Autologous Stem Cell Transplantation in Adult Hodgkin Lymphoma at a Tertiary Care Center in India: Analysis of Outcomes and Prognostic Factors.

High-dose chemotherapy and autologous stem cell transplant (ASCT) is the standard of care treatment in relapsed/refractory Hodgkin lymphoma (rrHL). Published long-term follow-up data concerning this modality from the Indian subcontinent is lacking. In this retrospective study, the data on adults (> 16 years) with biopsy-confirmed rrHL who were autografted from 1 January 2000 to 31 December 2021 at our transplant unit were analyzed. Progression-free survival (PFS) was defined as time from transplant to disease progression or death due to any cause. Overall survival (OS) was determined from date of transplant to date of death due to any cause. Overall, 134 patients with Hodgkin lymphoma underwent ASCT. At a median follow-up of 38.2 (range, 0.1-240) months, 5 years PFS was 45.3% (95% CI 35.4-54.4). The probability of OS at 5 years was 60.5% (95% CI 49.6-69.6). Eleven (8.2%) patients suffered transplant-related mortality by 100 days. Post-transplant persistent disease, pre-transplant serum hypoalbuminemia (< 3.5 g/dl) and chemo-resistance (< PR after last salvage regimen) of tumour at transplant were independent prognostic factors associated with worse PFS in multivariable analysis. Likewise, age ≥ 30 years, ECOG performance status ≥ 1 and residual disease after transplantation correlated with inferior OS. Long-term outcomes of rrHL patients undergoing ASCT in India match those from the developed world in the era of peripheral blood stem cell transplantation. Pre-transplant performance status, chemo-sensitivity of disease, serum albumin and post-transplant remission status determined survival in our cohort. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01690-x.

Clinical significance of MUC-4 and associated proteins in Pancreatic and Periampullary Cancers.

OBJECTIVE: This study primarily aimed to assess the expression of MUC-4 in patients with Pancreatic Ductal Adenocarcinoma (PDAC) as compared with controls and assess its clinical relevance. METHODS: Serum MUC-4 levels and MUC-4 gene expression in snap-frozen tissue were analyzed through Surface Plasmon Resonance (SPR) and quantitative PCR respectively. Tumor tissues and control tissues were analyzed for MUC-4 and other mucins through IHC. RESULT: MUC-4 expression in tumor tissue was found to be significantly elevated in PDAC patients as compared to chronic pancreatitis (CP) tissues and normal pancreatic tissues. Periampullary carcinoma and cholangiocarcinoma tissue also showed increased expression of MUC-4 and other mucins. CONCLUSION: Differential expression of MUC-4 in pancreatic tumor tissues can help to differentiate PDAC from benign conditions.

Quality of life and symptom burden in hematological cancer patients receiving hematopoietic stem cell transplantation: an observational study at Regional Cancer Centre, India.

PURPOSE: Hematopoietic stem cell transplant (HSCT) is an intense form of treatment, resulting in major symptom burden but can prove curative. The quality of life (QOL) is a major endpoint for these patients as the survival rate in them has improved over time. The aim of the study is to assess the QOL and symptom burden of hematological malignancy patients at admission to hospital for HSCT, at 1 month and at 3 months following HSCT. METHODS: This prospective observational study was done on hematological malignancy patients who were admitted for HSCT in a regional cancer center. The study subjects were assessed by the Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale (FACT-BMT Scale), Edmonton Symptom Assessment Scale-revised (r-ESAS), and Depression, Anxiety and Stress Scale-21 Items (DASS-21) at the time of hospital admission for transplantation, on day 30 (~ 1 month) and day100 (~ 3 months) of transplantation. RESULTS: A total of 68 patients were included in this study. FACT-BMT scores have decreased from baseline (F0) to the first follow-up (F1) and then increased in the third follow-up (F2). The maximum r-ESAS mean score was for tiredness among all other symptoms at F0 as well as at F1 and at F2. The DASS 21 scores for depression, anxiety, and stress were maximum during F1 and minimum during F2. CONCLUSION: Symptom burden is maximum during the first month of BMT, which improves later and QOL becomes improved with time.

Methylation study of tumor suppressor genes in human aberrant crypt foci, colorectal carcinomas, and normal colon.

BACKGROUND: Aberrant crypt foci (ACF) are the earliest preneoplastic lesions in human colon, identifiable on chromoendoscopic screening. Our objective was to evaluate the %methylation of APC, CDKN2A, MLH1, RASSF1, MGMT, and WIF1 tumor suppressor genes (TSG) in ACF, corresponding colorectal carcinomas (CRC), and normal colonic mucosal controls. METHODS: In this study, macroscopically normal-appearing mucosal flaps were sampled 5-10 cm away from the tumor mass from 302 fresh colectomy specimens to identify ACF-like lesions. Thirty-five cases with multiple ACFs were selected (n 35) as the main study group, with corresponding sections from CRC (n 35) as disease controls, and mucosal tissue blocks from 20 colectomy specimens (normal controls), operated for non-neoplastic pathologies. Genomic DNA was extracted, and methylation-specific polymerase chain reaction (PCR) was performed on a customized methylation array model. %Methylation data were compared among the groups and with clinicopathological parameters. Selected target mRNA and protein expression studies were performed. RESULTS: %Methylation of TSGs in ACF was intermediate between normal colon and CRC, although a statistically significant difference was observed only for the WIF1 gene (P < 0.01). Also, there was increased nuclear ß-catenin expression and upregulation of CD44-positive cancer-stem cells in ACF and CRCs than in controls. Right-sided ACFs and dysplastic ACFs had a higher %methylation of CDKN2A (P < 0.01), whereas hyperplastic ACFs had a higher %methylation of RASSF1 (P 0.04). The topographic characteristics of ACFs did not correlate with TSG %methylation. CONCLUSIONS: Early epigenetic methylation of WIF1 gene is one of the mechanisms for ACF development in human colon.

Immunophenotypic characterization of leukemic stem cells in acute myeloid leukemia using single tube 10-colour panel by multiparametric flow cytometry: Deciphering the spectrum, complexity and immunophenotypic heterogeneity.

INTRODUCTION: Despite extensive research, comprehensive characterization of leukaemic stem cells (LSC) and information on their immunophenotypic differences from normal haematopoietic stem cells (HSC) is lacking. Herein, we attempted to unravel the immunophenotypic (IPT) characteristics and heterogeneity of LSC using multiparametric flow cytometry (MFC) and single-cell sequencing. MATERIALS AND METHODS: Bone marrow aspirate samples from patients with acute myeloid leukaemia (AML) were evaluated using MFC at diagnostic and post induction time points using a single tube-10-colour-panel containing LSC-associated antibodies CD123, CD45RA, CD44, CD33 and COMPOSITE (CLL-1, TIM-3, CD25, CD11b, CD22, CD7, CD56) with backbone markers that is, CD45, CD34, CD38, CD117, sCD3. Single-cell sequencing of the whole transcriptome was also done in a bone marrow sample. RESULTS: LSCs and HSCs were identified in 225/255 (88.2%) and 183/255 (71.6%) samples, respectively. Significantly higher expression was noted for COMPOSITE, CD45RA, CD123, CD33, and CD44 in LSCs than HSCs (p < 0.0001). On comparing the LSC specific antigen expressions between CD34+ (n = 184) and CD34- LSCs (n = 41), no difference was observed between the groups. More than one sub-population of LSC was demonstrated in 4.4% of cases, which further revealed high concordance between MFC and single cell transcriptomic analysis in one of the cases displaying three LSC subpopulations by both methods. CONCLUSION: A single tube-10-colour MFC panel is proposed as an easy and reproducible tool to identify and discriminate LSCs from HSCs. LSCs display both inter- and intra-sample heterogeneity in terms of antigen expressions, which opens the facets for single cell molecular analysis to elucidate the role of subpopulations of LSCs in AML progression.

Carboplatin in Patients With Metastatic Castration-Resistant Prostate Cancer Harboring Somatic or Germline Homologous Recombination Repair Gene Mutations: Phase II Single-Arm Trial.

BACKGROUND: Approximately 20%-25% of patients with metastatic castration-resistant prostate cancer (mCRPC) harbor a deleterious germline or somatic mutation in the homologous recombination repair (HRR) pathway genes, which is involved in the repair of double-stranded DNA damage. Half of these mutations are germline, while the remaining are exclusively somatic. While polyadenosine 5'diphosphoribose [poly (ADP-ribose)] polymerase inhibitors, such as olaparib and rucaparib, are effective in this subgroup, their widespread use is limited due to the associated high cost, especially in resource-constrained settings. Notably, platinum agents like carboplatin have exquisite sensitivity to cells with defective DNA repair machinery. Carboplatin, a conventional, inexpensive chemotherapeutic agent, offers a potential alternative treatment in such patients. Several retrospective small case series support this hypothesis. However, there are no prospective clinical trials of carboplatin in patients with mCRPC with HRR mutations. OBJECTIVE: The primary objective is to assess the objective response rate of 3 weekly carboplatin treatments in patients with mCRPC harboring deleterious mutations in the HRR pathway genes and previously treated with a taxane or a novel antiandrogen agent. The secondary objectives include progression-free survival, health-related quality of life, and safety profile of carboplatin. METHODS: Patients diagnosed with mCRPC harboring HRR pathway mutations previously treated with docetaxel or novel antiandrogen agents (abiraterone, enzalutamide, apalutamide, or darolutamide) or both will be eligible. Genes involved directly or indirectly in the HRR pathway will be tested. In this single-arm phase II study, we will screen approximately 200 patients to enroll 49 patients, and carboplatin (dosing at the area under curve=5) will be administered every 3 weeks until progression or intolerable side effects. The primary end point will be assessed as the proportion of patients with a reduction of serum prostate-specific antigen by more than 50% from enrollment. Secondary outcomes include progression-free survival-soft-tissue disease progression (by response evaluation criteria in solid tumors, version 1.1, and bone lesion progression using Prostate Cancer Clinical Trials Working Group 3 criteria), health-related quality of life during carboplatin treatment using the Functional Assessment of Cancer Therapy-Prostate questionnaire and the European Organisation for Research and Treatment of Cancer questionnaire and safety profile of carboplatin (National Cancer Institute's Common Terminology Criteria for Adverse Events version 5.0). RESULTS: The trial started enrollment in September 2023. This trial is ongoing, and 12 patients have been recruited to date. All 49 participants will be enrolled according to plan. CONCLUSIONS: This prospective phase II trial represents a critical step toward addressing the therapeutic gap in patients with mCRPC harboring HRR pathway mutations, particularly in demographic regions with limited access to poly (ADP-ribose) polymerase inhibitors. Outcomes from this study will inform clinical practice and guide future phase III randomized trials, ultimately improving patient outcomes globally. TRIAL REGISTRATION: Clinical Trials Registry of India CTRI/2023/04/051507; https://ctri.nic.in/Clinicaltrials/pmaindet2.php?EncHid=Njc0NjU=&Enc=&userName=. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54086.

Decoding the genetic symphony: Profiling protein-coding and long noncoding RNA expression in T-acute lymphoblastic leukemia for clinical insights.

T-acute lymphoblastic leukemia (T-ALL) is a heterogeneous malignancy characterized by the abnormal proliferation of immature T-cell precursors. Despite advances in immunophenotypic classification, understanding the molecular landscape and its impact on patient prognosis remains challenging. In this study, we conducted comprehensive RNA sequencing in a cohort of 35 patients with T-ALL to unravel the intricate transcriptomic profile. Subsequently, we validated the prognostic relevance of 23 targets, encompassing (i) protein-coding genes-BAALC, HHEX, MEF2C, FAT1, LYL1, LMO2, LYN, and TAL1; (ii) epigenetic modifiers-DOT1L, EP300, EML4, RAG1, EZH2, and KDM6A; and (iii) long noncoding RNAs (lncRNAs)-XIST, PCAT18, PCAT14, LINC00202, LINC00461, LINC00648, ST20, MEF2C-AS1, and MALAT1 in an independent cohort of 99 patients with T-ALL. Principal component analysis revealed distinct clusters aligning with immunophenotypic subtypes, providing insights into the molecular heterogeneity of T-ALL. The identified signature genes exhibited associations with clinicopathologic features. Survival analysis uncovered several independent predictors of patient outcomes. Higher expression of MEF2C, BAALC, HHEX, and LYL1 genes emerged as robust indicators of poor overall survival (OS), event-free survival (EFS), and relapse-free survival (RFS). Higher LMO2 expression was correlated with adverse EFS and RFS outcomes. Intriguingly, increased expression of lncRNA ST20 coupled with RAG1 demonstrated a favorable prognostic impact on OS, EFS, and RFS. Conclusively, several hitherto unreported associations of gene expression patterns with clinicopathologic features and prognosis were identified, which may help understand T-ALL's molecular pathogenesis and provide prognostic markers.

SMART-ESAS: Smartphone Monitoring and Assessment in Real Time of Edmonton Symptom Assessment System Scores for Patients With Cancer.

PURPOSE: Serial patient-reported outcome (PRO) measurements in clinical practice are associated with a better quality of life and survival. Recording electronic PROs using smartphones is an efficient way to implement this. We aimed to assess the feasibility of the electronically filled Edmonton Symptom Assessment System (e-ESAS) scale in the lower-middle-income country (LMIC) setting. METHODS: Baseline clinical features and conventional paper-based ESAS (p-ESAS) were collected in newly diagnosed patients with solid organ tumors. Text message link was sent to these patients for filling e-ESAS. ESAS was categorized into physical, psychological, and total symptom domains. Scores were divided into none to mild (0-3) and moderate to severe (4-10). Intraclass correlation coefficients (ICCs) were used to determine the correlation between p-ESAS and e-ESAS. Multivariable logistic regression was used to identify independent factors affecting symptom burden. RESULTS: Of 1,160 participants who filled out p-ESAS, 595 completed both e-ESAS and p-ESAS questionnaires and were included in the final analysis. Moderate to severe physical, psychological, and total symptom scores were seen in 39.8%, 40%, and 39% of participants. Tiredness and anxiety were the most common physical and psychological symptoms, respectively. ICCs between the p-ESAS and e-ESAS varied between 0.75 and 0.9. Total symptom scores were independently predicted by metastatic disease (odds ratio [OR], 1.83; 95% CI, 1.26 to 2.67; P = .001) and a higher level of education (OR, 0.42; 95% CI, 0.25 to 0.72; P = .001). CONCLUSION: Paper-based and electronically filled ESASs have good intraobserver reliability across individual symptoms and domain scores in a representative cohort at a tertiary care institute in the LMIC. This may help us incorporate e-ESAS in routine clinical care in the real-world setting with financial, infrastructural, and manpower limitations.

Swallowing dysfunction between the community-living older adults with and without comorbid conditions using Patient-Reported Outcome Measures (PROM).

OBJECTIVE: The present study aimed to investigate older adults' perspective on their swallowing physiology using a PROM tool. The study further explored the swallowing issues among older adults with and without comorbid conditions. METHOD: One hundred twenty-two (122) participants participated in the e-survey. A questionnaire was developed to assess the swallowing deficits among older adults, and Eating Assessment Tool-10 (EAT-10) was administered to assess the PROM. RESULTS: The results revealed that 40% of older adults with comorbid conditions had EAT-10 scores greater than 3, suggesting swallowing deficits. A significant difference was observed between the two groups with respect to swallowing deficits, as reported on EAT-10. CONCLUSION: Based on the results, it can be delineated that swallowing deficits emerge with aging. More of older adults with comorbid conditions reported swallowing deficits in comparison to those without comorbid conditions. Hence, their nutritional and health status gets compromised, leading to poor quality of life.

Topical Diclofenac for Prevention of Capecitabine-Associated Hand-Foot Syndrome: A Double-Blind Randomized Controlled Trial.

PURPOSE: Hand-foot syndrome (HFS) is a dose-limiting side effect of capecitabine. Celecoxib prevents HFS by inhibiting cyclooxygenase-2 (COX-2) that is upregulated because of the underlying associated inflammation. However, systemic side effects of celecoxib have limited routine prescription. Topical diclofenac inhibits COX-2 locally with minimal risk of systemic adverse events. Therefore, we conducted this study to assess the efficacy of topical diclofenac in the prevention of capecitabine-induced HFS. METHODS: In this single-site phase III randomized double-blind trial, we enrolled patients with breast or GI cancer who were planned to receive capecitabine-based treatment. Participants were randomly assigned in a 1:1 ratio to receive topical diclofenac or placebo gel for 12 weeks or until the development of HFS, whichever occurred earlier. The primary end point was the incidence of grade 2 or 3 HFS (Common Terminology Criteria for Adverse Events version 5), which was compared between the two groups using simple logistic regression. RESULTS: In total, 264 patients were randomly assigned to receive topical diclofenac gel (n = 131) or placebo (n = 133). Grade 2 or 3 HFS was observed in 3.8% of participants in the diclofenac group compared with 15.0% in the placebo group (absolute difference, 11.2%; 95% CI, 4.3 to 18.1; P = .003). Grade 1-3 HFS was lower in the diclofenac group than in the placebo group (6.1% v 18.1%; absolute risk difference, 11.9%; 95% CI, 4.1 to 19.6). Capecitabine dose reductions because of HFS were less frequent in the diclofenac group (3.8%) than in the placebo group (13.5%; absolute risk difference, 9.7%; 95% CI, 3.0 to 16.4). CONCLUSION: Topical diclofenac prevented HFS in patients receiving capecitabine. This trial supports the use of topical diclofenac to prevent capecitabine-associated HFS.

Ultrasensitive electrochemical sensor for detection of salivary cortisol in stress conditions.

A natural stress response induces elevated cortisol levels in biological fluids, such as saliva. While current sensor technologies can detect cortisol in real time, their sensitivity and reliability for human subjects have not been assured. This is due to relatively low concentrations of salivary cortisol, which fluctuate throughout the day and vary significantly between individuals. To address these challenges, we present an improved electrochemical biosensor leveraging graphene's exceptional conductivity and physicochemical properties. A 1-pyrenebutyric acid N-hydroxysuccinimide ester (PBASE-NHS)-modified commercial graphene foam (GF) electrode is presented to realize an ultra-sensitive biosensor for cortisol detection directly in human saliva. The biosensor fabrication process entails the attachment of anti-cortisol monoclonal antibodies (mAb-cort) onto a PBASE-NHS/GF electrode through noncovalent immobilization on the vertically stratified graphene foam electrode surface. This unique immobilization strategy preserves graphene's structural integrity and electrical conductivity while facilitating antibody immobilization. The binding of cortisol to immobilized mAb-cort is read out via differential pulse voltammetry using ferri/ferro redox reactions. The immunosensor demonstrates an exceptional dynamic range of 1.0 fg mL-1 to 10,000 pg mL-1 (R2 = 0.9914) with a detection limit of 0.24 fg mL-1 (n = 3) for cortisol. Furthermore, we have established the reliability of cortisol sensors in monitoring human saliva. We have also performed multiple modes of validation, one against the established enzyme-linked immunosorbent assay (ELISA) and a second by a third-party service Salimetric on 16 student volunteers exposed to different stress levels, showing excellent correlation (r = 0.9961). These findings suggest the potential for using mAb-cort/PBASE-NHS/GF-based cortisol electrodes for monitoring salivary cortisol in the general population.

Stimuli-responsive and self-healing supramolecular Zn(II)-guanosine metal-organic gel for Schottky barrier diode application.

Spontaneous formation of a supramolecular metal-organic hydrogel using unsubstituted guanosine as a ligand and Zn2+ ions is reported. Guanosine, in the presence of NaOH, self-assembled into a stable G-quadruplex structure, which underwent crosslinking through Zn2+ ions to afford a stable hydrogel. The gel has been characterized using several spectroscopic as well as microscopic studies. The hydrogel demonstrated excellent stimuli responsiveness towards various chemicals and pH. Furthermore, the gel exhibited intrinsic thixotropic behavior and showed self-healing and injectable properties. The optical properties of the Zn-guanosine metallo-hydrogel suggested a semiconducting nature of the gel, which has been exploited for fabricating a thin film device based on a Schottky diode interface between metal and a semiconductor. The fabricated device shows excellent charge transport characteristics and linear rectifying behavior. The findings are likely to pave the way for newer research in the area of soft electronic devices fabricated using materials synthesized by employing simple biomolecules.

Dexamethasone-free antiemetic strategy for highly emetogenic chemotherapy: safety and efficacy-pilot study.

OBJECTIVES: Dexamethasone sparing strategies have shown success. The feasibility of a dexamethasone-free antiemetic strategy remains undetermined. A prospective, single-arm, pilot study was planned to determine the efficacy of an olanzapine-based, dexamethasone-free, three-drug antiemetic regimen. METHODS: Chemotherapy naïve, adult patients (≥18 years) who received ondansetron, aprepitant and olanzapine during the first cycle of highly emetogenic chemotherapy were enrolled. The primary endpoint was the rate of complete response (CR: no vomiting and no use of rescue medications) during the overall period (0-120 hours). RESULTS: Out of the total of 101 patients enrolled, most were women (82%) and received anthracycline cyclophosphamide (73%) combination therapy. The rate of CR for the overall period was 65% (95% CI 55.2% to 74.5%). The rate of CR for the acute and delayed period was 79% (95% CI 70% to 86.7%) and 76% (95% CI 66.7% to 84.1%). The rate of nausea control rates for the acute, delayed and overall periods were 34%, 29% and 24%, respectively. The grade I, II and III sedation rates over the 5 days were 8%, 5% and 1%, respectively. CONCLUSIONS: The dexamethasone-free antiemetic strategy showed modest efficacy with low incidence of clinically significant somnolence. There is a need to prospectively investigate the role of dexamethasone in the era of newer potent antiemetics in a randomised fashion. TRIAL REGISTRATION NUMBER: CTRI/2021/07/034813.

SMARCB1/INI1-Deficient Poorly Differentiated Carcinoma of the Colon With Rhabdoid Features-A Rare Tumor With Serrated Phenotype: Case Report and Review of Literature.

Poorly differentiated colonic carcinoma with rhabdoid features is a rarely described entity. Our knowledge regarding the molecular phenotype of the tumor is evolving. We herein report a similar tumor with rhabdoid differentiation identified in the splenic flexure, which on histological examination showed a poorly differentiated phenotype with epithelioid to spindled morphology, tumor giant cells, and rhabdoid differentiation. The tumor was mismatch repair-proficient, deficient of INI1/SMARCB1, KRAS mutated (A146×), BRAFV600E mutated (c.1799T > A), and NRAS wild-type, indicating serrated differentiation in the tumor. The patient died after 3.5 months post-surgery. INI1-deficient poorly differentiated carcinoma of the colon is a rare, aggressive colonic malignancy showing a serrated phenotype. Routine identification and subtyping are important keeping in mind the distinct tumor phenotype, resistance to conventional chemotherapy, and dismal prognosis.

Are we teaching the health impacts of climate change in a clinically relevant way? A systematic narrative review of biomechanism-focused climate change learning outcomes in medical curricula.

PURPOSE: Introducing biomedical approaches to the health impacts of climate change can improve medical student engagement with relevant climate-related issues, improve the development of medical schemas, and minimise displacement into crowded medical curricula. This paper aims to systematically review the medical education curricula related to climate change, with a particular focus on systems-based biomechanisms for the health impacts of climate change. We do this to provide a clear agenda for further development of learning outcomes (LOs) in this area to maximize the clinical applicability of this knowledge. MATERIAL AND METHODS: A systematic review was undertaken following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA; Liberati et al. 2009) guidelines for both the published and grey literature. Five databases (PubMed, SCOPUS, ERIC, Open Access Thesis and Dissertation, and Proquest Global Dissertation and Theses) were searched for works published between 2011 and June 2023. Full texts that contained LOs were the main inclusion criteria for the final review. Descriptive and content extraction guided the final narrative synthesis. RESULTS: Analysis indicated that biomechanism-related LOs represented about 25% of each published LO set, on average. These outcomes were primarily at the "understand" level of Bloom's taxonomy and were spread across a range of body systems and climate-change aspects. Infectious diseases and extreme heat were strong focuses. Authorship analysis indicated that the majority of these sets of published LOs are from Western contexts and authored by researchers and educators with medical and population health qualifications. CONCLUSIONS: Biomechanism-focused teaching about the health impacts of climate change is relatively rare in published curricula. Of the available sets of LOs, the majority are sourced from Western authors and are focused on a fairly circumscribed set of biomedical topics. There is scope to both broaden and deepen curriculum in this area, and we would recommend the field prioritise collaboration with medical educators from the Global South, where the effects of climate change are already the most acutely felt.

Sella Turcica Size in Women with Sheehan Syndrome-A Case-Control Study.

Introduction: Sheehan syndrome is a common cause of hypopituitarism in developing countries. Among risk factors, in addition to post-partum haemorrhage, a smaller sellar volume is also believed to predispose to pituitary necrosis. Some earlier studies have reported smaller sellar volume in these patients but involved a small number of patients and lacked matched controls. The main of the present study was to study the sellar volume in a large cohort of patients with Sheehan syndrome and compare it with age- and parity-matched controls. Methods: Fifty women with Sheehan syndrome and an equal number of age- and parity-matched controls were studied. Baseline investigations, relevant hormonal assay, and MRI of pituitary were studied in all. Results: Sellar volume was significantly lower in patients with Sheehan syndrome (334.50 ± 129.08 mm3 in patients as against 456.64 ± 169.25 mm3 in controls, P = 0.000). Far more women with Sheehan syndrome than controls had decreased sellar volume (40% vs. 12%). Conclusions: Patients with Sheehan syndrome have a smaller sellar volume that may be a non-modifiable risk factor for the development of post-partum pituitary necrosis.

Smart sensing flexible sutures for glucose monitoring in house sparrows.

There is a need for flexible chemical sensors for the ecological and physiological research of avian species such as house sparrows (Passer domesticus). Current methods in this field are invasive and require multiple physical interactions with the birds. Emerging research in flexible bioelectronics can enable realization of implantable devices that are mechanically compliant with the underlying tissues for continuous real-time sensing in situ. However, challenges still remain in forming an intimate flexible interface. One of the promising flexible bioelectronic platforms for tissue-embedded sensing is based on functionalizing surgical sutures or threads. Threads have three-dimensional flexibility, high surface-area-to-volume ratio, inherent wicking properties, and are easily functionalizable using reel-to-reel dip coating. Threads are ideal as they are lightweight, therefore, would not interfere with flight motion and would only require minimal interaction with the bird. However, the challenge remains in achieving a highly conductive yet flexible electrode for electrochemical sensing using materials such as gold. In this study, we address this issue through novel gold deposition directly on thread substrate followed by enzyme immobilization to realize flexible electrochemical glucose biosensors on medical-grade sutures. These sensors were calibrated and tested in a range that is wide enough to include the expected range of glucose concentration in house sparrows (0-8.55 mM). Glucose monitoring in house sparrows will provide insights into energy metabolism and regulation during stress responses. In addition, the stability, repeatability, and selectivity of the sensor were tested with final validation in a real bird. Our innovative gold-coated, thread-based flexible electrochemical glucose sensor can also be used in other small and large animals. This can also be extended to monitoring other metabolites in future.

Human Resources for Health in Haryana, India: What can be Done Better?

Introduction: Health systems in developing countries suffers from both input and productivity issues. We examined the status of three domains of human resources for health, i.e., availability and distribution, capacity and productivity, and motivation and job-satisfaction, of the health-care workforce employed in the public health system of Haryana, a North Indian state. Methodology: The primary data were collected from 377 public health facilities and 1749 healthcare providers across 21 districts. The secondary data were obtained from government reports in the public domain. Bivariate and multivariate statistical techniques were used for evaluating district performances, making inter-district comparisons and identifying determinants of motivation and job-satisfaction of the clinical cadres. Results: We found 3.6 core health-care workers (doctors, staff nurses, and auxiliary nurses-midwives) employed in the public health-care system per 10,000 population, ranging from 1.35 in Faridabad district to 6.57 in Panchkula district. Around 78% of the sanctioned positions were occupied. A number of inpatient hospitalizations per doctor/nurses per month were 17 at the community health center level and 29 at the district hospital level; however, significant differences were observed among districts. Motivation levels of community health workers (85%) were higher than clinical workforce (78%), while health system administrators had lowest motivation and job satisfaction levels. Posting at primary healthcare facility, contractual employment, and co-habitation with family at the place of posting were found to be the significant motivating factors. Conclusions: A revamp of governance strategies is required to improve health-care worker availability and equitable distribution in the public health system to address the observed geographic variations. Efforts are also needed to improve the motivation levels of health system administrators, especially in poorly performing districts and reduce the wide gap with better-off districts.

Ingestible pH sensing device for gastrointestinal health monitoring based on thread-based electrochemical sensors.

There exists a strong correlation between the pH levels of the gastrointestinal (GI) tract and GI diseases such as inflammatory bowel disease (IBS), ulcerative colitis, and pancreatis. Existing methods for diagnosing many GI diseases predominantly rely on invasive, expensive, and time-consuming techniques such as colonoscopy and endoscopy. In this study, an autonomous ingestible smart biosensing system in a pill format with integrated pH sensors is reported. The smart sensing pills will measure the pH profile as they transit through the GI tract. The data is then downloaded from the pills after they are collected from the feces. The sensor is based on electrodeposited PANI on carbon-coated conductive threads providing high pH sensitivity. Engineering innovations allowed integration of thread-based sensors on 3D-printed pill surfaces with front-end readout electronics, memory, and microcontroller assembled on mm-size circular printed circuit boards. The entire smart sensing pill possesses an overall length of 22.1 mm and an outer diameter of 9 mm. The modular biosensing system allows integration of thread-based biosensors to monitor other biomarkers in GI tract that mitigates the complex sensor fabrication process as well as overall pill assembly.