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Fatal grand mal seizure in a Dutch trekker.

A 35-year-old healthy Dutch woman went on a trek (Lang Tang) in Nepal up to an approximate altitude of about 3800 meters. She had no prior h … t she played tennis on a regular basis and was an outdoor person. She had not trekked before in the Himalayas and it was uncertain if she had been to high altitude before. She was on no medications at the time. There was no history of drug abuse. She did not smoke and consumed few alcoholic beverages. She had not consumed any alcohol on the trek. She was ad …

Using modified Fenn diagrams to assess ventilatory acclimatization during ascent to high altitude: Effect of acetazolamide.

High altitude (HA) ascent imposes systemic hypoxia and associated risk of acute mountain sickness. Acute hypoxia elicits a hypoxic ventilatory response (HVR), which is augmented with chronic HA exposure (i.e., ventilatory acclimatization; VA). However, laboratory-based HVR tests lack portability and feasibility in field studies. As an alternative, we aimed to characterize area under the curve (AUC) calculations on Fenn diagrams, modified by plotting portable measurements of end-tidal carbon dioxide ( P ETC O 2 ${P_{{\mathrm{ETC}}{{\mathrm{O}}_{\mathrm{2}}}}}$ ) against peripheral oxygen sa

The effects of high altitude ascent on splenic contraction and the diving response during voluntary apnoea.

NEW FINDINGS: What is the central question of this study? What is the relative contribution of a putative tonic splenic contraction to the haematological acclimatization process during high altitude ascent in native lowlanders? What is the main finding and its importance? Spleen volume decreased by -14.3% (-15.2 ml) per 1000 m ascent, with an attenuated apnoea-induced [Hb] increase, attesting to a tonic splenic contraction during high altitude ascent. The [Hb]-enhancing function of splenic contraction may contribute to restoring oxygen content early in the acclimatization process at high altit

Chemico-biological evaluation of carpachromene against key antimicrobial protein targets: an integrated in-silico, in-vitro approach for mechanistic insights.

ETHNOPHARMACOLOGICAL RELEVANCE: Verbascum thapsus L. is a prized medicinal plant from the Kashmir Himalaya traditionally utilized to treat many ailments, yet its active metabolites against antimicrobial mechanisms remain unclear. AIM OF THE STUDY: This work envisages an integrated in-silico and in-vitro approach to mechanistically investigate broad-spectrum antimicrobial activity of carpachromene, a supradecorated phytochemical from V. thapsus. MATERIALS AND METHODS: Carpachromene was isolated through cold extraction from V. thapsus, followed by silica gel column chromatography with an optim

Aucklandia costus (Syn. Saussurea costus): Ethnopharmacology of an endangered medicinal plant of the himalayan region.

ETHNOPHARMACOLOGICAL RELEVANCE: Aucklandia costus Falc. a medicinal plant is native to the Himalayan region and synonymous with Saussurea co … vel. An evaluation of phytochemicals in A. costus collected from different geographical location in Himalayas may be drawn to identify and conserve the higher yielding plant.

Evaluation of anti-hypertensive activity of Ulmus wallichiana extract and fraction in SHR, DOCA-salt- and L-NAME-induced hypertensive rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Ulmus wallichiana Planchon (Himalayan Elm), a traditional medicinal plant, used in fracture healing in folk tradition of Uttarakhand, Himalaya, India. It is also used as diuretic. U. rhynchophylla, native to China, known as Gou Teng in Chinese medicine, is used for hypertension (WHO). U. macrocarpa has antihypertensive and vasorelaxant activity. However, no detailed studies related to hypertension have been reported previously, so we have explored the antihypertensive activity of U. wallichiana. AIM OF THE STUDY: To investigate the pharmacological effect of eth

High altitude pulmonary edema (HAPE) in a Himalayan trekker: a case report.

INTRODUCTION: High altitude pulmonary edema is a non-cardiogenic form of pulmonary edema that develops in unacclimatized individuals at alti … of age Indian ethnic South African lady was emergency air-lifted from 4410 m altitude in the Nepal Himalayas to Kathamandu (1300 m) with a suspected case of high altitude pulmonary edema. She had continued ascending despite experiencing mild altitude symptoms at Namche (3440 m), and these symptoms worsened considerably at Tengboche (3860 m). At the very st …

IMbrave152/SKYSCRAPER-14: a Phase III study of atezolizumab, bevacizumab and tiragolumab in advanced hepatocellular carcinoma.

Atezolizumab plus bevacizumab is a standard of care, first-line therapy for advanced hepatocellular carcinoma (HCC). Myeloid and T regulatory cells are key immunosuppressive cell types within the hepatic tumor microenvironment associated with clinical resistance to atezolizumab and bevacizumab therapy for HCC and overall poor prognosis. Therapeutic targeting of TIGIT, which is highly expressed in these cells, with tiragolumab may overcome the immunosuppressive environment and improve clinical benefit, a hypothesis supported by positive efficacy signals in the Phase Ib/II MORPHEUS-Liver study.

The unusual first sign of presentation of hepatocellular carcinoma: a rare case report.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common primary liver malignancy, characterized by aggressive biological behavior and a high propensity for extrahepatic spread. The most common sites of metastasis are the lungs, regional lymph nodes, bones, adrenal glands, and peritoneum. In contrast, the paranasal sinuses are an unusual site for metastatic HCC, and involvement of the sphenoid sinus represents an even rarer event. CASE DESCRIPTION: We report the case of a 67-year-old male patient who presented with transient diplopia, left eyelid ptosis, and refractory epistaxis as the i

Novel Molecular Targets for Immune Surveillance of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a common and aggressive cancer with a high mortality rate. The incidence of HCC is increasing worldwide, and the lack of effective screening programs often results in delayed diagnosis, making it a challenging disease to manage. Immunotherapy has emerged as a promising treatment option for different kinds of cancers, with the potential to stimulate the immune system to target cancer cells. However, the current immunotherapeutic approaches for HCC have shown limited efficacy. Since HCC arises within a complex tumour microenvironment (TME) characterized by the p

Beyond First-Line Immune Checkpoint Inhibitor Therapy in Patients With Hepatocellular Carcinoma.

Until recently, the treatment landscape for hepatocellular cancer (HCC) was dominated by tyrosine kinase inhibitors (TKIs) which offered an overall survival (OS) benefit when used both in the first-and second-line setting compared to best supportive care. However, the treatment landscape has changed with the introduction of immune checkpoint inhibitors (ICIs) for the treatment of HCC with significant improvement in OS and progression free survival reported with combination atezolizumab and bevacizumab compared to sorafenib in the first-line setting. Nonetheless, the response to ICIs is 20-30%

Amelioration of the cyclophosphamide induced genotoxic damage in mice by the ethanolic extract of Equisetum arvense.

In the present study, we evaluated the potential of the plant E. arvense against the cytotoxic and mutagenic effects induced by cyclophosphamide (chemotherapeutic agent) in the bone marrow cells of mice using the Chromosome assay (CA) and Mitotic index (MI) in vivo as the biomarkers. The study was performed following 3 protocols: pre-treatment, simultaneous treatment and post-treatment with the ethanolic extract of the plant. The results demonstrated that the plant extract was not cytotoxic and mutagenic and has a protective effect against the mutagenicity induced by cyclophosphamide in pre, s

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… It is distributed throughout Canada and the USA except the southeast (Florida, Georgia, Alabama, Louisiana, Mississippi, and Tennessee), throughout Europe and Asia south to Turkey, Iran, the Himalayas and across China (except the southeastern part), Korea and Japan [9] . … GC–MS analysis and evaluation of mutagenic and antimutagenic activity of ethyl acetate extract of Ajuga bracteosa wall ex. benth: an endemic medicinal plant of Kashmir himalaya, India J. Clin. Toxicol. 6 2016 0495 2161 51 De Flora S. Ferguson L.R. …

Simultaneous Inhibition of Mcl-1 and Bcl-2 Induces Synergistic Cell Death in Hepatocellular Carcinoma.

Despite the recent approval of new therapies, the prognosis for patients with hepatocellular carcinoma (HCC) remains poor. There is a clinical need for new highly effective therapeutic options. Here, we present a combined application of BH3-mimetics as a potential new treatment option for HCC. BH3-mimetics inhibit anti-apoptotic proteins of the BCL-2 family and, thus, trigger the intrinsic apoptosis pathway. Anti-apoptotic BCL-2 proteins such as Bcl-2 and Mcl-1 are frequently overexpressed in HCC. Therefore, we analyzed the efficacy of the two BH3-mimetics ABT-199 (Bcl-2 inhibitor) and MIK665

Resistance to Antiangiogenic Therapy in Hepatocellular Carcinoma: From Molecular Mechanisms to Clinical Impact.

Antiangiogenic drugs were the only mainstay of advanced hepatocellular carcinoma (HCC) treatment from 2007 to 2017. However, primary or secondary resistance hampered their efficacy. Primary resistance could be due to different molecular and/or genetic characteristics of HCC and their knowledge would clarify the optimal treatment approach in each patient. Several molecular mechanisms responsible for secondary resistance have been discovered over the last few years; they represent potential targets for new specific drugs. In this light, the advent of checkpoint inhibitors (ICIs) has been a new o

Serum Interleukin-6 is Not Linked with Sleep-Quality, Restless Legs Syndrome, and Depression, But with 6-Month Survival in Hematological Malignancies.

BackgroundSerum interleukin (IL)-6 has been found to be associated with sleep quality, mood, and survival in patients with solid tumors. Results in these studies were confounded by knowledge of diagnosis to study subjects. Moreover, such data among subjects with hematological malignancies and data regarding restless legs syndrome is limited. The present study was, therefore, conducted to assess the sleep quality, depression, and restless leg syndrome in hematological malignancies and to study if there is any role of IL6 associated with it.MethodsSixty-six subjects having hematological malignan

Antibodies to watch in 2023.

In this 14th installment of the annual Antibodies to Watch article series, we discuss key events in commercial monoclonal antibody therapeutics development that occurred in 2022 and forecast events that might occur in 2023. As of mid-November, 12 antibody therapeutics had been granted first approvals in either the United States or European Union (tebentafusp (Kimmtrak), faricimab (Vabysmo), sutimlimab (Enjaymo), relatlimab (Opdualag), tixagevimab/cilgavimab (Evusheld), mosunetuzumab (Lunsumio), teclistamab (TECVAYLI), spesolimab (SPEVIGO), tremelimumab (Imjudo; combo with durvalumab), nirsevim

Мультиэкологические испытания на взаимодействие G×E и выявление высокоурожайных, стабильных, среднесрочных генотипов голубей с использованием анализа AMMI, бипло ГПЭ и YREM.

Pigeonpea [Cajanus cajan (L.) Millspaugh] — широко распространенный пульс с высоким содержанием семян белка, который способствует продовольственной безопасности и безопасности питания в индийском субконтиненте. Большинство сортов голубей, выращиваемых в Индии, имеют среднюю продолжительность (см.<180 - дни до зрелости), что делает необходимым, чтобы селекционеры сосредоточили свое внимание на развитии стабильных высокоурожайных разновидностей. Разнообразие агроэкологического режима в индийском субконтиненте требует проведения эффективного многостороннего исследования окружающей среды с учетом

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… Stability analysis of garden pea (Pisum sativum L.) genotypes under North Western Himalayas using joint regression analysis and GGE biplots. Genet. Resour. Crop Evol. 68, 999–1010. doi: 10.1007/s10722-020-01040-0 Rao P., SandhyaKishore N., Sandeep S., Neelima G., Rao P. M., Das D. …

Hypoxia-inducible factor-prolyl hydroxylase inhibitors in treatment of anemia with chronic disease.

AbstractAnemia of chronic disease (ACD) is the most frequent clinical issue in patients with chronic disease. ACD is usually secondary to chronic kidney disease (CKD), cancer, and chronic infection, which is associated with poor health outcomes, increased morbidity and mortality, and substantial economic costs. Current treatment options for ACD are very limited. The discovery of the hypoxia-inducible factor-prolyl hydroxylase (HIF-PHD) pathway made it possible to develop novel therapeutic agents (such as hypoxia-inducible factor-prolyl hydroxylase inhibitor, HIF-PHI) to treat ACD by stabilizin

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… | NCT01906489 (NDD, 2013); NCT03054337 (NDD, 2017); NCT03054350 (DD, 2017) | JapicCTI-152892 (DD, 2015) | – | CTRI/2017/05/008534 (NDD, 2017) Phase 3 | NCT02652819 (NDD, 2017), OLYPMPUS (NDD, 2017), ALPS (NDD, 2017), ANDES (NDD, 2018); NCT02652806 (DD, 2017), ROCKIES (DD, 2018), SIERRAS (DD, 2018), HIMALAYAS …

Unravelling T cell exhaustion through co-inhibitory receptors and its transformative role in cancer immunotherapy.

Persistent stimulation from cancer antigens leads to T lymphocytes (T cells) exhaustion, with up-regulated expression of co-inhibitory receptors, including programmed death-1 (PD-1), cytotoxic T lymphocyte-associated antigen-4 (CTLA-4), lymphocyte-activation gene 3 (LAG-3), T cell immunoglobulin and mucin domain 3 (TIM-3) and T cell immunoreceptor with Ig and ITIM domains (TIGIT). These receptors collectively impair T cell function via distinct molecular pathways, contributing to immune evasion and cancer progression. This review highlights the therapeutic promise of immune checkpoint inhibito

Potential Immunotherapy Targets for Liver-Directed Therapies, and the Current Scope of Immunotherapeutics for Liver-Related Malignancies.

Liver cancer, including hepatocellular carcinoma and intrahepatic cholangiocarcinoma, is increasing in incidence and mortality across the globe. An improved understanding of the complex tumor microenvironment has opened many therapeutic doors and led to the development of novel pharmaceuticals targeting cellular signaling pathways or immune checkpoints. These interventions have significantly improved tumor control rates and patient outcomes, both in clinical trials and in real-world practice. Interventional radiologists play an important role in the multidisciplinary team given their expertise