BACKGROUND: Recent evidence indicates that insulin resistance in skeletal muscle may be related to reduce mitochondrial number and oxidation capacity. However, it is not known whether increasing mitochondrial number and function improves insulin resistance. In the present study, we investigated the effects of a combination of nutrients on insulin resistance and mitochondrial biogenesis/function in skeletal muscle of type 2 diabetic Goto-Kakizaki rats. METHODOLOGY/PRINCIPAL FINDINGS: We demonstrated that defect of glucose and lipid metabolism is associated with low mitochondrial content and reduced mitochondrial enzyme activity in skeletal muscle of the diabetic Goto-Kakizaki rats. The treatment of combination of R-alpha-lipoic acid, acetyl-L-carnitine, nicotinamide, and biotin effectively improved glucose tolerance, decreased the basal insulin secretion and the level of circulating free fatty acid (FFA), and prevented the reduction of mitochondrial biogenesis in skeletal muscle. The nutrients treatment also significantly increased mRNA levels of genes involved in lipid metabolism, including peroxisome proliferator-activated receptor-alpha (Ppar alpha), peroxisome proliferator-activated receptor-delta (Ppar delta), and carnitine palmitoyl transferase-1 (Mcpt-1) and activity of mitochondrial complex I and II in skeletal muscle. All of these effects of mitochondrial nutrients are comparable to that of the antidiabetic drug, pioglitazone. In addition, the treatment with nutrients, unlike pioglitazone, did not cause body weight gain. CONCLUSIONS/SIGNIFICANCE: These data suggest that a combination of mitochondrial targeting nutrients may improve skeletal mitochondrial dysfunction and exert hypoglycemic effects, without causing weight gain.

BACKGROUND:Silver nanoparticles (AgNPs) are potential antimicrobials agents, which can be considered as an alternative to antibiotics for the treatment of infections caused by multi-drug resistant bacteria. The antimicrobial effects of double and triple combinations of AgNPs, visible blue light, and the conventional antibiotics amoxicillin, azithromycin, clarithromycin, linezolid, and vancomycin, against ten clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) were investigated.

METHODS:The antimicrobial activity of AgNPs, applied in combination with blue light, against selected isolates of MRSA was investigated at 1/2-1/128 of its minimal inhibitory concentration (MIC) in 24-well plates. The wells were exposed to blue light source at 460 nm and 250 mW for 1 h using a photon emitting diode. Samples were taken at different time intervals, and viable bacterial counts were determined. The double combinations of AgNPs and each of the antibiotics were assessed by the checkerboard method. The killing assay was used to test possible synergistic effects when blue light was further combined to AgNPs and each antibiotic at a time against selected isolates of MRSA.

RESULTS:The bactericidal activity of AgNPs, at sub-MIC, and blue light was significantly (p < 0.001) enhanced when both agents were applied in combination compared to each agent alone. Similarly, synergistic interactions were observed when AgNPs were combined with amoxicillin, azithromycin, clarithromycin or linezolid in 30-40 % of the double combinations with no observed antagonistic interaction against the tested isolates. Combination of the AgNPs with vancomycin did not result in enhanced killing against all isolates tested. The antimicrobial activity against MRSA isolates was significantly enhanced in triple combinations of AgNPs, blue light and antibiotic, compared to treatments involving one or two agents. The bactericidal activities were highest when azithromycin or clarithromycin was included in the triple therapy compared to the other antibiotics tested.

CONCLUSIONS:A new strategy can be used to combat serious infections caused by MRSA by combining AgNPs, blue light, and antibiotics. This triple therapy may include antibiotics, which have been proven to be ineffective against MRSA. The suggested approach would be useful to face the fast-growing drug-resistance with the slow development of new antimicrobial agents, and to preserve last resort antibiotics such as vancomycin.

OBJECTIVE:This study was designed to compare the reduction in myopia progression in patients treated with atropine eyedrops alone with patients treated with a combined treatment of atropine and stimulation of the auricular acupoints.

METHODS:This study was a randomized single-blind clinical controlled trial. A total of 71 school-aged children with myopia, who fulfilled the eligibility criteria, were recruited. They were randomly assigned into three groups. These were 22 treated with the 0.25% atropine (0.25A) only, 23 treated with the 0.5% atropine (0.5A) only and 26 treated with 0.25% atropine together with stimulation of the auricular acupoints (0.25A+E). The differences in the post-treatment effects among these three groups were statistically assessed. The primary outcome parameter was myopia progression, which was defined as diopter change per year (D/Y) after cycloplegic refraction measurement.

RESULTS:The mean myopia progression of the 0.25A group was 0.38+/-0.32 D/Y. No significant difference in mean myopia progression was found between the 0.5A (0.15+/-0.15 D/Y) and 0.25A+E (0.21+/-0.23 D/Y) groups. However, there was a markedly reduced myopia progression in the 0.25A+E group compared to the 0.25A group (p<0.05). Furthermore, there was no statistical difference among these three groups in axial length elongation (ALE) of eye during this stage of the investigation.

CONCLUSIONS:This study demonstrates that there was efficacy in stimulating the auricular acupoints and this enhanced the action of 0.25% atropine as a means of myopia control. The result was an effect almost equal to that of 0.5% atropine alone. There is also a need that the ALE of the eye should be further investigated over a longer period using the combined therapy.

OBJECTIVE:This study was designed to compare the reduction in myopia progression in patients treated with atropine eyedrops alone with patients treated with a combined treatment of atropine and stimulation of the auricular acupoints.

METHODS:This study was a randomized single-blind clinical controlled trial. A total of 71 school-aged children with myopia, who fulfilled the eligibility criteria, were recruited. They were randomly assigned into three groups. These were 22 treated with the 0.25% atropine (0.25A) only, 23 treated with the 0.5% atropine (0.5A) only and 26 treated with 0.25% atropine together with stimulation of the auricular acupoints (0.25A+E). The differences in the post-treatment effects among these three groups were statistically assessed. The primary outcome parameter was myopia progression, which was defined as diopter change per year (D/Y) after cycloplegic refraction measurement.

RESULTS:The mean myopia progression of the 0.25A group was 0.38+/-0.32 D/Y. No significant difference in mean myopia progression was found between the 0.5A (0.15+/-0.15 D/Y) and 0.25A+E (0.21+/-0.23 D/Y) groups. However, there was a markedly reduced myopia progression in the 0.25A+E group compared to the 0.25A group (p<0.05). Furthermore, there was no statistical difference among these three groups in axial length elongation (ALE) of eye during this stage of the investigation.

CONCLUSIONS:This study demonstrates that there was efficacy in stimulating the auricular acupoints and this enhanced the action of 0.25% atropine as a means of myopia control. The result was an effect almost equal to that of 0.5% atropine alone. There is also a need that the ALE of the eye should be further investigated over a longer period using the combined therapy.

As part of a population-based approach to combating obesity, the American Heart Association has published specific dietary guidelines for the management of obesity and cardiovascular disease prevention. These guidelines give a primary view of healthy dietary changes and goals which may reduce cardiovascular risk. The American Heart Association guideline on Cardiovascular Prevention focuses on the benefits of a Plant-Based Diet and the Mediterranean diet. In addition to these recommendations, several other diets exist with variable long-term cardiovascular outcomes. In recent years, the ketogenic and intermittent fasting diets have been emerging and have garnered their own respective followings as weight loss strategies, and we will include them in our discussion of the potential long-term benefits related to cardiovascular risks. As the guidelines emphasize, all of the diets we will cover throughout this review must be discussed at the level of the individual patient with their primary care provider, and cannot be exercised without informed consent regarding the potential outcomes. Further research is required, and caution is advised before prescribing any of these diets to patients in the long-term, due to the potential to exacerbate cardiovascular risk factors.

Evidence suggests that physical exercise can serve as a preventive strategy against Alzheimer's disease (AD). In contrast, much less is known about the impact of exercise when it is introduced after cognitive deficits are established. Using the TgCRND8 mouse model of amyloidosis, we compared the effects of exercise as an intervention strategy aimed at altering disease progression. Voluntary running for 1 month or 2 months was introduced in 3-month-old TgCRND8 mice, which exhibit amyloid-beta (Aβ) plaque pathology and cognitive deficits at this age. Specifically, we examined Aβ plaque load, spatial memory, and neurogenesis in the dentate gyrus in the hippocampus. After 1 month of running, TgCRND8 mice spent more time in the novel arm of the Y-maze compared to the familiar arms, indicating improved memory. The levels of doublecortin (a marker of immature neurons) were increased in TgCRND8 mice running for 1 month, but with no significant difference in the number of new mature neurons or plaque burden. As the disease progressed, running prevented further deficits in the Y-maze performance and hippocampal neurogenesis and it reduced plaque load pathology in TgCRND8 mice running for 2 months, compared to non-running transgenics. Therefore, the impact of running on memory, neurogenesis, and amyloid pathology was of greater significance when sustained through later stages of the disease.

BACKGROUND:In this clinical trial we compared the effects of broccoli sprouts powder, as an alternative and complementary treatment, to those of standard triple therapy, as a common medical treatment, on cardiovascular risk factors following the H.pylori eradication in patients with type 2 diabetes.

METHODS:Eighty-six type 2 diabetic patients with positive H.pylori stool antigen test (HpSAg) were randomized to receive one of the three following regimens: STT) Standard triple therapy (omeprazole 20 mg, clarithromycin 500 mg, amoxicillin 1000 mg, twice a day for 14 days), BSP) 6 g/d broccoli sprouts powder for 28 days, and combination of these as STT + BSP. After 4 weeks of treatment, H.pylori eradication rates were assessed by HpSAg. Anthropometric measures, blood pressure, serum lipids and lipoproteins as well as serum high sensitive- C reactive protein were also assessed at baseline and at the second examination.

RESULTS:Seventy-seven participants completed the study [STT (n = 28), BSP (n = 25), STT + BSP (n = 24)]. The H.pylori eradication rates were 89.3%, 56.0% and 91.7% in STT, BSP and STT + BSP groups, respectively. After the treatment, both systolic and diastolic blood pressure significantly decreased in STT + BSP group (P < 0.05). Serum triglycerides and TG/HDL-C ratio increased in STT patients group (<0.05). Serum hs-CRP levels significantly decreased in the patients who were treated with BSP per se (3.0 ± 2.5 at baseline vs. 2.3 ± 2.1 after the treatment, P < 0.05).

CONCLUSION:Compared to standard triple therapy, BSP regimen in addition to considerable effects on H.pylori eradication had also favorable properties on cardiovascular risk factors following the H.pylori eradication.

This study aimed at evaluating the effects of red and blue light-emitting diodes (LED) and low-level laser (LLL) on the regeneration of the transected sciatic nerve after an end-to-end neurorrhaphy in rabbits. Forty healthy mature male New Zealand rabbits were randomly assigned into four experimental groups: control, LLL (680 nm), red LED (650 nm), and blue LED (450 nm). All animals underwent the right sciatic nerve neurotmesis injury under general anesthesia and end-to-end anastomosis. The phototherapy was initiated on the first postoperative day and lasted for 14 consecutive days at the same time of the day. On the30th day post-surgery, the animals whose sciatic nerves were harvested for histopathological analysis were euthanized. The nerves were analyzed and quantified the following findings: Schwann cells, large myelinic axons, and neurons. In the LLL group, as compared to other groups, an increase in thenumber of all analyzed aspects was observed with significance level (P < 0.05). This finding suggests that postoperative LLL irradiation was able to accelerate and potentialize the peripheral nerve regeneration process in rabbits within 14 days of irradiation.

The work is aimed to compare the relative strength of dextroamphetamine and yogic meditation on the performance of 3 different groups of medical students to concentrate on the task to balance on a balance board. Group A subjects were mediators, group B subjects were given orally 5 and 10 mg of dextroamphetamine in a capsule, 1 hr prior to the test. Group C subjects were given same capsule but with lactose in place of the drug (placebo). This last groups served as control for the study. The balance index calculated taking into account their balance time and error score at each trial of 5 min duration showed that the performance of the group B (drug) had declined with overall percentile fall of 40.6% as compared to the performance of the controls (placebo) whereas, the performance of Group A (meditators) went on steadily and progressively increasing throughout the period of 10 trial days with overall percentile rise of 27.8%. The results were conclusive to confirm earlier reports that amphetamine is not of use for improvement of task rather, it deteriorates the task performance. Contrary to that, yogic meditation is of merit to achieve concentration for mental as well as physical task.

BACKGROUND:Depression is one of the most common mental disorders. Finding effective treatments for such a disorder with higher efficiency lower side effects and affordability is an active area of research in psychiatry. This study aimed to comparatively analyze the effects of the cognitive group therapy and aerobic exercises on depression, automatic negative thoughts and dysfunctional attitudes of students at Kermanshah University of Medical Science.

METHODS:In this clinical trial, 46 associate and undergraduate students at Kermanshah University of Medical Science were randomly divided into three groups: cognitive therapy, aerobic exercise, and control. The data was gathered both before and 8 weeks after the intervention. Beck Depression Inventory (BDI-II), automatic negative thoughts (ATQ), and the Dysfunctional Attitude Scale (DAS) were used as the data collection instruments. The data were analyzed with SPSS version 15 using paired samples T-test, chi-square test, Kruskal-Wallis test, and analysis of variance (ANOVA).

RESULTS:Cognitive therapy caused a significant decrease in depression, belief in automatic negative thoughts, and dysfunctional attitudes in comparison to the control group (p<0.05). Although aerobics compared to the control group causes more reductions in the variables, however, It was only meaningful for the depression variable (p=0.049). Cognitive therapy also reduced the variables more than the aerobic exercise, but the decrease was not statistically significant.

CONCLUSIONS:Cognitive group therapy and aerobic exercise are effective in treating depression. For treating depression, aerobic exercise can be used as a therapy itself or along with cognitive-behavioral therapy and pharmacotherapy.

INTRODUCTION:Oral intake of vitamins which present antioxidant characteristics can protect living organisms against oxidative damage caused by exposure to ionizing radiation. It was previously reported that administration of high levels of vitamin C can lead to increased DNA damage through production of hydroxyl radicals from hydrogen peroxide by the Fenton reaction. However, our early experiments did not confirm this hypothesis. The main goal of this study was to determine if high doses of Vit C can show life-saving radioprotective effects.

MATERIALS AND METHODS:Phase I: Seventy two male Balb/c mice weighing 20-25g were randomly divided into six groups of 12 animals each. Group I; Vit E for five days, Groups II and III; Vit C and Vit A. Group 4; all three vitamins. Group V; an over-the-counter multivitamin. Group VI; none of the above. Phase II: 120 male BALB/c mice weighing 20-25g were randomly divided into 12 groups of 10 each. Group I; Vit A for five days. Groups II-IV; Vit C 200 mg/kg, 400 mg/kg, 800 mg/kg, respectively. Group V-VII; Vit E at daily doses of 200 iu/kg, 400 iu/kg, 800 iu/kg, respectively. Group VIII and IX; all three vitamins at low and high doses, respectively. Group X; an over-the-counter multivitamin. Group XI; controls group and Group XII; received pure olive oil. All animals (Phases I and II) were exposed to a lethal dose of gamma rays and the survival rates of the animals were monitored and recorded continuously for 16 days after exposure.

RESULTS:Phase I: 14 days after irradiation the survival rate for control group was 33.33%, while the survival rates for the 1st to 5th groups were 45.45%, 81.81%, 50%, 57.14%, and 9.09% , respectively. Phase II: The survival rates in the control group and the group that only received pure olive oil, were 50% and 60%, respectively. Survival rate in the animals received Vit C at daily doses of 200 mg/kg, 400 mg/kg, 800 mg/kg, were 90%, 90% and 90%, respectively. Log rank (Mantel-Cox) test showed statistically significant differences between the survival rates in control irradiated mice (no vitamins) and mice received Vit C at daily doses of 200 mg/kg (P=0.042), 400 mg/kg (P=0.042) and 800 mg/kg (P=0.042).

CONCLUSION:Altogether, findings of this study showed that even high doses of Vit C can show life-saving radioprotective effects. The significant radioprotective effect of Vit C at doses used in this study, opens new horizons in developing non-toxic, cost effective, easily available radioprotectors in life-threatening situations such as exposure to lethal doses of ionizing radiation.  The radioprotective effect of Vit A and Vit E seem to be less efficient compared to that of Vit C.

BACKGROUND: Frozen shoulder is a kind of spontaneous, progressive peri-arthritis over the shoulder joint. The etiology is not yet clear. Traditional treatments for frozen shoulder included conservative medical therapy, physical therapy, nerve block and acupuncture and so on. The purpose of our study is to determine the pain relief effect of electroacupuncture (EAP), regional nerve block (RNB) and the combination of EAP + RNB for frozen shoulder. MATERIALS&METHODS: One hundred and fifty patients with fresh frozen shoulder were, randomly divided into 3 groups. Group I patients (n = 50) had RNB with stellate ganglion block and suprascapular nerve block by 1% xylocaine 10 ml. Group II patients (n = 50) had EAP with local acupoint--Chien-Yu, Chien-Ching, Chien-Nei-Ling, Ah-Shih Hsueh treatment and Group III (n = 50) patients had RNB+EAP performed with acupuncture first, then followed by the regional nerve block. Six vectors of movements were checked in all methods. Four graded Bromage score was used for pain assessment, Grade 1 means complete painless; Grade 2 means slight pain (i.e. pain on motion); Grade 3 means moderate pain (i.e. pain on silence); Grade 4 means severe pain (i.e. need analgesics). The range of shoulder joint was also recorded. Patients were requested for second treatment if pain recurred. The onset (time from injection to maximal pain relief), duration (time from injection to grade 3) Bromage score and side effects were recorded. RESULTS: The results showed that the combined EAP and RNB method had significant high pain control quality, longer duration, and better range of movement of the shoulder joint than that of EAP or RNB performed alone.

PURPOSE OF REVIEW:As the legalization of medical cannabis continues across the USA, oncology care providers will be increasingly asked to provide recommendations regarding its use in the cancer setting. In this article, we review recent literature that analyzes cannabis use specifically in patients with cancer and provide an accessible guide for clinicians, researchers, and patients.

RECENT FINDINGS:We aimed to answer questions about the availability of cannabis in the USA, the trials supporting its use in the cancer setting, and the important factors to consider related to safety. Thirty states plus the District of Columbia have established comprehensive medical cannabis programs, each with different regulations and products available. In June 2018, Epidiolex, a cannabis extraction product containing 99% CBD, was approved to treat refractory seizures; however, whole-plant products and non-prescription extraction products dominate the market. Recent randomized, placebo-controlled studies of nabiximols (Sativex) in patients with refractory cancer-pain have largely shown no significant benefits. Conversely, large observational studies suggest patients with cancer using cannabis report significant improvement of many common symptoms. Cannabis use appears well tolerated, with few serious adverse effects reported. Though prospective clinical trials are needed to provide the robust data required to establish the proper role of cannabinoid and cannabis-based therapy in cancer patients, physicians can draw upon the knowledge currently available to have informed discussions with their patients.

1. A controlled clinical trial was conducted to assess the effectiveness of a homoeopathic preparation in the treatment of influenza-like syndromes. 2. 237 cases received the test drug and 241 were assigned to placebo. Patients recorded their rectal temperature twice a day, and the presence or absence of five cardinal symptoms (headache, stiffness, lumbar and articular pain, shivers) along with cough, coryza and fatigue. 3. Recovery was defined as a rectal temperature less than 37.5 degrees C and complete resolution of the five cardinal symptoms. 4. The proportion of cases who recovered within 48 h of treatment was greater among the active drug group than among the placebo group (17.1% against 10.3%, P = 0.03). 5. The result cannot be explained given our present state of knowledge, but it calls for further rigorously designed clinical studies.

BACKGROUND:The objective of this study was to examine the effect of a mindfulness-based stress reduction (MBSR) program on women diagnosed with conditions such as multiple chemical sensitivity (MCS), chronic fatigue syndrome (CFS), and fibromyalgia (FM).

METHODS:The intervention group underwent a 10-week MBSR program. Symptoms Checklist Inventory (SCL-90R) was used as outcome measure and was administered before the start of the program (pre-), immediately upon completion (post-) and at three-month follow-up. Women on the wait list to receive treatment at the Nova Scotia Environmental Health Centre were used as control subjects for the study.

RESULTS:A total of 50 participants in the intervention group and 26 in the wait-list controls group were recruited for this study. Global scores in the intervention group reached statistical significance pre-post (<0.0001) and at pre-follow-up (<0.0001) while the global scores in the control group remained the same. Five of nine and eight of nine subscales of the SCL-90R showed improvement of statistical significance in MBSR group following treatment and at three-month follow-up.

CONCLUSIONS:The study showed the importance of complementary interventions such as MBSR techniques in the reduction of psychological distress in women with chronic conditions.

Antioxidants in the diet have long been thought to confer some level of protection against the oxidative damage that is involved in the pathology of Alzheimer's disease as well as general cognitive decline in normal aging. Nevertheless, support for this hypothesis in the literature is equivocal. In the case of vitamin C (ascorbic acid) in particular, lack of consideration of some of the specific features of vitamin C metabolism has led to studies in which classification of participants according to vitamin C status is inaccurate, and the absence of critical information precludes the drawing of appropriate conclusions. Vitamin C levels in plasma are not always reported, and estimated daily intake from food diaries may not be accurate or reflect actual plasma values. The ability to transport ingested vitamin C from the intestines into blood is limited by the saturable sodium-dependent vitamin C transporter (SVCT1) and thus very high intakes and the use of supplements are often erroneously considered to be of greater benefit that they really are. The current review documents differences among the studies in terms of vitamin C status of participants. Overall, there is a large body of evidence that maintaining healthy vitamin C levels can have a protective function against age-related cognitive decline and Alzheimer's disease, but avoiding vitamin C deficiency is likely to be more beneficial than taking supplements on top of a normal, healthy diet.

Approximately 30% of the 700,000 US veterans of the 1990-1991 Persian Gulf War developed multiple persistent symptoms called Gulf War illness. While the etiology is uncertain, several toxic exposures including pesticides and chemical warfare agents have shown associations. There is no effective medical treatment. An intervention to enhance detoxification developed by Hubbard has improved quality of life and/or reduced body burdens in other cohorts. We evaluated its feasibility and efficacy in ill Gulf War (GW) veterans in a randomized, waitlist-controlled, pilot study at a community-based rehabilitation facility in the United States. Eligible participants (= 32) were randomly assigned to the intervention (= 22) or a four-week waitlist control (= 10). The daily 4-6 week intervention consisted of exercise, sauna-induced sweating, crystalline nicotinic acid and other supplements. Primary outcomes included recruitment, retention and safety; and efficacy was measured via Veteran's Short Form-36 (SF-36) quality of life, McGill pain, multidimensional fatigue inventory questionnaires and neuropsychological batteries. Scoring of outcomes was blinded. All 32 completed the trial and 21 completed 3-month follow-up. Mean SF-36 physical component summary score after the intervention was 6.9 (95% CI; -0.3, 14.2) points higher compared to waitlist control and 11 of 16 quality of life, pain and fatigue measures improved, with no serious adverse events. Most improvements were retained after 3 months. The Hubbard regimen was feasible, safe and might offer relief for symptoms of GW illness.

This study reports on the case of an elderly patient, with diabetes, and a bullous wound on the left big toe that led to an amputation of the first and second left toes. The amputation was because of deep injury as it was not able to heal with a conventional treatment. After completing the normal treatment and the removal of a bacterial infection in the lesion, the patient underwent a treatment that was based on a hydrogel gel (0.9% saline solution) and hyperbaric oxygen therapy (HBOT). After 60 sessions of the therapy, almost complete closure of the wound was observed. There were no reports of discomfort or infection during the treatment. After seven months of treatment almost complete healing was observed with no infection. This treatment appears to be effective and should be recommended for the treatment of DFUs.

Dietary interventions have not been effective in the treatment of multiple sclerosis (MS). Here, we show that periodic 3-day cycles of a fasting mimicking diet (FMD) are effective in ameliorating demyelination and symptoms in a murine experimental autoimmune encephalomyelitis (EAE) model. The FMD reduced clinical severity in all mice and completely reversed symptoms in 20% of animals. These improvements were associated with increased corticosterone levels and regulatory T (Treg) cell numbers and reduced levels of pro-inflammatory cytokines, TH1 and TH17 cells, and antigen-presenting cells (APCs). Moreover, the FMD promoted oligodendrocyte precursor cell regeneration and remyelination in axons in both EAE and cuprizone MS models, supporting its effects on both suppression of autoimmunity and remyelination. We also report preliminary data suggesting that an FMD or a chronic ketogenic diet are safe, feasible, and potentially effective in the treatment of relapsing-remitting multiple sclerosis (RRMS) patients (NCT01538355).