Effects of low‐frequency intravaginal electrical stimulation on female urinary incontinence,quality of life,and urinary symptoms: A pilot study

This study investigated the effects of a low‐frequency home‐based incontinence therapy device on quality of life (QoL) and urinary symptoms in women with urinary incontinence. From May 2017 to February 2018, 34 patients, aged ≥ 20 years, with involuntary urine leakage >2 times/week, were recruited to this study. Patients with severe pelvic organ prolapse, pregnancy, virgin status, and psychological problems were excluded. The incontinence home‐care device treatments were administered in 12‐minute sessions, twice daily for 8 weeks. Simultaneously, hyperthermic conditions of 35°C to 40°C and microvibrations were administered. All patients completed urinary incontinence questionnaires (King's Health Questionnaire [KHQ], Bristol Female Lower Urinary Tract Symptoms [BFLUTS] questionnaire, and the Overactive Bladder Symptom Score [OABSS]) before treatment, as well as 4 and 8 weeks into treatment. Changes in the questionnaire responses over time were compared. Two participants dropped out of the study and there was one screening failure, leaving 31 patients for analysis. After 4 weeks treatment, there were significant improvements in symptoms, such as role limitation, physical limitation, social limitation, personal relationship, emotion, sleep/energy, and severity measures. After 8 weeks treatment, almost all parameters on the KHQ revealed symptomatic improvement. On the BFLUTS, voiding times during activity, nocturia, urgency, urge incontinence, incontinence frequency, stress incontinence, volume leakage, strain to start, intermittency, reduced stream, acute retention, incomplete emptying, and stopping flow showed significant improvements. On the OABSS, almost all storage symptoms improved. Low‐frequency electrical stimulation devices were effective at improving urinary incontinence, which became evident as the duration of treatment increased. Improvement of urgency and frequency was more evident after treatment.     

Phylogenetic Analyses of HBV Pre-S/S Genes in Mother-Child Pairs with Long-Term Infection by Presumed Vertical Transmission

Vertical transmission from mother to child, the main route of chronic hepatitis B virus (HBV) infection in the East Asia, is considered one of the most important predictors for the response to antiviral therapies as well as its complications such as cirrhosis and hepatocellular carcinoma. Therefore, it is critical in both etiologic and prognostic aspects to confirm whether or not chronic HBV infection is acquired vertically. This study investigated whether mother-to-child infection could be proved by the phylogenetic analyses of HBV pre-S/S genes ever since several decades have elapsed in mother-child pairs with presumed vertical transmission. The pre-S and S regions of HBVs were compared and analyzed phylogenetically in a total of 36 adults (18 mother-child pairs) with chronic HBV infection. All of the isolates of HBV were genotype C and serotype adr. The divergence between mothers and offsprings was 0 to 1.5%. Phylogenetic trees revealed that 17 of 18 pairs (94%) with presumed vertical transmission were grouped into the same cluster. Vertical transmission from mother to child could be strongly suggested even in adults with a history of several decades of HBV infection using the phylogenetic analyses of pre-S and S genes.

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Prevalence and prognosis of the 2018 vs 2008 AHA definitions of apparent treatment‐resistant hypertension in high‐risk hypertension patients

Resistant hypertension was defined according to the 2008 scientific statement as office blood pressure ≥ 140/90 mm Hg and the 2018 scientific statement as office blood pressure ≥ 130/80 mm Hg. We investigated the prognostic significance of lowered blood pressure threshold for defining resistant hypertension in the 2018 American Heart Association scientific statement compared with that in the 2008 scientific statement. The participants of this prospective cohort were enrolled from December 2013 to November 2018. Major adverse cardiovascular events (MACEs) were defined as a composite of cardiovascular death, non‐fatal myocardial infarction, non‐fatal stroke, and heart failure hospitalization. Renal event was defined as a ≥ 50% decline in estimated glomerular filtration rate or progression to end‐stage renal disease. A total of 206 patients among 2018 (10.2%) were diagnosed with resistant hypertension by the previous definition (≥140/90 mm Hg), and 276 patients among 2011 (13.7%) were diagnosed with resistant hypertension by the updated definition (≥130/80 mm Hg). During a median follow‐up of 4.5 years, 33 MACEs (3.7 per 1000 patient‐years) and 164 renal events (19.9 per 1000 patient‐years) occurred in the study population. Treatment‐resistant hypertension groups had a higher incidence rate of MACEs and renal events than the control groups. In multivariate Cox proportional hazards regression analysis, resistant hypertension by both definitions was significantly associated with increased risk of MACE and renal event. Both the previous and updated definitions of resistant hypertension were significant predictors of MACEs and renal events. This finding supports the adoption of the updated criteria for resistant hypertension in clinical practice.     

Association between muscle strength and metabolic syndrome in older Korean men and women: the Korean Longitudinal Study on Health and Aging

The objective of the study was to investigate the association between metabolic syndrome (MS) and muscle strength in community-dwelling older men and women in Korea. Korean men and women 65 years and older living in a single, typical South Korean city (n = 647) were enrolled in the Korean Longitudinal Study on Health and Aging study. The diagnosis of MS was evaluated according to the definition of the National Cholesterol Education Program Adult Treatment Panel III. Isokinetic muscle strength of the knee extensors, as determined by peak torque per body weight (newton meter per kilogram) and hand-grip strength per body weight (newton per kilogram), was measured. Participants without MS had greater leg muscle strength and grip strength per weight. The effect of MS on muscle strength was more prominent in men than in women in our study population. Only men showed a significant interaction between MS and age for muscle strength (P = .014), and the effect was greater in men aged 65 to 74 years compared with those older than 75 years (119.2 ± 31.2 vs 134.5 ± 24.3 N m/kg). Participants with MS had weaker knee extensor strength after controlling the covariates (β = -90.80, P = .003), and the interaction term (age × MS × male sex) was significant (β = 1.00, P = .017). Metabolic syndrome is associated with muscle weakness, and this relationship is particularly pronounced in men. Age can modify the impact of MS on muscle strength. Men aged 65 to 74 years with MS need a thorough assessment of muscle strength to prevent disability.     

The association between triglyceride to high-density-lipoprotein cholesterol ratio and insulin resistance in a multiethnic primary prevention cohort

The objective was to explore the clinical utility of triglyceride (TG) to high-density lipoprotein cholesterol (HDL-C) ratio in predicting insulin resistance (IR) in 4 ethnic groups and the relationship between IR and TG/HDL-C in comparison to that with other lipid measures. Apparently healthy Aboriginals, Chinese, Europeans, and South Asians (N = 784) were assessed for sociodemographics, lifestyle, anthropometry, lipids, glucose, and insulin. The homeostasis model assessment of IR was used as a measure of IR. Compared with other lipid parameters, TG/HDL-C was the highest correlate of the homeostasis model assessment of IR (age and sex adjusted) in Aboriginals (r = 0.499, P < .001), Chinese (r = 0.432, P < .001), Europeans (r = 0.597, P < .001), and South Asians (0.372, P < .001). For a 1-unit increase in TG/HDL-C, the odds of being insulin resistant increased about 4 times (odds ratio [OR], 3.95; 95% confidence interval [CI], 1.86-8.42; P < .001) in Aboriginals, 3.4 times in Chinese (OR, 3.44; 95% CI, 1.79-6.62; P < .001), 1.9 times in Europeans (OR, 1.94; 95% CI, 1.00-3.75; P = .049), and 1.8 times in South Asians (OR, 1.77; 95% CI, 0.91-3.45; P = .094) (age, sex, smoking, physical activity, body mass index, and waist circumference adjusted). Receiver operating characteristic curve analyses revealed areas under the curve (95% CI) of 0.777 (0.707-0.847) in Aboriginals, 0.723 (0.647-0.798) in Chinese, 0.752 (0.675-0.828) in Europeans, and 0.676 (0.590-0.762) in South Asians. Optimal cutoffs (sensitivity, specificity) of TG/HDL-C for identifying individuals with IR were 0.9 (93.0%, 51.9%), 1.1 (71.7%, 61.5%), 1.1 (73.5%, 70.9%), and 1.8 (52.0%, 77.9%) in Aboriginal, Chinese, European, and South Asian individuals, respectively. The TG/HDL-C ratio may be a good marker to identify insulin-resistant individuals of Aboriginal, Chinese, and European, but not South Asian, origin.     

Spatial navigation impairment is proportional to right hippocampal volume

Cognitive deficits in older adults attributable to Alzheimer's disease (AD) pathology are featured early on by hippocampal impairment. Among these individuals, deterioration in spatial navigation, manifested by poor hippocampus-dependent allocentric navigation, may occur well before the clinical onset of dementia. Our aim was to determine whether allocentric spatial navigation impairment would be proportional to right hippocampal volume loss irrespective of general brain atrophy. We also contrasted the respective spatial navigation scores of the real-space human Morris water maze with its corresponding 2D computer version. We included 42 cognitively impaired patients with either amnestic mild cognitive impairment (n = 23) or mild and moderate AD (n = 19), and 14 cognitively intact older controls. All participants underwent 1.5T MRI brain scanning with subsequent automatic measurement of the total brain and hippocampal (right and left) volumes. Allocentric spatial navigation was tested in the real-space version of the human Morris water maze and in its corresponding computer version. Participants used two navigational cues to locate an invisible goal independent of the start position. We found that smaller right hippocampal volume was associated with poorer navigation performance in both the real-space (β = -0.62, P < 0.001) and virtual (β = -0.43, P = 0.026) versions, controlling for demographic variables, total brain and left hippocampal volumes. In subsequent analyses, the results were significant in cognitively impaired (P ≤ 0.05) but not in cognitively healthy (P > 0.59) subjects. The respective real-space and virtual scores strongly correlated with each other. Our findings indicate that the right hippocampus plays a critical role in allocentric navigation, particularly when cognitive impairment is present.     

Type II p21-activated kinases (PAKs) are regulated by an autoinhibitory pseudosubstrate

The type II p21-activated kinases (PAKs) are key effectors of RHO-family GTPases involved in cell motility, survival, and proliferation. Using a structure-guided approach, we discovered that type II PAKs are regulated by an N-terminal autoinhibitory pseudosubstrate motif centered on a critical proline residue, and that this regulation occurs independently of activation loop phosphorylation. We determined six X-ray crystal structures of either full-length PAK4 or its catalytic domain, that demonstrate the molecular basis for pseudosubstrate binding to the active state with phosphorylated activation loop. We show that full-length PAK4 is constitutively autoinhibited, but mutation of the pseudosubstrate releases this inhibition and causes increased phosphorylation of the apoptotic regulation protein Bcl-2/Bcl-X_L antagonist causing cell death and cellular morphological changes. We also find that PAK6 is regulated by the pseudosubstrate region, indicating a common type II PAK autoregulatory mechanism. Finally, we find Src SH3, but not β-PIX SH3, can activate PAK4. We provide a unique understanding for type II PAK regulation.