Search

Abstract Background The deterioration of the central cholinergic system in aging is hypothesized to underlie declines in several cognitive domains, including memory and executive functions. However, there is surprisingly little direct evidence regarding acetylcholine’s specific role(s) in normal human cognitive aging. Methods We used short-latency afferent inhibition (SAI) with transcranial magnetic stimulation (TMS) as a putative marker of cholinergic activity in vivo in young (n = 24) and older adults (n = 31). Results We found a significant age difference in SAI, concordant with other evidence of cholinergic decline in normal aging. We also found clear age differences on several of the memory and one of the executive function measures. Individual differences in SAI levels predicted memory but not executive functions. Conclusion Individual differences in SAI levels were better predictors of memory than executive functions. We discuss cases in which the relations between SAI and cognition might be even stronger, and refer to other age-related biological changes that may interact with cholinergic activity in cognitive aging.

Abstract Background Haptic sensing with the fingers represents a unique class of manipulative actions, engaging motor, somatosensory and associative areas of the cortex while requiring only minimal forces and relatively simple movement patterns. Using transcranial magnetic stimulation (TMS), we investigated task-related changes in motor evoked potential (MEP) amplitude associated with unimanual haptic sensing in two related experiments. In Experiment I, we contrasted changes in the excitability of the hemisphere controlling the task hand in young and old adults under two trial conditions, i.e. when participants either touched a fine grating (smooth trials) or touched a coarse grating to detect its groove orientation (grating trials). In Experiment II, the same contrast between tasks was performed but with TMS applied over the hemisphere controlling the resting hand, while also addressing hemispheric (right vs. left) and age differences. Results In Experiment I, a main effect of trial type on MEP amplitude was detected (p = 0.001), MEPs in the task hand being ~50% larger during grating than smooth trials. No interaction with age was detected. Similar results were found for Experiment II, trial type having a large effect on MEP amplitude in the resting hand (p < 0.001) owing to selective increase in MEP size (~2.6 times greater) for grating trials. No interactions with age or side (right vs. left) were detected. Conclusions Collectively, these results indicate that adding a haptic component to a simple unilateral finger action can elicit robust corticomotor facilitation not only in the working hemisphere but also in the opposite hemisphere. The fact that this facilitation seems well preserved with age, when task difficulty is adjusted, has some potential clinical implications.

Abstract Background Recently, we showed a selective enhancement in corticospinal excitability when participants actively discriminated raised 2-D symbols with the index finger. This extra-facilitation likely reflected activation in the premotor and dorsal prefrontal cortices modulating motor cortical activity during attention to haptic sensing. However, this parieto-frontal network appears to be finely modulated depending upon whether haptic sensing is directed towards material or geometric properties. To examine this issue, we contrasted changes in corticospinal excitability when young adults (n = 18) were engaged in either a roughness discrimination on two gratings with different spatial periods, or a 2-D pattern discrimination of the relative offset in the alignment of a row of small circles in the upward or downward direction. Results A significant effect of task conditions was detected on motor evoked potential amplitudes, reflecting the observation that corticospinal facilitation was, on average, ~18% greater in the pattern discrimination than in the roughness discrimination. Conclusions This differential modulation of corticospinal excitability during haptic sensing of 2-D patterns vs. roughness is consistent with the existence of preferred activation of a visuo-haptic cortical dorsal stream network including frontal motor areas during spatial vs. intensive processing of surface properties in the haptic system.

Abstract Background Active contraction leads to facilitation of motor responses evoked by transcranial magnetic stimulation (TMS). In small hand muscles, motor facilitation is known to be also influenced by the nature of the task. Recently, we showed that corticomotor facilitation was selectively enhanced when young participants actively discriminated tactile symbols with the tip of their index or little finger. This tactile-dependant motor facilitation reflected, for the large part, attentional influences associated with performing tactile discrimination, since execution of a concomitant distraction task abolished facilitation. In the present report, we extend these observations to examine the influence of age on the ability to produce extra motor facilitation when the hand is used for sensory exploration. Methods Corticomotor excitability was tested in 16 healthy seniors (58-83 years) while they actively moved their right index finger over a surface under two task conditions. In the tactile discrimination (TD) condition, participants attended to the spatial location of two tactile symbols on the explored surface, while in the non discrimination (ND) condition, participants simply moved their finger over a blank surface. Changes in amplitude, in latency and in the silent period (SP) duration were measured from recordings of motor evoked potentials (MEP) in the right first dorsal interosseous muscle in response to TMS of the left motor cortex. Results Healthy seniors exhibited widely varying levels of performance with the TD task, older age being associated with lower accuracy and vice-versa. Large inter-individual variations were also observed in terms of tactile-specific corticomotor facilitation. Regrouping seniors into higher (n = 6) and lower performance groups (n = 10) revealed a significant task by performance interaction. This latter interaction reflected differences between higher and lower performance groups; tactile-related facilitation being observed mainly in the former group. Latency measurements and SP durations were not affected by task conditions. Conclusions The present findings provide further insights into the factors influencing task-dependant changes in corticomotor excitability in the context of aging. Our results, in particular, highlight the importance of adjusting task demands and controlling for attention when attempting to elicit task-specific motor facilitation in older persons engaged in fine manual actions. Such information could be critical in the future for planning interventions to re-educate or maintain hand function in the presence of neurological impairments.

Abstract Background At the last glacial maximum, Fennoscandia was covered by an ice sheet while the tundra occupied most of the rest of northern Eurasia. More or less disjunct refugial populations of plants were dispersed in southern Europe, often trapped between mountain ranges and seas. Genetic and paleobotanical evidences indicate that these populations have contributed much to Holocene recolonization of more northern latitudes. Less supportive evidence has been found for the existence of glacial populations located closer to the ice margin. Scots pine (Pinus sylvestris L.) is a nordic conifer with a wide natural range covering much of Eurasia. Fractures in its extant genetic structure might be indicative of glacial vicariance and how different refugia contributed to the current distribution at the continental level. The population structure of Scots pine was investigated on much of its Eurasian natural range using maternally inherited mitochondrial DNA polymorphisms. Results A novel polymorphic region of the Scots pine mitochondrial genome has been identified, the intron 1 of nad7, with three variants caused by insertions-deletions. From 986 trees distributed among 54 populations, four distinct multi-locus mitochondrial haplotypes (mitotypes) were detected based on the three nad7 intron 1 haplotypes and two previously reported size variants for nad1 intron B/C. Population differentiation was high (GST = 0.657) and the distribution of the mitotypes was geographically highly structured, suggesting at least four genetically distinct ancestral lineages. A cosmopolitan lineage was widely distributed in much of Europe throughout eastern Asia. A previously reported lineage limited to the Iberian Peninsula was confirmed. A new geographically restricted lineage was found confined to Asia Minor. A new lineage was restricted to more northern latitudes in northeastern Europe and the Baltic region. Conclusion The contribution of the various ancestral lineages to the current distribution of Scots pine was asymmetric and extant endemism reflected the presence of large geographic barriers to migration. The results suggest a complex biogeographical history with glacial refugia shared with temperate plant species in southern European Peninsulas and Asia Minor, and a genetically distinct glacial population located more North. These results confirm recent observations for cold tolerant species about the possible existence of refugial populations at mid-northern latitudes contributing significantly to the recolonization of northern Europe. Thus, Eurasian populations of nordic plant species might not be as genetically homogenous as assumed by simply considering them as offsets of glacial populations located in southern peninsulas. As such, they might have evolved distinctive genetic adaptations during glacial vicariance, worth evaluating and considering for conservation.

Abstract Background Primary prevention of breast cancer through prophylactic mastectomy can reduce the risk of malignancy in high-risk individuals. No type of mastectomy completely removes all breast tissue, but a subcutaneous mastectomy leaves more tissue in situ than does a simple mastectomy. Case presentation We report a case of invasive breast cancer in a BRCA2-positive woman 33 years after bilateral subcutaneous mastectomy. To our knowledge, only one case of primary breast cancer after prophylactic mastectomy in a BRCA1-positive patient has been reported in the literature and none in BRCA2-positive individuals. Conclusion Careful documentation and long follow-up is essential to fully assess the benefits and risks of preventive surgical procedures in BRCA1 and BRCA2 mutation carriers.

The objective of this phase II prospective single-arm trial is to assess the impact of targeted intraoperative radiotherapy (TARGIT) following breast conserving surgery (BCT) on locoregional recurrence (LRR), overall survival (OS), post-operative complications, and assess radiation therapy side effects in patients with early-stage breast cancer (BC). From September 2013 until March 2021, all patients aged 50 and above diagnosed with biopsy-proven hormone receptor-positive, low to intermediate grade cT1N0 invasive ductal carcinoma of the breast were eligible to be in the study upon consent. Enrolled patients underwent BCT followed by TARGIT of 20 Gy in 1 fraction. Upon final pathology, patients with low-risk breast cancer (LRBC) criteria were assigned to receive no further EBRT. Further EBRT was given to patients with the following high-risk breast cancer (HRBC) criteria; histological grade III, pathological tumor size > 2cm, positive lymphovascular invasion (LVI), multifocal disease, close margins, or positive nodal disease. A total of 61 patients were enrolled in the study. The median age was 70.1 years old. From all, 40 (65.6%) patients were LRBC and 21 (34.4%) were HRBC and received further EBRT as per protocol. The median follow-up was 3.9 years. For both groups, LRR was 0%. At 3.9 years the OS for LRBC group was 95.2% and for the HRBC group was 97.6%, with no significant difference among them. The most frequent indications for further EBRT were, close surgical margins in 66.6% (n=14), LVI in 28.6% (n=6) and other in 4.8% (n=1). In the LRBC group, one patient developed contralateral breast cancer, and in the HRBC group receiving further EBRT, one patient developed metastatic disease from a non-breast primary. No grade 3 or 4 radiation therapy toxicities were observed in either group. The most common postoperative complications were seroma and cellulitis, with no significant difference between groups. In patients with early-stage breast cancer undergoing BCT, the use of TARGIT showed excellent outcomes in terms of LRR and OS, with no grade 3-4 radiation therapy toxicities or postoperative complications. Altogether, these results highlight that TARGIT is a clinically safe treatment for carefully selected early-stage breast cancer patients with no pathological high-risk features. Nevertheless, the rate of patients receiving further EBRT was 34.4% in our series, suggesting that quality of life and cost-effectiveness analyses are needed to identify the potential benefits of offering TARGIT instead of conventional whole-breast EBRT. [ABSTRACT FROM AUTHOR]

Effect of interannual climate variations on radial growth was compared among jack pine (Pinus banksiana Lamb.) of diverse geographical origins in a 41-year-old common-garden experiment in Petawawa, Ontario. Provenance experiments established from seeds transferred from different parts of a species range (from the northern United States to northern Canada) to the same environment might be considered as a simulation model of climate change and a shift of climate zones. The following questions are addressed: Did the response of growth to interannual climate variations differ among the provenances transferred within the experimental site? What climatic factors affect interannual growth variations of jack pine provenances? Tree-ring chronologies for 16 populations were developed for the period 1970–2004. The best climate predictors of radial growth were precipitation of June and March of the current year and precipitation of December of the previous year. Although, climatic factors affecting growth were similar between the provenances, absolute radial growth was proportional to the growth potential of the provenances. We conclude that variability due to seeds origins is not a significant source of variation for dendroclimatic studies of jack pine. Increased frequency of summer droughts might result in a growth decrease of jack pine. Nous avons étudié les relations entre le climat et la croissance radiale annuelle de provenance de pin gris (Pinus banksiana Lamb.) établis depuis 41 ans dans un jardin commun à Petawawa en Ontario. Des tests de descendance établis dans des conditions similaires à partir de graines provenant de différentes parties de l’aire de distribution de l’espèce (depuis le Nord des Etats-unis jusqu’au nord du Canada) simulent des changements climatiques et des transitions entre différentes zones bioclimatiques. Nous avons tentés de répondre aux questions suivantes : Est-ce que la relation entre la croissance radiale interannuelle et le climat varie en fonction des provenances? Quelles sont les facteurs climatiques qui contrôlent la croissance radiale des différentes provenances. Des chronologies de la croissance radiale couvrant la période 1970–2004 ont été développées pour 16 provenances. Les facteurs climatiques les plus corrélés avec la croissance radiale sont les précipitations pour juin et mars de l’année en cours et les précipitations de décembre pour l’année précédente. Bien que les facteurs climatiques contrôlant la croissance sont les mêmes pour toutes les provenances, la croissance absolue variait en fonction du potentiel de croissance de chaque provenance. Nous concluons que la variabilité due à la provenance des graines ne constitue pas une source importante de variation dans la réponse dendroclimatique chez le pin gris. Une augmentation de la fréquence des sécheresses durant la période estivale pourrait entraîner une diminution de la croissance du pin gris. [ABSTRACT FROM AUTHOR]

The practice of intensive animal production in certain areas has resulted in excessive manure production for the available regional land base. Consequently, there is a need to develop treatment technologies to recover the valuable nutrients that manure contains so that the resulting product can be transported and used as fertilizer on agricultural land. The project presented here used electrodialysis in a dilution/concentration configuration to transfer the manure ammonia in the diluate solution by electromigration to an adjacent solution separated by an ion-exchange membrane under the driving force of an electrical potential. Then, air stripping from the electrodialysis-obtained concentrate solution without pH modification was used to isolate the ammonia in an acidic solution. An optimal process operating voltage of 17.5 V was first determined on the basis of current efficiency and total energy consumption. During the process, the swine manure pH varied from 8.5 to 8.2, values favourable for electromigration. Total ammonia nitrogen reached 21 352 mg/L in the concentrate solution, representing approximately seven times the concentration in the swine manure. Further increases in concentration were limited by water transfer from the diluate solution due to electroosmosis and osmosis. Applying vacuum to the concentrate reservoir was found to be more efficient than direct concentrate solution aeration for NH3 recuperation in the acid trap, given that the ammonia recuperated under vacuum represented 14.5% of the theoretical value of the NH3 present in the concentrate solution as compared to 6.2% for aeration. However, an excessively low concentrate solution pH (8.6–8.3) limited NH3volatilization toward the acid trap. These results suggest that the concentrate solution pH needs to be raised to promote the volatile NH3 form of total ammonia nitrogen. [Copyright &y& Elsevier]

Importance: Between 5% and 10% of breast cancer cases are associated with an inherited germline pathogenic or likely pathogenic variant (GPV) in a breast cancer susceptibility gene (BCSG), which could alter local and systemic therapy recommendations. Traditional genetic testing criteria misses a proportion of these cases., Objective: To evaluate the prevalence and clinicopathological associations of GPVs in 2 groups of BCSGs among an ethnically diverse cohort of women with newly diagnosed breast cancer., Design, Setting, and Participants: This cross-sectional study, conducted at 3 Montreal hospitals between September 2019 and April 2022, offered universal genetic counseling and testing to all women with a first diagnosis of invasive breast cancer. Women were offered an obligatory primary panel of BRCA1, BRCA2, and PALB2 (B1B2P2) and an optional secondary panel of 14 additional BCSGs. Eligible participants were women 18 years of age or older who received a diagnosis of a first primary invasive breast cancer not more than 6 months before the time of referral to the study. Data were analyzed from November 2023 to June 2024., Results: Of 1017 referred patients, 805 were eligible and offered genetic counseling and testing, and 729 of those 805 (90.6%) consented to be tested. The median age at breast cancer diagnosis was 53 years (range, 23-91 years), and 65.4% were White and of European ancestry. Fifty-four GPVs were identified in 53 patients (7.3%), including 39 patients (5.3%) with B1B2P2 and 15 patients (2.1%) with 6 of the 14 secondary panel BCSGs (ATM, BARD1, BRIP1, CHEK2, RAD51D, and STK11). On multivariable analysis, clinical factors independently associated with B1B2P2-positive status included being younger than 40 years of age at diagnosis (odds ratio [OR], 6.83; 95% CI, 2.22-20.90), triple-negative breast cancer (OR, 3.19; 95% CI, 1.20-8.43), high grade disease (OR, 1.68; 95% CI, 1.05-2.70), and family history of ovarian cancer (OR, 9.75; 95% CI, 2.65-35.85). Of 39 B1B2P2-positive patients, 13 (33.3%) were eligible for poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors., Conclusions and Relevance: In this cross-sectional universal genetic testing study of women with newly diagnosed invasive breast cancer, the prevalence of GPVs was 7.3%, with 5.3% of patients testing positive for B1B2P2. Among B1B2P2-women women, one-third were eligible for PARP inhibitors.

Background and Purpose: Preoperative partial breast irradiation (PBI) is a novel technique that can be used in patients with early-stage breast cancer with the goal of limiting the irradiated breast volume, toxicity and number of fractions. The aim of this trial is to assess the toxicity, surgical, oncologic and cosmetic outcomes of preoperative PBI., Materials and Methods: In this single-arm phase II trial, we enrolled women ≥ 60 years, with unifocal low-risk breast invasive ductal carcinoma (cT1N0, grade 1-2, ER+, Her2-). Patients were treated with a single fraction of 20 Gy of preoperative PBI using volumetric modulated arc therapy (VMAT). Patients then underwent breast-conserving surgery (BCS) +/- sentinel lymph node biopsy within 72 h of radiation. Primary outcomes were rate of surgical complications and early toxicity. Secondary outcomes were cosmesis at 12 months, chronic toxicity and ipsilateral breast tumor recurrence., Results: Twenty-five patients were recruited with a median age of 67 years, and a median follow-up of 60 months. Sentinel biopsy was positive in 1 out of 24 patients (4 %). Two patients received adjuvant RT for close margins or positive lymph nodes. Within the first 90 days, none of the patients had surgical complications; almost all had grade 0 to 1 acute and late RTOG skin toxicity. The cosmetic outcome was rated between good and excellent in all cases by physicians and patients, except for one patient who self-rated her cosmesis as fair as of the third year. There were no recurrences., Conclusion: Preoperative single-fraction PBI is a safe and feasible treatment for elderly patients with low-risk early-stage breast cancer, with no surgical complications, very low rates of acute and late radiation toxicity, and excellent cosmetic outcomes. Randomized controlled trials are needed to compare preoperative to adjuvant PBI in this patient population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Aim: The relative contributions of insulin secretory defects and possible additional contribution of insulin resistance for the development of cystic fibrosis (CF)-related diabetes (CFRD) are poorly understood. We aimed to (a) determine which indices of insulin resistance predict progression to CFRD, and (b) to model the relative contributions of insulin secretory function and insulin resistance to predict the risk of CFRD., Materials and Methods: Three hundred and three individuals living with CF underwent a 2-h oral glucose tolerance test with blood sampling every 30 min at 12-24-month intervals until they developed CFRD or until the end of follow-up (up to 15 years). Indices of insulin resistance (e.g. Stumvoll) and insulin secretion were calculated from oral glucose tolerance test glucose and insulin measurements. CFRD-free survival was assessed by survival analysis., Results: Estimated insulin resistance showed associations with glucose homeostasis and risk of progression to CFRD. The CFRD-free survival was significantly different between quartiles of insulin resistance (p < 0.0001). When patients were subdivided according to both insulin resistance and insulin secretion (insulinogenic index), CFRD-free survival was significantly lower in those with combined lowest insulin secretion and highest insulin resistance (Stumvoll) indices (hazard ratio: 11.2; p < 0.0001). There was no significant difference when the same analysis was performed for the nine other indices., Conclusions: Insulin resistance is correlated with glucose homeostasis and the risk of progression to CFRD. Patients combining low insulin secretion and high insulin resistance had the greatest odds of developing CFRD over a 15-year period., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: Up to 25% of patients requiring hip or knee arthroplasty have sleep apnea (SA), and these patients have historically been excluded from outpatient programs. The objectives of this study were to evaluate same-day discharge failure as well as 30-day complications, readmissions, and unexpected visits., Methods: A retrospective case-control study comparing patients who have and do not have SA matched for age, sex and arthroplasty type (total hip arthroplasty, total knee arthroplasty, unicompartimental knee arthroplasty) who underwent primary outpatient surgery between February 2019 and December 2022 in 2 academic hospitals was conducted. Cases with mild SA, moderate SA with a body mass index (BMI) <35, and SA of all severity treated by continuous positive airway pressure machines were eligible. There were 156 patients included (78 cases). Complications were assessed according to the Clavien-Dindo Classification and the Comprehensive Complication Index. Continuous variables were evaluated by Student's T or Mann-Whitney tests, while categorical data were analyzed by Chi-square or Fisher tests. Univariate analyses were performed to determine discharge failure risk factors., Results: There were 6 cases (7.7%) and 5 controls (6.4%) who failed to be discharged on surgery day (P = .754), with postoperative hypoxemia (6, [3.8%]) and apnea periods (3, [1.9%]) being the most common causes. Higher BMI (odds ratio = 1.19, P = .013) and general anesthesia (odds ratio = 11.97, P = .004) were found to be risk factors for discharge failure. No difference was observed on 30-day readmissions (P = .497), unexpected visits (P = 1.000), and complications on the Clavien-Dindo Classification (P > .269) and Comprehensive Complication Index (P > .334) scales., Conclusions: Selected patients who have SA can safely undergo outpatient hip or knee arthroplasty. Higher BMI and general anesthesia increased the odds of same-day discharge failure., Level of Evidence: Level III, Case-control Study., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Significance: Of patients with early-stage breast cancer, 60% to 75% undergo breast-conserving surgery. Of those, 20% or more need a second surgery because of an incomplete tumor resection only discovered days after surgery. An intraoperative imaging technology allowing cancer detection on the margins of breast specimens could reduce re-excision procedure rates and improve patient survival., Aim: We aimed to develop an experimental protocol using hyperspectral line-scanning Raman spectroscopy to image fresh breast specimens from cancer patients. Our objective was to determine whether macroscopic specimen images could be produced to distinguish invasive breast cancer from normal tissue structures., Approach: A hyperspectral inelastic scattering imaging instrument was used to interrogate eight specimens from six patients undergoing breast cancer surgery. Machine learning models trained with a different system to distinguish cancer from normal breast structures were used to produce tissue maps with a field-of-view of 1    cm 2 classifying each pixel as either cancer, adipose, or other normal tissues. The predictive model results were compared with spatially correlated histology maps of the specimens., Results: A total of eight specimens from six patients were imaged. Four of the hyperspectral images were associated with specimens containing cancer cells that were correctly identified by the new ex vivo pathology technique. The images associated with the remaining four specimens had no histologically detectable cancer cells, and this was also correctly predicted by the instrument., Conclusions: We showed the potential of hyperspectral Raman imaging as an intraoperative breast cancer margin assessment technique that could help surgeons improve cosmesis and reduce the number of repeat procedures in breast cancer surgery., (© 2024 The Authors.)

Sexually transmitted infections (STIs) are common among adolescents. According to the Health Belief Model, cues to action influence preventive behaviors. Cues to action can include health experiences such as being diagnosed with an STI. The impact of a history of STIs on subsequent condom use among adolescents remains largely unexamined, despite high rates of recurrence and their health impacts. This project aimed to systematically review the literature on the association between curable STIs and subsequent condom use among adolescents. The systematic review, reported following PRISMA guidelines, was conducted using the Joanna Briggs Institute method. Eligible studies, in the form of cohort studies, case-control studies, or cross-sectional studies, targeted adolescents aged 10 to 24, with or without a history of curable STIs; the outcome was subsequent condom use. MEDLINE (Ovid), Embase (Elsevier), and Web of Science were searched from January 2012 to December 2022 with the assistance of an information specialist. Two reviewers independently selected articles and extracted data. Risk of bias analysis was performed using ROBINS-E. The review explores results, with tables, based on population characteristics, exposure, and outcome, and addresses the influence of gender, ethnicity, and age. Of 3088 articles identified, seven studies were retained. Almost all the studies focused on African-American, Nigerian, or Rwandan adolescents, and several included only girls. Among girls, a history of STI increased subsequent condom use in combination with other contraceptive methods (n = 4). Among boys and older adolescents of both genders, a history of STI was associated with a decrease in condom use (n = 3). No study distinguished between different STIs. While all the studies (n = 7) presented a high risk of bias, six did not present a threat to conclusion validity. All the studies indicated that a history of STI could influence subsequent protective behaviors, possibly by acting as a cue to action, as posited by the Health Belief Model. This information enhances our understanding of factors leading to the adoption of preventive health measures among adolescents and could apply to other infectious experiences.Registration The protocol is registered in PROSPERO (CRD42023397443)., (© 2024. The Author(s).)

People living with cystic fibrosis (pwCF) homozygous for F508del present more severe phenotypes. PwCF with compound heterozygous genotypes F508del /A455E and F508del /L206W may have milder cystic fibrosis (CF) phenotypes. We compared F508del homozygotes and common compound heterozygotes (F508del and a second pathogenic variant) in adult patients. Nutritional, pulmonary function and glucose homeostasis indices data were collected from the prospective Montreal CF cohort. Two-hundred and three adults with CF having at least one F508del variant were included. Individuals were divided into subgroups: homozygous F508del/F508del (n=149); F508del/621+1G>T (n=17); F508del/711+1G>T (n=11); F508del/A455E (n=12); and F508del/L206W (n=14). Subgroups with the F508del/L206W and F508del/A455E had a lower proportion with pancreatic exocrine insufficiency (p<0.0001), a higher fat mass (p<0.0001), and lower glucose area under the curve (AUC) (p=0.027). The F508del/L206W subgroup had significantly higher insulin secretion (AUC; p=0.027) and body mass index (p<0.001). Pulmonary function (FEV1) was significantly higher for the F508del/L206W subgroup (p<0.0001). Over a median of 7.37 years, the risk of developing CFRD in 141 patients was similar between groups. PwCF with heterozygous F508del/L206W and F508del/A455E tended to have pancreatic exocrine sufficiency, better nutritional status, improved pulmonary function and better diabetogenic indices, but this does not translate into lower risk of CF-related Diabetes.

Background: Fractures have serious health consequences in older adults. While some medications are individually associated with increased risk of falls and fractures, it is not clear if this holds true for the use of many medications (polypharmacy). We aimed to identify what is known about the association between polypharmacy and the risk of fractures in adults aged ≥65 and to examine the methods used to study this association., Methods: We conducted a systematic review with narrative synthesis of studies published up to October 2023 in PubMed, Embase, CINAHL, PsychINFO, Cochrane Library, Web of Science, and the grey literature. Two independent reviewers screened titles, abstracts, and full texts, then performed data extraction and quality assessment., Results: Among the 31 studies included, 11 different definitions of polypharmacy were used and were based on three medication counting methods (concurrent use 15/31, cumulative use over a period 6/31, daily average 3/31, and indeterminate 7/31). Overall, polypharmacy was frequent and associated with higher fracture risk. A dose-response relationship between increasing number of medications and increased risk of fractures was observed. However, only seven studies adjusted for major confounders (age, sex, and chronic disease). The quality of the studies ranged from poor to high., Conclusions: Polypharmacy appears to be a relevant modifiable risk factor for fractures in older individuals that can easily be used to identify those at risk. The diversity of medication calculation methods and definitions of polypharmacy highlights the importance of a detailed methodology to understand and compare results., (© 2024 The Authors. Journal of Evidence‐Based Medicine published by Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd.)

Objectives: To identify patient-related factors and fracture characteristics influencing the functional outcomes of nonoperatively treated radial head fractures and to determine function at 1 year., Design: Prospective cohort study., Setting: Academic Level 1 trauma center., Patients/participants: Consecutive isolated radial head fractures fitting the inclusion criteria between May 2013 and July 2016., Intervention: Nonoperative treatment of isolated radial head fractures., Outcome Measurements: Logistic regressions between potential prognostic factors and function assessed with the Mayo Elbow Performance Score (MEPS), the Disabilities of the Arm, Shoulder, and Hand (DASH) score, and range of motion at 1.5-3-6-12 months., Results: One hundred fourteen patients were included (78% Mason I [OTA/AO 2R1B1], 20% Mason II [OTA/AO 2R1B3], and 2% Mason III [OTA/AO 2R1C3]). Mean MEPS and DASH score at the last follow-up were excellent [96.4 ± 7.6 and 3.7 ± 8.6] with, respectively, 79.8% and 92.7% of satisfactory results. Depressive symptoms at injury baseline (Quick Inventory of Depressive Symptomatology > 5) are a constant predictor of unsatisfactory function (MEPS <90 or DASH >17]). Older age and female sex were all linked to worse function at the first follow-ups ( P < 0.05), whereas lower socioeconomic class and receiving financial compensations were associated to unsatisfactory function at 1 year ( P < 0.05)., Conclusions: Although most nonoperatively treated radial head fractures heal with excellent function, some patients still exhibit unsatisfactory results at 1 year. Symptoms of depression at injury baseline are a constant and significant predictor of unsatisfactory function. Early detection of depressive symptoms would allow for interventions that may optimize function., Level of Evidence: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)