A selective and rapid high-performance liquid chromatography–tandem mass spectrometry method was developed and validated for the quantification of raltegravir using raltegravir-d3 as an internal standard (IS). The analyte and IS were extracted with methylene chloride and n-hexane solvent mixture from 100 mL human plasma. The chromatographic separation was achieved on a Chromolith RP-18e endcapped C18 (100 mm ? 4.6 mm) column in a run time of 2.0 min. Quantitation was performed in the negative ionization mode using the transitions of m/z 443.1-316.1 for raltegravir and m/z 446.1-319.0 for IS. The linearity of the method was established in the concentration range of 2.0–6000 ng/mL. The mean extraction recovery for raltegravir and IS was 92.6% and 91.8%, respectively, and the IS-normalized matrix factors for raltegravir ranged from 0.992 to 0.999. The application of this method was demonstrated by a bioequivalence study on 18 healthy subjects.

Protrusio acetabuli, or abnormal protrusion of the femoral head into the acetabulum, requires performance of a total hip arthroplasty (THA) for which various reconstruction techniques and outcomes have been described. The aim of this systematic review is to provide a comprehensive analysis of the current evidence, evaluate treatment efficacy, compare surgical techniques, and identify topics for future research along with improving evidence-based decision-making, improving patient outcomes in the management of this condition. A thorough systematic review of the PubMed, Embase, Cochrane Library databases, and Scopus library was conducted, and articles describing techniques of THA for treatment of protrusion acetabuli were extracted. The initial search generated 751 results. After exclusion, 18 articles were included. Of these, eight were prospective studies and 10 were retrospective. Surgery was performed on 783 hips with a mean age of 60 years; 80% of females who mostly had inflammatory arthritis were followed up for 8.86 years (range, 2-15.4 years). Good outcomes have been achieved with THA using uncemented cups with bone graft; however, no conclusion could be drawn with regard to the femoral side. It can be concluded that the concept of restoration of the anatomical hip center of rotation is paramount for good outcome and better survival of the implant is important when using uncemented cups with a bone graft. In addition, screw augmentation for fixation is not recommended unless absolutely necessary. The most common complications were aseptic loosening and heterotopic ossification. While the former required revision, conservative management was administered for the latter.

Protrusio acetabuli, or abnormal protrusion of the femoral head into the acetabulum, requires performance of a total hip arthroplasty (THA) for which various reconstruction techniques and outcomes have been described. The aim of this systematic review is to provide a comprehensive analysis of the current evidence, evaluate treatment efficacy, compare surgical techniques, and identify topics for future research along with improving evidence-based decision-making, improving patient outcomes in the management of this condition. A thorough systematic review of the PubMed, Embase, Cochrane Library databases, and Scopus library was conducted, and articles describing techniques of THA for treatment of protrusion acetabuli were extracted. The initial search generated 751 results. After exclusion, 18 articles were included. Of these, eight were prospective studies and 10 were retrospective. Surgery was performed on 783 hips with a mean age of 60 years; 80% of females who mostly had inflammatory arthritis were followed up for 8.86 years (range, 2-15.4 years). Good outcomes have been achieved with THA using uncemented cups with bone graft; however, no conclusion could be drawn with regard to the femoral side. It can be concluded that the concept of restoration of the anatomical hip center of rotation is paramount for good outcome and better survival of the implant is important when using uncemented cups with a bone graft. In addition, screw augmentation for fixation is not recommended unless absolutely necessary. The most common complications were aseptic loosening and heterotopic ossification. While the former required revision, conservative management was administered for the latter.

Protrusio acetabuli, or abnormal protrusion of the femoral head into the acetabulum, requires performance of a total hip arthroplasty (THA) for which various reconstruction techniques and outcomes have been described. The aim of this systematic review is to provide a comprehensive analysis of the current evidence, evaluate treatment efficacy, compare surgical techniques, and identify topics for future research along with improving evidence-based decision-making, improving patient outcomes in the management of this condition. A thorough systematic review of the PubMed, Embase, Cochrane Library databases, and Scopus library was conducted, and articles describing techniques of THA for treatment of protrusion acetabuli were extracted. The initial search generated 751 results. After exclusion, 18 articles were included. Of these, eight were prospective studies and 10 were retrospective. Surgery was performed on 783 hips with a mean age of 60 years; 80% of females who mostly had inflammatory arthritis were followed up for 8.86 years (range, 2-15.4 years). Good outcomes have been achieved with THA using uncemented cups with bone graft; however, no conclusion could be drawn with regard to the femoral side. It can be concluded that the concept of restoration of the anatomical hip center of rotation is paramount for good outcome and better survival of the implant is important when using uncemented cups with a bone graft. In addition, screw augmentation for fixation is not recommended unless absolutely necessary. The most common complications were aseptic loosening and heterotopic ossification. While the former required revision, conservative management was administered for the latter.

PURPOSE: The DNA methylation mediated by specific DNA methyltransferases (DNMTs), results in the epigenetic silencing of multiple genes which are implicated in human breast cancer. We hypothesized that the natural compounds modulate the expression of DNMTs and their associated proteins in the breast cancer cell lines and affect the methylation mediated gene silencing. METHODS: The DNMTs transcript expression was analyzed by reverse transcription-polymerase chain reaction (RT-PCR) in the tumors and the adjacent normal breast tissues of the patients with invasive ductal breast carcinoma. We tested the hypothesis that the natural compounds, viz., epigallocatechin gallate (EGCG), genistein, withaferin A, curcumin, resveratrol, and guggulsterone, have demethylation potential. To investigate this hypothesis, we analyzed the DNMTs expression at the transcript levels, followed by the analysis of DNMT1 and its associated proteins (HDAC1, MeCP2, and MBD2). RESULTS: The increased DNMTs transcripts expression, viz., DNMT1, DNMT3a, and DNMT3b, in the breast cancer tissues suggest involvement of the DNMTs in the breast carcinogenesis. Quantitative RT-PCR analysis revealed that the treatment with natural compounds, viz., EGCG, genistein, withaferin A, curcumin, resveratrol, and guggulsterone, resulted in a significant decrease in the transcript levels of all the DNMTs investigated. Importantly, these natural compounds decreased the protein levels of DNMT1, HDAC1, and MeCP2. CONCLUSION: Our results demonstrate that the natural compounds, EGCG, genistein, withaferin A, curcumin, resveratrol, and guggulsterone, have the potential to reverse the epigenetic changes. Moreover, their lack of toxicity makes these natural compounds promising candidates for the chemoprevention of the breast cancer. In-depth future mechanistic studies aimed to elucidate how these compounds affect the gene transcription are warranted.
Breast ; Breast Neoplasms ; Catechin ; Cell Line ; Chemoprevention ; Curcumin ; DNA ; DNA Methylation ; Epigenomics ; Genistein ; Humans ; Methylation ; Methyltransferases ; Pregnenediones ; Proteins ; Stilbenes ; Withanolides

OBJECTIVES: The objective of this study was to highlight the role of lateral arthroplasty along with interposition of the buccal fat pad (BFP) in the management of Sawhney type III temporomandibular joint (TMJ) ankylosis. MATERIALS AND METHODS: Ten patients with TMJ ankylosis (7 unilateral and 3 bilateral, total of 13 joints) were treated with lateral arthroplasty and BFP interposition. The bony bridge of the ankylotic mass on the lateral aspect was resected, leaving a distance of 1.5 to 2.0 cm from the base of the skull to the neck of the condyle. The condyle was left intact. Coronoidectomy was performed on the ipsilateral side via the same approach in all cases. The inter-incisal opening was measured at that time, and if it was less than 35 mm, contralateral coronoidectomy was performed by using the intra-oral approach. After satisfactory inter-incisal mouth opening (≥35 mm) was achieved, the TMJ surgical site was revisited, and BFP was retrieved and used to cover the lateral aspect of the medially placed condyle. RESULTS: With lateral arthroplasty, the medially displaced condyle can be left in-situ to maintain the mandibular ramal height and function and to act as a growth center in children. Interposition of the BFP prevents reformation of the lateral bony bridge that was removed. CONCLUSION Lateral arthroplasty along with interpositioning of the BFP is a novel technique for managing Sawhney type III ankylosis that achieves management goals while avoiding complex and advanced reconstructive surgical procedures.

OBJECTIVES: The objective of this study was to highlight the role of lateral arthroplasty along with interposition of the buccal fat pad (BFP) in the management of Sawhney type III temporomandibular joint (TMJ) ankylosis. MATERIALS AND METHODS: Ten patients with TMJ ankylosis (7 unilateral and 3 bilateral, total of 13 joints) were treated with lateral arthroplasty and BFP interposition. The bony bridge of the ankylotic mass on the lateral aspect was resected, leaving a distance of 1.5 to 2.0 cm from the base of the skull to the neck of the condyle. The condyle was left intact. Coronoidectomy was performed on the ipsilateral side via the same approach in all cases. The inter-incisal opening was measured at that time, and if it was less than 35 mm, contralateral coronoidectomy was performed by using the intra-oral approach. After satisfactory inter-incisal mouth opening (≥35 mm) was achieved, the TMJ surgical site was revisited, and BFP was retrieved and used to cover the lateral aspect of the medially placed condyle. RESULTS: With lateral arthroplasty, the medially displaced condyle can be left in-situ to maintain the mandibular ramal height and function and to act as a growth center in children. Interposition of the BFP prevents reformation of the lateral bony bridge that was removed. CONCLUSION: Lateral arthroplasty along with interpositioning of the BFP is a novel technique for managing Sawhney type III ankylosis that achieves management goals while avoiding complex and advanced reconstructive surgical procedures.
Adipose Tissue ; Ankylosis ; Arthroplasty ; Child ; Humans ; Mouth ; Neck ; Reconstructive Surgical Procedures ; Skull ; Temporomandibular Joint

Objective: To critically evaluate the trials that have assessed the efficacy and safety of ivermectin COVID-19 and to validate the rationality of using this drug in the management of COVID-19 either as a prophylactic or therapeutic agent. Methods: The authors conducted a systematic search through various databases, i.e., Cochrane library, PubMed, clincialtrials.gov, and preprint servers, for publications from 2020 to May 2021. The keywords used for the search were: "COVID-19 and ivermectin"(with filter set for "trials"). All the trials assessing efficacy in prophylaxis and treatment of COVID-19 were included for analysis. The primary outcome was the proportion of patients showing disease progression. Secondary outcomes were mean duration of hospitalization and resolution of symptoms, the proportion of patients testing positive on day 5-7, the mortality rate in severe cases, incidence of serious adverse events, and contacts of COVID-19 positive patients who turned RT-PCR positive after prophylaxis treatment. Results: A total of 17 clinical trials were included for the evaluation. Ivermectin proved to be a beneficial add-on therapy, as it reduced the risk of disease progression (OR 0.47, 95% CI 0.30-0.74, P =0.001), led to early resolution of symptoms (MD -1.16, 95% CI-1.52 - 0.81, P <0.001), and had less duration of hospitalization (MD -2.21, 95% CI -3.23 - 1.19, P <0.001). In addition, ivermectin was better in providing effective prophylaxis (OR 0.13, 95% CI 0.05-0.30, P <0.001). The incidence of serious adverse events was low. Conclusions: As an adjunct to standard care, ivermectin has shown its efficacy and safety in treating and prophylaxis in COVID-19 disease. These results should be interpreted cautiously as these trials had significant shortcomings.

Previously, we reported that Y, a new epigallocatechin gallate derivative, is efficacious in reversing doxorubicin (DOX)--mediated resistance in hepatocellular carcinoma BEL-7404/DOX cells. In this study, we evaluated the efficacy of Y in reversing drug resistance both and by determining its effect on the adenosine triphosphate-binding cassette protein B1 transporter (ABCB1 or P-glycoprotein, P-gp). Our results showed that Y significantly sensitized cells overexpressing the ABCB1 transporter to anticancer drugs that are ABCB1 substrates. Y significantly stimulated the adenosine triphosphatase activity of ABCB1. Furthermore, Y exhibited a higher docking score as compared with epigallocatechin gallate inside the transmembrane domain of ABCB1. In addition, in the nude mouse tumor xenograft model, Y (110 mg/kg, intragastric administration), in combination with doxorubicin (2 mg/kg, intraperitoneal injection), significantly inhibited the growth of BEL-7404/DOX cell xenograft tumors, compared to equivalent epigallocatechin gallate. In conclusion, Y significantly reversed ABCB1-mediated multidrug resistance and its mechanisms of action may result from its competitive inhibition of the ABCB1 drug efflux function.