Partial recovery of SARS-CoV-2 immunity after booster vaccination in renal transplant recipients.

The pandemic caused by the SARS-CoV-2 coronavirus has been especially detrimental to patients with end-stage renal disease. History with other vaccines suggests that patients with renal disease may not respond adequately to the SARS-CoV-2 vaccine. The aim of this study is to evaluate the immunity to SARS-CoV-2 mRNA vaccines in renal patients. Post SARS-CoV-2 vaccination first, and after the booster dose, antibodies and cellular immunity were studied in patients on hemodialysis (N = 20), peritoneal dialysis (N = 10) and renal transplantation (N = 10). After the two doses of vaccine, there was an effective immunity in dialysis patients, with 100% seroconversion and 87% detection of cellular immunity (85% in hemodialysis and 90% in peritoneal dialysis). In contrast, in renal transplant recipients there was only 50% seroconversion and cellular immunity was detected in 30% of patients. After the booster dose, all dialysis patients achieved a cellular and antibody immunity, whereas in transplant patients, despite improvement, 20% did not produce antibodies and in 37.5% cellular immunity could not be detected. The mRNA vaccine plus booster performs excellently in dialysis patients, whereas in kidney transplant recipients, despite the booster, complete immunization is not achieved.

HTS driven by fluorescence lifetime detection of FRET identifies activators and inhibitors of cardiac myosin.

Small molecules that bind to allosteric sites on target proteins to alter protein function are highly sought in drug discovery. High-throughput screening (HTS) assays are needed to facilitate the direct discovery of allosterically active compounds. We have developed technology for high-throughput time-resolved fluorescence lifetime detection of fluorescence resonance energy transfer (FRET), which enables the detection of allosteric modulators by monitoring changes in protein structure. We tested this approach at the industrial scale by adapting an allosteric FRET sensor of cardiac myosin to high-throughput screening (HTS), based on technology provided by Photonic Pharma and the University of Minnesota, and then used the sensor to screen 1.6 million compounds in the HTS facility at Bristol Myers Squibb. The results identified allosteric activators and inhibitors of cardiac myosin that do not compete with ATP binding, demonstrating high potential for FLT-based drug discovery.

High genetic diversity and zoonotic potential of Staphylococcus aureus strains recovered from bovine intramammary infections in Colombians dairy herds.

Genotyping of Staphylococcus aureus isolated from mastitis has become a fundamental tool to understand its complex epidemiology and to evaluate spillover events. The aim of this study was to describe the frequency of genotypes of the S. aureus strains isolated from intramammary infections by spa typing technique, and to evaluate the association between genotypes and the ability to form biofilm under in vitro conditions. Sixty-six strains of S. aureus recovered from bovines intramammary infections on 56 dairy herds located in 14 municipalities of the department of Antioquia were characterized. The majority of strains (65/66) were isolated from milk samples collected from dairy cows with subclinical intramammary infections. Nineteen different spa types were found in this study, t521 (19.70%), t267 (15.15%), and t605 (12.12%) being the most frequent. The strains from the t605 spa type showed the highest biofilm production. The high frequency of spa types with zoonotic potential found in this study, identified cattle as an important reservoir of theses clones for people in close proximity, such as milkers and consumers of unpasteurized dairy products.

Effects of concurrent exercise on health-related quality of life in middle-aged women.

OBJECTIVE: This study aimed to evaluate the influence of a 16-week concurrent exercise program on health-related quality of life in middle-aged women. METHODS: A total of 150 middle-aged women from the FLAMENCO project (age range 45-60 years) were randomized into a counseling (n = 75) or an exercise (n = 75) group. The exercise group followed a 16-week (3 days/week, 60 min/session) concurrent exercise program (aerobic + resistance training). The counseling group attended conferences on a healthy lifestyle. Participants' health-related quality of life was assessed with the EuroQol plus, a visual analog scale and the 36-item Short Form Health Survey (SF-36), where greater values indicate a better health-related quality of life. RESULTS: The visual analog scale increased by 9.0% in the exercise group, whereas it only increased by 3.5% in the counseling group (p = 0.040). The SF-36 physical function, physical role, bodily pain, vitality and emotional role increased by 5.5%, 11.3%, 10.8%, 9.6% and 8.9%, respectively, in the exercise group, whereas these only increased by 0.6%, decreased by 0.7% and increased by 1.4%, 3.8% and 0.6% in the counseling group (all p < 0.05). CONCLUSIONS: Our results suggest that a 16-week concurrent exercise program adapted for midlife women improved their health-related quality of life. CLINICALTRIALS.GOV IDENTIFIER: NCT02358109. Date of registration: 05/02/2015.

Safety of Bifidobacterium breve, Bif195, employing a human exercise-induced intestinal permeability model: a randomised, double-blinded, placebo-controlled, parallel group trial.

We have previously shown that the probiotic Bifidobacterium breve strain Bif195 alleviates mucosal injury including ulcer formation in the upper intestine induced by non-steroid anti-inflammatory drugs (NSAIDs). Here, we report additional safety use of Bif195 in 126 healthy humans undergoing an exercise-induced intestinal permeability challenge in a double-blinded, placebo-controlled randomised 6-week intervention trial. Intestinal permeability was assessed by urinary lactulose/rhamnose (L/R) ratio. L/R ratio, plasma intestinal fatty acid binding protein (I-FABP) and gastrointestinal symptom rating scale (GSRS) questionnaire were measured resting and after a 1 h treadmill challenge, prior to and at the end of the intervention. To be able to compare the equivalence of resting state at baseline, of this cohort of well-trained subjects, to non-trained subjects, a cohort of 63 healthy and non-trained subjects (<2 h/week of endurance sports) was included. Study subjects (well-trained) were 35.7% women with a mean age and body mass index (in kg/m2) of 35.0 years and 24.8, respectively. There were no differences between the Bif195 and placebo groups in effects on L/R ratio, I-FABP and GSRS questionnaire score. In addition, there were no differences between Bif195 and placebo in number of adverse events and change in cytokines, liver or kidney biomarkers. The exercise model successfully induced intestinal permeability by statistically significantly increasing L/R ratio by ~100% (P<0.0001) and cytokines after the exercise challenge. No significant difference was found between well-trained and non-trained subjects in baseline resting L/R ratio. In conclusion, the reported cytoprotective effects of Bif195 are unlikely to be primarily related to small bowel permeability, and the safety of Bif195 in individuals with increased permeability is supported by the present data. ClinicalTrials.gov: NCT03027583.

SELNET clinical practice guidelines for bone sarcoma.

Bone sarcoma are infrequent diseases, representing < 0.2% of all adult neoplasms. A multidisciplinary management within reference centers for sarcoma, with discussion of the diagnostic and therapeutic strategies within an expert multidisciplinary tumour board, is essential for these patients, given its heterogeneity and low frequency. This approach leads to an improvement in patient's outcome, as demonstrated in several studies. The Sarcoma European Latin-American Network (SELNET), aims to improve clinical outcome in sarcoma care, with a special focus in Latin-American countries. These Clinical Practice Guidelines (CPG) have been developed and agreed by a multidisciplinary expert group (including medical and radiation oncologist, surgical oncologist, orthopaedic surgeons, radiologist, pathologist, molecular biologist and representatives of patients advocacy groups) of the SELNET consortium, and are conceived to provide the standard approach to diagnosis, treatment and follow-up of bone sarcoma patients in the Latin-American context.

Therapeutic response to leflunomide in combo therapy and monotherapy is associated to serum teriflunomide (A77 1726) levels.

There is a significant rate of therapeutic failure in rheumatoid arthritis (RA) patients treated with leflunomide (LEF). This study investigates the utility values of teriflunomide levels (A77 1726) in identifying RA patients who remained with moderate or severe disease activity after the treatment with LEF. In this cross-sectional study, we compared: (a) RA patients who achieved a DAS28-ESR ≤ 3.2, and (b) RA patients who maintained a DAS28-ESR > 3.2 after treatment. ROC curves determined the cut-off of A77 1726 with the better performance to identify patients achieving a DAS28-ESR ≤ 3.2. Of the 115 patients treated with LEF, 69 (60%) remained with moderate/severe disease activity and 46 (40%) achieved low disease activity/remission. Higher A77 1726 levels showed a negative correlation with DAS28-ESR (r = - 0.42, p < 0.001) and other parameters of disease activity. We obtained the following utility values with the cut-off of A77 1726 > 10 µg/mL to identify RA patients who achieved a DAS28-ESR ≤ 3.2: sensitivity of 91.31%; specificity of 73.91%; positive predictive value of 70.00%; and negative predictive value of 92.73%. Serum A77 1726 discriminated between RA patients who remained with moderate/severe disease activity despite the treatment with LEF both as monotherapy and LEF as combo therapy.

Risk of caesarean delivery in labour induction: a systematic review and external validation of predictive models.

BACKGROUND: Despite the existence of numerous published models predicting the risk of caesarean delivery in women undergoing induction of labour (IOL), validated models are scarce. OBJECTIVES: To systematically review and externally assess the predictive capacity of caesarean delivery risk models in women undergoing IOL. SEARCH STRATEGY: Studies published up to 15 January 2021 were identified through PubMed, CINAHL, Scopus and ClinicalTrials.gov, without temporal or language restrictions. SELECTION CRITERIA: Studies describing the derivation of new models for predicting the risk of caesarean delivery in labour induction. DATA COLLECTION AND ANALYSIS: Three authors independently screened the articles and assessed the risk of bias (ROB) according to the prediction model risk of bias assessment tool (PROBAST). External validation was performed in a prospective cohort of 468 pregnancies undergoing IOL from February 2019 to August 2020. The predictive capacity of the models was assessed by creating areas under the receiver operating characteristic curve (AUCs), calibration plots and decision curve analysis (DCA). MAIN RESULTS: Fifteen studies met the eligibility criteria; 12 predictive models were validated. The quality of most of the included studies was not adequate. The AUC of the models varied from 0.520 to 0.773. The three models with the best discriminative capacity were those of Levine et al. (AUC 0.773, 95% CI 0.720-0.827), Hernández et al. (AUC 0.762, 95% CI 0.715-0.809) and Rossi et al. (AUC 0.752, 95% CI 0.707-0.797). CONCLUSIONS: Predictive capacity and methodological quality were limited; therefore, we cannot currently recommend the use of any of the models for decision making in clinical practice. TWEETABLE ABSTRACT: Predictive models that predict the risk of cesarean section in labor inductions are currently not applicable.

Association of objectively measured physical fitness with health-related quality of life of mid-life women: the FLAMENCO project.

OBJECTIVES: This study aimed to explore the association of physical fitness with health-related quality of life (HRQoL) in mid-life women and to examine the potential independent association of physical fitness components with the physical and mental components from the 36-Item Short-Form Health Survey (SF-36) in this population. METHODS: This cross-sectional study comprised 183 mid-life women from southern Spain who participated in the FLAMENCO project. Body composition was measured through an impedanciometer, a stadiometer, and dual-energy X-ray absorptiometry. Physical fitness was objectively measured with the Senior Fitness Test battery (cardiorespiratory fitness, flexibility, and dynamic balance/agility) plus handgrip strength (muscle strength). The SF-36 questionnaire was used to assess HRQoL of the participants. RESULTS: All the physical fitness components were associated with the SF-36 physical function (all p < 0.05) except for lower-body flexibility. The rest of the physical fitness components showed associations with most of the SF-36 dimensions (all p < 0.05). Dynamic balance/agility and upper-body flexibility were independently associated with the SF-36 physical component scale, explaining 15% and 17% of the SF-36 physical component scale, respectively. Any physical fitness component showed independent associations with the SF-36 mental component scale. CONCLUSIONS: Greater physical fitness levels are associated with better HRQoL of mid-life women. Dynamic balance/agility and upper-body flexibility were the strongest independent physical fitness components associated with the SF-36 physical component scale.

Natural sonic crystal absorber constituted of seagrass (Posidonia Oceanica) fibrous spheres.

We present a 3-dimensional fully natural sonic crystal composed of spherical aggregates of fibers (called Aegagropilae) resulting from the decomposition of Posidonia Oceanica. The fiber network is first acoustically characterized, providing insights on this natural fiber entanglement due to turbulent flow. The Aegagropilae are then arranged on a principal cubic lattice. The band diagram and topology of this structure are analyzed, notably via Argand representation of its scattering elements. This fully natural sonic crystal exhibits excellent sound absorbing properties and thus represents a sustainable alternative that could outperform conventional acoustic materials.

Polymorphisms CYP2R1 rs10766197 and CYP27B1 rs10877012 in Multiple Sclerosis: A Case-Control Study.

BACKGROUND: Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease. Low vitamin D levels have been reported to be a risk factor for MS, and genetic variances could be implicated. The aim of this study was to evaluate the association of MS with rs10766197 polymorphism of CYP2R1 gene and rs10877012 polymorphism of CYP27B1 gene. The second aim was to analyse whether these polymorphisms are associated with the severity of the progression of MS. Material and Methods. In a case-control study, we included 116 MS patients and 226 controls, all of whom were Mexican Mestizo. MS was diagnosed by McDonald criteria (2017). A complete neurological evaluation was performed to evaluate the severity of disease progression. Serum 25-hydroxyvitamin D [25(OH) vitamin D] levels were measured by ELISA. Single nucleotide polymorphisms rs10766197 of CYP2R1 gene and rs10877012 SNP of CYP27B1 gene were genotyped by real-time PCR. RESULTS: Serum 25(OH) vitamin D levels were lower in MS patients than in controls (p = 0.009). No differences were observed between serum 25(OH) vitamin D levels of MS patients with severe progression compared to low progression (p = 0.88). A higher frequency of the A allele of CYP2R1 rs10766197 was observed between MS patients and controls (p = 0.05). No differences were observed in the frequency of T allele of CYP27B1 rs10877012 (p = 0.65). In subanalysis, patients with GA + AA genotypes of CYP2R1 rs10766197 had an increased risk of MS compared to controls (p = 0.03). No increased risk was observed in GT + TT genotypes of CYP27B1 rs10877012 (p = 0.63). No differences were observed in allele frequencies of either polymorphism between patients with severe vs. low disease progression. CONCLUSION: Lower serum 25(OH) vitamin D levels were observed in MS patients than in controls, although these levels were not associated with disease progression. Carriers of GA + AA genotypes of CYP2R1 rs10766197 had an increased risk of MS. None of these polymorphisms was associated with severe progression of MS.

Beamforming for large-area scan and improved SNR in array-based photoacoustic microscopy.

Beamforming enhances the performance of array-based photoacoustic microscopy (PAM) systems for large-area scan. In this study, we quantify the imaging performance of a large field-of-view optical-resolution photoacoustic-microscopy system using an phased-array detector. The system combines a low-cost pulsed-laser diode with a 128-element linear ultrasound probe. Signal-to-noise ratio (SNR) and generalized contrast-to-noise ratio (gCNR) are quantified using the phased-array detector and applying three beamforming strategies: a no-beamforming method equivalent to a single-element flat transducer, a fixed focus beamforming method that mimics a single-element focused transducer, and a dynamic focus beamforming using a delay-and-sum (DAS) algorithm. The imaging capabilities of the system are demonstrated generating high-resolution images of tissue-mimicking phantoms containing sub-millimetre ink tubes and an ex vivo rabbit's ear. The results show that dynamic focus DAS beamforming increases and homogenizes SNR along 1-cm2 images, reaching values up to 15 dB compared to an unfocused detector and up to 30 dB compared to out-of-focus regions of the fixed focus configuration. Moreover, the obtained values of gCNR using the DAS beamformer indicate an excellent target visibility, both on phantoms and ex vivo. This strategy makes it possible to scan larger surfaces compared to standard configurations using single-element detectors, paving the way for advanced array-based PAM systems.

Walking in pregnancy and prevention of insomnia in third trimester using pedometers: study protocol of Walking_Preg project (WPP). A randomized controlled trial.

BACKGROUND: Previous studies in pregnancy have not focused in evaluating the effect of walking during pregnancy and prevention of insomnia. Our general objective is to determine the effect of a walking program in preventing the appearance of insomnia in the third trimester of pregnancy, increasing sleep quality and improving quality of life throughout pregnancy. METHODS: Randomized Controlled trial in parallel in healthy sedentary pregnant women (n = 265), Walking_Preg Project (WPP), from university hospital in Granada, Spain. At 12th gestational week (GW), they will be invited to participate and randomly assigned to one of the three arms of study: the intervention group I1 (pedometer, goal of 11,000 steps/day), intervention group I2 (pedometer, no goal) and control (no pedometer). Duration of intervention: 13-32 GW. At 12th, 19th and 31st GW the average steps/day will be measured in groups I1 and I2. At 13th, 20th and 32nd GW, Athens Insomnia Scale (AIS), Pittsburgh Sleep Quality Index (PSQI), Adherence to Mediterranean Diet (AMD), physical activity (short IPAQ), quality of life (PSI), and consumption of toxic substances (caffeine, illegal drugs, alcohol and tobacco) will be collected. Student t test or Mann-Whitney U will be used to compare 19th and 31st GW mean of daily steps between I1 and I2 groups. To compare differences between groups in terms of frequency of insomnia/quality of life for each trimester of pregnancy, Pearson's Chi-square test or Fisher's exact test will be used. To determine differences in hours of sleep and quality of sleep throughout each trimester of pregnancy, analysis of variance or Friedman test will be used. McNemar-Bowker test will be used to assess differences in life quality in pre-post analyses in the 3 arms. We will use Stata 15 statistical software. DISCUSSION: promoting walking in second half of pregnancy through use of pedometer and health pre-registration of a goal to be achieved -'10,000-11,000 steps a day'- should prevent appearance of insomnia in third trimester, will increase sleep quality and quality of life in pregnant women. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03735381 . Registered 8th November, 2018.

Mediterranean diet, tobacco consumption and body composition during perimenopause. The FLAMENCO project.

OBJECTIVE: To study the association of the adherence to the Mediterranean diet (MD) and tobacco consumption with body composition during perimenopause. STUDY DESIGN AND METHODS: A cross-sectional study in 176 perimenopausal women from the FLAMENCO project. A food frequency questionnaire and the Mediterranean Diet Score were assessed. Body composition was measured using dual-energy X-ray absorptiometry. MAIN OUTCOMES MEASURES: Body mass index (BMI), fat mass (FM), ratio of gynecoid to total fat mass (G/T), ratio of android to gynecoid fat mass (A/G), visceral adipose tissue (VAT) and waist circumference (WC). RESULTS: Intake of whole-grain cereals was associated with lower WC, FM percentage, android FM, VAT and higher G/T (all p < 0.05). Intake of nuts was associated with lower BMI and FM percentage and intake of fruits with lower BMI, WC, total and android FM, FM percentage, A/G, VAT and higher G/T (all p < 0.05). Intake of pulses was associated with lower weight, BMI and android FM. Intake of whole dairy products was associated with lower weight, BMI, WC, total and android FM and VAT (all p < 0.05). Intake of olive oil was associated with lower WC and FM percentage (all p < 0.05). Intake of sweetened beverages was associated with higher weight, BMI, WC, FM percentage, android FM, VAT and total FM (all, p < 0.05). Smokers had a lower MD adherence (p < 0.05). Finally, a greater MD adherence was associated with higher G/T (p < 0.01) and lower A/G (p < 0.05). CONCLUSIONS: A higher MD adherence, avoiding tobacco, an increased consumption of whole-grain cereals, nuts, fruits, pulses, whole dairy products and olive oil, and a lower consumption of sweetened beverages might contribute to a healthier body composition during perimenopause.

Disparities in Use of Subspecialty Concussion Care Based on Ethnicity.

Concussion is common and subspecialty care can be essential to ensure recovery. However, barriers may exist to accessing care. This study aimed to assess disparities in subspecialty concussion care related to ethnicity, limited English proficiency (LEP), and insurance status. We utilized logistic regression to analyze 2010-2015 administrative data from four Sports Medicine clinics, comparing odds of being seen for concussion to odds of being seen for fracture by ethnicity, insurance type, and interpreter usage, controlling for demographic factors. ICD-9 codes were used to identify concussion and fracture. Our final sample contained 25,294 subjects: 5621 with concussion and 19,673 with fracture. In bivariate analysis, youth seen for concussion had 83% lower odds of being Hispanic compared with youth seen for fracture (95%CI: 75-92%). Due to interactions between ethnicity and interpreter use, we utilized a stratified multivariate model as our final model. Youth with concussion had 1.8× greater odds of having private insurance compared with youth with fracture (Hispanic OR 1.8, 95% CI 1.5-2.3; Non-Hispanic OR 1.8, 95% CI 1.7-2.0). Youth with concussion also had greater odds of not using an interpreter, though the strength of this association was weaker for Hispanic youth compared with non-Hispanic youth (Hispanic OR 1.68, 95% CI 1.30-2.17; Non-Hispanic OR 4.36, 95% CI 3.00-6.35). Age and sex were included as covariates. In conclusion, our analysis suggests disparities in subspecialty concussion care for Hispanic youth, as well as for individuals with LEP and non-private insurance. Further research should explore means for improving access to concussion care for all youth.