Naltrexone’s Impact on Cancer Progression and Mortality: A Systematic Review of Studies in Humans, Animal Models, and Cell Cultures

xlomafota.13 shared this article with you from Inoreader Naltrexone's Impact on Cancer Progression and Mortality: A Systematic Review of Studies in Humans, Animal Models, and Cell Cultures Via Latest Results for Advances in T... Abstract Background Naltrexone (NTX) is an opioid antagonist traditionally used as a treatment for alcohol and opioid use disorders, but various studies have documented its involvement in cancer progression, exploring possible anticancer potential, when administered at high doses or as low dose naltrexone (LDN). Herein we present a systematic review of cancer-related outcomes from case reports, clinical trials, and retrospective and prospective studies conducted using cell cultures, animal models, and human subjects receiving NTX/LDN. Methods A systematic search of NTX in cancer therapy was conducted. Outcomes including tumor size and number, latency to tumor development, survival duration, progression of disease, and scan results were assessed in clinical and animal studies, and cell number was used as the outcome measure of culture studies. Results Several case reports demonstrate notable survival durations and metastatic resolutions in patients with late stage cancer when administered an average LDN dose of 3–5 mg/day. Animal and cell culture studies suggest an overarching principle of NTX involvement in cancer pharmacophysiology, suggesting that high doses and continuous administration can foster cancer progression, whereas low doses and intermittent treatment may hinder cell proliferation, impede tumorigenesis, and have potential anticancer efficacy. Conclusion This review emphasizes the value of potential future research on NTX in cancer therapy, and warrants need for a better understanding of underlying mechanisms. Future controlled studies with more robust sample sizes, particularly in humans, are needed to fully elucidate its potential in cancer therapy. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Pharmacokinetics and Bioequivalence of Cefprozil for Suspension and Granule Formulation in Healthy Chinese Volunteers: Two Single-Dose Crossover Studies

xlomafota.13 shared this article with you from Inoreader Pharmacokinetics and Bioequivalence of Cefprozil for Suspension and Granule Formulation in Healthy Chinese Volunteers: Two Single-Dose Crossover Studies Via Latest Results for Advances in T... Abstract Introduction Cefprozil, an oral second-generation semi-synthetic cephalosporin, possesses a broad spectrum of antimicrobial activity. A granule formulation has been developed to improve medication adherence of the patients. This study was conducted to assess the bioequivalence of the granule formulation to a dry suspension in healthy Chinese volunteers and estimate the pharmacokinetic (PK) profiles of cefprozil. Methods An open-label, randomized, single-dose, two-period, two-group, crossover study was conducted in 60 healthy Chinese volunteers under fasted or fed conditions (30 volunteers for each condition) to assess the bioequivalence between two formulations of cefprozil. Blood samples were collected at specified time intervals, and the plasma concentrations of cis- and trans-cefprozil were determined by a validated liquid chromatography-tandem mass spectrometry (LC–MS/MS) method. PK and bioavailability parameters were estimated via non-compartmental methods. Adverse events (AEs) were also recorded. Results Under fasted conditions, the mean Cmax was (3534.70 ± 634.67) ng/ml, Tmax was (0.98 ± 0.25) h, t1/2 was (1.37 ± 0.13) h and AUC0-t was (9302.86 ± 1618.39) ng·h/ml, respectively, after a single dose of 125 mg cefprozil for suspension. Under fed conditions, the mean Cmax was (2438.80 ± 493.78) ng/ml, Tmax was (1.66 ± 0.76) h, t1/2 was (1.36 ± 0.24) h and AUC0-t was (9332.36 ± 1373.61) ng·h/ml, respectively. The PK parameters of the granule formulation of cefprozil were similar to those of the suspension. The 90% CI values of the GMRs of Cmax, AUC0-t and AUC0-∞ under both fasted and fed conditions were within the prespecified bioequivalence range (80.00–125.00%). Conclusions According to the criteria for bioequivalence, the test granule formulations of cefprozil and "Cefprozil for Suspension®" were determined to be bioequivalent whether under fasted or fed conditions by measurement of cis-, trans- and total cefprozil. Trial registration ClinicalTrials.gov identifier, NCT04414254. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Targeted Use of Prednisolone with Intravenous Immunoglobulin for Kawasaki Disease

xlomafota.13 shared this article with you from Inoreader Targeted Use of Prednisolone with Intravenous Immunoglobulin for Kawasaki Disease Via Latest Results for Clinical Drug Investigation Abstract Background and Objectives Intravenous immunoglobulin (IVIG) therapy for acute-stage Kawasaki disease (KD) is the first-line treatment for preventing the development of coronary artery aneurysms (CAA). Corticosteroids (prednisolone) and infliximab are often used in patients at a high risk of CAA or those with CAA at diagnosis; however, there are only a few reports of non-responders to corticosteroids as an adjuvant therapy or rescue alternative to IVIG. In this study, we compared the therapeutic effects of primary and secondary prednisolone with IVIG for KD. Methods We established the following three protocols: A was a secondary rescue prednisolone protocol; B was no prednisolone and second-line infliximab protocol, and C was the primary prednisolone protocol. The indication for prednisolone administration was based on the following: primary prednisolone administration, Kobayashi score; and secondary administration, Shizuoka score. Results Four hundred and sixty-nine patients were enrolled in the three protocols. A comparison between primary and secondary prednisolone and IVIG, as the first-line therapy revealed that the number of first non-responders in C group was 7 (8.3%), which was significantly lower than the 50 (20.9%) in A group. There was a significant difference in the first and second non-responders among the three groups, and the number of non-responders in A group was 6 (2.5%), which was significantly lower than the 13 (9.9%) in B group (p < 0.001, by Bonferroni test). The multivariate logistic regression analysis showed that IVIG non-responders among the protocol groups had an adjusted odds ratio of 6.47. Fifteen IVIG non-responders were administered infliximab as a second-line therapy, and of them, 9 (60%) showed therapy resistance. CAA occurred in 21 patients (4.6%). There was no significant difference among each protocol group. Conclusions The number of IVIG non-responders in the group with prednisolone administration was lower than that in the group without prednisolone administration. Secondary rescue infliximab therapy for IVIG non-responders resulted in a lower defervescence effect than the secondary rescue IVIG with prednisolone administration. Further prospective randomized studies are needed to identify factors useful for preventing IVIG non-responders and determine the optimal rescue therapy for preventing CAA. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Walking the line: mechanisms underlying directional mRNA transport and localisation in neurons and beyond

xlomafota.13 shared this article with you from Inoreader Walking the line: mechanisms underlying directional mRNA transport and localisation in neurons and beyond Via Latest Results for Cellular and Molecular Life Sciences Abstract Messenger RNA (mRNA) localisation enables a high degree of spatiotemporal control on protein synthesis, which contributes to establishing the asymmetric protein distribution required to set up and maintain cellular polarity. As such, a tight control of mRNA localisation is essential for many biological processes during development and in adulthood, such as body axes determination in Drosophila melanogaster and synaptic plasticity in neurons. The mechanisms controlling how mRNAs are localised, including diffusion and entrapment, local degradation and directed active transport, are largely conserved across evolution and have been under investigation for decades in different biological models. In this review, we will discuss the standing of the field regarding directional mRNA transport in light of the recent discovery that RNA can hitchhike on cytoplasmic organelles, such as endolysosomes, and the impact of these transport modalities on our understanding o f neuronal function during development, adulthood and in neurodegeneration. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Obstetrics & Gynecology

Postscript No abstract available

Stand up for Equity No abstract available

Incorporating Preexposure Prophylaxis Into Routine Reproductive Health Care No abstract available

Low Human Immunodeficiency Virus (HIV) Testing Rates and No HIV Preexposure Prophylaxis Prescribed Among Female Patients Diagnosed With a Sexually Transmitted Infection, 2017–2018 No abstract available

Evaluating the Association of Stillbirths After Maternal Vaccination in the Vaccine Safety Datalink OBJECTIVE: To evaluate whether the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices recommended influenza and tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccinations in pregnancy are associated with increased risk of stillbirth. METHODS: We performed a case–control study in the Vaccine Safety Datalink that was matched 1:4 on site, month, and year of last menstrual period, comparing the odds of vaccination in pregnancies that ended in stillbirth (defined as fetal loss at or after 20 weeks of gestation) compared with those that ended in live birth from January 1, 2012, to September 30, 2015. We included patients with singleton pregnancies that ended in stillbirth or live birth who had at least one prenatal care visit, pregnancy dating information, and continuous health plan enrollment for the duration of pregnancy. Medical records for all stillbirths were reviewed. We were statistically powered to detect an odds ratio (OR) of 1.37 when evaluating the association between influenza or Tdap vaccination and stillbirth. We also examined stillbirth rates in pregnant patients aged 14–49 years in the Vaccine Safety Datalink between 2007 and 2015. RESULTS: In our matched analysis of 795 confirmed stillbirths in the case group and 3,180 live births in the control group, there was no significant association between influenza vaccination during pregnancy and stillbirth (343/795 [43.1%] stillbirths in the case group vs 1,407/3,180 [44.3%] live births in the control group, OR 0.94, adjusted OR 0.95, 95% CI 0.79–1.14, P=.54) and no significant association between Tdap vaccination during pregnancy and stillbirth (184/795 [23.1%] stillbirths in the case group vs 746/3,180 [23.5%] live births in the control group, OR 0.97, aOR 0.96, 95% CI 0.76–1.28, P=.91). From 2007 to 2015, the stillbirth rate in the Vaccine Safety Datalink was 5.2 per 1,000 live births and stillbirths. CONCLUSION: No association was found between vaccination during pregnancy and the odds of stillbirth. These findings support the safety of ACIP recommendations for vaccination during pregnancy.

Characteristics of Stillbirths Associated With Diabetes in a Diverse U.S. Cohort OBJECTIVE: To characterize stillbirths associated with pregestational diabetes and gestational diabetes mellitus (GDM) in a large, prospective, U.S. case–control study. METHODS: A secondary analysis of stillbirths among patients enrolled in a prospective; multisite; geographically, racially, and ethnically diverse case–control study in the United States was performed. Singleton gestations with complete information regarding diabetes status and with a complete postmortem evaluation were included. A standard evaluation protocol for stillbirth cases included postmortem evaluation, placental pathology, clinical testing as performed at the discretion of the health care professional, and a recommended panel of tests. A potential cause of death was assigned to stillbirth cases using a standardized classification tool. Demographic and delivery characteristics among women with pregestational diabetes and GDM were compared with characteristics of women with no diabetes in pairwise comparisons using χ2 or two-sample t tests as appropriate. Sensitivity analysis was performed excluding pregnancies with genetic conditions or major fetal malformations. RESULTS: Of 455 stillbirth cases included in the primary analysis, women with stillbirth and diabetes were more likely to be older than 35 years and have a higher body mass index. They were also more likely to have a gestational hypertensive disorder than women without diabetes (28% vs 9.1%; P<.001). Women with pregestational diabetes had more large-for-gestational-age (LGA) neonates (26% vs 3.4%; P<.001). Stillbirths occurred more often at term in women with pregestational diabetes (36%) and those with GDM (52%). Maternal medical complications, including pregestational diabetes and others, were more often identified as a probable or possible cause of death among stillbirths with maternal diabetes (43% vs 4%, P<.001) as compared with stillbirths without diabetes. CONCLUSION: Compared with stillbirths in women with no diabetes, stillbirths among women with pregestational diabetes and GDM occur later in pregnancy and are associated with hypertensive disorders of pregnancy, maternal medical complications, and LGA.

Universal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) Testing Uptake in the Labor and Delivery Unit: Implications for Health Equity OBJECTIVE: To understand severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing uptake in the labor and delivery unit and rationales for declining testing, and to institute a process to increase equitable testing uptake. METHODS: We conducted a quality-improvement initiative from May 28–June 25, 2020, during the first 4 weeks of universal SARS-CoV-2 testing in the Barnes-Jewish Hospital labor and delivery unit. All consecutive patients presenting for delivery without coronavirus disease 2019 (COVID-19) symptoms were offered testing over four 1-week phases. Phase I documented the rate of testing uptake. Phase II recorded patients' reasons for declining testing. Phase III used phase II findings to create and implement shared decision-making tools. Phase IV offered each patient who declined nasopharyngeal testing an oropharyngeal alternative. The primary outcome was rate of SARS-CoV-2 testing uptake by phase. RESULTS: Of 270 patients, 223 (83%) accepted testing and 47 (17%) declined. Maternal age and mode of delivery were similar between groups, whereas testing uptake was higher among nulliparous, White, Hispanic, or privately insured patients. There was a significant increase in the primary outcome of SARS-CoV-2 testing across phases I–IV, from 68% to 76% to 94% to 95%, respectively (Somers' D 0.45; 95% CI of association 0.30–0.59). The most commonly cited reason for declining testing was concern regarding testing discomfort. In subgroup analyses by race and insurance type, there was a significant increase in testing uptake across phases I–IV for Black patients (56%, 54%, 91%, 92%; Somers' D 0.36; 95% CI of association 0.28–0.64), White patients (76%, 93%, 96%, 100%; Somers' D 0.59; 95% CI of association 0.38–0.8), those with Medicaid insurance (60%, 64%, 88%, 92%; 95%; Somers' D 0.39; CI of association 0.22 to 0.56), and those with private insurance (77%, 96%, 97%, 100%; Somers' D 0.63; 95% CI of association 0.40–0.86). CONCLUSION: Universal SARS-CoV-2 testing uptake significantly increased through a rapid-cycle improvement initiative. Aligning hospital policy with patient-centered approaches led to nearly universally acceptable testing.

High Concentrations of Nitric Oxide Inhalation Therapy in Pregnant Patients With Severe Coronavirus Disease 2019 (COVID-19) BACKGROUND: Rescue therapies to treat or prevent progression of coronavirus disease 2019 (COVID-19) hypoxic respiratory failure in pregnant patients are lacking. METHOD: To treat pregnant patients meeting criteria for severe or critical COVID-19 with high-dose (160–200 ppm) nitric oxide by mask twice daily and report on their clinical response. EXPERIENCE: Six pregnant patients were admitted with severe or critical COVID-19 at Massachusetts General Hospital from April to June 2020 and received inhalational nitric oxide therapy. All patients tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A total of 39 treatments was administered. An improvement in cardiopulmonary function was observed after commencing nitric oxide gas, as evidenced by an increase in systemic oxygenation in each administration session among those with evidence of baseline hypoxemia and reduction of tachypnea in all patients in each session. Three patients delivered a total of four neonates during hospitalization. At 28-day follow-up, all three patients were home and their newborns were in good condition. Three of the six patients remain pregnant after hospital discharge. Five patients had two negative test results on nasopharyngeal swab for SARS-CoV-2 within 28 days from admission. CONCLUSION: Nitric oxide at 160–200 ppm is easy to use, appears to be well tolerated, and might be of benefit in pregnant patients with COVID-19 with hypoxic respiratory failure.

Excess Maternal Deaths Associated With Coronavirus Disease 2019 (COVID-19) in Mexico No abstract available

Clinical Presentation of Coronavirus Disease 2019 (COVID-19) in Pregnant and Recently Pregnant People OBJECTIVE: To describe the clinical presentation, symptomology, and disease course of coronavirus disease 2019 (COVID-19) in pregnancy. METHODS: The PRIORITY (Pregnancy CoRonavIrus Outcomes RegIsTrY) study is an ongoing nationwide prospective cohort study of people in the United States who are pregnant or up to 6 weeks postpregnancy with known or suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed the clinical presentation and disease course of COVID-19 in participants who tested positive for SARS-CoV-2 infection and reported symptoms at the time of testing. RESULTS: Of 991 participants enrolled from March 22, 2020, until July 10, 2020, 736 had symptoms of COVID-19 at the time of testing; 594 tested positive for SARS-CoV-2 infection and 142 tested negative in this symptomatic group. Mean age was 31.3 years (SD 5.1), and 37% will nulliparous. Ninety-five percent were outpatients. Participants who tested positive for SARS-CoV-2-infection were a geographically diverse cohort: 34% from the Northeast, 25% from the West, 21% from the South, and 18% from the Midwest. Thirty-one percent of study participants were Latina, and 9% were Black. The average gestational age at enrollment was 24.1 weeks, and 13% of participants were enrolled after pregnancy. The most prevalent first symptoms in the cohort of patients who tested positive for SARS-CoV-2 infection were cough (20%), sore throat (16%), body aches (12%), and fever (12%). Median time to symptom resolution was 37 days (95% CI 35–39). One quarter (25%) of participants who tested positive for SARS-CoV-2 infection had persistent symptoms 8 or more weeks after symptom onset. CONCLUSION: COVID-19 has a prolonged and nonspecific disease course during pregnancy and in the 6 weeks after pregnancy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04323839.

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

Telephone consultation 11855 int 1193,

Ophthalmology Clinics

COVID-19 and the Eye: A Comprehensive Review of the Literature No abstract available

A Review and Update on Surgical Management of Intraocular Lens Dislocation No abstract available

Updates in the Management of Corneal Ectasia No abstract available

Review: Optimizing DMEK Technique, 2018-2020 No abstract available

Recent Advances in Pediatric Endothelial Keratoplasty No abstract available

Recent Updates in Femtosecond Laser-assisted Cataract Surgery No abstract available

Alpha-Gal Syndrome in Ophthalmology and Medicine: Erratum No abstract available

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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,alsfakia@gmail.com,

Telephone consultation 11855 int 1193,

Cancers, Vol. 12, Pages 3821: Interaction between GRP78 and IGFBP-3 Affects Tumourigenesis and Prognosis in Breast Cancer Patients

Alexandros G.Sfakianakis shared this article with you from Inoreader Cancers, Vol. 12, Pages 3821: Interaction between GRP78 and IGFBP-3 Affects Tumourigenesis and Prognosis in Breast Cancer Patients Μέσω Cancers Cancers, Vol. 12, Pages 3821: Interaction between GRP78 and IGFBP-3 Affects Tumourigenesis and Prognosis in Breast Cancer Patients Cancers doi: 10.3390/cancers12123821 Authors: Hanna A. Zielinska Carl S. Daly Ahmad Alghamdi Amit Bahl Muhammed Sohail Paul White Sarah R. Dean Jeff M. P. Holly Claire M. Perks Insulin-like growth factor binding protein 3 (IGFBP-3) plays a key role in breast cancer progression and was recently shown to bind to the chaperone protein glucose-regulated protein 78 (GRP78); however, the clinical significance of this association remains poorly investigated. Here we report a direct correlation between the expression of GRP78 and IGFBP-3 in breast cancer cell lines and tumour sections. Kaplan–Meier survival plots revealed that patients with low GRP78 expression that are positive for IGFBP-3 had poorer survival rates than those with low IGFBP-3 levels, and we observed a similar trend in the publicly available METABRIC gene expression database. With breast cancer cells, in vitro IGFBP-3 enhanced induced apoptosis, however when GRP78 expression was silenced the actions of IGFBP-3 were switched from increasing to inhibiting ceramide (C2)-induced cell death and promoted cell invasion. Using immunofluorescence and cell surface biotinylation, we showed that knock-down of GRP78 negated the entry of IGFBP-3 into the cells. Together, our clinical and experimental results suggest that loss of GRP78 reduces IGFBP-3 entry into cells switching its actions to promote tumorigenesis and predicts a poor prognosis in breast cancer patients. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.