Deeper insight into ferroptosis: association with Alzheimer's, Parkinson's disease, and brain tumors and their possible treatment by nanomaterials induced ferroptosis.

Ferroptosis is an emerging and novel type of iron-dependent programmed cell death which is mainly caused by the excessive deposition of free intracellular iron in the brain cells. This deposited free iron exerts a ferroptosis pathway, resulting in lipid peroxidation (LiPr). There are mainly three ferroptosis pathways viz. iron metabolism-mediated cysteine/glutamate, and LiPr-mediated. Iron is required by the brain as a redox metal for several physiological activities. Due to the iron homeostasis balance disruption, the brain gets adversely affected which further causes neurodegenerative diseases (NDDs) like Parkinson's and Alzheimer's disease, strokes, and brain tumors like glioblastoma (GBS), and glioma. Nanotechnology has played an important role in the prevention and treatment of these NDDs. A synergistic effect of nanomaterials and ferroptosis could prove to be an effective and efficient approach in the field of nanomedicine. In the current review, the authors have highlighted all the latest research in the field of ferroptosis, specifically emphasizing on the role of major molecular key players and various mechanisms involved in the ferroptosis pathway. Moreover, here the authors have also addressed the correlation of ferroptosis with the pathophysiology of NDDs and theragnostic effect of ferroptosis and nanomaterials for the prevention and treatment of NDDs.

Towards further understanding the applications of endophytes: enriched source of bioactive compounds and bio factories for nanoparticles.

The most significant issues that humans face today include a growing population, an altering climate, an growing reliance on pesticides, the appearance of novel infectious agents, and an accumulation of industrial waste. The production of agricultural goods has also been subject to a great number of significant shifts, often known as agricultural revolutions, which have been influenced by the progression of civilization, technology, and general human advancement. Sustainable measures that can be applied in agriculture, the environment, medicine, and industry are needed to lessen the harmful effects of the aforementioned problems. Endophytes, which might be bacterial or fungal, could be a successful solution. They protect plants and promote growth by producing phytohormones and by providing biotic and abiotic stress tolerance. Endophytes produce the diverse type of bioactive compounds such as alkaloids, saponins, flavonoids, tannins, terpenoids, quinones, chinones, phenolic acids etc. and are known for various therapeutic advantages such as anticancer, antitumor, antidiabetic, antifungal, antiviral, antimicrobial, antimalarial, antioxidant activity. Proteases, pectinases, amylases, cellulases, xylanases, laccases, lipases, and other types of enzymes that are vital for many different industries can also be produced by endophytes. Due to the presence of all these bioactive compounds in endophytes, they have preferred sources for the green synthesis of nanoparticles. This review aims to comprehend the contributions and uses of endophytes in agriculture, medicinal, industrial sectors and bio-nanotechnology with their mechanism of action.

BPS-induced ovarian dysfunction: Protective actions of melatonin via modulation of SIRT-1/Nrf2/NFĸB and IR/PI3K/pAkt/GLUT-4 expressions in adult golden hamster.

Ever-increasing occurrence of plastic-manufacturing industries leads to environmental pollution that has been associated with declined human health and increased incidence of compromised reproductive health. Female subfertility/infertility is a complex phenomenon and environmental toxicants as well as lifestyle factors have a crucial role to play. Bisphenol S (BPS) was believed to be a "safer" replacement of bisphenol A (BPA) but recent data documented its neurotoxic, hepatotoxic, nephrotoxic, and reprotoxic attributes. Hence based on the scarcity of reports, we investigated molecular insights into BPS-induced ovarian dysfunction and protective actions of melatonin against it in adult golden hamsters, Mesocricetus auratus. Hamsters were administered with melatonin (3 mg/kg BW i.p. alternate days) and BPS (150 mg/kg BW orally every day) for 28 days. BPS treatment disrupted hypothalamo-pituitary-ovarian (HPO) axis as evident by reduced gonadotropins such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH), ovarian steroids such as estradiol (E2) and progesterone (P4), thyroid hormones namely triiodothyronine (T3) and thyroxine (T4) and melatonin levels along with their respective receptors (ERα, TRα, and MT-1) thereby reducing ovarian folliculogenesis. BPS exposure also led to ovarian oxidative stress/inflammation by increasing reactive oxygen species and metabolic disturbances. However, melatonin supplementation to BPS restored ovarian folliculogenesis/steroidogenesis as indicated by increased number of growing follicles/corpora lutea and E2/P4 levels. Further, melatonin also stimulated key redox/survival markers such as silent information regulator of transcript-1 (SIRT-1), forkhead box O-1 (FOXO-1), nuclear factor E2-related factor-2 (Nrf2), and phosphoinositide 3-kinase/protein kinase B (PI3K/pAkt) expressions along with enhanced ovarian antioxidant capacity. Moreover, melatonin treatment reduced inflammatory load including ovarian nuclear factor kappa-B (NFĸB), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) expressions, serum tumor necrosis factor α (TNFα), C-reactive protein (CRP) and nitrite-nitrate levels as well as upregulated ovarian insulin receptor (IR), glucose uptake transporter-4 (GLUT-4), connexin-43, and proliferating cell nuclear antigen (PCNA) expressions in ovary thereby ameliorating inflammatory and metabolic alterations due to BPS. In conclusion, we found severe deleterious impact of BPS on ovary while melatonin treatment protected ovarian physiology from these detrimental changes suggesting it to be a potential preemptive candidate against environmental toxicant-compromised female reproductive health.

Kidney transplantation from brain-dead donors in Nepal: Report of first six cases.

Introduction: and importance: Kidney transplantation is one of the best treatment options for patients with end-stage renal disease. More than 90% of patients awaiting renal transplantation die without getting the kidney for transplantation. Brain dead donor kidney transplantation can bridge this gap proficiently. We aim to report details of the first six patients who had undergone brain-dead donor kidney transplantation in the history of transplantation in Nepal. Case presentation: We conducted a descriptive analysis of clinical data of six adult recipients with kidney transplantation from three brain-dead donors. We described postoperative complications, length of stay, graft function which was documented with serum creatinine, acute rejection episode, delayed graft function, and patient/graft survival of recipient. Recipients were between 15 and 56 years old. Three patients experienced delayed graft function. Urinary tract infection was observed in two patients, both of whom were treated with antibiotics. One patient had acute graft rejection. None of our patients required reoperation. Length of hospital stay ranged from 9 to 32 days. The postoperative graft function was 100% in all patients. There was no graft loss, and no death was observed during follow-up. Clinical discussion: Following the initiation of the brain-dead donor transplantation program, a lot of work needs to be done to make it a regular practice. Thus, this program needs support from all sections of society and government. This can be the only solution to decrease the huge gap between the supply and demand of organs in Nepal. Conclusion: This case reports indeed revealed impressive success in initiating a brain-dead donor kidney transplantation program in a developing country that in terms of quality, meets comprehensive standard with acceptable graft function and patient/graft survival in under limited resources healthcare setting.

Impact of photoperiod on uterine redox/inflammatory and metabolic status of golden hamster, Mesocricetus auratus.

Photoperiod modulates reproductive physiology at multiple levels in seasonally breeding animals. Golden hamsters are long-day breeders that diminish their fertility during the short days. Photoperiod is known to regulate hormonal milieu and uterus is a hormone-sensitive dynamic tissue. However, there is lack of molecular insight regarding the impact of photoperiod on uterine physiology with respect to redox and metabolic status in Mesocricetus auratus. We evaluated the impact of photoperiod on circulatory hormonal parameters (triiodothyronine [T3], thyroxin [T4], estradiol [E2], progesterone [P4], melatonin, and insulin), their receptor expressions and key markers associated with redox (SIRT-1/FOXO-1), inflammatory (NFĸB/COX-2) and metabolic (IR/GLUT4) status in uterus. Adult female golden hamsters were exposed to different photoperiodic regimes, that is, short photoperiod (SP; 8L:16D) and long photoperiod (LP; 16L:8D) for 12 weeks. SP drastically decreased peripheral hormone profiles (T3, T4, E2, and P4) and compromised uterine histoarchitecture when compared with LP-exposed hamsters. Further, SP markedly decreased thyroid hormone receptor-α (TRα), insulin receptor, and glucose uptake transporter-4 (GLUT-4) expressions in uterus. We noted enhanced uterine oxidative (increased MDA and decreased SOD/CAT levels), SIRT-1/FOXO-1 expression and inflammatory (NFĸB/COX-2) load in SP condition. Further, elevated levels of circulatory insulin, melatonin, and its receptor (MT-1) expression in uterus was noted under SP condition. Thus, we may suggest that photoperiod might regulate uterine seasonality through modulation of local hormonal and redox/metabolic homeostasis thereby may restrict offspring bearing capacity under short days.

Melatonin attenuates LPS-induced ovarian toxicity via modulation of SIRT-1, PI3K/pAkt, pErk1/2 and NFĸB/COX-2 expressions.

The association between inflammation and metabolic disturbances leads to various female pathophysiological conditions. Bacterial lipopolysaccharide (LPS), found in the outer membrane of gram-negative bacteria, elicits an oxidative and inflammatory response that profoundly interferes with female reproductive health. We investigated the ameliorative action of melatonin on LPS-induced ovarian pathophysiology in golden hamsters, Mesocricetus auratus. Hamsters were administered with exogenous melatonin (5 mg/kg BW) and LPS (100 µg/kg BW) intraperitoneally for 7 days. LPS treatment impaired ovarian folliculogenesis as evident by histoarchitecture (elevated number of atretic follicles, reduced number of growing follicles and corpus luteum) and steroidogenesis (decreased aromatase/ERα, estradiol and progesterone). On the other hand, LPS administration also perturbed thyroid hormone (T3 and T4) homeostasis, ovarian melatonin receptor (MT-1) expression, antioxidant potential (SOD and catalase) and concomitantly elevated nitro-oxidative stress (decreased SOD, catalase and elevated CRP, TNFα and nitrate/nitrite level) and inflammatory load (NFĸB and COX-2) which culminated into ovarian follicular apoptosis (elevated caspase-3). LPS also disrupted metabolic homeostasis as indicated by hyperinsulinemia with a simultaneous decrease in ovarian IR/GLUT-4 and glucose content. Moreover, LPS treatment decreased expressions of key markers of ovarian physiology (SIRT-1, pErk1/2, PI3K and pAkt). Melatonin co-treatment with LPS improve these detrimental changes proposing melatonin as a potent therapeutic candidate against ovarian dysfunction induced by endotoxin.

Living donor kidney paired exchange: An observational study.

Background: Kidney transplantation is the treatment of choice for patients with end-stage renal disease (ESKD). Kidney paired donation (KPD) provides the chance to match an incompatible donor/recipient pair with another donor and recipient in a similar condition. We aimed to compare the outcomes of pair exchange kidney transplantation with traditional live donor kidney transplantation in our context. Method: A review of medical records of 62 patients (31 pairs) who underwent two-way conventional living kidney pair exchange from July 2016 to June 2021 was done. The control group was considered those 62 patients who had undergone classic live donor kidney transplantation (LDKT) during the study period. The patient's demographics, intraoperative and postoperative variables including delayed graft function, length of hospital stay, graft survival, patient survival, and rejections rates were compared between the groups (KPD and LDKT). Results: The majority of recipients were male (77.4 and 80.6%) while donors were female (77.4 and 69.4%) in KPD and the LDKT groups. Mean ages were 37 years (range: 19-59) and 37 years (range: 17-65) for the recipient's in KPD and the LDKT. KPD transplantation was performed in 62 recipients to avoid blood group incompatibility. There were no significant differences in outcomes comprising delayed graft function (1.6 and 3.2%), graft survival (100% in both groups), patient survival (95.2 and 96.8%), and rejections rates (1.6 and 1.6%) between KPD and LDKT group (P > 0.005). The length of stay was similar (5.9 and 5.7 days) in KPD and LDKT groups (P > 0.005). Conclusions: The outcomes of KPD were comparable with classic LDKT in terms of delayed graft function, length of hospital stay, graft survival, patient survival, and rejections rates in our study. Therefore, the kidney paired donation program should be encouraged and promoted in centers where the ABO-incompatible transplant is expensive with added risk and the rate of deceased donor transplantation is very low.

Photoperiodic modulation of ovarian metabolic, survival, proliferation and gap junction markers in adult golden hamster, Mesocricetus auratus.

Female reproductive physiology is greatly dependent on tight regulation of metabolic and survival factors. Photoperiod regulates female reproductive rhythms but very less information exists explaining whether photoperiod could modulate thyroid hormone homeostasis, metabolic/energy parameters along with survival, proliferation and gap junction proteins in the ovary of a long-day breeder, Mesocricetus auratus. Adult female hamsters were exposed to different photoperiodic regimes i.e., critical photoperiod (CP; 12.5L:11.5D), short photoperiod (SP; 8L:16D) and long photoperiod (LP; 16L:8D) for 12 weeks. LP upregulated thyroidal and gonadal activity as apparent by histoarchitecture, thyroid hormone profile [triiodothyronine (T3), thyroxin (T4) and thyroid stimulating hormone (TSH)], luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2) and progesterone (P4) levels when compared with SP exposed hamsters. Further, LP increased thyroid hormone receptor-α/deiodinase-2 (TRα/Dio-2), estrogen receptor-α (ERα)/aromatase and insulin receptor/glucose transporter-4 (IR/GLUT-4) expressions in ovary. Interestingly, ovarian sirtuin-1 (SIRT-1) expression was also upregulated under LP condition along with cell proliferation (proliferating cell nuclear antigen or PCNA), survival (B cell lymphoma-2 or Bcl-2) and gap junction (connexin-43) markers when compared to SP exposed hamsters. We also noted elevated levels of circulatory leptin, insulin along with melatonin and its receptor (MT-1) in ovary under SP condition. Thus, we suggest that photoperiod plays a vital role in regulation of thyroid and reproductive hormone homeostasis along with key metabolic and survival markers in the ovary of adult golden hamsters, M. auratus providing further insight into the regulation of female reproductive seasonality in a long-day breeder.

Low NCOR2 levels in multiple myeloma patients drive multidrug resistance via MYC upregulation.

MYC upregulation is associated with multidrug refractory disease in patients with multiple myeloma (MM). We, isolated patient-derived MM cells with high MYC expression and discovered that NCOR2 was down-regulated in these cells. NCOR2 is a transcriptional coregulatory protein and its role in MM remains unknown. To define the role of NCOR2 in MM, we created NCOR2 knockout human myeloma cell lines and demonstrated that NCOR2 knockout led to high MYC expression. Furthermore, NCOR2 knockout conferred resistance to pomalidomide, BET and HDAC inhibitors, independent of Cereblon (CRBN), indicating high MYC expression as a cause of multidrug resistance. Moreover, NCOR2 interacted with the nucleosome remodeling and deacetylase (NuRD) complex and repressed the expression of CD180 by directly binding to its promoter and inducing MYC expression. Next, we generated lenalidomide-resistant and pomalidomide-resistant human myeloma cell lines. Whole-exome sequencing revealed that these cell lines acquired the same exonic mutations of NCOR2. These cell lines showed NCOR2 downregulation and MYC upregulation independent of CRBN and demonstrated resistance to BET and HDAC inhibitors. Our findings reveal a novel CRBN independent molecular mechanism associated with drug resistance. Low NCOR2 expression can serve as a potential biomarker for drug resistance and needs further validation in larger prospective studies.

Melatonin Ameliorates LPS-Induced Testicular Nitro-oxidative Stress (iNOS/TNFα) and Inflammation (NF-kB/COX-2) via Modulation of SIRT-1.

Lipopolysaccharide (LPS) - an endotoxin that is being extensively used in laboratory to mimic microbial infection that adversely affects male fertility. This study investigated the protective effects of melatonin on LPS-induced testicular nitro-oxidative stress, inflammation, and associated damages in the testes of male golden hamsters, Mesocricetus auratus. Hamsters were administered with melatonin and LPS for 7 days. Testes of LPS treated hamsters showed degenerative changes (appearance of vacuoles, exfoliation, and depletion of germ cells in the seminiferous tubules), adverse effects on spermatogenesis (sperm count and viability), and steroidogenesis (declined serum and testicular testosterone). Furthermore, LPS treatment decreased melatonin content, melatonin receptor (MT1), and antioxidant potential (catalase and SOD), and simultaneously increased nitro-oxidative stress (CRP, nitrate, TNFα). LPS upregulated NF-kB, COX-2, and iNOS expressions to increase testicular inflammatory load that resulted in the decrease of germ cell proliferation and survival, thus culminating into germ cell apoptosis as indicated by AO-EB staining and caspase-3 expression. Administration of melatonin with LPS showed improved testicular histoarchitecture, sperm parameters, and testosterone level. Melatonin increased testicular antioxidant status (SOD, catalase) to counteract the LPS-induced testicular ROS and thus reduced testicular nitro-oxidative stress. Furthermore, melatonin treatment upregulated testicular SIRT-1 expression to inhibit LPS-induced inflammatory proteins, i.e., NF-kB/COX-2/iNOS expression. The rescue effect of melatonin was further supported by increased germ cell survival (Bcl-2), proliferation (PCNA), and declined apoptosis (caspase-3). In conclusion, our result demonstrated that melatonin rescued testes from LPS-induced testicular nitro-oxidative stress, inflammation, and associated damages by upregulation of SIRT-1.

Immunologic and tumor responses of pegilodecakin with 5-FU/LV and oxaliplatin (FOLFOX) in pancreatic ductal adenocarcinoma (PDAC).

Background Treatment options for pancreatic ductal adenocarcinoma (PDAC) are limited and checkpoint blockade inhibitors have been disappointing in this disease. Pegilodecakin has demonstrated single agent anti-tumor activity in immune-sensitive tumors. Phase 1 and preclinical data indicate synergy of pegilodecakin with 5-FU and platins. We assessed the safety and activity of pegilodecakin+FOLFOX in patients with PDAC. Methods IVY (NCT02009449) was an open-label phase 1b trial in the United States. Here we report on all enrolled patients from cohort C. Heavily pretreated patients were treated with pegilodecakin (self-administered subcutaneously daily at 2.5, 5, or 10 µg/kg) + 5-flurouracil/leucovorin/oxaliplatin (FOLFOX), dosed per manufacturers prescribing information, until tumor progression. Eligible patients had measurable disease per immune-related response criteria (irRC), were ≥ 18 years of age, and had ECOG performance status of 0 or 1. Patients were evaluated for primary(safety) and secondary (tumor response per irRC) endpoints. Results From 5 August 2014-12 July 2016, 39 patients enrolled in cohort C. All patients were evaluable for safety. In this advanced population, regimen had manageable toxicities with no immune-related adverse events (irAEs) greater than grade 1. The most common grade 3/4/5 TEAEs were thrombocytopenia (21[53.8%] of 39) and anemia (17[43.6%] of 39). In evaluable PDAC patients, the best overall response of pegilodecakin+FOLFOX was 3(14%) with CRs in 2(9%) patients. Conclusions Pegilodecakin+FOLFOX had an acceptable tolerability profile in PDAC, with no substantial irAEs seen, and promising efficacy with the combination yielding a 2-year OS of 24% (95% CI 10-42). These data led to the phase 3 study with pegilodecakin+FOLFOX as second-line therapy of PDAC (SEQUOIA).

Hemoptysis as a rare presenting symptom of hypertrophic obstructive cardiomyopathy.

A 36-year-old female presented with two episodes of hemoptysis induced by exertion and acute dyspnea. She was diagnosed as a case of hypertrophic obstructive cardiomyopathy (HOCM) with systolic anterior motion (SAM)-induced severe mitral regurgitation (MR). She underwent extended septal myectomy with mitral valve replacement under cardiopulmonary bypass and recovered successfully. This is a unique and rare combination of HOCM with hemoptysis.

Glomerular endothelial cells and podocytes can express CD80 in patients with minimal change disease during relapse.

BACKGROUND: Urinary CD80 has emerged as potential biomarker in idiopathic nephrotic syndrome (INS). However, its cellular source remains controversial. The aim of the study was to assess whether CD80 is truly expressed by glomerular cells in INS patients during relapse and in the LPS mouse model of podocyte injury. METHODS: The presence of CD80 in glomeruli was evaluated by combining immunostaining, immunogold labeling, and in situ hybridization techniques. RESULTS: CD80 was present along the surface of glomerular endothelial cells (GEC) and rarely in podocytes in six of nine minimal change disease (MCD) patients in relapse, two of eleven patients with focal segmental glomerulosclerosis in relapse, and absent in controls. In mice, CD80 was upregulated at mRNA and protein level in GEC and podocytes, in a similar pattern to that seen in MCD patients. CONCLUSIONS: Glomerular endothelial cells and podocytes can express CD80 in patients with MCD during relapse. A better understanding of the role of CD80 in glomerular cells may provide further insights into the mechanisms of proteinuria in INS.

Pegilodecakin combined with pembrolizumab or nivolumab for patients with advanced solid tumours (IVY): a multicentre, multicohort, open-label, phase 1b trial.

BACKGROUND: IL-10 has anti-inflammatory and CD8+ T-cell stimulating activities. Pegilodecakin (pegylated IL-10) is a first-in-class, long-acting IL-10 receptor agonist that induces oligoclonal T-cell expansion and has single-agent activity in advanced solid tumours. We assessed the safety and activity of pegilodecakin with anti-PD-1 monoclonal antibody inhibitors in patients with advanced solid tumours. METHODS: We did a multicentre, multicohort, open-label, phase 1b trial (IVY) at 12 cancer research centres in the USA. Patients were assigned sequentially into cohorts. Here, we report on all enrolled patients from two cohorts treated with pegilodecakin combined with anti-PD-1 inhibitors. Eligible patients were aged at least 18 years with histologically or cytologically confirmed advanced malignant solid tumours refractory to previous therapies, and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients with uncontrolled infectious diseases were excluded. Pegilodecakin was provided in single-use 3 mL vials and was self-administered subcutaneously by injection at home at 10 µg/kg or 20 µg/kg once per day in combination with pembrolizumab (2 mg/kg every 3 weeks or 200 mg every 3 weeks) or nivolumab (3 mg/kg every 2 weeks or 240 mg every 2 weeks or 480 mg every 4 weeks at the approved dosing), both of which were given intravenously at the study site. Patients received pembrolizumab or nivolumab with pegilodecakin until disease progression, toxicity necessitating treatment discontinuation, patient withdrawal of consent, or study end. The primary endpoints were safety and tolerability, assessed in all patients enrolled in the study who received any amount of study medication including at least one dose of pegilodecakin, and pharmacokinetics (previously published). Secondary endpoints included objective response by immune-related response criteria in all patients who were treated and had evaluable measurements. The study is active but no longer recruiting, and is registered with ClinicalTrials.gov, NCT02009449. FINDINGS: Between Feb 13, 2015, and Sept 12, 2017, 111 patients were enrolled in the two cohorts. 53 received pegilodecakin plus pembrolizumab, and 58 received pegilodecakin plus nivolumab. 34 (31%) of 111 patients had non-small-cell lung cancer, 37 (33%) had melanoma, and 38 (34%) had renal cell carcinoma; one (<1%) patient had triple-negative breast cancer and one (<1%) had bladder cancer. Data cutoff was July 1, 2018. Median follow-up was 26·9 months (IQR 22·3-31·5) for patients with non-small-cell lung cancer, 33·0 months (29·2-35·1) for those with melanoma, and 22·7 months (20·9-27·0) for those with renal cell carcinoma. At least one treatment-related adverse event occurred in 103 (93%) of 111 patients. Grade 3 or 4 events occurred in 73 (66%) of 111 patients (35 [66%] of 53 in the pembrolizumab group and 38 [66%] of 58 in the nivolumab group), the most common of which were anaemia (12 [23%] in the pembrolizumab group and 16 [28%] in the nivolumab group), thrombocytopenia (14 [26%] in the pembrolizumab group and 12 [21%] in the nivolumab group), fatigue (11 [21%] in the pembrolizumab group and 6 [10%] in the nivolumab group) and hypertriglyceridaemia (three [6%] in the pembrolizumab group and eight [14%] in the nivolumab group). There were no fatal adverse events determined to be related to the study treatments. Of the patients evaluable for response, objective responses were 12 (43%) of 28 (non-small-cell lung cancer), three (10%) of 31 (melanoma), and 14 (40%) of 35 (renal cell carcinoma). INTERPRETATION: In this patient population, pegilodecakin with anti-PD-1 monoclonal antibodies had a manageable toxicity profile and preliminary antitumour activity. Pegilodecakin with pembrolizumab or nivolumab could provide a new therapeutic opportunity for previously treated patients with renal cell carcinoma and non-small-cell carcinoma. FUNDING: ARMO BioSciences, a wholly owned subsidiary of Eli Lilly and Company.

Excision of innumerable hydatid cysts from the myocardium of the left ventricle via the left thoracotomy along with myoplasty on beating heart.

Cardiac hydatid cyst is a rare disease with frequency of less than 2%. The left ventricle is the most common site. Symptoms depend upon site of involvement ranging from asymptomatic to acute coronary syndrome, arrhythmias, valvular lesions, etc. It is a surgical emergency, therefore early diagnosis and surgical treatment is required even in asymptomatic patients. Surgical excision on beating heart along with preparedness with cardiopulmonary bypass and fibrillator via left anterolateral thoracotomy can be done successfully, followed by medical treatment with albendazole. Increased awareness and high degree of suspicion among cardiac physicians in the endemic area is essential for early diagnosis. Echocardiography remains the gold standard for diagnosis and follow-up of patient.

Interaction of niobium with iron-oxide colloids and the role of humic acid.

In this work, we report the sorption of Nb on iron oxides and the effect of humic acid. Iron oxides viz. goethite, hematite and magnetite were chemically synthesised and characterised by X-ray diffraction, particle size, surface area and zeta potential measurement. The sorption of Nb on all the three iron oxides was low (∼40%) at pH 1, increased to âˆ¼ 90% at pH 8 and decreased marginally above pH 8. The effect of humic acid on the sorption was very small. Thermodynamic parameters viz. activation energy, enthalpy, entropy, free energy and sticking probability were calculated to understand the mechanism of the sorption process. Although the enthalpy was positive, the free energy change was negative i.e. the sorption was entropy driven process. The sorption followed pseudo-second-order kinetics and sticking probability model indicated that the process was chemisorption. This study is important to understand the probable migration of 94Nb (half life 20300 y) during underground storage of radioactive waste.

Clinical and Serologic Responses After a Two-dose Series of High-dose Influenza Vaccine in Plasma Cell Disorders: A Prospective, Single-arm Trial.

BACKGROUND: Patients with multiple myeloma (MM) and other plasma cell disorders are highly susceptible to influenza infections, which are major causes of morbidity in this population, despite the routine administration of a seasonal influenza vaccination. Existing data are limited by small and retrospective studies, which suggest poor seroprotection rates of < 20% after standard influenza vaccination in patients with MM. PATIENTS AND METHODS: Patients with plasma cell dyscrasia (n = 51) were treated with a 2-dose series of high-dose inactivated trivalent influenza vaccine during the 2014 to 2015 influenza season. Laboratory-confirmed influenza infections were identified through seasonal surveillance, sera were collected for influenza hemagglutination antibody inhibition (HAI) titer assays, and logistic regression models were used to identify the clinical correlates to the HAI serologic responses. RESULTS: Influenza vaccine was well tolerated, without any vaccine-related grade ≥ 2 adverse events. Only 3 patients (6%) experienced laboratory-confirmed influenza. The rates of HAI seroprotection against all 3 vaccine strains (A/California/7/2009 [H1N1] pdm09-like virus; A/Texas/50/2012 [H3N2]-like virus; and a B/Massachusetts/2/2012-like virus) increased from 4% at baseline to 49% and 65% after 1 and 2 doses, respectively. The risk factors associated with a lower likelihood of HAI serologic response included plasma cell disorder requiring therapy, less than a partial response found on disease response assessment, and active conventional chemotherapy. Alternatively, active therapy with an immunomodulatory drug alone or with a proteasome inhibitor was associated with a greater likelihood of an HAI serologic response. CONCLUSION: These data have demonstrated that, in contrast to the historically poor results with standard influenza vaccination, this novel high-dose booster vaccination strategy leads to high rates of seroprotection. Randomized controlled studies are needed to compare this novel strategy to the standard vaccination strategy.