Anticancer potential of fermented milk with autochthonous lactic acid bacteria.

AIMS: The purpose of this study was to investigate the effect of fermented milk supernatants of autochthonous lactic acid bacteria, including Lactobacillus helveticus KMCH1 (ON561781), Lactococcus lactis KMCM3 (ON561782), and Lactiplantibacillus plantarum KMJC4 (ON615217), on human colon cancer (HT-29) and normal mouse fibroblast (L929) cells in vitro. METHODS AND RESULTS: Proteolytic activity, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide test, evaluation of apoptosis induction, and cell cycle arrest by flow cytometry were the assays performed in this study. The measurement of proteolytic activity of three types of fermented milk supernatant using an orthophthalaldehyde reagent showed that the fermented milk supernatant of L. helveticus KMCH1 included the highest proteolysis. Three types of fermented milk supernatant showed anticancer effects on HT-29 cell in a time- and concentration-based manner (at a concentration of 16 mg ml-1 for 72 h of incubation), while the effect of three types of supernatant on inhibition of L929 cell was 3%-10%. Besides, three types of supernatant inhibited HT-29 cell proliferation by inducing apoptosis and cell cycle arrest in the S phase. CONCLUSIONS: Autochthonous lactic acid bacteria strains were able to produce bioactive peptides with anticancer effects in fermented milk. Inhibition of HT-29 cell proliferation was dependent on peptide concentration.

Implementation of a formal sleep center-based screening protocol for primary aldosteronism in patients with obstructive sleep apnea.

BACKGROUND: There is a bidirectional association between primary aldosteronism and obstructive sleep apnea, with evidence suggesting that the treatment of primary aldosteronism can reduce obstructive sleep apnea severity. Current guidelines recommend screening for primary aldosteronism in patients with comorbid hypertension and obstructive sleep apnea, identifying potential candidates for treatment. However, emerging data suggest current screening practices are unsatisfactory. Moreover, data regarding the true incidence of primary aldosteronism among this population are limited. This study aimed to assess the primary aldosteronism screening rate among patients with obstructive sleep apnea and hypertension at our institution and estimate the prevalence of primary aldosteronism among this population. METHODS: Sleep studies conducted at our institution between January and September 2021 were retrospectively reviewed. Adult patients with a sleep study diagnostic of obstructive sleep apnea (respiratory disturbance index ≥5) and a diagnosis of hypertension were included. Patient medical records were reviewed and laboratory data of those with biochemical screening for primary aldosteronism were assessed by an experienced endocrinologist. Screening rates were compared before and after initiation of a screening protocol in accordance with the 2016 Endocrine Society guidelines. RESULTS: A total of 1,005 patients undergoing sleep studies were reviewed; 354 patients had comorbid obstructive sleep apnea and hypertension. Patients were predominantly male (67%), with a mean age of 58 years (standard deviation = 12.9) and mean body mass index of 34 (standard deviation = 8.1). The screening rate for primary aldosteronism among included patients was 19% (n = 67). The screening rate was significantly higher after initiation of a dedicated primary aldosteronism screening protocol (23% vs 12% prior; P = .01). Fourteen screens (21%) were positive for primary aldosteronism, whereas 45 (67%) were negative and 8 (12%) were indeterminate. Four had prior abdominal cross-sectional imaging, with 3 revealing an adrenal adenoma. Compared with patients without primary aldosteronism, patients with positive primary aldosteronism screens were more likely to have a history of hypokalemia (36% vs 4.4%; P = .002). The frequency of hyperlipidemia, diabetes mellitus, and left ventricular hypertrophy did not differ between patients with positive versus negative screens. CONCLUSION: Current screening practices for primary aldosteronism among patients with comorbid obstructive sleep apnea and hypertension are suboptimal. Patients evaluated at sleep centers may represent an optimal population for screening, as the prevalence of primary aldosteronism among this cohort appears high.

Evaluation of the effect of a gel made with amniotic fluid formulation on the healing of diabetic foot ulcers: A triple-blind clinical trial.

Aim: The aim of this study was to evaluate the effect of a gel made with amniotic fluid (AF) formulation on wound healing in diabetic foot ulcers. Methods: This clinical trial was performed on 92 type 2 diabetic patients referring to the Diabetes Clinic of Golestan Hospital of Ahvaz, southwest of Iran in 2019-2020. Patients were randomly divided into three groups of intervention and one placebo group. The wounds of the three intervention groups were dressed with gauze impregnated with an AF formulation gel while wounds of the control group were dressed with plain gauze without any topical agent. Chi-square tests and generalized estimating equations (GEE) with a significance level of 0.05 were used to analyze the data. Results: At the end of the eighth week of intervention, there was a statistically significant difference among the four groups in terms of wound grade, wound color, condition of the tissues surrounding the wound, the overall condition of the wound, and the duration of wound healing (P < 0.05). Conclusions: Based on our experience with the patients in the present study, we believe that AF represents a useful and safe option for the treatment of chronic diabetic foot ulcers. Clinical trial registration: https://en.irct.ir/trial/51551, Identifier: IRCT20201010048985N1.

A Case of Recurrent Hypersomnia With Autonomic Dysfunction.

ABSTRACT: We report the case of a 50-year-old man with disabling recurrent hypersomnia with autonomic instability due to catatonia in the setting of atypical bipolar disorder. Treatment with valproic acid for bipolar disorder resulted in complete resolution of symptoms.

A Case of Recurrent Insomnia: Extending the Spectrum of Autoimmune Encephalitis.

ABSTRACT: Recurrent insomnia is an uncommon manifestation that is encountered rarely in a sleep clinic. We report a woman with recurrent insomnia due to an autoimmune process that resolved after a course of immunotherapy.

Tongue biting: a case of sporadic geniospasm during sleep.

ABSTRACT: We report a healthy teenager with involuntary nocturnal tongue biting resulting in recurrent tongue injury. Causes for tongue biting during sleep in children include seizures, bruxism, faciomandibular myoclonia, hypnic myoclonia, and rarely geniospasm, which has been described as a rare inherited movement disorder accompanied with chin quivering. In the absence of family history, we diagnosed our patient with sporadic geniospasm based on polysomnographic findings with good response to clonazepam. Geniospasm should be considered in the differential diagnosis of cases with unexplained tongue injury in sleep.

The impact of gender on timeliness of narcolepsy diagnosis.

STUDY OBJECTIVES: To examine the impact of gender in narcoleptic patients on timeliness of diagnosis, symptomology, and health and lifestyle impairment. METHODS: This is a cross-sectional study of 109 consecutive patients (68 women) with newly diagnosed narcolepsy with and without cataplexy, from a University sleep disorders center. Consecutive patients were administered an 8-page questionnaire at the time of their diagnosis regarding sleep habits, medications, and medical conditions, lifestyle impairments, as well as details regarding narcolepsy-related symptoms. RESULTS: Men and women presented with remarkably similar narcolepsy related symptoms, yet women were more likely to be delayed in diagnosis; 85% of men were likely to be diagnosed by 16 years after symptom onset, compared to 28 years in women. More women were likely to remain undiagnosed at any given time point after symptom onset (hazard ratio for diagnosis of men compared to women 1.53; 95% CI 1.01-2.32; p = 0.04). Men and women reported similar degree of subjective sleepiness as measured by the Epworth Sleepiness Scale (mean 16.2 ± 4.5; p = 0.18), though women demonstrated significantly more severe objective sleepiness on multiple sleep latency testing (MSLT) (mean sleep latency in women = 5.4 min (± 4.1), in men 7.4 min (± 3.5); p = 0.03). Despite being more objectively sleepy, women were less likely to report lifestyle impairments in the areas of personal relationships (71% men, 44% women, p = 0.01) and physical activity (36% men, 16% women, p = 0.02), but were also more likely to self-medicate with caffeine (63.4% men, 82.4% women; p = 0.03). CONCLUSIONS: Narcolepsy impacts men and women's health and lifestyle differently, and may cause delays diagnosis for women.

The cost-effectiveness of oral direct factor Xa inhibitors compared with low-molecular-weight heparin for the prevention of venous thromboembolism prophylaxis in total hip or knee replacement surgery.

INTRODUCTION: Major orthopedic surgery is associated with a high risk of venous thromboembolism (VTE). Anticoagulants are recommended to prevent VTE, and recently an oral direct factor Xa inhibitor (FXaI) was approved for this indication. We compared the cost-effectiveness of FXaIs with low-molecular-weight heparin (LMWH) in patients undergoing total hip replacement (THR) or total knee replacement (TKR) surgery. DESIGN: A decision-tree model was developed to compare the cost-effectiveness of oral direct FXaIs (rivaroxaban, apixaban, and edoxaban) to subcutaneous LMWHs (enoxaparin and dalteparin), with separate models for THR and TKR. The analysis was conducted over a 180-day postoperative time horizon from the U.S. Medicare perspective. The model was developed using TreeAge Pro 2011 (TreeAge Software Inc., Williamstown, MA, USA). METHODS: Efficacy and safety data (probabilities of distal and proximal deep vein thrombosis, symptomatic pulmonary embolism, and major bleeding) were derived from a systematic review and meta-analysis of phase II and III clinical trials. Costs and quality-adjusted life-years (QALYs) are reported. One-way and probabilistic sensitivity analyses were performed to evaluate parameter uncertainty. RESULTS: In the THR model, the average costs per patient for FXaIs and LMWHs were $18,762 and $18,897, respectively, and the QALYs were 0.938 and 0.932. In the TKR model, the average cost per patient for FXaIs and LMWHs were $18,804 and $18,991, respectively, and the QALYs were 0.935 and 0.931. In both models, FXaIs dominated LMWH (less costly and more efficacious). Neither model was sensitive to changes in any of the variables in the one-way sensitivity analyses. Probabilistic sensitivity analysis indicated that FXaIs were cost-effective in more than 99% of iterations in the THR population and in 98% of iterations in the TKR population assuming a willingness-to-pay threshold of $50,000/QALY. CONCLUSION: Oral direct FXaIs may be an economically dominant strategy compared with LMWHs for VTE prophylaxis in patients undergoing either THR or TKR surgery.

Optimal timing for postprandial glucose measurement in pregnant women with diabetes and a non-diabetic pregnant population evaluated by the Continuous Glucose Monitoring System (CGMS).

OBJECTIVE: Using the Continuous Glucose Monitoring System (CGMS; Medtronic Minimed) for a group of pregnant women with and without glucose intolerance, we attempted to answer the following questions: (1) when does the physiological peak of postprandial glucose occur?; (2) do non-diabetic pregnant women and pregnant women with diabetes have different postprandial glucose profiles?; and (3) what is the optimal time for postprandial glucose measurement rated according to clinical outcome? METHODS: We included 53 pregnant women in our study. Based on the criteria of the German Diabetes Association (fasting, 5.0 mmol/L; 1-h, 10.0 mmol/L; 2-h, 8.6 mmol/L) we included 13 women with gestational diabetes, four with type 1 diabetes and 36 non-diabetic pregnant (NDP) women. Gestational and type 1 diabetics were classed as one group: pregnancy complicated by diabetes (PCD). Patients with carbohydrate intolerance underwent dietary counseling in accordance with the recommendations of the American Diabetes Association. Patients received a CGMS for use over 72 h. This was calibrated seven times a day with an Accu-Check. The pre- and postprandial glucose levels were documented at 15-min intervals for 3 h from the beginning of each meal. The postprandial data from the three meals were added. The group was divided according to three clinical outcome parameters: mode of delivery, birth weight percentile, and diabetes-associated complications. RESULTS: Statistically significant differences between groups were found for body mass index, fetal birth weight and oral glucose tolerance test. No significant differences were found for age, parity and gestational age, mode of delivery, and diabetes-associated complications. The sensor provided similar numbers of measurements in both groups (278+/-43 vs. 298+/-73, P = 0.507). The postprandial glucose peak was reached after 82+/-18 min in the non-diabetics vs. 74+/-23 min in the PCD group (not significant). Postprandial glucose values were normally slightly higher in PCD (not significant). We added the postprandial glucose values at each time interval for the three meals for each day. For the sum, there was a significant difference between the measurements at 120 min and at 135 min postprandial (P < 0.05). Dividing the group by clinical outcome showed a significant difference between the postprandial time intervals of 75 min and 105 min (P < 0.05). In addition, the time interval was different from 60 min to 135 min for the mode of delivery and birth weight percentile (P < 0.05). CONCLUSION: The 120-min interval is too long and has a lower correlation to clinical outcome parameters than earlier measurements. Our findings show that the optimal time for testing is between 45 and 120 min postprandial. Based on our practical experience and dietary recommendations, we would prefer a 60-min interval, because patients can calculate this more easily and can have more freedom to eat the recommended number of snacks.