Elevated L-lactate Promotes Major Cellular Pathologies Associated with Neurodegenerative Diseases

Dear Editor,Small,short-chain fatty acids(SCFAs)(acetic acid,propionic acid,and butyric acid:conjugate bases,acetate,propionate,and butyrate)as well as the alpha-hydroxy acid,L-lactic acid(conjugate base,L-lactate)are important energy substrates and signaling molecules in the central nervous system(CNS)[1,2].L-lactic acid is produced by glycolysis[3]and gut microbes[4]and is released in large quantities during exercise[5].     

Family mealtime emotions and food parenting practices among mothers of young children: Development of the Mealtime Emotions Measure for Parents (MEM‐P)

Family mealtimes can be important for supporting children''s healthy development, yet the emotional context of mealtimes can vary considerably, likely impacting their overall success and enjoyment. Yet, despite having an important role, little is known about how parents emotionally experience mealtimes with their family. The first aim of the current study was to assess the factor structure of a novel self‐report measure to assess parents’ emotional responses experienced during family mealtimes (Mealtime Emotions Measure for Parents; MEM‐P). The second aim was to examine relationships between maternal mealtime emotions and their food parenting practices. Mothers of children aged between 1.5 and 6 years participated in this study. Mothers were invited to complete an online questionnaire measuring family mealtime emotions, anxiety, depression and food parenting practices. Exploratory factor analysis produced a three‐factor solution comprising both positive and negative emotion subscales: MEM‐P Efficacy; MEM‐P Anxiety; MEM‐P Stress and Anger. Mothers'' positive mealtime emotions (mealtime efficacy) were related to greater use of practices promoting autonomy, providing a healthy home food environment, and modelling healthy eating. Higher anxiety about mealtimes was related to greater reports of child control over eating, and mealtime stress and anger was associated with greater use of food to regulate emotions. These findings highlight novel relationships between how mothers emotionally experience family mealtimes and the food parenting practices they use with their children. It is important to develop resources to help promote positive maternal experiences of family mealtimes and food‐based interactions.     

Duloxetine, a serotonin and noradrenaline reuptake inhibitor (SNRI) for the treatment of stress urinary incontinence: a systematic review

OBJECTIVE: Surgery and pelvic floor muscle training are established methods for treating stress urinary incontinence (SUI). A new serotonin and noradrenaline reuptake inhibitor, duloxetine, has been studied in multiple phase 3 trials as a form of medical management of this condition. This systematic review determined the effectiveness and acceptability of duloxetine in managing SUI. METHODS: We reviewed all randomised controlled trials comparing duloxetine with placebo or no treatment. The search included the Cochrane Incontinence Group specialised register, CENTRAL, MEDLINE, PREMEDLINE, dissertation abstracts, and the reference lists of relevant articles. The primary outcome was the number of participants whose symptoms were "cured" while on treatment. Secondary outcomes included subjective improvement, incontinent episodes, quality of life, adverse events, and discontinuation rates. RESULTS: Nine trials were included, totalling 3063 women with predominantly SUI, all randomised to receive duloxetine or placebo. Treatment duration was 3-36 wk. Subjective cure favoured duloxetine (from three trials, 10.8% vs. 7.7%; RR=1.42; 95%CI, 1.02-1.98, p=0.04). The limited data available to assess objective cure rates were consistent with this. Individual studies showed a significant reduction in the Incontinence Episode Frequency (IEF) by approximately 50% during treatment. Duloxetine groups had significantly better quality-of-life scores (weighted mean difference for Incontinence Quality of Life Index for participants on 80 mg daily: 4.5; 95%CI, 2.83-6.18; p<0.00001) and rates of symptom improvement. Adverse effects were common (71% vs. 59%) but are reported as not serious and were equivalent to about one in eight participants reporting adverse effects (most commonly nausea) directly related to duloxetine treatment. About one in eight stopped treatment as a consequence of taking duloxetine (17% vs. 4%). CONCLUSIONS: Duloxetine can significantly improve the quality of life of patients with SUI, but it is unclear whether or not benefits are sustainable. Side-effects such as nausea are common.     

Free vascularized fibular grafting following failed core decompression for femoral head osteonecrosis

The results of treatment of femoral head osteonecrosis with free vascularized fibular grafting (FVFG) following failed core decompression (core decompression-FVFG [CD-FVFG] group: 32 hips) were reviewed and compared with those of a control group that underwent FVFG only (54 hips). Outcome was considered unsuccessful if total hip arthroplasty was subsequently performed. Total hip arthroplasty was performed in 15 and 20 hips of the CD-FVFG and control groups, respectively. When considering age, sex, and presence of bilateral disease, patients with previous core decompression did not have a significantly different failure rate from patients with FVFG only. However, patients with preoperative stage V osteonecrosis or corticosteroid use had worse outcomes after vascularized fibular grafting if they had a previous core decompression of the femoral head.     

Vascularized periosteal flaps of distal forearm and hand

BACKGROUND: Vascularized periosteal flaps (VPFs) are flexible osteogenic flaps, suitable for the reconstruction of small skeletal defects. Pedicled VPFs, harvested near the recipient site, minimize donor-site morbidity and procedure duration. The donor sites and the potential recipient sites for pedicled VPFs of the distal forearm-hand were identified in this study. METHODS: In 16 fresh cadaver upper extremities, the dimensions and arcs of rotation of the VPF pedicle(s) were studied. RESULTS: Pedicled VPFs with mean dimensions ranging between 0.5 x 3 cm and 2.5 x 4 cm could cover, after adequate mobilization, the distal half of the forearm, wrist, and hand to the proximal interphalangeal joints. CONCLUSION: The VPFs identified in this study can be used for the reconstruction of small skeletal defects and for the treatment of osteonecrotic lesions and nonunions of the distal forearm, wrist, and hand. The choice of the most suitable VPF will be based on the anatomic location and the dimensions of the recipient site.     

Loss-of-Function Mutations in the ALPL Gene Presenting with Adult Onset Osteoporosis and Low Serum Concentrations of Total Alkaline Phosphatase

Hypophosphatasia (HPP) is a rare inherited disorder characterized by rickets and low circulating concentrations of total alkaline phosphatase (ALP) caused by mutations in ALPL. Severe HPP presents in childhood but milder forms can present in adulthood. The prevalence and clinical features of adult HPP are poorly defined. The aim of this study was to evaluate the prevalence and clinical significance of low serum total alkaline phosphatase (ALP) levels in a clinic-based population of adult osteoporotic patients. We searched for patients with low ALP in a cohort of 3285 patients referred to an osteoporosis clinic over a 10-year period and performed mutation screening of ALPL in those with low ALP (≤40 U/L) on two or more occasions. These individuals were matched with four clinic controls with a normal ALP. We also evaluated the prevalence of low ALP and ALPL mutations in 639 individuals from the general population from the same region. We identified 16/3285 (0.49%) clinic patients with low ALP and 14 (87.5%) had potentially pathogenic variants in ALPL. Eight of these individuals were heterozygous for mutations previously described in HPP and 2 were heterozygous for novel mutations (p.Arg301Trp and p.Tyr101X). These mutations were not found in clinic controls or in the general population. Eight patients with low ALP, including 4 with ALPL mutations, were treated with bisphosphonates for an average of 6.5 years. In these individuals, the rate of fractures during treatment was comparable to that in normal ALP clinic controls who were treated with bisphosphonates. We conclude that heterozygous loss-of-function mutations in ALPL are common in osteoporosis patients with low ALP. Further studies are required to determine how best these individuals should be treated. © 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.     

Best practices to optimize utilization of the National Living Donor Assistance Center for the financial assistance of living organ donors

Living organ donors face direct costs when donating an organ, including transportation, lodging, meals, and lost wages. For those most in need, the National Living Donor Assistance Center (NLDAC) provides reimbursement to defray travel and subsistence costs associated with living donor evaluation, surgery, and follow‐up. While this program currently supports 9% of all US living donors, there is tremendous variability in its utilization across US transplant centers, which may limit patient access to living donor transplantation. Based on feedback from the transplant community, NLDAC convened a Best Practices Workshop on August 2, 2018, in Arlington, VA, to identify strategies to optimize transplant program utilization of this valuable resource. Attendees included team members from transplant centers that are high NLDAC users; the NLDAC program team; and Advisory Group members. After a robust review of NLDAC data and engagement in group discussions, the workgroup identified concrete best practices for administrative and transplant center leadership involvement; for individuals filing NLDAC applications at transplant centers; and to improve patient education about potential financial barriers to living organ donation. Multiple opportunities were identified for intervention to increase transplant programs’ NLDAC utilization and reduce financial burdens inhibiting expansion of living donor transplantation in the United States.     

Cosmetic treatment of nails

Nail cosmetics are an important part of personal expression. Although their use can result in a variety of dermatologic issues, the popularity of nail cosmetics is huge. Dermatologists must recognize problems associated with nail cosmetics and understand the process for using these cosmetics. Many problems can be avoided through careful use or a change in the application procedure.