Female Age Research Articles

Gonadotropin elevation is ootoxic to ovulatory oocytes and inhibits oocyte maturation, and activin decoy receptor ActRIIB:Fc therapeutically restores maturation

BackgroundElevated FSH often occurs in women of advanced maternal age (AMA, age ≥ 35) and in infertility patients undergoing controlled ovarian stimulation (COS). There is controversy on whether high endogenous FSH contributes to infertility and whether high exogenous FSH adversely impacts patient pregnancy rates.MethodsThe senescence-accelerated mouse-prone-8 (SAMP8) model of female reproductive aging was employed to assess the separate impacts of age and high FSH activity on the percentages (%) of viable and mature ovulated oocytes recovered after gonadotropin treatment. Young and midlife mice were treated with the FSH analog equine chorionic gonadotropin (eCG) to model both endogenous FSH elevation and exogenous FSH elevation. Previously we showed the activin inhibitor ActRIIB:Fc increases oocyte quality by preventing chromosome and spindle misalignments. Therefore, ActRIIB:Fc treatment was performed in an effort to increase % oocyte viability and % oocyte maturation.ResultsThe high FSH activity of eCG is ootoxic to ovulatory oocytes, with greater decreases in % viable oocytes in midlife than young mice. High FSH activity of eCG potently inhibits oocyte maturation, decreasing the % of mature oocytes to similar degrees in young and midlife mice. ActRIIB:Fc treatment does not prevent eCG ootoxicity, but it restores most oocyte maturation impeded by eCG.ConclusionsFSH ootoxicity to ovulatory oocytes and FSH maturation inhibition pose a paradox given the well-known pro-growth and pro-maturation activities of FSH in the earlier stages of oocyte growth. We propose the FOOT Hypothesis (“FSH OoToxicity Hypothesis), that FSH ootoxicity to ovulatory oocytes comprises a new driver of infertility and low pregnancy success rates in DOR women attempting spontaneous pregnancy and in COS/IUI patients, especially AMA women. We speculate that endogenous FSH elevation also contributes to reduced fecundity in these DOR and COS/IUI patients.Restoration of oocyte maturation by ActRIB:Fc suggests that activin suppresses oocyte maturation in vivo. This contrasts with prior studies showing activin A promotes oocyte maturation in vitro. Improved oocyte maturation with agents that decrease endogenous activin activity with high specificity may have therapeutic benefit for COS/IVF patients, COS/IUI patients, and DOR patients attempting spontaneous pregnancies.

Age-related enhancement of the association between episodic memory and gray matter volume in medial temporal and frontal lobes

BackgroundEpisodic memory (EM) deteriorates as a result of normal aging as well as Alzheimer’s disease. The neural underpinnings of such age-related memory impairments in older individuals are not well-understood. Although previous research has unveiled the association between gray matter volume (GMV) and EM in the elderly population, such findings exhibit variances across distinct age cohorts. Consequently, an investigation into the dynamic evolution of this relationship with advancing age is imperative.ResultThe present study utilized a sliding window approach to examine how the correlation between EM and GMV varied with age in a cross-sectional sample of 926 Chinese older adults. We found that both verbal EM (VEM) and spatial EM (SEM) exhibited positive correlations with GMV in extensive areas primarily in the temporal and frontal lobes and that these correlations typically became stronger with older age. Moreover, there were variations in the strength of the correlation between EM and GMV with age, which differed based on sex and the specific type of EM. Specifically, the association between VEM and GMVs in the insula and parietal regions became stronger with age for females but not for males, whereas the association between SEM and GMVs in the parietal and occipital regions became stronger for males but not for females. At the brain system level, there is a significant age-related increase in the correlations between both types of EM and the GMV of both the anterior temporal (AT) system and the posterior medial (PM) system in male group. In females, both types of EM show stronger age-related correlations with the GMV of the AT system compared to males.ConclusionsOur study revealed a significant positive correlation between GMV in most regions associated with EM and age, particularly in the frontal and temporal lobes. This discovery offers new insights into the connection between brain structure and the diminishing episodic memory function among older individuals.

In cases with raised sperm DNA fragmentation, can sperm selection by magnetic-activated cell sorting or testicular sperm aspiration help improve reproductive outcomes?

To evaluate the efficacy of magnetic-activated cell sorting (MACS) or testicular sperm aspiration (TESA) to improve reproductive outcomes in cases with elevated sperm DNA fragmentation undergoing assisted reproduction. This randomized controlled trial included couples with failed IVF cycles and sperm DNA fragmentation > 30%. Sperm DNA fragmentation was assessed using the sperm chromatin structure assay (SCSA) method. Participants were randomly assigned to either the MACS or TESA group. Testicular sperm retrieval was performed for the TESA group, while MACS involved sperm selection using magnetic beads. Extended blastocyst culture, freeze all policy of blastocysts by vitrification, and frozen embryo transfer were undertaken as per clinic's standard operating protocols. Blastocyst formation rate, implantation rate, miscarriage rate, multiple pregnancy rate, and live birth rate were analyzed and compared between MACS and TESA groups. There were no significant differences in female age, male age, or sperm DNA fragmentation index (DFI) between the MACS and TESA groups. The blastocyst conversion rate was slightly higher in the TESA group (39%) compared to the MACS group (32%). However, the MACS group had a higher implantation rate (50%) than the TESA group (35%). Miscarriage rates, multiple pregnancy rates, and live birth rates did not show statistically significant differences between the groups. A chi-squared test was conducted to compare categorical variables, and t-tests were done to compare continuous variables. In cases with raised sperm DNA fragmentation, sperm selection by MACS or TESA seems to offer comparable reproductive outcomes. There seems no superiority of one intervention over the other in cases with raised sperm DNA fragmentation undergoing assisted reproduction. Both interventions seem to be beneficial for couples seeking assisted reproduction with raised sperm DNA fragmentation.

Is this an adenocarcinoma? A case report of extragenital endometriosis with hydroureteronephrosis

Introduction and Importance: Endometriosis is a prevalent condition within the female reproductive age group, but its presentation and diagnosis still pose a challenge as it mimics other diseases and affects multiple organ systems. Case Presentation: A 24-year-old nulliparous female presented with complaints of menorrhagia, lower abdominal pain, post-coital bleeding, and significant weight loss for 7 months. Clinical Discussion: The case highlights the challenge of diagnosing endometriosis due to its ability to mimic other conditions, such as carcinoma cervix and rectum. The presence of elevated Cancer Antigen-125 (CA-125), typically associated with malignancy, underscores the need for a comprehensive evaluation to differentiate between endometriosis and other pathologies. Furthermore, the involvement of multiple organ systems emphasizes the systemic nature of endometriosis and the importance of considering it in the differential diagnosis of pelvic masses and symptoms in young women. Conclusion: Endometriosis, although a common disease among females of reproductive age its variation in presentation causes significant misdiagnosis and undertreatment. Multi-modal diagnosis and early treatment are necessary for proper outcomes.

High prevalence of iron deficiency and socioeconomic disparities in laboratory screening of non-pregnant females of reproductive age: A retrospective cohort study.

Iron deficiency anemia (IDA) and non-anemic iron deficiency (NAID) are highly prevalent among non-pregnant females of reproductive age. Canada has no national screening guidelines for this population. Screening, when performed, is often with a complete blood count alone without ferritin or iron indices. The primary objective was to determine the prevalence of screening for NAID and IDA over a 3-year period in non-pregnant females of reproductive age who had tests performed at outpatient laboratories in Ontario, Canada. Retrospective cohort study of non-pregnant females ages 15-54 in Ontario, from 2017 to 2019. NAID was defined as ferritin <30 μg/L, anemia as hemoglobin <120 g/L, and IDA as ferritin <30 μg/L and hemoglobin <120 g/L. Annual household income was estimated using patient postal codes. A total of 784 132 non-pregnant females were included. The 82.1% were screened for iron deficiency, 38.3% had NAID and 13.1% had IDA; 55.6% with IDA had normal mean corpuscular volumes. The median household income was $89454.80 compared with a provincial median of $65285.00. Patients in the lowest income quintile had the highest odds of being anemic, and the lowest odds of having a ferritin checked. A large proportion of non-pregnant females of reproductive age in this cohort were screened for iron deficiency. In this relatively privileged cohort, NAID affected nearly 40%, and IDA 13%. Most patients with IDA did not have microcytosis. Low household income was associated with the greatest odds of anemia and the lowest odds of being screened, highlighting inequitable access to screening for IDA in Ontario, Canada.

Abstract PO3-17-04: HER2-directed biosimilar Ogivri in the treatment of breast cancer: real world reporting of symptoms and wellbeing using electronic patient reported outcome (ePRO)

Abstract Introduction: Trastuzumab has a major impact on the treatment of HER2 positive breast cancer (BC). Anti-HER2 biosimilars, such as OgivriTM, demonstrated safety and clinical equivalency to the reference product HerceptinTM in clinical trials. However, real-world reporting of side effects, quality of life (QoL) and outcome in patients treated with biosimilars has not yet been performed using electronic PROs. Here standardized and structured ePROs are dynamically recorded with the mediduxTM app during OgivriTM treatment and are applied to perform a comparative analysis with ePROs derived from 38 historical patients treated with HerceptinTM in two previous studies (NCT02004496, NCT03578731). Methodology: In this prospective observational study, patients with HER2-positive BC were treated with OgivriTM alone +/- Pertuzumab, +/- Chemotherapy and hormone therapy in neo-adjuvant, adjuvant and non-curative settings. Over an observational period of 6 weeks, patients used the mediduxTM app to dynamically record symptoms (according to CTCAE), well-being, EQ-5D-5L, cognitive capabilities, and vital parameters. Comparative analysis was performed with historical data from 38 patients that had reported 5217 ePROs and more than 1400 reports of well-being in similar therapeutic settings. Results: 52 females (age 37-86 yrs) were treated with OgivriTM. From 92 different symptoms available, 84 were entered (average &amp;gt; 2 symptoms/day) resulting in 10`532 individual patient entries. Among the most common symptoms reported in both groups were fatigue, taste disorder, nausea, diarrhea, dry mucosa, joint discomfort, tingling, sleep disorder, headache, appetite loss. As compared to HerceptinTM, overall, symptoms associated with OgivriTM were reported with a similar incidence and distribution among groups (p=0.68), although slightly but not significantly lower scores (p=0.24; CI: 0.08-0.31). Distribution of symptom grades in the OgivriTM cohort revealed that the vast majority of patients experienced mild and grade 1 toxicities, 13% grade 2, 2% grade 3 and 0.4% grade 4 toxicities, respectively. The latter finding could possibly also be attributed to a trend towards de-escalation in chemotherapeutic regimes during the past 5 years since data acquisition, affecting anthracyclines and taxanes, and that. Of note, when treatments were compared restricted to the trastuzumab antihormones and trastuzumab- paclitaxel therapies, this reported trend seamed weaker. Importantly, well-being of patients undergoing HER2 directed treatment did not differ (p=0.24; CI: 0.39-0.88) in both cohorts. Conclusion: No difference was reported for symptoms, adverse events, and well-being with respect to the Trastuzumab biosimilar OgivriTM in comparison with HerceptinTM. The integration of ePRO into research and clinical practice provides reliable information when investigating real world tolerability and outcomes of similar therapeutic compounds. Citation Format: Andreas Trojan, Sven Roth, Reinhard Zenhäusern, Yannick Kadvany, Christian Jackisch, Matti Aapro, Alexandru Eniu. HER2-directed biosimilar Ogivri in the treatment of breast cancer: real world reporting of symptoms and wellbeing using electronic patient reported outcome (ePRO) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-17-04.

Abstract PO3-05-08: Updated results from VERITAC evaluating vepdegestrant, a PROteolysis TArgeting Chimera (PROTAC) estrogen receptor (ER) degrader, in ER–positive/human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer

Abstract Background: Vepdegestrant (ARV-471) is an oral PROTAC ER degrader with activity toward wild-type and mutant ER. The phase 2 expansion (VERITAC) of a phase 1/2 study (NCT04072952) tested 2 vepdegestrant doses (200 mg once daily [QD] and 500 mg QD) in heavily pretreated patients with ER+/HER2- advanced breast cancer. Vepdegestrant 200 mg QD was selected as the phase 3 monotherapy dose based on comparable efficacy and favorable tolerability vs 500 mg QD and robust ER degradation (data cutoff: Jun 6, 2022). We present updated data for the vepdegestrant 200 mg QD cohort after 12 additional months of follow-up. Methods: Vepdegestrant was administered to patients with ER+/HER2- locally advanced/metastatic breast cancer who had received ≥1 prior endocrine therapy for ≥6 months, ≥1 cyclin-dependent kinase (CDK)4/6 inhibitor, and ≤1 chemotherapy regimen. The primary endpoint was clinical benefit rate (CBR; rate of confirmed complete response, partial response, or stable disease ≥24 weeks). Results: As of Jun 6, 2023, 35 patients received vepdegestrant 200 mg QD; 34 (97.1%) were female and median age was 63 y (range: 42–79). Patients had received a median of 4 prior regimens (range: 1–9) in all settings and 3 prior regimens (range: 0–7) in the metastatic setting; 100% had prior CDK4/6 inhibitors, 88.6% had prior aromatase inhibitors, 74.3% had prior fulvestrant, and 74.3% had prior chemotherapy (45.7% in metastatic setting). CBR with vepdegestrant 200 mg QD was 37.1% (95% CI: 21.5–55.1) in all evaluable patients (n=35) and the objective response rate was 8.3% (95% CI: 1.0–27.0) among 24 patients with measurable disease at baseline. Median progression-free survival in all evaluable patients was 3.5 months (95% CI: 1.8–8.2). As of the data cutoff date, 14 patients in the 200 mg QD cohort received treatment for ≥24 weeks (4 for ≥48 weeks) with 1 patient ongoing. No patients required a dose reduction due to a treatment-emergent adverse event (TEAE); 2 (5.7%) patients had a TEAE that led to vepdegestrant discontinuation (grade 3 QT prolongation and grade 3 anemia). The most common treatment-related adverse events (≥10%) were fatigue (43%), hot flush (20%), nausea (17%), arthralgia (11%), increased aspartate aminotransferase (11%), and increased blood alkaline phosphatase (11%); all were grade 1/2. Substantial on-treatment decreases in mutant ESR1 circulating tumor DNA levels were observed with vepdegestrant 200 mg QD and sustained for multiple treatment cycles. Conclusions: With 12 months of additional follow-up from the first data report, durable clinical activity with vepdegestrant 200 mg QD was seen in heavily pretreated patients with ER+/HER2- advanced breast cancer, in addition to sustained reduction in circulating mutant ESR1 tumor DNA levels. Vepdegestrant 200 mg QD continued to show a favorable safety profile. The ongoing global, randomized phase 3 VERITAC-2 study (NCT05654623) is evaluating vepdegestrant 200 mg QD vs intramuscular fulvestrant in patients with ER+/HER2- advanced breast cancer after prior combination CDK4/6 inhibitor therapy and endocrine therapy. Citation Format: Sara Hurvitz, Anne Schott, Cynthia Ma, Rita Nanda, George Zahrah, Natasha Hunter, Antoinette Tan, Melinda Telli, Jesus Anampa Mesias, Rinath Jeselsohn, Pamela Munster, Eric Zhi, Elizabeth Duperret, Cecile Mather, Erika Hamilton, Hyo Han. Updated results from VERITAC evaluating vepdegestrant, a PROteolysis TArgeting Chimera (PROTAC) estrogen receptor (ER) degrader, in ER–positive/human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-05-08.

Health-related quality of life among paediatric patients with coarctation of the aorta: an observational study

ABSTRACT Advancements in early diagnosis and paediatric cardiac surgery have improved the long-term survival of patients with congenital heart disease, necessitating a thorough assessment of their health-related quality of life (HRQoL). This study aimed to assess HRQoL in paediatric patients with coarctation of the aorta (CoA) (both as reported by patients and caregivers), and to evaluate associated factors. Patients aged 5–18 years diagnosed with CoA and their parents were enrolled at Bambino Gesù Children’s Hospital between September 2016 and December 2017. Socio-demographic characteristics were recorded using a family form, and the Pediatric Quality of Life Inventory (PedsQL) 3.0 cardiac module was used to evaluate HRQoL. Clinical data were retrieved from medical chart reviews. In this observational study, sixty-five pediatric patients (39 males, median [IQR] age 12 [9–14]) with CoA and their parents (65 mothers and 65 fathers) were enrolled. These patients exhibited overall good HRQoL. Mothers reported significantly lower total HRQoL scores compared to patient self-reports (p = .037), as well as treatment anxiety (p = .033), and cognitive problems (p = .021). Pediatric patients with CoA perceived their HRQoL better than their mothers did. Female sex and older age were associated with lower HRQoL scores.

Effect of baseline prolactin levels on the pregnancy outcomes after fresh embryo transfer.

There is clinical disagreement on whether to treat hyperprolactinemia with medication before embryo transfer. The aim of this study is to identify the impact of basal prolactin (PRL) levels on pregnancy outcomes in fresh embryo transfer cycles. This retrospective study involved 2,648 women who underwent basal PRL level testing and fresh embryo transfer between January 2015 and December 2020 at our Hospital's Department of Assisted Reproduction. Basal PRL levels can be classified into three categories:<30 (n=2339), 30‑60 (n=255), and ≥60 (n=54) µg/l. Pregnancy outcome was defined as the primary outcome measure, and the live birth rate was defined as the second outcome measure. Subsequently, univariate and multivariable logistic regression analysis was used to reveal the association between basal PRL levels and pregnancy outcomes after considering several potential confounding factors. Elevated basal PRL levels were found not a risk factor for pregnancy outcomes in patients receiving good-quality embryo transfer (p>.05). For pregnancy or not, female age (OR: 1.03; 95% CI: 1.01-1.05), embryos transferred (OR: 0.52; 95% CI: 0.41-0.65), and normal fertilization rate (OR: 0.68; 95% CI: 0.48-0.97) were found to be an independent risk factor. For ongoing pregnancy or not, female age (OR: 1.07; 95% CI: 1.03-1.11), embryos transferred (OR: 0.57; 95% CI: 0.37-0.88), and menstrual cycle (OR: 1.76; 95% CI: 1.22-2.54) were also independent risk factors. There is no adverse impact on pregnancy outcomes during embryo transfer cycles with good-quality embryos when PRL levels are elevated.

The relationship between menorrhagia, iron deficiency, and anaemia in recreationally active females: an exploratory population based screening study

ObjectivesIron deficiency, anaemia, and Menorrhagia - or heavy menstrual bleeding (HMB) - are interrelated conditions that are highly prevalent and commonly underrecognized in exercising females of reproductive age. This study utilised a screening tool to identify risk factors and symptoms associated with HMB, iron deficiency, and anaemia in this population. DesignAn observational, cross sectional survey study was employed. Here, 1042 active females (aged 18–65) completed a comprehensive screening questionnaire and 887 (85 % compliance) provided a fingerprick blood sample for haemoglobin (Hb) concentration measurement. Women that presented as anaemic (defined as a [Hb] < 120 g/L) or deemed to be at risk of iron deficiency (120 < [Hb] < 130 g/L) were asked to complete follow-up blood tests to screen for iron studies. ResultsAverage [Hb] was 134.2 ± 12.1 g/L, with 94 individuals considered anaemic (10.6 %). Of the sample, 104 underwent follow-up blood tests; 51 (~49 %) presented with iron deficiency (defined as ferritin <30 μg/L). Based on survey responses, 274 (30.9 %) participants were determined to have HMB. Those presenting with HMB were younger, exercised fewer hours per week, and were more likely to have a history of iron deficiency or anaemia (all p < 0.05). Participants reporting a history of anaemia or iron deficiency were more likely to have HMB (anaemia: 39.7 %; iron deficiency; 36.9 %; both p < 0.05). ConclusionIn this cohort of exercising females of reproductive age, the prevalence of anaemia was 10.6 %. There is a strong association between HMB and a self-reported history of ID and anaemia. Greater awareness of HMB and its relationship with ID and anaemia is needed in this population. Non-invasive screening should be conducted to raise awareness and further understand the associated risk factors and symptomatology.

Penciclovir pharmacokinetics after oral and rectal administration of famciclovir in African elephants (Loxodonta africana) shows that effective concentrations can be achieved from rectal administration, despite lower absorption.

To evaluate the pharmacokinetics of famciclovir and its metabolite penciclovir following a single dose administered orally and rectally in African elephants (Loxodonta africana). 15 African elephants (6 males and 9 females) of various ages. Famciclovir (15 mg/kg) was administered orally or per rectum once, with at least a three-week washout period between administrations. Blood was collected at 13 different timepoints per administration for 6 elephants, occurring between February and March 2020. An additional 9 elephants were sampled at variable timepoints per administration utilizing a sparse sampling design between July 2020 and January 2021. Plasma famciclovir and penciclovir levels were measured via HPLC and fluorescence detection. Pharmacokinetic analysis was completed in the summer of 2021 using noncompartmental analysis and nonlinear mixed-effects modeling. Famciclovir was not detected in any sample, suggesting complete metabolism. Key pharmacokinetic parameters for penciclovir following oral administration were time to maximum concentration (tmax; 2.12 hours), area under the concentration-versus-time curve (AUC; 33.93 μg·h/mL), maximum observed concentration (Cmax; 3.73 μg/mL), and absorption half-life (t1/2; 0.65 hours). Following rectal administration, the values were: tmax, 0.65 hours; AUC, 15.62 μg·h/mL; Cmax, 2.52 μg/mL; and absorption t1/2, 0.13 hours. Famciclovir was rapidly metabolized to penciclovir. Oral administration resulted in slower absorption but higher maximum plasma concentration and higher AUC compared to rectal administration. African elephants administered famciclovir via oral and rectal routes resulted in measurable serum penciclovir, and these findings may be utilized by clinicians treating viral infections in this species.

Total Hip Replacement with a Fully Hydroxyapatite-Coated Shortened Stem: Five- to Thirteen-Year Follow-Up Results

Background: Shortened femoral stems aim to mimic the biomechanical performance of traditional stems while preserving more bone and minimizing soft tissue damage. Our objective is to assess the outcomes of patients treated with a shortened stem (Furlong Evolution, JRI Orthopaedics, Sheffield, UK) to analyze the implant’s efficacy and survivorship. Methods: This retrospective observational study included all patients aged 18 to 70 undergoing uncemented shortened stem total hip replacement at Hospital del Mar between 2010 and 2018. Hip function and pain were assessed with the Merle d’Aubigné–Postel scale and visual analog scale, respectively. A radiographic analysis measured stem and cup orientation, leg length discrepancy, stem subsidence, and radiolucencies around the cup. Perioperative complications, prosthetic failures, and reoperations were documented. Results: A total of 109 patients (74 male, 35 female) of a mean age of 51.8 ± 8.8 years were included. The average follow-up was 91 ± 17.4 months. Radiographically, 71 (65.1%) of the stems had been inserted at the appropriate angulation (±3°), and 102 (93.6%) of the cups had been placed in the Lewinnek safety zone. Leg length discrepancy was observed in 19 (17.4%) cases. The mean Merle d’Aubigné–Postel score improved from 13.1 ± 1.39 preoperatively to 17.8 ± 0.49 at 6 months postoperatively (p &lt; 0.001). Merle d’Aubigné–Postel subscales also reflected a statistically significant improvement (p &lt; 0.001). The mean pain score 12 months postoperatively was 0.52 ± 1.22, with 95.4% of patients declaring themselves satisfied or highly satisfied. The expected 13-year survival according to a Kaplan–Meier analysis was 100% in the absence of infection and 91.3% if revision for any cause is taken as a survival endpoint. Conclusions: The shortened stem under analysis provides excellent functional results and long-term survival rates.

Interlimb kinetic asymmetries during the tuck jump assessment are more exposed following kinetic stabilization

ObjectiveTo analyse interlimb kinetics and asymmetries during the tuck jump assessment (TJA), before and after kinetic stabilization, to identify injury risk in healthy female athletes. DesignCross-sectional study. SettingLaboratory. ParticipantsTwenty-five healthy females (age 21.0 ± 1.83 yrs; height 1.68 ± 0.06 m; body mass 69.4 ± 10.7 kg). Main outcome measuresKinetics were measured during 10-s trials of the TJA and absolute asymmetries compared, before and after kinetic stabilization using paired sample t-tests. Statistical parametric mapping (SPM) compared vertical ground reaction force (VGRF) data for each limb during the jumping cycles before and after stabilization. ResultsSmall to moderate increases in interlimb asymmetries were observed after stabilization for VGRF, relative vertical leg stiffness, average loading rate, total and propulsive impulse, peak braking and propulsive force (p < 0.05). SPM revealed significant interlimb differences between 77-98% and 83–99% of ground contact for the jumping cycles pre- and post-stabilization respectively. ConclusionsLarger asymmetries were evident after kinetic stabilization, with increased VGRF in the non-dominant limb. We speculate that participants sacrificed interlimb landing symmetry to achieve kinetic stability, which may reflect a primal landing strategy that forgoes movement quality. Assessing lower limb biomechanics using the TJA should involve examining kinetic stability and interlimb kinetic asymmetries.

The Impact of Obesity on Reproductive Health and Metabolism in Reproductive Age Females.

Obesity is a highly prevalent chronic disease that impacts over 40% of reproductive-aged females. The pathophysiology of obesity is complex and can be understood simply as a chronic energy imbalance whereby caloric intake exceeds caloric expenditure with energy surplus stored in adipose tissue. Obesity may be categorized into degrees of severity as well as different phenotypes based on metabolic health and underlying pathophysiology. Obesity and excess adiposity have a significant impact on fertility and reproductive health with direct effects on the hypothalamic-pituitary-ovarian axis, the ovary/oocyte, and the endometrium. There are significant adverse pregnancy outcomes related to obesity and together with excess weight gain prior to, during, and after pregnancy, can alter lifelong risk for metabolically unhealthy obesity. Given the high-prevalence and pervasive impact of obesity on reproductive health, there is a need for better and individualized care for reproductive-aged females that considers obesity phenotype, underlying pathophysiology, and effective and sustainable interventions to treat obesity and manage weight gain prior to, during, and after pregnancy.

Prevalence of frailty among chronic respiratory disease patients.

Although frailty is one of the aging syndromes, it can occur at a younger age and in individuals with organ diseases. Identifying frailty and pre-frailty in patients with chronic respiratory diseases (CRDs) is an emerging assessment in the field of pulmonary medicine and rehabilitation. The aim of this study was to find out the prevalence of frailty among chronic respiratory disease patients. A single centre cross-sectional survey study with a total population of 381 patients, adults aged 18-90 years presenting to the pulmonology OPD was included based on the inclusion and exclusion criteria. Primary data collected were demographics, medical history, including comorbidities, use of long-term oxygen therapy (LTOT), BiPAP (Bilevel Positive Airway Pressure), previous hospital admissions, medication history and frailty assessment were done using the Fried frailty index. Univariate analysis showed that sex, ECHO abnormality, patients using LTOT, BiPAP, home nebulizers and patients who did not attend the pulmonary rehabilitation programme had a significant association with frailty. Multivariate analysis showed that female sex, LTOT use and older age were significantly associated with frailty. Frailty is frequent in CRD patients regardless of age. The prevalence of frailty has an association with female sex, patients using LTOT, and home BiPAP.

Effects of Oral Zinc Supplementation on Early Embryonic Development and Neonates of Aged Female Albino Mice

     Female reproductive aging is a normal phase of life that eventually leads to menopause and reproductive senescence. The current experimental investigation was intended to study zinc supplementation effects on early embryonic development and neonates in 26-28 weeks old female mice. In this investigation, 80 mature female mice were used that were divided into two groups of forty each. Two control groups received distilled water, while two Zn groups were given 0.115 mg/kg/day Zn orally daily during 2-3 estrous cycles. The female mice were all mated with adult males. Twenty female mice from both the control and Zn groups were euthanized by CO2 gas inhalation, and then a longitudinal incision in the abdomen of each female mouse was performed and uterine horns and oviducts were detached from the body in order to obtain two-cell embryos. On the other hand, 20 pregnant mice from each group were permitted to complete their pregnancy until birth and then their neonates were collected for macroscopic examination. The findings showed that the Zn supplementation significantly (P≤0.01) improved the mean embryonic development and the quality of 2-cell stage embryo grade A. Whereas, it decreased the mean embryonic development of 2-cell stage embryo grade D in aged female mice significantly (P≤0.01) in comparison with aged control groups. Also, the count and quality of neonates from Zn-treated aged female mice enhanced significantly (P≤0.01) as compared to non-treated aged female mice. It was concluded from these findings that the Zn can improve embryonic development and neonate count and quality in aged mice.

Ureteroscopy for urolithiasis in bedridden patients: it is feasible and acceptable.

To investigate the safety of transurethral ureteroscopy (URS) for urolithiasis in bedridden patients and to identify bedridden patient-specific risk factors for postoperative complications. The patients who underwent URS for urolithiasis were divided into bedridden patients and good performance status (PS) patients, and the groups were compared regarding their clinical characteristics and postoperative complications. A multivariable logistic regression analysis was performed to evaluate independent predictors of postoperative febrile urinary tract infection (fUTI). A total of 1626 patients were included, 276 in the bedridden patient group, and 1350 in the good PS patient group. The bedridden patient group had a significantly higher age and higher proportion of females and had multiple comorbidities. In 77 patients (27.9%), 88 postoperative complications developed for the bedridden patient group. Clavien-Dindo grade III or IV complications were observed in only 8 patients. No grade V complications were observed. The most common complication was fUTI. The frequency of fUTI with grade III or IV for the bedridden patient group (2.2%) was higher compared with the good PS patient group (0.5%), but the difference was not statistically significant (p = 0.13). Bedridden patient-specific risk factors for fUTI included female sex, diabetes mellitus, cerebrovascular comorbidities, lower extremity contracture, and prolonged operative time. URS for urolithiasis is a feasible and acceptable procedure in bedridden patients, despite the moderate rate of postoperative complications. The identified risk factors provide a framework for risk stratification and individualized care in this unique patient population.

The role of autoimmune thyroid disorders in patients with alopecia areata

Objective: The aim of this study was to investigate the association of thyroid autoimmunity with alopecia areata (AA) by examining thyroid stimulating hormone (TSH) and thyroid autoantibody levels. In addition, to compare the epidemiologic data obtained with the data of our country. Methods: Our study was organized as a cross-sectional, retrospective study. The study was performed on patients between the ages of 2-65 years who were admitted to our outpatient clinic between 01.01.2008 and 31.12.2011, who were clinically or histopathological diagnosed with AA, examined for etiology and thyroid autoantibodies were requested. Patients under two years of age and over 65 years of age, patients with no thyroid autoantibodies and pregnant patients were excluded. Results were expressed as mean±standard deviation and median values. Mann-Whitney U test was used to compare TSH, anti-TG antibody (Anti-TG) and anti-TPO (Anti-TPO) antibody values in the variables of nail involvement, psychiatry, comorbidity and family history. Spearman correlation analysis was used to examine the relationships between age and disease duration and TSH, Anti-TPO and Anti-TG variables. Results: In our study, 65 (42.8%) of 152 patients were female and 87 (57.2%) were male. The ages of the patients ranged between 2-65 years and the mean age was 26.5±14.6 years. The mean age of females was 27.5±14.4 and 25.7±14.9 in males. Elevated thyroid autoantibodies were found in a total of 29 patients, 21 of whom were female and 8 of whom were male. Of these 29 patients, 10 had hypothyroidism, 2 had chronic thyroiditis and 3 had toxic multinodular goiter. 14 patients did not return after the examination at the internal medicine outpatient clinic, so the diagnosis of thyroid disease could not be reached. The mean TSH, Anti-TG and Anti-TPO values were 2.27±1.57, 29.2±99 and 71.5±2.2, respectively. When these values were analyzed separately as men and women, they were found to be 2.6±2.02, 41.8±1.23 and 134±2.8 in women and 1.99±1.03, 19.8±75.6 and 24.5±1.32 in men. There was a significant difference between men and women in terms of Anti-TG and Anti-TPO values (p=0.011 and p=0.001, respectively). A significant correlation was found between disease duration and Anti-TPO positivity (p=0.045); however, a similar relationship was not found between disease duration and Anti-TG positivity (p=0.34). Conclusions: As a result of this study, although there was a significant correlation between anti-TPO and duration of AA, the association between thyroid autoimmunity and AA was not found to be statistically significant. This may be due to the fact that humoral autoimmunity plays a role in thyroid autoimmunity and primarily cellular autoimmunity plays a role in AA. In addition, the epidemiologic data of our study were similar to the data of studies conducted in our country.

Different radius of curvature at the talus trochlea from northern Chinese population measured using 3D model

BackgroundTo analyze the curvature characteristics of the talus trochlea in people from northern China in different sex and age groups.MethodsComputed tomography scanning data of talus from 61 specimens were collected and constructed as a three-dimensional model by Materialise’s Interactive Medical Image Control System(MIMICS) software, anteromedial(AM), posteromedial(PM), anterolateral(AL), and posterolateral(PL) edge, anterior edge of medial trochlea, posterior edge of medial trochlea and anterior edge of lateral trochlea were defined according to the anatomical landmarks on trochlear surface. The curvature radii for different areas were measured using the fitting radius and measure module.ResultsThere were significant differences among the talus curvatures in the six areas (F = 54.905, P = 0.000), and more trends in the analytical results were as follows: PM > PL > MP > AL > MA > AM. The average PL radius from specimens aged > 38 years old was larger than that from specimens aged < = 38 years (t=-2.303, P = 0.038). The talus curvature of the AM for males was significantly larger than that for females (t = 4.25, P = 0.000), and the curvature of the AL for males was larger than that for females (t = 2.629, P = 0.010). For observers aged < = 38 years, the AM curvature of the right talus in the male group was significantly larger than that in the female group (P < 0.01). In age < = 38years group, the MA curvature of right talus in male was significantly larger than in female group(P < 0.01), fitting radius of talus for male (21.90 ± 1.97 mm) was significantly greater than female of this(19.57 ± 1.26 mm)(t = 6.894, P = 000). The average radius of the talus in the male population was larger than that in the female population.ConclusionThere was no significant relationship between age and talus curvature for males and females. The radius of curvature in the posterior area was significantly larger than that in the anterior area. We recommend that this characteristic of the talus trochlea should be considered when designing the talus component in total ankle replacement (TAR).

Motor proficiency in young children with Prader-Willi syndrome: a preliminary report

BACKGROUND: Systematic documentation of motor characteristics in young children with Prader-Willi syndrome (PWS) is vital as access to treatments improves. AIM: To characterize motor proficiency (MP) in young children with PWS. METHOD: Participants included 6 children (3 male and 3 female) with PWS and 13 children with neurotypical development (NT), (9 male and 4 female) ages 4-6 years. Five out of six children with PWS had been on growth hormone replacement therapy (GHRT) for &gt;3 years. Some children with PWS exhibited cognitive delays and others performed within the average range (Intellectual quotient mean± standard deviation = 65.3 ± 7.62, range = 47 – 94). MP was measured using the Short Form of the Bruininks-Oseretsky Test of Motor Proficiency-Second Edition (BOT-2-SF). RESULTS: Children with PWS scored lower than children with NT in all areas of MP except for fine motor integration. All children with PWS scored well-below average for total MP; children with NT scored average (n=10) or above-average (n=3) for total MP, respectively. CONCLUSION: At this young age children with PWS universally exhibited poor MP despite most of them being on GHRT and some exhibited intellectual functioning in the average range. Evidence of BOT-2-SF floor effects underscores the need to refine assessment procedures and enhance measurement precision for this population.