Deciphering the impact of cold-adapted bioinoculants on rhizosphere dynamics, biofortification, and yield of kidney bean across varied altitudinal zones.

Agriculture stands as a thriving enterprise in India, serving as both the bedrock of economy and vital source of nutrition. In response to the escalating demands for high-quality food for swiftly expanding population, agricultural endeavors are extending their reach into the elevated terrains of the Himalayas, tapping into abundant resources for bolstering food production. Nonetheless, these Himalayan agro-ecosystems encounter persistent challenges, leading to crop losses. These challenges stem from a combination of factors including prevailing frigid temperatures, suboptimal farming practices, unpredictable climatic shifts, subdivided land ownership, and limited resources. While the utilization of chemical fertilizers has been embraced to enhance the quality of food output, genuine concerns have arisen due to the potential hazards they pose. Consequently, the present investigation was initiated with the objective of formulating environmentally friendly and cold-tolerant broad ranged bioinoculants tailored to enhance the production of Kidney bean while concurrently enriching its nutrient content across entire hilly regions. The outcomes of this study unveiled noteworthy advancements in kidney bean yield, registering a substantial increase ranging from 12.51 ± 2.39 % to 14.15 ± 0.83 % in regions of lower elevation (Jeolikote) and an even more remarkable surge ranging from 20.60 ± 3.03 % to 29.97 ± 5.02 % in higher elevated areas (Chakrata) compared to the control group. Furthermore, these cold-tolerant bioinoculants exhibited a dual advantage by fostering the enhancement of essential nutrients within the grains and fostering a positive influence on the diversity and abundance of microbial life in the rhizosphere. As a result, to effectively tackle the issues associated with chemical fertilizers and to achieve sustainable improvements in both the yield and nutrient composition of kidney bean across varying elevations, the adoption of cold-tolerant Enterobacter hormaechei CHM16, and Pantoea agglomerans HRM 23, including the consortium, presents a promising avenue. Additionally, this study has contributed significant insights-into the role of organic acids like oxalic acid in the solubilization of nutrients, thereby expanding the existing knowledge in this specialized field.

Case report: Enfortumab vedotin induced refractory DKA and multi organ failure - a rare fatal adverse event.

There are very few therapeutic options to treat patients with locally advanced or metastatic Urothelial Cancer (UC). Enfortumab vedotin (EV) was recently approved by the FDA and has become a new therapeutic option for patients previously managed with conventional treatments. Despite its efficacy, EV carries the potential for infrequent yet severe adverse effects. In this report, we present a case of a patient undergoing EV treatment for urothelial carcinoma who developed refractory diabetic ketoacidosis (DKA) unresponsive to escalating insulin doses and necessitating continuous renal replacement therapy. While DKA was resolved, the patient eventually succumbed to progressive maculopapular skin rash, liver failure, and respiratory failure. Additionally, the study delves into a review of cases of EV-induced refractory DKA in the literature, shedding light on the similarities in patient profiles, timelines of adverse effects and the treatment strategies employed to manage the ensuing complications.

Prevalence of Psychological Symptoms in Community-Dwelling Chinese American Patients with Chronic Cancer Pain.

Cancer is common among older Chinese American immigrants. Psychological distress may be associated with cancer pain, yet prior studies have not examined this relationship. We conducted a secondary analysis of 514 Chinese Americans with cancer-related pain. Patients completed validated questionnaires, including the Chinese Health Questionnaire-12 (CHQ-12). Analyses evaluated associations among sociodemographics, acculturation, psychological distress, and pain variables. Most patients had low acculturation and socioeconomic levels. Overall, 51.9% of patients reported moderate-severe psychological distress, 35.8% reported worst pain intensity ≥7/10 over the previous week and 41.2% had high pain-related distress. Higher CHQ-12 scores were associated with younger age (ß = -0.13); lower educational level (ß = -0.12); birthplace in China (ß = -0.18); lack of a caregiver (ß = -0.10); higher worst pain intensity (ß = 0.15); and higher pain-related distress (ß = 0.28; all p < 0.05; R2 = 0.23). Chinese American cancer patients with chronic pain experience high psychological distress, which is associated with pain characteristics and other social factors.

Providing End-of-Life Care for Patients With Left Ventricular Assist Devices: Experience of a Hospice Agency.

CONTEXT: Patients with left ventricular assist devices (LVADs) need expert palliative care at the end of life. In the U.S., hospice may provide this care, but few patients enroll, and information about hospice experience with LVAD-implanted patients is limited. OBJECTIVE: To describe hospice experience with LVAD-implanted patients. METHODS: This is a retrospective descriptive study of all LVAD-implanted patients admitted to a hospice agency. Data were extracted from the electronic health record. RESULTS: The 13 patients had a mean age of 63 years (range 20-89) and a mean LVAD duration of 32.5 months (range 8.2-70.0). Hospice diagnosis was heart failure in 10 patients and cancer in three patients; all patients were multimorbid. Eight patients enrolled in hospice on one occasion, four had two enrollments, and one had five. All patients received services for <180 days, three for <7 days, and four patients for >90 days. Just-in-time inservicing was used to prepare hospice teams for challenging care needs, including bleeding, delirium, infections, and mechanical failure. Of the nine patients who died while receiving hospice services, one enrolled with a plan to deactivate the LVAD immediately after hospice enrollment, and six died after discontinuation of the LVAD or other life-sustaining therapy during the course of hospice care. Five deaths occurred in a hospice inpatient unit. CONCLUSION: To provide specialist palliative care to LVAD-implanted patients, hospices must be prepared to manage complex and highly varied needs. To do this, hospices must have adequate staff support and access to acute care.

Strongyloides stercoralis Hyperinfection Syndrome: A Neglected Cause of Abdominal Pain.

Strongyloides stercoralis infection is usually acquired from tropics or subtropics, often causes asymptomatic chronic infection, but in immunosuppressed, it can lead to hyperinfection syndrome. We report a case of chronic abdominal pain resulting from Strongyloides infection in a 55-year-old male with a history of partial small bowel resection for small intestinal lymphoma and a recent diagnosis of chronic kidney disease with proteinuria on steroid therapy. He presented with chronic abdominal pain, nausea, loss of appetite, and weight loss. Initial laboratory workup and imaging including retroperitoneal ultrasound and CT of the abdomen/pelvis were within normal limits, and he was discharged on acid suppression therapy. He was readmitted with worsening symptoms and underwent esophagogastroduodenoscopy (EGD) and duodenal biopsy, which revealed Strongyloides infection. We later discovered a travel history to Cambodia. His symptoms resolved with ivermectin therapy. This case highlights the importance of travel history, which can prevent unnecessary investigations and delay in the diagnosis.

Thymic cancer in lynch syndrome: an unusual association.

Lynch syndrome has been associated with predominantly colorectal, endometrial, and ovarian cancer. We report hereby an unusual case of thymic carcinoma in a patient with Lynch syndrome. A 45-year-old Caucasian woman with a personal history of Lynch syndrome (MLH1 heterozygous mutation) presented with dyspnea, chest pain, and dysphagia. CT chest showed a bulky anterior mediastinal mass, pulmonary nodules, and pericardial effusion. Lung biopsy demonstrated a poorly differentiated carcinoma with squamous features with extensive necrosis, favouring thymic origin. Genomic studies on the tumour revealed deficient mismatch repair status with a two-copy deletion of MLH1 at 3p22.2 and c-Kit mutation. She received carboplatin and paclitaxel, with initial clinical improvement, but then died within 3 months after diagnosis. This case highlights that thymic cancer may be one of the malignancies associated with Lynch syndrome, and MLH1 gene mutation may have a role in the pathogenesis of thymic cancer.

Pulmonary Presentation of Kaposi-Sarcoma in a Renal Transplant Recipient.

Renal transplant patients on immunosuppression are at risk for malignancy. One form of malignancy that commonly affects this population is Kaposi-sarcoma. Kaposi-sarcoma is a human herpesvirus-8 (HHV-8)-driven process classically associated with skin lesions in immunocompromised patients. The pulmonary system may be involved in disseminated disease. In this case, a renal transplant patient was re-admitted with acute hypoxic respiratory failure and hemoptysis of an unclear etiology. Following a broad workup, HHV-8 PCR and a lymph node biopsy confirmed pulmonary Kaposi-sarcoma. Workup for multicentric Castleman disease was negative. The patient was treated with liposomal doxorubicin, ganciclovir, and prednisone. Her immunosuppression was changed to sirolimus and she is scheduled to complete six cycles of liposomal doxorubicin.

Direct physical interaction of active Ras with mSIN1 regulates mTORC2 signaling.

BACKGROUND: The mechanistic (or mammalian) target of rapamycin (mTOR), a Ser/Thr kinase, associates with different subunits forming two functionally distinct complexes, mTORC1 and mTORC2, regulating a diverse set of cellular functions in response to growth factors, cellular energy levels, and nutrients. The mechanisms regulating mTORC1 activity are well characterized; regulation of mTORC2 activity, however, remains obscure. While studies conducted in Dictyostelium suggest a possible role of Ras protein as a potential upstream regulator of mTORC2, definitive studies delineating the underlying molecular mechanisms, particularly in mammalian cells, are still lacking. METHODS: Protein levels were measured by Western blotting and kinase activity of mTORC2 was analyzed by in vitro kinase assay. In situ Proximity ligation assay (PLA) and co-immunoprecipitation assay was performed to detect protein-protein interaction. Protein localization was investigated by immunofluorescence and subcellular fractionation while cellular function of mTORC2 was assessed by assaying extent of cell migration and invasion. RESULTS: Here, we present experimental evidence in support of the role of Ras activation as an upstream regulatory switch governing mTORC2 signaling in mammalian cancer cells. We report that active Ras through its interaction with mSIN1 accounts for mTORC2 activation, while disruption of this interaction by genetic means or via peptide-based competitive hindrance, impedes mTORC2 signaling. CONCLUSIONS: Our study defines the regulatory role played by Ras during mTORC2 signaling in mammalian cells and highlights the importance of Ras-mSIN1 interaction in the assembly of functionally intact mTORC2.

Acute oxalate nephropathy associated with C lostridium difficile infection.

Acute oxalate nephropathy has been associated with chronic diarrheal illness and only one case has been reported due to acute diarrhea secondary to Clostridium difficile colitis. To the best of our knowledge, this is the second case report of acute oxalate nephropathy due to C . difficile colitis. A 75-year-old man with a medical history of hypertension, type 2 diabetes mellitus, chronic kidney disease stage IV, recent C . difficile colitis was admitted for acute kidney injury with a creatinine (Cr) of 8.54 mg/dL (baseline Cr, 2.3-2.6 mg/dL). His urinalysis did not show any eosinophils, casts or crystals. Antinuclear antibody, antineutrophil cytoplasmic antibody, complement levels (C3 and C4) and hepatitis screen were negative; a renal ultrasound visualized no hydronephrosis. A kidney biopsy showed widespread tubular oxalate crystal deposition suggestive of hyperoxaluria as the cause of acute kidney injury. In conclusion, an acute diarrheal illness like C . difficile colitis can cause acute oxalate nephropathy.

Mystery of neck lump: an uncommon presentation of urachal cancer.

We present the case of a 55-year-old male patient who presented with palpable cervical lymphadenopathy. Excisional biopsy showed metastatic adenocarcinoma of unknown origin. Imaging showed a bladder mass following which he underwent transurethral resection of bladder tumour. Histopathological evaluation of mass confirmed a poorly differentiated adenocarcinoma with signet-ring cell features. Immunohistochemistry was suggestive of metastatic urachal cancer. He agreed for enrollment in a clinical trial, however soon after 1st cycle, he developed immune pneumonitis requiring high dose steroids. On follow-up, MRI brain was done for evaluation of headache which showed metastatic intracranial disease. He completed radiotherapy following which he was started on FOLFOX chemo regimen (folinic acid, 5-fluorouracil and oxaliplatin).

Successful Treatment and Five Years of Disease-free Survival in a Donor Transmitted Metastatic Melanoma with Ipilimumab Therapy.

Approximately 7% of deceased donors have unknown cancer at the time of organ procurement. More than half of these have no apparent contraindication to organ donation. The commonest transmitted malignancy is renal cell cancer (19%), followed by melanoma (17%). Donor transmission of melanoma has been fatal in most cases as it is commonly metastatic at the time of diagnosis. Till date, there have been only a few cases with remission of melanoma following transplant nephrectomy and withdrawal of immunosuppression. To our knowledge, the evidence presented here is only the second case of donor-derived melanoma that was successfully treated with Ipilimumab. Our patient has the longest disease-free survival (five years) reported in the literature to date.

Chronic mesenteric ischaemia masked by candida esophagitis in a renal transplant patient.

Chronic mesenteric ischaemia is a severe disease that is often missed due to its non-specific presentation. Immunosuppressed patients are at risk for infectious gastrointestinal disease, which may further obscure the diagnosis of chronic mesenteric ischaemia. In this case, a patient's symptoms and diagnostic workup were consistent with candida esophagitis. Worsening leukocytosis despite treatment, however, prompted re-evaluation ultimately revealing a superior mesenteric artery thrombus causing mesenteric ischaemia. The patient required urgent surgical intervention for the management of his disease.

Insulin Pump in Difficult to Control Type 2 Diabetes: A Single Center, Five Years' Experience.

Objective Due to a progressive decline in beta-cell function, a considerable number of patients with type 2 diabetes mellitus (T2D) ultimately require multiple daily injections of large doses of insulin for glycemic control. Majority of studies have reported only short-term benefits of continuous subcutaneous insulin infusion (CSII) using an insulin pump in T2D. Our five-year follow-up data of CSII in T2D is one of the few studies showing persistent benefit in glucose control in this population. Research design and methods We did a chart review of patients treated with an insulin pump for five years. Inclusion criteria were: type 2 diabetes, 18-75 years of age, glycosylated hemoglobin (HbA1c) more than 6.5% (48 mmol/mol) on multiple doses of insulin (MDI > four injections per day) or more than 100 units of insulin/day, wide glycemic excursions, and intractable hypoglycemia. We identified a total of 13 patients. The primary endpoint was change in HbA1c from baseline to five years. We also reviewed the difference in weight, basal insulin requirements, hypoglycemia, and patient satisfaction questionnaire at one year. Exclusion criteria were: type 1 diabetes (T1D) and pregnancy. Results The HbA1c at five years was found to be 7.72% (61 mmol/mol) compared to a baseline of 8.89% (74 mmol/mol), p-value 0.0076. We did not find any increased risk of severe hypoglycemia, weight gain, and insulin requirement. Conclusions The beneficial effect of insulin pump persisted for five years of follow-up, suggesting it as a valuable treatment option for difficult to treat T2D.

Systematic investigation of ethanolic extract from Leea macrophylla: Implications in wound healing.

ETHNOPHARMACOLOGICAL RELEVANCE: Leea macrophylla Roxb. ex Hornem. (Leeaceae) commonly known as Hastikarnapalasa is mainly distributed throughout the tropical parts of India. Traditionally, the plant is found to be effective against guinea worm, ringworm and is applied to sores and wounds. AIM OF THE STUDY: The present study aims to validate traditional wound healing claim of Leea macrophylla scientifically. MATERIAL AND METHODS: Box-Behnken design (BBD) was used to optimize the extraction process. The optimized root tuber extract of Leea macrophylla was standardized with chlorogenic acid by HPLC for the first time. Both oral and topical routes were selected as administrative means for the wound healing study using excision and incision wound model. For topical treatment bioadhesive gel was formulated and characterized for mechanical and physical characteristics by texture profile analysis (TPA) and scanning electron microscopy (SEM). The effect on wound healing was also assessed by evaluating antioxidant enzymes viz. glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT), free radicals lipid peroxidation (LPO) and nitric oxide (NO), inflammatory marker myeloperoxidase (MPO), collagen markers hydroxyproline, hexosamine and hexuronic acid along with the histopathological examination. Furthermore, the effect on the level of the proinflammatory cytokines interleukin-1ß (IL-1ß), interleukin -6 (IL-6), tumor necrosis factor-α (TNF-α) and growth factor, vascular endothelial growth factor (VEGF) were determined. The expression of cell proliferation nuclear marker Ki-67 was also analyzed by Western blot analysis. RESULTS: With mesh openings Sieve no. 20, semi polar nature of solvent (92.5:7.5 ethanol-water blend) and extraction time of 18h, substantially greater extraction efficiency (29%) and phenolic yield (181.54mg/g) were obtained. The content of chlorogenic acid in ethanol extracts of Leea macrophylla was obtained as 9.01% w/w. In incision model, oral treatment with 500mg/kg ethanolic extract increased wound breaking strength by 23.41% while bioadhesive gel (5% w/v) showed a higher increase of 44.68%. Topical application produced complete wound contraction in 20 days against 22 days taken by oral treatment. Topical treatment also produced a significant (p<0.05) increase in antioxidants glutathione, superoxide dismutase and catalase whereas the level of enzymes lipid peroxidation and nitric oxide and inflammatory markers myeloperoxidase were reduced. Further advantageous effects were reflected by significantly (p<0.05) increased levels of hydroxyproline, hexosamine and hexuronic acid. Favorable effects on the level of proinflammatory cytokines interleukin-1ß, interleukin-6, tumor necrosis factor - α and growth factor, vascular endothelial growth factor were also observed. The wound healing potential of Leea macrophylla was further supported by its ability to promote cell proliferation during wound healing as demonstrated by Western blot analysis of proliferation marker Ki-67. CONCLUSION: The study justified traditional use of Leea macrophylla in wound healing and demonstrated that the bioadhesive gel of ethanolic extract produced faster and more significant healing as compared to oral treatment.