Risk of heart failure in ambulatory resistant hypertension: a meta-analysis of observational studies.

The impact of ambulatory resistant hypertension (ARH) on the occurrence of heart failure (HF) is not yet completely known. We performed for the first time a meta-analysis, by using published data or available data from published databases, on the risk of HF in ARH. Patients with ARH (24-h BP ≥ 130/80 mmHg during treatment with ≥3 drugs) were compared with those with controlled hypertension (CH, clinic BP < 140/90 mmHg and 24-h BP < 130/80 mmHg regardless of the number of drugs used), white coat uncontrolled resistant hypertension (WCURH, clinic BP ≥ 140/90 mmHg and 24-h BP < 130/80 mmHg in treated patients) and ambulatory nonresistant hypertension (ANRH, 24-h BP ≥ 130/80 mmHg during therapy with ≤2 drugs). We identified six studies/databases including 21,365 patients who experienced 692 HF events. When ARH was compared with CH, WCURH, or ANRH, the overall adjusted hazard ratio for HF was 2.32 (95% confidence interval (CI) 1.45-3.72), 1.72 (95% CI 1.36-2.17), and 2.11 (95% CI 1.40-3.17), respectively, (all P < 0.001). For some comparisons a moderate heterogeneity was found. Though we did not find variables that could explain the heterogeneity, sensitivity analyses demonstrated that none of the studies had a significant influential effect on the overall estimate. When we evaluated the potential presence of publication bias and small-study effect and adjusted for missing studies identified by Duval and Tweedie's method the estimates were slightly lower but remained significant. This meta-analysis shows that treated hypertensive patients with ARH are at approximately twice the risk of developing HF than other ambulatory BP phenotypes.

Clinical trial design for assessing hypertension medications: are critical circadian chronopharmacological principles being taking into account?

INTRODUCTION: Clinical hypertension trials typically rely on homeostatic principles, including single time-of-day office blood pressure (BP) measurements (OBPM), rather than circadian chronopharmacological principles, including ambulatory monitoring (ABPM) done around-the-clock to derive the asleep systolic BP (SBP) mean and sleep-time relative SBP decline - jointly the strongest prognosticators of cardiovascular disease (CVD) risk and true definition of hypertension - to qualify participants and assess outcomes. AREAS COVERED: Eight chronopharmacological elements are indispensable for design and conduct of hypertension medication trials, mainly those on ingestion-time differences in effects, and also a means of rating quality of investigations. Accordingly, we highlight the findings and shortcomings of: (i) 155 such ingestion-time trials, 83.9% finding at-bedtime/evening treatment more beneficial than conventional upon-awakening/morning treatment; (ii) HOPE and ONTARGET CVD outcomes investigations assessing in the former add-on ramipril at-bedtime and in the latter telmisartan, ramipril, or both in combination in the morning; and (iii) pragmatic TIME CVD outcomes trial. EXPERT OPINION: Failure to incorporate chronopharmacological principals - including ABPM to derive asleep SBP and SBP dipping to qualify subjects as hypertensive and assess CVD risk - results in deficient study design, dubious findings, and unnecessary medical controversy at the expense of advances in patient care.

Nonlocal damage evaluation of a sigmoid-based damage model for fibrous biological soft tissues.

The comprehension and modeling of the mechanical behavior of soft biological tissues are essential due to their clinical applications. This knowledge is essential for predicting tissue responses accurately and enhancing our ability to compute the behavior of biological structures and bio-prosthetic devices under specific loading conditions. The current research is centered on modeling the initiation and progression of soft tissues damage, which typically exhibit intricate anisotropic and nonlinear elastic characteristics. For this purpose, the following study presents a comparative analysis of the computational performance of two distinct damage modeling techniques. The first technique employs a well-established damage model, based on a piece-wise exponential damage function as proposed by Calvo et al. (Int J Numer Methods Eng 69:2036-2057, 2007. https://doi.org/10.1002/nme.1825 ). The second approach adopts a sigmoid function, as proposed by López-Campos et al. (Comput Methods Biomech Biomed Eng 23(6):213-223. https://doi.org/10.1080/10255842.2019.1710742 ). The aim of this study is to verify the validity of the López-Campos sigmoid-based damage model to be used in finite element simulation, the implementation of which is unknown. For this proposal, both models were implemented within a commercial Finite Element software package, and their responses to local and non-local damage algorithms were assessed in depth through two standard benchmark tests: a plate with a hole and a ball burst. The results of this study indicate that, for a wide range of cases, such as in-plane stresses, out-plane stresses, stress concentration and contact, all over large displacement conditions, the López-Campos damage model shows a good response to non-local algorithms achieving mesh independence and convergence in all these cases. The results obtained are in line with those obtained for the Calvo's damage model, showing, in addition, larger deformations under in-plane stress and stress concentration conditions and a lower number of iterations under out-plane stress and contact conditions. Consequently, the López-Campos' damage model emerges as a valuable and useful tool in the field of mechanical damage research in biological systems.

Leptin resistance in children with in utero exposure to maternal obesity and gestational diabetes.

BACKGROUND: Leptin resistance occurs with obesity, but it is unknown if individuals at risk for obesity develop leptin resistance prior to obesity. OBJECTIVE: Investigate whether leptin resistance is independent of weight status in children at risk for obesity due to intrauterine exposure to maternal obesity or gestational diabetes mellitus (GDM). METHODS: Mother-child dyads (N = 179) were grouped by maternal pregnancy weight and GDM status: (1) normal weight, no GDM; (2) overweight/obesity, no GDM; (3) overweight/obesity with GDM. Children (4-10 years) were further stratified by current body mass index (BMI) <85th or ≥85th percentile. Leptin resistance of children and mothers was calculated as fasting leptin/fat mass index. Two-way ANOVA was used to assess whether leptin concentrations and leptin resistance differed by current weight status or in utero exposure group, after adjusting for race, sex and Tanner stage. RESULTS: Children with a BMI ≥85th percentile had more leptin resistance than those with a BMI <85th percentile (p < 0.001), but leptin resistance did not differ by in utero exposure. Similarly, leptin resistance in women was associated with weight status and not prior GDM. CONCLUSIONS: Results suggest that leptin concentrations are associated with obesity but not risk for obesity based on in utero exposure to maternal obesity or GDM.

Critical appraisal of recent translational chronopharmacology and chronotherapeutic reviews, meta-analyses, and pragmatic patient trials discloses significant deficiencies of design and conduct and suspect findings.

The conduct of molecular and laboratory animal circadian rhythm research has increased exponentially in the past few decades, such that today investigations are being performed by scientists of many diverse disciplines. Knowledge gained from past works is now being explored for translational applications to clinical medicine, often termed "circadian medicine," through the implementation of patient trials. However, these trials are being led, more often than not, by investigators who have little or no formal training and in-depth expertise in the methods of human circadian rhythm research, causing them to be deficient in design and produce dubious findings that have already led to unnecessary medical controversy at the expense of advances in patient care. Evidence of the very significant shortcomings of today's translational circadian medicine research is exemplified in two recent publications in well-read reputable medical journals concerning the chronotherapy of blood pressure (BP) medications: one a review and meta-analysis by Maqsood et al. published in the journal Hypertension in 2023 that pertains to ingestion-time differences in the extent of BP reduction exerted by hypertensive medications and the other a report by Mackenzie et al. in the journal Lancet in 2022 that details the results of the pragmatic TIME study that assessed ingestion-time differences in cardiovascular disease outcomes. Herein, we appraise the inaccurate trial selection, lack of quality assessment, and the numerous other shortcomings that culminated in suspect findings and faulty conclusions of the former, as well as the deficiencies in design and conduct of the latter using as reference the eight items identified in 2021 by a working committee of the International Society for Chronobiology and American Association for Medical Chronobiology and Chronotherapeutics as being necessary for high-quality research of circadian rhythm-dependencies of the therapeutic effects of BP-lowering medications. The TIME study when rated for its quality according to the extent to which its investigational methods satisfy all of the eight recommended items attains a very low overall score of + 1 out of a possible range of -1 to + 7. Moreover, our review of the methods of the currently ongoing pragmatic BedMed trial discloses major deficiencies of the same sort rending a poor quality score of + 0.5. Although the focus of this article is the appraisal of the quality of contemporary circadian medicine hypertension chronotherapy research, it additionally exposes the inadequacies and dubious quality of the critique of such manuscripts submitted for publication to influential journals, in that some peer reviewers might also be deficient in the knowledge required to properly rate their merit.

Twenty-four hour pattern of childhood febrile seizures substantiated by time series meta-analysis: Circadian medicine perspectives.

Major objectives of this work were to: (1) substantiate the 24-hour pattern in the occurrence of childhood febrile seizures (CFSs) by a novel time series meta-analysis of past reported time-of-day data and (2) discuss its potential circadian rhythm-dependencies. Comprehensive search of the published literature retrieved eight articles that met inclusion criteria. Three investigations were conducted in Iran, two in Japan, and one each in Finland, Italy, and South Korea, representing a total of 2461 mostly simple febrile seizures of children who were on average about 2 years of age. Population-mean cosinor analysis validated (p < .001) a 24-hour pattern in the onset of CFSs, with an approximate four-fold difference in the proportion of children expressing seizures at its peak at 18:04 h (95% confidence interval: 16:40-19:07 h) vs trough at 06:00 h, in the absence of meaningful time-of-day differences in mean body temeprarure. The CFS time-of-day pattern likely derives from the actions of multiple circadian rhythms, particularly the cytokines that comprise the pyrogenic inflammatory pathway and melatonin that influences the excitation level of central neurons and helps regulate body temperature. Past laboratory animal and patient investigations document that the vulnerability to a seizure by a provoking trigger of the same intensity is not the same but different in a predictable-in-time manner during the 24 h as a circadian susceptibility/resistance rhythm. Knowledge of the marked disparity in the time-of-day risk of CFSs can be translated into improved prevention, particularly during the late afternoon and early evening when highest, through proper timing of prophylactic interventions.

Oleic acid regulates the circadian rhythm of adipose tissue in obesity.

The effect of oleic acid (OA) on the regulation of the circadian rhythm present in human visceral (VAT) and subcutaneous (SAT) adipose tissue from patients with morbid obesity has not been analyzed yet. VAT and SAT explants from patients with morbid obesity were incubated with OA to analyze the circadian regulation of clock and other genes related to lipid metabolism (SREBP-1c, FAS, LPL and CPT1), and their association with baseline variables and the improvement of these patients after bariatric surgery. There were significant differences in amplitude and acrophase in VAT with respect to SAT. In VAT, body weight negatively correlated with BMAL1 and CRY1 amplitude, and REVERBα acrophase; body mass index (BMI) negatively correlated with REVERBα acrophase; and waist circumference negatively correlated with PER3 acrophase. In SAT, BMI negatively correlated with CLOCK amplitude, and CLOCK, REVERBα and CRY2 MESOR; and waist circumference negatively correlated with PER3 amplitude and acrophase. A greater short-term improvement of body weight, BMI and waist circumference in patients with morbid obesity after bariatric surgery was associated with a lower CRY1 and CRY2 amplitude and an earlier PER1 and PER3 acrophase in SAT. OA produced a more relevant circadian rhythm and increased the amplitude of most clock genes and lipid metabolism-related genes. OA regulated the acrophase of most clock genes in VAT and SAT, placing CLOCK/BMAL1 in antiphase with regard to the other genes. OA increased the circadian rhythmicity, although with slight differences between adipose tissues. These differences could determine its different behavior in obesity.

Elevated asleep blood pressure and non-dipper 24h patterning best predict risk for heart failure that can be averted by bedtime hypertension chronotherapy: A review of the published literature.

Several prospective studies consistently report elevated asleep blood pressure (BP) and blunted sleep-time relative systolic BP (SBP) decline (non-dipping) are jointly the most significant prognostic markers of cardiovascular disease (CVD) risk, including heart failure (HF); therefore, they, rather than office BP measurements (OBPM) and ambulatory awake and 24 h BP means, seemingly are the most worthy therapeutic targets for prevention. Published studies of the 24 h BP pattern in HF are sparse in number and of limited sample size. They report high prevalence of the abnormal non-dipper/riser 24 h SBP patterning. Despite the established clinical relevance of the asleep BP, past as do present hypertension guidelines recommend the diagnosis of hypertension rely on OBPM and, when around-the-clock ambulatory BP monitoring (ABPM) is conducted to confirm the elevated OBPM, either on the derived 24 h or "daytime" BP means. Additionally, hypertension guidelines do not advise the time-of-day when BP-lowering medications should be ingested, in spite of known ingestion-time differences in their pharmacokinetics and pharmacodynamics. Between 1976 and 2020, 155 unique trials of ingestion-time differences in the effects of 37 different single and 14 dual-combination hypertension medications, collectively involving 23,972 patients, were published. The vast majority (83.9%) of them found the at-bedtime/evening in comparison to upon-waking/morning treatment schedule resulted in more greatly enhanced: (i) reduction of asleep BP mean without induced sleep-time hypotension; (ii) reduction of the prevalence of the higher CVD risk non-dipper/riser 24 h BP phenotypes; (iii) improvement of kidney function, reduction of cardiac pathology, and with lower incidence of adverse effects. Most notably, no single published randomized trial found significantly better BP-lowering, particularly during sleep, or medical benefits of the most popular upon-waking/morning hypertension treatment-time scheme. Additionally, prospective outcome trials have substantiated that the bedtime relative to the upon-waking, ingestion of BP-lowering medications not only significantly reduces risk of HF but also improves overall CVD event-free survival time.

Epidemiological Characterization of Patients in the First Eight Weeks Following Detection of SARS-CoV-2 B.1.1.529 (omicron) Variant in Cuba.

INTRODUCTION: In November 2021, omicron-a new SARS-CoV-2 variant-was identified in South Africa and almost immediately, WHO declared it a 'variant of concern'. In view of its rapid worldwide spread and its imminent introduction in Cuba, genomic surveillance was strengthened. OBJECTIVE: Describe cases during the first eight epidemiological weeks (epiweeks) of SARS-CoV-2 infection attributable to omicron variant in Cuba by clinical and epidemiological variables. METHODS: From epiweek 48, 2021 to epiweek 4, 2022, 288 nasopharyngeal swabs were processed for sequencing of a 1836 bp fragment of the S gene. Variants were identified according to GISAID database and confirmed by phylogenetic analysis. Variants' association with clinical and epidemiological outcomes was assessed. RESULTS: The first cases of omicron variant were imported, mostly from African countries and the United States. During the period studied, omicron was detected in 83.0% (239/288) of cases processed, while the delta variant was found in 17.0% (49/288). Most persons infected with omicron were symptomatic (63.2%; 151/239) and fully vaccinated (65.3%; 156/239); severe cases and deaths occurred mainly among patients aged ≥65 years (92.9%; 13/14), and 12 of these deaths occurred in fully vaccinated persons (92.3%; 12/13). Omicron spread rapidly throughout the country (from 10% of cases in epiweek 48, 2021, to 100% by epiweek 4, 2022), displacing the formerly predominant delta variant. CONCLUSIONS: Omicron's rapid expansion in Cuba was associated with increased incidence but not with a higher case fatality rate. The relatively milder disease in those infected with this variant could be influenced by the high vaccination coverage, along with the natural immunity acquired as a consequence of previous virus infection.

Renoportal Anastomosis and Its Complications: A Complex Case Report.

BACKGROUND: Renoportal anastomosis (RPA) is an effective technique in cases of complex portal vein thrombosis with the presence of a splenorenal shunt. The objective of this report is to describe the possible complications related to RPA. CASE REPORT: A 50-year-old man with alcohol-related and hepatitis C-related cirrhosis and 2 hepatocellular carcinomas underwent liver transplant. He presented a portal vein thrombosis Yerdel IV, a splenorenal shunt, and another shunt between the inferior mesenteric vein (IMV) and the perirectal plexus. During surgery, the flow of the left renal vein was 891 mL/min, and this rose to 1050 mL/min after IMV clamping. RPA was made through iliac vein graft interposition, and the IMV was ligated. Portal flow was 832 mL/min but drastically decreased because of mesenteric root compression. After finishing the liver transplant, a renoiliac graft percutaneous transhepatic stent was put in place. The patient presented graft dysfunction and acute kidney injury. On postoperative day +18, a second stent was put in place because of a thrombosis in the splenomesenteric confluence. The patient subsequently presented partial distal rethrombosis and a pancreaticoduodenal arteriovenous fistula, which required several embolizations. The patient developed ascites, recurrent gastrointestinal bleeding, and persistent bacterial peritonitis. Finally, a modified Sugiura procedure (without splenectomy) was performed, achieving a portal flow of 1800 mL/min. However, the patient developed sepsis and multiorgan failure, and died on postoperative day +70. CONCLUSIONS: Despite long-term patient and graft survival within accepted limits after LT, RPA is a challenging technique not exempt from complications.

Nonsplenorenal Spontaneous Portosystemic Shunts in Liver Transplant Attitude and Outcomes: A Single-Center Series.

BACKGROUND: Management of nonsplenorenal spontaneous portosystemic shunts (NSRSPSS) in liver transplant (LT) is controversial. Reports on the influence of its ligation suggest improvements in morbidity and survival. METHODS: Retrospective study of a single-center series. The objective was to analyze the outcomes and post-LT survival after the closure of NSRSPSS. RESULTS: Between January 2005 and April 2021 a total of 23 patients with NSRSPSS underwent LT. The shunt was superior mesenteric vein-vena cava in 12 (52.2%), inferior mesenteric vein-vena cava in 6 (26.1%), through the left gastric vein in 4 (17.4%), and portocava in 1 (4.3%). Seven patients presented portal vein thrombosis, with thrombectomy being performed in 5. Moreover, 21 patients had portoportal anastomosis, 1 patient required portal reconstruction at the splenomesenteric confluence, and 1 had a coronary-portal anastomosis. The NSRSPSS was closed in 22 cases (95.7%). The mean (SD) portal flow before and after the closure of NSRSPSS was 1395 (572) mL/min and 1773 (583) mL/min (104.4 [47.9] mL/min/100 g and 127.9 [4.9] mL/min/100 g, respectively). Six patients (26.1%) presented primary graft dysfunction, 13 (56.5%) acute kidney injury, and 9 (39%) ascites. Three arterial stenoses (13%), 2 biliary stenoses (8.6%), and 1 intrahepatic portal thrombosis (4.3%) occurred. Median intensive care unit and hospital stay was 5 days (range, 3-8 days) and 15 days (range, 13-21 days). After a mean follow-up of 5.18 (3.2) years, all patients except 1 are alive. CONCLUSIONS: The closure of the NSRSPSS during LT can optimize portal flow, with potential influence in morbidity and survival rates.

Body fat percentage assessment using skinfold thickness agrees with measures obtained by DXA scan in African American and Caucasian American women.

Dual-energy x-ray absorptiometry (DXA) is considered to have high accuracy in estimating fat mass; however, DXA is not always available. We hypothesized that the equations most commonly used for predicting body fat percentage (BF%) using skinfold thickness agree with direct measures of BF% obtained by DXA scan in African American (AA) and Caucasian American (CA) women. Data from 42 women from Alabama who were 21 to 45 years of age, who self-identify as AA (n = 20) or CA (n = 22) were included. BF% was estimated using DXA scan and through 6 different skinfold thickness equations. Agreement between DXA-BF% and BF% based on the skinfold thickness equations was assessed following the Bland-Altman method (bias and agreement limits). Agreement analysis showed in both AA and CA women that the BF%-Siri equation reflects better agreement and lower mean differences (bias) with BF%-DXA than the BF%-Brozek equation after applying 4 body density (BD) equations. Limits showed that BF%-Siri and BF%-Brozek predictive equations overestimate BF% compared with DXA-BF% in both AA and CA women. In AAs, equations that overestimated less were Wilmore and Behnke-Siri (by 1.81%) and Durnin and Womersley-Siri (by 2.5%) equations. Regarding CAs, equations that overestimated less were Durnin and Womersley-Siri (by 2.74%) and Wilmore and Behnke-Siri (by 3.11%) equations. The results of this study show that the BF%-Siri equation is a more accurate alternative than the BF%-Brozek equation for the calculation of BF%. In the calculation of BD, the Wilmore and Behnke equation in AA women and Durnin and Womersley in CA women were those that overestimated BF% to a lesser degree.

SIG-1451, a Novel, Non-Steroidal Anti-Inflammatory Compound, Attenuates Light-Induced Photoreceptor Degeneration by Affecting the Inflammatory Process.

Age-related macular degeneration is a progressive retinal disease that is associated with factors such as oxidative stress and inflammation. In this study, we evaluated the protective effects of SIG-1451, a non-steroidal anti-inflammatory compound developed for treating atopic dermatitis and known to inhibit Toll-like receptor 4, in light-induced photoreceptor degeneration. SIG-1451 was intraperitoneally injected into rats once per day before exposure to 1000 lx light for 24 h; one day later, optical coherence tomography showed a decrease in retinal thickness, and electroretinogram (ERG) amplitude was also found to have decreased 3 d after light exposure. Moreover, SIG-1451 partially protected against this decrease in retinal thickness and increase in ERG amplitude. One day after light exposure, upregulation of inflammatory response-related genes was observed, and SIG-1451 was found to inhibit this upregulation. Iba-1, a microglial marker, was suppressed in SIG-1451-injected rats. To investigate the molecular mechanism underlying these effects, we used lipopolysaccharide (LPS)-stimulated rat immortalised Müller cells. The upregulation of C-C motif chemokine 2 by LPS stimulation was significantly inhibited by SIG-1451 treatment, and Western blot analysis revealed a decrease in phosphorylated I-κB levels. These results indicate that SIG-1451 indirectly protects photoreceptor cells by attenuating light damage progression, by affecting the inflammatory responses.

Emergence and evolution of SARS-CoV-2 genetic variants during the Cuban epidemic.

The SARS CoV-2 D614G variant circulated in Cuba in 2020. New viral variants were detected after the opening of the border in November 2020. We show the results of the genomic surveillance in Cuba from December 28, 2020, to September 28, 2021 and their relationship to the epidemiological situation in the country. A total of 1,406 nasopharyngeal exudates from COVID-19 patients were processed for RNA extraction and the 1836 bp fragment of the spike gene was amplified and sequenced. The mutations present were determined using the GISAID database. Prevalence ratios were estimated by fitting Poisson univariate and multivariate regression models to investigate associations between SARS-CoV-2 variant group (VOC, non-VOC) and disease outcome. Seventeen genetic variants were detected including VOC Alpha, Beta, Gamma and Delta, one variant of interest (VOI) (Lambda) and two previous VOI (A.2.5.1 and Zeta/P.2). Beta (34.77%), Delta (24.89%) and D614G (19%) variants were the most frequently detected. By June, Delta increased in frequency, displacing Beta. Disease severity increased significantly with age and VOC (PR =1.98, IC 95%: 1.33-3.05, p <0.05). Genomic surveillance allowed us to identify the upsurge of novel variants. Coinciding with the higher epidemic period, multiple variants were co-circulating. Although we cannot rule out that failure in the transmission containment measures occurred, the increase in the number of cases associated with the circulation of several variants, particularly the Beta and Delta variants is highly suggestive. A greater association of Beta variant with clinical severity and Delta variant with a greater transmissibility was observed.

In Vitro and Clinical Evaluation of Cannabigerol (CBG) Produced via Yeast Biosynthesis: A Cannabinoid with a Broad Range of Anti-Inflammatory and Skin Health-Boosting Properties.

Cannabigerol (CBG) is a minor non-psychoactive cannabinoid present in Cannabis sativa L. (C. sativa) at low levels (<1% per dry weight) that serves as the direct precursor to both cannabidiol (CBD) and tetrahydrocannabinol (THC). Consequently, efforts to extract and purify CBG from C. sativa is both challenging and expensive. However, utilizing a novel yeast fermentation technology platform, minor cannabinoids such as CBG can be produced in a more sustainable, cost-effective, and timely process as compared to plant-based production. While CBD has been studied extensively, demonstrating several beneficial skin properties, there are a paucity of studies characterizing the activity of CBG in human skin. Therefore, our aim was to characterize and compare the in vitro activity profile of non-psychoactive CBG and CBD in skin and be the first group to test CBG clinically on human skin. Gene microarray analysis conducted using 3D human skin equivalents demonstrates that CBG regulates more genes than CBD, including several key skin targets. Human dermal fibroblasts (HDFs) and normal human epidermal keratinocytes (NHEKs) were exposed in culture to pro-inflammatory inducers to trigger cytokine production and oxidative stress. Results demonstrate that CBG and CBD reduce reactive oxygen species levels in HDFs better than vitamin C. Moreover, CBG inhibits pro-inflammatory cytokine (Interleukin-1ß, -6, -8, tumor necrosis factor α) release from several inflammatory inducers, such as ultraviolet A (UVA), ultraviolet B (UVB), chemical, C. acnes, and in several instances does so more potently than CBD. A 20-subject vehicle-controlled clinical study was performed with 0.1% CBG serum and placebo applied topically for 2 weeks after sodium lauryl sulfate (SLS)-induced irritation. CBG serum showed statistically significant improvement above placebo for transepidermal water loss (TEWL) and reduction in the appearance of redness. Altogether, CBG's broad range of in vitro and clinical skin health-promoting activities demonstrates its strong potential as a safe, effective ingredient for topical use and suggests there are areas where it may be more effective than CBD.

Rural and Urban Differences in Vegetable and Fruit Consumption Among Older Cancer Survivors in the Deep South: An Exploratory Cross-Sectional Study.

BACKGROUND: Cancer survivors, especially those who are older, experience increased comorbidity and risk for secondary cancers. A varied dietary pattern rich in vegetables and fruits (V&F) is recommended to improve health. However, V&F intake can differ by rural vs urban status. OBJECTIVE: Our objective was to assess the differences in V&F consumption among older cancer survivors residing in urban- and rural-designated areas, and to explore whether differences exist according to sex, race, and cancer type. DESIGN: This was a cross-sectional secondary analysis. PARTICIPANTS/SETTING: Screening data from the Harvest for Health trial were obtained from October 2016 to November 2019 on 731 Medicare-eligible cancer survivors across Alabama. MAIN OUTCOME MEASURES: V&F consumption was measured by 2 items from the National Cancer Institute's dietary screener Eating at America's Table. Rural and urban residence was coded at the ZIP-code level using the US Department of Agriculture's Rural-Urban Commuting Area coding schema using 5 different classifications (A through E). Sex, race, and cancer type were dichotomized as male or female, non-Hispanic White or non-Hispanic Black, and gastrointestinal or other cancers, respectively. STATISTICAL ANALYSES: Kruskal-Wallis rank sum and post-hoc tests were performed to detect differences in V&F consumption (α < .05). RESULTS: The study sample was largely female (66.2%) and non-Hispanic White (78.1%); mean age was 70 years and reported average V&F intake was 1.47 cups/d. V&F consumption of cancer survivors living in isolated, small, rural towns was roughly one-half that consumed by survivors living elsewhere; thus, statistically significant rural-urban differences were found in models that accounted specifically for this subgroup, that is, Rural-Urban Commuting Area categorizations A and E. V&F consumption also was significantly lower in non-Hispanic Black (1.32 ± 0.98 cups/d) than non-Hispanic White survivors (1.51 ± 1.10 cups/d) (P = .0456); however, no statistically significant differences were detected by sex and cancer type. CONCLUSIONS: Analyses that address the variability within rural-designated areas are important in future studies. Moreover, a greater understanding is needed of factors that adversely affect V&F consumption of those most vulnerable, that is, older, non-Hispanic Black cancer survivors, as well as those living in isolated, small, rural towns to best target future interventions. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02985411.

Ingestion-time differences in the pharmacodynamics of dual-combination hypertension therapies: Systematic review and meta-analysis of published human trials.

The pharmacodynamics of hypertension medications can be significantly affected by circadian rhythms in the biological mechanisms of the 24 h blood pressure (BP) pattern. Hypertension guidelines fail to recommend the time of day when patients, including those who require treatment with multiple medications, are to ingest BP-lowering therapy. We conducted a systematic review of published prospective trials that investigated hypertension medications for ingestion-time differences in BP-lowering, safety, patient adherence, and markers of target organ pathology. Among the search-retried 155 trials, 17 published between 1991 and 2020 totaling 1,508 hypertensive participants concerned the differential ingestion-time dependent effects of 14 unique dual-combination therapies. All but one (94.1%) of the trials, involving 98.5% of the total number of investigated individuals, reported clinically and statistically significant benefits - including enhanced reduction of asleep BP without induction of sleep-time hypotension, reduced prevalence of BP non-dipping, decreased adverse effects, improved kidney function, and reduced cardiac pathology - when dual-combination hypertension medications were ingested at-bedtime/evening rather than upon-waking/morning. A systematic and comprehensive review of the literature published in the past three decades reveals no single dual-combination hypertension trial reported significantly better benefit of the still conventional, yet unjustified by medical evidence, upon-waking/morning hypertension treatment scheme.