Diagnosing and treating Krukenberg tumor: a gynecologist’s dilemma

Krukenberg tumor is a rare tumor of ovary. It is a metastatic ovarian tumor usually from a primary in gastrointestinal tract. The lesions are usually not discovered until primary disease is advanced and therefore most patients die within a year. In some cases primary is never found and their prognosis worsens. We are reporting a case on which right ovariotomy was done for a complex right ovarian mass from another hospital. Even after surgery her symptoms persisted and on further evaluation, she was found to have primary gastric carcinoma with carcinoma of recto sigmoid and left Krukenberg tumor. Here the diagnosis of a metastatic disease was missed during the initial evaluation. 80% of these tumors are bilateral and usually both ovaries are affected at the same time. But in this case, left ovary was normal which later increased in size within just 2 weeks. No optimal treatment strategy is clearly mentioned in literature. Whether to give her a palliative care or a definitive cytoreductive surgery was debated. Recent literature says that if we can render the patient free of gross residual disease, we should do a primary debulking surgery rather than palliative care. Many studies have shown that aggressive debulking of macroscopic disease improves the survival rate

Physical Activity Related Risk Factor Assessment for Altered Drug Pharmacokinetics in Human Population

The study examined the intensity of an individual’s physical activity by using self administered International Physical Activity Questionnaire Short Form 7 (IPAQ-SF7) as a measuring tool and assessed its impact on the various body physiological functions likely to alter drug pharmacokinetic processes. The study was conducted in normal, subjects inhabited at different regions in India, with the translated versions of IPAQ-SF7 in Hindi and Tamil languages found the high intensities of vigorous, moderate activities and walking and showed excellent reproducibility as similar as it has been studied in different population worldwide. The resting state systolic and diastolic blood pressures, heart rate and respiratory rate were significantly higher in the subjects. The diaphragmatic breathing pattern was found used by majority of the subjects. The energy utilization of the subjects on their physical activity was obtained in high Metabolic Equivalence of Task (METs) minutes per week. Thus significance in the physiological parameters was strong enough to alter the pharmacokinetics of drugs whose metabolism and elimination are primarily dependent on renal function. This results which will be helpful in optimizing and selecting the drug doses for the people under extreme physical activity with less oxygen consumption in muscles, low level of respiratory rates and high energy utilization in their body

ASSESSMENT OF PSYCHOLOGICAL STRESSORS OF DEPRESSION AND ANXIETY USING DEPRESSION ANXIETY STRESS SCALE-21 IN SOUTH INDIAN HEALTHY VOLUNTEERS

Objective: The objective of this study was to assess the prevalence of the components of psychological stresses like depression, anxiety as a measure of the perception of the stress response (SR) and its influences on physiological functions in healthy human volunteers under various occupational stresses by using depression anxiety stress scale-21 (DASS-21). Methods: A total of 128 healthy subjects from various sites of Ooty were enrolled in this study, according to the inclusion-exclusion criteria in the study protocol. DASS-21 was administered to the subjects, by ‘Questerview' method. The intensity of psychological stresses of depression, anxiety and other mental stress was measured.Results: The incidence of depression, anxiety and their components such as hopelessness, dysphoria, anhedonia, low self-esteem, autonomic arousal, musculoskeletal symptoms, etc. were found high in both men and women participants. In men blood pressures were 136.16±6.6; 84.34±6.4 and in women 130.5±3.9; 86.48±3.4 as systolic, diastolic respectively. The body temperatures and heart rate were not altered, but the respiratory rate was found significantly elevated. The abdominal breathing was 45.21% in men and 52.77% in women indicated poor adaptation response towards the perception of stress. Conclusion: The results are concluding high prevalence of moderate to high-level depression and anxiety indicated stress response triggers a cascade producing a series of changes in human vital physiological functions such as blood pressure, respiratory rate, heart rate were significantly higher. We suggest future researchers are potential for the cumulative health benefits of patients in secondary or tertiary level treatment.Keywords: Psychological stressors, Stress response (SR), Depression anxiety stress scale-21 (DASS-21), Depression, Anxiety, Autonomic ArousalÂ

On-stack replacement, distilled

On-stack replacement (OSR) is essential technology for adaptive optimization, allowing changes to code actively executing in a managed runtime. The engineering aspects of OSR are well-known among VM architects, with several implementations available to date. However, OSR is yet to be explored as a general means to transfer execution between related program versions, which can pave the road to unprecedented applications that stretch beyond VMs. We aim at filling this gap with a constructive and provably correct OSR framework, allowing a class of general-purpose transformation functions to yield a special-purpose replacement. We describe and evaluate an implementation of our technique in LLVM. As a novel application of OSR, we present a feasibility study on debugging of optimized code, showing how our techniques can be used to fix variables holding incorrect values at breakpoints due to optimizations

Twisted large cellular fibroma of the ovary with pelvic effusion-revisiting incomplete demons Meigs’ syndrome

Fibromas of the ovary are benign tumours arising from the stromal component of the ovary. They represent 1% of ovarian neoplasms and are generally benign. The cellular subtype accounts for around 10% of these and is a tumour of uncertain malignant potential. Recurrence may occur or it could be associated with peritoneal implants. Usually these are solid tumours, sometimes with small areas of cystic degeneration. Occasionally, large fibromas may undergo torsion causing acute abdominal pain and generally tends to occur in post-menopausal women. The solid areas, ORADS and ascites simulated a malignant ovarian tumour on both MRI, USG and gross pathologic examination. Here we present a case of a postmenopausal woman presented with abdominal pain and postprandial vomiting with a large twisted ovarian fibroma leading to diagnostic and therapeutic challenges masquerading as a malignant ovarian neoplasm

Haematology profile of dogs with primary uterine inertia

Primary uterine inertia is the inherent inability of the uterus to contract and expel a fully grown foetus after the end of the gestation period, through a normal birth canal, in the absence of obstructive dystocia.There are conflicting reports regarding the blood parameters in parturient animals, and animals with dystocia and its role in uterine inertia are not well documented. Haematology analysis was performed in dogs with Complete Primary Uterine Inertia (CPUI, n=9) and Partial Primary Uterine Inertia (PPUI, n=6), as well as control animals with the Foetal Cause of Dystocia (FCD, n=7).Blood samples were collected from the study population and total leucocyte count (TLC), total erythrocyte count (TEC), differential leucocyte count (DLC), erythrocytic indices, haemoglobin and haematocrit values were estimated in an autoanalyzer. Haematology analysis revealed no significant difference between the groups. Differential leucocyte counts exhibited lymphocytosis across the groups suggestive of the active immune response related to CL lysis, a characteristic associated with the termination of the pregnancy in canines. Erythrocyte count, haemoglobin concentration and haematocrit revealed anaemia across the group. The study characterised the haematology profile of prepartum canines, which indicated anaemia associated with haemodilution and lymphocytosis associated with active immune status. It also proved that the haematology profile doesnot have any significant role in the pathogenesis of canine uterine inertia

The Effect of Fluid Flow Shear Stress and Substrate Stiffness on Yes-Associated Protein (YAP) Activity and Osteogenesis in Murine Osteosarcoma Cells

Osteosarcoma (OS) is an aggressive bone cancer originating in the mesenchymal lineage. Prognosis for metastatic disease is poor, with a mortality rate of approximately 40%; OS is an aggressive disease for which new treatments are needed. All bone cells are sensitive to their mechanical/ physical surroundings and changes in these surroundings can affect their behavior. However, it is not well understood how OS cells specifically respond to fluid movement, or substrate stiffness—two stimuli of relevance in the tumor microenvironment. We used cells from spontaneous OS tumors in a mouse engineered to have a bone-specific knockout of pRb-1 and p53 in the osteoblast lineage. We silenced Sox2 (which regulates YAP) and tested the effect of fluid flow shear stress (FFSS) and substrate stiffness on YAP expression/activity—which was significantly reduced by loss of Sox2, but that effect was reversed by FFSS but not by substrate stiffness. Osteogenic gene expression was also reduced in the absence of Sox2 but again this was reversed by FFSS and remained largely unaffected by substrate stiffness. Thus we described the effect of two distinct stimuli on the mechanosensory and osteogenic profiles of OS cells. Taken together, these data suggest that modulation of fluid movement through, or stiffness levels within, OS tumors could represent a novel consideration in the development of new treatments to prevent their progression

Optical analysis of samarium doped sodium bismuth silicate glass

Samarium doped sodium bismuth silicate glass was synthesized using the melt quenching method. Detailed optical spectroscopic studies of the glassy material were carried out in the UV–Vis-NIR spectral range. Using the optical absorption spectra Judd-Ofelt (JO) parameters are derived. The calculated values of the JO parameters are utilized in evaluating the various radiative parameters such as electric dipole line strengths (Sed), radiative transition probabilities (Arad), radiative lifetimes (τrad), fluorescence branching ratios (β) and the integrated absorption cross- sections (σa) for stimulated emission from various excited states of Sm3 +‡ ion. The principal fluorescence transitions are identified by recording the fluorescence spectrum. Our analysis revealed that the novel glassy system has the optimum values for the key parameters viz. spectroscopic quality factor, optical gain, stimulated emission cross section and quantum efficiency, which are required for a high performance optical amplifier. Calculated chromaticity co-ordinates (0.61, 0.38) also confirm its application potential in display devices

Profiling antibody epitopes induced by mRNA-1273 vaccination and boosters

BackgroundCharacterizing the antibody epitope profiles of messenger RNA (mRNA)-based vaccines against SARS-CoV-2 can aid in elucidating the mechanisms underlying the antibody-mediated immune responses elicited by these vaccines.MethodsThis study investigated the distinct antibody epitopes toward the SARS-CoV-2 spike (S) protein targeted after a two-dose primary series of mRNA-1273 followed by a booster dose of mRNA-1273 or a variant-updated vaccine among serum samples from clinical trial adult participants.ResultsMultiple S-specific epitopes were targeted after primary vaccination; while signal decreased over time, a booster dose after >6 months largely revived waning antibody signals. Epitope identity also changed after booster vaccination in some subjects, with four new S-specific epitopes detected with stronger signals after boosting than with primary vaccination. Notably, the strength of antibody responses after booster vaccination differed by the exact vaccine formulation, with variant-updated mRNA-1273.211 and mRNA-1273.617.2 booster formulations inducing significantly stronger S-specific signals than a mRNA-1273 booster.ConclusionOverall, these results identify key S-specific epitopes targeted by antibodies induced by mRNA-1273 primary and variant-updated booster vaccination

Aberrant Lck Signal via CD28 Costimulation Augments Antigen-Specific Functionality and Tumor Control by Redirected T Cells with PD-1 Blockade in Humanized Mice

Combination therapy of adoptively transferred redirected T cells and checkpoint inhibitors aims for higher response rates in tumors poorly responsive to immunotherapy like malignant pleural mesothelioma (MPM). Only most recently the issue of an optimally active chimeric antigen receptor (CAR) and the combination with checkpoint inhibitors is starting to be addressed. Fibroblast activation protein (FAP)-specific CARs with different costimulatory domains, including CD28, Δ-CD28 (lacking lck binding moiety), or 4-1BB were established. CAR-T cells were characterized and antitumor efficacy was tested in a humanized mouse model in combination with PD-1 blockade. Finally, the Δ-CD28 CAR was tested clinically in a patient with MPM. All the three CARs demonstrated FAP-specific functionality Gene expression data indicated a distinct activity profile for the Δ-CD28 CAR, including higher expression of genes involved in cell division, glycolysis, fatty acid oxidation, and oxidative phosphorylation. only T cells expressing the Δ-CD28 CAR in combination with PD-1 blockade controlled tumor growth. When injected into the pleural effusion of a patient with MPM, the Δ-CD28 CAR could be detected for up to 21 days and showed functionality. Overall, anti-FAP-Δ-CD28/CD3ζ CAR T cells revealed superior functionality, better tumor control in combination with PD-1 blockade in humanized mice, and persistence up to 21 days in a patient with MPM. Therefore, further clinical investigation of this optimized CAR is warranted