Caffeic acid phenethyl ester (CAPE) is the major pharmacologically-active component of some propolis types, rich in polyphenols, such as poplar propolis types. CAPE has the potential to be applied as a pharmaceutical as it possesses most of the pharmacological activities of propolis, such as anti-proliferative, antioxidant, immunomodulatory, antidiabetic, anti-inflammatory and antimicrobial. Its advantage is that it lacks some of the downsides of total propolis extracts, such as inability for unified standardization, which is cornerstone for implementing its therapeutic potential as a drug. The current paper provides an overview on the pharmacodynamic principles of CAPE. We present literature search outcomes form ClinicalTrials.gov database and from scientific publications, available on Scopus and Crossref databases. We take a round view of CAPE’s potential therapeutic implications in light of approved drugs with related modes of action.

Purpose: We explored the efficacy of selenium and/or or N-acetyl-cysteine for improving semen parameters in infertile men, and the associations among semen quality and the concentrations of selenium and N-acetyl-cysteine in seminal plasma. Materials and Methods: The study included 468 infertile men with idiopathic oligo-asthenoteratospermia who were randomized to receive 200 g selenium orally daily (selenium group of 116), 600 mg N-acetyl-cysteine orally daily (N-acetyl-cysteine group of 118), 200 g selenium plus 600 mg N-acetyl-cysteine orally daily (selenium plus N-acetyl-cysteine group of 116) or similar regimen of placebo (control group of 118) for 26 weeks, followed by a 30-week treatment-free period. These patients provided blood samples for the measurement of serum testosterone, estradiol, follicle-stimulating hormone, luteinizing hormone, prolac-tin, inhibin B, selenium and N-acetyl-cysteine. Semen samples were also obtained for routine semen analysis, and the measurement of seminal plasma selenium and N-acetyl-cysteine. Results: In response to selenium and N-acetyl-cysteine treatment serum follicle-stimulating hormone decreased but serum testosterone and inhibin B increased. All semen parameters significantly improved with selenium and N-acetyl-cys-teine treatment. Administering selenium plus N-acetyl-cysteine resulted in additive beneficial effects. A significant positive correlation existed between the seminal plasma concentrations of selenium and N-acetyl-cysteine, and semen parameters. A strong correlation was observed between the sum of the selenium and N-acetyl-cysteine concentrations, and mean sperm concentration (r ϭ 0.67, p ϭ 0.01), sperm motility (r ϭ 0.64, p ϭ 0.01) and percent normal morphology (r ϭ 0.66, p ϭ 0.01). Conclusions: These results indicate that supplemental selenium and N-acetyl-cysteine improve semen quality. We advocate their use for male infertility treatment. Abbreviations and Acronyms E2 ϭ estradiol FSH ϭ follicle-stimulating hormone GSH ϭ glutathione LH ϭ luteinizing hormone NAC ϭ N-acetyl-cysteine PRL ϭ prolactin RIA ϭ radioimmunoassay assay ROS ϭ reactive oxygen species TEAE ϭ treatment emergent adverse event

OBJECTIVE:

To compare the efficacy of sustained-release (SR) bupropion to placebo in treating hypoactive sexual desire disorder (HSDD) in ovulating women.
PATIENTS AND METHODS:

After a 1-week, placebo lead-in phase, 232 treatment-seeking women with regular menstrual cycles were randomly assigned to bupropion SR 150 mg/daily (116) or placebo (116) for 12 weeks under double-blind conditions. Efficacy was assessed with the Brief Index of Sexual Functioning for Women (BISF-W), the Personal Distress Scale (PDS), the global efficacy question (GEQ; 'Did the treatment you received during the 12-week improve meaningful your sexual desire?') and overall patient satisfaction question ('Are you satisfied with the efficacy of your treatment?').
RESULTS:

The mean (sd) composite score on the BISF-W, increased from 15.8 (2.6) and 15.5 (2.2) at baseline to 33.9 (4.2) and 16.9 (2.6) in the bupropion and placebo groups, respectively (P= 0.001). The odds ratio (95% confidence interval) for response in the bupropion group relative to placebo was 3.2 (2.1-6.3). The thoughts/desire score more than doubled in patients treated with bupropion (P= 0.001). At the 12-week evaluation the reduction in the PDS scale was 29.4% in bupropion and 4.7% in the placebo group (P= 0.01). In response to the GEQ, of patients in the bupropion and placebo groups, 65.3%, and 4.3%, respectively, responded 'Definitely yes' (P= 0.001). Of patients in the bupropion and placebo groups, 71.8%, and 3.7%, respectively, were definitely satisfied with the efficacy of their treatment, (P= 0.001). After 12 weeks of treatment, 82 women (78.1%) in the bupropion and five (4.9%) in the placebo group were willing to continue therapy (P= 0.001).
CONCLUSIONS:

The results from this study indicate that bupropion SR is an effective and well-tolerated treatment for HSDD in ovulating women. Further controlled trials are warranted.

Purpose: To determine the effects of therapy with Urtica dioica for symptomatic relief of lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). Material and Methods: A 6-month, double-blind, placebo-controlled, randomized, partial crossover, comparative trial of Urtica dioica with placebo in 620 patients was conducted. Patients were evaluated using the International Prostate Symptom Score (IPSS), the maximum urinary flow rate (Qmax), postvoid residual urine volume (PVR), Serum Pros-tatic-Specific Antigen (PSA), testosterone levels, and prostate size. At the end of the 6-month trial, unblinding revealed that patients who initially received the placebo were switched to Urtica dioica. Both groups continued the medication up to 18 months. Results: Five hundred fifty-eight patients (90%) completed the study (287/305, 91% in the Urtica dioica group, and 271/315, 86% in the placebo group). By intention-to-treat analysis, at the end of the 6-month trial, 232 (81%) of 287 patients in the Urtica dioica group reported improved LUTS compared with 43 (16%) of 271 patients in the placebo group (P < 0.001). Both IPSS and Qmax showed greater improvement with drugs than with placebo. The IPSS went from 19.8 down to 11.8 with Urtica

Despite the high costs of treatment of people with kidney disease and associated comorbid conditions, the amount of reliable information available to guide the care of such patients is very limited. Some treatments have been assessed in randomized trials, but most such trials have been too small to detect treatment effects of a magnitude that would be realistic to achieve with a single intervention. Therefore, KDIGO convened an international, multidisciplinary controversies conference titled &quot; Challenges in the Conduct of Clinical Trials in Nephrology &quot; to identify the key barriers to conducting trials in patients with kidney disease. The conference began with plenary talks focusing on the key areas of discussion that included appropriate trial design (covering identification and evaluation of kidney and nonkidney disease outcomes) and sensible trial execution (with particular emphasis on streamlining both design and conduct). Break out group discussions followed in which ...

Context: According to Persian medicine text, there are some topical herbal remedies for insomnia such as pumpkin oil as a nasal drop.

Aims: To evaluate the effect of pumpkin oil (a Persian medicine product) in patients with chronic insomnia.

Methods: This study was conducted as a randomized double-blind clinical trial on pumpkin oil efficacy in 74 patients with chronic insomnia. The participants received two drops of intranasal pumpkin oil or placebo every night for two weeks. The effects of pumpkin oil and placebo on the pattern of sleep and sleep quality were assessed at baseline and at the end of two weeks of treatment by Insomnia Severity Index (ISI) and Pittsburgh Sleep Quality Index (PSQI) questionnaires.

Results: The scores of the ISI questioner were statistically different between groups after two weeks of intervention and patients in the pumpkin oil group had fewer scores for ISI questioner (p<0.001). The reduction of the total score of the Pittsburgh questioner was 10.08 ± 3.21 in the pumpkin oil group and 0.28 ± 0.98 (p<0.001) in the control group.

Conclusions: Pumpkin oil could have a significant positive effect on the quantity and the quality of sleep in patients with chronic insomnia.

Heart Rate variability (HRV) is the method to capture the electrical signals of the heart and analyze the beat-to-beat timing of the heart. The capability of HRV to derive the behavior of the Central Nervous system (CNS) can be a useful feature to get consensus in clinical practice. In this study, we have conducted random trials on positive and control subjects (n=97) for validating the effect of HRV on the autonomic nervous system (ANS) and Vagus Imbalance. Spandan ECG portable Device is used for the recording of the 5-minute Lead II HRV test. The computer Interpreted diagnosis of the HRV test is then validated with the clinical diagnosis of HRV and lead II trace study. The validation is done by evaluating the validation parameters of Specificity, Sensitivity, Negative predictive value, and Positive Predictive Value.

Biopure Corporation has two new products that are Oxyglobin and Hemopure. Oxyglobin is the first new blood substitute for the veterinary market and is ready for consumer use. Hemopure is another new blood substitute for the human market and it will take two years to launch the product from now on. Ted Jacobs, vice president for Human Clinical Trials, is concerned about creating an unrealistic price expectation for Hemopure by marketing Oxyglobin before Hemopure.

Asthma is a disease characterized by wide variations in
pathogenesis that cause resistance to flow in intrapulmonary
airways. The dramatic changes in the architecture of the airway
walls are usually connected to allergic reaction or other forms of
hyper sensitivity, causing marked spasms that lead to difficulty in
breathing. It is possible to relieve or remove the symptoms in the
majority of patients by adopting the clinical guidelines for
pharmacotherapy of asthma which include inhaled corticosteroids,
long and short acting beta agonists, muscarinic antagonists,
leukotriene modifiers, xanthine drugs and some allergy medicines.
The proper use of these agents can aid in reducing or reversing
many symptoms of asthma. Certain methods of using medicines,
for example the correct use of the inhaler for relief and
maintenance therapy, are also associated with a significant
reduction in symptoms. This can be achieved by a pharmacist’s
intervention that can provide a detailed understanding of the
current rational drug choices and proper medication use to the
patient. Nowadays massive resources are being ploughed into
research in a concerted effort to halt the progress of this illness
that can strike in all ages.

Since 2006, there has been a resurgent interest in the pharmacology and therapeutics of psychedelic drugs. Psilocybin, the 4-phosphoryl ester of N,N-dimethyltryptamine (DMT), has been studied most often, but DMT itself is also appealing because of its brief but profound psychological effects and its presence as an endogenous substance in mammalian brain. Although there have been a few studies of ayahuasca, a DMT-containing water infusion, only one human study with pure DMT has been reported since the early 2000s. Newly planned clinical trials to assess the safety and efficacy of DMT in humans with major depressive disorder require high-purity water-soluble DMT for intravenous administration. Accordingly, we synthesized and characterized DMT hemifumarate for these upcoming studies. The synthetic approach of Speeter and Anthony was slightly modified to gain some efficiency in time. In particular, this is the first known report to use aluminum hydride, generated in situ from lithium aluminum hydride, to reduce the intermediate 2-(1H-indol-3-yl)-N,N-dimethyl-2-oxoacetamide to DMT. A quench protocol was developed to produce a good yield of exceptionally pure free base DMT upon workup, which was then converted to the hemifumarate salt. Analysis of the final product included differential scanning calorimetry, thermogravimetric analysis, gas chromatography-mass spectrometry, 1H and 13C nuclear magnetic resonance spectroscopy, high-performance liquid chromatography, residual solvent analysis by gas chromatography headspace sampling, X-ray powder diffraction analysis, and residual lithium analysis by inductively coupled plasma-mass spectrometry. The DMT hemifumarate was minimally 99.9% pure, with no significant impurities or residual solvents, thus meeting regulatory standards for administration to humans.

-----ÖZET: İnsanlar üzerinde gerek geçmişte Nazi Almanyası'nda yapılan deneyler, gerekse sonraki yıllarda gerçekleştirilen Tuskegee sifilis ve Guatemala CYBH araştırmaları ve de günümüzde de sürmekte olan klinik farmasötik deneyler sonucunda, insan deneklerin uğrayabileceği zararlar ve sömürü uzun zamandır ciddi bir sorun olarak tartışılagelmiştir. Özellikle Nazi bilim adamlarınca insanlar üzerinde yapılan deneylere dair Nürnberg'de gerçekleştirilen yargılamalar sırasında bu çalışmaları düzenleyici, uluslararası geçerlilikte bir kod olmadığı fark edilmiş ve bu eksikliği gidermek için Nürnberg Kodu oluşturularak ülkelerce kabul edilmiştir. Günümüzde in vivo farmasötik deneyler, in vitro prosedürler, kök hücre çalışmaları vb. ile, insanlar ve de insan doku ve hücreleri üzerinde tarihte daha önce hiç olmadığı kadar çeşitli ve karmaşık bilimsel araştırmalar gerçekleştirilmektedir. İnsan üzerindeki deneyler konusunda temel gerilim, bu deneyler sonucunda insan deneklerin uğrayabileceği zararlar ile bilim ve tüm insanlık için sağlanabilecek yararlar arasındadır. Bu yararlardan vazgeçmeden, ama söz konusu deneklere de zarar vermeden ilerleyebilmek için, birtakım bilimsel ve ahlaki kod ve kurallar geliştirilmiş, bunlar etik bildirgelerde ve hukuki mevzuatta ilan edilmiştir. Söz konusu deney ve araştırmalarda gerçekleşen değişikliklere paralel olarak, bu metinler de yeni gereksinimlere göre tadil edilmekte ya da bunlara yenileri eklenmektedir. Örneğin Helsinki Bildirgesi bugüne dek yedi kez revize edilmiştir. Sistematik bir derleme olan bu makale, insan denekli araştırmalarla ilgili ulusal ve uluslararası geçerlilikteki bu etikolegal metinleri bir yerde toplayan bir kaynak olmak amacındadır.

-----ABSTRACT: Due to the human experimentation conducted in the Nazi Germany in the past, the subsequent Tuskegee syphilis and Guatemala STD studies, and the ongoing clinical pharmaceutical trials, potential harms to and exploitation of human subjects have long been discussed as a serious problem. Especially during the trials held in Nuremberg regarding the human experimentation that had been conducted by Nazi scientists the important lack of an internationally binding regulatory code was recognized, and the Nuremberg Code was created and adopted by countries to fill this gap. Given the ongoing in vivo pharmaceutical trials, in vitro procedures, stem cell research, etc., more various and complicated scientific research than ever before is conducted today on humans and human cells and tissues. The main tension in the field of human experimentation is between potential harms to the human subjects and potential benefits for science and humanity. A variety of scientific and ethical codes and rules have been developed and declared both in ethical declarations and in legal regulations in order to proceed to achieve these benefits without harming the subjects. In parallel with changes in these trials and research, these texts have also been either modified or supplemented by new texts. The Helsinki Declaration , for instance, has been revised for seven times up to the present. This systematic review aims to provide a source that gathers these nationally and internationally binding ethicolegal texts concerning human experimentation.

Background: Although the headgear appliance has been used extensively to correct anteroposterior discrepancies, its treatment effects have not yet been adequately assessed in an evidence-based manner. Objective: Aim of this systematic review was to assess the therapeutic and adverse effects of early headgear treatment from controlled clinical trials on human patients in an evidence-based manner. Search methods: An unrestricted electronic search of six databases from inception to December 2015. Selection criteria: Randomized and prospective non-randomized controlled trials assessing the effects of headgear treatment on human patients. Data collection and analysis: After duplicate study selection, data extraction, and risk of bias assessment according to the Cochrane guidelines, random-effects meta-analyses of mean differences (MDs) and relative risks (RRs), including their 95% confidence intervals (CIs) were performed, followed by subgroup and sensitivity analyses. Results: A total of 18 unique studies with a total of 930 (56% male/44% female) patients were included. Headgear treatment was associated with a posterior translation of the anterior maxilla border in the short term, as seen by the mean annualized change in the SNA angle (MD = −1.63°/ year; 95% CI = −2.20 to −1.06°/year; high quality evidence) compared to untreated patients. This effect was independent of the rotation of the palatal plane and the inclination of the upper incisors, while a proportional relationship with the initial discrepancy in SNA was seen. The clinical significance of this improvement diminished in the long term, although only limited evidence existed. Additionally, early headgear treatment might decrease the risk of dental trauma during the following years (RR = 0.34; 95% CI = 0.14 to 0.80; moderate quality evidence). Low quality evidence on the effect of headgear on the rotation of the palatal plane, the nasolabial angle, the occlusal outcome, and signs of temporomandibular disorders precluded robust assessments, due to risk of bias, inconsistency, imprecision, and small-study effects. Conclusions: Based on existing trials, headgear is a viable treatment option to modify sagittal growth of the maxilla in the short term in Class II patients with maxillary prognathism. Registration: PROSPERO (CRD42015029837). Funding: None.

Review Soft tissue changes following extraction vs. nonextraction orthodontic fixed appliance treatment: a systematic review and meta-analysis Konstantonis D, Vasileiou D, Papageorgiou SN, Eliades T. Soft tissue changes following extraction vs. nonextraction orthodontic fixed appliance treatment: a systematic review and meta-analysis. Eur J Oral Sci 2018; 00: 1–13. © 2018 Eur J Oral Sci The aim of this systematic review was to assess the effect of systematic extraction protocols during orthodontic fixed appliance treatment on the soft tissue profile of human patients. Nine databases were searched until December 2016 for controlled clinical studies including premolar extraction or nonextraction treatment. After elimination of duplicate studies, data extraction, and risk-of-bias assessment according to the Cochrane guidelines, random-effects meta-analyses of mean differences (MD) or standardized mean differences (SMD) and their 95% CIs were performed, followed by subgroup, meta-regression, and sensitivity analyses. Extraction treatment was associated with increased lower lip retraction (24 studies; 1,456 patients; MD = 1.96 mm), upper lip retraction (21 studies; 1,149 patients; MD = 1.26 mm), nasolabial angle (21 studies; 1,089 patients; MD = 4.21°), soft-tissue profile convex-ity (six studies; 408 patients; MD = 1.24°), and profile pleasantness (three studies; 249 patients; SMD = 0.41). Patient age, extraction protocol, and amount of upper incisor retraction during treatment were significantly associated with the observed extraction effects, while the quality of evidence was very low in all cases due to risk of bias, baseline confounding, inconsistency, and imprecision. Although tooth extractions seem to affect patient profile, existing studies are heterogenous and no consistent predictions of profile response can be made.

Cold spinal spray and cold spinal bath are the hydrotherapy treatments which are commonly used by naturopathy physicians, for the better employment of such treatments used in various disease conditions, the basic physiological effects should be well understood. Hence, this study aims at comparing the effects of cold spinal spray and cold spinal bath on autonomic variables in healthy volunteers. 60 healthy volunteers were randomly allocated into cold spinal spray and cold spinal bath. Intervention was given for the duration of 20 minutes. Subjects were assessed for blood pressure and Heart rate variability (HRV) before, after and at the end of one hour of intervention. Following result of cold spinal spray (CSS) and cold spinal bath (CSB), the immediate assessment showed a significant increase in the square root of the mean squared difference between adjacent N-N interval (RMSSD) and decrease low frequency (LF), systolic blood pressure (SBP) and diastolic blood pressure (DBP) in both groups and increases consecutive normal sinus (NN) intervals exceeds 50 ms (NN50) in CSS group and decrease in low frequency/high frequency ratio (LH/HF ratio) in CSB group. Whereas assessments after one hour in both groups showed a significant increase in RMSSD and increase in NN50, the fraction of consecutive NN intervals that differ by more than 50 ms (pNN50) and reduction in heart rate (HR), very low frequency (VLF), SBP, and DBP in CSS group is noted. When both the groups are compared with each other, there were significant changes seen in RMSSD in the immediate assessments and there were no significant differences were noted when assessed after one hour. Both immediate and post one hour results of these two hydrotherapeutic interventions reported a shift of sympatho-vagal balance towards parasympathetic dominance. Therefore, these treatments can be applied for improving cardiac health and for achieving relaxation.

Objective: The aim of this systematic review was to assess the occlusal outcome and duration of fixed orthodontic therapy from clinical trials in humans with the Objective Grading System (OGS) proposed by the American Board of Orthodontics. Methods: Nine databases were searched up to October 2016 for prospective/ retrospective clinical trials assessing the outcomes of orthodontic therapy with fixed appliances. After duplicate study selection, data extraction, and risk of bias assessment according to the Cochrane guidelines, random-effects meta-analyses of the mean OGS score and treatment duration were performed and 95% confidence intervals (CIs) were calculated. Results: A total of 34 relevant clinical trials including 6,207 patients (40% male, 60% female; average age, 18.4 years) were identified. The average OGS score after treatment was 27.9 points (95% CI, 25.3–30.6 points), while the average treatment duration was 24.9 months (95% CI, 24.6–25.1 months). There was no significant association between occlusal outcome and treatment duration, while considerable heterogeneity was identified. In addition, orthodontic treatment involving extraction of four premolars appeared to have an important effect on both outcomes and duration of treatment. Finally, only 10 (39%) of the identified studies matched compared groups by initial malocclusion severity, although meta-epidemiological evidence suggested that matching may have significantly influenced their results. Conclusions: The findings from this systematic review suggest that the occlusal outcomes of fixed appliance treatment vary considerably, with no significant association between treatment outcomes and duration. Prospective matched clinical studies that use the OGS tool are needed to compare the effectiveness of orthodontic appliances. [Korean J Orthod 2017;47(6):401-413]

No oral medication has proved to be clearly beneficial for Peyronie's disease (PD). We investigated the safety and efficacy of coenzyme Q(10) (CoQ(10)) supplementation in patients with early chronic PD. We conducted a randomized clinical trial of 186 patients with chronic early PD. Patients were randomly assigned to either 300 mg CoQ(10) daily (n=93) or similar regimen of placebo (n=93) for 24 weeks. Erectile function (EF), pain during erection, plaque volume, penile curvature and treatment satisfaction using patient versions of the Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) questionnaire were assessed at baseline and every 4 weeks during study period. EF was assessed using International Index of Erectile Function (IIEF-5), and pain was evaluated with a visual analog scale (VAS, 0-10). All patients also responded to a Global Assessment Question, 'Has the treatment you have been taking during this study improved your erections?' After 24 weeks, mean IIEF-5 score, mean VAS score and mean EDITS score improved significantly in patients receiving CoQ(10) (all P<0.01). Mean plaque size and mean penile curvature degree were decreased in the CoQ(10) group, whereas a slight increase was noted in the placebo group (both P=0.001). Mean index of IIEF-5 in 24-week treatment period was 17.8 ± 2.7 in the CoQ(10) group and 8.8 ± 1.5 in the placebo group (P=0.001). Of the patients in CoQ(10) group, 11 (13.6%) had disease progression vs 46 (56.1%) in placebo group (P=0.01). In patients with early chronic PD, CoQ(10) therapy leads plaque size and penile curvature reduction and improves EF.

"The clinical bacteria of multi-drug resistant to some antibiotics are
considered a common problem in the world wide. Alternative
antibacterial strategies are urgently needed, and thus this situation
has led to a re-evaluation of the therapeutic use of ancient
remedies, such as plants and plant-based products, including
Nigella sativa (N. sativa). This study aimed to evaluate the
antibacterial activity of Yemeni N. sativa oil against some Clinical
Bacterial Isolates (CBI) and Control Strains of Bacteria (CSB) in
comparison with Augmentin® (Amoxicillin and Clavulanic Acid).
This study was carried out in Sana’a city during the period of one
year from May 2012 to April 2013. The antibacterial activity of oil
with different concentrations was determined by using disc agar
diffusion technique against CBI (Staphylococcus aureus and
Pseudomonas aeruginosa) and CSB (Staphylococcus aureus
ATCC25619, Pseudomonas aeruginosa ATCC29737), also the
Minimum Inhibition Concentration (MIC) of oil extract was
determined. The results indicated that, the highest significant
antibacterial activity was at the maximum concentration of the oil
against Staphylococcus aureus and Pseudomonas aeruginosa in
comparison with Augmentin ® discs (p < 0.05) respectively. This
study observed that, there was strong positive correlation between
the diameter zone (DZ-mm) and oil concentrations (%). In
addition, the DZ (mm) of the oil for CSB was higher than CBI.
Also the oil activity was found to be more effective against
Staphylococcus aureus than Pseudomonas aeruginosa. On the
other hand, the MIC of the oil against CBI were ranged between ≥
0.5% and 4%. Whereas, the CSB particularly Staphylococcus
aureus were sensitive to low concentrations of oil. It could be
concluded that, the oil had high antibacterial effect against CSB
and CBI with high concentration and more effective than
Augmentin® discs."

PURPOSE:

We investigated the effects of the administration of ubiquinol (a reduced form of coenzyme Q(10)) on semen parameters and seminal plasma antioxidant capacity in infertile men with idiopathic oligoasthenoteratozoospermia.
MATERIALS AND METHODS:

A total of 228 men with unexplained infertility were randomly assigned 1:1 into 2 groups. Group 1 (114) received 200 mg ubiquinol daily by mouth for 26 weeks and group 2 (114) received a similar regimen of placebo. After completion of the 26-week treatment phase, all participants were followed for another 12-week off-drug period. Primary outcomes were improvement in sperm density, sperm motility and sperm strict morphology.
RESULTS:

At the end of the 26-week treatment period mean ± SD sperm density in the ubiquinol and placebo groups was 28.7 ± 4.6 × 10(6)/ml and 16.8 ± 4.4 × 10(6)/ml (p = 0.005), sperm motility was 35.8% ± 2.7% and 25.4% ± 2.1% (p = 0.008), and sperm strict morphology was 17.6% ± 4.4% and 14.8% ± 4.1% (p = 0.01) of normal sperm, respectively. During the treatment period serum follicle-stimulating hormone levels decreased significantly (p = 0.02) and serum inhibin B concentrations increased significantly (p = 0.01). During the off-drug period semen parameters gradually returned to baseline values but the differences were still significant for sperm density (p = 0.03) and sperm motility (p = 0.03). The correlation coefficients analysis revealed a positive association between the duration of treatment with ubiquinol and sperm density (r = 0.74, p = 0.017), sperm motility (r = 0.66, p = 0.024) and sperm morphology (r = 0.57, p = 0.027).
CONCLUSIONS:

Ubiquinol was significantly effective in men with unexplained oligoasthenoteratozoospermia for improving sperm density, sperm motility and sperm morphology.

T he availability of large number of medicines and the constant efflux of new information make them practically impossible for any health care professional to be updated in all aspects. This leads to the emergency of the concept of pharmaceutical care. The role of clinical pharmacists in the hospital setting have the potential to positively impact the quality of patient care and provide cost savings. A number of papers done in Ethiopia were used to see how pharmaceutical care is practiced in Ethiopia. Pharmaceutical care is given high value starting from our country's health policy to stalk holders (hospitals, schools, other governmental and non governmental institutions). The importance of pharmaceutical care services in saving lives and protecting public health is particularly relevant in resource limited settings with a high prevalence of major medicine treatable diseases and systems wide opportunities related to pharmaceutical care. Pharmaceutical care providers participate in ward rounds. Their clinical knowledge and skill has been improved and they have also trying to do more clinical based researches (complex case reports, drug therapy problem identification and intervention. Thus 'Clinical Pharmacists' is the heart of pharmaceutical care. Resistance of health care professionals to work with pharmaceutical care providers, unable to uphold responsibilities in their job, unable to get benefits for their activity, inadequate clinical skills, almost no role and responsibility of clinical pharmacist (lecturers) in their university hospitals, curriculum related problem and lack of sufficient number of specialists pose challenge for the emerging role of pharmacists. C alleandria portoricensis is a plant that has a lot of potentials or bioactive compounds. They have been used for different purposes in Nigeria especially in the southwestern part of the country. It is called 'tude " among the yorubas that dominate the south western part of Nigeria. It is majorly used as antifungal and antibacterial in infant diseases. Their antifungal and antibacterial properties might be due to any or some of these chemical compounds or bioactive ingredients that we have identify in these work. The leaf and roots part were cut and dried in the laboratory. After drying, they are grinded and extracted using ethanol. The ethanol extract is kept in 0.9% saline. Phytochemical screenings were carried out on the ethanol extract. The results of the screening shows that flavonoids, cardiac glycosides, steroid, alkaloids were present in the roots and flavonoids, saponin, alkaloids are present in the leaves. Saponins, tannins, steroids, cardiac glycosides, anthraquinine (free and combined) were absent in the leave extract. In the root extract, tannins, saponins, anthraquinines (free and combined) are all absent. From the results, the leafy part of the plant contain more active ingredient than the root part. The mixture of the two also shows a significant amount of the active ingredients.

background:  We have previously shown in patients with heart failure and type II diabetes that treatment with DC improves mitochondrial structure, indicators of mitochondrial biogenesis and oxidative stress in skeletal muscle (SkM).Methods:  Seventeen sedentary subjects (mean age of 50) were randomized to placebo (n=8) or DC groups (n=9) and consumed 2 squares of Hershey’s Extra Dark chocolate or placebo (20 g) for 3 months. Epicatechin levels were measured in a subset of patients to optimize dosing (~100 nM based on prior studies). Subjects underwent bicycle ergometry to assess VO2 max and power, lipid profile and SkM biopsy to investigate underlying biochemical mechanisms.Results:  In the DC group, there was a trend for an increase in VO2 max (p=0.056 before vs. after) with no changes in the placebo group. In the DC group post treatment (Figure 1) there was an increase in maximum work (watts) achieved (p=0.026). The DC group showed significant increases in HDL levels (p=0.005). SkM biochemistry (Western blots) showed significant increases in protein levels for metabolic and/or mitochondrial biogenesis control enzymes (PGC1α, AMPK and LKB1) and in their phosphorylation levels.conclusion:  Treatment of sedentary, older subjects with DC improves HDL cholesterol in association with upstream regulators of SkM metabolic control. There were improvements in maximum work without an apparent concomitant increase in VO2 max which may suggest that DC enhances efficiency of SkM mitochondria.

To evaluate the safety and efficacy of cabergoline in men with erectile dysfunction (ED) who did not respond to sildenafil. Four hundred two sildenafil nonresponders aged from 21 to 59 years were included in the study. Patients were randomly divided into group 1, those who received 0.5-1 mg cabergoline weekly for 6 months and group 2, who received placebo for the same period. They underwent preliminary assessment, including medical and sexual history, self-administered International Index of Erectile Function (IIEF) and intravaginal ejaculatory latency time (IVELT) evaluation. Standard biochemistry and hematological laboratory tests, and measurement of serum testosterone and prolactin levels were also carried out. When indicated, other tests were used to establish the diagnosis of vasculogenic and neurogenic ED, including penile color duplex Doppler ultrasonography, pudendal nerve conduction test and impaired sensory-evoked potentials studies. The efficacy of two treatments was assessed every 2 weeks during treatment, at the end of the study, using responses to IIEF, IVELT evaluation, mean intercourse satisfaction domain, mean weekly coitus episodes and adverse drug effects. The trial was completed by 370 (92%) men. Positive clinical results were seen in 31.2% of patients in the cabergoline group compared with 7.1% of patients in the placebo group (P ¼ 0.04). The mean weekly intercourse episodes increased from pretreatment values of 1.4 and 1.2 to 2.2 and 1.4, for cabergoline and placebo, respectively (P ¼ 0.04). Baseline mean intercourse satisfaction domain values of IIEF 10 and 11 reached to 15 and 10 at 6-month treatment in groups 1 and 2, respectively (P ¼ 0.04). The IVELT after cabergoline and placebo gradually increased from 98 and 101 s to approximately 242 and 116 s, respectively (P ¼ 0.001). More drug-related adverse effects occurred in cabergoline group and 12 (5.9%) had to discontinue treatment (P ¼ 0.001). Cabergoline is moderately effective salvage therapy for sildenafil nonresponse. Further studies with different dosages and treatment regimens are necessary to draw final conclusions on the efficacy of this drug in ED.

-----ÖZET: Dünyadaki en büyük ilaç şirketlerinden biri olan X, yeni bir antibiyotik ajanı test etmek için 1996'da Nijerya'da çocuklar üzerinde kanuna ve tıp ahlakına aykırı faz III bir klinik deney gerçekleştirmiş olmakla suçlanmıştır. Uluslararası medyada yer bulan bu iddialar sonrasında şiddetli tepkilere neden olmuş ve mahkemeye taşınmıştır. Vakaya dair Nijerya hükumetince hazırlatılan inceleme raporunda varılan ve yıllarca gizli tutulan sonuç, X'in Helsinki Bildirgesi'ne ve Birleşmiş Milletler Çocuk Hakları Sözleşmesi'ne aykırı bir araştırma gerçekleştirdiği olmuştur. Nitekim yalnızca sözlü onam almış olduğunu kabul eden X, dava edilince, denek çocukların ailelerine tazminat niteliğinde ödemeler yapmıştır. Bu retrospektif çalışmada, yirminci yüzyıl ortalarındaki gayriahlaki klinik deneylerin yinelenmemesi için geliştirilmiş olan tüm çağdaş etikolegal mevzuata karşın doksanlar gibi yakın bir tarihte yine de gerçekleşmiş olan bu olay, dönemin belge, rapor ve haberleri üzerinden sunulmaktadır. Söz konusu skandal, ahlaken yol gösterici metinlerin varlığı kadar bu metinlerde yazanı yapmayı ya da yapmamayı seçecek olan ahlaki öznenin karakterinin de önemli olduğuna dair, tarihten bir başka örnek niteliğindedir.

-----ABSTRACT: X, one of the globally leading pharmaceutical companies, has been accused of having performed an illegal and unethical phase III clinical trial on Nigerian children to test its new antibiotic agent in 1996. The allegations reported by the international media subsequently met with intense reaction and were brought to court. The conclusion arrived at in the long-obscured investigation report ordered by the Nigerian government was that the company X conducted a clinical trial violating the Helsinki Declaration and the United Nations Convention on the Rights of the Child. Indeed, the company admitting having obtained only verbal consent made, when litigated, compensatory payments to the families of the child subjects. The present retrospective study reviewing the contemporaneous reports and documents aims to present this case that did occur as recently as the mid-1990s despite the vast body of contemporary ethicolegal regulations developed to prevent the reoccurrence of unethical clinical trials similar to those in the mid-20th century. The discussed scandal constitutes another historical example indicating that what is as important as the presence of a body of established ethical guidelines is the character of the moral agent who is to choose to follow or not to follow what has been recommended in these texts.

In 2007, WHO/UNAIDS recommended male circumcision (MC) as an HIV preventive measure based on 3 sub-Saharan African RCTs into female-to-male (FTM) sexual transmission. A related RCT investigated male-to-female (MTF) transmission. Yet, the trials were compromised by inadequate equipoise; selection bias; inadequate blinding; problematic randomisation; trials stopped early with exaggerated treatment effects; and not investigating non-sexual transmission. Several questions remain unanswered. Why were the trials carried out in countries where more intact men were HIV+ than in those where more circumcised men were HIV+? Why were men sampled from specific ethnic subgroups?  Why were so many participants lost to follow-up?  Why did men in the MC groups receive additional counselling on safe sex practices?  The absolute reduction in HIV transmission associated with MC was only 1.3%. Relative reduction (RR) was reported as 60%, but after correction for lead-time bias averaged 49% across the 3 FTM trials.  In the Ugandan MTF trial, there was a 61.4% relative increase in HIV among female partners of HIV+ circumcised men. In the Kenyan trial, MC was associated with 4 new incident infections. Since MC diverts resources from known preventive measures and increases risk-taking behaviours, any long-term benefit in reducing HIV transmission remains uncertain.

KEYWORDS Organophosphorous, Pesticides, Malondialdehyde, Reduced glutathione, Serum total antioxidant Capacity, L-carnitine. Organophosphorus compounds are widely used pesticides. They are associated with a significant risk of acute intoxication. Oxidative stress is a contributing factor of acute organophosphorus poisoning morbidity and mortality. L-carnitine was found to have free-radical scavenging and antioxidant properties. Therefore, we aimed to evaluate the efficacy and safety of L-carnitine as an adjuvant in treatment of patients with acute organophosphorus poisoning. A randomized clinical trial was conducted on 30 patients suffering from acute organophosphorus poisoning admitted to Poison Control Center, Tanta University Emergency Hospital, Egypt, from April 2017 till January 2018. Patients were randomly divided into two equal groups. Group I received the standard treatment only and group II received the standard treatment plus L-carnitine in a dose of 1gm/8 hours IV.At time of admission, malondialdehyde, reduced glutathione, serum total antioxidant capacity and psudocholinesterase enzyme activity registered no significant difference between the two studied groups. After treatment, malondialdehyde, reduced glutathione and serum total antioxidant capacity showed significant improvement in group II. The mean value of atropine dose in group II (5.6mg) was significantly lower than group I(10.9mg). We concluded that the use of L-carnitine improved the antioxidant status and reduced total atropine dose required for treatment of patients with acute organophosphorus poisoning.

Background-Little is known about the relationship between attention-deficit/hyperactivity disorder (ADHD) subtypes and substance-use disorder (SUD). As there is literature suggesting different subtype phenotypes, there may be subtype differences in regard to the risk for developing SUD and substance treatment response.

Tuberculosis (TB), an ongoing public health threat, is worsened by the emergence of drug resistance. With an estimated 630000 cases per year of multidrug resistant (MDR)-TB, and 9% of those being extensively drug resistant (XDR)-TB, there is an urgent need for new and more effective anti-TB drugs. New TB treatment regimens should be able to shorten the duration of therapy that currently takes at least six months. The non-compliance with this long treatment duration is one of the reasons for the development of drug resistance. In spite of the difficulties and alleged lack of interest from the pharmaceutical industry for the discovery and development of new antibiotics, several new or repurposed drugs are being evaluated in clinical trials. This review article summarizes the information available and presents an update on the drugs currently in clinical trials for TB and briefly introduces some new compounds in pre-clinical development.

Here we explore how an effective early treatment for covid19 came to be seen as a dangerous drug which the World Health Organisation tried to prevent the use of throughout the world. We then go on to explore why this might have happened. The article is also available here: https://www.lifesitenews.com/opinion/hcq-behe
Dr Meryl Nass's website is available here http://anthraxvaccine.blogspot.com/

Beyond placebo: Alternative options to the randomized control trial design in rare disease studies. ABSTRACT Unique difficulties and challenges can arise for rare diseases and orphan disease indications within a clinical trial. Some of the challenges encountered by trials that are working on rare diseases can include recruitment and enrollment. One of the explanations for the challenges that are encountered in rare disease trials is because of the trial design of study, where the investigational product is being compared to the placebo. This review paper discusses the usage of placebo and when other options could be taken into consideration while creating the protocol, specifically with consideration to rare disease studies. It is essential for the investigators and those designing the protocol to consider alternative options from the standard randomized controlled trial. The aim of this paper is to review alternative trial design options. The trial designs discussed in this review paper include crossover trials, single arm studies and historical data, and n-of-1 trials.

The Horizon 2020 “Unit Cost” is an instrument that mimics, to some extent, the ‘per-patient’ cost structure, to allow more flexibility in patient recruitment in projects funded by the Horizon 2020 programme. Beneficiaries that properly utilize the “Unit Cost” will benefit from easier project execution (there is no need to document actual costs, e.g. timesheet management), and as a result, a simpler and easier financial audit later on.
The Horizon 2020 “Unit Cost” complements the commonly-used traditional form of “Actual cost” that is widely implemented in the programme. In Horizon 2020 clinical trial projects, it is possible to combine “Actual costs” and “Unit costs” in the budget structure, subject to the guidelines presented in Commission Decision C(2016) 7553.

Wersja robocza. Artykuł opublikowano w: Kaczmarek E., Biopraca -nowa twarz wyzysku?, Przegląd Humanistyczny 1 (448) 2015, str. 55-62. 1 1 Emilia Kaczmarek (Uniwersytet Warszawski) Biopracanowa twarz wyzysku? Pojęcie biopracy jest intuicyjnie zrozumiałe, ale niełatwe do ścisłego zdefiniowania. Na potrzeby tego artykułu można przyjąć, że biopraca oznacza zarabianie pieniędzy poprzez udostępnianie funkcji biologicznych własnego ciała. Oczywiście każda praca, nawet praca umysłowa, opiera się na biologicznym wymiarze ludzkiej egzystencji, jest wykorzystaniem zasobów jakie daje ciało. Granicę między pracą, a biopracą trudno jednoznacznie uchwycić, mimo to, wydaje się ona bardzo istotna. Mianem biopracy można określić takie formy zarobkowania jak: surogacja (macierzyństwo zastępcze), odpłatne dawstwo komórek lub organów (np. dawstwo komórek jajowych, sprzedaż nerki) czy odpłatny udział w badaniach klinicznych rozważany w tym tekście. Biopraca to nie nowe zjawiskojej makabrycznym historycznym przykładem była choćby praca w charakterze karmiciela wszy, której w Instytucie Badań nad Tyfusem Plamistym podejmowali się lwowscy intelektualiści w czasie okupacji niemieckiej; innym, nie wzbudzającym takich emocji przykładem, była praca w charakterze mamki karmiącej cudze dzieci swoim mlekiem. Jednak biorąc pod uwagę dynamiczny rozwój biotechnologii można zaryzykować hipotezę, że nowe formy biopracy będą pojawiać się coraz częściej. Refleksja nad naturą i dopuszczalnością biopracy wydaje się więc bardzo potrzebna. Choć biopraca przybiera różne formywszystkie z nich wzbudzają pewne społeczne kontrowersje. Problematyczny charakter biopracy ujawnia się w burzliwych Wersja robocza. Artykuł opublikowano w: Kaczmarek E., Biopraca -nowa twarz wyzysku?, Przegląd Humanistyczny 1 (448) 2015, str. 55-62. 2

Technology innovation has brought vital changes to the health sector. The research will focus on virtual healthcare as a current trend in the medical industry. It will highlight the clinical evolution of virtual healthcare before and during the COVID-19 pandemic and examine the Impacts of Virtual Healthcare on Humans on their Mental health. The research will use the available data from medical research institutions such as the American Well study, Center for Disease Control (CDC), World Health Organization, American Psychiatric Association, and literary works from health scholars' research on telemedicine.

On 11 January 2016, a Phase I trial of an experimental fatty acid amide hydrolase inhibitor for pain developed by Bial-Portela was halted after six healthy volunteers were admitted to the University of Rennes Hospital in France. One volunteer died and four suffered severe neurological injuries. It is a dreadful reminder of the Tenegero trial that also hospitalized six volunteers in 2006. Three major similarities were observed between the Tegenero and Bial trials. The first similarity is related to the dosing interval protocol. There is a lack of information about whether the multiple-dose regimen included adequate time intervals between individuals receiving the drug. The second similarity is on the dosing calculation that was based on the 'no adverse effect level' (NOAEL). The third similarity is observed in terms of how there was no prior publication of preclinical findings in the public domain before the start of both trials. There have been calls for the full release of the Investigation Medicinal Product Dossier and the Investigator's Brochure, as these data are critical to maximize patient safety in the future and should outweigh considerations of commercial confidentiality. Likewise, it is necessary for the Brest Regional Ethics Committee to release its documents, which captured the risk-benefit assessment in approving the Bial trial, for external scrutiny.

(−)-Epicatechin ((−)-EPI), a naturally occurring flavanol, has emerged as a likely candidate for cocoa-based product reported reductions in cardiometabolic risk. The present study aimed to determine the safety, tolerability, pharmacokinetics and pharmacodynamics of purified (−)-EPI administered to healthy volunteers. In this phase I, open-label, two-part single-and multiple-dose study, subjects received either a single dose (n = 9) of 50, 100 or 200 mg or multiple doses (n = 8) of 50 mg daily (q.d.) or twice daily (b.i.d) for 5 days. Blood was collected at 0, 0.5, 1, 2, 4 and 6 h after (−)-EPI administration in the single and multiple dose groups (blood collection repeated in day 5). Samples were analyzed by HPLC-HR-ESI-MS for EPI and metabolite quantification. In the q.d. and b.i.d. groups, blood samples were analyzed for NO surrogates and follistatin levels as well as, platelet mitochondrial complexes I, V and citrate synthase activity levels. (−)-EPI was well tolerated and readily absorbed with further phase 2 metabolism. On day 5, in the q.d. and b.i.d. groups, there were significant increases in plasma nitrite of 30% and 17%, respectively. In the q.d. group on day 5 vs. day 1, platelet mitochondrial complexes I, IV and citrate synthase activities demonstrated a significant increase of ∼92, 62 and 8%, respectively. Average day 5 follistatin AUC levels were ∼2.5 fold higher vs. day 1 AUC levels in the b.i.d. group. (−)-EPI was safe to use, with no observed adverse effects, and our findings suggest that increases in NO metabolites, mitochondrial enzyme function and plasma follistatin levels may underlie some of the beneficial effects of cocoa products or (−)-EPI as reported in other studies.

Clinical trial adaptation refers to any adjustment of the trial protocol after the onset of the trial. The main goal is to make the process of introducing new medical interventions to patients more efficient by reducing the cost and the time associated with evaluating their safety and efficacy. The principal question is how should adaptation be performed so as to minimize the chance of distorting the outcome of the trial. We propose a novel method for achieving this. Unlike previous work our approach focuses on trial adaptation by sample size adjustment. We adopt a recently proposed stratification framework based on collected auxiliary data and show that this information together with the primary measured variables can be used to make a probabilistically informed choice of the particular sub-group a sample should be removed from. Experiments on simulated data are used to illustrate the effectiveness of our method and its application in practice.