Retrospective analysis of intrauterine granulocyte colony-stimulating factor in controlled ovarian stimulation with intrauterine insemination cycle

Background: Persistent thin endometrium affects <1% of patients. Various treatments have been proposed with no satisfactory results. GCSF is one such treatment modality which improves endometrial thickness and implantation. Aim of this study was to analyse the effects of dose and the site of instilling intrauterine G-CSF in COS IUI cycles in patients with unexplained infertility and to note the pregnancy rates among them.Methods: It is a 3-year retrospective study done in obstetrics and gynecology department of AJ Institute of Medical Sciences and Research Centre, that included all unexplained infertility cycles with controlled ovulation stimulation-IUI protocols where for a thin endometrium GCSF was used. The method of ovarian stimulation, the drug and dose used, the trigger for ovulation and the ovarian and endometrial response was noted. The day of the intrauterine GCSF and the dose and the site of instillation was noted. The endometrial response to GCSF the outcome for pregnancy was noted. All the data was analyzed statistically.Results: Significant endometrial response was seen with a dose of 100 mg,150 mg and 300 mg. Pregnancy outcome was better when GCSF was instilled just above the level of the os. GCSF instilled at the level of the fundus increases the possibility of ectopic pregnancy.Conclusions: Instillation of GCSF of 100 mg dosage just above the os; is a safe and effective method for improving the endometrial thickness and increasing pregnancy rate

A new pharmacogenetic algorithm to predict the most appropriate dosage of acenocoumarol for stable anticoagulation in a mixed Spanish population

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.There is a strong association between genetic polymorphisms and the acenocoumarol dosage requirements. Genotyping the polymorphisms involved in the pharmacokinetics and pharmacodynamics of acenocoumarol before starting anticoagulant therapy would result in a better quality of life and a more efficient use of healthcare resources. The objective of this study is to develop a new algorithm that includes clinical and genetic variables to predict the most appropriate acenocoumarol dosage for stable anticoagulation in a wide range of patients. We recruited 685 patients from 2 Spanish hospitals and 1 primary healthcare center. We randomly chose 80% of the patients (n = 556), considering an equitable distribution of genotypes to form the generation cohort. The remaining 20% (n = 129) formed the validation cohort. Multiple linear regression was used to generate the algorithm using the acenocoumarol stable dosage as the dependent variable and the clinical and genotypic variables as the independent variables. The variables included in the algorithm were age, weight, amiodarone use, enzyme inducer status, international normalized ratio target range and the presence of CYP2C9∗2 (rs1799853), CYP2C9∗3 (rs1057910), VKORC1 (rs9923231) and CYP4F2 (rs2108622). The coefficient of determination (R2) explained by the algorithm was 52.8% in the generation cohort and 64% in the validation cohort. The following R2 values were evaluated by pathology: atrial fibrillation, 57.4%; valve replacement, 56.3%; and venous thromboembolic disease, 51.5%. When the patients were classified into 3 dosage groups according to the stable dosage (&lt;11 mg/week, 11-21 mg/week, &gt;21 mg/week), the percentage of correctly classified patients was higher in the intermediate group, whereas differences between pharmacogenetic and clinical algorithms increased in the extreme dosage groups. Our algorithm could improve acenocoumarol dosage selection for patients who will begin treatment with this drug, especially in extreme-dosage patients. The predictability of the pharmacogenetic algorithm did not vary significantly between diseases.This study was funded by a grant from the Spanish Ministry of Health and Social Policy (Instituto de Salud Carlos III, PI07/0710) and the Andalusian Regional Ministry of Health (Progress and Health Foundation, PI-0717-2013

Botulinum toxin injection for the treatment of chronic anal fissure: uni- and multivariate analysis of the factors that promote healing

Purpose Anal fissure is caused by a pathological contraction of the internal anal sphincter. Lateral internal sphincterotomy remains the gold standard for the treatment of fissure. Botulinum toxin injections have been proposed to treat this condition without any risk of permanent injury of the internal sphincter. We investigate clinical and pathological variables and the effects of different dosage regimens of botulinum toxin to induce healing in patients with idiopathic anal fissure. Methods This is a retrospective study at a single center. The patients underwent a pre-treatment evaluation that included clinical inspection of the fissure and anorectal manometry. We collected and analyzed demographic data, pathological variables, associated pathological conditions, and treatment variables. Success was defined as healing of the fissure, and improvement of symptoms was defined as asymptomatic persistent fissure. Results The findings of 1003 patients treated with botulinum toxin injections were reported. At 2 months evaluation, complete healing was evident in 780 patients (77.7%). Resting anal tone (77.1 +/- 18.9 mmHg) was significantly lower from baseline (P &lt; 0.0001) and from 1-month value (P = 0.0008). Thirty-nine not healed patients underwent lateral internal sphincterotomy, and 184 were re-treated with 50 UI of botulinum toxin. In these patients, the healing rate was 93.9% (171 patients). Dose and injection site of toxin correlates with healing rate. There were no relapses during an average of about 71 months. Conclusion Our data show that injection of botulinum toxin into the internal anal sphincter is a safe and effective alternative to surgery in patients with chronic anal fissure

Buspirone Dose-Response on Facilitating Forelimb Functional Recovery in Cervical Spinal Cord Injured Rats

Buspirone, widely used as a neuropsychiatric drug, has also shown potentials for motor function recovery of injured spinal cord. However, the optimum dosages of such treatment remain unclear. In this study, we investigated the dose-response of Buspirone treatment on reaching and grasping function in cervical cord injured rats. Seventeen adult Sprague-Dawley rats were trained to reach and grasp sugar pellets before a C4 bilateral dorsal column crush injury. After 1 week post-injury, the rats were divided into 3 groups to receive 1 of 3 different dosages of Buspirone (i.p., 1 dose/day: 1.5, n = 5; 2.5, n = 6 and 3.5 mg/kg b.w., n = 6). Forelimb reaching and grip strength test were recorded once per week, within 1 hour of Buspirone administration for 11 weeks post-injury. Different dose groups began to exhibit differences in reaching scores from 4 weeks post-injury. From 4-11 weeks post-injury, the reaching scores were highest in the lowest-dose group rats compared to the other 2 dose groups rats. Average grip strength was also found higher in the lowest-dose rats. Our results demonstrate a significant dose-dependence of Buspirone on the recovery of forelimb motor functions after cervical cord injury with the best performance occurring at the lowest dose tested

Immunogenicity of Fractional Doses of Tetravalent A/C/Y/W135 Meningococcal Polysaccharide Vaccine: Results from a Randomized Non-Inferiority Controlled Trial in Uganda

Meningitis are infections of the lining of the brain and spinal cord and can cause high fever, blood poisoning, and brain damage, as well as result in death in up to 10% of cases. Epidemics of meningitis occur almost every year in parts of sub-Saharan Africa, throughout a high-burden area spanning Senegal to Ethiopia dubbed the “Meningitis Belt.” Most epidemics in Africa are caused by Neisseria meningitidis (mostly serogroup A and W135). Mass vaccination campaigns attempt to control epidemics by administering meningococcal vaccines targeted against these serogroups, among others. However, global shortages of these vaccines are currently seen. We studied the use of fractional (1/5 and 1/10) doses of a licensed vaccine to assess its non-inferiority compared with the normal full dose. In a randomized trial in Uganda, we found that immune response and safety using a 1/5 dose were comparable to full dose for three serogroups (A, Y, W135), though not a fourth (C). In light of current shortages of meningococcal vaccines and their importance in fighting meningitis epidemics around the world, we suggest fractional doses be taken under consideration in mass vaccination campaigns

Meditation smartphone application effects on prehypertensive adults' blood pressure: Dose-response feasibility trial

OBJECTIVE: Essential hypertension (EH) is the most common chronic disease in the United States and a major cause of morbidity and mortality. Lifestyle interventions (e.g., diet, exercise, stress management) to reduce blood pressure (BP) are often complex with varying effectiveness. Breathing awareness meditation (BAM) is a stress management strategy with encouraging effects on BP, though widespread dissemination is hampered by the lack of an easy-to-use methodology to train and monitor BAM practices. A smartphone application (Tension Tamer [TT]) that implements BAM and tracks adherence has shown promise in addressing these gaps. This 6-month dose-response feasibility trial evaluated effects of the app on BP to further optimize BAM user guidelines. METHODS: Sixty-four adults with prehypertension were randomized to complete TT-guided BAM sessions for 5-, 10-, or 15-min intervals twice daily over 6 months. Continuous heart rate readings derived from the phone's video camera via reflective photoplethysmography were used as feedback and as an index of time-stamped adherence. Outcomes (resting BP, HR) were collected at baseline, 1-, 3-, and 6-months. RESULTS: Mixed modeling results showed a significant time effect for systolic BP (SBP) with a dose-response effect at Months 3 and 6. Adherence declined over time and was lowest in the 15-min dose condition, though SBP reductions were maintained. Generally, adherence was negatively associated with dose as the study progressed. CONCLUSIONS: Smartphone-implemented BAM appears to reduce SBP and can be a low-cost method to reach large populations. (PsycINFO Database Recor

A single dose of ChAdOx1 Chik vaccine induces neutralising antibodies against four chikungunya virus lineages in a phase 1 clinical trial

Chikungunya virus (CHIKV) is a reemerging mosquito-borne virus that causes swift outbreaks. Major concerns are the persistent and disabling polyarthralgia in infected individuals. Here we present the results from a first-in-human trial of the candidate simian adenovirus vectored vaccine ChAdOx1 Chik, expressing the CHIKV full-length structural polyprotein (Capsid, E3, E2, 6k and E1). 24 adult healthy volunteers aged 18–50 years, were recruited in a dose escalation, open-label, nonrandomized and uncontrolled phase 1 trial (registry NCT03590392). Participants received a single intramuscular injection of ChAdOx1 Chik at one of the three preestablished dosages and were followed-up for 6 months. The primary objective was to assess safety and tolerability of ChAdOx1 Chik. The secondary objective was to assess the humoral and cellular immunogenicity. ChAdOx1 Chik was safe at all doses tested with no serious adverse reactions reported. The vast majority of solicited adverse events were mild or moderate, and self-limiting in nature. A single dose induced IgG and Tcell responses against the CHIKV structural antigens. Broadly neutralizing antibodies against the four CHIKV lineages were found in all participants and as early as 2 weeks after vaccination. In summary, ChAdOx1 Chik showed excellent safety, tolerability and 100% PRNT50 seroconversion after a single dose

An Economic Evaluation of Selected Treatments for Avian Botulism in Waterfowl on Utah Marshes, 1953-54

Purpose and scope Each year thousands of western waterfowl succumb to disease, predators, mechanical injury and other decimating factors . Based on a review of records it is conservatively estimated that an average of 25,000 ducks have succumbed to botulism on western marsh areas annually. In a recent study, the United States Fish and Wildlife Service valued each duck and goose at $8.00 (McLeod, 1950). Applying this value to the estimated annual numerical loss, a total of$200,000 has been lost each season in mortality of western waterfowl from botulism. Control of this malady would reduce annual waterfowl and monetary losses. Prevention and cure are the only means of controlling botulism in wild ducks. At present, no economical preventative measure exists and control is based on curing stricken birds. The purpose of this study was to evaluate the cost of treatment and rate of recovery of birds stricken with botulism when treated by selected methods . The 4 treatments selected for evaluation were: (1) hospital inoculation, (2) fresh water, (3) field inoculation, and (4) no treatment or control . Research included a comprehensive evaluation of factors such as age, sex, species, body condition, degree of affliction, reaction to various amounts of antitoxin, and reaction t o selected treatment methods, thought to be pertinent in botulism control. This study was conducted during botulism outbreaks of 1953 and 1954, and was confined to state-owned marshlands of Utah. Study areas Three major areas provided sick birds used in this research: (1) Ogden Bay Refuge, (2) Farmington Bay Refuge, and (3) the Public Shooting Grounds . These man-made marsh areas are located on the saline flat lands adjacent to Great Salt Lake. The majority, 1,979 or 89.3 percent, of sick birds were taken from Ogden Bay Refuge on the Weber River Delta. This state-owned waterfowl refuge contains approximately 13,700 acres of diversified habitat . Excellent conditions for the production and existence of Clostridium botulinum, type c, the causative agent of botulism, were apparently present throughout the area. Farmington Bay Refuge, approximately 20 miles south of Ogden Bay Refuge in Davis County, Utah, was dried for improvements in 1953, but was traversed regularly during the 1954 season. In preparation for the hunting season, water was diverted into the north lake of Farmington Bay on October 1, 1953. A two-man crew picked up and disposed of approximately 2,000 dead ducks from approximately 20 acres of the reflooded marsh on October 6, 1953. This was the most serious outbreak of the study and indicated the rapidity with which sickness advanced. Few sick birds were noted, which indicated that the crisis had passed. Farmington Bay Refuge provided 121 of the 2,214 ducks treated during 1953 and 1954. Not more than 12 sick or dead birds were seen on the Public Shooting Grounds, 8 miles west of Corinne, Utah, in 1953. During the 1953 season, 3 sick birds were transported from the area to Ogden Bay Refuge for treatment. In 1954 this state-owned shooting area supplied lll sick birds for treatment. Other areas were observed during the study but did not provide sick birds for treatment. These areas consisted of : (1) State -owned lands beyond Bear River Migratory Bird Refuge, and (2) Smith and Utah Lakes west of Provo, Utah

Efficacy of Urtoxazumab (TMA-15 Humanized Monoclonal Antibody Specific for Shiga Toxin 2) Against Post-Diarrheal Neurological Sequelae Caused by \u3ci\u3eEscherichia coli\u3c/i\u3e O157:H7 Infection in the Neonatal Gnotobiotic Piglet Model

Enterohemorrhagic Escherichia coli (EHEC) is the most common cause of hemorrhagic colitis and hemolytic uremic syndrome in human patients, with brain damage and dysfunction the main cause of acute death. We evaluated the efficacy of urtoxazumab (TMA-15, Teijin Pharma Limited), a humanized monoclonal antibody against Shiga toxin (Stx) 2 for the prevention of brain damage, dysfunction, and death in a piglet EHEC infection model. Forty-five neonatal gnotobiotic piglets were inoculated orally with 3 x 109 colony-forming units of EHEC O157:H7 strain EDL933 (Stx1+, Stx2+) when 22–24 h old. At 24 h post-inoculation, piglets were intraperitoneally administered placebo or TMA-15 (0.3, 1.0 or 3.0 mg/kg body weight). Compared to placebo (n = 10), TMA-15 (n = 35) yielded a significantly greater probability of survival, length of survival, and weight gain (