Skeletal Muscle Wasting: The Estrogen Side of Sexual Dimorphism

The importance of defining sex differences across various biological and physiological mechanisms is more pervasive now than it has been over the last 15-20 years. As the muscle biology field pushes to identify small molecules and interventions to prevent, attenuate or even reverse muscle wasting, we must consider the effect of sex as a biological variable. It should not be assumed that a therapeutic will affect males and females with equal efficacy or equivalent target affinities under conditions where muscle wasting is observed. With that said, it is not surprising to find that we have an unclear or even a poor understanding of the effects of sex or sex hormones on muscle wasting conditions. Although recent investigations are beginning to establish experimental approaches that will allow investigators to assess the impact of sex-specific hormones on muscle wasting, the field still has not established enough published scientific tools that will allow the field to rigorously address critical hypotheses. Thus, the purpose of this review is to assemble a current summary of knowledge in the area of sexual dimorphism driven by estrogens with an effort to provide insights to interested physiologists on necessary considerations when trying to assess models for potential sex differences in cellular and molecular mechanisms of muscle wasting.

Evaluation of a capped dosing telavancin regimen compared to standard dosing at a large community teaching hospital

Telavancin, a lipoglycopeptide antibiotic, is traditionally dosed as 10 mg/kg based on total body weight, but is associated with toxicities that limit its use. This study supports the use of a capped dosing regimen of 750 mg in obese patients, which is associated with equal efficacy and fewer adverse effects compared to traditional dosing.

Evaluation of Efficacy of Triphala as a Preprocedural Mouth Rinse - A Comparative Study

BACKGROUND The objective of the study was to determine the efficacy of Triphala as a preprocedural mouth rinse & comparing the efficacy with chlorhexidine and betadine in reducing the viable microbial load in dental aerosols. METHODS 32 patients with chronic periodontitis were randomly allocated into 4 groups (A, B, C & D) of 8 patients each who received 0.2 % chlorhexidine (CHX), 6 % Triphala (TRP), 2 % betadine and water respectively as a pre-procedural mouth rinse. Blood agar plates were placed on the operator’s chest area and the patient’s chest area for collecting the aerosols. The agar plates were then incubated at 370C for 48 hours and colony-forming units (CFUs) were counted. RESULTS CFU was significantly reduced in groups A, B & C compared to group D. Intergroup comparison showed no significant difference in the efficacy of 0.2 % CHX and 6 % TRP with P-value 0.058 in the operator’s area and with a significant difference of Pvalue 0.014 in the patient’s area. 2 % betadine was found to be least effective among the 3 test groups. The number of CFUs was greater at the patient’s chest area than that of the operator. CONCLUSIONS This study reinforces the importance of preprocedural mouth rinse. Triphala showed near equal efficacy to CHX, which is considered the gold standard in aerosol reduction and also better than 2 % betadine. Therefore, it can be considered as an alternative to CHX as a preprocedural mouth rinse. KEY WORDS Triphala, Chlorhexidine, Betadine, Aerosols, Colony Forming Units (CFUs)

Intra-articular therapy with methotrexate or tumor necrosis factor inhibitors in rheumatoid arthritis: a systematic review

Background Persistent monoarthritis in otherwise well-controlled rheumatoid arthritis presents a therapeutic challenge. Intra-articular (IA) steroids are a mainstay of treatment, though some have queried whether IA disease modifying anti-rheumatic drugs (DMARD) and biologics can be used in those who fail steroid injections. Methods A systematic literature review was conducted using four medical databases to identify randomized, controlled trials assessing IA therapies in RA patients. Included studies underwent Cochrane Risk of Bias 2 assessment for quality. Results Twelve studies were included, 6 of which examined intra-articular (IA) TNF inhibitors (TNFi), and 6 studies evaluating IA methotrexate. Of those evaluating IA TNFi, one study reported statistical improvement in TNFi therapy when compared with placebo. The remaining 5 studies compared IA TNFi therapy with steroid injections. IA TNFi had statistically improved symptom scores and clinical assessments comparable with IA steroid treatments. In the 6 studies evaluating IA methotrexate, the addition of methotrexate to steroid intra-articular therapy was not found to be beneficial, and singular methotrexate injection was not superior to the control arms (saline or triamcinolone). Risk-of-bias (ROB) assessment with the Revised Cochrane ROB tool indicated that 2 of 6 TNFi studies were at some risk or high risk for bias, compared with 5 out of 6 methotrexate studies. Conclusion For persistent monoarthritis in rheumatoid arthritis, IA methotrexate was not found to have clinical utility. Intra-articular TNFi therapy appears to have equal efficacy to IA steroids, though the optimal dose and frequency of injections is yet unknown.

Early-Pregnancy Dydrogesterone Supplementation Mimicking Luteal-Phase Support in ART Patients Did Not Provoke Major Reproductive Disorders in Pregnant Mice and Their Progeny

Progestogens are frequently administered during early pregnancy to patients undergoing assisted reproductive techniques (ART) to overcome progesterone deficits following ART procedures. Orally administered dydrogesterone (DG) shows equal efficacy to other progestogens with a higher level of patient compliance. However, potential harmful effects of DG on critical pregnancy processes and on the health of the progeny are not yet completely ruled out. We treated pregnant mice with DG in the mode, duration, and doses comparable to ART patients. Subsequently, we studied DG effects on embryo implantation, placental and fetal growth, fetal-maternal circulation, fetal survival, and the uterine immune status. After birth of in utero DG-exposed progeny, we assessed their sex ratios, weight gain, and reproductive performance. Early-pregnancy DG administration did not interfere with placental and fetal development, fetal-maternal circulation, or fetal survival, and provoked only minor changes in the uterine immune compartment. DG-exposed offspring grew normally, were fertile, and showed no reproductive abnormalities with the exception of an altered spermiogram in male progeny. Notably, DG shifted the sex ratio in favor of female progeny. Even though our data may be reassuring for the use of DG in ART patients, the detrimental effects on spermatogenesis in mice warrants further investigations and may be a reason for caution for routine DG supplementation in early pregnancy.

562 Home Microsurgical Method: A Zero-Cost, Accessible, Simulator Using Home-Based Technologies

Microsurgery is an advanced practice that demands a steep learning curve. Skill acquisition is reliant on repetition which is challenging with decreased trainee operating hours. Evidence indicates early skill acquisition in low-fidelity simulation is of equal efficacy to operating time. Our aim was to create a zero-cost, low-fidelity, microsurgery simulator using home-based technology. The simulator has five components; a smartphone (iPhone/Android), laptop/computer, USB/lightning wire, ruler, and two supports of equal height. The ruler creates a platform between the supports on which to place the phone, camera focused downwards. The phone camera captures the surgical field between the supports, projecting the image onto the laptop screen via the USB connection. The trainee operates in a ‘hands down, eyes up’ fashion, looking forwards at the laptop/computer screen whilst operating below in the field of the camera. Latest smartphones achieve magnifications equivalent to a microscope, preserving image quality whilst allowing recording of sim tasks for technical review. Initial verbal feedback in informal advisory groups has been resoundingly positive. There is clear educational benefit with potential to work with consultant surgeons to develop free, accessible, online training modules. These would provide structured, remote, platforms for both qualitative and quantitative tracking of skill development.

Evaluation of the economic effect of biological therapy in patients with severe COVID-19 and cytokine storm

Aim. The study aimed to assess the economic effect of biological therapy with anti-interleukin (IL)-6 drugs: tocilizumab, olokizumab, and levilimab in patients with severe COVID-19 and cytokine storm.Materials and Methods. An assessment of the economic consequences of severe COVID-19 therapy was carried out using the cost of illness analysis in a model developed in Microsoft Excel 2016 (Microsoft, USA). The direct medical costs of providing care for COVID-19 were taken into account (ICU service, the cost of biological therapy, and the use of glucocorticosteroids (GC)). Data from a prospective, historical controlled CHIC study conducted in the Netherlands were used as a source of efficacy. A mathematical model has been developed for extrapolating the CHIC study results to clinical outcomes (transfer to mechanical ventilation, discharge from ICU, lethal outcome) and forecasting the costs of managing severe patients with COVID-19 in real clinical practice in the Russian Federation.Results. The reduction in the cost of therapy when the hypothesis of equal efficacy of tocilizumab, olokizumab, and levilimab is accepted by reducing the cost of drug therapy will be 1,251,698.99 rubles per 72 patients when comparing olokizumab with tocilizumab and 939,718.84 rubles per 72 patients when comparing olokizumab with levilimab.Conclusion. Anti-interleukin (IL)-6 drugs in combination with GC are an effective treatment option for moderate to severe patients with COVID-19 and cytokine storm symptoms. This group of drugs is indicated as the main one for the treatment of this condition.

Fenbendazole efficacy in lambs: a comparison of oral dosing and feed block additive modes of administration

Twenty-four, 3-month old West African Dwarf (WAD) Lambs were divided into 3 groups of 8 each. Each group was given free access to a common pasture by day, but housed separately in concrete floored and netted pens provided with varied but equal supplements by night. Two of the groups were treated with 2.5% Fenbendazole suspension at a dose rate of 10mg/kg body weight administered orally once a month for 3 consecutive months for one group, dissolved in molasses mixed with Brewer's grains in 5 divided daily doses per month for 3 consecutive months for the second group, while the third 3 group was left us untreated control. The mean haematocrit values, mean percentage egg reduction and mean liveweight gains were higher at the end of the trial for the single monthly dosed group than for the untreated control group, while the same measurements were insignificantly different (P>0.05) for the two treated groups. Significant appreciation in the mean hematocrit values, mean percentage egg reduction and mean liveweight gains were proofs of the effectiveness of treatment and molasses supplementation, while the insignificance of the difference of the same measurements in the two treated groups implied equal efficacy of the two different schedules of administration. The in-feed scheme was easier and convenient for use on weak and pregnant eves that could abort on rough handling

Individual responses to topical ibuprofen gel or capsaicin cream for painful knee osteoarthritis: a series of n-of-1 trials

Objectives To determine individual responses to ibuprofen gel or capsaicin cream for painful, radiographic knee OA using a series of n-of-1 trials. Methods Twenty-two participants were allocated 5% ibuprofen gel (A) and 0.025% capsaicin cream (B) in random sequence (AB or BA). Patients underwent up to 3 treatment cycles, each comprising one treatment for 4 weeks, an individualized washout period (maximum 4 weeks), then the other treatment for 4 weeks. Differential (ibuprofen or capsaicin) response was defined when change-from-baseline pain intensity scores (0–10 NRS) differed by ≥1 between treatments in ≥2 cycles within a participant. Results A total of 104 treatment periods were aggregated. Mean pain reduction was 1.2 (95% CI: 0.5, 1.8) on ibuprofen and 1.6 (95% CI: 0.9, 2.4) on capsaicin (P = 0.221). Of 22 participants, 4 (18%) had a greater response to ibuprofen, 9 (41%) to capsaicin, 4 (18%) had similar responses, and 5 (23%) were undetermined. Conclusion Irrespective of equal efficacy overall, 59% of people displayed a greater response to one treatment over the other. Patients who do not benefit from one type of topical treatment should be offered to try another, which may be more effective. N-of-1 trials are useful to identify individual response to treatment. Clinical trial registration https://clinicaltrials.gov, NCT03146689