Low Threshold Research Articles

Effect of CD4 count on Mycobacterium tuberculosis infection rates in people living with HIV: a comparative study in prison and community

To evaluate the impact of the CD4 count on ESAT6-CFP10 (EC) skin test, QuantiFERON-TB Gold In-tube test (QFT) and tuberculin skin test (TST) in a large prison and communities in Jiangsu Province among people living with HIV (PLHIV). Participants in communities were tested with the QFT and EC skin test and in prison were tested with the QFT, TST and EC skin test. A 4-knotted restricted cubic spline fitted for Logistic models was used to explore the cutoff point of CD4 count and the associations between changes in CD4 count and Mycobacterium tuberculosis (M.tb) infection. Among 1,815 PLHIV included, 19.3% (350) were from prisons and 80.7% (1465) were identified through community screenings. M.tb infection rates were 12.2% and 8.3% through QFT and EC tests, respectively. Odd Ratios (ORs) for infection increased with CD4 counts, peaking at 618 cells/mm3 for EC, 392 cells/mm3 for QFT, then plateaued. However, the pattern differed for EC between prison and screening scenarios. In prison settings, M.tb infection increased with CD4 count from 0 to 350 cells/mm3, plateaued until 500 cells/mm3, and then persistently increased. Conversely, for community, ORs decreased until 300 cells/mm3, followed by an increase between 300 and 729 cells/mm3, after which they continued to rise persistently. Our cross-sectional study among PLHIV revealed a higher rate of M.tb infection in prison compared to the community. The relationship between CD4 count and infection became negative after a certain threshold. This pivotal point differed with detection methods, with QFT showing lower CD4 thresholds than EC.

Therapeutic drug monitoring in children and adolescents with schizophrenia-spectrum, affective, behavioural, tic and other psychiatric disorders treated with aripiprazole: results of the TDM-VIGIL pharmacovigilance study.

Aripiprazole is approved for various severe mental disorders in adults and adolescents. However, off-label prescribing is common, especially in children and adolescents (youth) in whom aripiprazole therapeutic serum level reference ranges are lacking for any disorders. The aim of the study was to evaluate the relationship between aripiprazole dose and serum concentrations and provide further knowledge on the use of aripiprazole in order to improve drug safety and effectiveness in the treatment of minors. The clinical course of youth treated with aripiprazole in the multicentre pharmacovigilance study TDM-VIGIL was systematically followed and serum concentrations measured. Sex, age, weight and comedications were analysed to identify possible effect modifiers. A preliminary therapeutic reference range was estimated for youth with schizophrenia-spectrum disorders, affective disorders and behavioural/emotional/tic disorders coded as treatment responders based on a Clinical-Global Impressions-Improvement (CGI-I) score of much or very much improved. In 93 youth (mean age = 15.2 ± 2.6, range = 7.4-18.2 years, females = 53%, CGI-Severity = 4.4 ± 1.1, responders = 64%), a positive, moderate correlation between the weight-normalized daily dose (WNDD) and aripiprazole serum concentration (=0.791, p < 0.0001) was found. The WNDD and co-medications that interact with CYP2D6 and CYP3A4 affected aripiprazole serum levels, explaining 64% of the variance. In patients within the preliminary therapeutic ranges determined by interquartile ranges (IQRs), slightly better outcomes and fewer adverse drug reactions were found versus patients within preliminary therapeutic ranges determined by the mean ± SD. The preliminary reference range for paediatric patients with schizophrenia-spectrum disorders calculated by the IQR showed an identical lower threshold (100-230 ng/ml) compared to adult schizophrenia-spectrum disorders patients (100-350 ng/ml). The preliminary therapeutic ranges for patients with affective disorders was: 60-160 ng/ml and for patients with behavioural/tic disorders 60-140 ng/ml. The therapeutic reference ranges for aripiprazole in youth estimated via the 25th and 75th IQRs may result in more clinically relevant therapeutic windows. Further studies need to confirm these results, especially in patients with affective and behavioural/tic disorder diagnoses.

Analysis of platelet transfusion efficacy during extracorporeal membrane oxygenation (ECMO) treatment in pediatric patients post-cardiac surgery-a retrospective cohort study.

Postoperative extracorporeal membrane oxygenation (ECMO) may be necessary for pediatric patients following cardiac surgery, with associated risks of thrombocytopenia and bleeding. Prophylactic platelet transfusions are utilized to mitigate these risks, but the effectiveness of platelet transfusion cannot be reliably predicted. The aim of this study was to investigate the effect of platelet transfusion during postoperative treatment with ECMO in children undergoing cardiac surgery and to explore the optimal transfusion thresholds to reduce the number of platelet transfusions in patients and reduce the risk of death. We included in our study patients from the Pediatric Cardiac Surgery Department at the First Affiliated Hospital of Tsinghua University who underwent cardiac surgery and received ECMO treatment from January 1, 2019, to December 31, 2023, and received platelets transfusion at least once during the ECMO therapy. The platelet counts were determined both before and 24 hours posttransfusion of the platelet product. The corrected count increment (CCI) was calculated for the effectiveness estimation of platelet transfusion. The research subjects were divided into 3 groups based on the platelet count before transfusion (pretransfusion platelet count ≤30×109/L was the low-threshold group, pretransfusion count 31-50×109/L was the medium-threshold group, and ≥51×109/L was the high-threshold group) and the effective rates of each group were calculated. A total of 11 patients received 47 platelet transfusions, an average of 4.27 ± 1.67 per patient. According to the 24-hour postinfusion platelet (Plt) corrected critical control increase index (24-hour CCI) ≥4500, the infusion was considered to be effective, and ineffective when the CCI was <4500. Out of these, 22 transfusions (46.8%) proved effective, whereas 25 (53.2%) were deemed ineffective. The effective transfusion rates across the 3 groups were 69.2%, 50%, and 27.7%, respectively. The efficacy of platelet transfusion may be higher if a low threshold of platelet transfusion is chosen during ECMO treatment, on the premise of ensuring life safety.

A biopsychosocial approach to phenotyping people with knee osteoarthritis awaiting total knee arthroplasty: A secondary cohort analysis

BackgroundPrevious research showed chronic post-total knee arthroplasty (TKA) pain in 20% of people with knee osteoarthritis (KOA). Various preoperative biopsychosocial-related factors have been described, but phenotyping people with KOA awaiting TKA based on these factors is still lacking. This could be relevant to understanding differences in TKA surgery responses. ObjectiveTo identify phenotypes in people with KOA awaiting TKA and differences in post-TKA pain based on preoperative biopsychosocial factors. MethodsPeople with KOA awaiting TKA in 4 hospitals in Belgium and the Netherlands were included. A cross-sectional latent profile analysis was conducted on structural, metabolic, functional, pain-related, psychological and social variables. Concurrent validity was tested using 3-step multinomial logistic regression. The difference in one-year post-TKA pain was examined with linear mixed model analysis. ResultsTwo hundred and seventeen participants were included in the latent profile analysis with a mean (SD) age of 65.5 (7.7) years, including 109 women. A model with 2 phenotypes differed in 14 out of 21 variables. Participants with phenotype 2 (28%) had a higher body mass index (BMI), higher chance of having less structural damage (KOA grade), lower mean quadriceps strength and physical function (Knee Society Scoring System functional and 30-second chair stand test), higher pain intensity, number of pain locations, and indices of central sensitisation (temporal summation, central sensitisation inventory score, and lower pressure pain thresholds), higher pain catastrophising, anxiety and depression, and higher post-TKA pain intensity compared to phenotype 1 (72%). Concurrent validity was confirmed in 3 out of 4 variables. ConclusionsPhenotype 2 (28%) with nociplastic pain characteristics in combination with worse psychological factors, BMI, functional and structural factors, and phenotype 1 (72%) not representing these characteristics were identified. Phenotype 2 had worse pain intensity scores after TKA compared to phenotype 1. Attention to the characteristics of phenotype 2 is warranted concerning post-TKA pain. Database registrationThe protocol is registered at ClinicalTrials.gov (NCT05380648).

Hydrological drought life-cycle: Faster onset and recovery in humid than semi-arid basins in China

The hydrological drought life-cycle begins at the onset and includes intensification and recovery stages. Previous studies have mainly considered each stage separately, so a comprehensive life-cycle pattern analysis is lacking. Moreover, differences in hydrological drought life-cycle patterns across different climatic basins still need in-depth research. This study proposed an integrated framework for analyzing the life-cycle patterns of hydrological droughts and used it to compare semi-arid and humid basins of China. The empirical analysis involved long-term (≥30 years) monthly runoff and precipitation data from six basins—three in semi-arid and three in humid zones of China. We identified the onset thresholds of hydrological drought events from the response relationship of hydrological drought to meteorological drought, considering both duration and severity thresholds. Then, using the “time–speed” process relationship, the intensification and recovery stages of hydrological drought events were quantified. Finally, the life-cycle patterns of hydrological drought in humid and semi-arid basins of China were compared. The results indicated that: (1) the proposed integrated framework, utilizing life-cycle analysis techniques to investigate the onset thresholds, intensification, and recovery of hydrological drought, provided valuable insights into their differences across different climatic basins; (2) compared to the semi-arid basins of northern China, the humid basins exhibited lower onset thresholds, slower intensification, and quicker recovery. This indicated that, in the humid basins of southern China, the onset thresholds for hydrological drought are reached rapidly after meteorological drought, followed by more gradual intensification and faster recovery stages. This underscored the importance of recognizing the distinctive life-cycle patterns of hydrological drought in different climatic zones so that tailored strategies for effective drought prevention and mitigation can be devised

Thiamine: An indispensable regulator of paediatric neuro-cardiovascular health and diseases.

Physicians are recommended to have a low threshold for suspecting thiamine deficiency especially in vulnerable populations. Laboratory diagnosis of thiamine deficiency needs to be implemented as a standard of care, especially in endemic regions. Further, public health policies on food fortification, mandatory supplementation, and surveillance are imperative to eliminate thiamine deficiency-induced health hazards. • South Asian countries report a higher incidence of neonatal and under-five mortalities, many of which are attributed to maternal and perinatal micronutrient deficiencies. • Preventable causes of neonatal/ infantile deaths include birth factors (low birth weight, birth asphyxia), infectious diseases (pneumonia, diarrhoea, tetanus, tuberculosis, measles, diphtheria, malaria, acute infections), deficiency diseases and genetic diseases (vitamin & mineral deficiencies, IEMs, congenital heart disease, unexplained PPHN, SIDS etc). • Acute thiamine deficiency presenting as multisystemic syndromes, has unfortunately been a long standing unresolved public health concern. However, accessible surveillance and diagnostic strategies remain elusive in most clinical settings. • Despite decades of reports and emerging guidelines, diagnosis of thiamine deficiency is often missed and policy mandates at national level are yet to be implemented even in endemic countries. • This review provides a comprehensive summary of the biochemical role of thiamine, its key functions and effects on major organ systems, the diagnostic gap, the enigmatic presentation of acute thiamine deficiency, the plausible role of thiamine in other pathologies and the preventive measures at individual and community level.

Informing HPV vaccine pricing for government-funded vaccination in mainland China: a modelling study

The high price of HPV vaccines remains a significant barrier to vaccine accessibility in China, hindering the country's efforts toward cervical cancer elimination and exacerbating health inequity. We aimed to inform HPV vaccine price negotiations by identifying threshold prices that ensure that a government-funded HPV vaccination programme is cost-effective or cost-saving. We used a previously validated transmission model to estimate the health and economic impact of HPV vaccination over a 100-year time horizon from a healthcare payer perspective. Threshold analysis was conducted considering different settings (national, rural, and urban), cervical cancer screening scenarios (cytology-based or HPV DNA-based, with different paces of scale-up), vaccine types (four types available in China), vaccine schedules (two-dose or one-dose), mode of vaccination (routine vaccination with or without later switching to high-valency vaccines), willingness-to-pay thresholds, and decision-making criteria (cost-effective or cost-saving). Furthermore, we examined the budget impact of introducing nationwide vaccination at the identified threshold prices. Using the current market price, national routine HPV vaccination with any currently available vaccine is unlikely cost-effective. Under a two-dose schedule, the prices of the four available HPV vaccine types cannot exceed $26-$36 per dose (44.1%-80.2% reduction from current market prices) depending on vaccine type to ensure the cost-effectiveness of the national programme. Adopting vaccination at threshold prices would require an annual increase of 72.18%-96.95% of the total annual National Immunization Programme (NIP) budget in China. A cost-saving routine vaccination programme requires vaccine prices of $5-$10 per dose (depending on vaccine type), producing a 21.38%-34.23% increase in the annual NIP budget. Adding the second dose is unlikely to be cost-effective compared to a one-dose schedule, with the threshold price approaching or even falling below zero. Rural pilot vaccination programmes require lower threshold prices compared with a national programme. Our study could inform vaccine price negotiation and thus facilitate nationwide scale-up of current HPV vaccination pilot programmes in China. The evidence may potentially be valuable to other countries facing HPV introduction barriers due to high costs. This approach may also be adapted for other contexts that involve the introduction of a pricy vaccine. CAMS Innovation Fund for Medical Sciences (CIFMS); Bill & Melinda Gates Foundation.

The Relationship Between the Elastic Properties and Pain Pressure Threshold in Cesarean Scar Tissue—An Observational Study

Background/Objectives: Cesarean section (C-section) scars can lead to chronic pain due to changes in tissue properties. Combining elastography and algometry can assess these scars comprehensively by identifying areas of increased rigidity and quantifying pain sensitivity. This study aims to evaluate the efficacy of using elastography and algometry together to assess cesarean scar tissue, correlating tissue stiffness with pain thresholds for targeted pain management. Methods: Thirty-one non-pregnant women who had undergone a C-section between six months and two years prior participated. Elastography measured tissue stiffness, while algometry provided quantitative measures of pain sensitivity on and around the scar. The correlation between tissue stiffness and pain thresholds was analyzed. Results: Elastography identified areas of increased rigidity within the scar tissue, which corresponded with lower pain thresholds measured by algometry, indicating higher pain sensitivity. A significant correlation was found between increased tissue stiffness and reduced pain thresholds (p &lt; 0.05). Conclusions: Combining elastography and algometry offers a powerful diagnostic tool for evaluating C-section scars. This approach identifies areas that may benefit from targeted pain management interventions, enhancing understanding and treatment of pain associated with cesarean scars. Incorporating these techniques into clinical practice could improve patient outcomes and quality of life.

LiLnGeS4 (Ln=La-Nd): Designing High Performance Infrared Nonlinear Optical Sulfides through "Band Reformation of AGS".

AgGaS2 (AGS) is the most commonly used commercial infrared nonlinear optical (IR NLO) material. However, AGS has a narrow band gap (Eg=2.58 eV) and a low laser-induced damage threshold (LIDT), primarily attributed to its mobile liquid-like Ag+ constituent and the unstable Ag-S chemical bond. Herein, we propose a "band reformation of AGS" strategy, which leads to the successful syntheses of four lanthanide sulfides, LiLnGeS4 (Ln=La-Nd), crystalizing in an asymmetric Ama2 structure. LiLaGeS4 demonstrates that eliminating the presence of Ag-4d band increases the Eg to 3.32 eV and enhances the LIDT (14-29×AGS, measured by both powder and single crystal); while increasing the nonbonding density of states of the S-3p band enhances the 2nd-nonlinear optical coefficient (1.06×AGS). Besides, the bond length discrepancy between [LiS4], [GeS4] and [LaS8] units leads to a moderate birefringence (Δn=0.052). Such a unique structure further results in extremely small thermal expansion with αL=0.41-1.74×10-5 K-1, along different crystallographic axes. Our theoretical studies indicate that the synergy of the structure building units contribute to the second harmonic generation performance. These results suggest that the "band reformation of AGS" strategy provides effective guidance to discover new NLO crystals with optimized performance.

Influence of SST‐Precipitation Relationship Over the Equatorial Western Pacific on Simulation of the Madden‐Julian Oscillation

AbstractCapabilities of 43 models of the Coupled Model Intercomparison Project Phase 6 (CMIP6) to simulate the Madden‐Julian Oscillation (MJO) were compared in this study. Models with higher MJO simulation skills reproduce organized large‐scale convection more frequently over the equatorial western Pacific (EWP), suggesting that MJO simulations are tightly connected to organization of large‐scale precipitation over the EWP. MJO simulation skills are not significantly correlated with the mean sea surface temperature (SST) over the EWP, but tightly connected to SST threshold for convection there. The top simulations exhibit lower SST threshold and more realistic SST‐precipitation relationship over the EWP, suggesting that convection can be organized more efficiently and intensified more rapidly with the increasing SST in these simulations. Our results emphasize that reproducing the relationship between SST and large‐scale precipitation over the EWP is critical to MJO simulations.

A study to explore the role of a low threshold, fitness focussed physical rehabilitation intervention with protein supplementation to target physical function and frailty in people with problematic substance use and homelessness: protocol for a single-arm pre-post intervention study.

Background People who are homeless are more likely to experience poor mental health and addiction as well as suffering from non-communicable diseases. There is evidence of frailty and accelerated physical ageing among people experiencing homelessness. Appropriate physical rehabilitation and nutritional supplementation strategies can stabilise or reverse frailty and general physical decline, but it is not known how this type of intervention would work in practice in this population. Aim To evaluate the feasibility and pre-post intervention impact of a low threshold physical rehabilitation intervention with protein supplementation to target physical functioning and frailty in people with problematic substance use who are experiencing homelessness. Methods The intervention will consist of a 12-week low threshold rehabilitation programme with protein supplementation. Participants will be service users of the Ballyfermot Advance Project, a day services centre for people with addiction issues and experiencing homelessness. Primary outcomes will be feasibility including numbers recruited, retention of participants and adherence to the exercise intervention and protein supplement. Any adverse events will be recorded. Secondary outcomes will be strength and muscular mass, physical performance and lower extremity physical function, pain, frailty and nutritional status. Discussion An immediate impact may be simply a distraction from difficult circumstances and potentially an improvement of physical health of participants, which can be a conduit for the emergence of other positive behaviours and recovery. Longer term, this study will generate preliminary data on which to inform the design of a definitive randomised controlled trial of physical rehabilitation and protein supplementation, if indicated. Ethics and dissemination Ethical approval was granted by the Faculty of Health Sciences Research Ethics Committee in TCD. Study findings will be disseminated through publication into an international peer-reviewed journal and presented at national and international conferences.

Enhanced Optical Bistability of a Metasurface Based on Asymmetrically Optimized Mirror-Induced Magnetic Anapole States

In the field of modern optical computing and communication, optical bistability plays a crucial role. With a weak third-order nonlinear coefficient, low switch thresholds of optical bistability from Si-based nanophotonic structures remain a challenge. In this work, a metasurface consisting of silicon nanostrip arrays placed on the optically thick silver film is proposed. The light–matter interaction is enhanced by mirror-inducing the magnetic anapole states (MASs) and asymmetrically optimizing its silicon nanostrip. Numerical results show that the average enhancement factor (EF) of an electric field can be greatly enhanced to be 1524.8. Moreover, the optical bistability of the proposed metasurface achieves the thresholds of ION-OFF and IOFF-ON of 8.5 MW/cm2 and 7.1 MW/cm2, respectively, which is the lowest threshold when compared to the previous works based on silicon nanostructures. The angular dependance of the bistability performance is also investigated. This work facilitates the proposed hybrid metasurface in the fields of miniaturized all-optical switches and modulators, which are key components in optical computing and communication.

Spinal hyperexcitability in patients with chronic musculoskeletal pain or headache as evidenced by alterations in the nociceptive withdrawal reflex: a systematic review and meta-analysis.

The nociceptive withdrawal reflex (NWR) is a spinal withdrawal reflex induced by painful stimulation. It is a measure of spinal hyperexcitability, which is believed to contribute to chronic musculoskeletal pain (MSKP) and headache. Previous syntheses of the evidence for alterations in the NWR in patients with chronic MSKP and headache needed a comprehensive update. This systematic review and meta-analysis was performed after the Preferred Items for Systematic reviews and Meta-Analyses guidelines. Studies examining NWR-related outcome measures in patients with chronic MSKP and headache compared to pain-free controls were identified through electronic database searches and included after screening against predefined eligibility criteria. Standardized mean differences or mean differences and 95% confidence intervals (CI) were calculated. Thirty-one studies were included in the systematic review and 25 in the meta-analysis. Moderate-quality evidence was found indicating lower NWR threshold (-3.68; 95% CI, -4.56 to -2.80; P < 0.001), larger NWR area (standardized mean difference = 0.69; 95% CI, 0.37-1.01; P < 0.001), and shorter NWR latency (mean difference = -13.68; 95% CI, -22.69, -4.67; P = 0.003) in patients compared to controls. These findings remained robust when performing meta-regressions based on subgroups (ie, headache, fibromyalgia, whiplash-associated disorder, and osteoarthritis). Low-quality evidence demonstrated facilitated temporal summation of NWR threshold (-2.48; 95% CI, -3.13 to -1.83; P < 0.001) in patients compared to controls. Spinal hyperexcitability as evidenced by lowered NWR threshold values and temporal summation of the NWR is present in patients with chronic MSKP and headache. No evidence was found for alterations in NWR duration and NWR magnitude. Future research is needed to address the gap in research on NWR-related outcome measures other than NWR threshold.

Formative feedback through digital MCQs: Students´ perceived learning in a bachelor-level physiology course

Feedback is defined as a process in which students can benefit from information about their own performance to improve the quality of their work and learning strategies. This case study examines how students in a bachelor-level physiology course experienced their learning when receiving formative feedback through digital multiple-choice questions (MCQs) in the web-based learning platform Canvas. The poorly attended colloquia in the course were replaced by a compulsory assignment comprising eight modules of MCQs. The MCQs could be repeated multiple times by the students providing ample low threshold, low risk opportunities to test knowledge and understanding and to receive feedback on whether they had achieved the learning objectives of the course (“feedback loops”). A student survey at the end of the course underlined the potential of using MCQs for automated feedback and learning. Thematic analysis of semi-structured one-on-one interviews with eight random students from the course identified two main themes related to student learning: the importance of the MCQs format and how student characteristics can affect MCQ-aided learning. Challenges were related to the formulations of the MCQs, and the feedback received, and to procrastination of the students’ work with the MCQs reducing the learning outcome of the work. We discuss the potential of further developing and integrating online formative feedback loops through MCQs as a systematic approach to enhance learning and emphasize the importance of student and teacher feedback literacy when working with assessments tasks such as MCQs.

Anatomical characteristics of the phrenic nerve and the spontaneous conduction block between the right atrium and the superior vena cava

Abstract Introduction Although the superior vena cava isolation (SVCI) with minimal radiofrequency application using a spontaneous right atrium – superior vena cava (RA-SVC) conduction block has been reported, the anatomical characteristics of the spontaneous RA-SVC conduction block is not clear. Purpose The aim of this study to evaluate the anatomical relationship between the spontaneous RA-SVC conduction block and the phrenic nerve (PN). Methods This study consisted of 73 patients who attempted to undergo SVCI using a RA-SVC conduction block. The RA-SVC conduction block was visualized using the extended early meets late tool with the CARTO3 system. We set the first lower threshold at 1800/total local activation time to optimize the visualization of spontaneous RA-SVC conduction block. If the SVC was not isolated by ablation to the gap of the visualized conduction block line, the lower threshold was increased by 5%, and the new gap was ablated each time. The course of the right PN was detected by pacing with 20 mA /2 ms. The RA-SVC conduction block and the course of the PN were measured with reference to the height of the left atrial roof. The extend of the RA-SVC conduction block and PN were measured in angles with respect to the ventral side (Figure 1). These anatomical parameters were compared between the RA-SVC block line and the PN. Results Sixty-one patients (83.6%) had spontaneous RA-SVC conduction block, and the remaining 12 patients (16.4%) did not. Anatomical characteristics were evaluated in 61 patients with spontaneous RA-SVC conduction block. Compared with the course of the PN, RA-SVC conduction block extended more posteriorly (110 degrees vs 128 degrees, P = 0.013) and more caudally (9.5 mm vs 16.1 mm, P&amp;lt;0.0001) (Figure 2). In the patients who underwent SVCI using a RA-SVC conduction block, any patients did not undergo radiofrequency application on the course of the PN. Conclusion Since the caudal end of the RA-SVC conduction block is posterior to the caudal end of the phrenic nerve, SVCI using the RA-SVC conduction block may be able to avoid ablation near the PN.Figure1Figure2

Residual risk post acute coronary syndroms after 1 year of cardiac rehabilitation. Can we improve it?

Abstract How much do we reduce residual risk with a cardiac rehabilitation program? What is left to do? Which would be the impact of a lower cholesterol threshold for the use of more potent lipid lowering drugs on residual risk? We explored these issues. Methods We retrospectively analyzed clinical and biochemical data from patients after 1 year of cardiac rehabilitation following an acute coronary event. Changes in residual risk of combined myocardial infarction, stroke and cardiovascular death, and its modification with optimization of treatment in patients with suboptimal lipid control, and with the use of PCSK9 inhibitors in those with a LDL-cholesterol over 70 mg/dl, were estimated using the SMART-REACH model calculator. Wilcoson and McNemar tests for paired-samples were used in the statistical análisis. Results 262 consecutive patients were included. Median age was 63.5 years, 80.5% men, 89.3% stented. Baseline use of high intensity statins was 90.8%. After 1 year, the use of Ezetimibe was doubled to 77.1%, empaglifozin to 26%, and PCSK inhibitors were used only in 5%, with a residual use of colchicine. Blood pressure and Cholesterol profile improved after 1 year, with no change in HbA1c. Absolute 10- years and life-long residual risk were reduced 4.8% (95%CI:3.6-5.9) and 6% (95%IC: 4.5-7.5) respectively (both p&amp;lt;0.001). LDL-cholesterol was &amp;gt;55 mg/dl with a suboptimal lipid lowering treatment in 29.8% of patients: an optimization to higher dose of rosuvastatin/atorvastatin plus ezetimibe would decrease absolute 10-years and life-long residual risk in 7.2% (95%CI: 4.9-9.4) and 9.9% (95%CI: 6.4-13.5%) respectively (both p&amp;lt;0.001). LDL-cholesterol remained &amp;gt; 70 mg/dl after higher dose of statin plus ezetimibe in 13.7% of patients: use of PCSK9 inhibitors in this group would reduce absolute 10-year and life-long residual risk in an additional 5.4% (95%CI:2.4-7,6;p=0,018) and 7% (95%CI: 3,8-10,1) compared to maximal dose of statins plus ezetimibe. Conclusions Cardiac rehabilitation programs reduce cardiac risk 1 year after an acute coronary event. Residual risk remain very high, and a significant proportion of patients do not reach recommended targets and optimal lipid lowering treatment. Optimization of lipid lowering drugs, and a lower LDL-cholesterol threshold for the use of PCSK9 inhibitors, would have a significant impact on residual risk.Changes in residual riskPCSK9-inhibitors in LDLchol &amp;gt;70 mg/dl

Vibration Thresholds Using Conventional Audiometry are Clinically Useful Indicators of Postural Instability in Older Adults.

Falls are a major health concern with potentially dramatic consequences for people over 65 years of age. One crucial determinant in the risk of falls in older adults is postural control, a complex process that requires the contribution of different sensory modalities, namely visual, vestibular, auditory, and somatosensory. While there are well-established methods to screen for age-related vision, hearing, tactile, and vestibular impairments, there are very few widely available methods to screen for somatosensory function, but studies indicate that ankle audiometry (vibration thresholds) using a common B-71 bone vibrator can serve that purpose. To date, unfortunately, this technique has received little attention as a tool to measure postural instability in older adults. The objective of the present study was to examine postural control in older adults with and without degradation of the somatosensory functions, as determined with ankle audiometry. This was standard group comparison. In total, 36 healthy elderly aged between 65 and 80 years old were divided into two groups (low vibration threshold [n = 18] and high vibration threshold [n = 18]). Standard audiometry, video head impulse test, vibration thresholds (big toe, ankle, and tibia), and static postural control task using a force platform were performed. Greater postural instability in participants with higher (worse) vibration thresholds as compared with participants with lower (better) vibration thresholds was observed even though both groups were comparable on hearing threshold and vestibular function. The results indicate that performing a simple vibration threshold evaluation, using a clinically available B-71 with a cut-off value of 42 dB hearing loss, could be an effective, fast, and easy-to-use procedure for detecting people at risk of falls.

That's Not a Hybrid: How to Distinguish Patterns ofAdmixture and Isolation By Distance.

Describing naturally occurring genetic variation is a fundamental goal of molecular phylogeography and population genetics. Popular methods for this task include STRUCTURE, a model-based algorithm that assigns individuals to genetic clusters, and principal component analysis (PCA), a parameter-free method. The ability of STRUCTURE to infer mixed ancestry makes it popular for documenting natural hybridisation, which is of considerable interest to evolutionary biologists, given that such systems provide a window into the speciation process. Yet, STRUCTURE can produce misleading results when its underlying assumptions are violated, like when genetic variation is distributed continuously across geographic space. To test the ability of STRUCTURE and PCA to accurately distinguish admixture from continuous variation, we use forward-time simulations to generate population genetic data under three demographic scenarios: two involving admixture and one with isolation by distance (IBD). STRUCTURE and PCA alone cannot distinguish admixture from IBD, but complementing these analyses with triangle plots, which visualise hybrid index against interclass heterozygosity, provides more accurate inference of demographic history, especially in cases of recent admixture. We demonstrate that triangle plots are robust to missing data, while STRUCTURE and PCA are not, and show that setting a low allele frequency difference threshold for ancestry-informative marker (AIM) identification can accurately characterise the relationship between hybrid index and interclass heterozygosity across demographic histories of admixture and range expansion. While STRUCTURE and PCA provide useful summaries of genetic variation, results should be paired with triangle plots before admixture is inferred.

The importance of taste salt sensitivity in the development of kidney damage in patients with high-risked arterial hypertension

Abstract Purpose of the study to evaluate the diagnostic significance of determining taste salt sensitivity in kidney damage development in patients with high-risked arterial hypertension. Material and methods The study included 1021 patients with arterial hypertension (AH), 60% women, 40% men, aged 58.05±7.95 years. All patients underwent the R.Henkin test to determine the threshold of taste sensitivity to table salt in the family polyclinics of Aral Sea region. All patients underwent a complete blood count, a complete urinalysis, biochemical tests, determination of serum creatinine with calculation of glomerular filtration rate, microalbuminuria, urine albumin-to-creatinine ratio and uric acid level. Results Low and medium thresholds of taste salt sensitivity were determined in 149 patients (14.6%, group 1), the average NaCl concentration was 0.15±0.02%. A high threshold of taste salt sensitivity was detected in 872 patients (85.4%, group 2), the average NaCl concentration was 0.64±0.57% (p=0.0001). Patients of the 1st and 2nd groups differed in the level of systolic and diastolic blood pressure (SBP and DBP): 150.8±10.0 mmHg. versus 172.0±16.7 mmHg. p=0.0001 for SBP, 91.4±3.8 mmHg versus 100.7±10.13 mmHg, p=0.0001 for DBP in the 1st and 2nd groups respectively. At the same time, there was a noticeable direct correlation between hemodynamic parameters – SBP / DBP and NaCl concentration in the test for determining the taste sensitivity to table salt threshold (r = 0.646; r = 0.610, respectively). As a result, were detected significantly differences in GFR: 97.22±11.42 versus 70.33±16.56 (p=0.0001); MAU: 58.64±35.45 vs. 215.9±126.65 (p=0.0001); albumin to creatinine ratio: 47.88±42.73 vs. 268.46±261.05 (p=0.0001); uric acid: 227.67±43.75 vs. 337.17±86.52 (p=0.0001), for 1st and 2nd groups respectively. Conclusion A high threshold of taste salt sensitivity, determined by the R.Henken method, is associated with the level of SBP, DBP, markers of kidney damage and the level of uric acid, which increases the diagnostic significance of determining taste salt sensitivity in patients with hypertension.

Molybdenum temporary epicardial pacing wires: function and biodegradation

Abstract Cardiac pacing with temporary epicardial pacing wires (TEPW) is used to treat rhythm disturbances after cardiac surgery. Wires typically begin to fail around postoperative day four and are extracted. Occasionally, TEPW cannot be mechanically removed, have to stay in the thorax and may rarely cause serious complications like migration and infection. We aim to develop novel, bioresorbable TEPW which will dissolve over time, even if postoperative removal is unsuccessful. We manufactured prototypical braided molybdenum (Mo) leads (16 Mo wires of 40 µM diameter each, length 18 cm for ex vivo, 7.5 cm for in vivo experiments) coated with the biodegradable polymers poly(lactide-co-glycolic acid) (PLGA, inner coating) and polycaprolactone (PCL, outer coating) for shaping and electrical insulation. Mo electrodes showed similar pacing and sensing properties to conventional steel electrodes (Osypka) in Langendorff-perfused rat hearts, even with somewhat lower stimulation thresholds. In artificial body fluid at 37°C, the polymer-coated Mo electrodes dissolved at a rate of 1.6 ± 0.3 µg/cm2·d (n = 5) compared to uncoated electrodes with 30.3 ± 0.8 µg/cm2·d (n = 4, p &amp;lt; 0.001). Assessing apoptosis and necrosis in human cardiomyocytes and cardiac fibroblasts, we detected no toxicity at Mo concentrations up to 0.52 mM. To test the in vivo properties of Mo TEPW, we sutured them epicardially onto the anterior wall of the heart of female Wistar rats, led them out of the thorax through an intercostal space and placed them in a subcutaneous pocket. We tested electrophysiological properties directly after implantation and after different time periods. Mo TEPW showed similar pacing and sensing properties directly upon implantation and after 2 weeks, with only impedance and slew rate of the sensed R-wave decreasing time-dependently. After one month, all but one pair of Mo electrodes were mechanically broken at their exit from the thorax, the site of assumedly highest mechanical stress. Progressive Mo degradation led to multiple fragmentation of the Mo TEPW after 6 months. The conventional steel TEPW we used as control had similar electrical properties directly after implantation, after 2 weeks and one month without signs of broken electrodes. After 6 months, all but one pair of steel electrodes were mechanically broken at their thorax exit site. Comparing urinary Mo concentration of Mo TEPW treated rats to controls, we saw similar values of 1.9 ± 1.9 µM (n = 6) vs. 0.6 ± 0.2 µM (n = 5, n.s.) after one week. In contrast, we saw a significant increase of 12.1 ± 9.7 µM (n = 5) vs. 1.0 ± 0.9 µM (n = 5, p &amp;lt; 0.001) after 6 months, reflecting the degradation progress. We demonstrate that Mo TEPW are a feasible option for epicardial pacing in vivo for up to 2 weeks and observed the progress of Mo degradation up to 6 months. These findings represent an important step in the development of bioresorbable TEPW as a novel and even safer approach to temporary epicardial pacing.Graphical AbstractIn Vivo Degradation Progress