Explore the vast range of titles available.

Background Quality by design (QbD) refers to the achievement of certain predictable quality with desired and predetermined specifications. A quality-by-design approach to method development can potentially lead to a more robust/rugged method due to emphasis on risk assessment and management than traditional or conventional approach. An important component of the QbD is the understanding of dependent variables, various factors, and their interaction effects by a desired set of experiments on the responses to be analyzed. The present study describes the risk based HPLC method development and validation of ceftriaxone sodium in pharmaceutical dosage form. Results An efficient experimental design based on central composite design of two key components of the RP-HPLC method (mobile phase and pH) is presented. The chromatographic conditions were optimized with the Design Expert software 11.0 version, i.e., Phenomenex ODS column C18 (250 mm × 4.6 mm, 5.0 μ), mobile phase used acetonitrile to water (0.01% triethylamine with pH 6.5) (70:30, v/v), and the flow rate was 1 ml/min with retention time 4.15 min. The developed method was found to be linear with r 2 = 0.991 for range of 10–200 μg/ml at 270 nm detection wavelength. The system suitability test parameters, tailing factor and theoretical plates, were found to be 1.49 and 5236. The % RSD for intraday and inter day precision was found to be 0.70–0.94 and 0.55–0.95 respectively. The robustness values were less than 2%. The assay was found to be 99.73 ± 0.61%. The results of chromatographic peak purity indicate the absence of any coeluting peaks with the ceftriaxone sodium peak. The method validation parameters were in the prescribed limit as per ICH guidelines. Conclusion The central composite design experimental design describes the interrelationships of mobile phase and pH at three different level and responses to be observed were retention time, theoretical plates, and peak asymmetry with the help of the Design Expert 11.0 version. Here, a better understanding of the factors that influence chromatographic separation with greater confidence in the ability of the developed HPLC method to meet their intended purposes is done. The QbD approach to analytical method development was used for better understanding of method variables with different levels.

Recent hypotheses propose that the human placenta and chorioamniotic membranes (CAMs) experience telomere length (TL)-mediated senescence. These hypotheses are based on mean TL (mTL) measurements, but replicative senescence is triggered by short and dysfunctional telomeres, not mTL. We measured short telomeres by a vanguard method, the Telomere shortest length assay, and telomere-dysfunction-induced DNA damage foci (TIF) in placentas and CAMs between 18-week gestation and at full-term. Both the placenta and CAMs showed a buildup of short telomeres and TIFs, but not shortening of mTL from 18-weeks to full-term. In the placenta, TIFs correlated with short telomeres but not mTL. CAMs of preterm birth pregnancies with intra-amniotic infection showed shorter mTL and increased proportions of short telomeres. We conclude that the placenta and probably the CAMs undergo TL-mediated replicative aging. Further research is warranted whether TL-mediated replicative aging plays a role in all preterm births.

Bleeding from the small intestine remains a clinically challenging diagnostic and therapeutic problem. It may be minor, requiring only supplemental iron treatment, to patients who have severe overt bleeding that requires multimodal intervention. This article provides an up-to-date review of the state-of-the-art of diagnosis and treatment of small intestinal bleeding.

This paper describes the three-step synthesis of TBS-MAC, a masked acyl cyanide (MAC) and a versatile one-carbon oxidation state three synthon. We have developed a scalable and detailed synthesis that involves: (1) acetylation of malononitrile to form the sodium enolate, (2) protonation of the enolate to form acetylmalononitrile, and (3) epoxidation of the enol, rearrangement to an unstable alcohol, and TBS-protection to form the title compound. Both the sodium enolate and acetylmalononitrile are bench-stable precursors to the intermediate hydroxymalononitrile, which can be converted to other MAC reagents beyond TBS by varying the protecting group (Ac, MOM, EE, etc.).

Objective: The objective was to provide evidence-based care for patients with traumatic cataracts, we assessed whether a posterior capsulotomy and anterior vitrectomy, as part of the primary surgical procedure, could be a positive predictor of final visual outcome. Materials and Methods: This is a prospective randomized control trial. Patients presenting at our hospital between January 2010 and December 2012 having ocular trauma and traumatic cataracts were enrolled, according to the inclusion criteria. We enrolled two groups: Those with and without primary posterior capsulotomy and vitrectomy. Information regarding demographic and ocular trauma were collected using the World Eye Trauma Registry form at the first visit and follow-up, and specific information was collected for both the group who underwent posterior capsulectomies and vitrectomies as a part of the primary procedure, and the control group. Data were analyzed to evaluate the predictive value of primary posterior capsulectomy and anterior vitrectomy. Results: We enrolled 120 cases, 60 in each group, comprising 31 females and 89 males. When all other variables were controlled for, the visual outcome (best corrected visual acuity) differed significantly (P < 0.001) between the groups. Conclusion: Performance of posterior capsulectomy and anterior vitrectomy as part of the primary procedure improves the final visual outcome.

Immune checkpoint inhibitors have opened a new era in treating advanced malignancies, resulting in a rapid increase in utilization, given the remarkable clinical outcomes. The incidence of immune-related adverse events increased due to the immunologic effects of these therapeutic agents. However, immune-related renal adverse events remain low, representing only a small incidence of reported cases. Common renal toxicity described includes acute interstitial nephritis, minimal change disease, and immune complex glomerulonephritis. Renal tubular acidosis has occasionally been reported but is highly uncommon. This report presents a case of a 68-year-old woman with a known history of metastatic melanoma undergoing treatment with ipilimumab+nivolumab, who developed distal renal tubular acidosis requiring stress dose steroids and sodium bicarbonate for treatment. We describe the clinical characteristics, potential mechanisms, and management of this case, highlighting the need among clinicians utilizing immune check inhibitors to be aware of this immune-related disease entity.