Gait Analysis of Amputee Dogs Using a Pressure-Sensitive Walkway.

OBJECTIVE: The aim of this study was to perform gait analysis using a pressure-sensitive walkway in dogs submitted to high (total) or low amputation (partial) of one forelimb or hindlimb. STUDY DESIGN: A total of 39 dogs met the inclusion criteria. The reasons for the amputations were motor vehicle accidents in 38 dogs and possible limb malformation in 1 dog. The amputee dogs were divided into four groups: G1 (n = 10)-high forelimb; G2 (n = 10)-low forelimb; G3 (n = 9)-high hindlimb; and G4 (n = 10)-low hindlimb. For kinetic evaluation, the dogs were walked across a pressure-sensitive walkway. RESULTS: In dogs with forelimb amputation, the percentage of body weight (%BW) distribution on the contralateral forelimb was 50.7% in cases of high amputation and 55.5% in cases of low amputation, while the %BW distribution on the hindlimbs, mainly in the ipsilateral hindlimb, was 27.9% in cases of high amputation and 27.1% in cases of low amputation. In cases of high amputation of the hindlimb, the %BW distribution was 71.5% on the forelimbs and 29.7% on the contralateral hindlimb, while in cases of low amputation, the distribution was mainly for the contralateral hindlimb and ipsilateral forelimb. No statistical difference was noted between the amputation levels, except for the contralateral limb in cases of low and high amputation of the hindlimbs concerning the overload percentage and %BW distribution. CONCLUSION: The amputation level of one forelimb did not influence the %BW distribution; however, in the hindlimb, this was higher for the contralateral limb in dogs submitted to high amputation.

Strengthening Blood Regulatory Systems to Tackle Africa's Unmet Needs for Blood and Blood Products.

Background: Assuring the quality and safety of blood and blood components is an essential element of health care in all countries and requires government commitment and legal frameworks. Ineffective regulation of blood and blood components has far-reaching consequences that are not limited to the affected countries but also have extensive global implications. Summary: In this review, we summarize the work of the project BloodTrain funded by the German Ministry of Health within the framework of the Global Health Protection Programme to strengthen regulatory structures in Africa that are imperative to guarantee the improved availability, safety, and quality of blood and blood products. Key Messages: Intense interaction with the stakeholders in African partner countries lead to first measurable successes in the strengthening of blood regulation, as shown here for hemovigilance.

Suspected adverse reactions reported for blood, blood components, and blood products in VigiBase.

INTRODUCTION: Since being designated as medicines by World Health Organization (WHO), blood components are subject to pharmacovigilance reporting. Using VigiBase, the WHO global database of individual case safety reports (ICSRs), we characterized reports of adverse reactions for all blood products. STUDY DESIGN AND METHODS: ICSRs involving blood products as the suspected medicine in VigiBase between 1968 and 2021 were extracted. MedDRA preferred terms and the International Society of Blood Transfusion haemovigilance definitions were used to stratify adverse reactions. Descriptive statistics were used to characterize ICSR demographics. RESULTS: A total of 111,033 ICSRs containing 577,577 suspected adverse reactions with 6152 MedDRA preferred terms were reported for 34 blood products. There were 12,153 (10.9%) reports for blood components, 98,135 (88.4%) reports for plasma-derived medicines, and 745 (0.7%) reports for recombinant products. The majority of reports (21.0% and 19.7%, respectively) were from patients aged 45-64 and over 65 years. The Americas contributed the most ICSRs (49.7%). Top reported suspected adverse reactions were for the following MedDRA preferred terms: headache (3.5%), pyrexia (2.8%), chills (2.8%), dyspnoea (1.8%), and nausea (1.8%). CONCLUSION: VigiBase already has a large number of reports on blood products. When compared to other existing haemovigilance databases, our study found reports from a broader range of countries and reporters. This may provide us with new perspectives, but for VigiBase to reach its full potential in haemovigilance some alterations in what is captured in reports are required.

Histological, Immunohistochemical, Biomechanical, and Wettability Evaluations of the Leukocyte- and Platelet-Rich Fibrin Membranes Derived from Canine Blood.

This study aimed to perform histological, immunohistochemical, biomechanical, and wettability assessments of leukocyte- and platelet-rich fibrin (L-PRF) membranes obtained from the blood of healthy dogs. Ten client-owned Labrador Retriever dogs were enrolled. Blood samples were obtained from the external jugular vein using a vacuum tube without anticoagulant, which was immediately centrifuged at 400g for 12 min in a dedicated centrifuge. The L-PRF clot was removed from the tube, and the red clot was released from the buffy coat using a spatula. The membrane was produced using a PRF box. Histological examination identified the three portions of the L-PRF membranes. The first portion was composed mainly of red blood cells with the presence of a low number of leukocytes among them. The second portion was composed of white blood cells, mainly neutrophils. The third portion was composed of the fibrin network which was characterized by acidophilic staining. The immunohistochemical analysis showed that vascular endothelial growth factor and platelet-derived growth factor were expressed in all samples at different intensities, both in cellular components and fibrin mesh. The tensile test and wettability assessments were measured in membranes 30 min and 3 h after production. The 30 min L-PRF membranes supported twice the ultimate tensile strength compared to 3 h L-PRF membranes. The wettability of the 30 min sample membranes was statistically higher than the 3 h sample membranes. In conclusion, the centrifugation protocol allowed production of the L-PRF membrane using canine blood and this was confirmed by histological and immunohistochemical analysis. The mechanical resistance and wettability of the L-PRF membrane were significantly reduced over time.

Report on the GHPP-BloodTrain online workshop on "Authorisation and Licensing of Blood Establishments - Review of quality documentation of blood and blood components", 5th-8th of July 2021.

The GHPP BloodTrain team developed an e-learning concept in response to the COVID-19 travel restrictions, providing training formats with virtual stages that can be completed during the pandemic (and beyond) and on-site stages, where practical exercises and case reports in smaller groups can lead to a deeper understanding of the content. The virtual training workshop on "Authorisation and Licensing of Blood Establishments", hosted by the PEI GHPP BloodTrain from the 5th to the 8th of July 2021, was the first application of this concept. The number of participants could be substantially increased compared to an on-site event thanks to the virtual setting. Participants came mainly from national regulatory authorities and national blood transfusion services. There were also some Ministry of Health representatives from 19 countries from the WHO regions of AFRO, EMRO, and from Indonesia in attendance. The virtual workshop focused on reviewing and evaluating the quality documentation required for approval of processes used by blood establishments to prepare blood components. Presentations were given by members of the GHPP BloodTrain team as well as by representatives of the German Red Cross. The program was complemented by contributions from the WHO HQ and presentations on country-specific experiences from Ghana and Zimbabwe.

Implementation and performance of haemovigilance systems in 10 sub-saharan African countries is sub-optimal.

BACKGROUND: Haemovigilance is an important element of blood regulation. It includes collecting and evaluating the information on adverse events resulting from the use of blood and blood components with the aim to improve donor and patient safety. We describe the results of the pilot of the integrated GBT+ Blood for the haemovigilance function in 10 sub-Saharan African countries. METHODS: We piloted the integrated WHO Global Benchmarking Tool plus Blood (GBT+ Blood) to assess the haemovigilance function of national regulatory authorities (NRAs) in Ethiopia, Kenya, Malawi, Nigeria, Liberia, Rwanda, South Africa, Tanzania, Uganda, and Zimbabwe. Data obtained from documents and face to face interviews were used to determine the status of implementation and performance of the following six indicators; legal provisions regulations and guidelines, organisation and governance, human resources, regulatory processes, transparency and accountability and finally, monitoring progress and assessing impact, by estimating median scores across 20 sub-indicators. In addition, a cluster analysis was performed. RESULTS: The countries showed inter-organisation variability in implementation and performance of the haemovigilance function. The overall median score (all sub-indicators) was 44 % (range: 7.5 % - 70 %). The lowest average performance scores were for the arrangement for effective organisation and coordination (35 %) and human resources (35 %) indicators. The highest average scores were observed for the mechanism to promote transparency and mechanism to monitor regulatory performance indicators (50 % and 60 %, respectively). We identified clusters of best-implemented sub-indicators from the procedures for haemovigilance and poorly implemented sub-indicators from the legal provisions, regulations and guidelines for haemovigilance and human resources. CONCLUSIONS: Implementation of sub-indicators and performance of haemovigilance systems varied greatly for all countries with a few countries performing reasonably well in the implementation of some sub-indicators under procedures for haemovigilance. Most countries were poorly implementing sub-indicators in the legal provisions, arrangement for effective organisation and human resources indicators. The legislative provisions in most countries were at a nascent stage. There is a need to set up targeted and customised technical support coupled with prioritised interventions to strengthen the capacities of NRAs.

Report from the GHPP-BloodTrain inspection workshop in Harare the 20th to the 24th of May 2019.

During the training workshop on Inspection of Blood Establishments, which was hosted by the PEI GHPP BloodTrain in Harare from the 20th to the 24th of May 2019, participants from the National Regulatory Authorities from seven Sub-Sahara African countries presented their current experiences related to regulation and inspection of blood establishments in their respective countries. While in all seven countries regulation and inspection of conventional medicinal products manufacturer is performed, the regulatory situation of blood and blood components as well as inspection of blood establishments is still heterogeneous.

Selection of Blood, Blood Components, and Blood Products as Essential Medicines in 105 Low- and Middle-Income Countries.

Blood products of human origin are essential treatment options for several diseases, for example, hemophilia. We studied the alignment of national essential medicines lists (NEMLs) of low- and middle-income countries (LMICs) with the World Health Organization (WHO) Model List for the selection of blood products of human origin. The most recent versions of NEMLs from all LMICs were studied for the inclusion of blood products of human origin (blood and blood components, plasma products, and immunoglobulins). Data obtained from 105 NEMLs were compared to the 2017 WHO Model List. The median number of blood products of human origin on the NEMLs was 4 (range: 0-10). Immunoglobulins were most frequently included (73%). Blood and blood components were the least selected products (15%). The uptake of plasma products was around 50%. Nine countries did not have any blood products of human origin on their NEMLs. Some NEMLs included blood products not listed on the WHO Model List (albumin, hepatitis A immunoglobulin, and cryoprecipitate). We observed variation in selection according to WHO region, income level, and year of NEML update. Alignment of NEMLs with the WHO Model List varied greatly for different groups of blood products, ranging from good uptake for immunoglobulins, reasonable uptake for plasma products, to poor uptake for blood and blood components. This heterogeneity in selection and inclusion of blood products of human origin on NEMLs may be partly explained as being due to specific country characteristics, but some of it may not be explained. Policy makers need to rely on evidence in making decisions about which blood products to select, include, and remove on their NEMLs.

Development and mechanical properties of a locking T-plate / Desenvolvimento e as propriedades mecânicas de uma placa bloqueada em formato de T

This study aimed to develop a locking T-plate and to evaluate its mechanical properties in synthetic models. A titanium 2.7mm T-plate was designed with a shaft containing three locked screw holes and one dynamic compression hole, and a head with two locked screw holes. Forty T-shaped polyurethane blocks, and 20 T-plates were used for mechanical testing. Six bone-plate constructs were tested to failure, three in axial compression and three in cantilever bending. Fourteen bone-plate constructs were tested for failure in fatigue, seven in axial compression and seven in cantilever bending. In static testing higher values of axial compression test than cantilever bending test were observed for all variables. In axial compression fatigue testing all bone-plate constructs withstood 1,000,000 cycles. Four bone-plate constructs failure occurred before 1,000,000 cycles in cantilever bending fatigue testing. In conclusion, the locking T-plate tested has mechanical properties that offer greatest resistance to fracture under axial loading than bending forces.(AU)

O objetivo deste estudo foi desenvolver uma placa bloqueada em formato de T e avaliar as propriedades mecânicas em um modelo sintético. Uma placa-T em liga de titânio 2,7mm foi desenhada com uma haste contendo três orifícios para parafusos bloqueados e um orifício para realização de compressão dinâmica. 40 blocos de poliuretano em formato de T e 20 placas-T foram utilizados para os ensaios mecânicos. Seis montagens osso-placa foram testados até a falha, sendo três em força de compressão axial e três em flexão engastada. 14 montagens osso-placa foram testadas até a falha em fatiga, sendo 7 em força de compressão axial e 7 em flexão engastada. No teste estático, os valores mais altos foram observados em todas as variáveis no teste de compressão axial quando comparado à flexão engastada. Já nos testes de fadiga na força de compressão axial, todas as montagens osso-placa resistiram à 1000000 de ciclos. No teste de fadiga em flexão engastada, quatro montagens osso-placa falharam antes de alcançarem 1000000 de ciclos. Em conclusão, a placa-T estudada apresenta propriedades mecânicas que oferecem uma melhor resistência em estabilizar as fraturas na atuação das forças de compressão axial que nas forças de flexão.(AU)

PGC-1α4 gene expression is suppressed by the IL-6-MEK-ERK 1/2 MAPK signalling axis and altered by resistance exercise, obesity and muscle injury.

AIM: PGC-1α4 is a novel regulator of muscle hypertrophy; however, there is limited understanding of the regulation of its expression and role in many (patho)physiological conditions. Therefore, our purpose was to elicit signalling mechanisms regulating gene expression of Pgc1α4 and examine its response to (patho)physiological stimuli associated with altered muscle mass. METHODS: IL-6 knockout mice and pharmacological experiments in C2C12 myocytes were used to identify regulation of Pgc1α4 transcription. To examine Pgc1α4 gene expression in (patho)physiological conditions, obese and lean Zucker rats with/without resistance exercise (RE), ageing mice and muscle regeneration from injury were examined. RESULTS: In IL-6 knockout mice, Pgc1α4mRNA was ~sevenfold greater than wild type. In C2C12 cells, Pgc1α4mRNA was suppressed ~70% by IL-6. Suppression of Pgc1α4 by IL-6 was prevented by MEK-ERK-MAPK inhibition. RE led to ~260% greater Pgc1α4mRNA content in lean rats. However, obese Zucker rats exhibited ~270% greater Pgc1α4mRNA than lean, sedentary with no further augmentation by RE. No difference was seen in IL-6mRNA or ERK-MAPK phosphorylation in Zucker rats. Aged mice demonstrated ~50% lower Pgc1α4mRNA and ~fivefold greater ERK-MAPK phosphorylation than young despite unchanged Il-6mRNA. During muscle regeneration, Pgc1α4 content is ~30% and IL-6mRNA >threefold of uninjured controls 3 days following injury; at 5 days, Pgc1α4 was >twofold greater in injured mice with no difference in IL-6mRNA. CONCLUSION: Our findings reveal a novel mechanism suppressing Pgc1α4 gene expression via IL-6-ERK-MAPK and suggest this signalling axis may inhibit Pgc1α4 in some, but not all, (patho)physiological conditions.

Owner׳s Perception for Detecting Feline Body Condition Based on Questionnaire and Scores.

To evaluate the owner׳s ability to identify body condition in cats, based on questionnaire and scores, as well as to obtain others׳ information about the cat and the owner that may be related to the body condition. Seventy-seven owned cats, aged above 11 months, were evaluated. Initially, information was obtained on age, sex, breed, and whether they had been neutered. Next, owners were asked to fill a questionnaire: the first section was about the cat׳s diet type, feeding regime, and activity level, and the second section was on the owners׳ diet, physical activity, and physical condition. The owners estimated body condition of their cats before and after seeing drawings with images. The authors also estimated body condition. Only a 5-point visual scale showed significant difference between the cat׳s body score assigned by the owner before and after seeing drawings, and before seeing drawings compared with the cat׳s body score assigned by the authors. A weak positive correlation was detected between cat׳s body score assigned by the 2 authors and access to any type of cat climbing systems, and weak negative correlation was detected for the variable spayed or neutered. The cat׳s physical activity level showed weak negative correlation with cat׳s body score. There was a strong positive correlation between cat׳s body weight and cat׳s body score. The owners showed ability to identify body condition in cats after seeing the drawings in both visual scales, and there was a relationship between cat׳s body weight and body condition score.

Translational machinery of mitochondrial mRNA is promoted by physical activity in Western diet-induced obese mice.

AIM: Mitochondria-encoded proteins are necessary for oxidative phosphorylation; however, no report has examined how physical activity (PA) and obesity affect mitochondrial mRNA translation machinery. Our purpose was to determine whether Western diet (WD)-induced obesity and voluntary wheel running (VWR) impact mitochondrial mRNA translation machinery and whether expression of this machinery is dictated by oxidative phenotype. METHODS: Obesity was induced with 8-wk WD feeding, and in the final 4 wks, half of mice were allowed VWR. Mitochondrial mRNA translation machinery including initiation factors (mtIF2/3), elongation factor Tu (TUFM) and translational activator (TACO1), and mitochondria-encoded proteins (CytB and ND4) was assessed by immunoblotting. The relation of mitochondrial mRNA translation to muscle oxidative phenotype was assessed using PGC-1α transgenic overexpression (MCK-PGC-1α vs. wild-type mice) and comparing across muscle groups in wild-type mice. RESULTS: mtIF3 and TACO1 proteins were ~45% greater in VWR than sedentary (SED), and TACO1 and mtIF2 proteins were ~60% and 125% greater in WD than normal chow (NC). TUFM protein was ~50% lower in WD-SED than NC-SED, but ~50% greater in WD-VWR compared to NC-SED. CytB and ND4 were ~40% greater in VWR and ND4 was twofold greater with WD. TUFM, TACO1, ND4 and CytB were greater in MCK-PGC-1α compared to wild-type, and mtIF2/3 contents were not different. In oxidative muscle (soleus), mitochondrial translation machinery was elevated compared to mixed (gastrocnemius) or glycolytic (extensor digitorum longus) muscles. CONCLUSION: These data suggest a novel mechanism promoting mitochondrial function by translation of mitochondrial protein following PA. This may act to promote muscle health by PA in obesity.

Kinetic and temporospatial gait parameters in a heterogeneous group of dogs.

BACKGROUND: A prime concern of the gait analysis in a heterogeneous group of dogs is the potential influence of factors such as individual body size, body mass, type of gait, and velocity. Thus, this study aimed to evaluate in a heterogeneous group of dogs a possible correlation of the stride frequency with kinetic and temporospatial variables, as well as the percentage of body weight distribution (%BWD), and compare symmetry index (SI) between trotting and walking dogs. Twenty-nine clinically healthy dogs moving in a controlled velocity were used. The dogs were organized into two groups based on duty factor. Group 1 comprised 15 walking dogs, aged from 9 months to 8 years and weighing about 22.3 kg. Group 2 had 14 trotting dogs, aged from 1 to 6 years and weighing about 6.5 kg. The kinetic data and temporospatial parameters were obtained using a pressure-sensing walkway. The velocity was 0.9-1.1 m/s. The peak vertical force (PVF), vertical impulse (VI), gait cycle time, stance time, swing time, stride length, and percentages of body weight distribution among the four limbs were determined. For each variable, the SIs were calculated. Pearson's coefficient was used to evaluate correlation between stride frequency and other variables, initially in each group and after including all animals. RESULTS: Except for the %BWD (approximately 60% for the forelimbs and 40% for the hind limbs), all other parameters differed between groups. Considering each Group individually a strong correlation was observed for most of the temporospatial parameters, but no significant correlation occurred between stride frequency and PVF, and stride frequency and %BWD. However, including all dogs a strong correlation was observed in all temporospatial parameters, and moderate correlation between stride frequency and VI, and weak correlation between stride frequency and PVF. There was no correlation between stride frequency and %BWD. Groups 1 and 2 did not differ statistically in SIs. CONCLUSIONS: In a heterogeneous group of dogs conducted at a controlled velocity, the %BWD and most of SIs presented low variability. However, %BWD seems to be the most accurate, since factors such as the magnitude of the variables may influence the SIs inducing wrong interpretation. Based on results obtained from correlations, the standardization of stride frequency could be an alternative to minimize the variability of temporospatial parameters.

Diet-induced obesity alters anabolic signalling in mice at the onset of skeletal muscle regeneration.

AIM: Obesity is classified as a metabolic disorder that is associated with delayed muscle regeneration following damage. For optimal skeletal muscle regeneration, inflammation along with extracellular matrix remodelling and muscle growth must be tightly regulated. Moreover, the regenerative process is dependent on the activation of myogenic regulatory factors (MRFs) for myoblast proliferation and differentiation. The purpose of this study was to determine how obesity alters inflammatory and protein synthetic signalling and MRF expression at the onset of muscle regeneration in mice. METHODS: Forty-eight male C57BL/6J mice (3 weeks old) were randomly assigned to either a high-fat diet (HFD, 60% fat) or a lean diet (10% fat) for 12 weeks. At 15 weeks, bupivacaine was injected into the tibialis anterior (TA) of the injured group (n = 5-8/group) and PBS was injected into the control (n = 5-6). The TA was excised 3 or 28 days after injection. RESULTS: We demonstrated impaired muscle regeneration in obese mice. The obese mice had reduced IL-6, MyoD and IGF-1 mRNA abundance compared to the lean mice (P < 0.05). Three days following muscle damage, TNF-α mRNA and protein levels of P-STAT3 and P-Akt were 14-fold, fourfold and fivefold greater in the lean mice respectively. However, there were no differences observed in the obese injured group compared to the uninjured group. Moreover, p70S6K1 was threefold greater in lean injured mice compared to uninjured but was reduced by 28% in the obese injured mice. CONCLUSION: Obese mice have impaired inflammatory and protein synthetic signalling that may negatively influence muscle regeneration.

Kinematic analysis of forelimb and hind limb joints in clinically healthy sheep.

BACKGROUND: Variations associated with sex, age, velocity, breed and body geometry should be considered in the determination of kinematic parameters for a gait considered normal. Therefore, this study aimed to evaluate kinematic patterns of forelimbs and hind limbs in clinically normal sheep from two different age groups walking at a constant velocity. The hypothesis was that the age may influence sagittal plane kinematic patterns. Fourteen clinically healthy female sheep were divided into Group 1--seven animals aged from 8 to 12 months, and Group 2--seven animals aged above 5 years. Before starting data collection, the sheep were trained to be conducted for walking in a pre-determined space at constant velocity. A minimum of 5 valid trials were obtained from the right and left sides of each sheep. Data were analyzed by use of a motion-analysis program. Flexion and extension joint angles (maximum, minimum, displacement), and angular velocity (maximum, minimum) were determined for the shoulder, elbow, carpal, hip, stifle, and tarsal joints. RESULTS: Within each group, no significant differences were observed between the right and left limbs in all kinematic variables. Significant differences were observed in the following kinematic parameters between G1 and G2: minimum angle (G1 < G2), angular displacement (G1 > G2), maximum angular velocity (G1 > G2), minimum angular velocity (G1 > G2) of the carpus; angular displacement (G1 > G2), minimum angular velocity (G1 > G2) of the shoulder; minimum angle (G1 > G2), angular displacement (G1 < G2) of the tarsus; maximum angular velocity (G1 < G2) of the stifle; maximum angular velocity G1 > G2 of the hip. The lengths of both forelimbs and hind limbs differed between groups (G1 < G2). The Froude number differed between groups for forelimbs and hind limbs. CONCLUSIONS: In conclusion, sheep of two different ages walking at a constant velocity present, within the same group, similar kinematic data between sides, and exhibit some differences in kinematic variables that may be age-related or body size. Further studies using sheep walking at similar Froude numbers are necessary to exclude the body size.

Updated and expanded study of polycythemia vera and other myeloproliferative neoplasms in the tri-county area.

INTRODUCTION: The results of a 2001-2005 polycythemia vera (PV) investigation in Eastern Pennsylvania revealed a disease cluster plus underreporting and false reporting to the Pennsylvania Cancer Registry (PCR). PURPOSE: The objectives of this study were 1) to assess PV reporting to the PCR in 2006-2009, 2) to determine whether a cancer cluster persisted, and 3) to determine whether other myeloproliferative neoplasms (MPNs), including essential thrombocytopenia (ET), were subject to similar reporting problems. METHODS: Cases were identified from: 1) PCR records from the Tri-County, 2) reviewing billing records at Tri-County hematologist/oncologist offices, and 3) self-identification. An expert panel of physicians reviewed medical records and determined "true," "false," or "indeterminate" cases reported to the PCR. The analyses were conducted to determine sensitivity and positive predictive value (PPV) of case reporting to the PCR, estimate cancer incidence rates, and evaluate the presence of cancer clusters. RESULTS: Of 290 cases identified, 90% were from the original PCR, 9% from billing records, and 1% from self-report. Fifty-five cases consented to participate, and medical records were obtained for 44. The expert panel determined that 45% were true cases, 32% were false cases, and 23% were indeterminate. PV had 100% (95% CI, 59-100) sensitivity, but only 47% PPV (95% CI, 20-70): ET had 78% (95% CI, 47-99) sensitivity and 100% PPV (95% CI, 59-100). Low participation and chart review rates led to rates with wide confidence intervals. We did not identify any PV cancer clusters, but we did identify a cluster of 9 ET cases in the Wilkes-Barre, Pennsylvania area. CONCLUSION: The current study was limited by the low response rate (22%) from MPN patients in the Tri-County area. This study identified 47% PPV for PV reporting and 100% PPV for ET.

Skeletal muscle mass recovery from atrophy in IL-6 knockout mice.

AIM: Skeletal muscle interleukin-6 (IL-6) expression is induced by continuous contraction, overload-induced hypertrophy and during muscle regeneration. The loss of IL-6 can alter skeletal muscle's growth and extracellular matrix remodelling response to overload-induced hypertrophy. Insulin-like growth factor-1 (IGF-1) gene expression and related signalling through Akt/mTOR is a critical regulator of muscle mass. The significance of IL-6 expression during the recovery from muscle atrophy is unclear. This study's purpose was to determine the effect of IL-6 loss on mouse gastrocnemius (GAS) muscle mass during recovery from hindlimb suspension (HS)-induced atrophy. METHODS: Female C57BL/6 [wild type (WT)] and IL-6 knockout (IL-6 KO) mice at 10 weeks of age were assigned to control, HS or HS followed by normal cage ambulation groups. RESULTS: GAS muscle atrophy was induced by 10 days of HS. HS induced a 20% loss of GAS mass in both WT and IL-6 KO mice. HS+7 days of recovery restored WT GAS mass to cage-control values. GAS mass from IL-6 KO mice did not return to cage-control values until HS+14 days of recovery. Both IGF-1 mRNA expression and Akt/mTOR signalling were increased in WT muscle after 1 day of recovery. In IL-6 KO muscle, IGF-1 mRNA expression was decreased and Akt/mTOR signalling was not induced after 1 day of recovery. MyoD and myogenin mRNA expression were both induced in WT muscle after 1 day of recovery, but not in IL-6 KO muscle. CONCLUSION: Muscle IL-6 expression appears important for the initial growth response during the recovery from disuse.

Testosterone deficiency as a risk factor for cardiovascular disease.

Testosterone deficiency (TD) has become a frequently diagnosed condition in our current society with an obesity epidemic. Men diagnosed with TD often have co-morbidities including metabolic syndrome. Challenging aspects in diagnosing and treating patients with TD include intra-individual variation of symptoms combined with lack of its correlation with serum levels of testosterone. Apart from sexual aspects including libido and erectile function, replacement therapy with testosterone might have beneficial metabolic effects, whereas untreated TD might increase cardiometabolic risk and disease. In this article, we review the cardiovascular and metabolic risks associated with TD, as well as risks and benefits of testosterone replacement therapy. We also provide insights into potential mechanisms of the association between cardiometabolic risks with TD (treated and untreated) and propose an individual treatment algorithm.

Overload-induced skeletal muscle extracellular matrix remodelling and myofibre growth in mice lacking IL-6.

AIM: Overloading healthy skeletal muscle produces myofibre hypertrophy and extracellular matrix remodelling, and these processes are thought to be interdependent for producing muscle growth. Inflammatory cytokine interleukin-6 (IL-6) gene expression is induced in overloaded skeletal muscle, and the loss of this IL-6 induction can attenuate the hypertrophic response to overload (OV). Although the OV induction of IL-6 in skeletal muscle may be an important regulator of inflammatory processes and satellite cell proliferation, less is known about its role in the regulation of extracellular matrix remodelling. The purpose of the current study was to examine if OV-induced extracellular matrix remodelling, muscle growth, and associated gene expression were altered in mice that lack IL-6, when compared with wild-type mice. METHODS: Male C57/BL6 (WT) and C57/BL6 x IL-6(-/-) (IL-6(-/-)) mice (10 weeks of age) were assigned to either a sham control or synergist ablation OV treatments for 3, 21 or 56 days. RESULT: Plantaris muscle mass increased 59% in WT and 116% in IL-6(-/-) mice after 21 day OV. Myofibre CSA was also increased by 21 day OV in both WT and IL-6(-/-) mice. OV induced a twofold greater increase in the volume of non-contractile tissue in IL-6(-/-) muscle compared to WT. OV also induced a significantly greater accumulation of hydroxyproline and procollagen-1 mRNA in IL-6(-/-) muscle, when compared with WT muscle after 21 day OV. Transforming growth factor-beta and insulin-like growth factor-1 mRNA expression were also induced to a greater extent in IL-6(-/-) muscle when compared with WT muscle after 21 day OV. There was no effect of IL-6 loss on the induction of myogenin, and cyclin D1 mRNA expression after 3 day OV. However, MyoD mRNA expression in 3 day OV IL-6(-/-) muscle was attenuated when compared with WT OV mice. CONCLUSION: IL-6 appears to be necessary for the normal regulation of extracellular matrix remodelling during OV-induced growth.