Organ Function Research Articles

Reducing Hospitalization Rates: The Preventive Benefits of Blood Transfusions in HIV Care

Hospitalization rates among individuals living with HIV remain a significant challenge due to various complications, including opportunistic infections, anemia, and comorbidities. This review article explores the preventive benefits of blood transfusions as a strategic intervention in reducing hospitalization rates in HIV care. By correcting anemia, enhancing oxygen delivery, and improving overall health status, blood transfusions can play a vital role in preventing adverse health outcomes that often lead to hospitalization. We discuss the mechanisms through which transfusions provide these benefits, supported by clinical evidence and the implications for comprehensive HIV management. The role of blood transfusions extends beyond mere therapeutic intervention for severe anemia; they are increasingly recognized for their potential to improve patient outcomes and quality of life. By alleviating symptoms of anemia, enhancing organ function, and supporting immune responses, transfusions can contribute significantly to the health and well-being of individuals living with HIV. Clinical evidence indicates that timely blood transfusions can lead to fewer hospitalizations, better treatment outcomes, and overall improved health status. Keywords: anemia, blood transfusions, HIV, hospitalization rates, preventive care

Effect of Probiotic Consortium Administration in Improving Organ Function and Blood Biochemistry in Laying Chickens

Effect of Probiotic Consortium Administration in Improving Organ Function and Blood Biochemistry in Laying Chickens

IGF signaling pathway in bone and cartilage development, homeostasis, and disease.

The skeleton plays a fundamental role in the maintenance of organ function and daily activities. The insulin-like growth factor (IGF) family is a group of polypeptide substances with a pronounced role in osteoblast differentiation, bone development, and metabolism. Disturbance of the IGFs and the IGF signaling pathway is inextricably linked with assorted developmental defects, growth irregularities, and jeopardized skeletal structure. Recent findings have illustrated the significance of the action of the IGF signaling pathway via growth factors and receptors and its interactions with dissimilar signaling pathways (Wnt/β-catenin, BMP, TGF-β, and Hh/PTH signaling pathways) in promoting the growth, survival, and differentiation of osteoblasts. IGF signaling also exhibits profound influences on cartilage and bone development and skeletal homeostasis via versatile cell-cell interactions in an autocrine, paracrine, and endocrine manner systemically and locally. Our review summarizes the role and regulatory function as well as a potentially integrated gene network of the IGF signaling pathway with other signaling pathways in bone and cartilage development and skeletal homeostasis, which in turn provides an enlightening insight into visualizing bright molecular targets to be eligible for designing effective drugs to handle bone diseases and maladies, such as osteoporosis, osteoarthritis, and dwarfism.

Microfluidic Platform for Generating and Releasing Patient-Derived Cancer Organoids with Diverse Shapes: Insight into Shape-Dependent Tumor Growth.

Multicellular spheroids and patient-derived organoids find many applications in fundamental research, drug discovery, and regenerative medicine. Advances in the understanding and recapitulation of organ functionality and disease development require the generation of complex organoid models, including organoids with diverse morphologies. Microfluidics-based cell culture platforms enable time-efficient confined organoid generation. However, the ability to form organoids with different shapes with a subsequent transfer from microfluidic devices to unconstrained environments for studies of morphology-dependent organoid growth is yet to be demonstrated. Here, a microfluidic platform is introduced that enables high-fidelity formation and addressable release of breast cancer organoids with diverse shapes. Using this platform, the impact of organoid morphology on their growth in unconstrained biomimetic hydrogel is explored. It is shown that proliferative cancer cells tend to localize in high positive curvature organoid regions, causing their faster growth, while the overall growth pattern of organoids with diverse shapes tends to reduce interfacial tension at the organoid-hydrogel interface. In addition to the formation of organoids with diverse morphologies, this platform can be integrated into multi-tissue micro-physiological systems.

The impact of trial inclusion criteria on outcomes in DLBCL patients treated with R-CHOP in the first line: a Danish nationwide study

Up to 50% of diffuse large B-cell lymphoma (DLBCL) patients are ineligible for participation in clinical trials. Ineligible patients have inferior outcomes, but less is known about the impact of commonly used organ-function-based inclusion criteria on drug efficacy estimates. Data on DLBCL patients treated with CHOP+/-rituximab were retrieved from the Danish Lymphoma Registry. Trial inclusion criteria were extracted from four international DLBCL trials (REMoDL-B, GOYA, POLARIX, and HOVON-84). Differences in overall survival (OS) and 5-year restricted mean survival differences (5 y-RMSDs) between trial eligible and ineligible patients were computed. The effectiveness of adding rituximab to CHOP was quantified by the 5 y-RMSD between CHOP and R-CHOP-treated patients and the impact of individual trial criteria on estimated effectiveness was quantified by Shapley-values. In total, 4,083 R-CHOP-treated and 890 CHOP-treated DLBCL patients were included. Across the trials, 18.6-29.3% of the included R-CHOP-treated patients were deemed ineligible for trial based on organ function and performance status alone. Ineligible patients had significantly worse survival, with adjusted absolute differences in 5-year OS of 9-15%. The impact of individual criteria on the estimated effectiveness of adding rituximab to CHOP was small (Shapley-value range, −2.74-0.31). Using a smaller set of criteria derived from a data-driven approach, the number of eligible patients increased by 16-38% and the 5 y-RMSD increased by 0.7-3.1 months. In conclusion, OS among trial ineligible DLBCL patients is inferior as expected, but relaxing trial criteria would have increased the number of trial participants without making major changes in estimated efficacy for a hypothetical CHOP versus R-CHOP trial. This does not necessarily imply that trial findings based on selected patients are unreliable, as the estimated effectiveness of adding rituximab to CHOP was only slightly affected by omitting selected inclusion criteria.

Protein kinase N promotes cardiac fibrosis in heart failure by fibroblast-to-myofibroblast conversion

Chronic fibrotic tissue disrupts various organ functions. Despite significant advances in therapies, mortality and morbidity due to heart failure remain high, resulting in poor quality of life. Beyond the cardiomyocyte-centric view of heart failure, it is now accepted that alterations in the interstitial extracellular matrix (ECM) also play a major role in the development of heart failure. Here, we show that protein kinase N (PKN) is expressed in cardiac fibroblasts. Furthermore, PKN mediates the conversion of fibroblasts into myofibroblasts, which plays a central role in secreting large amounts of ECM proteins via p38 phosphorylation signaling. Fibroblast-specific deletion of PKN led to a reduction of myocardial fibrotic changes and cardiac dysfunction in mice models of ischemia-reperfusion or heart failure with preserved ejection fraction. Our results indicate that PKN is a therapeutic target for cardiac fibrosis in heart failure.

The effect of epidermal growth factor receptor mutation on adjuvant chemotherapy with tegafur/uracil for patients with completely resected, non-lymph node metastatic non-small cell lung cancer (> 2cm): a multicenter, retrospective, observational study as exploratory analysis of the CSPOR-LC03 study.

The use of adjuvant osimertinib for epidermal growth factor receptor (EGFR) mutants is expected to expand to earlier stage I in the future, potentially competing with the current standard of care, oral tegafur/uracil (UFT), in Japan. However, the effect of EGFR mutation status on the therapeutic effect of UFT remains unclear. This study was conducted as an exploratory analysis of a retrospective observational study that investigated the real-world data of postoperative adjuvant chemotherapy in Japan (CSPOR-LC03). Between 2008 and 2013, 1812 patients with completely resected adenocarcinoma diagnosed as pathologic stage I (T1>2cm, TNM classification, sixth edition) who have maintained organ function, and no history of other cancers were included. The primary endpoint was the 5-year disease-free survival (DFS) rate, and we compared this rate between four groups classified based on the administration of adjuvant UFT and EGFR mutation status. Of the 933 (51%) patients with EGFR mutations, 394 underwent adjuvant UFT therapy. Of the 879 (49%) patients without EGFR mutations, 393 underwent adjuvant UFT therapy. The 5-year DFS of UFT+/EGFR+ and UFT-/EGFR+ patients were 82.0 and 87.1%, respectively, and those of UFT+/EGFR- and UFT-/EGFR- patients were 80.0 and 86.9%, respectively. DFS was significantly worse in the UFT+ group than in the UFT- group (P=0.015). Adjuvant UFT therapy was not an independent prognostic factor for DFS, regardless of the EGFR mutation status. In pathologic stage I (>2cm) lung adenocarcinomas with EGFR mutation, the survival benefit of adjuvant UFT was not observed.

Neoadjuvant Immunotherapy Alone for Patients With Locally Advanced and Resectable Metastatic Colorectal Cancer of dMMR/MSI-H Status.

The use of programmed death-1 blockade has a significant therapeutic effect in patients with mismatch repair-deficient/microsatellite instability-high metastatic colorectal cancer. However, data on preoperative single-agent programmed death-1 blockade are rare. This study aims to evaluate the effectiveness and safety of preoperative programmed death-1 blockade as a conversion strategy in patients with locally advanced and resectable metastatic mismatch repair-deficient/microsatellite instability-high colorectal cancer. This is a retrospective observational study. This study was conducted at a high-volume tertiary referral cancer center in China. Twenty-four patients of consecutive cases since 2020 to 2022 with mismatch repair-deficient/microsatellite instability-high colorectal cancer who received preoperative single-agent programmed death-1 blockade were retrospectively reviewed. These patients had either bulking tumors scheduled for multivisceral resection, a strong desire for organ preservation, or potentially resectable metastatic lesions. Pathological complete response, clinical complete response, toxicity, R0 resection rate, and complications were evaluated. Patients tolerated preoperative immunotherapy well. The R0 resection rate was 95.2%, and the pathological complete response rate was 47.6%. Three patients (12.5%) were evaluated as having a clinical complete response and then underwent "watch and wait." One-half of the patients with cT4b were spared multivisceral resection, whereas 60% (3/5) achieved pathological complete response. All 3 patients with liver metastases obtained complete response of all liver lesions after programmed death-1 blockade treatment. Grade III postoperative complications occurred in 2 patients. The limitations of this study are as follows: retrospective study, small sample size, and short follow-up. Preoperative anti-programmed death-1 therapy alone as a conversion strategy in initially resected difficult mismatch repair-deficient/microsatellite instability-high colorectal cancer can achieve a high tumor complete response. The use of immunopreoperative therapy in patients with T4b colon cancer or low rectal cancer can reduce multivisceral resection and achieve high organ function preservation. See the Video Abstract . ANTECEDENTES:El uso del bloqueo de muerte programada-1 tiene un efecto terapéutico significativo en pacientes con cáncer colorrectal metastásico deficiente en reparación de desajustes/inestabilidad de microsatélites-alta (dMMR/MSI-H). Sin embargo, los datos sobre el bloqueo preoperatorio de muerte programada-1 con un solo agente son escasos.OBJETIVO:Este estudio tiene como objetivo evaluar la eficacia y seguridad del bloqueo preoperatorio de muerte programada-1 como estrategia de conversión en pacientes con cáncer colorrectal localmente avanzado y metastásico resecable con dMMR/MSI-H.DISEÑO:Este es un estudio observacional retrospectivo.ESCENARIO:Este estudio se realizó en un centro oncológico terciario de referencia de gran volumen en China.PACIENTES:Se revisaron retrospectivamente veinticuatro pacientes de casos consecutivos desde 2020-2022 con cáncer colorrectal y dMMR/MSI-H que recibieron bloqueo preoperatorio de muerte programada-1 con un solo agente. Estos pacientes tenían un tumor voluminoso programado para resección multivisceral, un fuerte deseo de preservación del órgano o lesiones metastásicas potencialmente resecables.PRINCIPALES MEDIDAS DE RESULTADO:Se evaluaron la respuesta patológica completa, la respuesta clínica completa, la toxicidad, la tasa de resección R0 y las complicaciones.RESULTADOS:Los pacientes toleraron bien la inmunoterapia preoperatoria. La tasa de resección R0 fue del 95,2% y la tasa de respuesta patológica completa fue del 47,6%. Tres pacientes (12,5%) fueron evaluados como respuesta clínica completa y luego sometidos a "observar y esperar". La mitad de los pacientes cT4b se salvaron de la resección multivisceral, mientras que el 60% (3/5) lograron una respuesta patológica completa. Los tres pacientes con metástasis hepáticas obtuvieron respuesta completa de todas las lesiones hepáticas después del tratamiento de bloqueo de muerte programada-1. En dos pacientes se produjeron complicaciones postoperatorias de grado III.LIMITACIONES:Las limitaciones de este estudio son las siguientes: estudio retrospectivo, tamaño de muestra pequeño y seguimiento corto.CONCLUSIONES:La terapia preoperatoria anti muerte programada-1 sola como estrategia de conversión en el cáncer colorrectal inicialmente difícil de resecar con dMMR/MSI-H puede lograr una alta respuesta completa tumoral. El uso de terapia inmunopreoperatoria en pacientes con cáncer de colon T4b o cáncer de recto bajo puede reducir la resección multivisceral y lograr una alta preservación de la función del órgano. (Traducción-Dr. Felipe Bellolio ).

Cannabis sativa (Linnaeus, 1753): The use of its extract against Rhipicephalus linnaei (Audouin, 1826) ticks

To minimize the damage caused by synthetic acaricides to non-target organisms, the use of bioactives compounds extracted from plants has been considered. In this study, semi-engorged females of Rhipicephalus linnaei ticks were exposed to Cannabis sativa flower extract (submersion for 5 minutes in different concentrations diluted in ethanol 30 %) evaluated alterations in the integument and salivary glands. The results demonstrated that lower concentrations of the extract caused damage to both the integument and salivary glands, affecting the cuticular epithelial cells responsible for synthesizing all layers of the cuticle. The concentration of 2.5 mg/mL caused more extensive damage than 5.0 mg/mL, and 40 mg/mL completely disrupted the epithelium. Exposure of the salivary glands showed that at 2.5 ug/mL dose the glandular acini was disrupted, leaving only a heterogeneous mass with some nuclei of acinar cells, leading to acinar rupture. These findings indicate that the extract from Cannabis sativa flowers irreversibly alters the morphology and consequently, interferes with the functionality of different vital organs.

Management of cardiogenic shock: state-of-the-art.

The management of cardiogenic shock is an ongoing challenge. Despite all efforts and tremendous use of resources, mortality remains high. Whilst reversing the underlying cause, restoring/maintaining organ perfusion and function are cornerstones of management. The presence of comorbidities and preexisting organ dysfunction increases management complexity, aiming to integrate the needs of vital organs in each individual patient. This review provides a comprehensive overview of contemporary literature regarding the definition and classification of cardiogenic shock, its pathophysiology, diagnosis, laboratory evaluation, and monitoring. Further, we distill the latest evidence in pharmacologic therapy and the use of mechanical circulatory support including recently published randomized-controlled trials as well as future directions of research, integrating this within an international group of authors to provide a global perspective. Finally, we explore the need for individualization, especially in the face of neutral randomized trials which may be related to a dilution of a potential benefit of an intervention (i.e., average effect) in this heterogeneous clinical syndrome, including the use of novel biomarkers, artificial intelligence, and machine learning approaches to identify specific endotypes of cardiogenic shock (i.e., subclasses with distinct underlying biological/molecular mechanisms) to support a more personalized medicine beyond the syndromic approach of cardiogenic shock.

A race against time – an evaluation of lifesaving treatment pathways for patients following cardiac arrest in a non-hospital setting.

BackgroundCardiac arrest occurs when the heart ceases pumping blood around the body. Most take place outside hospital. A sequence of effective interventions (a “chain of survival”) is essential for patient survival and recovery of organ function. Out of Hospital Cardiac Arrest (OHCA) requires prompt recognition and call for help, proficient CPR, early defibrillation and conveyance by the emergency services to an appropriate hospital. If initial resuscitation is successful, effective post-resuscitation care is required, delivered usually in the intensive care unit (ICU). New patient pathways were introduced following an update to national guidelines, which recommend conveyance of patients to centres with percutaneous coronary intervention (PCI) services where possible. ObjectiveWe have evaluated outcomes for patients, comparing those conveyed to PCI settings and those conveyed elsewhere to quantify the effect of the new patient pathway on mortality, survival and length of hospital stay. ApproachWe have linked electronic health records from emergency departments, acute hospital settings, ICUs and the national deaths register for OHCA patients living in Wales, UK. We have undertaken temporal analysis and time to event analysis to compare patient subgroups. ResultsVariation in patient pathways will be described using characteristics of conveyance method, the type of treating hospital and transfers between PCI and non-PCI settings adjusted for individual patient level confounders such as age, sex and comorbidities. ConclusionThis work is important to evaluate efficacy of operational procedures and inform national policies which aim to improve survival following OHCA and save lives.

The implications of frailty in older adults with epilepsy.

Older adults constitute a large proportion of people with epilepsy (PWE) due to the changing demographics worldwide and epilepsy's natural history. Aging-related pathophysiological changes lower the tolerance and increase our vulnerability to stressors, which manifests as frailty. Frailty is closely associated with adverse health outcomes. This narrative review examines the interplay between frailty and epilepsy, especially in older adults, emphasizing its clinical implications, including its role in managing PWE. Mechanistically, frailty develops through complex interactions among molecular and cellular damage, including genomic instability, mitochondrial dysfunction, and hormonal changes. These contribute to systemic muscle mass, bone density, and organ function decline. The concept of frailty has evolved from a primarily physical syndrome to include social, psychological, and cognitive dimensions. The "phenotypic frailty" model, which focuses on physical performance, and the "deficit accumulation" model, which quantifies health deficits, provide frameworks for understanding and assessing frailty. PWE are potentially more prone to developing frailty due to a higher prevalence of risk factors predisposing to frailty. These include, but are not limited to, polypharmacy, higher comorbidity, low exercise level, social isolation, low vitamin D, and osteoporosis. We lack commercial biomarkers to measure frailty but can diagnose it using self- or healthcare provider-administered frailty scales. Recent attempts to develop a PWE-specific frailty scale are promising. Unlike chronological age, frailty is reversible, so its management using multidisciplinary care teams should be strongly considered. Frailty can affect antiseizure medication (ASM) tolerance secondary to its impact on pharmacokinetics and pharmacodynamics. While frailty's effect on seizure control efficacy of ASM is poorly understood, its undoubted association with overall poor outcomes, including epilepsy surgery, behooves us to consider its presence and implication while treating older PWE. Incorporation of frailty measures in future research is essential to improve our understanding of frailty's role in PWE health. PLAIN LANGUAGE SUMMARY: Frailty is the declining state of the human body. People with epilepsy are more prone to it. It should be factored into their management.

Evaluation of Withania somnifera (L.) Dunal (Ashwagandha) on Physical Performance, Biomarkers of Inflammation, and Muscle Status in Healthy Volunteers: A Randomized, Double-Blind, Placebo-Controlled Study.

Sarcopenia is associated with chronic inflammation, a sedentary lifestyle, and ageing.However, there exists no drug, which is safe and effective for long-term use. Ashwagandha (Withaniasomnifera (L.) Dunal) has the potential to fill this therapeutic gap based on its efficacy and safety profile; hence, the present study was planned to evaluate its effect on inflammatory biomarkers and muscle status in healthy volunteers. A prospective, double-blind, randomized, placebo-controlled clinical study was conducted to evaluate the effects of Ashwagandha extract in healthy volunteers (February 2021 to May 2022) who received either Ashwagandha extract tablets 250 mgor a placebo twicedaily for 60 days. The physical performance on a bicycle ergometer, inflammatory/muscle status biomarkers, body composition, reaction time, hemogram, and organ function tests was assessed at baseline, day 30, and day 60. In the Ashwagandha group, there was a statistically significant (p<0.05) improvement in total distance travelled (Ashwagandha 2.85 ± 0.54 km vs placebo 2.16 ± 0.62 km), average speed achieved (Ashwagandha 25.6 ± 5.7 km/hour vs placebo 22.2 ± 5.48 km/hour) on a bicycle ergometer from the baseline visit (V3) to the last visit (V7) as compared to the placebo group. The observations on hand-grip strength, back-leg press, skeletal muscle mass, and VO2 max showed an increasing trend from V3to V7, whereas the results of thethree inflammatory markers (hs-C-reactive protein (CRP) mg/L; IL-6; TNF-alpha ) and the muscle marker (myostatin)revealed a decreasing trend from V3 to V7 in the Ashwagandha group.Ashwagandha extract was found to be safe in healthy volunteers as evidenced by the clinical profile, laboratory investigations, and reaction time test. Ashwagandha extract supplementation was safe and effective in enhancing physical performance and strengthening muscle mass and could be a potential candidate for treating sarcopenia.

Covalent Triazine Based Frameworks with Donor‐Donor‐π‐Acceptor Structures for Dendrite‐Free Lithium Metal Batteries

AbstractThe appearance of disordered lithium dendrites and fragile solid electrolyte interfaces (SEI) significantly hinder the serviceability of lithium metal batteries. Herein, guided by theoretical predictions, a multi‐component covalent triazine framework with partially electronegative channels (4C‐TA0.5TF0.5‐CTF) is incorporated as a protective layer to modulate the interface stability of the lithium metal batteries. Notably, the 4C‐TA0.5TF0.5‐CTF with optimized electronic structure at the molecular level by fine‐tuning the local acceptor‐donor functionalities not only enhances the intermolecular interaction thereby providing larger dipole moment and improved crystallinity and mechanical stress, but also facilitates the beneficial effect of lithiophilic sites (C−F bonds, triazine cores, C=N linkages and aromatic rings) to further regulate the migration of Li+ and achieve a uniform lithium deposition behavior as determined by various in‐depth in/ex situ characterizations. Due to the synergistic effect of multi‐component organic functionalities, the 4C‐TA0.5TF0.5‐CTF modified full cells perform significantly better than the common two/three‐component 2C‐TA‐CTF and 3C‐TF‐CTF electrodes, delivering an excellent capacity of 116.3 mAh g−1 (capacity retention ratio: 86.8 %) after 1000 cycles at 5 C and improved rate capability. This work lays a platform for the prospective molecular design of improved organic framework relative artificial SEI for highly stable lithium metal batteries.

Contributions of mirror-image hair cell orientation to mouse otolith organ and zebrafish neuromast function.

Otolith organs in the inner ear and neuromasts in the fish lateral-line harbor two populations of hair cells oriented to detect stimuli in opposing directions. The underlying mechanism is highly conserved: the transcription factor EMX2 is regionally expressed in just one hair cell population and acts through the receptor GPR156 to reverse cell orientation relative to the other population. In mouse and zebrafish, loss of Emx2 results in sensory organs that harbor only one hair cell orientation and are not innervated properly. In zebrafish, Emx2 also confers hair cells with reduced mechanosensory properties. Here, we leverage mouse and zebrafish models lacking GPR156 to determine how detecting stimuli of opposing directions serves vestibular function, and whether GPR156 has other roles besides orienting hair cells. We find that otolith organs in Gpr156 mouse mutants have normal zonal organization and normal type I-II hair cell distribution and mechano-electrical transduction properties. In contrast, gpr156 zebrafish mutants lack the smaller mechanically-evoked signals that characterize Emx2-positive hair cells. Loss of GPR156 does not affect orientation-selectivity of afferents in mouse utricle or zebrafish neuromasts. Consistent with normal otolith organ anatomy and afferent selectivity, Gpr156 mutant mice do not show overt vestibular dysfunction. Instead, performance on two tests that engage otolith organs is significantly altered - swimming and off-vertical-axis rotation. We conclude that GPR156 relays hair cell orientation and transduction information downstream of EMX2, but not selectivity for direction-specific afferents. These results clarify how molecular mechanisms that confer bi-directionality to sensory organs contribute to function, from single hair cell physiology to animal behavior.

Long-term survival after unrelated donor marrow transplantation for aplastic anaemia after optimized conditioning regimen: a retrospective multicentre cohort study

Almost all acquired severe aplastic anaemia is immune mediated and characterised by hypocellular bone marrow and ≥2 affected haematopoietic lineages. The optimal preparartive regimen for unrelated donor transplantation remains to be established. We aimed to study long-term outcomes after unrelated donor transplantation for severe aplastic anaemia with de-escalation of cyclophosphamide (Cy) dose in steps of 50mg/kg (150, 100, 50, 0mg/kg) in combination with total body irradiation (TBI) 2Gy, anti-thymocyte globulin (ATG) and fludarabine. Ninety-six patients with severe aplastic anaemia aged ≤65 years with adequate organ function enrolled on a trial of human leukocyte antigen (HLA)-matched or 1 HLA-locus mismatched unrelated donor marrow transplantation conducted between 02/2006 and 12/2013 in the United States (NCT00326417). Exclusion criteria were Karnofsky performance status of less than 60, clonal cytogenetic abnormalities and inherited marrow failure syndormes. The primary outcome was day-100 engraftment (achievement of absolute neutrophil recovery to at least 0.5×109/L without subsequent decline) and day-100 survival. The trial determined the lowest effective Cydose as 50mg/kg (n=38) for day-100 engraftment and survival. Cy dose 100mg/kg (n=41) was also acceptable. Accrual to Cy doses 150mg/kg (n=15) and 0mg/kg (n=3) was terminated early for toxicities. The current study is an extended follow up of patients enrolled on the trial (NCT00326477) and includes 76 of 96 patients alive ≥1 year after transplantation. There were 20 deaths in the first year after transplantation (Cy 0mg/kg [n=2], Cy 50mg/kg [n=1], Cy 100mg/kg [n=10], Cy 150mg/kg [n=7]). Patients were followed prospectively from transplantation and data reported using standardized data collection forms until death, loss to follow up or last contact through November 2023. The incidence of graft failure was calculated using the cumulative incidence estimator and the probability of survival using the Kaplan-Meier estimator. The median follow up of the cohort is 8.02 (IQR) 5.16-10.12) years. With Cy 50mg/kg, there was one graft failure and five deaths ≥1 year after transplantation. With Cy 100mg/kg there was only one late death and no graft failure. The 8-year probabilities of survival were 85.0% (95% CI 67.3-93.5) and 75.6% (95% CI 59.4-86.1) after Cy50mg/kg and 100mg/kg, respectively, P=0.31. With Cy 0mg/kg and 150mg/kg, there were no graft failures or death ≥1 year after transplantation. Regardless of Cy dose 12 of 15 patients aged ≥50 years died. Cy 50mg/kg or 100mg/kg with TBI 2Gy, ATG and fludarabine are effective conditioning regimens for unrelated donor marrow transplants for aplastic anaemia. Identification of an optimized transplantation approach for patients aged ≥50 years is needed. US National Institutes of Health.

The Impact of Oral Maternal Colostrum Administration on the Immune System of Premature Babies

In children under five years of age, premature complications are now the second leading cause of death. Colostrum has important benefits in promoting the maturity of premature infants' organ functions and preventing infections. Preterm infants are recommended to be given colostrum orally and pharyngeally as early as possible after birth to provide immune protective effects for their bodies. However, the sucking and swallowing functions of preterm infants are often not optimal, partly due to comorbidities, which poses a significant challenge. As a result, the immune system of preterm infants is often low. This literature review aimed to evaluate the effect of oropharyngeal colostrum feeding through subgroup analysis based on complications. Descriptive research was conducted in April-June 2024 using the literature review method with PRISMA guidelines for RCTs. Literature sources were obtained from Pubmed (MEDLINE), Science Direct, Google Scholar, and Cochrane with a publication limit of the last ten years (2014-2023). Of the 1,657 results, 13 articles met the criteria. A total of 1,451 preterm infants were included in the 13 RCT studies. Results showed a lower incidence of late-onset sepsis and Necrotizing Enterocolitis (NEC) in the group that received oropharyngeal colostrum. The administration of oropharyngeal colostrum was shown to have a positive impact on the development and defense of the immune system of preterm infants, reduce health problems such as sepsis and NEC, accelerate the recovery of birth weight, and reduce the incidence of mortality.

Coconut oil affects aging-related changes in Mongolian gerbil liver morphophysiology

Aging causes changes in liver morphophysiology, altering hepatocyte morphology and organ function. Due to its antioxidant and anti-inflammatory properties, coconut oil has been used as a therapeutic agent in diets, in an attempt to attenuate alterations in the liver naturally caused by aging. Herein, we evaluated the effects of coconut oil consumption during aging on Mongolian gerbil liver morphophysiology. The animals were divided into three experimental groups: the gerbils in the Adult Control Group (AC) were euthanized at 3 months of age, the gerbils in the Old Control Group (OC) at 15 months of age, and the gerbils in the Coconut Oil Group (CO) received 0.1 ml/day of coconut oil for 12 months and were euthanized at 15 months of age. Prolonged consumption of coconut oil during aging prevented the animals and the liver from gaining mass. However, the other results showed that coconut oil intensified the morphophysiological alterations of aging, promoting an increase in the hepatocyte cytoplasm and nuclei. In addition, an increase in blood vessels, reticular fibers, lipid droplets, and lipofuscin granules were observed in the CO group. Finally, the results also demonstrated that coconut oil promotes an increase in lipid peroxidation, indicated by an increase in MDA levels. We therefore conclude that coconut oil has the potential to intensify the morphophysiological alterations that occur in the liver during aging.

Melatonin in animal husbandry: functions and applications.

Melatonin (N-acetyl-5-methoxytryptamine) is an essential small molecule with diverse biological functions. It plays several key roles, including regulating the secretion of reproductive hormones and the reproductive cycle, enhancing the functionality of reproductive organs, improving the quality of sperm and eggs, and mitigating oxidative stress in the reproductive system. Melatonin effectively inhibits and scavenges excess free radicals while activating the antioxidant enzyme system and reduces the production of inflammatory factors and alleviates tissue damage caused by inflammation by regulating inflammatory pathways. Additionally, melatonin contributes to repairing the intestinal barrier and regulating the gut microbiota, thereby reducing bacterial and toxin permeation. The use of melatonin as an endogenous hormone in animal husbandry has garnered considerable attention because of its positive effects on animal production performance, reproductive outcomes, stress adaptation, disease treatment, and environmental sustainability. This review explores the characteristics and biological functions of melatonin, along with its current applications in animal production. Our findings may serve as a reference for the use of melatonin in animal farming and future developmental directions.

Role of Excessive Mitochondrial Fission in Seawater Immersion Aggravated Hemorrhagic Shock-Induced Cardiac Dysfunction and the Protective Effect of Mitochondrial Division Inhibitor-1.

Aims: Seawater immersion significantly aggravated organ dysfunction following hemorrhagic shock, leading to higher mortality rate. However, the effective treatment is still unavailable in clinic. Mitochondria were involved in the onset and development of multiple organ function disorders; whether mitochondria participate in the cardiac dysfunction following seawater immersion combined with hemorrhagic shock remains poorly understood. Hence, we investigated the role and possible mechanism of mitochondria in seawater immersion combined with hemorrhage shock-induced cardiac dysfunction. Results: Mitochondrial fission protein dynamin-related protein 1 (Drp1) was activated and translocated from the cytoplasm to mitochondria in the heart following seawater immersion combined with hemorrhagic shock, leading to excessive mitochondrial fission. Excessive mitochondrial fission disrupted mitochondrial function and structure and activated mitophagy and apoptosis. At the same time, excessive mitochondrial fission resulted in disturbance of myocardial structure and hemodynamic disorders and ultimately provoked multiple organ dysfunction and high mortality. Further studies showed that the mitochondrial division inhibitor mitochondrial division inhibitor-1 can significantly reverse Drp1 mitochondrial translocation and inhibit mitochondrial fragmentation, reactive oxygen species (ROS) accumulation, mitophagy, and apoptosis and then protect circulation and vital organ functions, prolonging animal survival. Innovation: Our findings indicate that Drp1-mediated mitochondrial fission could be a novel therapeutic targets for the treatment of seawater immersion combined with hemorrhagic shock. Conclusion: Drp1 mitochondrial translocation played an important role in the cardiac dysfunction after seawater immersion combined with hemorrhage shock. Drp1-mediated excessive mitochondrial fission leads to cardiac dysfunction due to the mitochondrial structure and bioenergetics impairment.