Precision detection of select human lung cancer biomarkers and cell lines using honeybee olfactory neural circuitry as a novel gas sensor.

Human breath contains biomarkers (odorants) that can be targeted for early disease detection. It is well known that honeybees have a keen sense of smell and can detect a wide variety of odors at low concentrations. Here, we employ honeybee olfactory neuronal circuitry to classify human lung cancer volatile biomarkers at different concentrations and their mixtures at concentration ranges relevant to biomarkers in human breath from parts-per-billion to parts-per-trillion. We also validated this brain-based sensing technology by detecting human non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) cell lines using the 'smell' of the cell cultures. Different lung cancer biomarkers evoked distinct spiking response dynamics in the honeybee antennal lobe neurons indicating that those neurons encoded biomarker-specific information. By investigating lung cancer biomarker-evoked population neuronal responses from the honeybee antennal lobe, we classified individual human lung cancer biomarkers successfully (88% success rate). When we mixed six lung cancer biomarkers at different concentrations to create 'synthetic lung cancer' vs. 'synthetic healthy' human breath, honeybee population neuronal responses were able to classify those complex breath mixtures reliably with exceedingly high accuracy (93-100% success rate with a leave-one-trial-out classification method). Finally, we employed this sensor to detect human NSCLC and SCLC cell lines and we demonstrated that honeybee brain olfactory neurons could distinguish between lung cancer vs. healthy cell lines and could differentiate between different NSCLC and SCLC cell lines successfully (82% classification success rate). These results indicate that the honeybee olfactory system can be used as a sensitive biological gas sensor to detect human lung cancer.

Using a Walking Test to Assess Firefighter Fitness.

Tactical populations face increased risk on the job, and it is known that firefighters have high levels of cardiac-related death. Aerobic fitness is a modifiable cardiac risk factor, but many fire stations lack the proper equipment to easily assess aerobic fitness levels of their firefighters. Additionally, many fire stations lack wellness programs to hold firefighters accountable for maintaining their fitness levels. Purpose: We assessed the validity of the submaximal 6-minute walk test (6MWT) as a measure of aerobic capacity compared to a maximal treadmill test and the submaximal Gerkin protocol. Methods: Twenty-four firefighters (19 male, 5 female, 34.8 ± 9.7 years; 38.1 ± 3.6 kg·m-2) completed the 6MWT, the submaximal Gerkin protocol, and a maximal treadmill test. Data were analyzed with Bland-Altman plots and correlation analysis. Results: We found equivalence between the 6MWT and directly measured VO2max and between the 6MWT and Gerkin protocol using Bland-Altman plots. In our cohort, the 6MWT underestimated VO2max (31.57 ml·kg-1·min-1) compared to directly measured VO2max (38.1 ml·kg-1·min-1) by 17% and to the Gerkin (40.48 ml·kg-1·min-1) by 22%. Conclusion: Considering its equivalence, using the 6MWT could be a more accessible way to quantify aerobic capacity in firefighters. Despite underestimation, having an easy to administer protocol may encourage more fire stations to assess pre- and post- fitness levels regularly.

A literature review and expert consensus statement on diagnostics in suspected metal implant allergy.

BACKGROUND: Although rare, allergic reactions to metal implants represent a diagnostic challenge in view of missing guidelines. OBJECTIVES: To develop an European expert consensus on characteristics of metal allergy reactions and the utility of various diagnostic tools in suspected metal implant allergy. METHODS: A nominal group technique (NGT) was applied to develop consensus statements. Initially an online literature database was created on a secure server to enable a comprehensive information. Twenty-three statements were formulated on potential aspects of metal implant allergy with a focus on diagnostics and grouped into five domains. For the consensus development, the panel of 12 experts initially did refine and reformulate those statements that were ambiguous or had unclear wording. By face-to-face (9/12) or virtual participation (3/12), an anonymous online voting was performed. RESULTS: Consensus (≥80% of agreement) was reached in 20/23 statements. The panel agreed that implant allergy despite being rare should be considered in case of persistent unexplained symptoms. It was, however, recommended to allow adequate time for resolution of symptoms associated with healing and integration of an implant. Obtaining questionnaire-aided standardized medical history and standardized scoring of patient outcomes was also considered an important step by all experts There was broad consensus regarding the utility/performance of patch testing with additional late reading. It was recognized that the lymphocyte transformation test (LTT) has to many limitations to be generally recommended. Prior to orthopaedic implant, allergy screening of patients without a history of potential allergy to implant components was not recommended. CONCLUSIONS: Using an expert consensus process, statements concerning allergy diagnostics in suspected metal implant allergy were created. Areas of nonconsensus were identified, stressing uncertainty among the experts around topics such as preoperative testing in assumed allergy, histological correlate of periimplant allergy and in vitro testing, which underscores the need for further research.

Changes in Weight or Body Composition by Frailty Status: A Pilot Study.

Weight loss may benefit older adults with obesity. However, it is unknown whether individuals with different frailty phenotypes have different outcomes following weight loss. Community-dwelling adults aged ≥65 (n = 53) with a body mass index ≥30 kg/m2 were recruited for a six-month, single-arm, technology-based weight loss study. A 45-item frailty index identified frailty status using subjective and objective measures from a baseline geriatric assessment. At baseline, n = 22 participants were classified as pre-frail (41.5%) and n = 31 were frail (58.5%), with no differences in demographic characteristics. While weight decreased significantly in both groups (pre-frail: 90.8 ± 2.7 kg to 85.5 ± 2.4 kg (p < 0.001); frail: 102.7 ± 3.4 kg to 98.5 ± 3.3 kg (p < 0.001), no differences were observed between groups for changes in weight (p = 0.30), appendicular lean mass/height2 (p = 0.47), or fat-free mass (p = 0.06). Older adults with obesity can safely lose weight irrespective of frailty status using a technology-based approach. Further investigation is needed to determine whether the impact of specific lifestyle interventions differ by frailty status.

Impairments of cerebellar structure and function in a zebrafish KO of neuropsychiatric risk gene znf536.

Genetic variants in ZNF536 contribute to the risk for neuropsychiatric disorders such as schizophrenia, autism, and others. The role of this putative transcriptional repressor in brain development and function is, however, largely unknown. We generated znf536 knockout (KO) zebrafish and studied their behavior, brain anatomy, and brain function. Larval KO zebrafish showed a reduced ability to compete for food, resulting in decreased total body length and size. This phenotype can be rescued by segregating the homozygous KO larvae from their wild-type and heterozygous siblings, enabling studies of adult homozygous KO animals. In adult KO zebrafish, we observed significant reductions in anxiety-like behavior and social interaction. These znf536 KO zebrafish have decreased cerebellar volume, corresponding to decreased populations of specific neuronal cells, especially in the valvular cerebelli (Va). Finally, using a Tg[mbp:mgfp] line, we identified a previously undetected myelin structure located bilaterally within the Va, which also displayed a reduction in volume and disorganization in KO zebrafish. These findings indicate an important role for ZNF536 in brain development and implicate the cerebellum in the pathophysiology of neuropsychiatric disorders.

Acute Effect of Dynamic and Gluteal Resistance Exercise Warm-up Protocols on Jump Landing Mechanics in College-Aged Females.

ABSTRACT: Rauseo, ML, Feairheller, DL, LaRoche, DP, and Cook, SB. Acute effect of dynamic and gluteal resistance exercise warm-up protocols on lower-extremity jump landing mechanics in college-aged females. J Strength Cond Res 38(2): 259-265, 2024-Inadequate neuromuscular control of the femur by the gluteal musculature is associated with noncontact and overuse injuries to the knee. Acute bouts of resistance exercises targeting the gluteal musculature can be prescribed as part of a warm-up protocol with the goal of improving subsequent neuromuscular control and performance. The purpose of this study was to determine the effect that a warm-up protocol including moderate-intensity gluteal resistance exercises (GRE) has on single leg jump landing biomechanics. Seventeen healthy, college-aged, recreationally active females (mean ± SD ; age = 21.4 ± 1.9 years; height = 166.9 ± 5.7 cm; body mass = 62.5 ± 7.4 kg) performed 3 single leg hop trials per leg after completing no warm-up (CON), a dynamic warm-up (DWU), and a dynamic warm-up with gluteal resistance exercises (DWU + GRE) across 3 laboratory visits. Lower extremity kinetic and kinematic variables were assessed during single leg hops from the point of initial foot contact to deepest knee flexion. Biomechanical differences between dominant and nondominant limb landings were also assessed. Dominant limb hip internal rotation angle after DWU + GRE (2.03 ± 9.92°) was significantly greater ( p ≤ 0.05) compared with CON (-3.36 ± 7.74°). Peak knee adduction moment (56.8%), peak knee flexion angle (5.7%), and peak knee external rotation angle (17.0%) were significantly greater ( p ≤ 0.017) in the dominant limb, compared with the nondominant limb, across warm-up protocols. The combined DWU + GRE warm-up protocol did not have a substantial impact on landing biomechanics. Clinicians prescribing GRE before activity should not expect significant changes in movement patterns after a single bout.

Protein Supplementation May Dampen Positive Effects of Exercise on Glucose Homeostasis: A Pilot Weight Loss Intervention.

BACKGROUND: The role of protein in glucose homeostasis has demonstrated conflicting results. However, little research exists on its impact following weight loss. This study examined the impact of protein supplementation on glucose homeostasis in older adults >65 years with obesity seeking to lose weight. METHODS: A 12-week, nonrandomized, parallel group intervention of protein (PG) and nonprotein (NPG) arms for 28 older rural adults (body mass index (BMI) ≥ 30 kg/m2) was conducted at a community aging center. Both groups received twice weekly physical therapist-led group strength training classes. The PG consumed a whey protein supplement three times per week, post-strength training. Primary outcomes included pre/post-fasting glucose, insulin, inflammatory markers, and homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Mean age and baseline BMI were 72.9 ± 4.4 years and 37.6 ± 6.9 kg/m2 in the PG and 73.0 ± 6.3 and 36.6 ± 5.5 kg/m2 in the NPG, respectively. Mean weight loss was -3.45 ± 2.86 kg in the PG and -5.79 ± 3.08 kg in the NPG (p < 0.001). There was a smaller decrease in pre- vs. post-fasting glucose levels (PG: -4 mg ± 13.9 vs. NPG: -12.2 ± 25.8 mg/dL; p = 0.10), insulin (-7.92 ± 28.08 vs. -46.7 ± 60.8 pmol/L; p = 0.01), and HOMA-IR (-0.18 ± 0.64 vs. -1.08 ± 1.50; p = 0.02) in the PG compared to the NPG. CONCLUSIONS: Protein supplementation during weight loss demonstrated a smaller decrease in insulin resistance compared to the NPG, suggesting protein may potentially mitigate beneficial effects of exercise on glucose homeostasis.

Safety and efficacy of arimoclomol for inclusion body myositis: a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Inclusion body myositis is the most common progressive muscle wasting disease in people older than 50 years, with no effective drug treatment. Arimoclomol is an oral co-inducer of the cellular heat shock response that was safe and well-tolerated in a pilot study of inclusion body myositis, reduced key pathological markers of inclusion body myositis in two in-vitro models representing degenerative and inflammatory components of this disease, and improved disease pathology and muscle function in mutant valosin-containing protein mice. In the current study, we aimed to assess the safety, tolerability, and efficacy of arimoclomol in people with inclusion body myositis. METHODS: This multicentre, randomised, double-blind, placebo-controlled study enrolled adults in specialist neuromuscular centres in the USA (11 centres) and UK (one centre). Eligible participants had a diagnosis of inclusion body myositis fulfilling the European Neuromuscular Centre research diagnostic criteria 2011. Participants were randomised (1:1) to receive either oral arimoclomol 400 mg or matching placebo three times daily (1200 mg/day) for 20 months. The randomisation sequence was computer generated centrally using a permuted block algorithm with randomisation numbers masked to participants and trial staff, including those assessing outcomes. The primary endpoint was the change from baseline to month 20 in the Inclusion Body Myositis Functional Rating Scale (IBMFRS) total score, assessed in all randomly assigned participants, except for those who were randomised in error and did not receive any study medication, and those who did not meet inclusion criteria. Safety analyses included all randomly assigned participants who received at least one dose of study medication. This trial is registered with ClinicalTrials.gov, number NCT02753530, and is completed. FINDINGS: Between Aug 16, 2017 and May 22, 2019, 152 participants with inclusion body myositis were randomly assigned to arimoclomol (n=74) or placebo (n=78). One participant was randomised in error (to arimoclomol) but not treated, and another (assigned to placebo) did not meet inclusion criteria. 150 participants (114 [76%] male and 36 [24%] female) were included in the efficacy analyses, 73 in the arimoclomol group and 77 in the placebo group. 126 completed the trial on treatment (56 [77%] and 70 [90%], respectively) and the most common reason for treatment discontinuation was adverse events. At month 20, mean IBMFRS change from baseline was not statistically significantly different between arimoclomol and placebo (-3·26, 95% CI -4·15 to -2·36 in the arimoclomol group vs -2·26, -3·11 to -1·41 in the placebo group; mean difference -0·99 [95% CI -2·23 to 0·24]; p=0·12). Adverse events leading to discontinuation occurred in 13 (18%) of 73 participants in the arimoclomol group and four (5%) of 78 participants in the placebo group. Serious adverse events occurred in 11 (15%) participants in the arimoclomol group and 18 (23%) in the placebo group. Elevated transaminases three times or more of the upper limit of normal occurred in five (7%) participants in the arimoclomol group and one (1%) in the placebo group. Tubulointerstitial nephritis was observed in one (1%) participant in the arimoclomol group and none in the placebo group. INTERPRETATION: Arimoclomol did not improve efficacy outcomes, relative to placebo, but had an acceptable safety profile in individuals with inclusion body myositis. This is one of the largest trials done in people with inclusion body myositis, providing data on disease progression that might be used for subsequent clinical trial design. FUNDING: US Food and Drug Administration Office of Orphan Products Development and Orphazyme.

Surgical versus non-surgical management for patients with malignant bowel obstruction (S1316): a pragmatic comparative effectiveness trial.

BACKGROUND: Malignant small bowel obstruction has a poor prognosis and is associated with multiple related symptoms. The optimal treatment approach is often unclear. We aimed to compare surgical versus non-surgical management with the aim to determine the optimal approach for managing malignant bowel obstruction. METHODS: S1316 was a pragmatic comparative effectiveness trial done within the National Cancer Trials Network at 30 hospital and cancer research centres in the USA, Mexico, Peru, and Colombia. Participants had an intra-abdominal or retroperitoneal primary cancer confirmed via pathological report and malignant bowel disease; were aged 18 years or older with a Zubrod performance status 0-2 within 1 week before admission; had a surgical indication; and treatment equipoise. Participants were randomly assigned (1:1) to surgical or non-surgical treatment using a dynamic balancing algorithm, balancing on primary tumour type. Patients who declined consent for random assignment were offered a prospective observational patient choice pathway. The primary outcome was the number of days alive and out of the hospital (good days) at 91 days. Analyses were based on intention-to-treat linear, logistic, and Cox regression models combining data from both pathways and adjusting for potential confounders. Treatment complications were assessed in all analysed patients in the study. This completed study is registered with ClinicalTrials.gov, NCT02270450. FINDINGS: From May 11, 2015, to April 27, 2020, 221 patients were enrolled (143 [65%] were female and 78 [35%] were male). There were 199 evaluable participants: 49 in the randomised pathway (24 surgery and 25 non-surgery) and 150 in the patient choice pathway (58 surgery and 92 non-surgery). No difference was seen between surgery and non-surgery for the primary outcome of good days: mean 42·6 days (SD 32·2) in the randomised surgery group, 43·9 days (29·5) in the randomised non-surgery group, 54·8 days (27·0) in the patient choice surgery group, and 52·7 days (30·7) in the patient choice non-surgery group (adjusted mean difference 2·9 additional good days in surgical versus non-surgical treatment [95% CI -5·5 to 11·3]; p=0·50). During their initial hospital stay, six participants died, five due to cancer progression (four patients from the randomised pathway, two in each treatment group, and one from the patient choice pathway, in the surgery group) and one due to malignant bowel obstruction treatment complications (patient choice pathway, non-surgery). The most common grade 3-4 malignant bowel obstruction treatment complication was anaemia (three [6%] patients in the randomised pathway, all in the surgical group, and five [3%] patients in the patient choice pathway, four in the surgical group and one in the non-surgical group). INTERPRETATION: In our study, whether patients received a surgical or non-surgical treatment approach did not influence good days during the first 91 days after registration. These findings should inform treatment decisions for patients hospitalised with malignant bowel obstruction. FUNDING: Agency for Healthcare Research and Quality and the National Cancer Institute. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Behavioral analysis through the lifespan of disc1 mutant zebrafish identifies defects in sensorimotor transformation.

DISC1 is a genetic risk factor for multiple psychiatric disorders. Compared to the dozens of murine Disc1 models, there is a paucity of zebrafish disc1 models-an organism amenable to high-throughput experimentation. We conducted the longitudinal neurobehavioral analysis of disc1 mutant zebrafish across key stages of life. During early developmental stages, disc1 mutants exhibited abrogated behavioral responses to sensory stimuli across multiple testing platforms. Moreover, during exposure to an acoustic sensory stimulus, loss of disc1 resulted in the abnormal activation of neurons in the pallium, cerebellum, and tectum-anatomical sites involved in the integration of sensory perception and motor control. In adulthood, disc1 mutants exhibited sexually dimorphic reduction in anxiogenic behavior in novel paradigms. Together, these findings implicate disc1 in sensorimotor processes and the genesis of anxiogenic behaviors, which could be exploited for the development of novel treatments in addition to investigating the biology of sensorimotor transformation in the context of disc1 deletion.

Multiple adaptations underly co-option of a CRISPR surveillance complex for RNA-guided DNA transposition.

CRISPR-associated transposons (CASTs) are natural RNA-directed transposition systems. We demonstrate that transposon protein TniQ plays a central role in promoting R-loop formation by RNA-guided DNA-targeting modules. TniQ residues, proximal to CRISPR RNA (crRNA), are required for recognizing different crRNA categories, revealing an unappreciated role of TniQ to direct transposition into different classes of crRNA targets. To investigate adaptations allowing CAST elements to utilize attachment sites inaccessible to CRISPR-Cas surveillance complexes, we compared and contrasted PAM sequence requirements in both I-F3b CAST and I-F1 CRISPR-Cas systems. We identify specific amino acids that enable a wider range of PAM sequences to be accommodated in I-F3b CAST elements compared with I-F1 CRISPR-Cas, enabling CAST elements to access attachment sites as sequences drift and evade host surveillance. Together, this evidence points to the central role of TniQ in facilitating the acquisition of CRISPR effector complexes for RNA-guided DNA transposition.

A single-cell transcriptome atlas of the maturing zebrafish telencephalon.

The zebrafish telencephalon is composed of highly specialized subregions that regulate complex behaviors such as learning, memory, and social interactions. The transcriptional signatures of the neuronal cell types in the telencephalon and the timeline of their emergence from larva to adult remain largely undescribed. Using an integrated analysis of single-cell transcriptomes of approximately 64,000 cells obtained from 6-day-postfertilization (dpf), 15-dpf, and adult telencephalon, we delineated nine main neuronal cell types in the pallium and eight in the subpallium and nominated novel marker genes. Comparing zebrafish and mouse neuronal cell types revealed both conserved and absent types and marker genes. Mapping of cell types onto a spatial larval reference atlas created a resource for anatomical and functional studies. Using this multiage approach, we discovered that although most neuronal subtypes are established early in the 6-dpf fish, some emerge or expand in number later in development. Analyzing the samples from each age separately revealed further complexity in the data, including several cell types that expand substantially in the adult forebrain and do not form clusters at the larval stages. Together, our work provides a comprehensive transcriptional analysis of the cell types in the zebrafish telencephalon and a resource for dissecting its development and function.

Distributional Validation of Precipitation Data Products with Spatially Varying Mixture Models.

The high mountain regions of Asia contain more glacial ice than anywhere on the planet outside of the polar regions. Because of the large population living in the Indus watershed region who are reliant on melt from these glaciers for fresh water, understanding the factors that affect glacial melt along with the impacts of climate change on the region is important for managing these natural resources. While there are multiple climate data products (e.g., reanalysis and global climate models) available to study the impact of climate change on this region, each product will have a different amount of skill in projecting a given climate variable, such as precipitation. In this research, we develop a spatially varying mixture model to compare the distribution of precipitation in the High Mountain Asia region as produced by climate models with the corresponding distribution from in situ observations from the Asian Precipitation-Highly Resolved Observational Data Integration Towards Evaluation (APHRODITE) data product. Parameter estimation is carried out via a computationally efficient Markov chain Monte Carlo algorithm. Each of the estimated climate distributions from each climate data product is then validated against APHRODITE using a spatially varying Kullback-Leibler divergence measure. Supplementary materials accompanying this paper appear online. Supplementary materials for this article are available at 10.1007/s13253-022-00515-0.

Early Emergence of Rumination has no Association with Performance on a Non-affective Inhibitory Control Task.

Rumination is a vulnerability for depression and potentially linked to inhibitory control weaknesses. We aimed to replicate the association observed in adults between inhibitory control and rumination in adolescents, and to examine putative moderating roles of childhood maltreatment and perceived family cohesion in an adolescent sample at risk for depression due to familial/personal history. Ninety adolescents aged 11-17 (M = 14.6, SD = 1.8) completed self-report scales of rumination, maltreatment, and family cohesion, and performed a task assessing inhibitory control. Hierarchical regression models showed no significant relation between inhibitory control and moderator variables on rumination. However, adolescents who reported higher levels of maltreatment and who perceived lower family cohesion tended to indicate higher levels of rumination (BChilhood Maltreatment = 27.52, 95% CIs [5.63, 49.41], BFamily Cohesion = -0.40, 95% CIs [-0.65, -0.15]). These findings demonstrate an alternative understanding of factors that increase depression onset risk and recurrence in adolescents.

Comparison of the H:Q Ratio Between the Dominant and Nondominant Legs of Soccer Players: A Meta-analysis.

CONTEXT: Soccer players often have a dominant (D) leg, which could influence the relative strength between the quadriceps and hamstrings. The hamstring-to-quadriceps (H:Q) ratio can be assessed on a dynamometer at various velocities to provide information on injury risk. OBJECTIVE: To assess the concentric hamstrings and concentric quadriceps strength ratio (conventional H:Q ratio) assessed in D and nondominant (ND) legs at various speeds in male soccer players. DATA SOURCES: A systematic literature search was completed from inception to 2020 in PubMed, Academic Search Ultimate, CINAHL, and SPORTDiscus. STUDY SELECTION: Keywords associated with the H:Q ratio were connected with terms for soccer players. Titles and abstracts were screened by 2 reviewers based on inclusion and exclusion criteria related to sex, playing level, language, and measurement. A total of 81 studies were reviewed and 17 studies (21%) were used. STUDY DESIGN: A meta-analysis with random effects modeling generated standardized mean differences with 95% CIs between legs and speeds. LEVEL OF EVIDENCE: Level 3. DATA EXTRACTION: A total of 38 cohorts were identified, with 14, 13, and 11 cohorts assessed at low, intermediate, and high velocities, respectively. The Quality Assessment Tool for Observational Cohort and Cross-sectional Studies from the National Institutes of Health was used. RESULTS: The mean H:Q ratio at low velocities was 59.8 ± 9.5% in D leg and 58.6 ± 9.9% in ND leg, 64.2 ± 10.7% (D) and 63.6 ± 11.3% (ND) at the intermediate velocity, and 71.9 ± 12.7% (D) and 72.8 ± 12.7% (ND) at the high velocity. Low, intermediate, and high velocities had small effects of 0.13, 0.10, and -0.06, respectively. CONCLUSION: Conventional H:Q ratios vary across velocities but did not differ between D and ND limbs in male soccer players. This study may provide the foundation to establish norms and clinically meaningful differences.

Acute physiological responses to steady-state arm cycling ergometry with and without blood flow restriction.

PURPOSE: To compare heart rate (HR), oxygen consumption (VO2), blood lactate (BL), and ratings of perceived exertion (RPE) during arm cycling with and without a blood flow restriction (BFR). METHODS: Twelve healthy males (age: 23.9 ± 3.75 years) completed four, randomized, 15-min arm cycling conditions: high-workload (HW: 60% maximal power output), low-workload (LW: 30% maximal power output), low-workload with BFR (LW-BFR), and BFR with no exercise (BFR-only). In the BFR conditions, cuff pressure to the proximal biceps brachii was set to 70% of occlusion pressure. HR, VO2, and RPE were recorded throughout the exercise, and BL was measured before, immediately after, and five minutes post-exercise. Within-subject repeated-measures ANOVA was used to evaluate condition-by-time interactions. RESULTS: HW elicited the greatest responses in HR (91% of peak; 163.3 ± 15.8 bpm), VO2 (71% of peak; 24.0 ± 3.7 ml kg-1 min-1), BL (7.7 ± 2.5 mmol L-1), and RPE (14 ± 1.7) and was significantly different from the other conditions (p < 0.01). The LW and LW-BFR conditions did not differ from each other in HR, VO2, BL, and RPE mean of conditions: ~ 68%, 41%, 3.5 ± 1.6 mmol L-1, 10.4 ± 1.6, respectively; p > 0.05). During the BFR-only condition, HR increased from baseline by ~ 15% (on average) (p < 0.01) without any changes in VO2, BL, and RPE (p > 0.05). CONCLUSIONS: HW arm cycling elicited the largest and most persistent physiological responses compared to LW arm cycling with and without a BFR. As such, practitioners who prescribe arm cycling for their clients should be advised to augment the demands of exercise via increases in exercise intensity (i.e., power output), rather than by adding BFR.

Primary Care and Mental Health Staff Perspectives on Universal Suicide Risk Screening and Care Coordination.

Little is known about staff or patient perspectives on suicide risk screening programs. The objectives of this study were to characterize Veterans Health Administration (VHA) primary care and mental health staff perspectives regarding the VHA Suicide Risk Identification Strategy screening and assessment program and to describe coordination of suicide prevention-related care following positive screening results. Qualitative interviews were conducted with 40 primary care and mental health staff at 12 VHA facilities. An inductive-deductive hybrid approach was used to conduct a thematic analysis. Several key themes were identified. Primary care and mental health staff participants accepted having a structured process for screening for suicidal ideation and conducting risk assessments, but both groups noted limitations and challenges with initial assessment and care coordination following screening. Mental health staff reported more concerns than primary care staff about negative impacts of the screening and assessment process on treatment. Both groups felt that better training was needed for primary care staff to effectively discuss and evaluate suicide risk. The results suggested that additional modifications of the screening and assessment process are needed for patients already known to have elevated risk of suicide or chronic suicidal ideation.

An interleukin-1 polymorphism additionally intensified by atopy as prognostic factor for aseptic non-mechanical complications in metal knee and hip arthroplasty.

Background: In contrast to infection or mechanical issues joint replacement failure following inflammatory adverse reactions is poorly understood. Objective: To assess the association of IL-1ß polymorphisms and history of allergy with aseptic non-mechanical complications following arthroplasty. Methods: In 102 patients with aseptic non-mechanically caused symptomatic knee or hip arthroplasty (SA) and 93 patients with asymptomatic arthroplasty (AA) questionnaire-based history, patch test with at least standard series, lymphocyte transformation test (LTT) with nickel, cobalt and chromium and interleukin-1 polymorphism analysis were done. Three polymorphisms of the IL1B gene [IL-1b -3954 (rs1143634), IL-1b -511 (rs16944) and IL-1b -31 (rs1143627)] and one polymorphism of the IL1RN gene [IL1RN intron 2, variable number of tandem repeats, VNTR (rs2234663)] were assessed by PCR and gel electrophoresis. Results: We found no significant difference in smoking history and atopy but 25% versus 10% of self-reported metal allergy in SA versus AA; the patch test (respective, LTT) for metal sensitivity was more often positive in SA patients. The allele 498 bp of the IL1RN polymorphism occurred significantly more often in the SA group (37% versus 11%; p < 0.0001). Upon additional presence of atopy, the difference was even greater (60% vs 10%) (p < 0.000001). There was no association of IL-1 polymorphisms with metal allergy. Conclusion: The IL1RN VNTR allele 498 bp was strongly associated with SA. In patients with a history of atopy, presence of the IL1RN VNTR allele 498 bp led to a four-fold higher SA prevalence compared to patients without this allele.

Increased sensitivity of insula to supraliminal faces in adults with histories of mood disorders and self-injury.

BACKGROUND: Mood disorders are associated with neurobiological disruptions in subliminal and supraliminal emotion processing. There may be additional variation based on sex and the presence of self-injurious thoughts and behaviors (SITBs). Examining individuals in remission allows us to understand trait-like emotion processing characteristics that persist in the absence of symptoms. This study investigates neural processing in response to supraliminal and subliminal emotional stimuli based upon mood disorder diagnosis, sex, and SITBs. METHODS: Seventy-five participants with a history of any mood disorder (AMD; 52 female) and 27 healthy controls (HC; 14 female) completed a fMRI task presenting subliminal and supraliminal facial stimuli. Within the AMD group, 20 had no history of SITBs, 26 had histories of suicidal ideation only, and 27 had histories of both SI and self-injurious behavior. We examined activation of salience network regions of interest including the amygdala, insula, and subgenual anterior cingulate cortex (sgACC) during the task. RESULTS: AMD showed greater insula activation in response to happy faces relative to sad faces, which was not seen in the HC group. Males exhibited lower insula activation in response to sad faces relative happy faces, a pattern not seen in females. Individuals with SITBs demonstrated a lack of sgACC blunting during supraliminal versus subliminal trials. CONCLUSIONS: We found different patterns of neural responses related to mood disorder status, sex, and SITBs. Findings highlight the importance of considering heterogeneity within diagnoses and examining neurobiological features in the context of remission.