Decline In Count Research Articles

O-052 Male fertility testing - new horizons, ideas and research

Abstract The diagnosis of male infertility is primarily based on the macroscopic analysis of semen and microscopic analysis of sperm (mainly concentration and count, motility, and morphology) through the seminogram. Although six different editions of the “WHO Manual for the Laboratory Examination and Processing of Human Semen” have been published to date, the diagnostic potential of this approach has been called into question. Additionally, recent studies report a significant decline in sperm counts and fecundability in general. Therefore, the need for alternative diagnostic approaches that effectively predict fertility in men is urgently needed. In this talk we will cover what the limitations of the current semen analysis are, what novel tests are available and more important the new horizons, ideas and research in male fertility testing. We will focus in: 1) the usefulness of sperm functionality analyses (e.g., vitality, plasma membrane and acrosome integrity, plasma membrane lipid disorder, mitochondrial membrane potential, mitochondrial peroxide and superoxide levels, intracellular levels of ROS and Ca2+, and sperm chromatin condensation, among others), 2) the clinical implications of sperm DNA fragmentation and the newest recommendations for assisted reproduction clinics, 3) the newly described monogenic causes of human male infertility, and 4) how comorbidities are related with infertility.

Abstract 3860: Drug resistance-mediating collagens (drmCOLs) are themselves druggable by an FDA/EMA-approved medicine to cause cancer cell arrest and apoptosis: Proof-of-conceptin vitro

Abstract Purpose of study: Tumor-generated collagen types I and III, identified two decades ago as factors of progression-free interval and survival in ovarian cancer (https://pubmed.ncbi.nlm.nih.gov/12468338/), mediate chemotherapeutic resistance, as do types VI and XI (https://pubmed.ncbi.nlm.nih.gov/34645978/, Table S1). All occur in pan-cancer gene signatures (https://pubmed.ncbi.nlm.nih.gov/27609069/). Collagens require Pro/Lys hydroxylation by 2-oxoacid utilizing dioxygenases (2OUDs) for native fold-dependent secretion and extracellular function; underhydroxylated collagens misfold and clog the endoplasmic reticulum. The HAG mechanism resolves 2OUD catalysis at orbital level, classifies all possible 2OUD inhibitors (https://pubmed.ncbi.nlm.nih.gov/6281585/), and is ‘seminal ‘ (https://pubmed.ncbi.nlm.nih.gov/7857312/) for development of collagen-suppressive drugs. We read the collagen-suppressive potential of the lifelong administered medicine deferiprone (DEF) off the HAG mechanism. Hypothesis: By blocking ligand reaction-driven ferryl formation in 2OUD catalysis, DEF at clinical range (10-150 µM) causes misfolded drmCOLs to trigger the unfolded protein response (UPR), effecting proliferative arrest and apoptosis preferentially of cancer cells. Methods: Genetically defined cell line models for high grade serous ovarian cancer (KURAMOCHI), uterine serous cancer (ARK1), normal matrix (MRC5); metabolic labeling; RNA-seq; flow cytometry. Results: In MRC5, DEF inhibited [3H]Pro/[3H]Lys hydroxylation, not incorporation. Cells expressed numerous COL mRNAs, e.g. 32 in ARK1 that suffice to generate 21 of 28 types of collagen; mRNAs for types I, VI, and XI/II predominated. Intracellular drmCOLs were confirmed by flow cytometry, using sequence-specific antibodies against COL1A1 (NBP1-77457AF700), COL3A1 (ab237239), COL6A1 (sc-377143), and COL11A2 (bs-2924R-A350). Within 48 hrs, DEF caused COL1A1/COL3A1/COL11A2 reactivity to increase up to 3-fold over controls; after 96 hrs, reactivity returned to control values in MRC5, remained elevated in KURAMOCHI, and rose further in ARK1, revealing cell-specific UPR set points. DEF at 48 hrs caused COL6A1 mRNA to decrease yet COL6A1 reactivity to increase in ARK1, evidencing the adaptive UPR ineffectively controls the accumulation of proteotoxic collagen. Activation of the ablative UPR, via enhanced DDIT3, XBP1, TRIB3, BAK1, PMAIP1, and HRK expression, coincided with a decline in cancer cell count by >80% within 96 hrs, an effect not observed in MRC5. Conclusions: HAG mechanism-defined inhibitors of drmCOL hydroxylation, pioneered by DEF, activate cytoreductive UPR effects in cancer cells preferentially. DEF use lacks adverse UPR or matrix effects, encouraging a pilot trial and 2OUD inhibitor development for oncological indication. Citation Format: Spencer M. Goering, Sukhwinder Singh, Bernadette M. Cracchiolo, Angela A. Sadev, Isabel W. Cracchiolo, Mainul Hoque, Axel-Rainer Hanauske, Yasmin Abedin, Hartmut Martin Hanauske-Abel. Drug resistance-mediating collagens (drmCOLs) are themselves druggable by an FDA/EMA-approved medicine to cause cancer cell arrest and apoptosis: Proof-of-conceptin vitro [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3860.

Early Impacts of COVID-19 on Select Hospices: Operations, Care Delivery, and Service Utilization.

ObjectiveThe COVID-19 public health emergency (PHE) has important implications for health care service delivery. Little is understood about how the PHE impacted community-based hospice providers and service delivery to hospice-eligible beneficiaries. The aim of this study was to describe hospice response to the PHE and correlated impacts on beneficiary receipt of hospice support services delivered to hospice-eligible beneficiaries participating in the Centers for Medicare & Medicaid Services (CMS) Medicare Care Choices Model (MCCM), a national model testing the provision of certain hospice-like supportive services with concurrent usual care among seriously ill, community-residing Medicare beneficiaries that have not elected to receive hospice care.MethodsWe employed descriptive analysis using concurrent qualitative and quantitative data sources, consisting of provider surveys, beneficiary-level encounter data submitted by hospices, and Medicare administrative claims describing beneficiary service utilization. The sample included both hospice providers (N = 82) and beneficiaries (N = 2294) voluntarily participating in MCCM.ResultsNearly all participating MCCM hospices adopted operational changes to address their staff and beneficiaries’ safety during the COVID-19 PHE. We report changes to service delivery, including declines in total encounters as well as service modality, and the types of services provided.ConclusionsWhile the analyses reported indicate that seriously ill Medicare beneficiaries participating in MCCM were directly impacted by the PHE, we are still unclear whether changes in the service modality and encounters by provider type and the decline in average service counts per beneficiary are driven more by hospices or by beneficiary decisions to minimize exposure. Future research should attempt to disentangle these factors.

Raised initial total white cell count and lower post-operative decline of C reactive protein increases the risk of secondary surgery in septic arthritis of the native knee.

Septic arthritis is an orthopaedic emergency with high morbidity and mortality. The aim of this study is to determine the risk factors associated with secondary surgery for septic arthritis of the native knee joint. This is a retrospective study reviewing all patients who underwent surgery for septic arthritis of the knee from 2012 to 2019 in a single institution. A total of 117 patients were recruited. Patients were divided into 2 groups: Group I (79/117, 67.5%) underwent one surgery and Group II (38/117, 32.5%) underwent more than one surgery. Patients with a raised initial total white (TW) cell count of > 20 × 109/L had a significantly higher risk of secondary surgery. (Adjusted hazard ratio 2.42, p < 0.05) A decline of CRP level of less than 20% within 24h from initial operation was also a risk for secondary surgery. (Adjusted hazard ratio 0.34, p < 0.01) Patients in group II also had significantly higher post-operative median TW cell count and neutrophil count. There was no significant difference in the offending microbe, surgical approach, and duration of operation from initial presentation between the groups. Patients with septic arthritis of the native knee joint who present with raised initial total white cell count of > 20 × 109/L and decline of CRP level of less than 20% within 24h from initial operation are at higher risk of secondary operation. In these patients, more aggressive treatment strategies and appropriate counselling on the risks of repeated surgery are recommended. Level IV.

Early recognition and treatment of pre-VITT syndrome after adenoviral vector-based SARS-CoV-2 vaccination may prevent from thrombotic complications: review of published cases and clinical pathway.

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but highly morbid complication after adenoviral vector-based SARS-CoV-2 vaccination. The pre-VITT syndrome is defined as vaccine-induced immune thrombocytopenia without thrombosis typically presenting with new-onset headache. This review aims to identify at-risk patients before complications such as cerebral venous sinus thrombosis occur. We review previously published reports of 19 patients (median age 35 years, range 23–74; 16 females) who met the diagnostic criteria for a pre-VITT syndrome. Seven patients progressed to VITT, 12 patients did not. Patients who experienced VITT received delayed treatment. The median interval between the onset of headache and VITT-treatment (i.e. anticoagulation, immune globulins, or corticosteroids) was 5 days (range 1–8 days) compared with 2 days (0–5 days) in those without subsequent VITT (P = 0.033). The interval from onset of headache to anticoagulation was longer in patients with VITT (median 7 vs. 2 days; range 3–9 vs. 0–7 days; P = 0.01). Anticoagulation was safe in all patients with a pre-VITT syndrome as no haemorrhagic complications occurred after anticoagulation was started despite low platelets. The transient decline of platelet count after admission was significantly more pronounced in patients who progressed to VITT (median 67 vs. 0 × 103/µL; range 0–77 × 103/µL vs. 0–10 × 103/µL; P = 0.005). d-dimers did not differ between groups. Pre-VITT syndrome is a ‘red flag’ and allows to identify and preemptively treat patients at-risk of further progression to VITT. However, it must be distinguished from post-vaccination immune thrombocytopenia.

Harmful Consequences of Proton Pump Inhibitors on Male Fertility: An Evidence from Subchronic Toxicity Study of Esomeprazole and Lansoprazole in Wistar Rats.

Proton pump inhibitors (PPIs) are frequently prescribed as gastric acid-suppressing agents. Nevertheless, there is limited evidence supporting the risk of detrimental effects of PPIs on male fertility. The purpose of the current study was to evaluate the effect of subchronic use of proton pump inhibitors on male fertility. Seventy adult male Wistar rats were assigned into seven groups. The normal control group orally received solvent only. Groups 2, 3, and 4 were orally given esomeprazole while groups 5, 6, and 7 received lansoprazole at 2.5, 5, and 10 mg/kg/day, respectively. After 45 days of treatment, blood samples, epididymis, and testis were collected. Sperm count, motility, and morphology were determined. The level of hormones such as testosterone, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) and oxidative status of testis tissue, such as superoxide dismutase, catalase, reduced glutathione, malondialdehyde (MDA), and nitric oxide (NO) were estimated. Results demonstrated a significant decline in sperm count, motility, morphology, testosterone, and catalase at 10 mg/kg/day and GSH at 2.5 mg/kg/day. A significant increase in FSH, LH, and MDA at 10 mg/kg/day and NO at 2.5 mg/kg/day was found as compared to the control group. The pathological alterations specifically dilation of Leydig cells, vacuolization, and degeneration of the seminiferous tubules were also evident. It is concluded that PPIs had caused male reproductive toxicity in Wistar rats due to altered levels of hormones such as testosterone, FSH, and LH, elevated levels of NO, and oxidative stress.

Characterization of coagulopathy and outcomes in cancer patients with severe COVID ‐19 illness: Longitudinal changes in hospitalized cancer patients

There is a lack of data focused on the specific coagulopathic derangements in COVID‐19 versus non‐COVID‐19 acutely ill cancer patients. Our objective was to characterize features of coagulopathy in cancer patients with active COVID‐19 illness who required hospitalization at MD Anderson in the Texas Medical Center and to correlate those features with thrombotic complications, critical illness, and mortality within the first 30 days after hospital admission for COVID‐19 illness. COVID‐19 and non‐COVID‐19 hospitalized cancer patients, with at least five consecutive measures of PT, PTT, d‐dimer, and CBC during the same period, were matched 1:1 to perform a retrospective analysis. We reviewed complete blood cell counts with differential, PT, PTT, fibrinogen, D‐Dimer, serum ferritin, IL‐6, CRP, and peripheral blood smears. Clinical outcomes were thrombosis, mechanical ventilation, critical illness, and death. Compared with matched hospitalized cancer patients without COVID‐19, we found elevated neutrophil and lower lymphocyte counts in those with critical illness ( p = 0.00) or death ( p = 0.00); only neutrophils correlated with thrombosis. COVID‐19 cancer patients with a platelet count decline during the hospital stay had more frequent critical illness ( p = 0.00) and fatal outcomes ( p = 0.00). Of the inflammatory markers, interleukin‐6 showed consistently higher levels in the COVID‐19 patients with poor outcomes. The findings of unique platelet changes and coagulopathy during severe COVID‐19 illness in the cancer population are of interest to explore disease mechanisms and future risk stratification strategies to help with the management of cancer patients with COVID‐19.

Effect of Vupanorsen on Non-High-Density Lipoprotein Cholesterol Levels in Statin-Treated Patients With Elevated Cholesterol: TRANSLATE-TIMI 70.

Background:Genetic loss-of-function variants in ANGPTL3 are associated with lower levels of plasma lipids. Vupanorsen is a hepatically targeted antisense oligonucleotide that inhibits Angiopoietin-like 3 (ANGPTL3) protein synthesis.Methods:Adults with non–high-density lipoprotein cholesterol (non-HDL-C) ≥100 mg/dL and triglycerides 150 to 500 mg/dL on statin therapy were randomized in a double-blind fashion to placebo or 1 of 7 vupanorsen dose regimens (80, 120, or 160 mg SC every 4 weeks, or 60, 80, 120, or 160 mg SC every 2 weeks). The primary end point was placebo-adjusted percentage change from baseline in non–HDL-C at 24 weeks. Secondary end points included placebo-adjusted percentage changes from baseline in triglycerides, low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (ApoB), and ANGPTL3.Results:Two hundred eighty-six subjects were randomized: 44 to placebo and 242 to vupanorsen. The median age was 64 (interquartile range, 58–69) years, 44% were female, the median non–HDL-C was 132.4 (interquartile range, 118.0–154.1) mg/dL, and the median triglycerides were 216.2 (interquartile range, 181.4–270.4) mg/dL. Vupanorsen resulted in significant decreases from baseline over placebo in non–HDL-C ranging from 22.0% in the 60 mg every 2 weeks arm to 27.7% in the 80 mg every 2 weeks arm (all P<0.001 for all doses). There were dose-dependent reductions in triglycerides that ranged from 41.3% to 56.8% (all P<0.001). The effects on LDL-C and ApoB were more modest (7.9%–16.0% and 6.0%–15.1%, respectively) and without a clear dose-response relationship‚ and only the higher reductions achieved statistical significance. ANGPTL3 levels were decreased in a dose-dependent manner by 69.9% to 95.2% (all P<0.001). There were no confirmed instances of significant decline in renal function or platelet count with vupanorsen. Injection site reactions and >3× elevations of alanine aminotransferase or aspartate aminotransferase were more common at higher total monthly doses (up to 33.3% and 44.4%, respectively), and there was a dose-dependent increase in hepatic fat fraction (up to 76%).Conclusions:Vupanorsen administered at monthly equivalent doses from 80 to 320 mg significantly reduced non–HDL-C and additional lipid parameters. Injection site reactions and liver enzyme elevations were more frequent at higher doses, and there was a dose-dependent increase in hepatic fat fraction.Registration:URL: https://clinicaltrials.gov; Unique identifier: NCT04516291.

Telomere-length dependent T-cell clonal expansion: A model linking ageing to COVID-19 T-cell lymphopenia and mortality.

SummaryBackgroundSevere COVID-19 T-cell lymphopenia is more common among older adults and entails poor prognosis. Offsetting the decline in T-cell count during COVID-19 demands fast and massive T-cell clonal expansion, which is telomere length (TL)-dependent.MethodsWe developed a model of TL-dependent T-cell clonal expansion capacity with age and virtually examined the relation of T-cell clonal expansion with COVID-19 mortality in the general population.FindingsThe model shows that an individual with average hematopoietic cell TL (HCTL) at age twenty years maintains maximal T-cell clonal expansion capacity until the 6th decade of life when this capacity rapidly declines by more than 90% over the next ten years. The collapse in the T-cell clonal expansion capacity coincides with the steep increase in COVID-19 mortality with age.InterpretationShort HCTL might increase vulnerability of many older adults, and some younger individuals with inherently short HCTL, to COVID-19 T-cell lymphopenia and severe disease.FundingA full list of funding bodies that contributed to this study can be found in the Acknowledgements section.

Distinctive pattern of neutrophil count change in clozapine-associated, life-threatening agranulocytosis

The wider use of clozapine is limited by the risk of agranulocytosis and the associated requirement for monitoring of neutrophil counts. We searched local electronic patient records for cases of agranulocytosis occurring during clozapine treatment during the period 2007–2020. We found 23 episodes recorded as agranulocytosis in clozapine patients. Of these, nine met pre-defined criteria and were considered episodes of life-threatening agranulocytosis (LTA). These episodes of clozapine-induced LTA exhibited a distinct pattern of continuous and rapid neutrophil count decline to zero or near zero. Mean time for neutrophils to fall from ANC > 2 to ANC <0.5 × 109/L was 8.4 days (range 2–15 days). Each event was also characterised by a prolonged nadir and delayed recovery (range 4–16 days). Non-LTA episodes were, in contrast, brief and benign. We conclude that an important proportion of cases of agranulocytosis identified in people prescribed clozapine are not life-threatening and may not even be clozapine-related. Monitoring schemes should aim to identify true clozapine-induced LTA as opposed to threshold-defined nominal agranulocytosis. Genetics studies might benefit from examining associations with clozapine-induced LTA rather than with recorded cases of agranulocytosis or neutropenia.

Infection with HIV-1 subtype D among acutely infected Ugandans is associated with higher median concentration of cytokines compared to subtype A

ObjectiveThe observation that HIV-1 subtype D progresses faster to disease than subtype A prompted us to examine cytokine levels early after infection within the predominant viral subtypes that circulate in Uganda and address the following research questions: (1) Do cytokine levels vary between subtypes A1 and D? (2) Do cytokine profiles correlate with disease outcomes? MethodsTo address these questions, HIV-1 subtypes were determined by population sequencing of the HIV-1 pol gene and 37 plasma cytokine concentrations were evaluated using V-Plex kits on Meso Scale Discovery platform in 65 recent sero-converters. ResultsHIV-1 subtype D (pol) infections exhibited significantly higher median plasma concentrations of IL-5, IL-16, IL-1α, IL-7, IL-17A, CCL11 (Eotaxin-1), CXCL10 (IP-10), CCL13 (MCP-4) and VEGF-D compared to subtype A1 (pol) infections. We also found that IL-12/23p40 and IL-1α were associated with faster CD4+T cell count decline, while bFGF was associated with maintenance of CD4+ counts above 350 cells/microliter. ConclusionOur results suggest that increased production of cytokines in early HIV infection may trigger a disruption of the immune environment and contribute to pathogenic mechanisms underlying the accelerated disease progression seen in individuals infected with HIV-1 subtype D in Uganda.

Relationship between eosinophils counts and muscle mass decline in older people with type 2 diabetes: A prospective study of the KAMOGAWA-DM cohort.

Sarcopenia has become an important issue in older individuals with type 2 diabetes. However, no previous studies investigated the relationship between eosinophil count and muscle mass decline. In this prospective cohort study, we aimed to investigate this relationship in older people with type 2 diabetes. Impedance body composition was used to assess body composition and skeletal muscle mass index (SMI, kg/m2) was calculated as appendicular muscle mass (kg)/height squared (m2). The decrease in SMI (kg/m2 per year) was calculated as (baseline SMI [kg/m2] - follow-up SMI [kg/m2]) divided by the follow-up period (years). The rate of SMI decrease (%) was calculated as follows: (decrease in SMI [kg/m2 per year] ÷ baseline SMI [kg/m2])×100; muscle mass decline was defined as the rate of SMI decrease of ≥0.5%. Complete blood counts, including eosinophil counts, were also measured. Among 141 participants, 54.6% experienced muscle mass decline during mean (standard deviation)19.4 (7.3) months of follow-up. The eosinophil counts of participants with muscle mass decline were higher than those of participants without muscle mass decline (216.5 [147.8] vs. 158.6 [113.1] cells/mm3, p=0.004). Eosinophil counts were negatively associated with the rate of SMI decrease according to Spearman's rank correlation coefficient (r=0.182, p=0.031). According to logistic regression analyses, there was the relationship between eosinophil counts and incident muscle mass decline after adjusting for covariates (odds ratio of Δ 1 incremental of logarithm (eosinophil counts) 2.04 (95% confidence interval 1.15-3.61, p=0.011). This study showed that eosinophil counts are associated with incident muscle mass decline. If an individual with type 2 diabetes has high eosinophil counts in blood tests, then it is necessary to pay more attention to the possibility of progression of muscle atrophy.

Evaluation of haematological and behavioural changes in Channa punctatus (Bloch) on short-term exposure to a commercial-grade synthetic pyrethroid pesticide

This study aims to assess the acute toxicity of commercial-grade Cypermethrin (10% EC) and evaluate the hematological and behavioral alterations in a freshwater fish Channa punctatus upon short-term exposure to Cypermethrin. A four-day static acute toxicity test was performed to estimate the median lethal concentration (LC50) value of Cypermethrin. During the acute toxicity test, the behavior of the control and cypermethrin exposed fish was critically observed and recorded. After completing the acute toxicity test, the hematological effects of Cypermethrin in C. punctatus were evaluated using two sublethal dosages (0.08 mg/L and 0.12 mg/L). Results of the study revealed that this pesticide induced significant mortality in C. punctatus with a 96-h L50 value of 0.263 mg/L. Cypermethrin exposed fish showed hyperactivity, irritability, erratic swimming, frequent surface visit, etc. Exposure to sublethal concentrations of Cypermethrin for a short period resulted in a significant decline (P&lt;0.05) in total erythrocytes count (TEC), packed cell volume (PCV), mean corpuscular volume (MCV), and hemoglobin (Hb) concentration as compared to control groups. In contrast, pesticide-exposed groups had a significant increase (P&lt;0.05) in mean corpuscular hemoglobin concentration (MCHC) and total leucocyte count (TLC). It is apparent from the results of the study that this commercial formulation is toxic to the studied fish. This study also revealed hematological and behavioral alterations in C. Punctatus which could be used as biomarkers for incipient Cypermethrin intoxication.

Impact of extracorporeal photopheresis on blood and coagulation parameters.

Extracorporeal photopheresis (ECP) is considered a safe treatment modality. We aimed to assess blood parameters including coagulation during ECP over time. We performed a long-term retrospective single-center chart review (laboratory parameters) of adult patients (n= 172) who had received ECP for any indication. We observed a significant decrease (p< 0.05) in erythrocytes, hemoglobin, and leukocytes compared to baseline levels after only one ECP procedure. This decrease persisted after 3-, 6-, 9-, and 12-months of ECP. A significant pathological decline of hemoglobin was observed in a higher proportion (26.4% and 25.2%, respectively) of patients after 6 (p= 0.0007) and 12 (p= 0.012) months of ECP. Mean corpuscular volume as well as hematocrit was significantly decreased at 3-, 6-, 9-, and 12-months of evaluation compared to baseline (p< 0.05). After 9 and 12 months of ECP we observed a further decline in lymphocyte counts (p< 0.05). Various coagulation parameters did not change significantly during ECP treatment. Even though not all alterations observed in peripheral blood of ECP patients in the present study were of clinical significance, risk for developing persistent anemia must be considered in patients undergoing ECP.

Coagulopathy complicating intraoperative blood salvage in patients receiving cesarean section: three case reports and a literature review

Background: Intraoperative cell salvage (ICS) has been used in more than 1100 published obstetrics cases and can reduce the need for allogeneic transfusion effectively. However, ICS could lead to a life-threatening coagulopathy called salvaged blood syndrome (SBS). SBS was reported in several non-obstetric cases but has rarely been reported in obstetric patients. Cases: We reviewed all 841 cell savage cases that occurred in our hospital prior to October 2018. Here, we present 3 cases of coagulopathy in patients who received ICS after cesarean section. The rate of obstetrical SBS in our hospital was 0.46%. Dicussion: Cesarean section was performed without severe hemorrhage, and we performed the surgical hemostatic procedures as usual. Then, several hours after the surgery and after ICS, bleeding occurred, in which hypofibrinogenemia was more severe than expected based on the amount of postpartum hemorrhage. In addition, other marked changes in coagulation function-related parameters, including a decline in the platelet count and obvious prolongation of the PT and aPTT levels, were also observed. More specific and in-depth studies concerning obstetric SBS are needed.

Effects of Rosemary Oil (Rosmarinus officinalis) supplementation on the fate of the transplanted human olfactory bulb neural stem cells against ibotenic acid-induced neurotoxicity (Alzheimer model) in rat.

Rosemary oil (ROO) is known to have multiple pharmacological effects: it is an antioxidant, anti-inflammatory, and cytoprotective. In the present study, we examined the effects of ROO on Human olfactory bulb neuronal stem cells (hOBNSCs) after their transplantation into rats, with the ibotenic (IBO) acid-induced cognitive deficit model. After 7weeks, cognitive functions were assessed using the Morris water maze (MWM). After two months blood and hippocampus samples were collected for biochemical, gene expression, and histomorphometric analyses. Learning ability and memory function were significantly enhanced (P < 0.05) after hOBNSCs transplantation and were nearly returned to normal in the treated group. The IBO acid injection was associated with a significant decline (P < 0.05) of total leukocyte count (TLC) and a significant increase (P < 0.05) in total and toxic neutrophils. As well, the level of IL-1β, TNF-α CRP in serum and levels of MDA and NO in hippocampus tissue were significantly elevated (P < 0.05), while antioxidant markers (CAT, GSH, and SOD) were reduced (P < 0.05) in treated tissue compared to controls. The administration of ROO before or with cell transplantation attenuated all these parameters. In particular, the level of NO nearly returned to normal when rosemary was administrated before cell transplantation. Gene expression analysis revealed the potential protective effect of ROO and hOBNSCs via down-expression of R-βAmyl and R- CAS 3 and R-GFAP genes. The improvement in the histological organization of the hippocampus was detected after the hOBNSCs transplantation especially in h/ROO/hOBNSCs group.

This Month in Anesthesiology

This Month in Anesthesiology

South African winter rainfall zone shifts: A comparison of seasonality metrics for Cape Town from 1841–1899 and 1933–2020

Mounting evidence across South Africa’s southwestern winter rainfall zone (WRZ) reflects consistent drying since ~ 1980, and projected trends suggest this will continue. However, limited evidence exists for changes in the region’s rainfall seasonality. To improve our understanding of these WRZ drying trends, especially within the context of Cape Town’s 2015–2017 “Day Zero” drought, it is necessary to explore long-term rainfall seasonality trends. Thus, we use the longest WRZ meteorological record from the South African Astronomical Observatory (SAAO) in Cape Town to investigate rainfall seasonality shifts during 1841–2020. Consistent with recorded poleward migrations of the subtropical high-pressure belt and mid-latitude westerlies, known drivers behind the drought and drying trends, calculated trends demonstrate strengthening of WRZ conditions, primarily from a later start-date trend leading to a shorter wet-season. Long-term drying trends are quantified for the wet and dry seasons; however, analysis of trend evolution reveals much variability, reflecting that drying has only persisted since ~ 1892. Comparative analyses of the first and last 59 years of 1841–2020 reveal a rainfall decline of almost 10% across both seasons—highlighting that the extreme “Day Zero” drought was not only driven by wet-season rainfall declines. Results demonstrate that these drying trends were consistently driven by a long-term decline in rain day counts and a more recent decline in average rainfall per rain day. Correspondence between our results and projected rainfall seasonality trends suggests the trends we quantified will likely continue; thus, improvements and continuation of existing water conservation and management strategies are imperative for Cape Town.

Sperm Quality Parameters and Oxidative Stress: Exploring Correlation in Fluoride-Intoxicated Rats.

Assessment of male fertility needs evaluation of sperm quality parameters, namely sperm count, viability, motility and morphology. The present study aimed to analyse and correlate oxidative stress with sperm quality parameters. The male Wistar albino rats, weighing between 100 and 150 g, were employed in the present study under the Committee for the Purpose of Control and Supervision of Experiments on Animals guidelines with ethical clearance from the Institutional Ethical Committee. These rats were categorised into four groups with six rats in each as control and test animals. Young male Wistar albino rats, weighing between 100 and 150 g, were divided into four groups of six rats each. The first group of rats served as control (n = 6) and was maintained under normal laboratory condition and was provided with clean drinking water, whereas rats in the second (n = 6), third (n = 6) and fourth (n = 6) groups were orally intubated with sodium fluoride of 100 ppm, 200 ppm and 300 ppm, respectively, for 40 days. After the treatment period of 40 days, animals were sacrificed and alterations in sperm quality parameters were analysed by complete randomised design SAS 9.4 and Statistical Package for the Social Sciences (SPSS) IBM 17 and judged significant if P < 0.05. In the experiment, a negative correlation emerged between sperm motility, viability, count versus malondialdehyde (MDA) levels, whereas the level of MDA has a positive correlation with sperm abnormalities. Sperm motility, viability and count were positively correlated with activities of superoxide dismutase and catalase, whereas decreased activities of antioxidants were related to increased sperm morphological abnormalities. These results suggest that MDA causes a decline in sperm motility, count and viability and an increase in morphological abnormalities via oxidative damage of membrane lipids.

Impact of Multi-metal Mixture Administration Through Drinking Water on the Gut Bacterial Microflora and Oxidative Stress Parameters in Male and Female Mice

Background: Heavy metal containing wastes reaches to the food chain either directly or indirectly. These ingested toxic elements manifest direct impact on the gut ecosystem and its overall functioning. The present study explores the alteration in mice gut bacteria on exposure to mixture of toxic heavy metals through drinking water. Methods: Twelve experimental groups of Swiss albino male and female mice were exposed to the metal mixture of varying concentrations. Profiling of gut bacterial flora was done by periodical collection of fecal samples via culture-based technique. Redox status of all experimental animals was analyzed in blood samples collected on the day 30. Results: In comparison to the controls, nearly a 10-fold decline in colony forming units/ml was observed at higher modal concentrations (50× &amp; 100×) at the end of 15 days, but 100-fold reduced bacterial count was recorded following 30 days of dosing. Sex specific significant alteration in the bacteria count and diversity was also observed. Overall experimental results showed a heavy metal dose-dependent decline in bacterial count and loss in diversity. Disturbance in the oxidative stress markers was recorded in response to high dose of metal mixture. In group receiving 100× dose, malondialdehyde levels were increased in the erythrocytes (P&lt;0.05), and all of the other antioxidant parameters were decreased (P&lt;0.05), except for reduced glutathione in both male and female mice. Conclusion: The present work is the first report on the multiple heavy metals induced gut microbiota alterations and its correlation to oxidative stress.