Major Diseases Research Articles

Comprehensive Insight into the Functional Roles of NK and NKT Cells in HTLV-1-Associated Diseases and Asymptomatic Carriers.

Human T cell leukemia virus type 1 (HTLV-1) is the first human oncogenic retrovirus to be discovered and causes two major diseases: a progressive neuro-inflammatory disease, termed HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP), and an aggressive malignancy of T lymphocytes known as adult T cell leukemia (ATL). Innate and acquired immune responses play pivotal roles in controlling the status of HTLV-1-infected cells and such, the outcome of HTLV-1 infection. Natural killer cells (NKCs) are the effector cells of the innate immune system and are involved in controlling viral infections and several types of cancers. The ability of NKCs to trigger cytotoxicity to provide surveillance against viruses and cancer depends on the balance between the inhibitory and activating signals. In this review, we will discuss NKC function and the alterations in the frequency of these cells in HTLV-1 infection.

Natural language processing to identify lupus nephritis phenotype in electronic health records

BackgroundSystemic lupus erythematosus (SLE) is a rare autoimmune disorder characterized by an unpredictable course of flares and remission with diverse manifestations. Lupus nephritis, one of the major disease manifestations of SLE for organ damage and mortality, is a key component of lupus classification criteria. Accurately identifying lupus nephritis in electronic health records (EHRs) would therefore benefit large cohort observational studies and clinical trials where characterization of the patient population is critical for recruitment, study design, and analysis. Lupus nephritis can be recognized through procedure codes and structured data, such as laboratory tests. However, other critical information documenting lupus nephritis, such as histologic reports from kidney biopsies and prior medical history narratives, require sophisticated text processing to mine information from pathology reports and clinical notes. In this study, we developed algorithms to identify lupus nephritis with and without natural language processing (NLP) using EHR data from the Northwestern Medicine Enterprise Data Warehouse (NMEDW).MethodsWe developed five algorithms: a rule-based algorithm using only structured data (baseline algorithm) and four algorithms using different NLP models. The first NLP model applied simple regular expression for keywords search combined with structured data. The other three NLP models were based on regularized logistic regression and used different sets of features including positive mention of concept unique identifiers (CUIs), number of appearances of CUIs, and a mixture of three components (i.e. a curated list of CUIs, regular expression concepts, structured data) respectively. The baseline algorithm and the best performing NLP algorithm were externally validated on a dataset from Vanderbilt University Medical Center (VUMC).ResultsOur best performing NLP model incorporated features from both structured data, regular expression concepts, and mapped concept unique identifiers (CUIs) and showed improved F measure in both the NMEDW (0.41 vs 0.79) and VUMC (0.52 vs 0.93) datasets compared to the baseline lupus nephritis algorithm.ConclusionOur NLP MetaMap mixed model improved the F-measure greatly compared to the structured data only algorithm in both internal and external validation datasets. The NLP algorithms can serve as powerful tools to accurately identify lupus nephritis phenotype in EHR for clinical research and better targeted therapies.

Two intestinal microbiota-derived metabolites, deoxycholic acid and butyrate, synergize to enhance host defense peptide synthesis and alleviate necrotic enteritis

BackgroundNecrotic enteritis (NE) is a major enteric disease in poultry, yet effective mitigation strategies remain elusive. Deoxycholic acid (DCA) and butyrate, two major metabolites derived from the intestinal microbiota, have independently been shown to induce host defense peptide (HDP) synthesis. However, the potential synergy between these two compounds remains unexplored.MethodsTo investigate the possible synergistic effect between DCA and butyrate in regulating HDP synthesis and barrier function, we treated chicken HD11 macrophage cells and jejunal explants with DCA and sodium butyrate (NaB), either individually or in combination, for 24 h. Subsequently, we performed RNA isolation and reverse transcription-quantitative PCR to analyze HDP genes as well as the major genes associated with barrier function. To further determine the synergy between DCA and NaB in enhancing NE resistance, we conducted two independent trials with Cobb broiler chicks. In each trial, the diet was supplemented with DCA or NaB on the day-of-hatch, followed by NE induction through sequential challenges with Eimeria maxima and Clostridium perfringens on d 10 and 14, respectively. We recorded animal mortality after infection and assessed intestinal lesions on d 17. The impact of DCA and NaB on the microbiota in the ileum and cecum was evaluated through bacterial 16S rRNA gene sequencing.ResultsWe found that the combination of DCA and NaB synergistically induced multiple HDP genes in both chicken HD11 cells and jejunal explants. Additionally, the gene for claudin-1, a major tight junction protein, also exhibited synergistic induction in response to DCA and NaB. Furthermore, dietary supplementation with a combination of 0.75 g/kg DCA and 1 g/kg NaB led to a significant improvement in animal survival and a reduction in intestinal lesions compared to either compound alone in a chicken model of NE. Notably, the cecal microbiota of NE-infected chickens showed a marked decrease in SCFA-producing bacteria such as Bacteroides, Faecalibacterium, and Cuneatibacter, with lactobacilli becoming the most dominant species. However, supplementation with DCA and NaB largely restored the intestinal microbiota to healthy levels.ConclusionsDCA synergizes with NaB to induce HDP and claudin-1 expression and enhance NE resistance, with potential for further development as cost-effective antibiotic alternatives.

High-density bin-based genetic map reveals a 530-kb chromosome segment derived from wild peanut contributing to late leaf spot resistance.

Twenty-eight QTLs for LLS disease resistance were identified using an amphidiploid constructed mapping population, a favorable 530-kb chromosome segment derived from wild species contributes to the LLS resistance. Late leaf spot (LLS) is one of the major foliar diseases of peanut, causing serious yield loss and affecting the quality of kernel and forage. Some wild Arachis species possess higher resistance to LLS as compared with cultivated peanut; however, ploidy level differences restrict utilization of wild species. In this study, a synthetic amphidiploid (Ipadur) of wild peanuts with high LLS resistance was used to cross with Tifrunner to construct TI population. In total, 200 recombinant inbred lines were collected for whole-genome resequencing. A high-density bin-based genetic linkage map was constructed, which includes 4,809 bin markers with an average inter-bin distance of 0.43cM. The recombination across cultivated and wild species was unevenly distributed, providing a novel recombination landscape for cultivated-wild Arachis species. Using phenotyping data collected across three environments, 28 QTLs for LLS disease resistance were identified, explaining 4.35-20.42% of phenotypic variation. The major QTL located on chromosome 14, qLLS14.1, could be consistently detected in 2021 Jiyang and 2022 Henan with 20.42% and 12.12% PVE, respectively. A favorable 530-kb chromosome segment derived from Ipadur was identified in the region of qLLS14.1, in which 23 disease resistance proteins were located and six of them showed significant sequence variations between Tifrunner and Ipadur. Allelic variation analysis indicating the 530-kb segment of wild species might contribute to the disease resistance of LLS. These associate genomic regions and candidate resistance genes are of great significance for peanut breeding programs for bringing durable resistance through pyramiding such multiple LLS resistance loci into peanut cultivars.

Epigallocatechin gallate improves neuronal damage in animal model of ischemic stroke and glutamate-exposed neurons via modulation of hippocalcin expression.

Epigallocatechin gallate (EGCG) is a polyphenolic component of green tea that has anti-oxidative and anti-inflammatory effects in neurons. Ischemic stroke is a major neurological disease that causes irreversible brain disorders. It increases the intracellular calcium concentration and induces apoptosis. The regulation of intracellular calcium concentration is important to maintain the function of the nervous system. Hippocalcin is a neuronal calcium sensor protein that controls intracellular calcium concentration. We investigated whether EGCG treatment regulates the expression of hippocalcin in stroke animal model and glutamate-induced neuronal damage. We performed middle cerebral artery occlusion (MCAO) to induce cerebral ischemia. EGCG (50 mg/kg) or phosphate buffered saline was injected into the abdominal cavity just before MCAO surgery. The neurobehavioral tests were performed 24 h after MCAO surgery and cerebral cortex tissue was collected. MCAO damage induced severe neurobehavioral disorders, increased infarct volume, and decreased the expression of hippocalcin in the cerebral cortex. However, EGCG treatment improved these deficits and alleviated the decrease in hippocalcin expression in cerebral cortex. In addition, EGCG dose-dependently alleviated neuronal cell death and intracellular calcium overload in glutamate-exposed neurons. Glutamate exposure reduced hippocalcin expression, decreased Bcl-2 expression, and increased Bax expression. However, EGCG treatment mitigated these changes caused by glutamate toxicity. EGCG also attenuated the increase in caspase-3 and cleaved caspase-3 expressions caused by glutamate exposure. The effect of EGCG was more pronounced in non-transfected cells than in hippocalcin siRNA-transfected cells. These findings demonstrate that EGCG protects neurons against glutamate toxicity through the regulation of Bcl-2 family proteins and caspase-3. It is known that hippocalcin exerts anti-apoptotic effect through the modulation of apoptotic pathway. Thus, we can suggest evidence that EGCG has a neuroprotective effect by regulating hippocalcin expression in ischemic brain damage and glutamate-exposed cells.

Cloning, expression, and functional identification of aquaporin genes from Eimeria tenella

Avian coccidiosis, caused by Eimeria spp., is one of the major parasitic diseases in chicken. Aquaporins (AQP) are essential mediators of water regulation and nutritional intake in parasites, and it may be a suitable molecule for chemotherapeutic target and vaccine candidate. We identified two aquaporin genes in Eimeria tenella (EtAQP1 and EtAQP2) with their full sequence, and the expression profiles were analyzed across different stages of E. tenella life cycle. The expression of EtAQP1 and EtAQP2 in Xenopus oocytes renders them highly permeable for both water and glycerol. Sugar alcohols up to five carbons and urea pass the pore. The immunohistochemical analysis confirms the restriction of antiserum staining to the surface of transfected Xenopus oocytes. Like other AQP family, EtAQPs are transmembrane proteins that are likely important molecules that facilitate solute uptake for parasite intracellular growth and therapeutic targets.

Sema3A ameliorates the pathological progression of osteoarthritis by modulating mitochondrial damage in chondrocytes.

Osteoarthritis (OA) is a major disease that causes disability in middle-aged and elderly people. A comprehensive understanding of its pathogenesis is of great significance in finding new clinical diagnosis and treatment schemes. The role of Semaphorin 3A (Sema3A) in OS has attracted attention recently, and the purpose of this study is to analyze the mechanisms underlying its impact on OS. First, a rat model of OS was established. Hematoxylin-eosin (HE) and TUNEL staining showed that the modeled rats presented typical pathological manifestations of OS, confirming the success of the modeling. Sema3A was significantly underexpressed in OS rats. Subsequently, Sema3A abnormal expression vectors were constructed to intervene in chondrocytes isolated from OS rats. It was found that the proliferation of chondrocytes was decreased, the apoptosis was increased, and the mitochondrial damage and autophagy were intensified after silencing Sema3A expression, while the above pathological processes were reversed when Sema3A expression was increased. In conclusion, Sema3A has an important influence on the pathological progression of OS, and molecular therapies targeting to increase Sema3A expression may become a new treatment for OS in the future.

Biomolecular Actions by Intestinal Endotoxemia in Metabolic Syndrome.

Metabolic syndrome (MetS) is a combination of metabolic disorders that concurrently act as factors promoting systemic pathologies such as atherosclerosis or diabetes mellitus. It is now believed to encompass six main interacting conditions: visceral fat, imbalance of lipids (dyslipidemia), hypertension, insulin resistance (with or without impairing both glucose tolerance and fasting blood sugar), and inflammation. In the last 10 years, there has been a progressive interest through scientific research investigations conducted in the field of metabolomics, confirming a trend to evaluate the role of the metabolome, particularly the intestinal one. The intestinal microbiota (IM) is crucial due to the diversity of microorganisms and their abundance. Consequently, IM dysbiosis and its derivate toxic metabolites have been correlated with MetS. By intervening in these two factors (dysbiosis and consequently the metabolome), we can potentially prevent or slow down the clinical effects of the MetS process. This, in turn, may mitigate dysregulations of intestinal microbiota axes, such as the lung axis, thereby potentially alleviating the negative impact on respiratory pathology, such as the chronic obstructive pulmonary disease. However, the biomolecular mechanisms through which the IM influences the host's metabolism via a dysbiosis metabolome in both normal and pathological conditions are still unclear. In this study, we seek to provide a description of the knowledge to date of the IM and its metabolome and the factors that influence it. Furthermore, we analyze the interactions between the functions of the IM and the pathophysiology of major metabolic diseases via local and systemic metabolome's relate endotoxemia.

Ethnobotanical Uses and Pharmacological Activities of Moroccan Ephedra Species.

Ephedra species are among the most popular herbs used in traditional medicine for a long time. The ancient Chinese medical book "Treatise on Febrile Diseases" refers to the classic traditional Chinese medicine prescription Ge Gen decoction, which consists of seven herbs, including an Ephedra species. Ephedra species are utilized all over the world to treat symptoms of the common cold and coughs, and to combat major human diseases, such as asthma, cancers, diabetes, cardiovascular and digestive disorders, and microbial infections. This study aimed at identifying specific Ephedra species used traditionally in Morocco for therapeutic purposes. The plant parts, their preparation process, and the treated pathologies were identified and analyzed. The results revealed five ethnobotanically important species of Ephedra: Ephedra alata Decne, Ephedra altissima Desf., Ephedra distachya L., Ephedra fragilis Desf., and Ephedra nebrodensis Tineo. These species are used traditionally in Morocco for treating people with diabetes, cancer, rheumatism, cold and asthma, hypertension, influenza virus infection, and respiratory ailments. In addition, they are occasionally used as calefacient agents, to regulate weight, or for capillary care. Few studies have underlined the antibacterial and antioxidant activities of some of these Moroccan Ephedra species, but little information is available regarding the natural products at the origin of the bioactivities. Further phytochemical investigations and clinical data are encouraged to better support the use of these plants.

Prevention of cardiovascular disease, a major non-communicable disease, in a super-aging society: Health success and unsolved issues in Japan.

As far as non-communicable disease is concerned, Japan is unique in showing a substantial decline in stroke mortality and the lowest and declining mortality from ischemic heart disease during the past half century, which contributed to the elongation of a 4-year average life expectancy, leading to top longevity in the world. However, several issues have remained in the prevention of cardiovascular disease with super-aging: i) how to manage the screening and lifestyle modification for both individuals with metabolic syndrome and those with non-overweight/ obesity plus metabolic risk factors, and ii) how to enhance the referral of very high-risk individuals screened at health checks to physicians for seeking treatment and examine whether an early clinical visit was associated with a lower risk of cardiovascular disease and total mortality. Health counseling is needed for both persons with metabolic syndrome and high-risk individuals with non-obese/overweight because the population attributable risk fraction of ischemic cardiovascular disease was similar for both high-risk individuals. Standardized counseling for very high-risk individuals accelerated clinical visits and reduced levels of risk factors. In health counseling, public health nurses were more effective in increasing clinic visits. Furthermore, the earlier clinic visit after the counseling suggested a lower risk of hospitalization for stroke, coronary heart disease, heart failure, and all-cause mortality. This article reviews these epidemiological findings for health practitioners and policymakers to perform further prevention and control for cardiovascular disease in Japan and other Asian and African countries with emerging cardiovascular burden and aging.

A Comprehensive Analysis of Beekeeping Risks and Validation of Biosecurity Measures against Major Infectious Diseases in Apis mellifera in Europe

Background/Objectives: In a collaborative effort, FAO, the International Federation of Beekeepers’ Association “Apimondia”, the Appalachian State University, and the Istituto Zooprofilattico Sperimentale del Lazio e Toscana (IZSLT), the FAO Reference Centre for Animal Health and Food Security Discipline Apiculture, health, and biosecurity, designed an online international survey (“Knowledge, Awareness and Practice”-KAP) as a risk assessment tool to validate biosecurity measures able to prevent and control the main honeybee (Apis mellifera subsp.) infectious diseases. Methods: The KAP survey was disseminated through various channels for 14 months (January 2019–March 2020). Beekeepers’ knowledge on nosemosis, American foulbrood (AFB), and European foulbrood (EFB) management was assessed. Beekeepers’ attitudes were investigated by asking them to provide a score called “Acceptance by beekeepers”. Results: Of the 410 respondents, the majority of them (68.3%, n = 252) were from Europe. European beekeepers (n = 252) considered “Highly acceptable” the following practices: removing combs that show signs of dysentery and feeding colonies for nosemosis; the quick identification and management of affected hives for American foulbrood and European foulbrood. Instead, the following practices were considered as not acceptable by beekeepers: for nosemosis, the use of antibiotics and sampling of hive debris for early detection; for American foulbrood and European foulbrood, the shook swarm, the destruction of the whole apiary, as well as their treatment with antibiotics. Conclusion: This study demonstrated the validity of the present “Knowledge, Awareness and Practice” (KAP) survey to validate the best practices for the main infectious honeybee diseases, considering the pragmatic point of view of beekeepers. Sustainable practices for disease control are preferred by the European beekeepers. While having an adequate knowledge base for the early detection of the investigated honeybee diseases, European beekeepers tend to be aware of the health status of their hives, embracing advanced, practice-oriented training. Authors highlight that the selection of practices and their validation should be revised on a regular basis, to be adapted in a timely manner to the current infectious honeybee disease situation, in order to build up a resilient and effective stock of practices.

The ASPREE Healthy Ageing Biobank: Methodology and participant characteristics.

ASPirin in Reducing Events in the Elderly (ASPREE), a placebo-controlled prevention trial of low dose aspirin, provided the opportunity to establish a biospecimen biobank from initially healthy persons aged 70+ years for future research. The ASPREE Healthy Ageing Biobank (ASPREE Biobank) collected, processed and stored blood and urine samples at -80degC or under nitrogen vapour at two timepoints, three years apart, from a willing subset of Australian ASPREE participants. Written informed consent included separate opt-in questions for biomarker and genetic testing. Fractionated blood and urine were aliquoted into multiple low-volume, barcoded cryotubes for frozen storage within 4 hours of collection. Specially designed and outfitted mobile laboratories provided opportunities for participation by people in regional and rural areas. Detailed, high quality demographic, physiological and clinical data were collected annually through the ASPREE trial. 12,219 participants contributed blood/urine at the first timepoint, 10,617 of these older adults provided 3-year follow-up samples, and an additional 1,712 provided saliva for DNA. The mean participant age was 74 years, 54% were female and 46% lived outside major cities. Despite geographical and logistical challenges, nearly 100% of blood/urine specimens were processed and frozen within 4 hours of collection into >1.4 million aliquots. After a median of 4.7 years, major clinical events among ASPREE Biobank participants included 332 with dementia, 613 with cardiovascular disease events, 1259 with cancer, 357 with major bleeds and 615 had died. The ASPREE Biobank houses and curates a large number of biospecimens collected prior to the clinical manifestations of major disease, and 3-year follow-up samples, all linked to high quality, extensive phenotypic information. This provides the opportunity to identify or validate diagnostic, prognostic and predictive biomarkers, and potentially study biological effectors, of ageing-related diseases or maintenance of older-age good health.

A REVIEW ON TRIKATU CHURNA

Ayurveda has an ancient heritage of traditional herbs in which Trikatu is very precious. Trikatu is a poly herbal preparation. It consists of three crude drugs namely Maricha (Piper nigrum Linn). Pippali (Piper longum Linn) and Shunthi (Zingiber officinalis Rosc) in the ratio of (1:1:1; ww). Trikatu also called as Katutrikam, Tryusnam, Vyosa. Trikatu is used as solo drug rarely, but it is an essential ingredient of numerous formulations and prescriptions of Ayurvedic medicine. Trikatu churna is considered as one of the best drugs to treat the condition of Ama (improperly digested absorbed and improperly metabolised food particles including free radicles). Trikatu is regarded as the drug of choice in cases of Agnimandya (poor digestion due to faulty digestive process). In Brihattrayi, it is recommended for various diseases due to Agni (digestive fire) vitiation such as Grahaniroga (Malabsorption syndrome), Udara roga (major diseases of abdomen surgical and medical like hepatomegaly, splenomegaly and ascites), Arsharoga (piles) etc. Its contents are dipana and pacana in their action. By virtue of these properties the drug becomes effective in managing ama. The objective of this article is to highlight classification, synonyms, pharmacological actions as described in various diseases, and different formulations of Trikatu in ancient Ayurvedic.

Survey of Major Diseases on Medicinal and Aromatic Plants Growing Areas of Ethiopia

Medicinal and aromatic plants are industrial plant that are primarily used for therapeutic, aromatic and culinary purposes as components of cosmetics, medicinal products, health foods and other natural health products. Like other cereal crops, these potential medicinal and aromatic plants are constantly in grave danger from disease attack. The aim of this study was to assess the most prevalent diseases on prioritized medicinal and aromatic plants. Survey was conducted at Wondo Genet Agricultural research stations and herb growing companies in Ethiopia. Survey fields were observed from vegetative to maturity stage of the plant to assess the pest status. A total of 11 medicinal and aromatic plants were assessed in four different locations and these herbs were attacked by various diseases. Rust disease was the most serious problem on Aloe vera and Lemon grass, accounting for 30-40 percent of disease severity at Wondo Genet. In Butajira, powdery mildew was the most common disease found on sage, with a 20 percent severity. Downy mildew was recorded as a major disease on basil plants in Hawassa and Debre Zeit, with a 30-35 percent severity. Therefore, identification of the pathogen's causing agents and integrated disease management for the major recorded diseases of medicinal and aromatic plants needs further research.

Characterization of phenotypic traits associated with anthracnose resistance in selected common bean (Phaseolus vulgaris L.) breeding material

Anthracnose caused by Colletotrichum lindemuthianum is the major common bean disease worldwide causing complete yield loss under favourable disease conditions. This study aimed to determine phenotypic traits associated with anthracnose resistance for future use in breeding programmes. Twenty-two common bean varieties (CBVs) were selected basing on susceptibility to anthracnose, advanced breeding lines, improved variety resembling advanced breeding lines and the farmer variety widely grown in Tanzania. Selected varieties were planted in anthracnose hotspot fields and the same CBVs were planted in a screen house to validate resistance to anthracnose. Anthracnose infection score, leaf length, leaf width, length of fifth internode, length of petiole, plant vigour, canopy height and canopy width were recorded. Data on number of plants emerging; days to flowering; days to maturity; plant stands at harvest; and grain yield were also collected and analysed using R software. Phenotypic traits evaluated differed significantly among genotypes, environment and genotype by environment interaction. Seventy-five percent of phenotypic traits evaluated were positively correlated to anthracnose resistance.Highly-strong correlations to anthracnose were observed on number of days to maturity, plant stands at harvest, plant vigour and grain yield. Leaf length, leaf width, length of fifth internode, length of petiole and number of stands emerging were strongly correlated to anthracnose resistance. Additive main effects and multiplicative interaction analysis (AMMI) revealed highest contribution of environment on anthracnose infection-58.9% and grain yield −84.9% compared to genotype effects on anthracnose infection −32.7% and grain yield-15.7%. Based on these results, four traits – plant vigour, number of days to maturity, number of plant stands at harvest and grain yield – are recommended for selecting anthracnose-resistant varieties. NUA 48, NUA 64 and RWR 2154 were superior varieties, resistant to anthracnose and high yielding, while Sweet Violet and VTT 923-23-10 were most stable varieties across environments. Further on-farm research is suggested to assess their performance and identify traits preferred by farmers.

Management of Fusarium Wilt of Tomato (Fusarium oxysporum f. sp. lycopersici) and Related Soil-borne Diseases using Eco-friendly Methods: A Review

Tomato is rich in vitamins, minerals and contains anti-oxidant compounds, like vitamin C and lycopene that has significant role in human health as it has anti-cancer properties. Tomato production is significantly affected by several factors amongst which Fusarium Wilt is one of the major and widespread fungal soil borne diseases in Nigeria. Difficulty in controlling this disease is attributable to long survivability of the pathogen and its existence in diverse pathogenic races. Conventional strategies, such as the use of resistant cultivars and synthetic fungicides, are not completely effective in managing tomato wilt caused by Fusarium oxysporum f. sp. lycopersici and because of unintended effects of chemicals on the environments its application is highly cautioned. This paper has examined many non-pesticide approaches such as application of bio-control agents, use of suppressive soils, composts/vermicomposts and their extracts, animal manure and urine, soil solarization, botanical extracts, good agricultural practices and integrated disease management strategy to control Fusarium wilt and other related soil borne diseases. It is worth noting that no single method can effectively control such diseases. In order to achieve a sustainable and eco-friendly disease management strategy the use of integrated approach is highly recommended. This review will provide farmers with diverse methods to be integrated as management package for Fusarium wilt and related diseases.

Risk factors and predictive model for mortality in patients undergoing allogeneic hematopoietic stem cell transplantation admitted to the intensive care unit.

Hematological malignant tumors represent a group of major diseases carrying a substantial risk to the lives of affected patients. Risk factors for mortality in critically ill patients have garnered substantial attention in recent research endeavors. The present research aimed to identify factors predicting intensive care unit (ICU) mortality in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). Furthermore, the present study analyzed and compared the mortality rate between patients undergoing haploidentical hematopoietic stem cell transplantation (Haplo-SCT) and those undergoing identical sibling donor (ISD) transplantation. A total of 108 patients were included in the present research, 83 (76.9%) of whom underwent Haplo-SCT. ICU mortality was reported in 58 (53.7%) patients, with the values of 55.4 and 48.0% associated with Haplo-SCT and ISD, respectively (P=0.514). The mortality rate of patients undergoing Haplo-SCT was comparable to that of patients undergoing ISD transplantation. The present study found that reduced hemoglobin, elevated total bilirubin, elevated brain natriuretic peptide, elevated fibrinogen degradation products, need for vasoactive drugs at ICU admission, need for invasive mechanical ventilation and elevated APACHE II scores were independent risk factors for ICU mortality. Among patients presenting with 5-7 risk factors, the ICU mortality reached 100%, significantly exceeding that of other patients. The present research revealed that ICU mortality rates remain elevated among patients who underwent allo-HSCT, especially those presenting multiple risk factors. However, the outcome of patients undergoing Haplo-SCT were comparable to those of patients undergoing ISD transplants.

Persistence in risk and effect of COVID-19 vaccination on long-term health consequences after SARS-CoV-2 infection

The persisting risk of long-term health consequences of SARS-CoV-2 infection and the protection against such risk conferred by COVID-19 vaccination remains unclear. Here we conducted a retrospective territory-wide cohort study on 1,175,277 patients with SARS-CoV-2 infection stratified by their vaccination status and non-infected controls to evaluate the risk of clinical sequelae, cardiovascular and all-cause mortality using a territory-wide public healthcare database with population-based vaccination records in Hong Kong. A progressive reduction in risk of all-cause mortality was observed over one year between patients with SARS-CoV-2 infection and controls. Patients with complete vaccination or have received booster dose incurred a lower risk of health consequences including major cardiovascular diseases, and all-cause mortality than unvaccinated or patients with incomplete vaccination 30-90 days after infection. Completely vaccinated and patients with booster dose of vaccines did not incur significant higher risk of health consequences from 271 and 91 days of infection onwards, respectively, whilst un-vaccinated and incompletely vaccinated patients continued to incur a greater risk of clinical sequelae for up to a year following SARS-CoV-2 infection. This study provided real-world evidence supporting the effectiveness of COVID-19 vaccines in reducing the risk of long-term health consequences of SARS-CoV-2 infection and its persistence following infection.

Crosstalk between ALK3(BMPR1A) deficiency and autophagy signaling mitigates pathological bone loss in osteoporosis

Postmenopausal osteoporosis is recognized to be one of the major skeleton diseases strongly associated with impaired bone formation. Previous reports have indicated that the importance of bone morphogenetic protein (BMP) signaling of osteoblast lineage in bone development via classical Smad signaling, however, its critical role in osteoporosis is still not well understood. In the current study, we aim to investigate the pathological role of BMPR1A, a key receptor of BMPs, in osteoporosis and its underlying mechanism. We first found that knockdown of BMPR1A by using Col1a1-creER in osteoblasts mitigated early bone loss of osteoporosis in mice, yet along with late bone maturation defects by reducing mineral adherence rate and bone formation rate in vivo. At the cellular level, we then observed that BMPR1A deficiency promoted the proliferation of pre-osteoblasts under osteoporotic conditions but hindered their late-stage mineralization. We finally elucidated that BMPR1A deficiency compensatorily triggered mTOR-autophagy perturbation by a higher level in early osteoporotic pre-osteoblasts thus resulting in the enhancement of transient cell proliferation but impairment of final mineralization. Taken together, this study indicated the significance of BMPR1A-mTOR/autophagy axis, as a double-edged sword, in osteoporotic bone formation and provided new cues for therapeutic strategies in osteoporosis.

Systematic surveillance tools to reduce rodent pests in disadvantaged urban areas can empower communities and improve public health

Rodents are notorious pests, known for transmitting major public health diseases and causing agricultural and economic losses. The lack of site-specific and national standardised rodent surveillance in several disadvantaged communities has rendered interventions targeted towards rodent control as often ineffective. Here, by using the example from a pilot case-study in the Bahamas, we present a unique experience wherein, through multidisciplinary and community engagement, we simultaneously developed a standardised national surveillance protocol, and performed two parallel but integrated activities: (1) eight days of theoretical and practical training of selected participants; and (2) a three-month post-training pilot rodent surveillance in the urban community of Over-the-Hill, Nassau, The Bahamas. To account for social and environmental conditions influencing rodent proliferation in the Bahamas, we engaged selected influential community members through a semi-structured interview and gathered additional site-specific information using a modified Centers for Diseases Control and Prevention (CDC) exterior and interior rodent evaluation form, along with other validated instruments such as tracking plates and snap trapping, to test and establish a standardised site-specific rodent surveillance protocol tailored for the Bahamas. Our engagement with community members highlighted poor disposal of animal and human food, irregular garbage collection, unapproved refuse storage, lack of accessible dumpsters, poor bulk waste management, ownership problems and structural deficiencies as major factors fuelling rodent proliferation in the study areas. Accordingly, results from our pilot survey using active rodent signs (that is, the presence of rodent runs, burrows, faecal material or gnawed material) as a proxy of rodent infestation in a generalized linear model confirmed that the variables earlier identified during the community engagement program as significantly correlated with rodent activities (and capturing) across the study areas. The successful implementation of the novel site-specific protocol by trained participants, along with the correlation of their findings with those recorded during the community engagement program, underscores its suitability and applicability in disadvantaged urban settings. This experience should serve as a reference for promoting a standardised protocol for monitoring rodent activities in many disadvantaged urban settings of the Global South, while also fostering a holistic understanding of rodent proliferation. Through this pilot case-study, we advocate for the feasibility of developing sustainable rodent control interventions that are acceptable to both local communities and public authorities, particularly through the involvement of a multidisciplinary team of professionals and community members.