Molecular Identification of Fonsecaea monophora, Novel Agent of Fungal Brain Abscess.

A 3-year-old patient in India experiencing headaches and seizures was diagnosed with a fungal infection, initially misidentified as Cladophialophora bantiana. Follow-up sequencing identified the isolate to be Fonsecaea monophora fungus. This case demonstrates the use of molecular methods for the correct identification of F. monophora, an agent of fungal brain abscess.

Comparative analysis of simultaneous integrated boost and sequential boost radiotherapy in node-positive cervical cancer: dosimetric and radiobiological considerations.

For locally advanced cervical cancer, the standard therapeutic approach involves concomitant chemoradiation therapy, supplemented by a brachytherapy boost. Moreover, an external beam radiotherapy (RT) boost should be considered for treating gross lymph node (LN) volumes. Two boost approaches exist with Volumetric Intensity Modulated Arc Therapy (VMAT): Sequential (SEQ) and Simultaneous Integrated Boost (SIB). This study undertakes a comprehensive dosimetric and radiobiological comparison between these two boost strategies. The study encompassed ten patients who underwent RT for cervical cancer with node-positive disease. Two sets of treatment plans were generated for each patient: SIB-VMAT and SEQ-VMAT. Dosimetric as well as radiobiological parameters including tumour control probability (TCP) and normal tissue complication probability (NTCP) were compared. Both techniques were analyzed for two different levels of LN involvement - only pelvic LNs and pelvic with para-aortic LNs. Statistical analysis was performed using SPSS software version 25.0. SIB-VMAT exhibited superior target coverage, yielding improved doses to the planning target volume (PTV) and gross tumour volume (GTV). Notably, SIB-VMAT plans displayed markedly superior dose conformity. While SEQ-VMAT displayed favorable organ sparing for femoral heads, SIB-VMAT appeared as the more efficient approach for mitigating bladder and bowel doses. TCP was significantly higher with SIB-VMAT, suggesting a higher likelihood of successful tumour control. Conversely, no statistically significant difference in NTCP was observed between the two techniques. This study's findings underscore the advantages of SIB-VMAT over SEQ-VMAT in terms of improved target coverage, dose conformity, and tumour control probability. In particular, SIB-VMAT demonstrated potential benefits for cases involving para-aortic nodes. It is concluded that SIB-VMAT should be the preferred approach in all cases of locally advanced cervical cancer.

Differential contributions of circadian clock genes to cell survival in bipolar disorder patient derived neuronal progenitor cells distinguishes lithium responders and non-responders.

Bipolar disorder (BD) is characterized by disrupted circadian rhythms and neuronal loss. Lithium is neuroprotective and used to treat BD, but outcomes are variable. Past research identified that circadian rhythms in BD patient neurons are associated with lithium response (Li-R) or non-response (Li-NR). However, the underlying cellular mechanisms remain unknown. To study interactions among circadian clock genes and cell survival, and their role in BD and predicting lithium response, we tested selected genes (PER1, BMAL1 and REV-ERBα) and small molecule modulators of ROR/REV-ERB nuclear receptors in models of cell survival using mouse neurons and stem-cell derived neuronal progenitor cells (NPC) from BD patients and controls. In apoptosis assays using staurosporine (STS), lithium was neuroprotective. Knockdown of PER1, BMAL1 and REV-ERBα modified cell survival across models. In NPCs, reduced expression of PER1 and BMAL1 led to more extensive cell death in Li-NR vs. Li-R. Reduced REV-ERBα expression caused more extensive cell death in BD vs. control NPCs, without distinguishing Li-R and Li-NR. In IMHN, The REV-ERB agonist GSK4112 had strong effects on circadian rhythm amplitude, and was neuroprotective in mouse neurons and control NPCs, but not in BD NPCs. Expression of cell survival genes following STS and GSK4112 treatments revealed BD-associated, and Li-R associated differences in expression profiles. We conclude that the neuroprotective response to lithium is similar in NPCs from Li-R and Li-NR. However, knockdown of circadian clock genes or stimulation of REV-ERBs reveal distinct contributions to cell death in BD patient NPCs, some of which distinguish Li-R and Li-NR.

Busting the myth of spontaneous formation of H2O2 at the air-water interface: contributions of the liquid-solid interface and dissolved oxygen exposed.

Recent reports on the spontaneous formation of hydrogen peroxide (H2O2) at the air-water and solid-water interfaces challenge our current understanding of aquatic chemistry and have ramifications on atmosphere chemistry models, surface science, and green chemistry. Suggested mechanisms underlying this chemical transformation include ultrahigh instantaneous electric fields at the air-water interface and the oxidation of water and reduction of the solid at the solid-water interface. Here, we revisit this curious problem with NMR spectroscopy (with an H2O2 detection limit ≥50 nM) and pay special attention to the effects of nebulizing gas, dissolved oxygen content, and the solid-water interface on this chemical transformation in condensed and sprayed water microdroplets. Experiments reveal that the reduction of dissolved oxygen at the solid-water interface predominantly contributes to the H2O2 formation (not the oxidation of hydroxyl ions at the air-water interface or the oxidation of water at the solid-water interface). We find that the H2O2 formation is accompanied by the consumption (i.e., reduction) of dissolved oxygen and the oxidation of the solid surface, i.e., in the absence of dissolved oxygen, the formation of H2O2(aq) is not observed within the detection limit of ≥50 nM. Remarkably, the tendency of the solids investigated in this work towards forming H2O2 in water followed the same order as their positions in the classic Galvanic series. These findings bust the prevailing myths surrounding H2O2 formation due to the air-water interface, the ultrahigh electric fields therein, or the micro-scale of droplets. The hitherto unrealized role of the oxidation of the solid surface due to dissolved oxygen in the formation of H2O2 is exposed. These findings are especially relevant to corrosion science, surface science, and electrochemistry, among others.

Vetiver grass cleans up arsenic contaminated field for subsequent safe cultivation of rice with low arsenic in grains: A two year field study.

The presence of high concentrations of arsenic (As) in agricultural soils and its subsequent accumulation in rice crop is a serious issue threatening sustainability of agriculture and human health. In the present work, remediation of As contaminated field in Nadia, West Bengal, India was done through the cultivation of Vetiver (Vetiveria zizanoides L. Nash) and the same field was subsequently used for rice (Oryza sativa L.) cultivation. The results showed that V. zizanoides could reduce As concentrations in the field to bring it lower than the maximum permissible limit (20 mg kg-1) in 11 months' time. The rice plants grown in remediated field showed improvement in growth and photosynthesis parameters as compared to that of contaminated field. Importantly, yield related parameters (filled seed, 1000 grain weight, number of panicles etc.) were also significantly higher in remediated field than that in contaminated field. Arsenic concentration in roots, shoot, husk and grains of rice was found to be significantly lower in remediated field than in contaminated field. Grain As decreased from 0.75 to 0.77 µg g-1 dw in contaminated field to 0.15-0.18 µg g-1 dw. In conclusion, replacing rice for single year with V. zizanoides crop can significantly remediate the field and can be a viable option.

The Utility of Galactomannan and Polymerase Chain Reaction Assays in Bronchoalveolar Lavage for Diagnosis of Chronic Pulmonary Aspergillosis.

The diagnosis of chronic pulmonary aspergillosis (CPA) is established by combined clinic-radio-microbiological criteria. Out of the different microbiological criteria, a positive serology for Aspergillus-specific IgG levels is the cornerstone of diagnosis. Alternatively, other microbiological evidence are sometimes sought viz., positive Aspergillus antigen (broncho-alveolar lavage fluid, i.e., BALF galactomannan ≥ 1.0), histopathological demonstration of the fungi following lung biopsy or resection, demonstration of hyaline septate hyphae in direct microscopy resembling Aspergillus spp. or its growth on a respiratory specimen. However, the exact roles of BALF- GM and the newer BALF-PCR have not been confirmed by studies till date. This study enrolled 210 patients with suspected CPA. Of the participants, 88 patients met the criteria for CPA, whereas 122 patients had an alternative diagnosis. The sensitivity-specificity of AsperGenius® PCR and "in-house" PCR were 52.27(36.69-67.54) %-33.78 (23.19-45.72) % and 36.36 (22.41-52.23) %-39.19 (28.04-51.23) % respectively. The sensitivity/specificity of BALF (> 1.0) and serum galactomannan (> 1.0) were 46.55% (33.34-60.13)/64.08% (54.03-73.3) and 29.82% (22.05-37.6)/86.84% (81.1-92.59) respectively. The optimal cut-off values for BALF-Galactomannan and serum galactomannan in diagnosing CPA were found to be 0.69 (sensitivity: 64%; specificity: 53%) and 0.458 (sensitivity: 67%; specificity: 64%) respectively. This results of this study suggests that Aspergillus PCR from BAL may not be a good "rule-in" test for diagnosing CPA. While the performances of GM in BAL and serum may be better than PCR, it should be best used in conjunction with other clinical, radiological, and other microbiological characteristics.

Evaluation of survival outcome and prognostic factors for oral cavity cancer treated with volumetric arc therapy.

PURPOSE: This study aimed to evaluate the survival outcomes and identify prognostic factors for patients with oral cavity cancer (OCC) who underwent adjuvant treatment with volumetric arc therapy (VMAT) using simultaneous integrated boost (SIB). METHODS: Data was collected for post-operated patients of carcinoma of oral cavity who received adjuvant VMAT with SIB between June 2018 and December 2022. The data was entered and analyzed using SPSS software version 20.0. Survival rates were estimated using Kaplan Meier method. To determine survival difference between the groups, log rank test was used. Multivariate analyses were performed with Cox proportional hazard model and p value < 0.05 was considered as significant. RESULTS: A total of 178 patients were included in the study. The median follow-up period was 26 months (range 3-56 months). The 3-year OS, DFS, and LRC rates were 78% (95% CI 77-79%), 76% (95% CI 74-77%), and 81% (95% CI 80-82%), respectively. Univariate analysis identified age ≥ 50 years, lymph node involvement, extracapsular extension (ECE), and N2-N3 disease as significant adverse prognostic factors for OS, DFS, and LRC. Multivariate analysis confirmed age ≥ 50 years and nodal involvement as independent predictors of worse OS, DFS, and LRC. Additionally, ECE independently affected OS and DFS. CONCLUSION: Adjuvant treatment with VMAT using SIBin patients with OCC is effective. Age and nodal involvement had significant impact on LRC, DFSand OS while ECE on DFSand OS.

Survival outcome and prognostic factors post inadvertent hysterectomy in carcinoma cervix treated with salvage chemo-radiation.

INTRODUCTION: The standard of care for treating early invasive cervical cancer is radical hysterectomy or radiation alone while chemo-radiation is a definitive treatment for advanced disease. Occasionally, a simple hysterectomy is performed in the cancer cervix and these patients merit adjuvant treatment in view of the high chances of loco-regional recurrences. The aim of the study was to analyze the survival outcome of these patients treated with salvage chemo-radiotherapy and also to determine the prognostic factors affecting survival. MATERIALS AND METHODS: The medical records of all patients with cervical cancer post simple hysterectomy outside and who received salvage treatment in our department between 2014 and 2020 were retrieved. The data regarding clinical, treatment details and survival were analyzed. RESULTS: A total of 198 patients were included. Median follow-up duration was 45.5 months. Gross disease and lymphadenopathy were seen in 60% and 28% patients, respectively. The 5-year progression-free survival(PFS) and overall survival(OS) was 75% and 76%, respectively. Concurrent chemotherapy alone or in combination with induction chemotherapy using three-drug regimens showed better survival compared to those treated by radiation alone. On multivariate analysis, factors found to be adversely affecting OS and PFS were lymph node (LN) size of more than 2 cm, non-squamous histology, overall treatment time(OTT) of more than 12 weeks and use of non three-drug chemotherapy regimen. CONCLUSION: Subtotal hysterectomy results in a higher incidence of local recurrence of disease. Factors that impair the outcome in this sub-group of patients are gross lymphadenopathy, non-squamous histology and prolong OTT.

Small Angle Neutron Scattering in Drug Discovery Research: A Novel Tool for Advanced Study of Structures of Biological Macromolecules.

Small Angle Neutron Scattering (SANS) is a powerful and novel tool for the study of soft condensed matter, including the microscopic and nanomaterials used for drug discovery and delivery. The sample is exposed to a neutron beam, and neutron scattering occurs, which is studied as a function of the scattering angle to deduce a variety of information about the dynamics and structure of the material. The technique is becoming very popular in biomedical research to investigate the various aspects of structural biology. The low-resolution information on large heterogeneous, solubilized biomacromolecular complexes in solution is obtained with the use of deuterium labelling and solvent contrast variation. The article reviews the basics of the SANS technique, its applications in drug delivery research, and its current status in biomedical research. The article covers and overviews the precise characterization of biological structures (membranes, vesicles, proteins in solution), mesoporous structures, colloids, and surfactants, as well as cyclodextrin complexes, lipid complexes, polymeric nanoparticles, etc., with the help of neutron scattering. SANS is continuously evolving as a medium for exploring the complex world of biomolecules, providing information regarding the structure, composition, and arrangement of various constituents. With improving modelling software automation in data reduction and the development of new neutron research facilities, SANS can be expected to remain mainstream for biomedical research.

Does the first letter of one's name affect life decisions? A natural language processing examination of nominative determinism.

This research examines whether the phenomenon of nominative determinism (a name-driven outcome) exists in the real world. Nominative determinism manifests as a preference for a profession or city to live in that begins with the same letter as a person's own name. The literature presents opposing views on this phenomenon, with one stream of research documenting the influence and another stream questioning the existence and generalizability of the effect, as well as the proposed underlying process. To examine whether the effect occurs in the real world, we use large language models trained on Common Crawl, Twitter, Google News, and Google Books using two natural language processing word-embedding algorithms (word2vec and GloVe). After controlling for relevant variables, we find consistent evidence of the relationship between people's names and a preference for major life choices starting with the same letter as their first name. Our theoretical framework of identity expression builds on the implicit egotism explanation. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Contributions of circadian clock genes to cell survival in fibroblast models of lithium-responsive bipolar disorder.

Bipolar disorder (BD) is characterized by mood episodes, disrupted circadian rhythms and gray matter reduction in the brain. Lithium is an effective pharmacotherapy for BD, but not all patients respond to treatment. Lithium has neuroprotective properties and beneficial effects on circadian rhythms that may distinguish lithium responders (Li-R) from non-responders (Li-NR). The circadian clock regulates molecular pathways involved in apoptosis and cell survival, but how this overlap impacts BD and/or lithium responsiveness is unknown. In primary fibroblasts from Li-R/Li-NR BD patients and controls, we found patterns of co-expression among circadian clock and cell survival genes that distinguished BD vs. control, and Li-R vs. Li-NR cells. In cellular models of apoptosis using staurosporine (STS), lithium preferentially protected fibroblasts against apoptosis in BD vs. control samples, regardless of Li-R/Li-NR status. When examining the effects of lithium treatment of cells in vitro, caspase activation by lithium correlated with period alteration, but the relationship differed in control, Li-R and Li-NR samples. Knockdown of Per1 and Per3 in mouse fibroblasts altered caspase activity, cell death and circadian rhythms in an opposite manner. In BD cells, genetic variation in PER1 and PER3 predicted sensitivity to apoptosis in a manner consistent with knockdown studies. We conclude that distinct patterns of coordination between circadian clock and cell survival genes in BD may help predict lithium response.

Neural progenitor cells derived from lithium responsive and non-responsive bipolar disorder patients exhibit distinct sensitivity to cell death following methamphetamine.

Bipolar disorder (BD) is characterized by manic and depressive mood episodes and loss of brain gray matter. Lithium has antimanic and neuroprotective properties, but only 30% BD patients respond to lithium pharmacotherapy. Dopamine signaling has been implicated in BD and may contribute to lithium response. Methamphetamine (METH) stimulates dopamine release and models the clinical features of mania but has never been used to study cell death in BD patient neurons. We used BD patient derived neuronal progenitor cells (NPCs) to determine whether the vulnerability to cell death differed in samples from lithium responder (Li-R) and non-responder (Li-NR) BD patients and healthy controls following METH exposure in vitro. We hypothesized that NPCs from Li-R and Li-NR would differ in vulnerability to METH, dopamine signaling and neuroprotection from lithium. Following METH, NPCs from controls and Li-NR showed significantly greater cell loss compared to Li-R. Pre-treatment of NPCs with the D1 dopamine receptor antagonist SCH 23390 reversed the neurotoxic effects of METH. In Li-R NPCs, expression of phosho-ERK1/2 was significantly increased. In Li-NR NPCs, phospho-AKT, D1 and D2 dopamine receptor proteins were significantly increased. Pre-treatment of NPCs with lithium before METH reversed the neurotoxic effects of METH in control NPCs, whereas Li-NR showed less protective benefit. Li-R cells showed decreased levels of cell death after METH and comparatively high viability, and lithium treatment did not increase viability any further. This novel NPC model of mania reveals differences in cell death that could help identify mechanisms of lithium response in BD.

Hiccups: An atypical side effect experienced during chemo-radiotherapy in carcinoma nasopharynx.

ABSTRACT: Nasopharyngeal carcinoma is an uncommon cancer but has a distinct racial and geographic distribution. Patient presents with constellation of signs and symptoms due to its vicinity to critical structures and are best treated by conformal concurrent chemo-radiotherapy. We present a case of 45-year-old male diagnosed with carcinoma nasopharynx, referred to us for radiotherapy after three cycles of neoadjuvant chemotherapy. As per the prevailing standard of care, patient was planned for radiotherapy by volumetric arc technique with concurrent cisplatin. Initial days of treatment were uneventful. After fourth week of treatment, patient developed persistent hiccup which was not relieved on conservative medications. Plan was re-evaluated and it revealed maximum dose of 54.6 Gy to the brainstem. Radiotherapy induced edema that could have stimulated vagus nerve leading to hiccups was suspected. Patient was started on injectable steroid and chlorpromazine. There was prompt recovery from the symptom within five days of conservative treatment.

Clinico-epidemiological profile and treatment outcome in adolescents and young patients of rectal cancer attending a tertiary cancer center.

INTRODUCTION: The incidence of colorectal cancer in young adults is on an increasing trend. It is observed that this subgroup of patients has an aggressive disease and carries a poorer prognosis compared to its older counterpart. This study aimed to analyze the incidence, treatment outcome, and prognostic factors in adolescents and young adults with rectal cancer attending a tertiary cancer center in North India. MATERIALS AND METHODS: We retrospectively analyzed 50 patients of histologically proven rectal cancer, aged up to 30 years, treated at our center between 2015 and 2019. The clinical, demographic, and pathological parameters were studied in all these patients. Kaplan-Meier survival analysis was used to find out survival. Univariate analysis was performed to assess prognostic factors. RESULTS: The incidence was 26.4% at our center with a median age of 28 years. Bleeding per rectum was the commonest complaint. Most of them had signet ring cell histology (26%). The median overall survival was 16 months. Survival was significantly better in patients having bleeding per rectum as an initial complaint (P = 0.009), absence of lymphovascular invasion (LVI) (P = 0.005), and perineural invasion (PNI) (P = 0.002), who received complete planned treatment compared to patients who could not receive either of the modality (P < 0.001). Patients who did not receive radiotherapy (RT) had the worst outcomes compared to those who received RT in any form. RT dose of 50.4 Gy was found to be superior as compared to other schedules. There was no significant difference in survival with gender, tumor stage, grade, type of surgery, or chemotherapy regimen. CONCLUSION: The majority of patients presented in an advanced stage. Therefore, bleeding per rectum should be properly and timely investigated in all these young patients. Early detection and complete treatment are paramount to improving the outcome.

Evaluation of survival outcomes and prognostic factors of carcinoma anal canal at a tertiary cancer center.

CONTEXT: Concurrent chemoradiotherapy is considered a standard of care for patients with carcinoma anal canal. Being an unusual malignancy, there is limited Indian data regarding survival outcomes and prognostic factors. AIM: To evaluate survival outcomes and associated prognostic factors in patients with carcinoma anal canal treated with radical intent. METHODS AND MATERIAL: Patients with squamous cell carcinoma of the anal canal, treated with radical intent between 2015 and 2019 were included in the study. Data regarding the baseline characteristics of the patients and treatment outcomes were collected and analyzed. Survival rates were estimated using Kaplan-Meier method. To determine survival difference between the groups, log-rank test was used. Multivariate analyses were performed with Cox proportional hazard models and P value < 0.05 was considered significant. RESULTS: Forty-two patients were identified after applying suitable eligibility criteria. The median age was 55 years (range: 26-80 years).The median follow-up duration was 23.5 months (range: 1.9-51.9 months). The 3-year overall survival (OS), disease-free survival (DFS), and locoregional (LRC) were 78.5%, 53.1%, and 66.4%, respectively. On multivariate analysis, inferior DFS was significantly affected by lack of concurrent chemotherapy (CT) (hazard ratio [HR], 11.50; 95% confidence interval [CI], 1.92-68.78; P = 0.007) and radiotherapy (RT) dose of 45 Gy or less (HR, 35.96; 95% CI, 6.32-204.56; P = 0.000). CONCLUSION: For patients of carcinoma anal canal, concurrent CT and RT dose are independent prognostic factors influencing DFS.

Direct imaging of polymer filaments pulled from rebounding drops.

Polymer filaments form the foundation of biology from cell scaffolding to DNA. Their study and fabrication play an important role in a wide range of processes from tissue engineering to molecular machines. We present a simple method to deposit stretched polymer fibers between micro-pillars. This occurs when a polymeric drop impacts on and rebounds from an inclined superhydrophobic substrate. It wets the top of the pillars and pulls out liquid filaments which are stretched and can attach to adjacent pillars leaving minuscule threads, with the solvent evaporating to leave the exposed polymers. We use high-speed video at the microscale to characterize the most robust filament-forming configurations, by varying the impact velocity, substrate structure and inclination angle, as well as the PEO-polymer concentration. Impacts onto plant leaves or a randomized nano-structured surface leads to the formation of a branched structure, through filament mergers at the free surface of the drop. SEM shows the deposition of filament bundles which are thinner than those formed by evaporation or rolling drops. Raman spectroscopy identifies the native mode B stretched DNA filaments from aqueous-solution droplets.

Why did only one genus of insects, Halobates, take to the high seas?

Oceans cover more than 70% of the Earth's surface and house a dizzying array of organisms. Mammals, birds, and all manner of fish can be commonly sighted at sea, but insects, the world's most common animals, seem to be completely absent. Appearances can deceive, however, as 5 species of the ocean skater Halobates live exclusively at the ocean surface. Discovered 200 years ago, these peppercorn-sized insects remain rather mysterious. How do they cope with life at the ocean surface, and why are they the only genus of insects to have taken to the high seas?

On the formation of hydrogen peroxide in water microdroplets.

Recent reports on the formation of hydrogen peroxide (H2O2) in water microdroplets produced via pneumatic spraying or capillary condensation have garnered significant attention. How covalent bonds in water could break under such mild conditions challenges our textbook understanding of physical chemistry and water. While there is no definitive answer, it has been speculated that ultrahigh electric fields at the air-water interface are responsible for this chemical transformation. Here, we report on our comprehensive experimental investigation of H2O2 formation in (i) water microdroplets sprayed over a range of liquid flow-rates, (shearing) air flow rates, and air composition, and (ii) water microdroplets condensed on hydrophobic substrates formed via hot water or humidifier under controlled air composition. Specifically, we assessed the contributions of the evaporative concentration and shock waves in sprays and the effects of trace O3(g) on the H2O2 formation. Glovebox experiments revealed that the H2O2 formation in water microdroplets was most sensitive to the air-borne ozone (O3) concentration. In the absence of O3(g), we could not detect H2O2(aq) in sprays or condensates (detection limit ≥250 nM). In contrast, microdroplets exposed to atmospherically relevant O3(g) concentration (10-100 ppb) formed 2-30 µM H2O2(aq), increasing with the gas-liquid surface area, mixing, and contact duration. Thus, the water surface area facilitates the O3(g) mass transfer, which is followed by the chemical transformation of O3(aq) into H2O2(aq). These findings should also help us understand the implications of this chemistry in natural and applied contexts.