarcoding in resolving bacterial composition and diversity thereby providing new in situ insights into Arctic fjord systems.

Uncovering the Infection Strategy of Phyllachora maydis during Maize Colonization: A Comprehensive Analysis.

Tar spot, a disease caused by the ascomycete fungal pathogen Phyllachora maydis, is considered one of the most significant yield-limiting diseases of maize (Zea mays L.) within the United States. P. maydis may also be found in association with other fungi, forming a disease complex which is thought to result in the characteristic fish eye lesions. Understanding how P. maydis colonizes maize leaf cells is essential for developing effective disease control strategies. Here, we used histological approaches to elucidate how P. maydis infects and multiplies within susceptible maize leaves. We collected tar spot-infected maize leaf samples from four different fields in northern Indiana at three different time points during the growing season. Samples were chemically fixed and paraffin-embedded for high-resolution light and scanning electron microscopy. We observed a consistent pattern of disease progression in independent leaf samples collected across different geographical regions. Each stroma contained a central pycnidium that produced asexual spores. Perithecia with sexual spores developed in the stomatal chambers adjacent to the pycnidium, and a cap of spores formed over the stroma. P. maydis reproductive structures formed around but not within the vasculature. We observed P. maydis associated with two additional fungi, one of which is likely a member of the Paraphaeosphaeria genus; the other is an unknown fungi. Our data provide fundamental insights into how this pathogen colonizes and spreads within maize leaves. This knowledge can inform new approaches to managing tar spot, which could help mitigate the significant economic losses caused by this disease.

SINGLE CELL DISSECTION OF DEVELOPMENTAL ORIGINS AND TRANSCRIPTIONAL HETEROGENEITY IN B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA.

Sequencing of bulk tumor populations has improved genetic classification and risk assessment of B-ALL, but does not directly examine intratumor heterogeneity or infer leukemia cellular origins. We profiled 89 B-ALL samples by single-cell RNA-seq (scRNA-seq) and compared them to a reference map of normal human B-cell development established using both functional and molecular assays. Intra-sample heterogeneity was driven by cell cycle, metabolism, differentiation, and inflammation transcriptional programs. By inference of B lineage developmental state composition, nearly all samples possessed a high abundance of pro-B cells, with variation between samples mainly driven by sub-populations. However, ZNF384- r and DUX4- r B-ALL showed composition enrichment of hematopoietic stem cells, BCR::ABL1 and KMT2A -r ALL of Early Lymphoid progenitors, MEF2D -r and TCF3::PBX1 of Pre-B cells. Enrichment of Early Lymphoid progenitors correlated with high-risk clinical features. Understanding variation in transcriptional programs and developmental states of B-ALL by scRNA-seq refines existing clinical and genomic classifications and improves prediction of treatment outcome.

The Influence of Identity on Multiracial Emerging Adults' Health and Experiences Seeking Healthcare in the United States: a Qualitative Study.

BACKGROUND: The Multiracial population, defined as having parents who are of two or more racial groups, increased from 2.9% of the United States population in 2010 to 10.2% in 2020. Existing research focused on monoracial populations shows that racial disparities and discrimination affect health. This study explores how emerging adults ages 18-29, who identify as Multiracial, describe the impact of identity on their health and experiences seeking health care in the United States. METHODS: Semi-structured interviews were conducted with 21 participants in May 2021. Interview guide categories were the following: health and wellbeing, racial/ethnic identification, childhood upbringing, family influence, peer engagement, discrimination, forming resilience, language, and demographics. A thematic framework analysis was utilized. RESULTS: Overarching themes were as follows: mental health and Multiracial identity-related stress, childhood experiences, healthcare experiences, influences on seeking or not seeking care, and the impact of identity on physical health. Our findings suggest that Multiracial emerging adults perceive their identity to influence mental health more than physical health. CONCLUSION: Multiracial emerging adults face challenges with healthcare that are unique (e.g., discrimination based on identity defined or perceived by others) and others that are similar to their monoracial counterparts (e.g., structural racism, access to care). This study illustrates how structural factors trickle down to influence care sought and accessibility via socioeconomic status, insurance, childhood experiences, and racial and cultural beliefs about healthcare. Increased awareness and identification of Multiracial individuals and diversity in the workforce may help the US healthcare system better serve Multiracial emerging adults.

Bullet Wound Blues: A Case Report on Brachial Artery Pseudoaneurysm.

Pseudoaneurysms are typically iatrogenic due to the increasing use of the artery for arterial interventions such as invasive vascular radiological procedures, invasive coronary artery procedures, arterial punctures for an arteriogram, or catheterization. Other reasons for pseudoaneurysm formation are intravenous drug use and penetrating trauma. They are more commonly observed in the lower limbs than in the upper limbs. In this case report, we present the occurrence of a brachial artery pseudoaneurysm (BAP) in a 73-year-old male patient who suffered a gunshot wound (GSW) 25 years ago during the war and was admitted to the hospital because of a fall episode. This case represents one of the few documented instances of a pseudoaneurysm formation following a GSW in the United States. Along with that, we describe the subsequent medical care provided to the patient.

A study of beliefs towards mental illness among teachers in Sikar city, Rajasthan.

Background: Understanding the significance of adolescents' mental health, school-based mental health interventions are being implemented with the help of teachers globally. Aim: Owing to the dearth of literature concerning the beliefs, and stigma among the teachers, the present study was conducted with an aim to study the mental health beliefs among teachers. Methods: This is a cross-sectional study conducted among randomly selected teachers teaching in government and private schools of Sikar city of Rajasthan. A general sociodemographic questionnaire, Beliefs Towards Mental Illness Scale, and a questionnaire about prior exposure to mental health issues was administered. Stata 15.0 was used for statistical analysis, and independent t-test and one-way analysis of variance test were applied to find out associations. Results: Majority of the participants were in age group of 31-40 years, married, and postgraduate. The mean Beliefs Towards Mental Illness Scale score of 147 teachers was 49.95 ± 17.34 of 105. Only 2% of the study participants have ever received training related to mental health issues. Teachers who had prior exposure to mental health issues, residing in semi-urban and urban areas showed more positive beliefs. Conclusion: Study participants have displayed negative beliefs toward mental health. This brings to light the important interventions like creating knowledge and awareness among the study population by conducting trainings. More research is needed to explore the mental health beliefs among the teachers.

Chronic IFNα treatment induces leukopoiesis, increased plasma succinate and immune cell metabolic rewiring.

Although clinically effective, the actions of IFNα, either produced endogenously or by therapeutic delivery, remain poorly understood. Emblematic of this research gap is the disparate array of notable side effects that occur in susceptible individuals, such as neuropsychiatric consequences, autoimmune phenomena, and infectious complications. We hypothesised that these complications are driven at least in part by dysregulated cellular metabolism. Male Wistar rats were treated with either 170,000 IU/kg human recombinant IFNα-2a or BSA/saline (0.9% NaCl) three times per week for three weeks. Bone marrow (BM) immune cells were isolated from the excised femurs for glycolytic rate and mitochondrial function assessment using Agilent Seahorse Technology. Frequencies of immune cell populations were assessed by flow cytometry to determine whether leukopoietic changes had occurred in both blood and BM. Plasma levels of lactate and succinate were also determined. BMDMs were metabolically assessed as above, as well as their metabolic response to an antigenic stimulus (iH37Rv). We observed that BM immune cells from IFN-treated rats exhibit a hypermetabolic state (increased basal OCR/GlycoPER) with decreased mitochondrial metabolic respiration and increased non-mitochondrial OCR. Flow cytometry results indicated an increase in immature granulocytes (RP1- SSChi CD45lo) only in the blood, together with increased succinate levels in the plasma. BMDMs from IFN-treated rats retained the hypermetabolic phenotype after differentiation and failed to induce a step-up in glycolysis and mitochondrial respiration after bacterial stimulation. This work provides the first evidence of the effects of IFNα treatment in inducing hypermetabolic immune features that are associated with markers of inflammation, leukopoiesis, and defective responses to bacterial stimulation.

Image-based plant wilting estimation.

BACKGROUND: Environmental stress due to climate or pathogens is a major threat to modern agriculture. Plant genetic resistance to these stresses is one way to develop more resilient crops, but accurately quantifying plant phenotypic responses can be challenging. Here we develop and test a set of metrics to quantify plant wilting, which can occur in response to abiotic stress such as heat or drought, or in response to biotic stress caused by pathogenic microbes. These metrics can be useful in genomic studies to identify genes and genomic regions underlying plant resistance to a given stress. RESULTS: We use two datasets: one of tomatoes inoculated with Ralstonia solanacearum, a soilborne pathogen that causes bacterial wilt disease, and another of soybeans exposed to water stress. For both tomato and soybean, the metrics predict the visual wilting score provided by human experts. Specific to the tomato dataset, we demonstrate that our metrics can capture the genetic difference of bacterium wilt resistance among resistant and susceptible tomato genotypes. In soybean, we show that our metrics can capture the effect of water stress. CONCLUSION: Our proposed RGB image-based wilting metrics can be useful for identifying plant wilting caused by diverse stresses in different plant species.

Major complications following central neuraxial block - A multi-centre observational study in Maharashtra (MGMM CNB Study).

Background and Aims: Major complications of central neuraxial block (CNB) are rare and their incidence in India is not known. This information is essential for explaining risk and medico-legal concerns. The present multi-centre study in Maharashtra was conducted to provide insight into the characteristics of rare complications following this popular anaesthetic technique. Methods: Data were collected from 141 institutes to study the clinical profile of CNB. Incidence of complications like vertebral canal haematoma, abscess, meningitis, nerve injury, spinal cord ischaemia, fatal cardiovascular collapse, and drug errors was collected over one year. Complications were reviewed by audit committee to assess causation, severity, and outcome. 'Permanent' injury was defined as death or neurological symptoms persisting for more than six months. Results: Spinal anaesthesia (SA) was the most frequently used CNB in 88.76% patients. Bupivacaine and an adjuvant were used in 92.90% and 26.06% patients, respectively. Eight major complications (four neurological and four cardiac arrests) were reported in patients receiving SA. In seven of eight instances, SA was responsible or contributory for complication. The pessimistic incidence of complications (included cases where CNB was responsible; contribution was likely, unlikely and could not be commented) was 8.69/lakh and optimistic incidence (included cases where CNB was responsible or contribution was likely) was 7.61/lakh. 'Pessimistically' and 'optimistically' there were three deaths including one death due to quadriplegia following epidural haematoma after SA. Five out of eight patients recovered completely (62.5%). As only eight patients had complications of different types, it was difficult to establish statistical correlation of major complications with demographic or clinical parameters. Conclusion: This study was reassuring and suggested that the incidence of major complications following CNB was low in Maharashtra.