Augmenting Breast Implant Research: Accessible Methods for Fabricating Miniature Smooth and Textured Breast Implants in a Laboratory Setting.

BACKGROUND: Because of the association of textured breast implants with breast implant-associated anaplastic large cell lymphoma, anatomically shaped breast implants, which rely on a textured surface to maintain rotational stability, have been recalled from the market. The dearth of anatomically shaped implants on the market reflects a need for novel breast implant technology, which has been traditionally developed by commercial breast implant manufacturers due to the complexities of implant manufacturing. To increase the accessibility of preclinical breast implant research, miniature breast implants made from polydimethylsiloxane were designed and fabricated for high throughput and low-cost prototyping and in vivo testing of both smooth and textured implants in a laboratory setting. METHODS: Two-piece negative molds measuring 2 × 1 cm were constructed in Fusion360 and 3D printed in Polysmooth filament. Textured molds were painted with a mixture of an epoxy and fine sugar or granular salt to create textured surfaces, while molds for smooth implants were smoothed using ethanol spray. Molds were injected with polydimethylsiloxane and cured for 12 hours at 37°C. The surface topography of laboratory-made implants and commercial textured and smooth implant shells was analyzed using scanning electron microscopy and implants were evaluated in vivo in an immunocompetent rodent model. RESULTS: Implants retained the original dome shape of the 3D-printed molds. Qualitative assessment of scanning electron microscopy images demonstrated similar surface topography between laboratory-made and commercial smooth and textured implants. There was no statistical difference in the diameter or density of the surface indentations of the Allergan's textured implant compared with laboratory-made textured implants ( P > 0.05). Finally, the surface topography and thickness of laboratory-made implant capsules were similar to previously published data using industry made miniature silicone devices implanted in rats. CONCLUSIONS: This study demonstrates a low-cost, highly customizable approach to fabricate miniature smooth and textured breast implant prototypes for in vivo studies. The accessibility of this implant fabrication strategy allows nonindustry investigators to develop novel implant designs more rapidly for preclinical investigation.

Measurements of the Timescale and Conformational Space of AMPA Receptor Desensitization.

Ionotropic glutamate receptors are ligand-gated ion channels that mediate excitatory synaptic transmission in the central nervous system. Desensitization of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid subtype after glutamate binding appears critical for brain function and involves rearrangement of the ligand binding domains (LBDs). Recently, several full-length structures of ionotropic glutamate receptors in putative desensitized states were published. These structures indicate movements of the LBDs that might be trapped by cysteine cross-links and metal bridges. We found that cysteine mutants at the interface between subunits A and C and lateral zinc bridges (between subunits C and D or A and B) can trap freely desensitizing receptors in a spectrum of states with different stabilities. Consistent with a close approach of subunits during desensitization processes, the introduction of bulky amino acids at the A-C interface produced a receptor with slow recovery from desensitization. Further, in wild-type GluA2 receptors, we detected the population of a stable desensitized state with a lifetime around 1 s. Using mutations that progressively stabilize deep desensitized states (E713T and Y768R), we were able to selectively protect receptors from cross-links at both the diagonal and lateral interfaces. Ultrafast perfusion enabled us to perform chemical modification in less than 10 ms, reporting movements associated to desensitization on this timescale within LBD dimers in resting receptors. These observations suggest that small disruptions of quaternary structure are sufficient for fast desensitization and that substantial rearrangements likely correspond to stable desensitized states that are adopted relatively slowly on a timescale much longer than physiological receptor activation.

Osteopontin isoforms differentially promote arteriogenesis in response to ischemia via macrophage accumulation and survival.

Osteopontin (OPN) is critical for ischemia-induced neovascularization. Unlike rodents, humans express three OPN isoforms (a, b, and c); however, the roles of these isoforms in post-ischemic neovascularization and cell migration remain undefined. Our objective was to determine if OPN isoforms differentially affect post-ischemic neovascularization and to elucidate the mechanisms underlying these differences. To investigate if human OPN isoforms exert divergent effects on post-ischemic neovascularization, we utilized OPN-/- mice and a loss-of-function/gain-of-function approach in vivo and in vitro. In this study OPN-/- mice underwent hindlimb ischemia surgery and 1.5 × 106 lentivirus particles were administered intramuscularly to overexpress OPNa, OPNb, or OPNc. OPNa and OPNc significantly improved limb perfusion 30.4% ± 0.8 and 70.9% ± 6.3, respectively, and this translated to improved functional limb use, as measured by voluntary running wheel utilization. OPNa- and OPNc-treated animals exhibited significant increases in arteriogenesis, defined here as the remodeling of existing arterioles into larger conductance arteries. Macrophages play a prominent role in the arteriogenesis process and OPNa- and OPNc-treated animals showed significant increases in macrophage accumulation in vivo. In vitro, OPN isoforms did not affect macrophage polarization, whereas all three isoforms increased macrophage survival and decreased macrophage apoptosis. However, OPN isoforms exert differential effects on macrophage migration, where OPNa and OPNc significantly increased macrophage migration, with OPNc serving as the most potent isoform. In conclusion, human OPN isoforms exert divergent effects on neovascularization through differential effects on arteriogenesis and macrophage accumulation in vivo and on macrophage migration and survival, but not polarization, in vitro. Altogether, these data support that human OPN isoforms may represent novel therapeutic targets to improve neovascualrization and preserve tissue function in patients with obstructive artery diseases.

Quality of life is significantly impaired in both secretory and non-functioning pituitary adenomas.

OBJECTIVE: To evaluate the quality of life (QoL) in patients with pituitary adenomas in comparison with healthy Mexican population QoL scores. DESIGN & MEASUREMENTS: Cross-sectional study using the short form 36 questionnaire (SF-36) in 175 patients with pituitary adenomas grouped by adenoma subtype and disease activity, and compared them with the healthy Mexican population normative QoL scores. PATIENTS: A total of 44 patients with non-functioning pituitary adenomas (NFPA), 48 with acromegaly, 53 with prolactinomas and 30 with Cushing disease (CD) were enrolled in this study. RESULTS: Mental and physical components scores (MCS & PCS) of SF-36 questionnaire were lower in patients with active disease in all adenoma subtypes (P < 0.03). A significant negative relationship between prolactin levels and MCS (r = -0.30, P < 0.01) and PCS (r = -0.41, P < 0.01) were found in prolactinomas. Patients with CD showed 24 hours urine-free cortisol levels negatively correlated with MCS (r = -0.43, P < 0.01) but not with PCS. No significant correlation was found between IGF-1 ULN and QoL scores in acromegaly. NFPA patients had lower QoL scores than patients with controlled CD, acromegaly or prolactinoma (P < 0.02). Active CD and prolactinoma have lower QoL scores in comparison of NFPA (P < 0.05). Having an adenoma, secretory or non-functioning, decrease QoL scores in comparison of results in the healthy Mexican population register. Using an adjusted-multivariate model, we confirmed that disease activity in all secretory adenomas is an independent risk factor, reducing SF-36 scores significantly. CONCLUSION: Activity in all secretory pituitary adenomas' patients decrease mental and physical QoL. However, independently of disease activity, secretory and NFPA significantly decrease QoL in comparison with healthy Mexican population QoL register.

Adenovirus 5 produces obesity and adverse metabolic, morphological, and functional changes in the long term in animals fed a balanced diet or a high-fat diet: a study on hamsters.

Adenovirus 5 (Ad-5) infection is a common cause of acute respiratory infections and the main vector used in gene therapy. There are few studies on the relationship of Ad-5 to obesity. In the present study, we evaluated the chronic effects of Ad-5 infection on golden (Syrian) hamsters fed either a balanced diet (BD) or a high-fat diet (HFD). After a single inoculation with Ad-5 (1 × 107 pfu), the body weight of the animals was measured weekly. Medium-term (22 weeks) serum biochemical analyses and long-term (44 weeks) liver morphology, adiposity, and locomotive functionality (movement velocity) assessments were carried out. In the animals fed the BD, adenovirus infection produced hyperglycemia and hyperlipidemia. In the long term, it produced a 57% increase in epididymal pad fat and a 30% body weight gain compared with uninoculated animals. In addition, morphological changes related to non-alcoholic fatty liver disease (NAFLD) were observed. The animals fed the HFD had similar but more severe changes. In addition, the hamsters presented an obesity paradox: at the end of the study, the animals that had the most morphological and functional changes (significantly reduced movement velocity) had the lowest body weight. Despite the fact that an HFD appears to be a more harmful factor in the long term than adenovirus infection alone, infection could increase the severity of harmful effects in individuals with an HFD. Epidemiological studies are needed to evaluate the effect of adenovirus as a precursor of chronic liver and cardiovascular diseases, including the chronic effects of gene therapy.

Association between enrollment factors and incident cognitive impairment in Blacks and Whites: Data from the Alzheimer's Disease Center.

INTRODUCTION: We examined the influence of enrollment factors demonstrated to differ by race on incident mild cognitive impairment and dementia using Alzheimer's Disease Center data. METHODS: Differences in rates of incident impairment between non-Latino Whites and Blacks (n = 12,242) were examined with age-at-progression survival models. Models included race, sex, education, source of recruitment, health factors, and family history of dementia. RESULTS: No significant race differences in progression were observed in cognitively unimpaired participants. In those with mild cognitive impairment at baseline, Whites evidenced greater risk for progression than Blacks. Enrollment factors, for example, referral source, were significantly related to progression. DISCUSSION: The finding that Blacks demonstrated lower rate of progression than Whites is contrary to the extant literature. Nested-regression analyses suggested that selection-related factors, differing by race, may account for these findings and influence our ability to accurately estimate risk for progression. It is potentially problematic to make racial comparisons using Alzheimer's Disease Center data sets.

Dynamics of the Ligand Binding Domain Layer during AMPA Receptor Activation.

Ionotropic glutamate receptors are postsynaptic tetrameric ligand-gated channels whose activity mediates fast excitatory transmission. Glutamate binding to clamshell-shaped ligand binding domains (LBDs) triggers opening of the integral ion channel, but how the four LBDs orchestrate receptor activation is unknown. Here, we present a high-resolution x-ray crystal structure displaying two tetrameric LBD arrangements fully bound to glutamate. Using a series of engineered metal ion trapping mutants, we showed that the more compact of the two assemblies corresponds to an arrangement populated during activation of full-length receptors. State-dependent cross-linking of the mutants identified zinc bridges between the canonical active LBD dimers that formed when the tetramer was either fully or partially bound by glutamate. These bridges also stabilized the resting state, consistent with the recently published full-length apo structure. Our results provide insight into the activation mechanism of glutamate receptors and the complex conformational space that the LBD layer can sample.

The protective effect of peanut, walnut, and almond consumption on the development of breast cancer.

BACKGROUND/AIMS: Breast cancer is the most common gynecologic malignancy known worldwide. The consumption of certain foods may modify the risk for its development. Peanuts and other seeds have shown anticarcinogenic effects in vitro, but there are a few studies that evaluate the effect of their consumption on the development of breast cancer. The aim of the present study was to determine whether there is an association between the consumption of peanuts, walnuts, and almonds and the development of breast cancer. METHODS: We analyzed 97 patients presenting with breast cancer and 104 control subjects that did not have the pathology (BIRADS 1-2). An analysis of the main clinical characteristics and lifelong seed consumption was carried out. The association between the consumption of these foods and the risk for breast cancer was estimated by odds ratios and 95% confidence intervals, controlling other risk factors, using the Mantel-Haenszel analysis. RESULTS: The high consumption of peanuts, walnuts, or almonds significantly reduced the risk for breast cancer by 2-3 times. This protective effect was not found with low or moderate seed consumption when compared with null consumption. CONCLUSIONS: High consumption of peanuts, walnuts, and almonds appears to be a protective factor for the development of breast cancer.

Histological changes caused by meclofenamic acid in androgen-independent prostate cancer tumors: evaluation in a mouse model.

Meclofenamic acid is a nonsteroidal anti-inflammatory drug that has shown therapeutic potential for different types of cancers, including androgen-independent prostate neoplasms. The antitumor effect of diverse nonsteroidal anti-inflammatory drugs has been shown to be accompanied by histological and molecular changes that are responsible for this beneficial effect. The objective of the present work was to analyze the histological changes caused by meclofenamic acid in androgen-independent prostate cancer. Tumors were created in a nude mouse model using PC3 cancerous human cells. Meclofenamic acid (10 mg/kg/day; experimental group, n=5) or saline solution (control group, n=5) was administered intraperitoneally for twenty days. Histological analysis was then carried out on the tumors, describing changes in the cellular architecture, fibrosis, and quantification of cellular proliferation and tumor vasculature. Meclofenamic acid causes histological changes that indicate less tumor aggression (less hypercellularity, fewer atypical mitoses, and fewer nuclear polymorphisms), an increase in fibrosis, and reduced cellular proliferation and tumor vascularity. Further studies are needed to evaluate the molecular changes that cause the beneficial and therapeutic effects of meclofenamic acid in androgen-independent prostate cancer.

Regulator of G protein signaling transcript expression in human neural progenitor differentiation: R7 subfamily regulation by DNA methylation.

G protein-coupled receptors (GPCRs) and their ligands are critical regulators of neural progenitor differentiation, and GPCR signaling pathways are regulated by regulator of G protein signaling (RGS) proteins. RGS protein expression is dynamically regulated, and we have recently described the epigenetic regulation of RGS transcript expression. Given the potential of RGS proteins to regulate GPCR signaling and the established role of epigenetic regulation in progenitor differentiation, we explored the impact of epigenetic regulation of RGS transcripts during in vitro differentiation of human neural progenitors. Here, we demonstrate robust upregulation of the RGS transcripts RGS4, RGS5, RGS6, RGS7, and RGS11 during neuronal differentiation, while DNA methyltransferase (DNMT) and histone deacetylase enzyme expression is suppressed during differentiation. Transcripts encoding R7 subfamily RGS proteins and the R7-binding partners R7BP and R9AP showed the greatest upregulation. Further, we showed that direct pharmacological inhibition of DNMT activity enhances expression of RGS2, RGS4, RGS5, RGS6, RGS7, RGS8, RGS9L, RGS10, and RGS14 as well as R7BP and R9AP transcripts in progenitors, consistent with regulation by DNMTs. Our results reveal marked upregulation of RGS expression during neuronal differentiation and suggest that decreased expression of DNMT enzymes during differentiation contributes to upregulation.

Outbreak of Fusarium solani Meningitis in Immunocompetent Persons Associated With Neuraxial Blockade in Durango, Mexico, 2022-2023.

Background: Fungal meningitis can be associated with epidural anesthesia procedures. Fusariosis is a rare infection typically affecting immunocompromised patients and rarely causes meningitis. During 2022-2023, public health officials responded to a large outbreak of Fusarium solani meningitis associated with epidural anesthesia in Durango, Mexico. Methods: The public health response and epidemiological and clinical features of patients affected by this outbreak were described. Coordinated actions were addressed to identify the etiological agent, determine its drug susceptibility, develop diagnostic tests, and implement clinical and epidemiological protocols. Retrospective analyses of clinical variables and outcomes were performed to determine association with better patient survival. Results: A total of 1801 persons exposed to epidural anesthesia were identified, of whom 80 developed meningitis. Fusarium solani was found in 3 brain biopsies and showed susceptibility to voriconazole and amphotericin B. After F solani polymerase chain reaction (PCR) implementation, 57 patients with meningitis were PCR-screened, and 31 (38.8%) had a positive result. Most patients were female (95%), and cesarean section was the most common surgical procedure (76.3%). The case fatality rate was 51.3% (41 patients) and the median hospitalization duration was 39.5 days (interquartile range, 18-86 days). Seventy-one patients (88.8%) received voriconazole/amphotericin B and 64 subjects (80%) additionally received steroids. Cox regression analysis showed an increased lethality risk in patients who received antifungal treatment after 5 days (hazard ratio, 2.1 [95% confidence interval, 1.01-4.48], P < .05). Conclusions: The F solani meningitis outbreak in Durango was an unprecedented medical challenge. Timely treatment and effective healthcare management were associated with better survival outcomes.

Plasma Aß42/40 and cognitive variability are associated with cognitive function in Black Americans: Findings from the AA-FAIM cohort.

Introduction: It is critical to develop more inclusive Alzheimer's disease (AD) research protocols to ensure that historically excluded groups are included in preclinical research and have access to timely diagnosis and treatment. If validated in racialized groups, plasma AD biomarkers and measures of subtle cognitive dysfunction could provide avenues to expand diversity in preclinical AD research. We sought to evaluate the utility of two easily obtained, low-burden disease markers, plasma amyloid beta (Aß)42/40, and intra-individual cognitive variability (IICV), to predict concurrent and longitudinal cognitive performance in a sample of Black adults. Methods: Two hundred fifty-seven Black participants enrolled in the African Americans Fighting Alzheimer's in Midlife (AA-FAIM) study underwent at least one cognitive assessment visit; a subset of n = 235 had plasma samples. Baseline IICV was calculated as the standard deviation across participants' z scores on five cognitive measures: Rey Auditory Verbal Learning Test Delayed Recall, Trail Making Test Parts A and B (Trails A and B), and Boston Naming Test. Using mixed effects regression models, we compared concurrent and longitudinal models to baseline plasma Aß42/40 or IICV by age interactions. PrecivityAD assays quantified baseline plasma Aß42/40. Results: IICV was associated with concurrent/baseline performance on several outcomes but did not modify associations between age and cognitive decline. In contrast, plasma Aß42/40 was unrelated to baseline cognitive performance, but a pattern emerged in interactions with age in longitudinal models of Trails A and B and Rey Auditory Verbal Learning Test total learning trials. Although not significant after correcting for multiple comparisons, low Aß42/40 was associated with faster cognitive declines over time. Discussion: Our results are promising as they extend existing findings to an Black American sample using low-cost, low-burden methods that can be implemented outside of a research center, thus supporting efforts for inclusive AD biomarker research.

Regional and national burden of prostate cancer: incidence, mortality, years of life lost, and disability-adjusted life years, in Mexico and Latin America from 1990 to 2019.

PURPOSE: Prostate cancer (PC) is the second leading cause of cancer and the fifth cause of cancer-related death. This manuscript aims to determine the incidence, mortality, and Disability Adjusted Life Years (DALYs) trends of PC in the last 30 years in Latin America and Mexico. METHODS: We performed a cross-sectional analysis of a publicly available data set. Data regarding the burden of prostate cancer in 20 Latin-American countries, and the 32 states of Mexico, were retrieved from the Global Burden of Disease Study 2019. Collected information included incidence and mortality rates (per 100,000), as well as the DALYs as absolute numbers and rates (per 100,000) and the annual rates of change in rates from 1990 to 2019. RESULTS: In Latin America in males aged 55 years or older, the mean incidence rate was 344 cases per 100,000. The number of deaths attributable to prostate cancer observed was 67,110 and the mean mortality rate was 210 per 100,000. The overall burden of disease was 1,120,709 DALYs and the contribution of years of life lost (YLL) was 91.7% ([Formula: see text] = 1,027,946). Mexico presented an incidence rate (279.6) and mortality (99.1) rate (per /100 thousand). In Mexico, 13 states had a DALYs' rate above the national mean (883 per 100,000) and the highest burden (1360 DALYs/100,000) were documented in the state of Guerrero (Southwestern Mexico). CONCLUSION: Only two Latin-American countries (Brazil and Colombia) and eight states of Mexico showed a decreased trend about the rate of change of DALYs in the last 30 years.

Effect of Liposuction on Body Weight and Serum Concentrations of Leptin, Lipids, Glucose, and Insulin: A Meta-Analysis.

BACKGROUND: Abdominal obesity has been associated with an increased risk of insulin resistance, metabolic syndrome, and diabetes. Central fat removal procedures such as liposuction, lipectomy, and abdominoplasty are among the most common surgical procedures. The impact of the latter on the former is controversial and understudied. The authors aimed to explore the effect of subcutaneous fat elimination procedures on insulin resistance measures and adipokine levels. METHODS: Relevant studies regarding the effects of surgical subcutaneous fat removal on glucose, insulin, adipokines, and lipid metabolism, as well as blood pressure, were identified by searching PubMed and Ovid-Cochrane without limits in date, type of publication, or language. After the selection process, 24 studies were obtained. The results of the articles were summarized using descriptive statistics. For the final analysis, a randomized effects model was used to evaluate heterogeneity; averages and meta-analytic differences were expressed with a confidence interval of 95%. RESULTS: All studies reported a reduction in weight (-2.64 kg; 95% CI, -4.32 to -0.96; P = 0.002; I 2 = 36%; P of I 2 < 0.001) and body mass index after liposuction. A significant improvement in triglycerides (-10.06 mg/dL; 95% CI, -14.03 to -6.09; P < 0.001; I 2 = 48%; P of I 2 = 0.05), serum glucose concentration (-4.25 mg/dL; 95% CI, -5.93 to -2.56; P < 0.001; I 2 = 68%; P of I 2 < 0.001), serum insulin concentration (-2.86 µIU/mL; 95% CI, -3.75 to -1.97; P < 0.001; I 2 = 59%; P of I 2 = 0.003), and serum leptin concentration (-7.70 ng/mL; 95% CI, -11.49 to -3.92; P = 0.0001; I 2 = 96%; P of I 2 < 0.001) was consistently observed. CONCLUSION: In addition to weight loss, there is a significant decrease in leptin, triglyceride, glucose, and insulin serum concentrations after liposuction, a fact that should be considered in future discussions.

A single N-terminal cysteine in TRPV1 determines activation by pungent compounds from onion and garlic.

Some members of the transient receptor potential (TRP) family of cation channels mediate sensory responses to irritant substances. Although it is well known that TRPA1 channels are activated by pungent compounds found in garlic, onion, mustard and cinnamon extracts, activation of TRPV1 by these extracts remains controversial. Here we establish that TRPV1 is activated by pungent extracts from onion and garlic, as well as by allicin, the active compound in these preparations, and participates together with TRPA1 in the pain-related behavior induced by this compound. We found that in TRPV1 these agents act by covalent modification of cysteine residues. In contrast to TRPA1 channels, modification of a single cysteine located in the N-terminal region of TRPV1 was necessary and sufficient for all the effects we observed. Our findings point to a conserved mechanism of activation in TRP channels, which provides new insights into the molecular basis of noxious stimuli detection.

Racial Differences in Associations of Cognitive Health Status With Happiness, Helplessness, and Hopelessness Among Older Adults: An Exploratory Study.

Background: The relationship between healthy and positive aging and dementia and cognitive impairment has received limited attention in the field of aging. Affect impacts cognitive changes and processes, and cognitive impairment is associated with affective comorbidities. The purpose of the study was to examine (a) whether happiness, helplessness, and hopelessness are linked to cognitive health status, and (b) whether these associations differ by race. Methods: Participants were enrollees in the Wisconsin Alzheimer's Disease Research Center's Clinical Core (ADRC). Average age at baseline was 60.85 (SD = 8.65), 73.70 (SD = 8.02), and 73.80 (SD = 9.59) years for cognitively normal individuals, individuals with MCI, and individuals with dementia, respectively. Results: In the full sample, chi-square test results revealed associations between Cognitive Health Status (CHS) and (a) happiness, χ2(2) = 6.06, p < 0.05, (b) helplessness, χ2(2) = 6.44, p < 0.05, and (c) hopelessness, χ2(2) = 14.11, p < 0.01. Conclusion: This study provides support for the association of both positive and negative affect with cognitive health status in middle- to older-aged adults.

Efficacy of the use of mefenamic acid combined with standard medical care vs. standard medical care alone for the treatment of COVID­19: A randomized double­blind placebo­controlled trial.

Mefenamic acid is a non­steroidal anti­inflammatory drug exhibiting a wide range of anti­inflammatory, antipyretic, analgesic and probable antiviral activities. The present study evaluated the efficacy of treatment with mefenamic acid combined with standard medical care vs. standard medical care plus a placebo in ambulatory patients with coronavirus disease 2019 (COVID­19; nasal/oropharyngeal swabs reverse transcription­PCR test results positive for severe acute respiratory syndrome coronavirus 2). The present study is a phase II prospective, two­arm, parallel­group, randomized, double­blind placebo­controlled clinical trial which analyzed 36 patients. Two aspects were evaluated during the 14­day follow­up period: i) The time for reaching a patient acceptable symptom state (PASS), and ii) the last day of each COVID­19 symptom presentation. Adverse effects were evaluated. The clinical severity for all the patients in the study was mild (88.9%) and moderate (11.1%). The control (placebo) group achieved PASS on day 8.0±1.3, compared with day 4.4±0.8 in the mefenamic acid group (P=0.020, Kaplan­Meier analyses using log­rank tests). Patients that received mefenamic acid plus standard medical care had a ~16­fold higher probability of achieving PASS on day 8 (adjusted RR, 15.57; 95% CI, 1.22­198.71; P=0.035), compared with the placebo plus standard medical care group. All symptoms lasted for fewer days in the mefenamic acid group, compared with the placebo group; however, only the symptoms of headache (P=0.008), retro­orbital eye pain (P=0.049), and sore throat (P=0.029) exhibited statistically significant differences. The experimental treatment produced no severe adverse effects. On the whole, the present study demonstrates that the administration of mefenamic acid markedly reduced the symptomatology and time to reach PASS in ambulatory patients with COVID­19. Due to its probable antiviral effects and potent anti­inflammatory mechanisms, mefenamic acid may prove to be useful in the treatment of COVID­19, in combination with other drugs, including the new antivirals (remdesivir, molnupiravir, or favipiravir). However, future studies are also required to confirm these findings.

Improve cognitive impairment using mefenamic acid non-steroidal anti-inflammatory therapy: additional beneficial effect found in a controlled clinical trial for prostate cancer therapy.

Inflammation is an essential component of prostate cancer (PCa), and mefenamic acid has been reported to decrease its biochemical progression. The current standard therapy for PCa is androgen deprivation therapy (ADT), which has side effects such as cognitive dysfunction, risk of Alzheimer's disease, and dementia. Published results of in vitro tests and animal models studies have shown that mefenamic acid could be used as a neuroprotector. Objective: Examine the therapeutic potential of mefenamic acid in cognitive impairment used in a controlled clinical trial. Clinical trial phase II was conducted on patients undergoing ADT for PCa. Two groups of 14 patients were included. One was treated with a placebo, while the other received mefenamic acid 500 mg PO every 12hrs for six months. The outcome was evaluated through the Mini-Mental State Examination (MMSE) score at six months. At the beginning of the study, both groups had similar MMSE scores (mefenamic acid vs. placebo: 26.0±2.5 vs. 27.0±2.6, P=0.282). The mefenamic acid group improved its MMSE score after six months compared with the placebo group (27.7±1.8 vs. 25.5±4.2, P=0.037). Treatment with mefenamic acid significantly increases the probability of maintained or raised cognitive function compared to placebo (92% vs. 42.9%, RR=2.2, 95% CI: 1.16-4.03, NNT=2.0, 95% CI: 1.26-4.81, P=0.014). Furthermore, 42.9% of the placebo group patients had relevant cognitive decline (a 2-point decrease in the MMSE score), while in patients treated with mefenamic acid, cognitive impairment was not present. This study is the first conducted on humans that suggests that mefenamic acid protects against cognitive decline.

Evaluation of Medical Care for Diabetic and Hypertensive Patients in Primary Care in Mexico: Observational Retrospective Study.

INTRODUCTION: The present study evaluated the quality of medical care for patients diagnosed with diabetes mellitus (DM), hypertension (HBP), and both pathologies (DM+HBP) within a public health system in Mexico. METHODS: 45,498 patients were included from 2012 to 2015. All information was taken from the electronic medical record database. Each patient record was compared against the standard to test the quality of medical care. RESULTS: Glycemia with hypertension goals reached 29.6% in DM+HBP, 48.6% in DM, and 53.2% in HBP. The goals of serum lipids were reached by 3% in DM+HBP, 5% in DM, and 0.2% in HBP. Glycemia, hypertension, and LDL cholesterol reached 0.04%. 15% of patients had an undiagnosed disease. Clinical follow-up examinations reached 20% for foot examination and clinical eye examination. Specialty referrals reached 1% in angiology or cardiology. CONCLUSION: Goals for glycemic and hypertension reached 50% in the overall population, while serum lipids, clinical follow-up examinations, and referral to a specialist were deficient. Patients who had both diseases had more consultations, better control for hypertension and lipids, but inferior glycemic control. Overall, quality care for DM and/or HBP has not been met according to the standards.

Safety and efficacy of a COVID-19 treatment with nebulized and/or intravenous neutral electrolyzed saline combined with usual medical care vs. usual medical care alone: A randomized, open-label, controlled trial.

Coronavirus disease 2019 (COVID-19) is currently the major public health problem worldwide. Neutral electrolyzed saline solution that contains reactive chlorine and oxygen species may be an effective therapeutic. In the present study, the treatment efficacy of intravenous and/or nebulized neutral electrolyzed saline combined with usual medical care vs. usual medical care alone was evaluated in ambulatory patients with COVID-19. A prospective, 2-arm, parallel-group, randomized, open-label, multi-center, phase I-II clinical trial including 214 patients was performed. The following two outcomes were evaluated during the 20-day follow-up: i) The number of patients with disease progression; and ii) the patient acceptable symptom state. Serial severe acute respiratory syndrome coronavirus 2 naso/oro-pharyngeal detection by reverse transcription-quantitative (RT-q) PCR was performed in certain patients of the experimental group. Biochemical and hematologic parameters, as well as adverse effects, were also evaluated in the experimental group. The experimental treatment decreased the risk of hospitalization by 89% [adjusted relative risk (RR)=0.11, 95% confidence interval (CI): 0.03-0.37, P<0.001] and the risk of death by 96% (adjusted RR=0.04, 95% CI: 0.01-0.42, P=0.007) and also resulted in an 18-fold higher probability of achieving an acceptable symptom state on day 5 (adjusted RR=18.14, 95% CI: 7.29-45.09, P<0.001), compared with usual medical care alone. Overall, neutral electrolyzed saline solution was better than usual medical care alone. Of the patients analyzed, >50% were negative for the virus as detected by RT-qPCR in naso/oro-pharyngeal samples on day 4, with only a small number of positive patients on day 6. Clinical improvement correlated with a decrease in C-reactive protein, aberrant monocytes and increased lymphocytes and platelets. Cortisol and testosterone levels were also evaluated and a decrease in cortisol levels and an increase in the testosterone-cortisol ratio were observed on days 2 and 4. The experimental treatment produced no serious adverse effects. In conclusion, neutral electrolyzed saline solution markedly reduced the symptomatology and risk of progression in ambulatory patients with COVID-19. The present clinical trial was registered in the Cuban public registry of clinical trials (RPCEC) database (May 5, 2020; no. TX-COVID19: RPCEC00000309).