Effect of Resistance Training on Physical Function During Chemotherapy in Colon Cancer.

BACKGROUND: The decline of physical function during chemotherapy predicts poor quality of life and premature death. It is unknown if resistance training prevents physical function decline during chemotherapy in colon cancer survivors. METHODS: This multicenter trial randomized 181 colon cancer survivors receiving postoperative chemotherapy to home-based resistance training or usual care control. Physical function outcomes included the short physical performance battery (SPPB), isometric handgrip strength, and the physical function subscale of the Medical Outcomes Short-Form 36-item questionnaire. Mixed models for repeated measures quantified estimated treatment differences (ETD). RESULTS: At baseline, subjects had a mean (SD) age of 55.2 years (12.8); 67 (37%) were ≥60 years, and 29 (16%) had a composite SPPB score ≤9. Compared with control, resistance training did not improve the composite SPPB score [ETD: -0.01 (95% CI: -0.32, 0.31); P = 0.98], or the SPPB scores for balance [ETD: 0.01 (95% CI: -0.10, 0.11); P = 0.93], gait speed [ETD: 0.08 (95% CI: -0.06, 0.22) P = 0.28], and sit-to-stand [ETD: -0.08 (95% CI: -0.29, 0.13); P = 0.46]. Compared with control, resistance training did not improve isometric handgrip strength [ETD: 1.50 kg (95% CI: -1.06, 4.05); P = 0.25] or self-reported physical function [ETD: -3.55 (95% CI: -10.03, 2.94); P = 0.28]. The baseline SPPB balance score [r=0.21 (95% CI: 0.07, 0.35)] and handgrip strength [r=0.23 (95% CI: 0.09, 0.36)] correlated with chemotherapy relative dose intensity. CONCLUSION: Among colon cancer survivors with relatively high physical functioning, randomization to home-based resistance training did not prevent physical function decline during chemotherapy. CLINICAL TRIAL REGISTRATION: NCT03291951.

Fundamentals of wildlife dosimetry and lessons learned from a decade of measuring external dose rates in the field.

Methods for determining the radiation dose received by exposed biota require major improvements to reduce uncertainties and increase precision. We share our experiences in attempting to quantify external dose rates to free-ranging wildlife using GPS-coupled dosimetry methods. The manuscript is a primer on fundamental concepts in wildlife dosimetry in which the complexities of quantifying dose rates are highlighted, and lessons learned are presented based on research with wild boar and snakes at Fukushima, wolves at Chornobyl, and reindeer in Norway. GPS-coupled dosimeters produced empirical data to which numerical simulations of external dose using computer software were compared. Our data did not support a standing paradigm in risk analyses: Using averaged soil contaminant levels to model external dose rates conservatively overestimate the dose to individuals within a population. Following this paradigm will likely lead to misguided recommendations for risk management. The GPS-dosimetry data also demonstrated the critical importance of how modeled external dose rates are impacted by the scale at which contaminants are mapped. When contaminant mapping scales are coarse even detailed knowledge about each animal's home range was inadequate to accurately predict external dose rates. Importantly, modeled external dose rates based on a single measurement at a trap site did not correlate to actual dose rates measured on free ranging animals. These findings provide empirical data to support published concerns about inadequate dosimetry in much of the published Chernobyl and Fukushima dose-effects research. Our data indicate that a huge portion of that literature should be challenged, and that improper dosimetry remains a significant source of controversy in radiation dose-effect research.

Effects of exercise or metformin on myokine concentrations in patients with breast and colorectal cancer: A phase II multi-centre factorial randomized trial.

BACKGROUND: Physical activity and metformin pharmacotherapy are associated with improved clinical outcomes in breast and colorectal cancer survivors. Myokines are cytokines secreted from skeletal muscle that may mediate these associations. METHODS: This hypothesis-generating analysis used biospecimens collected from a multi-centre 2 × 2 factorial randomized design of 116 patients with stage I-III breast and colorectal cancer who were randomized to 12 weeks of (1) aerobic exercise (moderate intensity titrated to 220 min/week); (2) metformin (850 mg daily for 2 weeks and then titrated to 850 mg twice per day); (3) aerobic exercise and metformin; or (4) control. Fourteen myokines were quantified using a multiplex panel. Myokine concentrations were log-transformed, and main effects analyses were conducted using linear mixed-effects regression models. The type I error rate was controlled with the Holm sequential testing procedure. RESULTS: Randomization to exercise increased leukaemia inhibitory factor (1.26 pg/mL, 95% confidence interval [CI]: 0.69, 1.84; adjusted P = 0.001) and interleukin-15 (2.23 pg/mL, 95% CI: 0.87, 3.60; adjusted P = 0.013) compared with randomization to no exercise. Randomization to metformin decreased apelin (-2.69 pg/mL, 95% CI: -4.31, -1.07; adjusted P = 0.014) and interleukin-15 (-1.74 pg/mL, 95% CI: -2.79, -0.69; adjusted P = 0.013) compared with randomization to no metformin. Metformin decreased myostatin, irisin, oncostatin M, fibroblast growth factor 21 and osteocrin; however, these changes were not statistically significant after correction for multiple comparisons. CONCLUSIONS: This pilot study demonstrates that randomization to exercise and metformin elicit unique effects on myokine concentrations in cancer patients. This hypothesis-generating observation warrants further basic, translational and clinical investigation and replication.

Murine Progeria Model Exhibits Delayed Fracture Healing with Dysregulated Local Immune Response.

Background: Bone fracture is one of the most globally prevalent injuries, with an estimated 189 million bone fractures occurring annually. Delayed union or nonunion occurs in up to 15% of fractures and involves the interruption or complete failure of bone continuity following fracture. Preclinical testing is essential to support the translation of novel strategies to promote improved fracture repair treatment, but there is a paucity of small animal models that recapitulate clinical attributes associated with delayed fracture healing. This study explores whether the Zmpste24 -/- (Z24 -/- ) knockout mouse model of Hutchinson-Gilford progeria syndrome presents with delayed fracture healing. Leveraging the previously characterized Z24 -/- phenotype of genomic instability, epigenetic changes, and fragility, we hypothesize that these underlying alterations will lead to significantly delayed fracture healing relative to age-matched wild type (WT) controls. Methods: WT and Z24 -/- mice received intramedullary fixed tibia fractures at ∼12 weeks of age. Mice were sacrificed throughout the time course of repair for the collection of organs that would provide information regarding the local (fracture callus, bone marrow, inguinal lymph nodes) versus peripheral (peripheral blood, contralateral tibia, abdominal organs) tissue microenvironments. Analyses of these specimens include histomorphometry, µCT, mechanical strength testing, protein quantification, gene expression analysis, flow cytometry for cellular senescence, and immunophenotyping. Results: Z24 -/- mice demonstrated a significantly delayed rate of healing compared to WT mice with consistently smaller fracture calli containing higher proportion of cartilage and less bone after injury. Cellular senescence and pro-inflammatory cytokines were elevated in the Z24 -/- mice before and after fracture. These mice further presented with a dysregulated immune system, exhibiting generally decreased lymphopoiesis and increased myelopoiesis locally in the bone marrow, with more naïve and less memory T cell but greater myeloid activation systemically in the peripheral blood. Surprisingly, the ipsilateral lymph nodes had increased T cell activation and other pro-inflammatory NK and myeloid cells, suggesting that elevated myeloid abundance and activation contributes to an injury-specific hyperactivation of T cells. Conclusion: Taken together, these data establish the Z24 -/- progeria mouse as a model of delayed fracture healing that exhibits decreased bone in the fracture callus, with weaker overall bone quality, immune dysregulation, and increased cellular senescence. Based on this mechanism for delayed healing, we propose this Z24 -/- progeria mouse model could be useful in testing novel therapeutics that could address delayed healing. The Translational Potential of this Article: This study employs a novel animal model for delayed fracture healing that researchers can use to screen fracture healing therapeutics to address the globally prevalent issue of aberrant fracture healing.

Transfer of radionuclides through ecological systems: Lessons learned from 10 years of research within CERAD CoE.

Norway's Centre of Excellence for Environmental Radioactivity (CERAD) research programme included studies on transfer of radionuclides in various ecosystems within the context of environmental risk assessment. This article provides highlights from 10 years of research within this topic and summarises lessons learnt from the process. The scope has been extensive, involving laboratory-based experiments, field studies and the implementation of transfer models quantifying radionuclide uptake directly from the surrounding environment and via food chains. Field studies have had a global span and have, inter alia, covered sites contaminated with radionuclides associated with particles, ranging from nanoparticles to fragments, due to nuclear accidents (e.g., Chornobyl and Fukushima accidents) along with sites having enhanced levels of naturally occurring radioactive materials (e.g., Fen Complex in Norway and Taboshar in Tajikistan). Focus has been put on speciation and kinetics in determining radionuclide behavior and fate as well as on the influence of environmental factors that are potentially critical for the transfer of radionuclides. In particular, seasonal factors have been shown to greatly affect the dynamics of 137Cs and 90Sr bioaccumulation and loss in freshwater fish. The work has led to the collation of organism-specific (i) parameters important for kinetic models, i.e., uptake and depuration rates, and (ii) steady-state concentration ratios, CRs, where the use of stable analogue CRs as proxies for radionuclides has been brought into question. Dynamic models have been developed and applied for radiocaesium transfer to reindeer, radionuclide transfer in Arctic marine systems, transfer to fish via water and feed and commonly used agricultural food-chain transfer models applied in the context of nuclear emergency preparedness. The CERAD programme should contribute substantially to the scientific community's understanding of radionuclide transfer in environmental systems.

Restoring adiponectin via rosiglitazone ameliorates tissue wasting in mice with lung cancer.

AIM: To investigate systemic regulators of the cancer-associated cachexia syndrome (CACS) in a pre-clinical model for lung cancer with the goal to identify therapeutic targets for tissue wasting. METHODS: Using the Kras/Lkb1 (KL) mouse model, we found that CACS is associated with white adipose tissue (WAT) dysfunction that directly affects skeletal muscle homeostasis. WAT transcriptomes showed evidence of reduced adipogenesis, and, in agreement, we found low levels of circulating adiponectin. To preserve adipogenesis and restore adiponectin levels, we treated mice with the PPAR-γ agonist, rosiglitazone. RESULTS: Rosiglitazone treatment increased serum adiponectin levels, delayed weight loss, and preserved skeletal muscle and adipose tissue mass, as compared to vehicle-treated mice. The preservation of muscle mass with rosiglitazone was associated with increases in AMPK and AKT activity. Similarly, activation of the adiponectin receptors in muscle cells increased AMPK activity, anabolic signaling, and protein synthesis. CONCLUSION: Our data suggest that PPAR-γ agonists may be a useful adjuvant therapy to preserve tissue mass in lung cancer.

RAPID POINT-OF-CARE TESTING FOR DETECTION OF ANTIBODIES TO TOXOPLASMA GONDII IN BLACK VULTURES AND RING-BILLED GULLS FROM PENNSYLVANIA.

Toxoplasma gondii is a zoonotic protozoan parasite that infects most warm-blooded animals, including birds. Scavenging birds are epidemiologically important hosts because they can serve as indicators of environmental T. gondii levels. A rapid point-of-care (POC) test that detects antibodies to T. gondii in humans is commercially available. In this research, we assessed the ability of the human POC test to detect anti-T. gondii antibodies in 106 black vultures (Coragyps atratus) and 23 ring-billed gulls (Larus delawarensis) from Pennsylvania, USA. Serum samples were tested with the POC test and compared to the modified agglutination test (MAT) in a blinded study. Overall, anti-T. gondii antibodies were detected in 2.8% (3/106) of black vultures and 60.9% (14/23) of ring-billed gulls by the POC test. One false-positive POC test occurred in a black vulture that was negative by MAT. False-negative results were obtained in 2 black vultures and 4 ring-billed gulls that had MAT titers of 1:25 or 1:50. The sensitivity and specificity of the POC for both black vultures and ring-billed gulls combined were 95.7% and 95.5%, respectively. This is the first study using human POC tests to detect antibodies to T. gondii in birds. Further study of the rapid test as a screening tool for serological surveillance of T. gondii in birds is warranted.

Antibodies to Influenza A(H5N1) Virus in Hunting Dogs Retrieving Wild Fowl, Washington, USA.

We detected antibodies to H5 and N1 subtype influenza A viruses in 4/194 (2%) dogs from Washington, USA, that hunted or engaged in hunt tests and training with wild birds. Historical data provided by dog owners showed seropositive dogs had high levels of exposure to waterfowl.

Anatomical Location of the Vesical Branches of the Inferior Hypogastric Plexus in Human Cadavers.

We have demonstrated in canines that somatic nerve transfer to vesical branches of the inferior hypogastric plexus (IHP) can be used for bladder reinnervation after spinal root injury. Yet, the complex anatomy of the IHP hinders the clinical application of this repair strategy. Here, using human cadavers, we clarify the spatial relationships of the vesical branches of the IHP and nearby pelvic ganglia, with the ureteral orifice of the bladder. Forty-four pelvic regions were examined in 30 human cadavers. Gross post-mortem and intra-operative approaches (open anterior abdominal, manual laparoscopic, and robot-assisted) were used. Nerve branch distances and diameters were measured after thorough visual inspection and gentle dissection, so as to not distort tissue. The IHP had between 1 to 4 vesical branches (2.33 ± 0.72, mean ± SD) with average diameters of 0.51 ± 0.06 mm. Vesical branches from the IHP arose from a grossly visible pelvic ganglion in 93% of cases (confirmed histologically). The pelvic ganglion was typically located 7.11 ± 6.11 mm posterolateral to the ureteral orifice in 69% of specimens. With this in-depth characterization, vesical branches from the IHP can be safely located both posterolateral to the ureteral orifice and emanating from a more proximal ganglionic enlargement during surgical procedures.

Switching from natalizumab to an anti-CD20 monoclonal antibody in relapsing remitting multiple sclerosis: A systematic review.

BACKGROUND: Use of natalizumab (NTZ) is precluded in many Multiple Sclerosis (MS) patients by the risk of progressive multifocal leukoencephalopathy (PML). Regardless, some patients may commence natalizumab for short term disease control in spite of being seropositive, and others may seroconvert whilst on treatment. In these circumstances, discontinuation of NTZ should not occur until a clear exit strategy is established to prevent post-NTZ disease reactivation, which often exceeds the severity of disease activity prior to NTZ treatment. The objective of this systematic review was to summarise the available evidence for CD20-monoclonal antibodies (CD20mAb) as a suitable NTZ exit strategy, and to identify whether a superior switch protocol can be established. METHODS: In accordance with PRISMA guidelines, a total of 2393 references were extracted from a search of three online databases (PubMed, Scopus, MEDLINE). Following the application of inclusion/exclusion criteria, a total of 5 studies representing 331 patients were included. RESULTS: The overall incidence of clinical relapse during washout periods ranging from 4.4-10.7 weeks was 0 %. The incidence of clinical relapse during two-year follow-up ranged from 1.8 % to 10 % for switches to all types of CD20 monoclonal antibody. The weighted mean for clinical relapse at 12 months was 8.8 %. Three studies reported an annualised relapse rate (ARR) ranging from 0.02-0.12 with a weighted mean ARR of 0.07. The overall incidence of PML during washout was 0 % and the overall incidence of PML within 6 months follow-up was 0.6 %. CONCLUSIONS: This systematic review provides the first attempt at identifying a superior switch protocol in patients at risk of PML transitioning from NTZ to a CD20mAb. Our results indicate that CD20mAb's are a suitable transitional option for patients who discontinue NTZ, with our cohort demonstrating very low rates of carryover PML and low rates of clinical relapse. The most appropriate washout period is unclear due to confounding factors but is likely between 4 and 12 weeks.

Postoperative chemotherapy relative dose intensity and overall survival in patients with colon cancer.

PURPOSE: Quantifying the association of chemotherapy relative dose intensity (RDI) with overall survival may enable supportive care interventions that improve chemotherapy RDI to estimate their magnitude of potential clinical benefit. METHODS: This cohort study included 533 patients with stage II-III colon cancer who initiated a planned regimen of 12 cycles of 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) chemotherapy. The primary exposure was chemotherapy RDI. The primary outcome was overall survival. Restricted cubic splines estimated hazard ratios (HR). RESULTS: Chemotherapy regimen RDI was associated with overall survival in an L-shaped pattern (linear P = 0.006; nonlinear P = 0.057); the risk of death was flat above 85% but increased linearly below 85%. For example, a decrease in RDI from 85 to 75% was associated with an increased risk of death [HR: 1.20 (95% CI: 1.08, 1.52)], whereas an increase in RDI from 85 to 95% was not associated with the risk of death [HR: 1.06 (95% CI: 0.82, 1.38)]. CONCLUSION: If chemotherapy RDI is considered a potential surrogate of overall survival, supportive care interventions that improve chemotherapy RDI might confer a potential clinical benefit in this population.

Purpose in Life and Cognitive Function: Evidence for Momentary Associations in Daily Life.

Background and Objectives: Purpose in life is associated with healthier cognitive outcomes in older adulthood. This research examines within-person dynamics between momentary purpose and cognitive function to provide proof of concept that increases in purpose are associated with better cognitive performance. Research Design and Methods: Participants (N = 303; 54% female; Mage = 51.71, SD = 7.32) completed smartphone-based momentary assessments of purpose and short cognitive tasks 3 times a day for 8 days. Results: In moments when participants felt more purpose driven than their average, they had faster processing speed (b = -1.240, SE = 0.194; p < .001), independent of person, temporal, and contextual factors and practice effects. Momentary purpose was unrelated to visual working memory performance (b = -0.001, SE = 0.001; p = .475). In contrast to purpose, momentary hedonic affect (e.g., happiness) was unrelated to momentary cognition. Discussion and Implications: Feeling more momentary purpose may support faster processing speed in daily life. Such evidence provides stage 0 support for a purpose-based intervention for healthier cognition, which may be particularly useful in middle adulthood and the transition to older adulthood before the onset of cognitive impairment.

Otterly diverse - A high diversity of Dracunculus species (Spirurida: Dracunculoidea) in North American river otters (Lontra canadensis).

The genus Dracunculus contains numerous species of subcutaneous parasites of mammals and reptiles. In North America, there are at least three mammal-infecting species of Dracunculus. Reports of Dracunculus infections have been reported from river otters (Lontra canadensis) since the early 1900s; however, little is known about the species infecting otters or their ecology. Most reports of Dracunculus do not have a definitive species identified because females, the most common sex found due to their larger size and location in the extremities of the host, lack distinguishing morphological characteristics, and few studies have used molecular methods to confirm identifications. Thus, outside of Ontario, Canada, where both D. insignis and D. lutrae have been confirmed in otters, the species of Dracunculus in river otters is unknown. In the current study, molecular characterization of nematodes from river otters revealed a high diversity of Dracunculus species. In addition to confirming D. insignis infections, two new clades were detected. One clade was a novel species in any host and the other was a clade previously detected in Virginia opossums (Didelphis virginiana) from the USA and a domestic dog from Spain. No infections with D. lutrae were detected and neither new lineage was genetically similar to D. jaguape, which was recently described from a neotropical otter (Lontra longicaudis) from Argentina. These data also indicate that Dracunculus spp. infections in otters are widespread throughout Eastern North America. Currently the life cycles for most of the Dracunculus spp. infecting otters are unknown. Studies on the diversity, life cycle, and natural history of Dracunculidae parasites in wildlife are important because the related parasite, D. medinensis (human Guinea worm) is the subject of an international eradication campaign and there are increasing reports of these parasites in new geographic locations and new hosts, including new species in humans and domestic dogs.

Effect of Varus-Producing Distal Femoral Osteotomy and High Tibial Osteotomy on Compartment Pressures and Contact Area at Varying Degrees of Knee Flexion.

Background: In patients with valgus alignment and degenerative changes in the lateral compartment, both distal femoral osteotomy (DFO) and high tibial osteotomy (HTO) can be used to unload the lateral compartment. Prior studies have shown that in valgus knees, the tibial wear is posterior and DFO exerts the greatest effect in extension; however, its effect is decreased as flexion angle rises. Hypothesis: Medial closing-wedge (MCW) HTO would significantly decrease contact area, mean contact pressure (MCP), and peak contact pressure (PCP) in the lateral knee compartment through knee flexion to a greater extent compared with lateral opening-wedge (LOW) DFO. Study Design: Controlled laboratory study. Methods: MCWHTO and LOWDFO were performed, correcting a mean of 8° of valgus alignment, in 10 cadaveric knees using plate fixation. Tibiofemoral contact pressure of the medial and lateral compartments was measured in 0°, 30°, 60°, and 90° of knee flexion before and after osteotomy using thin electronic sensors and load applied through an Instron device. PCP, MCP, and contact area were measured for each condition. Results: The lateral MCP was significantly decreased in the HTO state compared with the native state in 30° (P = .015), 60° (P = .0199), and 90° (P < .0001) of flexion. The lateral MCP was also significantly decreased in the HTO state when compared with the DFO state in 60° (P = .0093) and 90° of flexion (P < .0001). After DFO, the lateral MCP returned to that of the native state in 60° (P > .999) and 90° (P > .999) of flexion. The lateral PCP decreased for all test states in all degrees of flexion; the HTO state was significantly decreased when compared with the native state in 60° (P < .0001) and 90° (P < .0001). Conclusion: With varus corrections of 8°, MCWHTO was more effective at unloading the lateral compartment than LOWDFO. This effect was significant as the knee flexion angle increased. This study should be considered as one aspect of the surgical decision-making process. Clinical Relevance: In patients with mild to moderate valgus deformity without hypoplastic lateral femoral condyle and without significant joint line obliquity, MCWHTO may improve offloading of the lateral compartment in flexion.

Longitudinal and Cross-Sectional Evaluation of Two Commercial Swine Breeding Herds to Characterize Neutralizing Antibody Levels following Porcine Epidemic Diarrhea Virus Outbreaks.

Neutralizing antibodies to Porcine Epidemic Diarrhea Virus (PEDV) can be detected by 3 weeks post-infection and remain detectable through at least 24 weeks post-infection. The objective of this study was to evaluate the levels of neutralizing antibodies in sow and piglet serum and sow milk to determine the duration of neutralizing antibodies following PEDV outbreaks. Two farms were selected for the study following outbreaks of PEDV. Monthly, cohorts of sows were sampled and followed through two farrowings. Following each farrowing, samples from piglets and milk were collected. Samples were evaluated for PEDV-neutralizing antibodies by a high-throughput fluorescent neutralization assay. Although neutralizing antibodies to PEDV can be detected throughout 15 months post-outbreak, a decrease in circulating neutralizing antibody levels is noted in farms beginning at six months post-outbreak. With decreasing levels, farms may become more vulnerable to PEDV outbreaks, and practitioners can focus on this time window to implement intervention strategies.

Nerve transfer for restoration of lower motor neuron-lesioned bladder, urethral and anal sphincter function. Part 4: Effectiveness of the motor reinnervation.

In pilot work, we showed that somatic nerve transfers can restore motor function in long-term decentralized dogs. We continue to explore the effectiveness of motor reinnervation in 30 female dogs. After anesthesia, 12 underwent bilateral transection of coccygeal and sacral (S) spinal roots, dorsal roots of lumbar (L)7, and hypogastric nerves. Twelve months postdecentralization, eight underwent transfer of obturator nerve branches to pelvic nerve vesical branches, and sciatic nerve branches to pudendal nerves, followed by 10 mo recovery (ObNT-ScNT Reinn). The remaining four were euthanized 18 mo postdecentralization (Decentralized). Results were compared with 18 Controls. Squat-and-void postures were tracked during awake cystometry. None showed squat-and-void postures during the decentralization phase. Seven of eight ObNT-ScNT Reinn began showing such postures by 6 mo postreinnervation; one showed a return of defecation postures. Retrograde dyes were injected into the bladder and urethra 3 wk before euthanasia, at which point, roots and transferred nerves were electrically stimulated to evaluate motor function. Upon L2-L6 root stimulation, five of eight ObNT-ScNT Reinn showed elevated detrusor pressure and four showed elevated urethral pressure, compared with L7-S3 root stimulation. After stimulation of sciatic-to-pudendal transferred nerves, three of eight ObNT-ScNT Reinn showed elevated urethral pressure; all showed elevated anal sphincter pressure. Retrogradely labeled neurons were observed in L2-L6 ventral horns (in laminae VI, VIII, and IX) of ObNT-ScNT Reinn versus Controls in which labeled neurons were observed in L7-S3 ventral horns (in lamina VII). This data supports the use of nerve transfer techniques for the restoration of bladder function.NEW & NOTEWORTHY This data supports the use of nerve transfer techniques for the restoration of bladder function.

Resolution of Clinical Signs of Sarcoptic Mange in American Black Bears (Ursus americanus), in Ivermectin-Treated and Nontreated Individuals.

The parasitic mite Sarcoptes scabiei causes mange in nearly 150 species of mammals by burrowing under the skin, triggering hypersensitivity responses that can alter animals' behavior and result in extreme weight loss, secondary infections, and even death. Since the 1990s, sarcoptic mange has increased in incidence and geographic distribution in Pennsylvania black bear (Ursus americanus) populations, including expansion into other states. Recovery from mange in free-ranging wildlife has rarely been evaluated. Following the Pennsylvania Game Commission's standard operating procedures at the time of the study, treatment consisted of one subcutaneous injection of ivermectin. To evaluate black bear survival and recovery from mange, from 2018 to 2020 we fitted 61 bears, including 43 with mange, with GPS collars to track their movements and recovery. Bears were collared in triplicates according to sex and habitat, consisting of one bear without mange (healthy control), one scabietic bear treated with ivermectin when collared, and one untreated scabietic bear. Bears were reevaluated for signs of mange during annual den visits, if recaptured during the study period, and after mortality events. Disease status and recovery from mange was determined based on outward gross appearance and presence of S. scabiei mites from skin scrapes. Of the 36 scabietic bears with known recovery status, 81% fully recovered regardless of treatment, with 88% recovered with treatment and 74% recovered without treatment. All bears with no, low, or moderate mite burdens (<16 mites on skin scrapes) fully recovered from mange (n=20), and nearly half of bears with severe mite burden (≥16 mites) fully recovered (n=5, 42%). However, nonrecovered status did not indicate mortality, and mange-related mortality was infrequent. Most bears were able to recover from mange irrespective of treatment, potentially indicating a need for reevaluation of the mange wildlife management paradigm.

Toxoplasma gondii Survey in Waterfowl and Gulls from Eight USA States.

Sera from 391 waterbirds from eight USA states were tested for Toxoplasma gondii antibodies using the modified agglutination test. Fifteen different waterbird species (26.6%; n=104) were seropositive. Of the adults, 25.4% (n=52) showed a significantly higher T. gondii seroprevalence compared with juveniles (13.4%; n=17); however, sex was not a significant factor.

A pilot study proposing an algorithm for pubertal induction in cerebral palsy.

OBJECTIVES: To explore delayed puberty in cerebral palsy (CP) and to test the acceptability of an interventional puberty induction algorithm. METHODS: A two phase cohort study in children and adolescents diagnosed with CP who have delayed puberty. Phase 1: Retrospective review of clinical records and interviews with patients who have been treated with sex-steroids and Phase 2: Prospective interventional trial of pubertal induction with a proposed algorithm of transdermal testosterone (males) or oestrogen (females). Phase 1 examined experiences with sex-steroid treatment. Phase 2 collected data on height adjusted bone mineral density (BMAD), fractures, adverse effects, mobility and quality of life over two years during the induction. RESULTS: Phase 1, treatment was well tolerated in 11/20 treated with sex-steroids; phase 2, using the proposed induction algorithm, 7/10 treated reached Tanner stage 3 by nine months. One participant reached Tanner stage 5 in 24 months. Mean change in BMAD Z-scores was +0.27 % (SD 0.002) in those who could be scanned by dual-energy X-ray absorptiometry (DXA). CONCLUSIONS: Delayed puberty may be diagnosed late. Treatment was beneficial and well tolerated, suggesting all patients with severe pubertal delay or arrest should be considered for sex hormone supplementation.