Significant Decrease In Frequency Research Articles

Numerical simulation of droplet formation in a Co-flow microchannel capillary device

In this article, a numerical simulation of the droplet formation in a Co-flow microchannel capillary device, and the influencing factors of the formation of droplets are studied. The level set method is used to track the two-phase interface and droplet formation. In the Co-flow focusing device, we explored the influencing factors of the size of the generated droplets. In the Co-flow focusing device, we explored the influences of various factors on the droplet size, generation frequency, and the droplet pressure at the centerline. The results demonstrate that an increased ratio of dispersed phase velocity to continuous phase velocity leads to a significant increase in the volume of generated droplets, a significant decrease in droplet generation frequency, and a significant decrease in droplet pressure at the centerline. Furthermore, as the viscosity of continuous phase increases, the volume of generated droplets decreases significantly, the frequency of droplet generation increases significantly, and the pressure of droplets at the centerline decreases significantly. Additionally, an elevated contact angle between the continuous phase and the wall results in a slight increase in the volume of generated droplets, alongside a reduction in droplet generation frequency and a decrease in droplet pressure at the centerline. Moreover, with the increase in interfacial tension, there is a significant increase in the volume of droplet generation, a significant decrease in the frequency of droplet generation, and a significant increase in the pressure of droplets at the centerline.

Divergent Immediate and Delayed Effects of Juvenile Exposure to Doxorubicin on the Thymus in C57BL/6 Mice.

The understanding of alterations within the immune system following doxorubicin (DOX) chemotherapy, and subsequent restoration, in childhood cancer survivors remains limited. This investigation endeavors to elucidate the immediate and delayed changes in thymic immune cell populations and their phenotypes in response to clinically relevant low doses of DOX in a juvenile mouse model. Male mice underwent a regimen of repeated low-dose DOX intraperitoneal injections at 4 mg/kg/week for three consecutive weeks. One week after the last dose of DOX, a subset of mice was euthanized to assess the immediate effects of DOX administration. A second subset of mice was euthanized five weeks after the last DOX dose to evaluate the delayed effects. Thymic samples were collected for multiparameter flow cytometry analysis to evaluate alterations in immune cell composition and phenotype. Additionally, quantitative real-time polymerase chain reaction (qRT-PCR) was employed to measure gene expression of- cytokines and senescence markers. One week following DOX administration, DOX treatment resulted in significant decline in thymus weight, with notable alterations in immune cell subpopulations. Reduced frequencies of mature CD3+CD4+ and CD3+CD8+ T cells were observed, along with changes in proliferation and exhaustion markers. Gene expression analysis revealed upregulation of Foxn, Pax1, Ifnγ, and Il7 alongside decreased Il6 and Il17 expression. Furthermore, Cdkn1a (p21Cip1) expression was elevated, suggesting immunosenescence. Five weeks following DOX administration, delayed effects of DOX treatment manifested in rebound increase in thymus weight and altered frequencies of CD4+ and CD8+ T cell subsets, with distinct patterns of proliferation and exhaustion observed. Notably, central memory CD4+ T cells exhibited significant decrease in frequency, while naive and effector memory CD4+ T cells showed reduced proliferation (Ki67+) and PD1 expression. Similar trends were observed in CD8+ T cell subsets, indicating selective effects of DOX on T cell differentiation and function. Although expression of thymus-related genes was normalized, p21Cip1 gene expression remained elevated. DOX treatment elicits a multifaceted influence on immune cell subsets and thymic weight. Immediate effects included thymic atrophy and reductions in mature T cell populations, while delayed effects showed rebound thymic hyperplasia and selective changes in CD4+ and CD8+ T cell subsets. Notably, both central memory and effector memory T cells exhibited reduced proliferation and exhaustion, suggesting unique impacts of DOX on immune cell function. The enduring elevation in p21Cip1 gene expression 5 weeks after DOX treatment suggests an immunosenescent phenotype. These observations collectively illuminate the formidable task of preserving immune competence and overall well-being in childhood cancer survivors subjected to DOX therapy.

Association Between HLA-DRB1 Alleles and Graves' Disease in Asian Populations: A Meta-Analysis.

Graves' disease (GD) is an autoimmune disease that primarily affects the thyroid gland. It is the most common cause of hyperthyroidism. Genetic studies have shown that human leukocyte antigen (HLA) plays an important role in the development of GD. In this article, we performed a meta-analysis determined to evaluate the relationship between HLA-DRB1 alleles and GD. This meta-analysis included 9 studies (3582 cases in the case group and 23070 cases in the control group) and 27 alleles was performed. The combined results showed that, compared with the control group, GD patients have a significant increase in the frequency of DRB1*1403 (OR=2.50, 95% CI=1.78-3.51, pc<0.0001) and have a significant decrease in frequencies of DRB1* 0101 (OR=0.45, 95% CI=0.34-0.59, pc<0.0001) and DRB1*0701 (OR=0.44, 95% CI=0.35-0.55, pc<0.0001). The meta-analysis indicated that, in Asian populations, DRB1*1403 is a risk allele for GD, and DRB1*0101 and DRB1*0701 are protective against the occurrence of GD. We surprisingly discovered that the susceptibility alleles for GD in Asian populations are completely different from Caucasians and the protective alleles for GD in Asians are quite similar to those of Caucasians. The results of our study may provide new opportunities for gene-targeted therapy for GD in Asian populations.

(009) Sexual Function &amp; Sexual Satisfaction Differences Between Cisgender Women of Different Age Groups

Abstract Introduction As the average life expectancy increases, so does the need to improve older adults’ quality of life. Sexual function and satisfaction have been intimately tied to well-being, and older age has been associated with a decline in sexual activity, sexual function, and desire. However, there is limited research that focuses on the association between age and specific measurements of sexual function, such as orgasm parameters, frequency of sexual activity, and sexual satisfaction. Objective To describe and compare measures of sexual activity, orgasm quality, and satisfaction between women of different ages. Methods Respondents were recruited via Qualtrics and administered an anonymous online survey. Respondents were separated into groups based on age ranges: younger adults (&amp;lt;40 years old), middle-aged adults (40 to 59 years old), and older adults (≥60 years old). Additional demographic characteristics and sexuality measures were documented, including sexual orientation, partnership status at the time of survey, ability to orgasm, frequency of masturbation and sexual activity, and sexual satisfaction (as measured by the validated New Sexual Satisfaction Scale (NSSS)). An orgasm quality inventory queried the following six variables, under the control condition of masturbation: (1) time to orgasm; (2) duration of orgasm; (3) refractory period between orgasms; (4) experience of orgasm as a single or multi-peak event; (5) bodily location of orgasm experience; and (6) satisfaction with orgasm quality. Results A total of 423 sexually active cisgender women (average age ± standard deviation: 48.9 ± 15.6 years old) completed our survey. Older women were significantly more likely to identify as heterosexual and deny dating or being in a current relationship (both p&amp;lt;0.001). Additionally, older women were significantly more likely to deny masturbation and sexual activity with a partner (p&amp;lt;0.001). There was no statistically significant difference in ability to achieve orgasm between age groups (p=0.5). With respect to orgasm parameters (Table 1), younger women reported a significantly lower refractory period between orgasms, as compared to middle-aged and older women. Compared to other age groups, significantly more older women reported their orgasm as a multi-peak event (p&amp;lt;0.04) and were more likely to report the location of orgasm sensation as occurring in their genitals, as opposed to extragenital areas (e.g., arms, thighs, face, back) or whole body (p&amp;lt;0.01). There were no statistically significant differences between age and lead time to orgasm, duration of orgasm, or satisfaction with orgasm. Differences in sexual satisfaction (as measured by the NSSS, with higher scores indicating greater sexual satisfaction) were found to be statistically insignificant as well. Conclusions While older women reported a significant decrease in frequency of masturbation and sexual activity, they only differed in three out of six measures in our orgasm inventory. While these measures indicate a difference in older women’s experience of orgasm, it is important to note that there were no significant differences across multiple measures of sexual satisfaction between women of different ages. Disclosure No.

Individualized Parent-Mediated Behavioral Treatment for Challenging Behavior: A Program Description.

Past research suggests behavioral treatments are effective for challenging behavior in children and young adults with neurodevelopmental disorders, such as autism spectrum disorder (ASD). However, access to these services can be limited and require substantial resources. To address this issue, the current study provides a programmatic description of an individualized parent-mediated service model targeting moderate challenging behavior. In the program, therapists coached parents to implement functional analyses and individualized function-based treatment packages. Forty-one families of children and young adults with neurodevelopmental disorders participated. Most clients (75.6%) met all admission treatment goals and parents reported significant decreases in frequency and severity of challenging behaviors at discharge. Parents also reported less stress at discharge. Outcomes of the study suggest this parent-mediated treatment model is a viable option to treating moderate challenging behavior in children and young adults with intellectual and developmental disorders.

Effect of zinc supplement on duration of acute watery diarrhea from 6 months to 5 year aged children.

Objective: To determine the effect of Zinc supplement on duration of acute watery diarrhea from 6 months to 5 year aged children. Study Design: Randomized Controlled Trial. Setting: Pediatric Unit, Mardan Medical Complex, Mardan, Pakistan. Period: 1st July 2022 to 31st December 2022. Material &amp; Methods: A total of 100 children aged from 6 months to 5 years presenting with acute watery diarrhea were included in the study. Patients were divided into 2 equal groups. In Group-A patients were given oral Zinc supplement at a dose of 20mg daily while in Group-B children were not given oral zinc supplement. Follow up visit was set on day 3 after start of treatment. Primary outcome was set as frequency of diarrheal episodes during 24 hours while the secondary outcome was character of stool. Results: The Mean±SD of age in this study was 13.51±6.27 months with an age range of 6-30 months. The ratio of male gender was higher than female (59% Vs 41%). Clinical outcomes showed a significant decrease in frequency of diarrheal episodes (3.88±1.11 vs 4.58±1.03, p=0.001) and in number of children with watery stool (42% vs 70%, p=0.05) in Group-A compared to group-B. Number of children recovering from diarrhea was higher in group-A compared to group-B (14% vs 2%, p=0.026). Conclusion: Zinc supplement significantly reduces frequency of diarrheal episodes and improves character of stool in children with acute watery diarrhea aged from 6 months to 5 year.

Treatment of refractory hematospermia with Finasteride: A prospective placebo-controlled study

Background: Finasteride is being used to treat recurrent hematuria due to BPH. Androgen has an essential role in the production of angiogenic factors such as VEGF. Vessel density &amp; VEGF decreases after finasteride treatment and thus improve haematospermia. Objective: To test the efficacy of finasteride to control refractory idiopathic hematospermia for which conservative treatment has failed. Methodology: This Prospective placebo-controlled study was carried out from July 2019 to June 2022 with 48 patients of hematospermia presented to the outpatient department of NIKDU. Twenty-two patients had refractory hematospermia of idiopathic nature. They were randomized into two equal groups, 11 patients in each group. One group received 5 mg finasteride daily for 3 months, and the other group received placebo. Patients were followed up with semen analysis and TRUS for 3 consecutive months and after 1 year. Result: In the finasteride-treated group, remission of hematospermia occurred in 5 patients (45%) within 1 month. Patients continued treatment for 3 months without the recurrence of hematospermia. After stopping finasteride treatment, hematospermia recurred in 3 out of 9 patients 12 months later. Two cases were not improved, but a significant decrease in frequency &amp; amount of bleeding was observed in semen analysis. In the placebo-treated group, cessation of hematospermia occurred in 3 cases (27%) versus 9 (81%) in the finasteride group (P = 0.03) after 3 months of treatment. Conclusion: Three months of treatment with finasteride for refractory idiopathic hematospermia significantly cures hematospermia with no undesirable side effects. Bangladesh J. Urol. 2022; 25(1): 33-66

Evaluation of Smectite Effect as a Food Thickener in Gastroesophageal Reflux Disease in Neonates Using Combined Esophageal Multichannel Intraluminal Impedance

Introduction Gastroesophageal reflux disease (GERD) occurs when reflux of the gastric contents causes symptoms, MII-pH offer several advantages over the traditional diagnostic measures as it detects reflux regardless of its pH and distinguishes swallows from GER. Thickening of infant formulas has been recommended for the treatment of GERD. Agents that have been used include cereal, rice, bean gum, sodium carboxymethyl cellulose, pectin, cellulose and carobel. We aimed to assess the efficacy of (Smectite) as a food thickener in treating GERD in neonates using MII-pH before and after Smectite. Patients and Methods Twenty preterm neonates ≤ 36 weeks of age from maternity hospital, Ain Shams University, enrolled during the period 2018 to 2020, all had signs suggestive of GERD, Feeding intolerance, and repeated chest infections due to frequent apneas, aspiration or associated with bronchopulmonary dysplasia as well as nonspecific behavioral signs including arching, irritability, and apparent discomfort associated with feedings, GERD was confirmed by MII-pH for 24hrs. Diagnosis of reflux was done by total number of liquid and mixed Reflux &amp;gt; 100 as per (1) López-Alonso et al., 2006. patients then were prescribed Smectite (3 g/day for 7 days). On the 8th day, a second 24-hour MII-pH was performed to assess the response. Results Preterm infants with more than 100 impedance events were diagnosed with GERD most of these attacks were non acidic and weakly acidic attacks. Using Smectite as a food thickener was followed by a significant decrease in total reflux time and total frequency of reflux episodes (P. value &amp;lt;0.001), there was also a significant decrease in the frequency of impedance events per 24hrs. Total frequency of reflux episodes before and after Smectite decreased in terms of number of signs related to reflux before and after treatment such as vomiting, acute life threatening events like bradycardia, apnea, wheezy chest, desaturations all of which improved significantly after treatment. Conclusion MII-pH is one of the most sensitive tools for the diagnosis of reflux and Smectite could be used as a feed thickener to decrease reflux signs and symptoms for more studies on a larger scale to confirm.

Assessing spatiotemporal trends of total and extreme precipitation in a subtropical highland region: A climateperspective.

This study used a dataset of 30 years (1990-2020) of daily observations from 24 meteorological stations in the northern highlands of Pakistan to assess trends in extreme precipitation indices. The RClimDex model was used to analyze the indices, and the Modified Mann-Kendal test and the Theil-Sen slope estimator were applied to determine trends and slopes, respectively. The results showed a significant decrease in total annual precipitation amount (PRCPTOT) with varying rates of negative trend from -4.44 mm/year to -19.63 mm/year. The total winter and monsoon precipitation amounts were also decreased during the past three decades. The intensity-based precipitation indices (RX1Day, RX5Day, R95p, R99p, and SDII) showed a significant decrease in extreme intensity events over time, while the count of consecutive dry days (CDD) and consecutive wet days (CWD) indicated a significant decrease in duration at multiple stations. The annual counts of days with precipitation more than or equal to 10 mm (R10), 20 mm (R20), and 25 mm (R25) exhibited a significant decrease in frequency of extreme precipitation events, with the decrease more pronounced in the northern parts of the study domain. The findings of this study indicate a significant decline in the intensity, frequency, and extent of precipitation extremes across the northern highlands of Pakistan over the past 30 years.

Effects of Oral Cannabinoids on Systemic Inflammation and Viral Reservoir Markers in People with HIV on Antiretroviral Therapy: Results of the CTN PT028 Pilot Clinical Trial.

Chronic HIV infection is characterized by persistent inflammation despite antiretroviral therapy (ART). Cannabinoids may help reduce systemic inflammation in people with HIV (PWH). To assess the effects of oral cannabinoids during HIV, ten PWH on ART were randomized (n = 5/group) to increasing doses of oral Δ9-tetrahydrocannabinol (THC): cannabidiol (CBD) combination (2.5:2.5-15:15 mg/day) capsules or CBD-only (200-800 mg/day) capsules for 12 weeks. Blood specimens were collected prospectively 7-21 days prior to treatment initiation and at weeks 0 to 14. Plasma cytokine levels were determined via Luminex and ELISA. Immune cell subsets were characterized by flow cytometry. HIV DNA/RNA were measured in circulating CD4 T-cells and sperm by ultra-sensitive qPCR. Results from both arms were combined for statistical analysis. Plasma levels of IFN-γ, IL-1β, sTNFRII, and REG-3α were significantly reduced at the end of treatment (p ˂ 0.05). A significant decrease in frequencies of PD1+ memory CD4 T-cells, CD73+ regulatory CD4 T-cells, and M-DC8+ intermediate monocytes was also observed (p ˂ 0.05), along with a transient decrease in CD28-CD57+ senescent CD4 and CD8 T-cells. Ki-67+ CD4 T-cells, CCR2+ non-classical monocytes, and myeloid dendritic cells increased over time (p ˂ 0.05). There were no significant changes in other inflammatory markers or HIV DNA/RNA levels. These findings can guide future large clinical trials investigating cannabinoid anti-inflammatory properties.

Double Negative B cells are decreased in patients with Idiopathic Inflammatory Myopathies.

Abstract Background: Idiopathic inflammatory myopathies (IIM) are systemic autoimmune diseases characterized by skeletal muscle inflammation, frequently accompanied by extra muscular features associated with specific autoantibodies. The detailed pathogenesis of IIM remains unclear, but evidence suggests autoreactive B cells may play an essential role in this process. However, little is known about changes in peripheral blood B cell subsets in adult IIM patients. Objective: This study aims to determine the frequency of B cell subsets among patients with IIM and their clinical correlation with disease activity. Methods: Using a multiparametric flow cytometric approach, we determined the frequencies of B cell subsets in a cohort of 36 patients with IIM and correlated their values with clinical and laboratory data. Results: DN B cells (CD27 −IgD −), which represent an atypical B cell subset associated with various autoimmune diseases, showed a significant decrease in frequencies and a correlation with the MMT8 score. Within the DN subset, the DN1 subpopulation (CD21 +CD11c −) showed a significant decrease compared to the control group. There was also a significant decrease in the memory B cell subpopulation (CD27 +CD38 −) and the non-classic memory B cell subpopulation (CD27 −CD38 −CD24 +). A significant increase in naive B cells (CD27 −IgD +) was observed. However, none of the previously described subpopulations correlated with clinical features. Conclusion: This study demonstrated a decrease in frequencies in the double negative B cell subset in adult IIM patients and showed a correlation with clinical features, which suggests that these B cells could be related to disease activity. UNAM-DGAPA-PAPIIT IN212122

AGEs-RAGE-KCa3.1 pathway mediates palmitic acid-induced migration of PBMCs from patients with type 2 diabetes

Type 2 diabetes mellitus (T2DM) is characterized by chronic low-grade systemic inflammation. Tissue infiltration by monocyte migration contributes to the pathogenesis of vascular complications in T2DM. We studied the role of intermediate-conductance Ca2+-activated K+ (KCa3.1) channels in the palmitic acid (PA)-induced migration of peripheral blood mononuclear cells (PBMCs) from T2DM patients and the influence of advanced glycation endproducts (AGEs). A total of 49 T2DM patients and 33 healthy subjects was recruited into this study. Using flow cytometry and Western blotting analysis as well as cell migration assay, we found that there was a significant decrease in frequency of T lymphocytes and monocytes in CD45+ leukocyte population. PA at 100 μM stimulated migration of PBMCs from T2DM individuals, which was inhibited by the specific KCa3.1 channel blocker TRAM-34 (1 μM). The PBMC migration was positively correlated with glycosylated hemoglobin A1 chain (HbA1c) level of T2DM patients, an indicator of AGEs, and PBMCs with higher level of HbA1c showed upregulated expression of toll-like receptor (TLR) 2/4 and KCa3.1 channels. In THP-1 cells, AGEs at 200 μg/ml increased protein expression of TLR 2/4 and KCa3.1 channels, and were synergistically involved in PA-induced migration through receptors of AGEs (RAGE)-mediated KCa3.1 upregulation. In conclusion, in PBMCs of T2DM patients, AGEs promotes PA-induced migration via upregulation of TLR2/4 and KCa3.1 channels.

A novel artificial intelligence based algorithm to reduce wearable cardioverter-defibrillator alarms.

The wearable cardioverter defibrillator (WCD) is an important tool in mitigating sudden cardiac death (SCD). The WCD provides patient alarms for detected arrhythmias or electrical noise/artifact. Some patients experience frequent alarms for artifact. We soughtto evaluate the effects of a novel artificial intelligence algorithm to reduce alarms related to electrical noise or artifact (advanced arrhythmia discrimination algorithm, AArD). A retrospective review of a large commercial database of prescribed WCD. Patients prescribed the WCD during the years 2017 (discrimination algorithm, DA group) or during 2019 (advanced arrhythmia discrimination algorithm, AArD) were analyzed. A total of 96,000 patients were sampled, 48,000 in the control group (using standard direct algorithm, DA) and compared to 48,000 in the intervention AArD (4000 per group per month) for 12 months. The AArD further discriminates ECG signals based on a machine-learning algorithm utilizing intensity and frequency beyond the standard DA. Outcomes regarding alarms, arrhythmias, and safety were analyzed. The AArD algorithm was associated with a significant decrease in frequency of alarms over the course of WCD use; 54% of patients in the AARD versus 27% of DA had 0 alarms (P < .001). In the entire cohort, there was a 56% relative reduction in alarms with the use of AArD. Appropriate arrhythmia treatment time was not significantly different between the groups (44 s DA vs 45 s AArD [p = ns]). A novel artificial intelligence algorithm reduces alarms without delaying appropriate therapy for VT/VF. These changes may improve compliance and quality of life in patients with a WCD.

HIP FRACTURES IN THE OLDER ADULT: ORTHOPAEDIC AND GERIATRIC SHARED CARE MODEL IN SOUTHLAND: A FIVE-YEAR FOLLOW-UP AUDIT

Fractures of the neck of femur are common in the older adult with significant morbidity and mortality rates. This patient cohort is associated with frailty and multiple complex medical and social needs requiring a multidisciplinary team to provide optimal care. The aim of this study was to assess the outcomes at 5 years following implementation of a collaborative service between the Orthopaedic and Geriatric departments of Southland Hospital in 2012.Retrospective data was collected for patients aged 65 years and older who were admitted with a fragility hip fracture. Data was collated for 2011 (pre-implementation) and 2017 (post-implementation). Demographics and ASA scores were recorded. We assessed 30-day and 1-year mortality, surgical data, length of stay and complications.There were 74 patient admissions in 2011 and 107 in 2017. Mean age at surgery was 84.2 years in 2011 and 82.6 years in 2017 (p&gt;0.05). Between the 2011 and 2017 groups there has been a non-significant reduction in length of stay on the orthopaedic ward (9.8 days vs 7.5 days, p=0.138) but a significant reduction in length of stay on the rehabilitation ward (19.9 vs 9 days, p&lt;0.001). There was a significant decrease in frequency of patients with a complication (71.6% vs 57%, p=0.045) and a marginal reduction in number of complications (p=0.057). Through logistic regression controlling for age, sex and ASA score, there was a reduction in the odds of having a complication by 12% between 2011 and 2017 (p&lt;0.001). There was no difference in mortality between the groups.The orthogeriatric model of care at Southland Hospital appears to have reduced both the frequency of complications and length of stay on the rehabilitation ward 5 years after its implementation. This is the first study in New Zealand demonstrating medium-term post-implementation follow-up of what is currently a nationally accepted standard model of care.

Effect of β3-adrenoceptor agonist on the micromotion of bilateral major pelvic ganglion-excised rat bladder.

Micromotion is an autonomous intramural movement of the bladder, and is believed to be an initial step in the generation of urinary urgency. Therefore, controlling micromotion may be a novel target in overactive bladder (OAB) treatment. However, developing micromotion treatment has been limited by the absence of a standardized animal model. We attempted to create a micromotion animal model and investigated the effectiveness of a β3 -adrenoceptor agonist (CL316,243) on micromotion. Bilateral major pelvic ganglia (MPGs) were excised in 18 male Sprague-Dawley rats, resulting in an almost completely denervated bladder. On postoperative Day 7, cystometry was performed. Rats were divided into three treatment groups: CL316,243; β3- adrenoceptor antagonist (SR59230A) pretreated CL316,243; and a nonselective antimuscarinic agent (oxybutynin). Changes in micromotion were evaluated after the intra-arterial administration of each agent. Low-amplitude oscillations in intravesical pressure (micromotion) were observed 1 week after MPGs excision. Micromotion frequency significantly (p = 0.003) decreased (2.17 ± 3.54 times/5 min) with CL316,243 compared with vehicle (6.33 ± 1.97 times/5 min). Micromotion amplitude also decreased with CL316,243 (1.15 ± 1.93 cmH2 O) compared with vehicle (5.96 ± 5.12 cmH2 O), approaching conventional significance (p = 0.090). No significant decreases in frequency or amplitude were observed with oxybutynin treatment. Systemic administration of the β3 -adrenoceptor agonist CL316,243 effectively controlled micromotion in bilateral MPGs-excised, almost completely denervated rat bladders. This result indicates that β3 -adrenoceptor agonist may affect the bladder directly, suggesting that it might be effective for overall OAB, regardless of the presence or level of neurological deficits. Bilateral MPGs-excised rats are considered a plausible micromotion animal model suitable for future research.

Frequency of essential elements in required advanced pharmacy practice experiences (FEER - APPE)

IntroductionThis study evaluated student reported achievement of essential elements (EE) across three required advanced pharmacy practice experiences (APPEs) to identify differences in the frequency of each EE during different delivery modalities. MethodsAPPE students from three different programs were assigned a self-assessment EE inventory after required acute care, ambulatory care, and community pharmacy APPEs between May 2018 and December 2020. Using a four-point frequency scale, students reported exposure to and completion of each EE. Pooled data were analyzed to compare differences in frequencies of EE during standard and disrupted delivery. All standard delivery APPEs were in-person, but during the study period APPEs shifted to a disrupted delivery using hybrid and remote formats. Frequency changes were reported as combined data and compared between programs. ResultsA total of 2191 of 2259 (97%) evaluations were completed. Acute care APPEs had a statistically significant change in frequency of evidence-based medicine elements. Ambulatory care APPEs had a statistically significant decrease in the frequency of reported pharmacist patient care elements. Community pharmacy had a statistically significant decrease in frequency in each category of EE except practice management. Statistically significant differences between programs were observed for select EEs. ConclusionsThe frequency of EE completion during disrupted APPEs revealed minimal change. Acute care was the least impacted whereas community APPEs experienced the greatest change. This may be attributable to shifts in direct patient interactions during the disruption. Ambulatory care was impacted to a lesser degree, potentially due to utilization of telehealth communications.

ETV6 Represses TNF during Stress Hematopoiesis and Regulates HSC Self Renewal

INTRO: ETS Variant Transcription Factor 6 (ETV6), formerly known as Translocation ETS Leukemia (TEL), functions primarily as a transcriptional repressor and is highly expressed in mouse and human HSPCs where it is essential for the development and maintenance of adult hematopoiesis. Nevertheless, it has remained poorly understood how ETV6 regulates the HSC compartment. In 2015, our group and others identified heterozygous pathogenic germline ETV6 variants in families with autosomal dominant thrombocytopenia and predisposition to hematologic malignancies (most often B-acute lymphoblastic leukemia), a condition now known as thrombocytopenia 5 (T5). METHODS: To elucidate the mechanisms by which germline ETV6 variants impact hematopoiesis and promote leukemogenesis, we generated a knock-in mouse model harboring Etv6 R355X, the murine equivalent of a human T5-associated variant (R359X). We used complementary in vitro and in vivo assays to comprehensively characterize the numbers and functions of Etv6R355X/+ and Etv6+/+ hematopoietic progenitors. RESULTS:Etv6R355X/+ mice display several of the cardinal features of T5, including abnormally rounded platelets with increased area compared to platelets from wild-type Etv6+/+ littermates. Further, Etv6R355X/+ platelets exhibit significantly delayed and incomplete clot formation as measured through clot retraction assays. Together, these findings indicate that this novel model will serve as a viable means to study the human disease. We observe that 3-month-old Etv6R355X/+mice maintain normal frequencies and numbers of lineage-sca1+cKit+ (LSK) cells in the bone marrow (BM); however, at 12 months of age, they exhibit a significant decrease in frequency in this compartment. At each of these timepoints, there are variable shifts in the proportions and/or numbers of certain HSC subpopulations. To examine whether the Etv6R355X/+mutation impacts HSC function, we carried out in vitrosEtv6R355X/+BM cells generate more colonies than wild-type cells in the first two rounds of plating, but significantly fewer or no colonies by the fourth plating. Similarly, Etv6R355X/+LSK cells exhibit significantly impaired engraftment when challenged via competitive transplantation, with near complete failure to reconstitute irradiated recipients by the tertiary transplant. Etv6R355X/+LSKs home to the bone marrow comparably to Etv6+/+cells, indicating that homing does not account for the defect in repopulation capacity. To investigate how ETV6 functions in HSCs, we performed RNA-seq of Etv6R355X/+LSKs and flow cytometry-purified HSPC subpopulations from 12-month-old mice, which revealed upregulation of genes associated with an active stem cell phenotype, downregulation of genes supporting stem cell quiescence, and upregulated expression of Tnf with enrichment for the Hallmark TNFa Signaling via NFKB geneset. Subsequent experiments using CUT&RUN of Etv6+/+LSK cells revealed several known and novel ETV6 target genes, including Tnf, a cytokine implicated in regulating stress hematopoiesis. The sites bound by ETV6 at the Tnf locus aligned with ATAC-seq peaks generated from HPC5 cells, a mouse bone marrow progenitor cell line, suggesting that this is a region of open chromatin and active transcriptional regulation. Corroborating these findings, examination of Etv6R355X/+HSPCs at 6 weeks post-transplant revealed increased cell cycling and intracellular TNF production. CONCLUSION: From these studies, we conclude that ETV6 regulates HSC maintenance. Further, it binds to a regulatory sequence within the Tnf locus, whereby it represses TNF expression. The loss or reduction of this repression in Etv6R355X/+HSCs is associated with increased cell cycling under conditions of hematopoietic stress and a loss of self-renewal capacity. Studies are ongoing to determine how these changes promote leukemogenesis and contribute to the other features of T5.

Effect of bisphenol F on sexual performance and quality of offspring in Male Wistar rats.

This study investigated the effect of BPF on male sexual performance and the quality of the offspring. Eighty (80) Male Wistar rats (n=10 per group) were randomised into normal saline-treated control and control recovery, BPF varied doses (low, medium, and high), and BPF varied doses recovery (low, medium, and high) groups. The study was terminated after 28 days of BPF oral administration. The animals were sacrificed after 24h from the last dose, while those in the recovery groups were allowed to recover for another 28 days before being sacrificed. BPF administration was found to impair sexual performance, as shown by a significant decrease in frequencies (mount, intromission, and ejaculation frequencies) and an increase in latencies (mount, intromission, and ejaculation latencies). This was accompanied by a significant decrease in plasma LH, FSH, testosterone, dopamine, acetylcholinesterase, nitric oxide, and penile cyclic guanosine monophosphate (cGMP) level. The level of plasma oestrogen and prolactin were significantly increased following BPF administration. BPF also reduced the sperm count, morphology, viability, and motility. Furthermore, BPF reduced fertility success and index, litter size, litter weight, and offspring survival rate. These toxic effects of BPF were dose-dependent and were not reversed by withdrawal following 28 days of recovery. This study concluded that BPF disrupts sexual competence and offspring quality by suppressing the hypothalamic-pituitary-gonadal axis and mediating oestrogen-induced hyperprolactinemia. These events were associated with reduced fertility index and success, poor semen quality, and reduced offspring survival rate. The observed toxic effects of BPF were dose-dependent and not reversed by cessation of BPF exposure.

Analysis Of A Decade Of Healthy DiplomaTm Program Outcomes: Physical Dimension

The University of Indianapolis’ Healthy Diploma Program™ (HD) was created to engage undergraduate students (n = ~5100) in healthy behaviors during their college career. Available to all majors, the HD is based on 8 Dimensions of Wellness: physical, financial, social, environmental, occupational, spiritual, emotional, and intellectual. Every HD participant must (a) meet regularly with an assigned Wellness Coach and (b) participate in semi-annual assessments (e.g., physical fitness testing including number of push-ups, curl-ups, 1.5-mile run, flexibility, and strength). Each HD student reports physical activity behavior which includes (1) days per week engaged in moderate to strenuous physical activity and (2) minutes per session. PURPOSE: To describe the volume of physical activity and physical fitness results from semi-annual assessments from 2009 -2019 HD members in order to evaluate the effectiveness of the HD program. METHODS: Data from HD students (n = 123; 113 females, 10 males) from 2009-2019 was analyzed and included mean and standard deviations for all measures. Non-Parametric Kruskal-Wallis analysis was used to determine any significant differences in physical activity and fitness across time. RESULTS: Over the last 10 years, aerobic fitness estimated from 1.5-mile run (37.5 ml*kg-1*min-1) was stable and at the 50th percentile for age- and sex- specific normative data while flexibility averaged ~53 cm, handgrip strength 56.9 kg, curl up number 44 and number of push-ups 31. There were non-significant increases in body weight from 60 to 68 kg during this decade and decreases in push-up and curl up number. The mean frequency and duration of physical activity was 3.6 days*week-1 and 49.3 minutes*session-1, respectively. There was a statistically significant difference in physical activity frequency for all semesters: Fall 14 – Fall 19 (4.0, 3.9, 3.6, 3.8, 3.4, and 2.6 days/week, respectively) indicating less time spent in moderate to vigorous physical activity per week. CONCLUSION: Analysis of 10 years of HD data reveal non-significant increases in body weight and decreases in physical fitness along with significant decreases in frequency of physical activity. It appears that a more targeted intervention seems advisable in order to increase physical fitness during a student’s four-year career.

Protective Effects of Epigallocatechin Gallate for Male Sexual Dysfunction in Streptozotocin-Induced Diabetic Rats.

Sexual dysfunction is a common problem for men with diabetes. Epigallocatechin gallate (EGCG) is known to ameliorate erectile function in aging rats. However, there has not yet been a report to evaluate its effects on diabetic male rat sexual behavior in the literature. In this study, we investigated the effects of EGCG on male sexual behavior in diabetic rats. Diabetic rats were induced by a single intraperitoneal injection of 65 mg/kg of streptozotocin. After streptozotocin injection for one week, animals were then orally treated with 40 mg/kg of EGCG or vehicle. Copulatory behavior and fasting blood glucose levels were recorded before treatment, as well as 7 and 14 days after treatment. Serum LH, testosterone, and PDE5a levels were measured by EIA assay after the last behavioral test. Data showed that diabetic rats who had diminished sexual functions demonstrated significantly increased latencies in mount, intromission, and ejaculation, as well as significant decreases in frequencies of intromission and ejaculation, compared to non-diabetic controls, indicating sexual function recovery. Lower blood glucose levels were also found in diabetic rats after EGCG treatment. Additionally, the lower LH and higher PDE5a levels in diabetic rats than controls were also noted. The findings declared that EGCG had a protective effect on male sexual behavior in diabetic rats.