ß-Alanine supplementation improves fractional anisotropy scores in the hippocampus and amygdala in 60-80-year-old men and women.

Recently, ß-alanine (BA) supplementation was shown to improve cognitive function in older adults with decreased cognitive function. Mechanisms supporting these improvements have not been well defined. This study examined the effects of 10-weeks of BA supplementation on changes in circulating brain inflammatory markers, brain derived neurotrophic factor (BDNF), and brain morphology. Twenty participants were initially randomized into BA (2.4 g·d-1) or placebo (PL) groups. At each testing session, participants provided a resting blood sample and completed the Montreal cognitive assessment (MoCA) test and magnetic resonance imaging, which included diffusion tensor imaging to assess brain tissue integrity. Only participants that scored at or below normal for the MoCA assessment were analyzed (6 BA and 4 PL). The Mann-Whitney U test was used to examine Δ (POST-PRE) differences between the groups. No differences in Δ scores were noted in any blood marker (BDNF, CRP, TNF-α and GFAP). Changes in fractional anisotropy scores were significantly greater for BA than PL in the right hippocampus (p = 0.033) and the left amygdala (p = 0.05). No other differences were noted. The results provide a potential mechanism of how BA supplementation may improve cognitive function as reflected by improved tissue integrity within the hippocampus and amygdala.

Early Life Androgen Administration Attenuates Aging Related Declines in Muscle Protein Synthesis.

PURPOSE: This study examined the acute and long-term effects of nandrolone decanoate (ND) on fractional synthetic rates (FSR). METHODS: Male C57BL/6 mice were randomized into ND ( n = 20) or sham ( n = 20) groups. ND injections (10 g·kg -1 ·wk -1 ) started at 7 months of ages and continued for 6 wk. Ten animals from each group were randomly separated and examined 1 wk following drug cessation. The remaining animals were examined at 16 months of age. Animals were injected IP with 1.5 mL of deuterated water 24 h before euthanasia. The kidney, liver, heart, gastrocnemius, and soleus were extracted. Samples were analyzed for deuterated alanine enrichment in the bound protein and intracellular fraction by liquid chromatography tandem mass spectrometry to measure estimated FSR (fraction/day (F/D)) of mixed tissue. RESULTS: One-way ANOVA, with treatment and age as fixed factors, indicated that kidney FSR was greater ( P = 0.027) in ND (0.41 ± 0.02 F/D) than sham (0.36 ± 0.014F/D) and higher ( P = 0.003) in young (0.42 ± 0.2 F/D) than old (0.35 ± 0.01 F/D). Liver and heart FSR values were greater ( P ≤ 0.001) in young (0.79 ± 0.06 F/D and 0.13 ± 0.01 F/D, respectively) compared with old (0.40 ± 0.01 F/D and 0.09 ± 0.01 F/D, respectively), but not between ND and sham. Gastrocnemius FSR was ( P ≤ 0.001) greater in young (0.06 ± 0.01 F/D) compared with old (0.03 ± 0.002 F/D), and greater ( P = 0.006) in ND (0.05 ± 0.01 F/D) compared with sham (0.04 ± 0.003 F/D). Soleus FSR rates were greater ( P = 0.050) in young (0.13 ± 0.01 F/D) compared with old (0.11 ± 0.003 F/D), but not between ND (0.12 ± 0.01 F/D) and sham (0.12 ± 0.01 F/D). Old animals who had received ND displayed elevated FSR in the gastrocnemius ( P = 0.054) and soleus ( P = 0.024). CONCLUSIONS: ND use in young adult animals appeared to maintain long-term elevations in FSR in muscle during aging.

Role of ß-Alanine Supplementation on Cognitive Function, Mood, and Physical Function in Older Adults; Double-Blind Randomized Controlled Study.

This study investigated 10 weeks of ß-alanine (BA) supplementation on changes in cognitive function, mood, and physical performance in 100 older adults (70.6 ± 8.7 y). Participants were randomized into a BA (2.4 g·d-1) or placebo (PL) group. Testing occurred prior to supplementation (PRE), at the midpoint (MID), and at week-10 (POST). Participants completed cognitive function assessments, including the Montreal cognitive assessment (MOCA) and the Stroop pattern recognition test, at each testing session. Behavioral questionnaires [i.e., the profile of mood states, geriatric depression scale (GDS), and geriatric anxiety scale (GAS)] and physical function assessments (grip strength and timed sit-to-stand) were also conducted. No difference between groups was noted in MoCA scores (p = 0.19). However, when examining participants whose MOCA scores at PRE were at or below normal (i.e., ≤26), participants in BA experienced significant improvements in MOCA scores at MID (13.6%, p = 0.009) and POST (11.8%, p = 0.016), compared to PL. No differences were noted in mood scores, GAS, or any of the physical performance measures. A significant decrease was observed in the GDS for participants consuming BA but not in PL. Results suggested that BA supplementation can improve cognitive function in older adults whose cognitive function at baseline was at or below normal and possibly reduce depression scores.

Does ultrasound guidance during Dilation and Curettage for first trimester missed abortion reduce complication rates?

BACKGROUND: Dilation and Curettage (D&C) may be performed with or without transabdominal ultrasound guidance. We aimed to evaluate the association between the use of ultrasound guidance during D&C for first-trimester missed abortion (MA) and D&C related complication rates. METHODS: A retrospective cohort study including women in the age of 20-45 years, who underwent D&C for first-trimester MA in a hospital-based setting between 2013-2019. The study population was divided into two groups - the study group which included women who underwent D&C with ultrasound guidance (US group) and the control group, which included women who underwent D&C without ultrasound guidance (N-US group). Gynecologic, obstetric and operative related data were collected from electronic medical records. RESULTS: Three-hundred and seventy-eight women were included in the study, 86 women in the US group and 292 women in N-US group. Baseline maternal characteristics and procedure-related characteristics did not differ between the groups. No significant difference between the US group and N-US group was shown when comparing D&C related complications - retained products of conception rate (2.3% vs. 5.5%, respectively; p=0.385), uterine perforation rate (1.2% vs. 0.3%, respectively; p=0.404), and the total complication rate (8.1% vs. 12.3%, respectively; p=0.338). In a multivariate analysis, the use of ultrasound guidance during D&C was not found to be associated with lower complication rate (adjusted Odds Ratio (aOR) 95% confidence interval (CI) 1.468 (0.578-3.729), p=0.419). CONCLUSIONS: Performance of D&C under ultrasound guidance for first-trimester MA, in a hospital-based setting, was not associated with lower complication rate, suggesting that the common practice of performing D&C without the use of ultrasound is an acceptable approach.

Examination of Amorphous Calcium Carbonate on the Inflammatory and Muscle Damage Response in Experienced Resistance Trained Individuals.

The effect of 3 weeks of amorphous calcium carbonate (ACC) supplementation (2000 mg per day) was examined on the recovery response to resistance exercise. Thirty men were randomized into a supplement (ACC) or placebo (PL) group. Following supplementation, participants performed six sets of 10 repetitions in the bench press (BP) and incline BP exercises, using 80% of maximal strength. Participants returned 24 (T4) and 48 h (T5) later and performed six sets of the BP exercise. Significant decreases in the number of repetitions (p < 0.001), peak power (p < 0.001), and mean power (p = 0.009) were noted over time, but no significant interactions were observed (p > 0.05). Magnitude-based inference analysis (MBI) indicated that the change in repetitions was possibly beneficial for ACC at T4 and likely beneficial at T5. No significant interaction was noted for general soreness (p = 0.452), but a trend toward an interaction was observed in upper body soreness (p = 0.089). Confidence intervals for mean percent change scores indicated significant differences between the groups at T4 and T5, and MBI analysis indicated that ACC was very likely or likely to be beneficial for reducing soreness at those time points. In conclusion, ACC supplementation may have a potential beneficial effect in attenuating the decline in performance, which is possibly due to the carbonate component.

Examination of Cognitive Function, Neurotrophin Concentrations, and both Brain and Systemic Inflammatory Markers Following a Simulated Game of American Football.

ABSTRACT: Hoffman, JR, Ostfeld, I, Zamir, A, Amedi, R, Fonville, TR, Horstemeyer, MF, and Gepner, Y. Examination of cognitive function, neurotrophin concentrations, and both brain and systemic inflammatory markers following a simulated game of American football. J Strength Cond Res 36(3): 686-694, 2022-This investigation examined the effect of a simulated American football game on cognitive function, neurotrophin concentrations, and markers of both systemic and brain inflammation. Members of the Israel national team (6 linemen and 9 skill position players) were examined 1 week before (PRE), immediately post (IP) and 24-hour post (24P) game. Blood was obtained, and cognitive function was measured at each assessment. No head injuries to any of the players participating in the study occurred. Significant (p < 0.001) decreases in acute memory, and a trend (p = 0.066) toward a decrease in delayed memory was noted at IP. Significant negative correlations were observed between playing time (number of plays) and concentration changes from PRE to IP (r = -0.801; p = 0.001) and from PRE to 24P (r = -0.549; p = 0.034). All cognitive function measures returned to PRE levels by 24P. Increases from PRE were noted in tumor necrosis factor-alpha (TNF-α) (p = 0.041) at IP and in brain-derived neurotrophic factor (p = 0.009) and C-reactive protein (CRP) (p = 0.019) concentrations at 24P. Circulating CRP concentrations and the cytokine markers, interleukin (IL)-4, IL-6, IL-10, and TNF-α, were significantly elevated in linemen compared with skill players. Brain inflammatory markers (S100B and glial fibrillary acidic protein) and total tau protein (a marker of brain injury) were not elevated from PRE. No change from PRE was noted in either myoglobin or creatine kinase-MM concentrations. In conclusion, muscle damage and inflammatory marker responses observed from the scrimmage game were consistent with muscle desensitization associated with football participation. In addition, the systemic inflammatory marker results observed in linemen were suggestive of chronic low-grade inflammation.

Manipulation of Dietary Intake on Changes in Circulating Testosterone Concentrations.

Elevations in the circulating concentration of androgens are thought to have a positive effect on the anabolic processes leading to improved athletic performance. Anabolic-androgenic steroids have often been used by competitive athletes to augment this effect. Although there has been concerted effort on examining how manipulating training variables (e.g., intensity and volume of training) can influence the androgen response to exercise, there has been much less effort directed at understanding how changes in both macronutrient and micronutrient intake can impact the androgen response. Thus, the focus of this review is to examine the effect that manipulating energy and nutrient intake has on circulating concentrations of testosterone and what the potential mechanism is governing these changes.

Diabetes associated risk for mortality increases with time among first stroke survivors - Findings from the Israeli National Stroke Registry.

BACKGROUND: Diabetes is a major risk factor for ischemic stroke and may affect post-stroke survival. Previous large scale studies of long-term post-stroke survival are limited and most of them excluded older patients from the study population. OBJECTIVES: To compare the risk factors and sociodemographic characteristics between first ischemic stroke cases with and without diabetes and to assess the mortality risk associated with diabetes. METHODS: Using population-based National Stroke Registry in Israel, all patients hospitalized for a first event of ischemic stroke between the years 2014-2018 were followed for all-cause mortality. Chi-square analysis was used to compare the differences in risk factors, sociodemographic profile and cumulative mortality between patients with and without diabetes. Cox proportional hazards models were used to estimate the hazard ratio for mortality in selected timeframes. RESULTS: Among 41,639 patients with a first event of ischemic stroke, 44.5% were previously diagnosed with diabetes. Diabetic patients were more likely to be males, members of the Arab ethnic group, with lower socioeconomic status and a higher prevalence of cardiovascular comorbidities, anemia, leukocytosis and abnormal kidney function. Diabetes was associated with a higher mortality risk in the first year and long term, but not in the first month following stroke. Diabetes-associated mortality risk interacted with time and age, was higher in younger age and increased with time. CONCLUSIONS: Our findings suggest that diabetes is associated with a higher prevalence of comorbidities among patients with first ischemic stroke and with a higher risk for mortality in the mid and long term, which is more profound in younger age.

Trends in antimicrobial resistance among bacteria causing septic arthritis in adults in a single center: A 15-years retrospective analysis.

Septic arthritis (SA) is commonly associated with Staphylococcal or Streptococcal infections. Overtime, there has been a global increase in the distribution of antimicrobial resistance within both Gram-positive bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative bacteria such as extended-spectrum beta-lactamase (ESBL) positive Enterobacteriacea. The aim of this study was to determine whether this change in epidemiology similarly affected the distribution of resistant pathogens causing SA. The study was conducted at the Shaare Zedek Medical Center in Jerusalem, Israel. All adult patients diagnosed with SA during 2002-2016 were included in the cohort. Antimicrobial resistance trends were examined over three periods: 2002-2009, 2010-2013, and 2014-2016. Of 85 patients with SA, mean age of patients was 66.8 (± 20.3) years, with male predominance (n = 62, 66%). Most SA cases involved native knee joints and more than 85% (n = 80) were acquired in the community. The most common isolates were S. aureus (n = 38, 45%) and beta-hemolytic streptococci (n = 13, 15%). MRSA SA was diagnosed in 8% of all SA cases (n = 7). An increasing, although non-significant trend in MRSA SA was observed during the study period (p = 0.3). Gram-negative infections were uncommon (n = 14). No ESBL-positive or carbapenem-resistant Enterobacteriacea were detected. Over a 15-year study period, no significant increase in resistant pathogens causing SA was observed. In the era of antibiotic stewardship, these results strengthen our practice of administering narrow-spectrum antimicrobials empirically for SA. However, our findings cannot be generalized to regions with higher rates of MRSA in the community.

p16(Ink4a)-induced senescence of pancreatic beta cells enhances insulin secretion.

Cellular senescence is thought to contribute to age-associated deterioration of tissue physiology. The senescence effector p16(Ink4a) is expressed in pancreatic beta cells during aging and limits their proliferative potential; however, its effects on beta cell function are poorly characterized. We found that beta cell-specific activation of p16(Ink4a) in transgenic mice enhances glucose-stimulated insulin secretion (GSIS). In mice with diabetes, this leads to improved glucose homeostasis, providing an unexpected functional benefit. Expression of p16(Ink4a) in beta cells induces hallmarks of senescence--including cell enlargement, and greater glucose uptake and mitochondrial activity--which promote increased insulin secretion. GSIS increases during the normal aging of mice and is driven by elevated p16(Ink4a) activity. We found that islets from human adults contain p16(Ink4a)-expressing senescent beta cells and that senescence induced by p16(Ink4a) in a human beta cell line increases insulin secretion in a manner dependent, in part, on the activity of the mechanistic target of rapamycin (mTOR) and the peroxisome proliferator-activated receptor (PPAR)-γ proteins. Our findings reveal a novel role for p16(Ink4a) and cellular senescence in promoting insulin secretion by beta cells and in regulating normal functional tissue maturation with age.