Pleomorphism in Biological Units of Life: Morphological Heterogeneity in Cells Does Not Translate Uniformly to Subcellular Components.

The interplay of the three-dimensional (3D) distribution of various subcellular components and their interactions are expected to control overall cellular morphology in biology. In this study, we aimed to determine whether the pleomorphy observed at the whole-cell level is being reflected by the components constituting the cells by focusing on the 3D distribution of pixel intensities at the single-cell level of the whole (cell) and its parts (the seven subcellular components of the cells-self-assemblies of smaller units). We rigorously acquired and analyzed the image data of RAW264.7 cells at the single-cell level. We report asymmetries in the spatial distribution of pixel intensities at the whole-cell and subcellular component levels along with the occurrence of alterations when pleomorphism is reduced by synchronization of the cell cycle. From our repertoire of seven subcellular components, we report ER, mitochondria, and tubulin to be independent of whole-cell apico-basal heterogeneity of optical density while nuclear, plasma membrane, lysosomal, and actin fluorescence distributions are found to contribute to the apico-basal polarity of the whole cell. While doing so, we have also developed an image analysis algorithm utilizing 2D segmentation to analyze the single cells in 3D using confocal microscopy, a technique that allows us to analyze cellular states in their native hydrated state.

Flow Cytometry as the Tool to Define Peripheral Blood Leukocyte Signatures in Acute EBV Infection.

Primary Epstein-Barr virus (EBV) infection which can manifest as infectious mononucleosis (IM) is commonly acquired during childhood. EBV primarily invades B cells leading to a lytic reaction; the control of the infection is handled by natural killer and T cells in immunocompetent individuals. The infection has a wide spectrum of clinical findings and can lead to serious complications in patients with certain underlying immunological dysfunctions. We retrospectively investigated peripheral white blood cell populations' surface marker characteristics in IM using a comprehensive flow cytometry marker panel. Twenty-one cases of IM and seventeen EBV-seropositive cases without IM serving as controls were included. We observed novel alterations in lymphocyte, neutrophil, and monocyte populations. In addition to increased activated cytotoxic T cells and low B cells, we demonstrated high T-large granular lymphocyte (T-LGL) populations in IM cases. Furthermore, despite T cells' increased HLA-DR expression, another activation marker, CD11b, was lower in T-LGL populations. Monocytes showed increased CD16 expression; CD64 was higher in neutrophils. Our findings point to monocyte and neutrophil activation which may account for acute clinical features and may contribute to the understanding of IM immunobiology. Furthermore, they may serve as a useful tool in investigating inherited and post-transplant conditions characterized by deficiencies in controlling EBV infection.

Hierarchical assembly and modeling of DNA nanotube networks using Y-shaped DNA origami seeds.

DNA nanotechnology offers many means to synthesize custom nanostructured materials from the ground up in a hierarchical fashion. While the assembly of DNA nanostructures from small (nanometer-scale) monomeric components has been studied extensively, how the hierarchical assembly of rigid or semi-flexible units produces multi-micron scale structures is less understood. Here we demonstrate a mechanism for assembling micron-scale semi-flexible DNA nanotubes into extended structures. These nanotubes assemble from nanometer-scale tile monomers into materials via heterogeneous nucleation from rigid, Y-shaped DNA origami seeds to form Y-seeded nanotube architectures. These structures then assemble into networks via nanotube end-to-end joining. We measure the kinetics of network growth and find that the assembly of networks can be approximated by a model of hierarchical assembly that assumes a single joining rate between DNA nanotube ends. Because the number of nucleation sites on Y-seeds and their spatial arrangement can be systematically varied by design, this hierarchical assembly process could be used to form a wide variety of networks and to understand the assembly mechanisms that lead to different types of material architectures at length scales of tens to hundreds of microns.

Quinolinic acid links kidney injury to brain toxicity.

Kidney dysfunction often leads to neurological impairment, yet the complex kidney-brain relationship remains elusive. We employed spatial and bulk metabolomics to investigate a mouse model of rapid kidney failure induced by mouse double minute 2 ( Mdm2) conditional deletion in the kidney tubules to interrogate kidney and brain metabolism. Pathway enrichment analysis of focused plasma metabolomics panel pinpointed tryptophan metabolism as the most altered pathway with kidney failure. Spatial metabolomics showed toxic tryptophan metabolites in the kidneys and brains, revealing a novel connection between advanced kidney disease and accelerated kynurenine degradation. In particular, the excitotoxic metabolite quinolinic acid was localized in ependymal cells adjacent to the ventricle in the setting of kidney failure. These findings were associated with brain inflammation and cell death. A separate mouse model of acute kidney injury also had an increase in circulating toxic tryptophan metabolites along with altered brain inflammation. Patients with advanced CKD similarly demonstrated elevated plasma kynurenine metabolites and quinolinic acid was uniquely correlated with fatigue and reduced quality of life in humans. Overall, our study identifies the kynurenine pathway as a bridge between kidney decline, systemic inflammation, and brain toxicity, offering potential avenues for diagnosis and treatment of neurological issues in kidney disease.

Evaluation of clinical outcomes of raised intraocular pressure following intravitreal triamcinolone acetonide injection.

Aim: To assess the incidence, risk factors, and treatment outcomes in intravitreal triamcinolone acetonide injection (IVTA) induced intraocular pressure rise and to compare IOP rise in 1-mg and 2-mg IVTA. Materials and methods: Prospective observational study conducted in all eyes receiving IVTA. Any pre-existing glaucoma and patients who received IVTA or dexamethasone implant in the last 6 months were excluded. Results: 9 between 61-70 years of age developed an IOP spike. The mean and standard deviation of age in years was 61.95 ± 8.70. Maximum eyes had ME due to Diabetic Retinopathy (53.3%). All cases of uveitic ME were reported to have an IOP spike. 2 out of 3 high myopic eyes and 1 eye with thyroid abnormality had an IOP spike. High IOP was found in 13 eyes, with more than 25 mm Hg rise in 4 eyes and more than 5 mm Hg rise from baseline IOP in 9 eyes. The mean and standard deviation of time taken for IOP raise (in days) was 46.39 ± 37.68. A total of 38 eyes received 1 mg of IVTA and the rest 22 received 2 mg of IVTA. 23.7% of 1 mg eyes experienced an IOP rise while it was 18.2% in eyes with 2 mg IVTA. The injection was repeated in 12 eyes and 41.7% developed an IOP spike among them. The independent "t" test results showed that there was a significant difference in the mean of IOP (Pre-injection) concerning the IOP rise (P=0.007*). 1 eye had IVTA crystals in the anterior chamber with raised IOP of 30 mm Hg. 1 out of 13 eyes with raised IOP needed 2 AGMs, the other 12 eyes responded well to 1 AGM. Discussion: IVTA is widely used in refractory cases of ME and steroid-induced glaucoma is the most common side effect of IVTA. To the best of our knowledge, there is a lack of literature on prospective studies on IVTA-associated risk factors, patterns of IOP elevation, and treatment outcomes. The pre-injection mean ± SD baseline IOP for uneventful eyes was 12.87±2.65 and the pre-injection mean IOP for eyes with IOP event was 15.23±2.89 (P=0.007*). Conclusion: We proposed that TA is an independent risk factor for post-intravitreal injection IOP spike. IVTA causes a maximum IOP spike at 1 to 2 months and has a protracted course that responds to anti-glaucoma medications. High baseline IOP, a repeated dose of IVTA, the presence of TA crystals in the anterior chamber, and high myopia were associated with significant IOP elevation. Abbreviations: ACD = Anterior chamber depth, AS = Anterior segment, AGM = Anti-glaucoma medications, ARMD = Age-related macular degeneration, BCVA = Best-corrected visual acuity, BRVO = Branch retinal vein occlusion, CCT = Central corneal thickness, CRVO = Central retinal vein occlusion, CME = Cystoid macular edema, CNVM = Choroidal neovascularization membrane, CSME = Clinically significant macular edema, DR = Diabetic retinopathy, ERM = Epiretinal membrane, IOP = Intraocular pressure, IGS = Irvine-Grass syndrome, GAGs = Glycosaminoglycans, IVTA = Intravitreal triamcinolone acetonide injection, ME = Macular edema, NVG = Neovascular glaucoma, OHT = Ocular hypertension, PDS = Pigment dispersion syndrome, PACG = Primary closed angle glaucoma, POAG = Primary open-angle glaucoma, PXF = Pseudoexfoliation, VA = Visual acuity, VEGF = Vascular endothelial growth factors, VH = Vonherick's grading, SD = Standard deviation, TA = Triamcinolone acetonide, TIGR = Trabecular meshwork inducible glucocorticoid response.

The Comprehensive Primary Care Plus Model and Health Care Spending, Service Use, and Quality.

Importance: Implemented in 18 regions, Comprehensive Primary Care Plus (CPC+) was the largest US primary care delivery model ever tested. Understanding its association with health outcomes is critical in designing future transformation models. Objective: To test whether CPC+ was associated with lower health care spending and utilization and improved quality of care. Design, Setting, and Participants: Difference-in-differences regression models compared changes in outcomes between the year before CPC+ and 5 intervention years for Medicare fee-for-service beneficiaries attributed to CPC+ and comparison practices. Participants included 1373 track 1 (1 549 585 beneficiaries) and 1515 track 2 (5 347 499 beneficiaries) primary care practices that applied to start CPC+ in 2017 and met minimum care delivery and other eligibility requirements. Comparison groups included 5243 track 1 (5 347 499 beneficiaries) and 3783 track 2 (4 507 499 beneficiaries) practices, matched, and weighted to have similar beneficiary-, practice-, and market-level characteristics as CPC+ practices. Interventions: Two-track design involving enhanced (higher for track 2) and alternative payments (track 2 only), care delivery requirements (greater for track 2), data feedback, learning, and health information technology support. Main Outcomes and Measures: The prespecified primary outcome was annualized Medicare Part A and B expenditures per beneficiary per month (PBPM). Secondary outcomes included expenditure categories, utilization (eg, hospitalizations), and claims-based quality-of-care process and outcome measures (eg, recommended tests for patients with diabetes and unplanned readmissions). Results: Among the CPC+ patients, 5% were Black, 3% were Hispanic, 87% were White, and 5% were of other races (including Asian/Other Pacific Islander and American Indian); 85% of CPC+ patients were older than 65 years and 58% were female. CPC+ was associated with no discernible changes in the total expenditures (track 1: $1.1 PBPM [90% CI, -$4.3 to $6.6], P = .74; track 2: $1.3 [90% CI, -$5 to $7.7], P = .73), and with increases in expenditures including enhanced payments (track 1: $13 [90% CI, $7 to $18], P < .001; track 2: $24 [90% CI, $18 to $31], P < .001). Among secondary outcomes, CPC+ was associated with decreases in emergency department visits starting in year 1, and in acute hospitalizations and acute inpatient expenditures in later years. Associations were more favorable for practices also participating in the Medicare Shared Savings Program and independent practices. CPC+ was not associated with meaningful changes in claims-based quality-of-care measures. Conclusions and Relevance: Although the timing of the associations of CPC+ with reduced utilization and acute inpatient expenditures was consistent with the theory of change and early focus on episodic care management of CPC+, CPC+ was not associated with a reduction in total expenditures over 5 years. Positive interaction between CPC+ and the Shared Savings Program suggests transformation models might be more successful when provider cost-reduction incentives are aligned across specialties. Further adaptations and testing of primary care transformation models, as well as consideration of the larger context in which they operate, are needed.

Extracellular Hsp90 Binds to and Aligns Collagen-1 to Enhance Breast Cancer Cell Invasiveness.

Cancer cell-secreted eHsp90 binds and activates proteins in the tumor microenvironment crucial in cancer invasion. Therefore, targeting eHsp90 could inhibit invasion, preventing metastasis-the leading cause of cancer-related mortality. Previous eHsp90 studies have solely focused on its role in cancer invasion through the 2D basement membrane (BM), a form of extracellular matrix (ECM) that lines the epithelial compartment. However, its role in cancer invasion through the 3D Interstitial Matrix (IM), an ECM beyond the BM, remains unexplored. Using a Collagen-1 binding assay and second harmonic generation (SHG) imaging, we demonstrate that eHsp90 directly binds and aligns Collagen-1 fibers, the primary component of IM. Furthermore, we show that eHsp90 enhances Collagen-1 invasion of breast cancer cells in the Transwell assay. Using Hsp90 conformation mutants and inhibitors, we established that the Hsp90 dimer binds to Collagen-1 via its N-domain. We also demonstrated that while Collagen-1 binding and alignment are not influenced by Hsp90's ATPase activity attributed to the N-domain, its open conformation is crucial for increasing Collagen-1 alignment and promoting breast cancer cell invasion. These findings unveil a novel role for eHsp90 in invasion through the IM and offer valuable mechanistic insights into potential therapeutic approaches for inhibiting Hsp90 to suppress invasion and metastasis.

Mechanisms of Copper Toxicity and Tolerance in the Aquatic Moss Taxiphyllum barbieri.

Aquatic habitats are very frequently polluted with different kinds of xenobiotics, including heavy metals. For biomonitoring studies of aquatic pollution, algae are frequently used, as they do not contain protective cuticle on the surface of their thalli and can accumulate pollutants over the whole surface of thalli. However, this is a feature of most cryptogams. For this reason, we assessed the sensitivity of the aquatic moss Taxiphyllum barbieri (Java moss) to copper excess in a short-term study. Moss T. barbieri belongs to the common aquatic plants originating from Southeast Asia. To test the sensitivity (or tolerance) of the moss to excess Cu, selected concentrations (50, 250 and 500 µM) were employed in our 24 h studies. Total and intracellular Cu accumulation positively correlated with Cu availability in the water. This total and intracellular Cu accumulation was negatively correlated with decreased intracellular K content. Excess Cu negatively affected the composition of assimilation pigments and soluble proteins. Cu caused increased peroxidation of membrane lipids assessed using TBARS assay. Excess Cu decreased GSH to GSSG ratio and ascorbic acid content. We did not observe phytochelatin synthesis in this moss. The roles of selected amino acids, their intermediates and derivatives, as well as S-containing nucleosides and phenolic acids in Cu homeostasis and toxicity or tolerance were evaluated. We assume that this moss has potential for future employment in water quality evaluation.

Rapid review of factors influencing dietary behaviors in Fiji.

Introduction: In Fiji, multiple burdens of malnutrition including undernutrition, overweight/obesity, and micronutrient deficiencies coexist at the individual, household, and population levels. The diets of children, adolescents, and adults are generally unhealthy. The objective of this review was to understand how the dietary behaviors of children, adolescents, and women in Fiji are influenced by individual, social, and food environment factors. Methods: This rapid review was conducted to synthesize existing evidence, identify research gaps in the evidence base, and make recommendations for future research. The Cochrane Rapid Reviews Methods and the updated guideline for reporting systematic reviews were used. The search strategy for this rapid review was based on the Population Context Outcome [P(E)CO] framework, including search terms for population (children, adolescents, and adults), context (Fiji), and outcome (dietary behaviors). Searches were conducted in PubMed, Scopus, PsycINFO, and Google Scholar. Results: The 22 studies included in this review identified different factors influencing dietary behaviors in Fiji. Individual preferences for processed and imported foods, especially of younger generations, and social dynamics, especially gender norms and social pressure, to serve meat and overeat appeared to be prominent in driving dietary habits. The ongoing nutrition transition has led to increasing availability and affordability of ultra-processed and fast foods, especially in urban areas. Concerns about food safety and contamination and climate change and its effect on local food production also appear to influence dietary choices. Discussion: This review identified different dynamics influencing dietary behaviors, but also research gaps especially with regard to the food environment, calling for an integrated approach to address these factors more systemically.

AI-Assisted Screening of Oral Potentially Malignant Disorders Using Smartphone-Based Photographic Images.

The prevalence of oral potentially malignant disorders (OPMDs) and oral cancer is surging in low- and middle-income countries. A lack of resources for population screening in remote locations delays the detection of these lesions in the early stages and contributes to higher mortality and a poor quality of life. Digital imaging and artificial intelligence (AI) are promising tools for cancer screening. This study aimed to evaluate the utility of AI-based techniques for detecting OPMDs in the Indian population using photographic images of oral cavities captured using a smartphone. A dataset comprising 1120 suspicious and 1058 non-suspicious oral cavity photographic images taken by trained front-line healthcare workers (FHWs) was used for evaluating the performance of different deep learning models based on convolution (DenseNets) and Transformer (Swin) architectures. The best-performing model was also tested on an additional independent test set comprising 440 photographic images taken by untrained FHWs (set I). DenseNet201 and Swin Transformer (base) models show high classification performance with an F1-score of 0.84 (CI 0.79-0.89) and 0.83 (CI 0.78-0.88) on the internal test set, respectively. However, the performance of models decreases on test set I, which has considerable variation in the image quality, with the best F1-score of 0.73 (CI 0.67-0.78) obtained using DenseNet201. The proposed AI model has the potential to identify suspicious and non-suspicious oral lesions using photographic images. This simplified image-based AI solution can assist in screening, early detection, and prompt referral for OPMDs.

Maxillary Leiomyosarcoma with Lymph Node Metastasis: Report of an Unusual Case.

Leiomyosarcoma is an unusual, malignant, mesenchymal neoplasm that is extremely rare in head and neck region. It clinically presents as a well-defined, painless mass which could easily be misdiagnosed as a benign lesion, posing a diagnostic challenge to the clinician. Head and neck leiomyosarcomas are very aggressive and have a poor prognosis. Hence, early diagnosis plays a vital role in its appropriate management.

Treatment Outcomes and Survival in Hypercalcemia of Malignancy: A Grave Metabolic Emergency.

BACKGROUND: Management of hypercalcemia is based on the manifestation of symptoms and serum calcium levels. It is considered an oncological emergency; therefore, management has to be done on an urgent basis. AIM: In the present study, we analyzed the clinicopathological profile, treatment, and outcome of patients with hypercalcemia in solid malignancies at our institute. METHODS: We retrospectively analyzed the medical records of patients diagnosed with cancer and admitted to the department of radiation oncology with hypercalcemia. The parameters studied were age, gender, performance status, date of diagnosis, the primary site of cancer, stage, histopathology, time of presentation of hypercalcemia since initial cancer diagnosis, clinical symptoms, parathyroid hormone levels, liver and renal function tests, bone metastases, management, outcome, and present status. RESULTS: In the present study, 47 patients of hypercalcemia from various solid malignancies were admitted during the study period between 1st January 2018 and 30th April 2022. Head and neck cancer (14, 29.7%) was the most common site of the primary malignancy. Twelve patients had incidental hypercalcemia and were asymptomatic. Management of hypercalcemia included intravenous saline hydration, bisphosphonates, and supportive medication. At the time of analysis, 17 patients were lost to follow-up, 23 patients died, and seven were alive and on follow-up. Median survival was 68.0 days (95% CI: 1.7-134.3 days). CONCLUSION: Hypercalcemia of malignancy is considered a metabolic oncological emergency and requires urgent and aggressive management. It gets complicated by a deranged kidney function test. Despite available treatment, it portends an abysmal prognosis.

Evaluation of dosimetric and volumetric changes in target volumes and organs at risk during adaptive radiotherapy in head and neck cancer: A prospective study.

BACKGROUND: During radiation therapy for head and neck malignancies, most patients experience significant anatomical alterations due to loss of weight, changes in tumor volumes, and immobilization issues. Adaptive radiotherapy adapts to the patient's actual anatomy through repetitive imaging and replanning. In the present study, dosimetric and volumetric changes in target volumes and organs at risk during adaptive radiotherapy in head and neck cancer was evaluated. MATERIAL AND METHODS: Thirty-four locally advanced Head and neck carcinoma patients with histologically proven Squamous Cell Carcinoma for curative treatment were included. Rescan was done at the end of 20 fractions of treatment. All quantitative data were analyzed with paired t-Test and Wilcoxon Signed Rank (Z) test. RESULTS: Most patients had oropharyngeal carcinoma (52.9%). There were significant volumetric changes in all the parameters - GTV-primary (10.95, p < 0.001), GTV- nodal (5.81, p = 0.001), PTV High Risk (26.1, p < 0.001), PTV - Intermediate Risk (46.9, p = 0.006), PTV - Low Risk (43.9, p = 0.003), lateral neck diameter (0.9, p < 0.001), right parotid volumes (6.36, p < 0.001) and left parotid volumes (4.93, p < 0.001). Dosimetric changes in the organs at risk were non-significant. CONCLUSION: Adaptive replanning has been seen to be labour intensive. However, the changes in the volumes of both target and the OARs credit a mid-treatment replanning to be done. Long term follow-up is required to assess locoregional control after adaptive radiotherapy in head and neck cancer.

Biomimicking dual drug eluting twisted electrospun nanofiber yarns for post-operative wound healing.

The morbidity rate following a surgical procedure increasing rapidly in the cases associated with surgical site infections. Traditional sutures lack the ability to deliver drugs as the incorporation of the drug in their structure would hamper their mechanical properties. To prevent such infections, we developed an extracellular matrix mimicking electrospun nanofibrous yarns of poly-(D,L)-lactic acid and polyvinyl alcohol loaded with vancomycin and ferulic acid, prepared by uniaxial electrospinning technique.In-vitrocharacterization such as scanning electron microscopy, Fourier transform infrared spectroscopy, x-ray diffraction, tensile strength testing, degradation studies, and antimicrobial studies along within-vivoevaluation done with help of incision wound healing rat model and simultaneous testing of microbial load in the incised tissue. Thein-vitrostudies indicated the nanofiber yarns have size range 200-300 nm with a tensile strength of 7.54 ± 0.58 MPa. The dual drug-loaded yarn showed sustained drug release over a period of 48 h.In-vitrowater uptake and biodegradation data indicated optimum results suitable for suturing applications. Antimicrobial study showed excellent antimicrobial activity against bothS. aureus and E. coli.Results obtained fromin-vivostudy suggested excellent wound healing potential of nanofiber yarns as compared with commercial silk sutures. The histopathological studies confirmed restoring ability of nanofiber yarn to the normal skin structure. Enzyme-linked immunosorbent assay (ELISA) study revealed the downregulation of inflammatory markers i.e. TNF-alpha and IL-6, making nanofibers sutures suitable for surgical wound healing applications. Overall, the present study may conclude that the developed dual drug-loaded nanofiber yarns have excellent potential in surgical wound healing applications.

A Study to Assess the Prevalence and Factors Affecting Menopausal Symptoms among Middle-Aged Females in the Garhwal Region of Uttarakhand.

Background: Middle age is a link between adulthood and old age, which requires special attention. During middle age among females, changes like menopause occur, which is responsible for causing various physical, vasomotor, psychological, and social changes, which may affect overall well-being and positive mental health status. Hence, the present study has been planned to assess the prevalence of menopausal symptoms among middle-aged females. Materials and Methods: The present study was a cross-sectional study carried out in rural and urban areas of district Dehradun among 400 females. A stratified systematic random sampling technique method was used. All the females fulfilling the inclusion criteria and aged 40-60 years were included in the study. The Menopause-Specific Quality of Life (MENQOL) questionnaire was used to assess the prevalence of menopausal symptoms. Results: A total of 400 women were recruited in the study, 200 from rural and urban areas each. The mean age of the total study participants was 50.00 ± 0.32 years. Among 400 middle-aged women, 189 were premenopausal and 211 were postmenopausal. The frequencies of occurrence of menopausal symptoms were explored in 189 premenopausal and 211 postmenopausal women. The mean age of premenopausal women was 44.21 ± 2.35 and postmenopausal was 54.39 ± 4.21. Females experienced varying grades of MENQOL symptoms. Conclusions: It was found that majority of the females' quality of life were found to be affected with different grades of menopausal symptoms. With increasing age, symptoms also increase and are significantly high among postmenopausal women.

A study on initiation of postpartum family planning in India based on NFHS-4: does urban poor differ significantly from rural?

OBJECTIVE: To explore the differentials of postpartum contraceptive adoption between rural and urban poor after adjusting for utilization of MCH services and other selected socioeconomic and demographic covariates. METHODS: The data for this study is taken from the 4th round of NFHS survey conducted in India during 2015-16. The analysis is limited to 125,340 currently married women whose menses had returned at the time of survey. Discrete time complementary log-log multilevel model was applied.  RESULTS: The results clearly indicate that women from rural areas had a lower chance of early initiation of modern spacing methods after having recent birth as compare to that of Urban Poor and Urban non-poor areas. The contributions of several socioeconomic and demographic characteristics that were important for family planning practice were also highlighted in this study. CONCLUSION: There is an urgent need of designing an intervention that will result in effective delivery of services to achieve the greatest impact. Policy planners must focus on targeted interventions for family planning use in the postpartum period than simply focusing on family planning.

Comparison of CT and MRI for contouring active bone marrow in bone marrow sparing IMRT of carcinoma cervix and its effects on functional outcomes.

OBJECTIVE: Intensity-modulated radiotherapy (IMRT) has been used to reduce dose to bone marrow (BM) irradiation during pelvic conformal radiotherapy by contouring bone marrow and sparing it during radiotherapy planning. The present study was done to compare CT & MRI for contouring bone marrow to spare functional bone marrow for Intensity-modulated radiotherapy (IMRT) in carcinoma cervix and to assess its effect on functional outcome. MATERIAL & METHODS: This prospective, observational study included newly diagnosed carcinoma cervix patients treated by radical chemoradiation. Patients were distributed in two arms i.e. CT arm and MRI for contouring bone marrow. Regions taken into consideration for bone marrow volumes contouring were 4th and 5th Lumbar vertebrae, whole pelvis and proximal femur upto lesser trochanter. In CT arm bone marrow regions were contoured using freehand method with window adjusted to bone range (Window - 2500/ Level - 400) and in MRI arm BM regions on the MR images that had pixel values similar to muscle or IDEAL IQ sequence based on fat fractions present in bone marrow (BM) was used to contour. RESULTS: 17 patients in CT arm and 19 patients in MRI arm were included. There was no significant difference between the groups in terms of Bone Marrow Volume (cm3) (W = 171.500, p = 0.763). The mean value of V10, V20, V30 and V40 all were lower in group II (MRI) but the differences in volume were not significant. Bone marrow V30 in CT arm was found to correlate with absolute neutrophil count drop which was statistically significant in univariate (Coefficient - 1.00 [0.14-2.01, p = 0.025] and multivariate analysis (Coefficient - [1.08 (0.14 to 2.01, p = 0.025]). Bone marrow V30 in MRI arm was found to correlate with total leucocyte count percentage drop, which on multivariate analysis was statistically significant (Coefficient - 1.29 [0.29-2.28, p = 0.013]). CONCLUSIONS: Dosimetric parameters of bone marrow V10 and V30 were found to be associated with absolute neutrophil and total leucocyte nadir respectively. Haematological toxicity was observed more in MRI arm but more propspective studies are required for further validation.

Chemical defense acquired via pharmacophagy can lead to protection from predation for conspecifics in a sawfly.

Chemical defense is a widespread anti-predator strategy exhibited by organisms, with individuals either synthesizing or extrinsically acquiring defensive chemicals. In some species, such defences can also be transferred among conspecifics. Here, we tested the effects of pharmacophagy on the defense capability of the turnip sawfly, Athalia rosae, which can acquire neo-clerodane diterpenoids (clerodanoids) via pharmacophagy when having access to the plant Ajuga reptans. We show that clerodanoid access mediates protection against predation by mantids for the sawflies, both in a no-choice feeding assay and a microcosm setup. Even indirect access to clerodanoids, via nibbling on conspecifics that had access to the plant, resulted in protection against predation albeit to a lower degree than direct access. Furthermore, sawflies that had no direct access to clerodanoids were consumed less frequently by mantids when they were grouped with conspecifics that had direct access. Most, but not all, of such initially undefended sawflies could acquire clerodanoids from conspecifics that had direct access to the plant, although in low quantities. Together our results demonstrate that clerodanoids serve as a chemical defense that can also be transferred by interactions among conspecifics. Moreover, the presence of chemically defended individuals in a group can confer protection onto conspecifics that had no direct access to clerodanoids.

Susceptibility Testing by Volatile Organic Compound Detection Direct from Positive Blood Cultures: A Proof-of-Principle Laboratory Study.

BACKGROUND: Bacteria produce volatile organic compounds (VOCs) during growth, which can be detected by colorimetric sensor arrays (CSAs). The SpecifAST® system (Specific Diagnostics) employs this technique to enable antibiotic susceptibility testing (AST) directly from blood cultures without prior subculture of isolates. The aim of this study was to compare the SpecifAST® AST results and analysis time to the VITEK®2 (bioMérieux) system. METHODS: In a 12-month single site prospective study, remnants of clinical positive monomicrobial blood cultures were combined with a series of antibiotic concentrations. Volatile emission was monitored at 37 °C via CSAs. Minimal Inhibitory Concentrations (MICs) of seven antimicrobial agents for Enterobacterales, Staphylococcus, and Enterococcus spp. were compared to VITEK®2 AST results. MICs were interpreted according to EUCAST clinical breakpoints. Performance was assessed by calculating agreement and discrepancy rates. RESULTS: In total, 96 positive blood cultures containing Enterobacterales, Staphylococcus, and Enterococcus spp. were tested (269 bug-drug combinations). The categorical agreement of the SpecifAST® system compared to the VITEK®2 system was 100% and 91% for Gram-negatives and Gram-positives, respectively. Errors among Gram-positives were from coagulase-negative staphylococci. Overall results were available in 3.1 h (±0.9 h) after growth detection without the need for subculture steps. CONCLUSION: The AST results based on VOC detection are promising and warrant further evaluation in studies with a larger sample of bacterial species and antimicrobials.