Regional differences in synaptic degeneration are linked to alpha-synuclein burden and axonal damage in Parkinson's disease and dementia with Lewy bodies.

Regional differences in synaptic degeneration may underlie differences in clinical presentation and neuropathological disease progression in Parkinson's Disease (PD) and Dementia with Lewy bodies (DLB). Here, we mapped and quantified synaptic degeneration in cortical brain regions in PD, PD with dementia (PDD) and DLB, and assessed whether regional differences in synaptic loss are linked to axonal degeneration and neuropathological burden. We included a total of 47 brain donors, 9 PD, 12 PDD, 6 DLB and 20 non-neurological controls. Synaptophysin+ and SV2A+ puncta were quantified in eight cortical regions using a high throughput microscopy approach. Neurofilament light chain (NfL) immunoreactivity, Lewy body (LB) density, phosphorylated-tau and amyloid-ß load were also quantified. Group differences in synaptic density, and associations with neuropathological markers and Clinical Dementia Rating (CDR) scores, were investigated using linear mixed models. We found significantly decreased synaptophysin and SV2A densities in the cortex of PD, PDD and DLB cases compared to controls. Specifically, synaptic density was decreased in cortical regions affected at Braak α-synuclein stage 5 in PD (middle temporal gyrus, anterior cingulate and insula), and was additionally decreased in cortical regions affected at Braak α-synuclein stage 4 in PDD and DLB compared to controls (entorhinal cortex, parahippocampal gyrus and fusiform gyrus). Synaptic loss associated with higher NfL immunoreactivity and LB density. Global synaptophysin loss associated with longer disease duration and higher CDR scores. Synaptic neurodegeneration occurred in temporal, cingulate and insular cortices in PD, as well as in parahippocampal regions in PDD and DLB. In addition, synaptic loss was linked to axonal damage and severe α-synuclein burden. These results, together with the association between synaptic loss and disease progression and cognitive impairment, indicate that regional synaptic loss may underlie clinical differences between PD and PDD/DLB. Our results might provide useful information for the interpretation of synaptic biomarkers in vivo.

An antimicrobial activity of oil extracted from Saara hardwickii

Abstract Present research work represents antiviral and antibacterial value of body fat of Saara hardwickii commonly called as spiny tailed lizard. Oil was extracted from body fats located in the ventral region of this animal using hydrocarbons e.g., n-hexane, methanol, butanol and ethyl acetate as a solvent. The antibacterial activity of lizard oil was tested against standard as well as multi-resistant lines ofEscherichia coli, Styphalococcus aureus, Pseudomonas aeruginosa and Proteus vulgaris alone and with antibiotic ampicillin. For antibacterial potential, Ethyl acetate and Butanol solvent extract showed best zone of inhibition (7mm) with P. aeruginosa and S. aureus respectively. For antiviral potential, Butanol and Methanol extract showed best HA (Hemagglutination) titer of 04 with NDV and IBV viral strain respectively. It is concluded that lizard oil has antimicrobial potential against different pathogens strains (virus, bacteria).

Resumo O presente trabalho de pesquisa apresenta a importância antiviral e antibacteriana da gordura corporal de Saara hardwickii, comumente chamado de lagarto de cauda espinhosa. O óleo foi extraído de gorduras corporais localizadas na região ventral desse animal usando hidrocarbonetos, por exemplo, n-hexano, metanol, butanol e acetato de etila, como solvente. A atividade antibacteriana do óleo do lagarto foi testada em linhagens padrão e multirresistentes de Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa e Proteus vulgaris, de forma isolada e com antibiótico ampicilina. Para o potencial antibacteriano, acetato de etila e extrato de butanol apresentaram melhor zona de inibição (7 mm) com P. aeruginosa e S. aureus, respectivamente. Para o potencial antiviral, o extrato de butanol e o extrato de metanol apresentaram melhor título de hemaglutinação de 4 com as cepas virais NDV e IBV, respectivamente. Conclui-se que o óleo do lagarto possui potencial antimicrobiano contra diferentes cepas de patógenos (vírus e bactérias).

An antimicrobial activity of oil extracted from Saara hardwickii / Atividade antimicrobiana do óleo extraído de Saara hardwickii

Present research work represents antiviral and antibacterial value of body fat of Saara hardwickii commonly called as spiny tailed lizard. Oil was extracted from body fats located in the ventral region of this animal using hydrocarbons e.g., n-hexane, methanol, butanol and ethyl acetate as a solvent. The antibacterial activity of lizard oil was tested against standard as well as multi-resistant lines ofEscherichia coli, Styphalococcus aureus, Pseudomonas aeruginosa and Proteus vulgaris alone and with antibiotic ampicillin. For antibacterial potential, Ethyl acetate and Butanol solvent extract showed best zone of inhibition (7mm) with P. aeruginosa and S. aureus respectively. For antiviral potential, Butanol and Methanol extract showed best HA (Hemagglutination) titer of 04 with NDV and IBV viral strain respectively. It is concluded that lizard oil has antimicrobial potential against different pathogens strains (virus, bacteria).

O presente trabalho de pesquisa apresenta a importância antiviral e antibacteriana da gordura corporal de Saara hardwickii, comumente chamado de lagarto de cauda espinhosa. O óleo foi extraído de gorduras corporais localizadas na região ventral desse animal usando hidrocarbonetos, por exemplo, n-hexano, metanol, butanol e acetato de etila, como solvente. A atividade antibacteriana do óleo do lagarto foi testada em linhagens padrão e multirresistentes de Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa e Proteus vulgaris, de forma isolada e com antibiótico ampicilina. Para o potencial antibacteriano, acetato de etila e extrato de butanol apresentaram melhor zona de inibição (7 mm) com P. aeruginosa e S. aureus, respectivamente. Para o potencial antiviral, o extrato de butanol e o extrato de metanol apresentaram melhor título de hemaglutinação de 4 com as cepas virais NDV e IBV, respectivamente. Conclui-se que o óleo do lagarto possui potencial antimicrobiano contra diferentes cepas de patógenos (vírus e bactérias).

Noise-induced hormonal & morphological malformations in breeding pigeons.

Environmental pollution has the potential to have a significant impact on animal's health especially on birds due to daily exposure and habitat. This experimental study was carried out for a 60 days period in which, a total of 24 pigeon birds with suitable weight (80-100 g) were kept in Animal house with suitable environmental conditions viz, controlled temperature, humidity & light source to minimize any other stress. Out of twenty-four, eighteen birds were divided into three treatment groups (6 birds in each group). Whole experiment was run in triplicate manner in breeding season. One served as Control (Group 1) and remaining three were experimental groups including Road traffic noise (Group 2), Military noise (Group 3) & Human activities noise (Group 4). Noise was applied as recorded high intensity music (1125 Hz/ 90 dB) through speakers for 5-6 hrs. daily. Blood sampling was done after 20, 40 and 60 days by sacrificing treatment birds. Noise stress significantly (p<0.05) increase the serum levels of corticosterone and thyroid stimulating hormone (TSH) in Group 2 while significantly (p<0.05) decrease the serum levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH) of Group 3 birds. Moreover, major fault bars formation was seen both in Group 2 and Group 3. It was concluded as that Noise stress caused rise in serum levels of Corticosterone and TSH but fall in LH and FSH. Along with fault bars formation was also prominent in all treatment groups due to stress hormone.

Capturing the Complex Relationship Between Internal and External Training Load: A Data-Driven Approach.

BACKGROUND: Training load is typically described in terms of internal and external load. Investigating the coupling of internal and external training load is relevant to many sports. Here, continuous kernel-density estimation (KDE) may be a valuable tool to capture and visualize this coupling. AIM: Using training load data in speed skating, we evaluated how well bivariate KDE plots describe the coupling of internal and external load and differentiate between specific training sessions, compared to training impulse scores or intensity distribution into training zones. METHODS: On-ice training sessions of 18 young (sub)elite speed skaters were monitored for velocity and heart rate during 2 consecutive seasons. Training session types were obtained from the coach's training scheme, including endurance, interval, tempo, and sprint sessions. Differences in training load between session types were assessed using Kruskal-Wallis or Kolmogorov-Smirnov tests for training impulse and KDE scores, respectively. RESULTS: Training impulse scores were not different between training session types, except for extensive endurance sessions. However, all training session types differed when comparing KDEs for heart rate and velocity (both P < .001). In addition, 2D KDE plots of heart rate and velocity provide detailed insights into the (subtle differences in) coupling of internal and external training load that could not be obtained by 2D plots using training zones. CONCLUSION: 2D KDE plots provide a valuable tool to visualize and inform coaches on the (subtle differences in) coupling of internal and external training load for training sessions. This will help coaches design better training schemes aiming at desired training adaptations.

A preliminary feasibility study of potential market applications for non-commercial technology magnets.

Climate change has spurred increased electrification through means of transportation, hydropower, and wind turbines which has caused an increased demand for permanent magnet materials. Current commercial magnet technologies rely heavily on several critical materials such as neodymium, praseodymium, dysprosium, samarium, and cobalt which are primarily sourced and refined outside of the United States (U.S.). To combat these problems, the Critical Materials Institute (CMI) has begun research into alternative magnet compositions to reduce critical material content. Additionally, these alternative magnets can fulfill a gap in the market between high performance neodymium-iron-boron (Nd-Fe-B) and samarium cobalt (Sm-Co) magnets and low performance ferrite or bonded Nd-Fe-B magnets, earning the term gap magnets. This research seeks to compile a simple strategy for identifying an application for these alternative magnets and assessing preliminary market impacts through substitution for two example magnets. The first magnet was identified to be applicable for ancillary motors and sensors in conventional gasoline vehicles with a maximum substitution of 4,825 metric tonnes (mt) per year by the year 2050. The second magnet was identified to be applicable for magnetic couplings in energy and industrial sectors with a maximum substitution of 978 mt per year by the year 2050.

Effects of syphilis infection among HIV-1-positive individuals on suppressive antiretroviral therapy.

INTRODUCTION: Incident syphilis leads to changes in plasma HIV-1 RNA and CD4 + T-cell level in people with HIV (PWH) with viraemia. Its effect in PWH on suppressive antiretroviral therapy (ART) is less clear. METHODS: PWH on suppressive ART (plasma HIV-1 RNA < 50copies/mL) followed at the Queen Elizabeth Hospital, Hong Kong, China were regularly screened for syphilis. Their plasma HIV-1 RNA, CD4 + and CD8 + T-cell, and total lymphocyte levels before syphilis, during syphilis, and after successful treatment were compared. RESULTS: Between 2005 and 2020, 288 syphilis episodes from 180 individuals were identified; 287 episodes were related to male, with a median age of 41 at diagnosis; 221 (77%) were syphilis re-infection. The rates of plasma HIV-1 suppression were statistically unchanged across the time-points (97% pre-syphilis, 98% during syphilis, and 99% post-treatment). Total lymphocyte, CD4+ and CD8+ T-cell levels decreased during incident syphilis (p<0.01), and rebounded post-treatment (p<0.01). VDRL titre was associated with declines in CD4+ T-cell (p=0.045), CD8+ T-cell (p=0.004), and total lymphocyte levels (p=0.021). Pre-syphilis CD4/CD8 ratio was associated with increases in CD8+ T-cell (p=0.001) and total lymphocyte levels (p=0.046) during syphilis. Syphilis re-infection was associated with an increase in total lymphocyte level (p=0.037). In the multivariable analysis, only pre-syphilis CD4/CD8 ratio was independently associated with increases in CD8+ T-cell (p=0.014) and total lymphocyte levels (p=0.039) during syphilis. CONCLUSIONS: Among virally-suppressed PWH, total lymphocyte, CD4+, and CD8+ T-cell levels declined during incident syphilis but rebounded post-treatment. The status of plasma HIV suppression was unaffected by syphilis.

Co-Operative Design of a Coach Dashboard for Training Monitoring and Feedback.

Athlete development depends on many factors that need to be balanced by the coach. The amount of data collected grows with the development of sensor technology. To make data-informed decisions for training prescription of their athletes, coaches could be supported by feedback through a coach dashboard. The aim of this paper is to describe the design of a coach dashboard based on scientific knowledge, user requirements, and (sensor) data to support decision making of coaches for athlete development in cyclic sports. The design process involved collaboration with coaches, embedded scientists, researchers, and IT professionals. A classic design thinking process was used to structure the research activities in five phases: empathise, define, ideate, prototype, and test phases. To understand the user requirements of coaches, a survey (n = 38), interviews (n = 8) and focus-group sessions (n = 4) were held. Design principles were adopted into mock-ups, prototypes, and the final coach dashboard. Designing a coach dashboard using the co-operative research design helped to gain deep insights into the specific user requirements of coaches in their daily training practice. Integrating these requirements, scientific knowledge, and functionalities in the final coach dashboard allows the coach to make data-informed decisions on training prescription and optimise athlete development.

Perceived Training of Junior Speed Skaters versus the Coach's Intention: Does a Mismatch Relate to Perceived Stress and Recovery?

The aim of this observational study was to examine the differences between training variables as intended by coaches and perceived by junior speed skaters and to explore how these relate to changes in stress and recovery. During a 4-week preparatory period, intended and perceived training intensity (RPE) and duration (min) were monitored for 2 coaches and their 23 speed skaters, respectively. The training load was calculated by multiplying RPE by duration. Changes in perceived stress and recovery were measured using RESTQ-sport questionnaires before and after 4 weeks. Results included 438 intended training sessions and 378 executed sessions of 14 speed skaters. A moderately higher intended (52:37 h) versus perceived duration (45:16 h) was found, as skaters performed fewer training sessions than anticipated (four sessions). Perceived training load was lower than intended for speed skating sessions (-532 ± 545 AU) and strength sessions (-1276 ± 530 AU) due to lower RPE scores for skating (-0.6 ± 0.7) or shorter and fewer training sessions for strength (-04:13 ± 02:06 hh:mm). All training and RESTQ-sport parameters showed large inter-individual variations. Differences between intended-perceived training variables showed large positive correlations with changes in RESTQ-sport, i.e., for the subscale's success (r = 0.568), physical recovery (r = 0.575), self-regulation (r = 0.598), and personal accomplishment (r = 0.589). To conclude, speed skaters that approach or exceed the coach's intended training variables demonstrated an increased perception of success, physical recovery, self-regulation, and personal accomplishment.

Introducing a Method to Quantify the Specificity of Training for Races in Speed Skating.

ABSTRACT: Roete, AJ, Stoter, IK, Lamberts, RP, Elferink-Gemser, MT, and Otter, RTA. Introducing a method to quantify the specificity of training for races in speed skating. J Strength Cond Res 36(7): 1998-2004, 2022-The specificity of training for races is believed to be important for performance development. However, measuring specificity is challenging. This study aimed to develop a method to quantify the specificity of speed skating training for sprint races (i.e., 500 and 1,000 m), and explore the amount of training specificity with a pilot study. On-ice training and races of 10 subelite-to-elite speed skaters were analyzed during 1 season (i.e., 26 weeks). Intensity was mapped using 5 equal zones, between 4 m·s-1 to peak velocity and 50% to peak heart rate. Training specificity was defined as skating in the intensity zone most representative for the race for a similar period as during the race. During the season, eight 500 m races, seven 1,000 m races, and 509 training sessions were analyzed, of which 414 contained heart rate and 375 sessions contained velocity measures. Within-subject analyses were performed. During races, most time was spent in the highest intensity zone (Vz5 and HRz5). In training, the highest velocity zone Vz5 was reached 107 ± 28 times, with 9 ± 3 efforts (0.3 ± 0.1% training) long enough to be considered 500 m specific, 6 ± 5 efforts (0.3 ± 0.3% training) were considered 1,000 m specific. For heart rate, HRz5 was reached 151 ± 89 times in training, 43 ± 33 efforts (1.3 ± 0.9% training) were considered 500 m specific, and 36 ± 23 efforts (3.2 ± 1.7% training) were considered 1,000 m specific. This newly developed method enables the examination of training specificity so that coaches can control whether their intended specificity was reached. It also opens doors to further explore the impact of training specificity on performance development.

Long-Term Heat Selection of the Coral Endosymbiont Cladocopium C1acro (Symbiodiniaceae) Stabilizes Associated Bacterial Communities.

Heat-tolerant strains of the coral endosymbiont, Cladocopium C1acro (Symbiodiniaceae), have previously been developed via experimental evolution. Here, we examine physiological responses and bacterial community composition (using 16S rRNA gene metabarcoding) in cultures of 10 heat-evolved (SS) and 9 wild-type (WT) strains, which had been exposed for 6 years to 31 °C and 27 °C, respectively. We also examine whether the associated bacterial communities were affected by a three-week reciprocal transplantation to both temperatures. The SS strains had bacterial communities with lower diversities that showed more stability and lower variability when exposed to elevated temperatures compared with the WT strains. Amplicon sequence variants (ASVs) of the bacterial genera Labrenzia, Algiphilus, Hyphobacterium and Roseitalea were significantly more associated with the SS strains compared with the WT strains. WT strains showed higher abundance of ASVs assigned to the genera Fabibacter and Tropicimonas. We hypothesize that these compositional differences in associated bacterial communities between SS and WT strains also contribute to the thermal tolerance of the microalgae. Future research should explore functional potential between bacterial communities using metagenomics to unravel specific genomic adaptations.

An antimicrobial activity of oil extracted from Saara hardwickii.

Present research work represents antiviral and antibacterial value of body fat of Saara hardwickii commonly called as spiny tailed lizard. Oil was extracted from body fats located in the ventral region of this animal using hydrocarbons e.g., n-hexane, methanol, butanol and ethyl acetate as a solvent. The antibacterial activity of lizard oil was tested against standard as well as multi-resistant lines ofEscherichia coli, Styphalococcus aureus, Pseudomonas aeruginosa and Proteus vulgaris alone and with antibiotic ampicillin. For antibacterial potential, Ethyl acetate and Butanol solvent extract showed best zone of inhibition (7mm) with P. aeruginosa and S. aureus respectively. For antiviral potential, Butanol and Methanol extract showed best HA (Hemagglutination) titer of 04 with NDV and IBV viral strain respectively. It is concluded that lizard oil has antimicrobial potential against different pathogens strains (virus, bacteria).

Why Train Together When Racing Is Performed Alone? Drafting in Long-Track Speed Skating.

PURPOSE: In long-track speed skating, drafting is a commonly used phenomenon in training; however, it is not allowed in time-trial races. In speed skating, limited research is available on the physical and psychological impact of drafting. The aim of this study was to determine the influence of "skating alone," "leading," or "drafting" on physical intensity (heart rate and blood lactate) and perceived intensity (perceived exertion) of speed skaters. METHODS: Twenty-two national-level long-track speed skaters with a mean age of 19.3 (2.6) years skated 5 laps, with similar external intensity in 3 different conditions: skating alone, leading, or drafting. Repeated-measures analysis of variance showed differences between the 3 conditions, heart rate (F2,36 = 10.546, P < .001), lactate (F2,36 = 12.711, P < .001), and rating of perceived exertion (F2,36 = 5.759, P < .01). RESULTS: Heart rate and lactate concentration were significantly lower (P < .001) when drafting compared with leading (heart rate Δ = 7 [8] beats·min-1, 4.0% [4.7%]; lactate Δ = 2.3 [2.3] mmol/L, 28.2% [29.9%]) or skating alone (heart rate Δ = 8 [7.1] beats·min-1, 4.6% [3.9%]; lactate Δ = 2.8 [2.5] mmol/L, 33.6% [23.6%]). Rating of perceived exertion was significantly lower (P < .01) when drafting (Δ = 0.8 [1.0], 16.5% [20.9%]) or leading (Δ = 0.5 [0.9], 7.7% [20.5%]) versus skating alone. CONCLUSIONS: With similar external intensity, physical intensity, as well as perceived intensity, is reduced when drafting in comparison with skating alone. A key finding of this study is the psychological effect: Skating alone was shown to be more demanding than leading, whereas leading and drafting were perceived to be similar in terms of perceived exertion. Knowledge about the reduction of internal intensity for a drafting skater compared with leading or skating alone can be used by coaches and trainers to optimize training conditions.

A Systematic Review on Markers of Functional Overreaching in Endurance Athletes.

PURPOSE: The aim of this brief review was to present an overview of noninvasive markers in trained to professional endurance athletes that can reflect a state of functional overreaching. METHODS: A systematic literature search was conducted in the PubMed, Scopus, and PsycINFO databases. After screening 380 articles, 12 research papers were included for the systematic review. RESULTS: Good consensus was found between the different papers in which noninvasive parameters were able to reflect a state of functional overreaching. Changes in power output (PO), heart rate (HR; [sub]maximal and HR recovery), rating of perceived exertion, and scores in the Daily Analysis of Life Demands for Athletes (DALDA) and/or Profile of Mood States (POMS) were shown to be able to reflect functional overreaching, whereas changes in maximal oxygen uptake and HR-variability parameters were not. CONCLUSION: Functional overreaching within a maximal performance test was characterized by a decrease in peak PO and a lower maximum HR, whereas a lower mean PO and a lower HR were observed during time trials. Changes in parameters during a standardized submaximal test when functionally overreached were characterized by a higher PO at a fixed HR or a lower HR at a fixed intensity, higher rating of perceived exertion, and a faster HR recovery. Although both the DALDA and POMS were able to reflect functional overreaching, the POMS was not able to differentiate this response from acute fatigue, which makes it unsuitable for accurately monitoring functional overreaching.

Critical material content in modern conventional U.S. vehicle electronics.

Critical materials (CMs) are vital to modern technology. Components of modern vehicles can be recycled to recover and reuse the CMs to help ensure a supply of these materials. Electronic components from a 2015 GMC Sierra truck (21 components) and 2016 Toyota Camry sedan (10 components) were analyzed for CMs. The components were processed via size reduction, aqua regia leaching and dissolution, and final solutions were analyzed for metal content. It was found that most electronic components of both vehicles contain CMs. The most concentrated CMs in the components were Sn, Nb, and Tb. Nd and Co were found in several of the magnetic components. CM economic value was found to be low compared to the overall value of the components, and the CM content would not allow for a viable pathway for recycling. Remanufacturing of components may be a more economic option of reuse in the future.

NdFeB content in ancillary motors of U.S. conventional passenger cars and light trucks: Results from the field.

Research into secondary recovery of rare earth elements (REE) has focused mostly on hard disk drives and automotive applications. While REE content in Japanese and European vehicles is relatively well-known, understanding of U.S. vehicles is mostly based on database analysis. An attempt to pinpoint which components contain the most REEs was conducted on four different vehicle models including the Ford F-150, Chevrolet Silverado, Toyota Corolla and Honda Accord. The disassembly data were combined with 2017 vehicles in operation to estimate stocks and flows of Neodymium-Iron-Boron (NdFeB). Results showed that U.S. vehicles had major differences compared to Japanese and European vehicles. NdFeB magnets were only found in speakers ranging from 16 to 114 g/vehicle. An estimated 3.0-14 tonnes of NdFeB could be available from end-of-life vehicles in 2018 from different cohorts of the four aforementioned models. While opportunities for recycling NdFeB in vehicles exist, challenges are also present.

Freeing Chinese Abused Women From Stereotype: A Pretest-Posttest Comparison Study on Group Intervention in Refuge Centers.

OBJECTIVE: The efficacy of heal-change group (HCG) intervention-brief trauma-recovery group intervention applying a gender-specific cognitive behavioral approach-for Chinese-abused women in refuge centers was examined in a pretest-posttest comparison study. METHODS: A total of 100 women at three refuge centers in Hong Kong participated. Among them, 50 women from two centers joined the HCG and 50 women from the remaining center participated in a comparison mutual support group. Participants and interviewers were blinded to the group assignment. Both groups were six sessions long. Linear regression analyses were performed using the intention-to-treat framework. RESULTS: Significant improvements in PTSD symptoms (overall mean change of -1.6, p < .001; subdomain scores; p < .001 to < .01) and depressive symptoms (BDI-II mean change; p < .01) were recorded in the intervention group. CONCLUSION: The results suggest HCG is beneficial to Chinese-abused women. Further research is needed to determine the intervention's effectiveness in improving longer-term outcomes in these women.

cGAS surveillance of micronuclei links genome instability to innate immunity.

DNA is strictly compartmentalized within the nucleus to prevent autoimmunity; despite this, cyclic GMP-AMP synthase (cGAS), a cytosolic sensor of double-stranded DNA, is activated in autoinflammatory disorders and by DNA damage. Precisely how cellular DNA gains access to the cytoplasm remains to be determined. Here, we report that cGAS localizes to micronuclei arising from genome instability in a mouse model of monogenic autoinflammation, after exogenous DNA damage and spontaneously in human cancer cells. Such micronuclei occur after mis-segregation of DNA during cell division and consist of chromatin surrounded by its own nuclear membrane. Breakdown of the micronuclear envelope, a process associated with chromothripsis, leads to rapid accumulation of cGAS, providing a mechanism by which self-DNA becomes exposed to the cytosol. cGAS is activated by chromatin, and consistent with a mitotic origin, micronuclei formation and the proinflammatory response following DNA damage are cell-cycle dependent. By combining live-cell laser microdissection with single cell transcriptomics, we establish that interferon-stimulated gene expression is induced in micronucleated cells. We therefore conclude that micronuclei represent an important source of immunostimulatory DNA. As micronuclei formed from lagging chromosomes also activate this pathway, recognition of micronuclei by cGAS may act as a cell-intrinsic immune surveillance mechanism that detects a range of neoplasia-inducing processes.

Polycystic ovarian syndrome (PCOS), related symptoms/sequelae, and breast cancer risk in a population-based case-control study.

PURPOSE: Despite the overlap between the clinical symptoms/sequelae of polycystic ovarian syndrome (PCOS) and many known reproductive risk factors for breast cancer, the relationship between PCOS and breast cancer remains unclear, possibly because of the complex heterogeneity and challenges in diagnosing PCOS over time. We hypothesized that PCOS, specific PCOS-related symptoms/sequelae, or clusters of PCOS-related symptoms/sequelae may be differentially associated with pre- versus postmenopausal breast cancer risk. MATERIALS AND METHODS: Cases were 1,508 women newly diagnosed with a first primary in situ or invasive breast, and the 1,556 population-based controls were frequency-matched by age. RESULTS: History of physician-diagnosed PCOS was reported by 2.2 % (n = 67), among whom oral contraceptive (OC) use, irregular menstruation, and infertility due to ovulatory dysfunction were common. Using unconditional logistic regression, adjusted odds ratios (95 % CI) for PCOS were increased for premenopausal [2.74 (1.13, 6.63)], but not postmenopausal breast cancer [0.87 (0.44, 1.71)]. We used cluster analysis to investigate whether risk among all women varied by PCOS-related symptoms/sequelae, such as reproductive irregularities, OC use, and components of insulin resistance. In the cluster analysis, odds ratios were elevated among premenopausal women who had a history of OC use and no ovulatory dysfunction [1.39 (1.03, 1.88)], compared to those with fewer number of PCOS-related symptoms/sequelae. CONCLUSION: PCOS and associated PCOS-related symptoms/sequelae including OC use may play a role in the development of premenopausal breast cancer. Our findings require confirmation in studies with a larger number of premenopausal women with systematically applied diagnostic criteria for PCOS.

A New Submaximal Rowing Test to Predict 2,000-m Rowing Ergometer Performance.

The purpose of this study was to assess predictive value of a new submaximal rowing test (SmRT) on 2,000-m ergometer rowing time-trial performance in competitive rowers. In addition, the reliability of the SmRT was investigated. Twenty-four competitive male rowers participated in this study. After determining individual HRmax, all rowers performed an SmRT followed by a 2,000-m rowing ergometer time trial. In addition, the SmRT was performed 4 times (2 days in between) to determine the reliability. The SmRT consists of two 6-minute stages of rowing at 70 and 80% HRmax, followed by a 3-minute stage at 90% HRmax. Power was captured during the 3 stages, and 60 seconds of heart rate recovery (HRR60s) was measured directly after the third stage. Results showed that predictive value of power during the SmRT on 2,000-m rowing time also increased with stages. CVTEE% is 2.4, 1.9, and 1.3%. Pearson correlations (95% confidence interval [95% CI]) were -0.73 (-0.88 to -0.45), -0.80 (-0.94 to -0.67), and -0.93 (-0.97 to -0.84). 2,000-m rowing time and HRR60s showed no relationship. Reliability of power during the SmRT improved with the increasing intensity of the stages. The coefficient of variation (CVTEM%) was 9.2, 5.6, and 0.4%. Intraclass correlation coefficients (ICC) and 95% CI were 0.91 (0.78-0.97), 0.92 (0.81-0.97), and 0.99 (0.97-1.00). The CVTEM% and ICC of HRR60s were 8.1% and 0.93 (0.82-0.98). In conclusion, the data of this study shows that the SmRT is a reliable test that it is able to accurately predict 2,000-m rowing time on an ergometer. The SmRT is a practical and valuable submaximal test for rowers, which can potentially assist with monitoring, fine-tuning and optimizing training prescription in rowers.