Double blind randomized controlled trial of efficacy of ormeloxifene for the treatment of fibroadenoma (The FIBROCENT study).

BACKGROUND: We evaluated the effectiveness of Ormeloxifene (Centchroman) on regression of Fibroadenoma in a double-blind randomized controlled trial. METHODS: Patients with biopsy proven Fibroadenoma were enrolled between March 2023 and October 2023 and divided in two arms- Ormeloxifene group and Placebo group. Effectiveness of the treatment was evaluated using USG. No residual mass was defined as complete regression and more than 30% decrease in size was considered as partial regression. RESULTS: A total of 130 consecutive patients with Fibroadenoma were randomized to Ormeloxifene group (n = 65) and Placebo Group (n = 65). Complete regression was observed in 9% (6/65) patients in Ormeloxifene group and 10.8% (7/65) in Placebo Group at the end of 12 weeks (p = 0.49). Twenty one patients taking Ormeloxifene reported adverse events as compared to none in the other group. CONCLUSION: In our study Ormeloxifene was not found to be effective in treatment of fibroadenoma and had concerning side effects.

What is the Long-term Wear of a 5-Mrad Highly Crosslinked Polyethylene Liner? A 14-year RSA Study.

BACKGROUND: Lower doses of irradiation (≤ 5 Mrad) during the manufacture of highly crosslinked polyethylene acetabular liners may result in less crosslinking and an increased wear rate. Radiostereometric analysis (RSA) studies have found that wear of more highly irradiated highly crosslinked polyethylene liners (7 to 10 Mrad) decreases at longer-term follow-up compared with earlier reports of the same cohorts. Although wear of 5-Mrad irradiated liners appears to increase at midterm follow-up, it is unclear whether that remains true at longer follow-up. QUESTIONS/PURPOSES: We asked: (1) In patients who underwent THA with a 5-Mrad highly crosslinked polyethylene liner, what is the wear rate evaluated with RSA during the first 14 years? (2) Does the wear rate decrease after 6 years in situ? METHODS: This is a brief follow-up of prior RSA studies performed at 2 and 6 years. We prospectively reviewed the longer-term wear rate in 13 patients who underwent primary THAs with the same design of a 5-MRad irradiated crosslinked acetabular liner and a 28-mm cobalt-chromium articulation. Of the initial 30 patients who were enrolled, 13 (43%) were available at the 14-year timepoint; nine patients had died, 1 patient had withdrawn, 1 had an intraoperative fracture, 3 patients were too infirm to have radiographs, 2 had no baseline RSA radiographs, and 1 had poor-quality RSA images. Tantalum markers were inserted during surgery, and all patients had RSA radiographic examinations at 1 week, 6 months, and 1, 2, 6, and 14 years postoperatively. RESULTS: The mean ± standard deviation proximal, 2D, and 3D wear rates calculated between 1 year and 14 years were 0.019 ± 0.013 mm, 0.022 ± 0.015 mm, and 0.025 ± 0.019 mm per year, respectively. No patient had proximal 2D or 3D wear rates exceeding 0.06 mm per year. An increasing wear rate over time was measured for proximal and 2D wear rates between 6 and 14 years (0.024 and 0.030 mm per year) compared with that between 1 and 6 years (0.008 and 0.010 mm per year; p = 0.03). CONCLUSION: The proximal, 2D, and 3D wear of a highly crosslinked polyethylene liner produced using 5-Mrad radiation remains low in the longer-term. With the small numbers available in a long-term RSA study such as this, we confirmed that the wear rate did not decrease at longer-term follow-up, unlike previous RSA studies of more highly irradiated highly crosslinked polyethylene liners. Nevertheless, the wear rate remains very low and below the threshold typically associated with the development of osteolysis (0.1 mm/year of wear). This should provide assurance to orthopaedic surgeons monitoring patients with this 5-Mrad irradiated liner in situ, while providing useful information to manufacturers of future highly crosslinked polyethylene liners. LEVEL OF EVIDENCE: Level IV therapeutic study.

Assessment of symptomatic response to intravesical alkalinized lidocaine, bupivacaine, heparin and steroids in patients with bladder pain syndrome.

Bladder Pain Syndrome (BPS) is a puzzling and complicated disorder. 12 such patients, with a mean age 48.3 years, were treated with weekly intravesical instillation of admixture of alkalinized lidocaine, bupivacaine, heparin and steroids for six weeks. Evaluating the benefits of this therapy, patients experienced 82.2% & 90.9% relief at 3rd & 6th week of instillation. After completion of six cycles of therapy, patients experienced 68.7% & 65.3% relief at 3rd & 6th month follow up, concluding the early and long term relief of BPS.

An investigation of the environmental implications of bioplastics: Recent advancements on the development of environmentally friendly bioplastics solutions.

The production and utilization of plastics may prove beneficial, but the environmental impact suggests the opposite. The single-use plastics (SUP) and conventional plastics are harmful to the environment and need prompt disposal. Bioplastics are increasingly being considered as a viable alternative to conventional plastics due to their potential to alleviate environmental concerns such as greenhouse gas emissions and pollution. However, the previous reviews revealed a lack of consistency in the methodologies used in the Life Cycle Assessments (LCAs), making it difficult to compare the results across studies. The current study provides a systematic review of LCAs that assess the environmental impact of bioplastics. The different mechanical characteristics of bio plastics, like tensile strength, Young's modulus, flexural modulus, and elongation at break are reviewed which suggest that bio plastics are comparatively much better than synthetic plastics. Bioplastics have more efficient mechanical properties compared to synthetic plastics which signifies that bioplastics are more sustainable and reliable than synthetic plastics. The key challenges in bioplastic adoption and production include competition with food production for feedstock, high production costs, uncertainty in end-of-life management, limited biodegradability, lack of standardization, and technical performance limitations. Addressing these challenges requires collaboration among stakeholders to drive innovation, reduce costs, improve end-of-life management, and promote awareness and education. Overall, the study suggests that while bioplastics have the potential to reduce environmental impact, further research is needed to better understand their life cycle and optimize their end-of-life (EoL) management and production to maximize their environmental benefits.

Large articulations do not increase wear rates of thin second-generation highly cross-linked polyethylene liners at ten years.

Aims: Radiostereometric analysis (RSA) is the most accurate radiological method to measure in vivo wear of highly cross-linked polyethylene (XLPE) acetabular components. We have previously reported very low wear rates for a sequentially irradiated and annealed X3 XLPE liner (Stryker Orthopaedics, USA) when used in conjunction with a 32 mm femoral heads at ten-year follow-up. Only two studies have reported the long-term wear rate of X3 liners used in conjunction with larger heads using plain radiographs which have poor sensitivity. The aim of this study was to measure the ten-year wear of thin X3 XLPE liners against larger 36 or 40 mm articulations with RSA. Methods: We prospectively reviewed 19 patients who underwent primary cementless THA with the XLPE acetabular liner (X3) and a 36 or 40 mm femoral head with a resultant liner thickness of at least 5.8 mm. RSA radiographs at one week, six months, and one, two, five, and ten years postoperatively and femoral head penetration within the acetabular component were measured with UmRSA software. Of the initial 19 patients, 12 were available at the ten-year time point. Results: The median proximal, 2D, and 3D wear rates calculated between one and ten years were all less than 0.005 mm/year, with no patient recording a proximal wear rate of more than 0.021 mm/year. Importantly, there was no increase in the wear rate between five and ten years. Conclusion: The very low wear rate of X3 XLPE liners with larger articulations remains encouraging for the future clinical performance of this material.

Quest for Active Species in Al/B-Catalyzed CO2 Hydrosilylation.

We demonstrate the catalytic role of aluminum and boron centers in aluminum borohydride [(2-Me2CH2C6H4)(C6H5)Al(µ-H)2B(C6H5)2] (6) during carbon dioxide (CO2) hydrosilylation. Preliminary investigations into CO2 reduction using [(2-Me2NCH2C6H4)(H)Al(µ-H)]2 (1) and [Ph3C][B(3,5-C6H3Cl2)4] (2) in the presence of Et3SiH and PhSiH3 resulted in CH2(OSiR3)2 and CH3OSiR3, which serve as formaldehyde and methanol surrogates, respectively. In pursuit of identifying the active catalytic species, three compounds, B(3,5-C6H3Cl2)3 (3), [(2-Me2NCH2C6H4)(3,5-C6H3Cl2)Al(µ-H)2B(3,5-C6H3Cl2)2] (4), and [(2-Me2NCH2C6H4)2Al(THF)][B(3,5-C6H3Cl2)4] (5), were isolated. Among compounds 2-5, the highest catalytic conversion was achieved by 4. Further, 4 and 6 were prepared in a straightforward method by treating 1 with 3 and BPh3, respectively. 6 was found to be in equilibrium with 1 and BPh3, thus making the catalytic process of 6 more efficient than that of 4. Computational investigations inferred that CO2 reduction occurs across the Al-H bond, while Si-H activation occurs through a concerted mechanism involving an in situ generated aluminum formate species and BPh3.

Patient Perspectives After Surgery-Related Complications Among Breast Cancer Patients from a LMIC.

Long-term quality of life in breast cancer patients has been studied and published regularly. However, the lived experiences of patients who develop complications after surgery are not well understood. Determining this experience of patients is challenging in most low- and middle-income countries where the majority of patients belong to poor strata of society and are uneducated. We aimed to explore the thoughts, feelings, and experiences of patients with surgery-related complications after breast cancer surgery. Purposive sampling was used to identify patients who developed any postoperative complication, and semi-structured interviews were conducted. Common patterns of patient experiences were identified and analyzed using descriptive thematic analysis. Twenty-eight patients out of 210 developing complications postoperatively were identified. The median age was 48 years (range 32-65 years). The majority (n = 26) were housewives, educated below the primary level (n = 11) and below the poverty line (n = 13). Complications included seroma (n = 17), flap necrosis and infection (n = 5), and hematoma (n = 1). Seven domains emerged from the interviews-knowledge of complications, psychological impact, burden, disruptiveness, social impact, relationship with the surgical team, and suggestions to improve the experience. The themes identified in the present study provide insights into the lived experiences and can inform the future development of patient-reported outcome measures and quality improvement programs, including more effective pre-operative counseling and consent. Supplementary Information: The online version contains supplementary material available at 10.1007/s13193-023-01721-z.

Assessing trait emotional intelligence and its relationship with stress and health behaviour in the education sector: An empirical study from Uttarakhand, India.

BACKGROUND: Emotional intelligence of teachers can affect their mental and physical health as well their performance in school. Both emotional intelligence and health behavior can have an impact on stress. The majority of Indian studies have examined only one type of teachers, have used indigenous scales which are not internationally valid, and have not studied health behaviour. The role of age and gender on emotional intelligence is also a debatable subject which requires larger studies The present study was undertaken to evaluate the trait emotional intelligence, stress and health behaviour of teachers and to determine their inter-relationship and to assess the role of demographic and professional attributes on emotional intelligence. METHODS: Teachers from different schools, colleges and professional institutes situated in Dehradun and nearby towns in the state of Uttarakhand, India were evaluated by internationally valid tools for the three parameters. RESULTS: Emotional Intelligence of teachers has no relation with age, gender, educational qualification, level of teaching or type of institute. It has a negative correlation with stress and a positive correlation with health behaviour. Further, health behaviour is inversely related to stress. CONCLUSIONS: Assessment of emotional intelligence and health behaviour of teachers should be a part of their routine evaluation and training so that specific interventions to reduce stress and to improve their overall health and performance can be appropriately planned.

The Role of Monocyte to High-density Lipoprotein Cholesterol Ratio in Predicting the Severity of Acute Ischemic Stroke and its Association with the NIHSS.

BACKGROUND: Atherosclerosis, an underlying abnormality, plays a significant role in the progression of ischemic stroke. Inflammation, oxidative stress, platelet activation, endothelial dysfunction, and lipid abnormalities are the primary factors involved in the development of atherosclerosis. Monocytes, key contributors to chronic inflammation, actively participate in the development, progression, and rupture of atherosclerotic plaques within blood vessels. Therefore, the objective of this study is to investigate the monocyte to high-density lipoprotein cholesterol (HDL-C) ratio (MHR) in acute ischemic stroke (AIS) and its correlation with the National Institute of Health Stroke Scale (NIHSS) to predict the severity of the condition. MATERIALS AND METHODS: A prospective observational study was conducted on 100 AIS patients and age/gender-matched controls at a hospital in Kota. Diagnostic methods included clinical examination, imaging, and laboratory tests. MHR was measured using a hematology analyzer and correlated with reference values and stroke severity. RESULTS: The mean MHR of AIS patients were higher (14.12 ± 2.95) than controls (7.09 ± 1.48) (p = 0.0001). Besides, a statistically significant positive correlation was obtained between his MHR and NIHSS scores at admission and discharge. MHR values were significantly greater from a reference point in patients who deteriorated (18.48 ± 4.02) compared to significantly lower values in patients who improved (13.66 ± 2.44). CONCLUSION: In our study, the MHR shows an increased value in patients with AIS, and a linear correlation is found with the NIHSS score. Thus, the method is a pocket-friendly, easily available, and simple-to-use novel inflammatory marker that may predict the severity of a disease.

Prospective randomised phase II trial evaluating adjuvant pelvic radiotherapy using either IMRT or 3-Dimensional planning for endometrial cancer.

OBJECTIVE: To compare the incidence of grade ≥2 gastrointestinal (GI) or genitourinary (GU) toxicity for patients undergoing 3DRT versus IMRT in the postoperative setting for endometrial cancer. METHODS: Eligible patients were post-operatively randomly assigned to one of two parallel groups in a 1:1 ratio, to have their RT delivered using either a 3DRT technique or using IMRT. The prescription dose was 45 Gy in 25 fractions over 5 weeks followed by vaginal vault brachytherapy. Toxicity was graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version (v) 3.0. Fisher's exact tests were used to test for associations between toxicity and arm. Differences in dosimetric parameters for patients with or without toxicity were tested using Mann-Whitney U-tests. RESULTS: 84 patients with a median age of 62 were evaluable for primary outcome. The median follow-up was 52 months. 14 (35%) participants from the 3DRT arm and 15 (34%) from the IMRT arm experienced acute grade ≥2 GI toxicity with older patients having a statistically higher risk of grade ≥2 acute GI toxicity. 20 (50%) participants from the 3DRT arm and 25 (57%) from the IMRT arm experienced acute grade ≥2 GI or GU toxicity (p = .662). 12 (30%) patients from the 3DRT arm and 17 (39%) from the IMRT arm experienced acute grade ≥2 GU toxicity (p = .493). CONCLUSION: Although IMRT can reduce dose to normal tissue, in this study no benefit in acute GI or GU toxicity outcome was seen.

Low-loss MIMO antenna wireless communication system for 5G cardiac pacemakers.

Cardiovascular diseases (CVDs) are one of the leading causes of death globally. The Internet of things (IoT) enabled with industrial, scientific, and medical (ISM) bands (2.45 and 5.8 GHz) facilitates pacemakers to remotely share heart health data to medical professionals. For the first time, communication between a compact dual-band two-port multiple-input-multiple-output (MIMO) antenna (integrated inside the leadless pacemaker) and an outside-body dual-band two-port MIMO antenna in the ISM 2.45 and 5.8 GHz frequency bands is demonstrated in this work. The proposed communication system offers an attractive solution for cardiac pacemakers as it can operate on a 5G IoT platform while also being compatible with existing 4G standards. The experimental verification of the proposed MIMO antenna low-loss communication capability is also presented by comparing it to the existing single-input-single-output communication between the leadless pacemaker and outside body monitoring device.

Unravelling the role of immunohistochemistry in giant cell lesions of jaws: A systematic review.

Controversies exist in literature regarding nature, pathogenesis, and behaviour of giant cell lesions (GCLs) of jaws. Studies were attempted to solve these mysteries with immunohistochemical analysis, using various biological markers. Thus, the aim of this review is to appraise the role of immunohistochemistry (IHC) in evaluating the pathogenesis, cellular phenotype, nature, and behaviour of GCLs of jaws. PubMed, PubMed Central, and Clinical Key (Medline) databases were searched electronically irrespective of date of publication with assortment of several independent terms. Fifty-five articles that fulfilled the eligibility criteria were included in the review. Out of 55 included articles, 49 were associated with nature, pathogenesis, and behaviour and six articles were associated with treatment and outcome prediction. Although IHC solved some of the controversies associated with GCLs of jaws such as the osteoclastic phenotype of multinucleated giant cells, immunoexpression of proliferative markers does not distinct non-aggressive from aggressive central GCL but the nature, histogenesis, pathogenesis, and exact behaviour still remain debatable. With regard to formulation of treatment plan, immunohistochemical analysis revealed that expression of glucocorticoid and calcitonin receptors could act as a tool to decide the therapeutic strategy and aid in therapeutic adjustments according to evolution of the lesion.

Targeting hypoxia-inducible factors with 32-134D safely and effectively treats diabetic eye disease in mice.

Many patients with diabetic eye disease respond inadequately to anti-VEGF therapies, implicating additional vasoactive mediators in its pathogenesis. We demonstrate that levels of angiogenic proteins regulated by HIF-1 and -2 remain elevated in the eyes of people with diabetes despite treatment with anti-VEGF therapy. Conversely, by inhibiting HIFs, we normalized the expression of multiple vasoactive mediators in mouse models of diabetic eye disease. Accumulation of HIFs and HIF-regulated vasoactive mediators in hyperglycemic animals was observed in the absence of tissue hypoxia, suggesting that targeting HIFs may be an effective early treatment for diabetic retinopathy. However, while the HIF inhibitor acriflavine prevented retinal vascular hyperpermeability in diabetic mice for several months following a single intraocular injection, accumulation of acriflavine in the retina resulted in retinal toxicity over time, raising concerns for its use in patients. Conversely, 32-134D, a recently developed HIF inhibitor structurally unrelated to acriflavine, was not toxic to the retina, yet effectively inhibited HIF accumulation and normalized HIF-regulated gene expression in mice and in human retinal organoids. Intraocular administration of 32-134D prevented retinal neovascularization and vascular hyperpermeability in mice. These results provide the foundation for clinical studies assessing 32-134D for the treatment of patients with diabetic eye disease.

Vascular cell-adhesion molecule 1 (VCAM-1) regulates JunB-mediated IL-8/CXCL1 expression and pathological neovascularization.

Vascular adhesion molecules play an important role in various immunological disorders, particularly in cancers. However, little is known regarding the role of these adhesion molecules in proliferative retinopathies. We observed that IL-33 regulates VCAM-1 expression in human retinal endothelial cells and that genetic deletion of IL-33 reduces hypoxia-induced VCAM-1 expression and retinal neovascularization in C57BL/6 mice. We found that VCAM-1 via JunB regulates IL-8 promoter activity and expression in human retinal endothelial cells. In addition, our study outlines the regulatory role of VCAM-1-JunB-IL-8 signaling on retinal endothelial cell sprouting and angiogenesis. Our RNA sequencing results show an induced expression of CXCL1 (a murine functional homolog of IL-8) in the hypoxic retina, and intravitreal injection of VCAM-1 siRNA not only decreases hypoxia-induced VCAM-1-JunB-CXCL1 signaling but also reduces OIR-induced sprouting and retinal neovascularization. These findings suggest that VCAM-1-JunB-IL-8 signaling plays a crucial role in retinal neovascularization, and its antagonism might provide an advanced treatment option for proliferative retinopathies.

Structural Understanding of Fungal Terpene Synthases for the Formation of Linear or Cyclic Terpene Products.

Terpene synthases (TPSs), known gatekeepers of terpenoid diversity, are the main targets for enzyme engineering attempts. To this end, we have determined the crystal structure of Agrocybe pediades linalool synthase (Ap.LS), which has been recently reported to be 44-fold and 287-fold more efficient than bacterial and plant counterparts, respectively. Structure-based molecular modeling followed by in vivo as well as in vitro tests confirmed that the region of 60-69aa and Tyr299 (adjacent to the motif "WxxxxxRY") are essential for maintaining Ap.LS specificity toward a short-chain (C10) acyclic product. Ap.LS Y299 mutants (Y299A, Y299C, Y299G, Y299Q, and Y299S) yielded long-chain (C15) linear or cyclic products. Molecular modeling based on the Ap.LS crystal structure indicated that farnesyl pyrophosphate in the binding pocket of Ap.LS Y299A has less torsion strain energy compared to the wild-type Ap.LS, which can be partially attributed to the larger space in Ap.LS Y299A for better accommodation of the longer chain (C15). Linalool/nerolidol synthase Y298 and humulene synthase Y302 mutations also produced C15 cyclic products similar to Ap.LS Y299 mutants. Beyond the three enzymes, our analysis confirmed that most microbial TPSs have asparagine at the position and produce mainly cyclized products (δ-cadinene, 1,8-cineole, epi-cubebol, germacrene D, ß-barbatene, etc.). In contrast, those producing linear products (linalool and nerolidol) typically have a bulky tyrosine. The structural and functional analysis of an exceptionally selective linalool synthase, Ap.LS, presented in this work provides insights into factors that govern chain length (C10 or C15), water incorporation, and cyclization (cyclic vs acyclic) of terpenoid biosynthesis.

Role of stereotactic body radiotherapy for inferior vena cava tumour thrombus in hepatocellular carcinoma.

INTRODUCTION: To evaluate the role of stereotactic body radiotherapy (SBRT) in hepatocellular carcinoma (HCC) patients with inferior vena cava tumour thrombus (IVCTT) who are not suitable for other loco-regional therapies. METHODS: This is an observational retrospective study done between May 2020 and April 2022. The data of 17 patients who underwent SBRT were collected. Patients of Child-Pugh score (CPS) A5-B7 and along with a liver reserve of ≥700 cc were included. Local control (LC), overall survival (OS) and adverse events including hepatic decompensation were carefully recorded. RESULTS: In the cohort, the tumour thrombus was extended to the right atrium in nine (52.9%) patients, and regional nodal and lung were found in 60% and 31.4% of patients respectively. The median gross tumour volume (GTV) was 745 cc (107-1,650 cc). The median SBRT dose prescription was 35 Gy (25-45 Gy) in 5-10 fractions. At 6 months, LC and OS were 80% and 75% respectively. On multivariate analysis, an ALBI score >-2.36 was found to be the predictor for the poor OS. Post-SBRT, a change in CPs by 2 points was observed in one patient (5.9%) which was managed conservatively. Post-radiation, improvement in pain and discomfort was observed in 92.3% and 87% of patients, respectively and bone metastasis related pain was also resolved. CONCLUSION: Stereotactic body radiotherapy is a safe and feasible option for HCC patients with IVC and right atrium tumour thrombosis. It not only improves the quality of life but also results in good LC and OS with acceptable toxicity. SBRT should be considered in a multidisciplinary fashion for patients presenting with tumour thrombosis extending to IVC and the right atrium.

To Study Mean Corpuscular Volume in Alcoholic Liver Disease Patients and to Compare with Child-Pugh Score to Predict the Severity.

INTRODUCTION: Liver injury caused by the alcohol abuse is called alcoholic liver disease (ALD). In particular, ethanol exposure induces cell membrane remodeling in different cells and lipid vesicles including membrane fluidization. These phenomena may be related to the effects of alcohol on the red blood cells (RBCs) membrane because unmetabolized ethanol can have a direct effect on membrane properties. MATERIALS: It was a cross sectional study conducted in 50 adult patients of both sex with a diagnosis of alcoholic liver disease and equal number of controls matched in age and sex. Blood sample collected at the time of admission and sent for investigations and child-pugh score calculated. RESULT: Maximum number of subjects were in 30 to 50 years of age group. Mean value of MCV in patients with alcoholic liver disease was 99.7fl (±8.176) and in control group was 84.2fl (±10.58) (P = 0.0001). Patients in child-pugh class A, B and C were 14%, 62% and 24% respectively. Moreover, there was statistically significant, positive correlation between MCV and child-pugh score. The raised MCV in alcoholic liver disease patients was associated with severity of ALD as mean MCV was 92.28 fl (±2.81) (P = 0.001) in child-pugh class A, 96.22fl (±8.20) (P = 0.001) in child-pugh class B and 113 fl (±11.25) (P = 0.005) in child-pugh class C. CONCLUSION: Mean corpuscular volume is a simple, cost effective and easily obtainable test that may help in predicting the severity of disease and prognosis in terms of life expectancy as evidenced by its increased value in patients of chronic liver disease as well as its linear positive correlation with child-pugh score.