Shatavarin-IV, a steroidal saponin from Asparagus racemosus, inhibits cell cycle progression and epithelial-to-mesenchymal transition in AGS cells under hyperglycemic conditions.

Gastric cancer (GC)-diabetes co-morbidity is nowadays growing into a rising concern. However, no separate treatment procedures have been outlined for such patients. Phytochemicals and their derivatives can therefore be used as therapeutics as they have greater effectiveness, reduced toxicity, and a reduced likelihood of developing multi-drug resistance in cancer treatments. The present study intended to assess the therapeutic efficacy of Shatavarin-IV - a major steroidal saponin from the roots of Asparagus racemosus, in human gastric adenocarcinoma cell line under hyperglycemic conditions and explore its mechanism of action in controlling GC progression. For the present study, AGS cells were incubated in high glucose-containing media and the effects of Shatavarin-IV therein have been evaluated. Cell proliferation, confocal microscopic imaging, flow-cytometric analysis for cell cycle and apoptosis, immunoblotting, zymography, reverse zymography, wound-healing, colony formation, and invasion assays were performed. Shatavarin-IV has a prominent effect on AGS cell proliferation; with IC50 of 2.463 µ M under hyperglycemic conditions. Shatavarin-IV induces cell cycle arrest at the G0/G1 phase, thereby preventing hyperglycemia-induced excessive cell proliferation that later on leads to apoptotic cell death at 36 h of incubation. Shatavarin-IV further inhibits the migratory and invasive potential of AGS cells by altering the expression patterns of different EMT markers. It also inhibits MMP-9 while promoting TIMP-1 activity and expression; thereby regulating ECM turnover. This is the first report demonstrating the therapeutic efficacy of Shatavarin-IV against AGS cells grown in hyperglycemic conditions, implicating new insights into the treatment paradigm of patients with GC-diabetes co-morbidity.

Supervision Unveiled: Navigating the Supervision Landscape in Medical Spas.

BACKGROUND: There is an ongoing increase in the demand for injectable procedures and an increase in the number of medical spas across the United States State regulations significantly vary regarding level of supervision at these medical spas. OBJECTIVE: The aim of this study was to determine who performs cosmetic procedures, provides medical supervision, and who is being informed of complications. METHODS: Descriptive study based on a standardized telephone interview performed by a prospective patient for injectable treatments performed at medical Spas in Las Vegas. Data were then extracted and analyzed. RESULTS: Of 63 medical spas reviewed, most of the injectable treatments (73%) were performed by nonphysicians. An onsite physician who supervised or personally performed the cosmetic procedures was present in only 38.1% of the spas surveyed. Only 46% of surveyed medical spas notify a medical director/supervising physician in the event of a complication and only 39.7% of surveyed spas had a number to call after regular business hours. CONCLUSION: The majority of treatments are performed by nonphysicians in the spas surveyed. Physician supervisors are not on site in most of the spas and about half of spas do not inform the medical director in the event of a complication.

Melatonin Inhibits AGS Cell Proliferation by Binding to the ATP Binding Site of CDK2 Under Hyperglycemic Conditions.

Cancer cells utilize glucose as their primary energy source. The aggressive nature of cancer cells is therefore enhanced in hyperglycemic conditions. This study has been adopted to investigate the therapeutic potential of melatonin against such aggressive proliferation of AGS cells-a human gastric cancer cell line, under hyperglycemic conditions. AGS cells were incubated with high glucose-containing media, and the effects of melatonin have been evaluated, therein. Cell proliferation, ROS generation, flow-cytometric analysis for cell cycle and apoptosis, wound healing, immunoblotting, zymography, reverse zymography assays, in-silico analysis, and kinase activity assays were performed to evaluate the effects of melatonin. We observed that melatonin inhibited the hyperglycemia-induced cell proliferation in a dose-dependent manner. It further altered the expression and activity of MMP-9 and TIMP-1. Moreover, melatonin inhibited AGS cell proliferation by arresting AGS cells in the G0/G1 phase after binding in the ATP binding site of CDK-2, thereby inhibiting its kinase activity. In association, a significant decrease in the expression of cyclin D1, cyclin E, CDK-4, and CDK-2 were observed. In conclusion, these findings suggest that melatonin has anti-gastric cancer potential. Melatonin could therefore be included in future drug designs for gastric cancer-hyperglycemia co-morbidity treatment.

Who Is Holding the Syringe? A Survey of Truth in Advertising Among Medical Spas.

BACKGROUND: The degree of supervision and level of expertise required for performing cosmetic procedures differs significantly from state to state. Medical spas providing cosmetic procedures have seen exponential growth since 2020. OBJECTIVE: To provide a representative sample of the medical spa industry in the Unites States regarding the expertise among providers performing cosmetic procedures and the degree of oversight at medical spas offering these procedures. MATERIALS AND METHOD: Descriptive study based on a standardized telephone interview performed by a secret shopper in Chicago and surrounding suburbs. Data were then extracted and analyzed. RESULTS: Of 127 medical spas reviewed, a supervising physician was not on-site at 81.1% of the facilities. Patients were informed of this at 64.6% of the surveyed medical spas. CONCLUSION: There is considerable variation in the oversight and in the training among those performing cosmetic procedures at surveyed medical spas. As cosmetic procedures become increasingly popular among the public, further regulation of medical spas is warranted to protect patient safety.

Dosimetric Evaluation of the Treatment Plan on Indigenous Heterogeneous Phantoms using Analytical Anisotropic Algorithm and Acuros-XB Algorithm for Different Photon Energies.

Background: Modern radiotherapy techniques are using advanced algorithms; however, phantoms used for quality assurance have homogeneous density; accordingly, the development of heterogeneous phantom mimicking human body sites is imperative to examine variation between planned and delivered doses. Objective: This study aimed to analyze the accuracy of planned dose by different algorithms using indigenously developed heterogeneous thoracic phantom (HT). Material and Methods: In this experimental study, computed tomography (CT) of HT was done, and the density of different parts was measured. The plan was generated on CT images of HCP with 6 and 15 Megavoltage (MV) photon beams using different treatment techniques, including three-dimensional conformal radiotherapy (3D-CRT), intensity-modulated radiation therapy (IMRT), and volumetric modulated arc therapy (VMAT). Plans were delivered by the linear accelerator, and the dose was measured using the ion chamber (IC) placed in HT; planned and measured doses were compared. Results: Density patterns for different parts of the fabricated phantom, including rib, spine, scapula, lung, chest wall, and heart were 1.849, 1.976, 1.983, 0.173, 0.855, and 0.833 g/cc, respectively. Variation between planned and IC estimated doses with the tolerance (±5%) for all photon energies using different techniques. Acuros-XB (AXB) showed a slightly higher variation between computed and IC estimated doses using HCP compared to the analytical anisotropic algorithm (AAA). Conclusion: The indigenous heterogeneous phantom can accurately simulate the dosimetric scenario for different algorithms (AXB or AAA) and be also utilized for routine patient-specific QA.

Management strategies and outcomes in renal transplant recipients recovering from COVID-19: A retrospective, multicentre, cohort study.

Background: There is an enormous knowledge gap on management strategies, clinical outcomes, and follow-up after kidney transplantation (KT) in recipients that have recovered from coronavirus disease (COVID-19). Methods: We conducted a multi-center, retrospective analysis in 23 Indian transplant centres between June 26, 2020 to December 1, 2021 on KT recipients who recovered after COVID-19 infections. We analyzed clinical and biopsy-confirmed acute rejection (AR) incidence and used cox-proportional modeling to estimate multivariate-adjusted hazard ratios (HR) for predictors of AR. We also performed competing risk analysis. Additional outcome measures included graft loss, all-cause mortality, waiting time from a positive real-time polymerase test (RT-PCR) to KT, laboratory parameters, and quality of life in follow-up. Findings: Among 372 KT which included 38(10·21%) ABO-incompatible, 12(3·22%) sensitized, 64(17·20%) coexisting donors with COVID-19 history and 20 (5·37%) recipients with residual radiographic abnormalities, the incidence of AR was 34 (9·1%) with 1(0·26%) death censored graft loss, and 4(1·07%) all-cause mortality over a median (interquartile range) follow-up of 241 (106-350) days. In our cox hazard proportional analysis, absence of oxygen requirement during COVID-19 compared to oxygen need [HR = 0·14(0·03-0·59); p-value = 0·0071], and use of thymoglobulin use compared to other induction strategies [HR = 0·17(0·03-0.95); p-value = 0·044] had a lower risk for AR. Degree of Human leukocyte antigen (HLA) DR mismatch had the highest risk of AR [HR = 10.2(1·74-65·83); p-value = 0·011]. With competing risk analysis, with death as a competing event, HLA DR mismatch, and oxygen requirement continued to be associated with AR. Age, gender, obesity, inflammatory markers, dialysis vintage, steroid use, sensitization and ABO-incompatibility have not been associated with a higher risk of AR. The median duration between COVID-19 real time polymerase test negativity to transplant was 88(40-145) days (overall), and ranged from 88(40-137), 65(42-120), 110(49-190), and 127(64-161) days in World Health Organization ordinal scale ≤ 3, 4, 5, and 6-7, respectively. There was no difference in quality of life, tacrolimus levels, blood counts, and mean serum creatinine assessed in patients with a past COVID-19 infection independent of severity. Interpretation: Our findings support that the outcomes of KT after COVID-19 recovery are excellent with absence of COVID-19 sequelae during follow-up. Additionally, there does not seem to be a need for changes in the induction/immunosuppression regimen based on the severity of COVID-19. Funding: Sanofi.

Zymography and Reverse Zymography for Testing Proteases and Their Inhibitors.

Zymography is a powerful technique for the assay of different hydrolases that act upon any biological macromolecule. In particular, zymography is used to assay the activities of serine proteases, e.g., matrix metalloproteinases (MMPs), and reverse zymography is used for tissue inhibitors of metalloproteinases (TIMPs) in multifarious experimental samples. Zymography is a method of electrophoretic separation of proteases under non-reducing conditions in a polyacrylamide gel containing substrate. The resolved proteins are renatured by exchange of the anionic detergent with a nonionic one, and the gel is incubated in a specific buffer for the specific proteases. After staining the gel by Coomassie blue staining solution, the proteolytic activities are visualized as clear colorless bands against a dark background. In contrast, reverse zymography is a parallel technique to detect protease inhibitors. In addition to substrate gelatin, proteases (i.e., MMPs) are also incorporated in proper ratio into the polyacrylamide gel. After electrophoresis, during the developing step, the MMPs specifically digest the substrate in regions where TIMPs are absent. Thus, inhibitors/TIMP is represented as dark zones of inhibition against a transparent background after staining. In this chapter, common troubleshoots during sample preparation, running zymography, and data interpretation are discussed. Notes are specified to enhance the sensitivity of the methods. In conclusion, zymography could be crucial for enzyme assay at the nanogram level and for the improvement of new investigative techniques for diseases such as endometriosis, rheumatoid arthritis, osteoarthritis, tumor invasion, and inflammation.

Mucormycosis as SARS-CoV2 sequelae in kidney transplant recipients: a single-center experience from India.

PURPOSE: Coronavirus disease (COVID-19) sequelae in the transplant population are scarcely reported. Post-COVID-19 mucormycosis is one of such sequelae, which is a dreadful and rare entity. The purpose of this report was to study the full spectrum of this dual infection in kidney transplant recipients (KTR). METHODS: We did a comprehensive analysis of 11 mucormycosis cases in KTR who recovered from COVID-19 in IKDRC, Ahmedabad, Gujarat, India during the study period from Nov 2020 to May 2021. We also looked for the risk factors for mucormycosis with a historical cohort of 157 KTR who did not develop mucormycosis. RESULTS: The median age (interquartile range, range) of the cohort was 42 (33.5-50, 26-60) years with 54.5% diabetes. COVID-19 severity ranged from mild (n = 10) to severe cases (n = 1). The duration from COVID-19 recovery to presentation was 7 (7-7, 4-14) days. Ten cases were Rhino-orbital-cerebral-mucormycosis (ROCM) and one had pulmonary mucormycosis. Functional endoscopic sinus surgery (FESS) was performed in all cases of ROCM. The duration of antifungal therapy was 28 (24-30, 21-62) days. The mortality rate reported was 27%. The risk factors for post-transplant mucormycosis were diabetes (18% vs 54.5%; p-value = 0.01), lymphopenia [12 (10-18) vs 20 (12-26) %; p-value = 0.15] and a higher neutrophil-lymphocyte ratio [7 (4.6-8.3) vs 3.85 (3.3-5.8); p-value = 0.5]. CONCLUSION: The morbidity and mortality with post-COVID-19 mucormycosis are high. Post-transplant patients with diabetes are more prone to this dual infection. Preparedness and early identification is the key to improve the outcomes.

Ultrasound-guided foam sclerotherapy is safe and effective in the management of superficial venous insufficiency of the lower extremity.

BACKGROUND: Superficial venous disease of the lower extremity has a significant impact on quality of life. Both truncal and tributary vein reflux contribute to this disease process. Endovenous foam sclerotherapy is a widely used technique throughout the world for the management of superficial venous reflux and ultrasound guidance improves its safety and efficacy. METHODS: A PubMed search for ultrasound-guided foam sclerotherapy (UGFS) was conducted and all abstracts were reviewed to identify clinical trials and systematic reviews for a full-text analysis. Additional articles were also identified through searching the references of the selected studies. RESULTS: The production of foam for sclerotherapy in a 1:3 or 1:4 ratio of air to sclerosant is optimal in a low silicone, low-volume syringe system. Physiologic gas may decrease any side effects, with the trade-off of decreased foam stability. Proper technique with appropriate sterility and cleansing protocols are paramount for safe and effective treatment. The technical success of UGFS for great saphenous vein disease is inferior to endothermal and surgical modalities and retreatment is more common. However, the clinical improvement in patient-reported quality of life is similar between these three modalities. When used for tributary veins in combination with endothermal approaches of the truncal veins, UGFS has high rates of success with excellent patient satisfaction. UGFS has demonstrated an excellent safety profile comparable with or superior to other modalities. CONCLUSIONS: With proper technique, UGFS is safe and effective for the management of superficial venous disease.

Cutaneous Manifestation as Initial Presentation of Metastatic Breast Cancer: A Systematic Review.

Metastatic breast cancer initially may present with cutaneous lesions. The goal of this systematic review was to evaluate available reports where the initial discovery of primary breast cancer occurred through the diagnosis of metastatic cutaneous lesions. We aimed to better understand these cases and the role of dermatologists in their diagnosis. A review of the literature for case reports and retrospective studies was conducted using the following databases: MEDLINE/PubMed, EMBASE, Cochrane library, CINAHL, and EBSCO. The PRISMA guidelines were utilized. Studies were included if they reported a cutaneous metastasis of a primary breast cancer in females. Studies were excluded if skin metastasis occurred in a patient with a history of breast cancer. Thirty-six publications were identified. Among these, 27 were case reports, and 9 were retrospective reviews. An enhanced understanding of how these cutaneous metastases present may be of clinical benefit to physicians, particularly dermatologists.

Feasibility and safety of remdesivir in SARS-CoV2 infected renal transplant recipients: A retrospective cohort from a developing nation.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection has drastically impacted the transplant communities. Remdesivir (RDV) has shown some promising results in coronavirus disease (COVID-19) albeit with low certainty. Data in kidney transplant recipients (KTR) are still lacking. METHODS: This was a retrospective cohort of 57 moderate to severe COVID-19 positive KTR in a single center who received RDV as a part of COVID-19 management. No dose adjustments were done. The outcomes were measured as acute kidney injury (AKI) recovery; liver function tests abnormalities; other side effects; graft loss and death. RESULTS: The median (inter-quartile range) age of presentation was 44 (31-51) years. The duration from onset of symptoms to RDV initiation was 6 (5-7) days. Thirty-two (56%) cases received RDV on the day of admission. Forty-six (81%) cases were on oxygen support upon initiation of RDV. Thirty-eight (66.6%) cases had acute kidney injury on admission. The median baseline, admission, and 28-day follow-up serum creatinine of the cohort were 1.59 (1.1-2.1), 2.13 (1.3-3.1), and 1.58 (1.05-2.1) mg/dl, respectively. A total of 8(14%) cases died in the study with 1 (1.7%) graft loss. All those cases that died were on oxygen therapy at the time of initiation of RDV. No liver function derangements or any other major adverse events with the drug were reported. CONCLUSION: RDV therapy is safe and clinically feasible in renal transplant recipients as seen in our cohort. Larger clinical registries and randomized clinical trials should be conducted to further explore the efficacy in transplant recipients.

Extensive Postchemotherapy Calcinosis Cutis in a Non-Hodgkin Lymphoma Patient With Spontaneous Resolution.

We report the case of a 30-year-old woman with stage IV, non-Hodgkin lymphoma. Baseline F-FDG PET/CT scan revealed lymphadenopathy with breasts and skeletal involvement. She received 3 cycles of R-CHOP (rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone) chemotherapy without significant adverse effects. Biochemical examinations before and after chemotherapies were unremarkable. InterimF-FDG PET/CT showed a partial treatment response. However, there was an appearance of FDG-avid coarse calcification in breasts. Cutaneous and subcutaneous regions of elbows, pelvis, and thighs showed similar calcifications. Posttherapy PET/CT showed a significant resolution of calcinosis cutis. This case presents a postchemotherapy idiopathic calcinosis cutis with rapid spontaneous resolution.

Two Decades of Deceased Donor Kidney Transplantation at Ahmedabad, India.

OBJECTIVES: Gujarat, Tamil Nadu, Telangana, Maharashtra, Kerala, Chandigarh, and Karnataka are states in India with active programs for deceased donor kidney transplant. We report our experience of 2 decades of deceased donor kidney transplant at the Institute of Kidney Diseases and Research Center, Dr. H. L. Trivedi Institute of Transplantation Sciences, Ahmedabad, Gujarat, India. MATERIALS AND METHODS: This single-center retrospective study comprised data from 831 deceased donor kidney transplant recipients between January 1, 1997 and December 31, 2018. Mean recipient age was 38 ± 14 years; 564 were male, and 267 were female. Mean donor age was 45.3 ± 17.13 years; 565 were men, and 266 were women. RESULTS: Between January 1, 1997 and March 15, 2020, 5838 kidney transplants were completed, including 4895 living donor kidney transplants, 943 deceased donor kidney transplants, and 440 kidney paired donation transplants. Over the mean follow-up time of 8 ± 5.4 years, patient survival rate was 70% (n = 581) and death-censored graft survival rate was 84% (n = 698). Delayed graft function was shown in 210 patients (25%) and biopsy-proven acute rejection rate in 180 patients (21%). Our experience of favorable outcomes with deceased donor kidney transplants has expanded the donor pool in many ways, including transplant from expanded criteria donors to younger recipients; transplant from older donors to older recipients; donation after cardiac death; successful intercity organ procurement; dual-kidney transplant; en bloc transplant from a pediatric deceased donor; and transplant from brain death deceased donors who died from neurotoxic snakebite, recurrent primary brain tumor, bacterial meningitis, or head injury, or with disseminated intravascular coagulation and deranged renal functions. The pathway to increase organ donation was investigated. CONCLUSIONS: Deceased donor kidney transplant can achieve acceptable graft function with patient/graft survival, which may encourage the use of this approach to increase the number of available organs.

Identifying the Therapeutic Significance of Mesenchymal Stem Cells.

The pleiotropic behavior of mesenchymal stem cells (MSCs) has gained global attention due to their immense potential for immunosuppression and their therapeutic role in immune disorders. MSCs migrate towards inflamed microenvironments, produce anti-inflammatory cytokines and conceal themselves from the innate immune system. These signatures are the reason for the uprising in the sciences of cellular therapy in the last decades. Irrespective of their therapeutic role in immune disorders, some factors limit beneficial effects such as inconsistency of cell characteristics, erratic protocols, deviating dosages, and diverse transfusion patterns. Conclusive protocols for cell culture, differentiation, expansion, and cryopreservation of MSCs are of the utmost importance for a better understanding of MSCs in therapeutic applications. In this review, we address the immunomodulatory properties and immunosuppressive actions of MSCs. Also, we sum up the results of the enhancement, utilization, and therapeutic responses of MSCs in treating inflammatory diseases, metabolic disorders and diabetes.

Rib Plasmacytoma With Unusual Sunburst Periosteal Reaction.

A 39-year-old man presented with progressive painful swelling on the left chest since 6 months. Examination revealed osseous consistency mass. CT of the thorax suggested mass arising from left fourth rib with intrathoracic and extrathoracic soft tissue components. It had extensive sunburst periosteal reaction consistent with primary malignant bone tumor. True cut biopsy revealed plasmacytoma. Routine hematological, biochemical, and bone marrow examinations were normal. Patient referred for whole-body F-FDG PET/CT to look for skeletal and bone marrow lesions. It revealed intensely metabolic left fourth rib lesion with periosteal reaction and no other lesion in the rest of the body.

Role of Ceramidases in Sphingolipid Metabolism and Human Diseases.

Human pathologies such as Alzheimer's disease, type 2 diabetes-induced insulin resistance, cancer, and cardiovascular diseases have altered lipid homeostasis. Among these imbalanced lipids, the bioactive sphingolipids ceramide and sphingosine-1 phosphate (S1P) are pivotal in the pathophysiology of these diseases. Several enzymes within the sphingolipid pathway contribute to the homeostasis of ceramide and S1P. Ceramidase is key in the degradation of ceramide into sphingosine and free fatty acids. In humans, five different ceramidases are known-acid ceramidase, neutral ceramidase, and alkaline ceramidase 1, 2, and 3-which are encoded by five different genes (ASAH1, ASAH2, ACER1, ACER2, and ACER3, respectively). Notably, the neutral ceramidase N-acylsphingosine amidohydrolase 2 (ASAH2) shows considerable differences between humans and animals in terms of tissue expression levels. Besides, the subcellular localization of ASAH2 remains controversial. In this review, we sum up the results obtained for identifying gene divergence, structure, subcellular localization, and manipulating factors and address the role of ASAH2 along with other ceramidases in human diseases.

Polycystic ovarian syndrome: Environmental/occupational, lifestyle factors; an overview

Polycystic ovary syndrome (PCOS) is a multifaceted disease of women with infertility that has diverse etiologic factors. Some women may have only a few PCOS-linked symptoms or mild symptoms, whereas others will have severe or all PCOS-linked symptoms. Therefore, PCOS symptoms can differ among women. PCOS is a state of hormonal imbalance, excess terminal hair (hirsutism), hair loss (alopecia), menstruation impairments, metabolic disorders, and cystic appearance on the ovaries. The cysts hamper ovulation, thus reducing the ability of women to become pregnant and result in infertility. The available data suggest that PCOS might originate in utero and the phenotypic appearance of PCOS symptoms may be developed in later life, which could be linked with host factors (endogenous) and exogenous factors like lifestyle, and dietary, environmental or occupational factors. Based upon the available information, it can be postulated that prenatal exposure to excessive androgens might be responsible for androgenization of the fetus, which in turn may alter the program of differentiating target tissues and the phenotypic characteristics of PCOS can be persuaded by exposure of female offspring to various endogenous and exogenous factors at later life. Genetic/host and environmental/lifestyle factors might be related to the pathophysiology of PCOS after prenatal exposure to androgen. Additional studies are necessary to understand the exact mechanism responsible for the manifestation of PCOS because it is a very important issue in female reproduction.