The AUstralian multidomain Approach to Reduce dementia Risk by prOtecting brain health With lifestyle intervention study (AU-ARROW): A study protocol for a single-blind, multi-site, randomized controlled trial.

INTRODUCTION: The Finnish Geriatric Intervention Study (FINGER) led to the global dementia risk reduction initiative: World-Wide FINGERS (WW-FINGERS). As part of WW-FINGERS, the Australian AU-ARROW study mirrors aspects of FINGER, as well as US-POINTER. METHOD: AU-ARROW is a randomized, single-blind, multisite, 2-year clinical trial (n = 600; aged 55-79). The multimodal lifestyle intervention group will engage in aerobic exercise, resistance training and stretching, dietary advice to encourage MIND diet adherence, BrainHQ cognitive training, and medical monitoring and health education. The Health Education and Coaching group will receive occasional health education sessions. The primary outcome measure is the change in a global composite cognitive score. Extra value will emanate from blood biomarker analysis, positron emission tomography (PET) imaging, brain magnetic resonance imaging (MRI), and retinal biomarker tests. DISCUSSION: The finalized AU-ARROW protocol is expected to allow development of an evidence-based innovative treatment plan to reduce cognitive decline and dementia risk, and effective transfer of research outcomes into Australian health policy. Highlights: Study protocol for a single-blind, randomized controlled trial, the AU-ARROW Study.The AU-ARROW Study is a member of the World-Wide FINGERS (WW-FINGERS) initiative.AU-ARROW's primary outcome measure is change in a global composite cognitive score.Extra significance from amyloid PET imaging, brain MRI, and retinal biomarker tests.Leading to development of an innovative treatment plan to reduce cognitive decline.

Comparison of Volume Measurements and Bioimpedance Spectroscopy Using A Stand-on Device for Assessment of Unilateral Breast Cancer-Related Lymphedema.

Objective: Breast cancer related lymphedema (BCRL) may be assessed through objective measurement of limb swelling with common techniques including volumetric measurement using a tape measure or perometry, and measurement of extracellular water using bioimpedance spectroscopy (BIS). This study aimed to evaluate the performance of a stand-on BIS device for detection of BCRL, introduce a novel graphical method to compare volumetric and BIS methods alongside traditional specificity and sensitivity analysis, and determine and compare BIS thresholds with those published previously. Materials and Methods: Female participants with indocyanine green lymphography confirmed unilateral arm lymphedema (n = 197) and healthy controls (n = 267) were assessed using a cross-sectional study design. BIS and volumetric measures were obtained in a single session. Results: The BIS lymphedema index (L-Dex) method had a significantly higher sensitivity than the excess volume approach (area under the curve = 0.832 vs. 0.649, p = 0.0001). A threshold of L-Dex 6.5 had a higher true positive rate (70.6%) than L-Dex 10 (68.5%) although false positive rate increased from 0.4% to 2.6%. A threshold of 5% excess volume improved the true positive rate (68.5%) compared with 10% excess volume (49.7%) however the false positive rate increased to an unacceptable 47%. The L-Dex ranges in this study were not significantly different from previously published ranges. Conclusion: BIS was superior for identifying BCRL compared with volume measurements, reaffirming the value of this technique. However, it is recommended that BIS be used in conjunction with comprehensive evaluation of symptoms and clinical presentation. The proposed graphical method provides a simple and easily interpretable approach to compare and define concordance between the two commonly used methods for BCRL assessment namely limb volume and BIS L-Dex indices. The existing BIS (L-Dex) thresholds for presence of BCRL were also validated.

Immune and behavioral correlates of protection against symptomatic post-vaccination SARS-CoV-2 infection.

Introduction: We sought to determine pre-infection correlates of protection against SARS-CoV-2 post-vaccine inzfections (PVI) acquired during the first Omicron wave in the United States. Methods: Serum and saliva samples from 176 vaccinated adults were collected from October to December of 2021, immediately before the Omicron wave, and assessed for SARS-CoV-2 Spike-specific IgG and IgA binding antibodies (bAb). Sera were also assessed for bAb using commercial assays, and for neutralization activity against several SARS-CoV-2 variants. PVI duration and severity, as well as risk and precautionary behaviors, were assessed by questionnaires. Results: Serum anti-Spike IgG levels assessed by research assay, neutralization titers against Omicron subvariants, and low home risk scores correlated with protection against PVIs after multivariable regression analysis. Commercial assays did not perform as well as research assay, likely due to their lower dynamic range. Discussion: In the 32 participants that developed PVI, anti-Spike IgG bAbs correlated with lower disease severity and shorter duration of illness.

Comparison of fluid and body composition measures in women with lipoedema, lymphoedema, and control participants.

Lipoedema is the disproportionate accumulation of adipose tissue in the lower body, often associated with hormonal changes in women. Lipoedema is commonly misdiagnosed as lymphoedema or obesity due to similarities in appearance. The aim of this study is to compare body composition and fluid measures of women with lipoedema, lymphoedema, and matched control participants, to determine differences that may help distinguish between each condition. One hundred and eleven participants aged over 18, who presented with the complaint of leg swelling and underwent indocyanine green lymphography were included in this study. Our analysis showed that the individuals with lymphoedema had a significantly higher overall total body water (lymphoedema: 9.6 ± 4.2 L, lipoedema: 7.4 ± 2.3 L, control: 7.5 ± 1.8 L; p < .001) and extracellular fluid (lymphoedema: 4.6 ± 1.6, lipoedema: 3.4 ± 1.0 L, control: 3.5 ± 0.7 L; p < .001) in the legs when compared to individuals with lipoedema and matched control participants. Individuals with lipoedema had a significantly higher overall fat mass as a percentage of body weight when compared to individuals with lymphoedema (lymphoedema: 33.1% ± 9.5%, lipoedema: 39.4% ± 6.5%; p = .003). We are unable to distinguish between individuals with lipoedema and control participants, therefore further research needs to be conducted to help reduce misdiagnosis.

Body composition and chemotherapy toxicities in breast cancer: a systematic review of the literature.

PURPOSE: Breast cancer is the most diagnosed cancer in women with chemotherapy being a common treatment. Toxicities due to chemotherapy can result in dose reduction, delay, and early cessation of treatment, which along with causing distress for individuals during their cancer treatment might also reduce the therapeutic effect. The purpose of this systematic review is to examine the role of body composition on chemotherapy toxicities in women with breast cancer. METHODS: A systematic search of the literature was completed on electronic databases Pubmed, Embase, CINHAHL, and Cochrane. Studies were included if the direct effect of body composition on chemotherapy toxicities was reported and excluded if body composition could not be isolated. A critical appraisal of the studies included was performed using McMasters University Critical Review Form for Quantitative Studies. RESULTS: Eleven studies were included with a total of 2881 female participants. All studies reported significant relationships between body composition and chemotherapy toxicities; however, individual parameters differed between the studies. Adding to the heterogeneity, different thresholds were reported to determine both sarcopenia and myosteatosis, making it difficult to identify a common finding. CONCLUSION: This review suggests that body composition may be an important factor in predicting the severity of chemotherapy toxicities during treatment for breast cancer; however, the lack of international consensus as to thresholds in the literature for sarcopenia and myosteatosis may result in bias. The review supports the need for further prospective studies, allowing for more robust, pre-determined data collection, to better understand the implications of body composition on toxicities and benefits of using body composition to individualize chemotherapy dosing. IMPLICATIONS FOR CANCER SURVIVORS: Toxicities due to chemotherapy can result in treatment being unable to be completed as planned, potentially resulting in poorer survival outcomes. Improved knowledge in this area may give rise to a more reliable way of individualizing chemotherapy dosage to help mitigate this risk.

Effects of Body Positioning When Assessing Lymphedema of the Lower Limb Using Bioimpedance Spectroscopy.

Background: Bioimpedance spectroscopy (BIS) measurements are conventionally performed in supine position with a lead device attached to gel-backed electrodes, and more recently, with a stand-on device that uses fixed stainless-steel electrodes under the hands and feet. The aim of this study was to assess and compare BIS measurements made in supine, sitting, and standing positions using lead and stand-on impedance devices in participants with and without unilateral leg lymphedema. Materials and Methods: Participants with self-ascribed unilateral leg lymphedema (n = 24) and healthy controls (n = 71) were recruited using a cross-sectional study design. Triplicate BIS measurements were taken for each device in each position. Results: Impedance measurements with either device were reliable with coefficient of variation of 0.6% or lower. The magnitude of mean differences in absolute impedance values between devices were between 1% and 6% dependent on condition. L-Dex scores between the two devices were highly correlated (r = 0.82) and ∼70% of participants in the lymphedema group were classified as having lymphedema using the recommended cut-off with either device. There was no significant interleg difference of controls using the lead device; however, small, but significant differences (p = 0.0001) were found when using the stand-on device. Conclusion: The findings demonstrate that reliable impedance measurements of the legs can be made with either device in lying, sitting, or standing positions. However, data between the devices were not directly interchangeable. Although the risk of misidentification was small, reference ranges appropriate to the device and measurement position should be used when converting data to L-Dex scores.

Natural killer cells and BNT162b2 mRNA vaccine reactogenicity and durability.

Introduction: Natural killer (NK) cells can both amplify and regulate immune responses to vaccination. Studies in humans and animals have observed NK cell activation within days after mRNA vaccination. In this study, we sought to determine if baseline NK cell frequencies, phenotype, or function correlate with antibody responses or inflammatory side effects induced by the Pfizer-BioNTech COVID-19 vaccine (BNT162b2). Methods: We analyzed serum and peripheral blood mononuclear cells (PBMCs) from 188 participants in the Prospective Assessment of SARS-CoV-2 Seroconversion study, an observational study evaluating immune responses in healthcare workers. Baseline serum samples and PBMCs were collected from all participants prior to any SARS-CoV-2 infection or vaccination. Spike-specific IgG antibodies were quantified at one and six months post-vaccination by microsphere-based multiplex immunoassay. NK cell frequencies and phenotypes were assessed on pre-vaccination PBMCs from all participants by multi-color flow cytometry, and on a subset of participants at time points after the 1st and 2nd doses of BNT162b2. Inflammatory side effects were assessed by structured symptom questionnaires, and baseline NK cell functionality was quantified by an in vitro killing assay on participants that reported high or low post-vaccination symptom scores. Results: Key observations include: 1) circulating NK cells exhibit evidence of activation in the week following vaccination, 2) individuals with high symptom scores after 1st vaccination had higher pre-vaccination NK cytotoxicity indices, 3) high pre-vaccination NK cell numbers were associated with lower spike-specific IgG levels six months after two BNT162b2 doses, and 4) expression of the inhibitory marker NKG2A on immature NK cells was associated with higher antibody responses 1 and 6 months post-vaccination. Discussion: These results suggest that NK cell activation by BNT162b2 vaccination may contribute to vaccine-induced inflammatory symptoms and reduce durability of vaccine-induced antibody responses.

The Prevalence of the Axillo-Inguinal Lymphatic Pathway in Lymphedema of the Extremities and Potential Therapeutic Implications.

Background: The axillo-inguinal (or inguino-axillary) is a compensatory lymphatic drainage pathway regularly utilized by lymphedema therapists when applying manual lymphatic drainage (MLD) for upper and lower extremity lymphedema. However, there is limited evidence of the frequency of this pathway and the characteristics of patients with lymphedema in which this pathway is present. Indocyanine green (ICG) lymphography is an imaging technique that has the capability to identify lymphatic drainage pathways in lymphedema when combined with MLD. In this study, we used ICG lymphography in patients with upper and lower extremity lymphedema to investigate the presence of this pathway and its clinical characteristics. Methods and Results: A retrospective cohort audit of 563 patients with lymphedema (285 with upper extremity and 278 with lower extremity) who underwent ICG lymphography was conducted in combination with MLD. Compensatory lymphatic drainage was investigated. Patients demonstrating the axillo-inguinal pathway were identified, and their clinical characteristics were recorded. The axillo-inguinal pathway was not demonstrated in any patient with upper extremity and only five patients with lower extremity lymphedema. Of these five patients, all were female with a history of secondary cancer-related lymphedema following gynecological cancer. The majority (four) had bilateral lymphedema extending to the lower abdomen and presented with a greater severity of lymphedema. Conclusions: These findings suggest that the axillo-inguinal pathway is an infrequent compensatory drainage pathway in lower extremity lymphedema and rare in upper extremity lymphedema. Our findings have clinical implications for lymphedema management, in particular, the sequence in which MLD is applied.

Differentiation of lipoedema from bilateral lower limb lymphoedema by imaging assessment of indocyanine green lymphography.

Lipoedema is characterized by disproportionate painful fat accumulation mostly in the lower limbs. The presence of lymphoedema in lipoedema remains controversial. This study aimed to assess the presence or absence of lymphoedema in the lower limbs of women with lipoedema using indocyanine green (ICG) lymphography. A cross-sectional retrospective study was undertaken in women with a clinical diagnosis of lipoedema whose lower limbs were examined with ICG lymphography. MD Anderson Cancer Center (MDACC) ICG staging was used to determine lymphoedema presence and severity. Patient characteristics, ICG lymphography findings, Stemmer sign, body mass index, waist-to-hip ratio, limb volume and bioimpedance spectroscopy measures were recorded. Forty women with lipoedema underwent ICG lymphography for the lower limbs from January 2018 to July 2022. Thirty-four women (85.0%) were determined by ICG lymphography as MDACC ICG Stage 0 representing normal lymphatics. Of the six women who demonstrated dermal backflow on ICG lymphography, all were determined as ICG Stage 1, four had localized traumatic dermal backflow area at their ankles, one had previously diagnosed with primary lymphoedema and one was classified as lipoedema stage 4. ICG lymphography findings suggested the absence of lymphoedema in a clear majority of women with lower limb lipoedema.

Cellular interferon-gamma and interleukin-2 responses to SARS-CoV-2 structural proteins are broader and higher in those vaccinated after SARS-CoV-2 infection compared to vaccinees without prior SARS-CoV-2 infection.

Class I- and Class II-restricted epitopes have been identified across the SARS-CoV-2 structural proteome. Vaccine-induced and post-infection SARS-CoV-2 T-cell responses are associated with COVID-19 recovery and protection, but the precise role of T-cell responses remains unclear, and how post-infection vaccination ('hybrid immunity') further augments this immunity To accomplish these goals, we studied healthy adult healthcare workers who were (a) uninfected and unvaccinated (n = 12), (b) uninfected and vaccinated with Pfizer-BioNTech BNT162b2 vaccine (2 doses n = 177, one dose n = 1) or Moderna mRNA-1273 vaccine (one dose, n = 1), and (c) previously infected with SARS-CoV-2 and vaccinated (BNT162b2, two doses, n = 6, one dose n = 1; mRNA-1273 two doses, n = 1). Infection status was determined by repeated PCR testing of participants. We used FluoroSpot Interferon-gamma (IFN-γ) and Interleukin-2 (IL-2) assays, using subpools of 15-mer peptides covering the S (10 subpools), N (4 subpools) and M (2 subpools) proteins. Responses were expressed as frequencies (percent positive responders) and magnitudes (spot forming cells/106 cytokine-producing peripheral blood mononuclear cells [PBMCs]). Almost all vaccinated participants with no prior infection exhibited IFN-γ, IL-2 and IFN-γ+IL2 responses to S glycoprotein subpools (89%, 93% and 27%, respectively) mainly directed to the S2 subunit and were more robust than responses to the N or M subpools. However, in previously infected and vaccinated participants IFN-γ, IL-2 and IFN-γ+IL2 responses to S subpools (100%, 100%, 88%) were substantially higher than vaccinated participants with no prior infection and were broader and directed against nine of the 10 S glycoprotein subpools spanning the S1 and S2 subunits, and all the N and M subpools. 50% of uninfected and unvaccinated individuals had IFN-γ but not IL2 or IFN-γ+IL2 responses against one S and one M subpools that were not increased after vaccination of uninfected or SARS-CoV-2-infected participants. Summed IFN-γ, IL-2, and IFN-γ+IL2 responses to S correlated with IgG responses to the S glycoprotein. These studies demonstrated that vaccinations with BNT162b2 or mRNA-1273 results in T cell-specific responses primarily against epitopes in the S2 subunit of the S glycoprotein, and that individuals that are vaccinated after SARS-CoV-2 infection develop broader and greater T cell responses to S1 and S2 subunits as well as the N and M proteins.

A new indocyanine green fluorescence lymphography protocol for diagnostic assessment of lower limb lymphoedema.

INTRODUCTION: The lower limbs are a common body site affected by chronic edema. Imaging examination of the lymphatic system is useful to diagnose lymphoedema, identify structural changes in individuals, and guide interventional strategies. In this study, we used a protocol combining indocyanine green (ICG) lymphography and ICG-guided manual lymphatic drainage (MLD) for the diagnostic assessment of lower limb lymphoedema. MATERIALS AND METHODS: Patients with lower limb lymphoedema were divided into three groups by their medical history: primary, secondary cancer-related, or secondary non-cancer-related. ICG lymphography was conducted in three phases: initial observation, MLD to accelerate ICG dye transit and reduce imaging time, and imaging data collection. Lymphatic drainage regions were recorded, and the MD Anderson Cancer Center ICG staging was applied. We collected routine lymphoedema assessment data, including limb volume and bioimpedance spectroscopy measurements. RESULTS: Three hundred and twenty-six lower limbs that underwent ICG lymphography were analyzed. Eight drainage regions were identified. The ipsilateral inguinal and popliteal were recognized as the original regions, and the remaining six regions were considered compensatory regions that occur only in lymphoedema. More than half of the secondary cancer-related lower limb lymphoedema (57.6%) continued to drain to the ipsilateral inguinal region. The incidence of drainage to the ipsilateral inguinal region was even higher for the primary (82.8%) and secondary non-cancer-related (87.1%) groups. Significant associations were observed between cancer-related lymphoedema and the presence of compensatory drainage regions. CONCLUSIONS: We proposed a prospective ICG lymphography protocol for the diagnostic assessment of lower limb lymphoedema in combination with MLD. Eight drainage regions were identified, including two original and six compensatory regions.

Retrograde lymph flow in the lymphatic vessels in limb lymphedema.

OBJECTIVE: Retrograde movement of lymph owing to damaged and/or incompetent valves in the lymphatic vessels has been considered a pathological feature of lymphedema. This study aimed to determine the prevalence of retrograde lymph flow and the characteristics of patients with this condition using indocyanine green (ICG) lymphography. METHODS: An audit of 679 patients with upper or lower limb swelling who underwent ICG lymphography was undertaken over a 4-year period. Harvey's technique was applied to identify retrograde flow in the lymph collecting vessel during ICG lymphography. The characteristics of patients with retrograde lymph flow were recorded. RESULTS: Twenty-one patients (3.7%; lower limb, n = 19; upper limb, n = 2) were identified as having retrograde flow in lymph collecting vessels out of 566 confirmed lymphedema patients (lower limb, n = 275; upper limb, n = 291). Of the two patients with upper limb lymphedema (ULLE), one had a short segment of retrograde lymph flow in the forearm. The other patient with ULLE and one patient with lower limb lymphedema (LLLE) were previously diagnosed with lymphedema-distichiasis syndrome. Of the remaining 18 patients with LLLE and retrograde lymph flow, nine had initiating insect bites with lymphangitis and three had palpable benign enlarged inguinal lymph nodes evident before lower limb swelling onset. None had cancer-related LLLE. CONCLUSIONS: Retrograde lymph flow with valve incompetence in the lymph-collecting vessels was a rare finding in ULLE and a relatively uncommon finding in LLLE, contradicting the conventional understanding of pathological changes in lymphedema. ICG lymphography identified anticipated retrograde lymph flow in two patients with lymphedema distichiasis. In the remaining patients, retrograde lymph flow may have resulted from toxic or asymptomatic lymphangitis but there was no association with secondary cancer-related lymphedema. These findings have implication for conservative management as well as lymphovenous anastomosis surgery where both ends of a transected lymph collecting vessel would be potential targets for anastomoses.

Durability of Antibody Response and Frequency of SARS-CoV-2 Infection 6 Months after COVID-19 Vaccination in Healthcare Workers.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies decay but persist 6 months postvaccination; lower levels of neutralizing titers persist against Delta than wild-type virus. Of 227 vaccinated healthcare workers tested, only 2 experienced outpatient symptomatic breakthrough infections, despite 59/227 exhibiting serologic evidence of SARS-CoV-2 infection, defined as presence of nucleocapsid protein antibodies.

Prospective Assessment of Symptoms to Evaluate Asymptomatic SARS-CoV-2 Infections in a Cohort of Health Care Workers.

BACKGROUND: The frequency of asymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections is unclear and may be influenced by how symptoms are evaluated. In this study, we sought to determine the frequency of asymptomatic SARS-CoV-2 infections in a prospective cohort of health care workers (HCWs). METHODS: A prospective cohort of HCWs, confirmed negative for SARS-CoV-2 exposure upon enrollment, were evaluated for SARS-CoV-2 infection by monthly analysis of SARS-CoV-2 antibodies as well as referral for polymerase chain reaction testing whenever they exhibited symptoms of coronavirus disease 2019 (COVID-19). Participants completed the standardized and validated FLU-PRO Plus symptom questionnaire scoring viral respiratory disease symptom intensity and frequency at least twice monthly during baseline periods of health and each day they had any symptoms that were different from their baseline. RESULTS: Two hundred sixty-three participants were enrolled between August 25 and December 31, 2020. Through February 28, 2021, 12 participants were diagnosed with SARS-CoV-2 infection. Symptom analysis demonstrated that all 12 had at least mild symptoms of COVID-19, compared with baseline health, near or at time of infection. CONCLUSIONS: These results suggest that asymptomatic SARS-CoV-2 infection in unvaccinated, immunocompetent adults is less common than previously reported. While infectious inoculum doses and patient factors may have played a role in the clinical manifestations of SARS-CoV-2 infections in this cohort, we suspect that the high rate of symptomatic disease was due primarily to participant attentiveness to symptoms and collection of symptoms in a standardized, prospective fashion. These results have implications for studies that estimate SARS-CoV-2 infection prevalence and for public health measures to control the spread of this virus.

Adverse Effects and Antibody Titers in Response to the BNT162b2 mRNA COVID-19 Vaccine in a Prospective Study of Healthcare Workers.

BACKGROUND: The relationship between postvaccination symptoms and strength of antibody responses is unclear. The goal of this study was to determine whether adverse effects caused by vaccination with the Pfizer/BioNTech BNT162b2 vaccine are associated with the magnitude of vaccine-induced antibody levels. METHODS: We conducted a single-center, observational cohort study consisting of generally healthy adult participants that were not severely immunocompromised, had no history of coronavirus disease 2019, and were seronegative for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein before vaccination. Severity of vaccine-associated symptoms was obtained through participant-completed questionnaires. Testing for immunoglobulin G antibodies against SARS-CoV-2 spike protein and receptor-binding domain was conducted using microsphere-based multiplex immunoassays performed on serum samples collected at monthly visits. Neutralizing antibody titers were determined by microneutralization assays. RESULTS: Two hundred six participants were evaluated (69.4% female, median age 41.5 years old). We found no correlation between vaccine-associated symptom severity scores and vaccine-induced antibody titers 1 month after vaccination. We also observed that (1) postvaccination symptoms were inversely correlated with age and weight and more common in women, (2) systemic symptoms were more frequent after the second vaccination, (3) high symptom scores after first vaccination were predictive of high symptom scores after second vaccination, and (4) older age was associated with lower titers. CONCLUSIONS: Lack of postvaccination symptoms after receipt of the BNT162b2 vaccine does not equate to lack of vaccine-induced antibodies 1 month after vaccination.

Small-Molecule Mn Antioxidants in Caenorhabditis elegans and Deinococcus radiodurans Supplant MnSOD Enzymes during Aging and Irradiation.

Denham Harman's oxidative damage theory identifies superoxide (O2•-) radicals as central agents of aging and radiation injury, with Mn2+-dependent superoxide dismutase (MnSOD) as the principal O2•--scavenger. However, in the radiation-resistant nematode Caenorhabditis elegans, the mitochondrial antioxidant enzyme MnSOD is dispensable for longevity, and in the model bacterium Deinococcus radiodurans, it is dispensable for radiation resistance. Many radiation-resistant organisms accumulate small-molecule Mn2+-antioxidant complexes well-known for their catalytic ability to scavenge O2•-, along with MnSOD, as exemplified by D. radiodurans. Here, we report experiments that relate the MnSOD and Mn-antioxidant content to aging and oxidative stress resistances and which indicate that C. elegans, like D. radiodurans, may rely on Mn-antioxidant complexes as the primary defense against reactive oxygen species (ROS). Wild-type and ΔMnSOD D. radiodurans and C. elegans were monitored for gamma radiation sensitivities over their life spans while gauging Mn2+-antioxidant content by electron paramagnetic resonance (EPR) spectroscopy, a powerful new approach to determining the in vivo Mn-antioxidant content of cells as they age. As with D. radiodurans, MnSOD is dispensable for radiation survivability in C. elegans, which hyperaccumulates Mn-antioxidants exceptionally protective of proteins. Unexpectedly, ΔMnSOD mutants of both the nematodes and bacteria exhibited increased gamma radiation survival compared to the wild-type. In contrast, the loss of MnSOD renders radiation-resistant bacteria sensitive to atmospheric oxygen during desiccation. Our results support the concept that the disparate responses to oxidative stress are explained by the accumulation of Mn-antioxidant complexes which protect, complement, and can even supplant MnSOD. IMPORTANCE The current theory of cellular defense against oxidative damage identifies antioxidant enzymes as primary defenders against ROS, with MnSOD being the preeminent superoxide (O2•-) scavenger. However, MnSOD is shown to be dispensable both for radiation resistance and longevity in model organisms, the bacterium Deinococcus radiodurans and the nematode Caenorhabditis elegans. Measured by electron paramagnetic resonance (EPR) spectroscopy, small-molecule Mn-antioxidant content was shown to decline in unison with age-related decreases in cell proliferation and radioresistance, which again are independent of MnSOD presence. Most notably, the Mn-antioxidant content of C. elegans drops precipitously in the last third of its life span, which links with reports that the steady-state level of oxidized proteins increases exponentially during the last third of the life span in animals. This leads us to propose that global responses to oxidative stress must be understood through an extended theory that includes small-molecule Mn-antioxidants as potent O2•--scavengers that complement, and can even supplant, MnSOD.

Strongyloides papillosus causes sudden death in weaned calves on New York dairies.

CASE DESCRIPTION: Outbreaks of sudden death in apparently healthy weaned dairy calves due to Strongyloides papillosus parasitism were diagnosed on 2 separate and independent New York (NY) dairies. CLINICAL FINDINGS: Most calves were found dead; however, 1 calf observed while dying showed signs of tachycardia, tachypnea, vocalization, and convulsions shortly before death. In 6 affected heifers that underwent post-mortem examination, precocious bilaterally symmetric mammary gland enlargement was seen. A portion of their parasitized living cohorts also demonstrated similar mammary gland enlargement. A diagnosis of S papillosus hyperinfection was made based upon the presence of high numbers of S papillosus ova in feces, and confirmation by S papillosus-specific PCR assays. Consistent histopathological findings in affected calves included generalized mammary gland vascular congestion, interstitial edema and hemorrhage with ductal hyperplasia. Mild multifocal cardiomyocyte degeneration was found in 5 of 14 calves examined. Factors believed to contribute to the parasite's environmental amplification and host hyperinfection included group housing on wood shavings and high environmental temperatures and humidity. TREATMENT AND OUTCOME: Treatment of calves with doramectin pour-on stopped mortality and resolved the udder enlargement. CLINICAL RELEVANCE: Similar outbreaks have previously been described in Japan and South Bohemia (Czech Republic), where researchers hypothesized that sudden death may be due to fatal arrhythmia caused by a parasite-associated cardiotoxin. This report highlights the importance of including S papillosus among the differential diagnoses for sudden death alone or together with precocious udder enlargement in calves kept in confinement housing.

The Effect of the Menstrual Cycle and Oral Contraceptive Cycle on Muscle Performance and Perceptual Measures.

Most reproductive-aged women are exposed to fluctuating female steroid hormones due to the menstrual cycle or oral contraceptive use. This study investigated the potential effect of the menstrual cycle and combined monophasic oral contraceptive cycle on various aspects of muscle performance. Thirty active females (12 with a natural menstrual cycle, 10 taking a high-androgenicity oral contraceptive and 8 taking a low-androgenicity oral contraceptive), aged 18 to 30 years, were tested three times throughout one menstrual or oral contraceptive cycle. Counter-movement jumps, bilateral hop jumps, handgrip strength, isometric knee extensor strength and isokinetic knee flexion and extension were assessed. Perceptual ratings of fatigue, muscle soreness, pain and mood were recorded. Most variables showed no significant changes over the menstrual or oral contraceptive cycle. However, for the menstrual cycle group, isokinetic knee flexion at 240° s-1, and time of flight in bilateral hopping and counter movement jumps showed better results during the mid-luteal phase compared with the late follicular phase. For the high-androgenicity oral contraceptive group, isokinetic knee flexion at 240° s-1 was significantly higher in the late hormone phase compared with the early hormone phase. For the low-androgenicity oral contraceptive group, time of flight for the counter-movement jumps was lower in the late hormone phase compared with the early hormone phase. The findings indicate that faster and explosive aspects of muscle performance may be influenced by endogenous and exogenous female hormones.

The acute effect of the menstrual cycle and oral contraceptive cycle on measures of body composition.

PURPOSE: This study aimed to investigate the effect of fluctuating female hormones during the menstrual cycle (MC) and oral contraceptive (OC) cycle on different measures of body composition. METHODS: Twenty-two women with a natural MC and thirty women currently taking combined monophasic OC were assessed over three phases of the menstrual or oral contraceptive cycle. Body weight, skinfolds, bioelectric impedance analysis (BIA), ultrasound, dual-energy X-ray absorptiometry (DXA), and peripheral quantitative computed tomography (pQCT) measurements were performed to assess body composition. Urine specific gravity (USG) was measured as an indication of hydration, and serum oestradiol and progesterone were measured to confirm cycle phases. RESULTS: Five participants with a natural MC were excluded based on the hormone analysis. For the remaining participants, no significant changes over the MC and OC cycle were found for body weight, USG, skinfolds, BIA, ultrasound and pQCT measures. However, DXA body fat percentage and fat mass were lower in the late follicular phase compared to the mid-luteal phase of the MC, while for the OC cycle, DXA body fat percentage was higher and lean mass lower in the early hormone phase compared with the late hormone phase. CONCLUSION: Our findings suggest that assessment of body fat percentage through BIA and skinfolds may be performed without considering the MC or OC cycle. Body adiposity assessment via DXA, however, may be affected by female hormone fluctuations and therefore, it may be advisable to perform repeat testing using DXA during the same phase of the MC or OC cycle.