Thermoneutral Temperature Exposure Enhances Slow Wave Sleep with a Correlated Improvement in Amyloid Pathology in a Triple-Transgenic Mouse Model of Alzheimer's Disease.

Accumulation of amyloid-ß (Aß) plays an important role in Alzheimer's disease (AD) pathology. There is growing evidence that disordered sleep may accelerate AD pathology by impeding the physiological clearance of Aß from the brain that occurs in normal sleep. Therapeutic strategies for improving sleep quality may therefore help slow disease progression. It is well documented that the composition and dynamics of sleep are sensitive to ambient temperature. We therefore compared Aß pathology and sleep metrics derived from polysomnography in 12-month-old female 3xTg-AD mice (n = 8) exposed to thermoneutral temperatures during the light period over four weeks to those of age- and sex-matched controls (n = 8) that remained at normal housing temperature (22°C) during the same period. The treated group experienced greater proportions of slow wave sleep (SWS)-i.e., epochs of elevated 0.5-2 Hz slow wave activity during non-rapid eye movement (NREM) sleep-compared to controls. Assays performed on mouse brain tissue harvested at the end of the experiment showed that exposure to thermoneutral temperatures significantly reduced levels of DEA-soluble (but not RIPA- or FA-soluble) Aß40 and Aß42 in the hippocampus, though not in the cortex. With both groups pooled together and without regard to treatment condition, NREM sleep continuity and any measure of SWS within NREM at the end of the treatment period were inversely correlated with DEA-soluble Aß40 and Aß42 levels, again in the hippocampus but not in the cortex. These findings suggest that experimental manipulation of SWS could offer useful clues into the mechanisms and treatment of AD.

Challenging diagnosis and successful treatment of localised Mycobacterium avium subsp. hominissuis glossitis in a dog on long-term immunomodulatory therapy.

CASE HISTORY: A 3-year-old, intact female mixed-breed dog, weighing 7 kg, was presented with generalised swelling of the tongue, leading to impaired deglutition and episodes of dyspnoea. From the age of 2 years, the dog had been under immunosuppressive therapy due to atopic dermatitis. CLINICAL FINDINGS AND TREATMENT: Multiple nodular lesions at the apex of the tongue were noted as well as mandibular and retropharyngeal lymph node enlargement. Serum biochemistry results showed inflammatory changes. The results of several biopsies taken over 7 months indicated persistent pyogranulomatous and necrotising glossitis despite ongoing antimicrobial treatment, first with amoxicillin/clavulanic acid and then pradofloxacin. No foreign material, acid-fast bacteria or fungal hyphae were detected throughout. The final diagnosis of Mycobacterium avium subsp. hominissuis (Mah) was reached after PCR and bacterial culture were carried out on the third biopsy sample. Therapy was initiated with rifampicin, clarithromycin and doxycycline, leading to complete remission of the lesions. DIAGNOSIS: Severe chronic pyogranulomatous and necrotising glossitis associated with infection by Mah. CLINICAL RELEVANCE: This report describes challenges in the diagnosis and therapy of a localised Mah infection in an iatrogenically immunocompromised dog. Successful treatment was only achieved with a specific combination of antibiotics administered long-term. ABBREVIATIONS: AF: Acid-fast; ALP: Alkaline phosphatase; CT: Computed tomography; MAC: Mycobacterium avium complex; Mah: Mycobacterium avium subsp. hominissuis.

Chronic Fragmentation of the Daily Sleep-Wake Rhythm Increases Amyloid-beta Levels and Neuroinflammation in the 3xTg-AD Mouse Model of Alzheimer's Disease.

Fragmentation of the daily sleep-wake rhythm with increased nighttime awakenings and more daytime naps is correlated with the risk of development of Alzheimer's disease (AD). To explore whether a causal relationship underlies this correlation, the present study tested the hypothesis that chronic fragmentation of the daily sleep-wake rhythm stimulates brain amyloid-beta (Aß) levels and neuroinflammation in the 3xTg-AD mouse model of AD. Female 3xTg-AD mice were allowed to sleep undisturbed or were subjected to chronic sleep fragmentation consisting of four daily sessions of enforced wakefulness (one hour each) evenly distributed during the light phase, five days a week for four weeks. Piezoelectric sleep recording revealed that sleep fragmentation altered the daily sleep-wake rhythm to resemble the pattern observed in AD. Levels of amyloid-beta (Aß40 and Aß42) determined by ELISA were higher in hippocampal tissue collected from sleep-fragmented mice than from undisturbed controls. In contrast, hippocampal levels of tau and phospho-tau differed minimally between sleep fragmented and undisturbed control mice. Sleep fragmentation also stimulated neuroinflammation as shown by increased expression of markers of microglial activation and proinflammatory cytokines measured by q-RT-PCR analysis of hippocampal samples. No significant effects of sleep fragmentation on Aß, tau, or neuroinflammation were observed in the cerebral cortex. These studies support the concept that improving sleep consolidation in individuals at risk for AD may be beneficial for slowing the onset or progression of this devastating neurodegenerative disease.

Tackling antimicrobial resistance in primary health care through promoting the appropriate use of antibiotics in Estonia, EVIPNet evidence brief for policy, number 8

This report is the second evidence brief for policy produced in Estonia within the framework of the WHO European Evidence-informedPolicy Network. It was prepared by the Public Health Institute of University of Tartu in collaboration with the Ministry of Social Affairsof Estonia and WHO Country Office in Estonia. The working group identified, selected, appraised, and synthesized relevant researchevidence on the problem, three options for tackling it and considerations in implementing them. The three options are: (1) Strengthening post-graduate education and continuing the education of primary care clinicians about the appropriate use of antibiotics and antimicrobial resistance (AMR); (2) Providing clinical decision support to PHCP (primary health care providers) for the prudent use of antibiotics; and (3) Using audit and feedback to improve prescribing behaviour.

[Telemedicine in heart failure]. / Telemedizin bei Herzinsuffizienz.

Improved outpatient care of heart failure patients is considered crucial to avoiding unplanned cardiovascular hospitalizations and reducing mortality. Making up for regional and rural differences in heart failure care poses a further challenge. Telemedical care as a supplement to outpatient point-of-care medicine by the general practitioner and medical specialist is considered relevant to implementing this goal. This article presents the technical and organizational basics of telemedical methods in outpatient heart failure care. Current evidence on the efficacy of telemedical co-management is also explained based on the results from the nine most important randomized studies on telemedicine in heart failure. Particular attention is paid to the TIM-HF2 study published in 2018, which showed the superiority of telemedical co-management in terms of mortality and morbidity following recent hospitalization for heart failure. Pre-stratified subgroup analysis revealed no significant interactions in terms of the primary endpoint between urban and rural regions. Scalability is required in order to translate the telemedical study concept from TIM-HF2 to a nationwide care program for all patients in Germany. Telemed5000 is the first project to set its goal as the development of a telemedicine center for the telemedical co-management of up to 5000 patients using artificial intelligence. It is being funded by the Federal Ministry of Economics and Technology for the period 2019-2022.

Calicivirus co-infections in herpesvirus pneumonia in kittens.

Felid herpesvirus-1 (FeHV-1) and feline calicivirus (FCV) are the most important infectious causes of respiratory disease in cats. FeHV-1 and FCV co-infections are common in cats with upper respiratory tract disease, but it is unknown whether such co-infections also occur in cats with pneumonia. This study examined the lungs of naturally infected cats with FeHV-1 pneumonia for FCV co-infection by histopathology and immunohistochemistry. The frequency of FCV (13/21, 62%) in this group of cats suggests that co-infection is common in kittens with FeHV-1 pneumonia. FCV infected macrophages were often found in the lumen of FeHV-1 affected airways. In 8/13 (62%) cats, typical FCV lesions were distant from changes induced by FeHV-1. FCV infection of type II pneumocytes/alveolar macrophages was apparent in histologically unaltered areas. It is likely that damage to airways induced by FeHV-1 facilitates secondary infection with FCV due to reduced mucociliary clearance and impaired immune defences.

Rheumatic Heart Disease: Pathogenesis and Vaccine.

Rheumatic fever (RF) and rheumatic heart disease (RHD) follow untreated S. pyogenes throat infections in children who present susceptible genes that favor the development of autoimmune reactions. In this review, we focus on the genes that confer susceptibility and on the autoimmune reactions that occur due to molecular mimicry between human-tissue proteins and streptococcal M protein. Polyarthritis is the initial manifestation, which can evolve to carditis and severe valve damage; these culminate in rheumatic heart disease (RHD) or Sydenham's chorea, which affects the central nervous system. A perspective on vaccine development to prevent the disease is also discussed.

Neuronal ceroid lipofuscinosis (NCL) is caused by the entire deletion of CLN8 in the Alpenländische Dachsbracke dog.

Neuronal ceroid lipofuscinoses (NCLs) are inherited lysosomal storage diseases that have been described in a variety of dog breeds, where they are caused by different mutations in different genes. However, the causative gene defect in the breed Alpenländische Dachsbracke remained unknown so far. Here we present two confirmed cases of NCL in Alpenländische Dachsbracke dogs from different litters of the same sire with a different dam harboring the same underlying novel mutation in the CLN8 gene. Case 1, a 2-year-old male Alpenländische Dachsbracke was presented with neurological signs including disorientation, character changes including anxiety states and aggressiveness, sudden blindness and reduction of food intake. Magnetic resonance imaging (MRI) scans showed cerebral atrophy with dilation of all cerebral ventricles, thinning of the intermediate mass of the thalamus and widening of the cerebral sulci. Postmortem examination of the central nervous system (CNS) showed neuronal loss in the cerebral cortex, cerebellum and spinal cord with massive intracellular deposits of ceroid pigment. Additional ceroid-lipofuscin deposits were observed in the enteric nervous system and in macrophages within spleen, lymph nodes and lung. Ultrastructural analyses confirmed NCL with the presence of osmiophilic membrane bounded lamellar-like structures. Case 2, a 1,5-year old female Alpenländische Dachsbracke was presented with progressive generalized forebrain disease including mental changes such as fearful reactions to various kinds of external stimuli and disorientation. The dog also displayed seizures, absence of menace reactions and negative cotton-ball test with normal pupillary light reactions. The clinical and post mortem examination yielded similar results in the brain as in Case 1. Whole genome sequencing of Case 1 and PCR results of both cases revealed a homozygous deletion encompassing the entire CLN8 gene as the most likely causative mutation for the NCL form observed in both cases. The deletion follows recessive inheritance since the dam and a healthy male littermate of Case 1 were tested as heterozygous carriers. This is the first detailed description of CLN8 gene associated NCL in Alpenländische Dachsbracke dogs and thus provides a novel canine CLN8 model for this lysosomal storage disease. The presence of ceroid lipofuscin in extracerebral tissues may help to confirm the diagnosis of NCL in vivo, especially in new dog breeds where the underlying mutation is not known.

Сокращение потребления сахаросодержащих напитков и их неблагоприятного воздействия на здоровье населения в Эстонии: Аналитический обзор EVIPNet для формирования политики, номер 1

Потребление сахаросодержащих напитков связано с повышенной калорийностью рациона, набором веса, избыточным весом и ожирением в большей степени, чем потребление любых других продуктов питания или напитков. Потребление сахаросодержащих напитков также приводит к развитию ряда неинфекционных заболеваний и болезней полости рта. Уже сейчас более половины населения Эстонии имеет избыточный вес или страдает ожирением, и этот показатель быстро растет, особенно среди детей и подростков. Важное место в данном аналитическом обзоре занимают дети, поскольку предпочтения в отношении напитков и их потребления формируются уже в раннем детстве и могут сохраняться впоследствии.

В обзоре представлены четыре направления политики, которые позволят снизить потребление сахаросодержащих напитков и их неблагоприятное воздействие на здоровье: регулирование рекламы продуктов питания; маркировка сахаросодержащих напитков и повышение осведомленности об их влиянии на здоровье; меры вмешательства и политики в области питания в школах; введение налогов на сахаросодержащие напитки, субсидирование других групп продуктов и/или замена сахаросодержащих напитков другими безалкогольными напитками.

Основываясь на сделанных нами выводах, мы пришли к заключению о том, что эти четыре направления политики дополняют друг друга, и осуществление их в комплексе поможет улучшить показатели здоровья населения. Комплексные и многокомпонентные вмешательства позволят снизить потребление сахаросодержащих напитков и их неблагоприятное воздействие на здоровье.

Reducing the consumption of sugar-sweetened beverages and their negative health impact in Estonia: EVIPNet evidence brief for policy, number 1

The consumption of sugar-sweetened beverages is associated with increased energy intake, weight gain, overweight and obesity more than for any other food or beverage as well as with the development of several non-communicable diseases and poor oral health. Already, more than half of all Estonians are overweight or obese, and the numbers are rising rapidly, especially among children and adolescents. The brief focuses on children, as beverage preferences and consumption patterns develop early in childhood and can persist over time.

Four policy options were selected for reducing the consumption of sugar-sweetened beverages and their negative health effects: regulation of food advertising, labelling of sugar-sweetened beverages and raising awareness about their health effects, school interventions and nutrition policies, and imposing taxes on sugar-sweetened beverages, subsidizing other food groups and/or substituting alternative beverages.

Based on the findings it was concluded that the four policy options complement each other and, if implemented in combination, would help to reach the goal of better health outcomes. Comprehensive, multicomponent interventions will reduce the consumption of sugar-sweetened beverages and their negative health effects.

[Role of the poultry red mite (Dermanyssus gallinae) in the transmission of avian influenza A virus]. / Rolle der Roten Vogelmilbe (Dermanyssus gallinae) bei der Übertragung von aviärem Influenza-A-Virus.

OBJECTIVE: The aim of this study was to investigate the role of the poultry red mite (Dermanyssus [D.] gallinae) in the horizontal transmission of avian influenza A virus (AIV) to chickens. This mite is the most common ectoparasite in poultry worldwide, and may play a role in the spread of infectious agents including AIV. Currently, the control of mites is difficult due to frequently developed resistance to many acaricides, their nocturnality and their ability to survive hidden without feeding for months. MATERIALS AND METHODS: D. gallinae were collected in a commercial layer farm and housed in self-made fibreboard boxes. SPF chickens were intravenously infected with AIV strain A/turkey/Ontario/7732/1966 (H5N9). The viraemia in chickens was monitored and at an appropriate time point about 1000 mites were allowed to suck on the AIV infected chickens. Re-isolation of the virus from blood-filled mites was tried daily for 14 days using chicken embryo fibroblast cultures and embryonated chicken eggs. Subsequently, the virus containing mites were placed into boxes that contained naïve SPF chickens to enable virus transmission from mites to chickens. Possible transmission to the chickens was examined using clinical signs, serology, gross lesions, histopathology and immunohistochemistry. RESULTS: Chickens developed a dose-dependent viraemia one day after infection, therefore this day was chosen for the bloodmeal of the mites. AIV was detected in mites after bloodsucking on AIV-infected chickens over a 10-day period. Naïve SPF chickens were infected during bloodsucking of AIV carrying mites. AIV isolates in mites and in chickens were undistinguishable from the original AIV inoculum by RT-PCR. CONCLUSIONS: D. gallinae ingested AIV during bloodmeals on AIV infected chickens and are able to transmit AIV to SPF chickens. Therefore, mites serve as mechanical vector of AIV and may play a major role in the circulation of AIV within a facility or area although the life span of infectious virus in the mite is limited. CLINICAL RELEVANCE: The proven transmission requires more than ever a systematic control of this ectoparasite in order to maintain poultry health and productivity. The demonstrated vector function of this mite is of great significance for poultry flocks all over the world.

Obesity, diabetes, and leptin resistance promote tau pathology in a mouse model of disease.

Obesity and type 2 diabetes mellitus (T2DM) convey an increased risk for developing dementia. The microtubule-associated protein tau is implicated in neurodegenerative disease by undergoing hyperphosphorylation and aggregation, leading to cytotoxicity and neurodegeneration. Enzymes involved in the regulation of tau phosphorylation, such as GSK3ß, are tightly associated with pathways found to be dysregulated in T2DM. We have shown previously that leptin-resistant mice, which develop obesity and a diabetic phenotype, display elevated levels of tau phosphorylation. Here we show cells cultured with leptin, an adipokine shown to have neuroprotective effects, reduces tau phosphorylation. To explore how this mechanism works in vivo we transduced an existing diabetic mouse line (Lepr(db/db)) with a tau mutant (tau(P301L)) via adeno-associated virus (AAV). The resulting phenotype included a striking increase in tau phosphorylation and the number of neurofibrillary tangles (NFTs) found within the hippocampus. We conclude that leptin resistance-induced obesity and diabetes accelerates the development of tau pathology. This model of metabolic dysfunction and tauopathy provides a new system in which to explore the mechanisms underlying the ways in which leptin resistance and diabetes influence development of tau pathology, and may ultimately be related to the development of NFTs.

Suhkruga magustatud jookide tarbimise ja sellest põhjustatud tervisekahjude vähendamine Eestis: EVIPNet Tõenduspõhisuse ülevaade, number 1

Suhkruga magustatud jookide tarbimine on kehakaalu tõusuga tugevamini seotud kui ühegi muu toidu või joogi tarbimine, samuti on nende tarbimine seotud mitmetesse mittenakkushaigustesse haigestumisega ja halvenenud suuõõnetervisega. Juba praegu on üle poole Eesti elanikest ülekaalulised või rasvunud ja nende osatähtsus rahvastikus kasvab kiiresti, eriti laste ja noorukite seas. Tõenduspõhisuse ülevaade keskendub eelkõige just lastele ja noortele, sest joogieelistused ja tarbimismustrid kujunevad välja juba varases lapsepõlves ja need võivad püsida pikka aega.

Suhkruga magustatud jookide tarbimise ja nende negatiivse tervisemõju vähendamiseks käsitleti nelja poliitikavalikut: toiduturunduse meetmed, suhkruga magustatud jookide märgistus ja teadlikkuse tõstmine nende tervisemõjust, sekkumismeetmed koolides ja koolide toidupoliitika ning suhkruga magustatud jookide maksustamine, muude toidugruppide subsideerimine ja/või alternatiivsete jookidega asendamine.

Tulemuste põhjal järeldati, et neli poliitikavalikut on üksteist täiendavad ja nende kombineerimine aitab saavutada parema tervisetulemi eesmärki. Laiahaardelised, mitme komponendiga sekkumismeetmed vähendavad suhkruga magustatud jookide tarbimist ja nende negatiivset tervisemõju.

A prospective randomised phase-II trial with gemcitabine versus gemcitabine plus sunitinib in advanced pancreatic cancer: a study of the CESAR Central European Society for Anticancer Drug Research-EWIV.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is one of the most common malignant tumours and is still associated with a poor prognosis in advanced disease. To improve the standard therapy with gemcitabine, we initiated a prospective randomised phase-II trial with gemcitabine (GEM) versus gemcitabine plus sunitinib (SUNGEM) based on data of in vitro trials and phase-I data for the combination treatment. The rational of adding sunitinib was its putative antiangiogenic mechanism of action. METHODS: A total of 106 eligible patients with locally advanced, unresectable or metastatic PDAC without previous system therapy were randomised to receive GEM at a dosage of 1.000mg/m(2) d1, 8, 15 q28 versus a combination of SUNGEM at a dosage of GEM 1.000mg/m(2) d1+8 and sunitinib 50mg p.o. d1-14, q21d. The primary end-point was progression free survival (PFS), secondary end-points were overall survival (OS), toxicity and overall response rate (ORR). RESULTS: The confirmatory analysis of PFS was based on the intend-to-treat (ITT) population (N=106). The median PFS was 13.3 weeks (95% confidence interval (95%-CI): 10.4-18.1 weeks) for GEM and 11.6 weeks for SUNGEM (95%-CI: 7.0-18.0 weeks; p=0.78 one-sided log-rank). The ORR was 6.1% (95%-CI: 0.7-20.2%) for GEM and for 7.1% (95%-CI: 0.9-23.5%) for SUNGEM (p=0.87). The median time to progression (TTP) was 14.0 weeks (95%-CI: 12.4-22.3 weeks) for GEM and 18.0 weeks (95%-CI: 11.3-19.3 weeks) for SUNGEM (p=0.60; two-sided log-rank). The median OS was 36.7 weeks (95%-CI: 20.6-49.0 weeks) for the GEM arm and 30.4 weeks (95%-CI: 18.1-37.6 weeks) for the SUNGEM (p=0.78, one-sided log-rank). In regard to toxicities, suspected SAEs were reported in 53.7% in the GEM arm and 71.2% in the SUNGEM arm. Grade 3 and 4 neutropenia was statistically significantly higher in the SUNGEM arm with 48.1% versus 27.8% in the GEM arm (p=0.045, two sided log-rank). CONCLUSIONS: The combination SUNGEM was not sufficient superior in locally advanced or metastatic PDAC compared to GEM alone in regard to efficacy but was associated with more toxicity.

Dietary ergot alkaloids as a possible cause of tail necrosis in rabbits.

This study describes the association between tail necrosis in rabbits and mycotoxins in rabbit feed. Clinical cases of tail necrosis were observed in 14 out of 103 rabbits kept in an outdoor group housing, fed with hay and a commercial pelleted feed. The observed clinical symptoms, alopecia, erosions, crusts and necrosis were restricted to the tail area and exclusively occurred in young rabbits aged 113 ± 20 days. Dermatological examination suggested that ischemia had caused necrosis. Analysis of blood samples showed an elevated level of creatine kinase. No weight loss occurred in affected rabbits. Trauma caused by injuries or technopathic lesions was also excluded. Histopathologically, the lesions were characterized by acute muscle fibre degeneration and chronic active dermatitis with granulation tissue formation. Necropsy of one rabbit revealed hepatocellular degeneration and necrosis as remarkable findings. Feed analysis for ergot alkaloids by enzyme immunoassays yielded a mean and maximum ergot alkaloid content of 410 ± 250 µg/kg and 1,700 µg/kg, respectively. Faeces of affected rabbits contained ergot alkaloids at levels up to 200 µg/kg. The mean and maximum dietary intake of total ergot alkaloids were 17 and 71 µg/kg bodyweight, respectively. Fusarium toxins (trichothecenes, zearalenone, fumonisins) were also found in the feed, but at levels which did not explain the observed effects. The results indicate that ergot alkaloids may have been the cause of tail necrosis, which is supported by literature data showing that rabbits are especially sensitive towards these toxins.

Alveolar macrophages are the main target cells in feline calicivirus-associated pneumonia.

Feline calicivirus (FCV) is a pathogen of felids and one of the most common causative agents of feline upper respiratory disease (URD). Reports of natural FCV pneumonia in the course of respiratory tract infections are sparse. Therefore, knowledge on the pathogenesis of FCV-induced lung lesions comes only from experimental studies. The aim of the present study was to assess the type and extent of pulmonary involvement in natural respiratory FCV infections of domestic cats and to identify the viral target cells in the lung. For this purpose, histology, immunohistochemistry and RNA-in situ hybridisation for FCV and relevant cell markers were performed on diagnostic post-mortem specimens collected after fatal URD, virulent systemic FCV or other conditions. All groups of cats exhibited similar acute pathological changes, dominated by multifocal desquamation of activated alveolar macrophages (AM) and occasional type II pneumocytes with fibrin exudation, consistent with diffuse alveolar damage (DAD). In fatal cases, this was generally seen without evidence of epithelial regeneration. In cats without clinical respiratory signs, type II pneumocyte hyperplasia was present alongside the other changes, consistent with the post-damage proliferative phase of DAD. FCV infected and replicated in AM and, to a lesser extent, type II pneumocytes. This study shows that lung involvement is an infrequent but important feature of FCV-induced URD. AM are the main viral target cell and pulmonary replication site, and their infection is associated with desquamation and activation, as well as death via apoptosis.

[Old and immobile in rural areas? Limited mobility of the elderly in the context of increasingly problematic health care in rural regions]. / Alt und immobil auf dem Land? Mobilitätseinschränkungen älterer Menschen vor dem Hintergrund einer zunehmend problematischen Gesundheitsversorgung in ländlichen Regionen.

Against the background of considerable population ageing processes in rural areas, it is expected that access to the health care system in these regions will deteriorate. Within this context, the question arises as to whether elderly people have the ability to overcome increasing distances in order to receive adequate medical care. Hence the objective of this study is an in-depth analysis of the everyday mobility of elderly people living in rural areas. The empirical analysis is based on the German National Travel Survey "Mobilität in Deutschland 2008". Findings show that older women in particular experience limitations in their mobility options. Only 63% of mobility-impaired women (aged > 75 years) were mobile outside their homes, and only 37% had access to a car, which can be regarded as the crucial factor for being mobile. It follows that older and mobility-impaired women have to cope with everyday life under difficult conditions. In the context of the growing problem of access to the health care system in rural areas, the challenge is to ensure adequate primary health care for a large proportion of the immobile elderly.

Acute metabolic, hormonal, and psychological responses to different endurance training protocols.

In the last years, mainly 2 high-intensity-training (HIT) protocols became common: first, a Wingate-based "all-out" protocol and second, a 4×4 min protocol. However, no direct comparison between these protocols exists, and also a comparison with high-volume-training (HVT) is missing. Therefore, the aim of the present study was to compare these 3 endurance training protocols on metabolic, hormonal, and psychological responses. Twelve subjects performed: 1) HVT [130 min at 55% peak power output (PPO)]; 2) 4×4 min at 95% PPO; 3) 4×30 s all-out. Human growth hormone (hGH), testosterone, and cortisol were determined before (pre) and 0', 30', 60', 180' after each intervention. Metabolic stimuli and perturbations were characterized by lactate, blood gas (pH, BE, HCO3⁻, pO2, PCO2), and spirometric analysis. Furthermore, changes of the person's perceived physical state were determined. The 4×30 s training caused the highest increases in cortisol and hGH, followed by 4 × 4 min and HVT. Testosterone levels were significantly increased by all 3 exercise protocols. Metabolic stress was highest during and after 4×30 s, followed by 4×4 min and HVT. The 4×30 s training was also the most demanding intervention from an athlete's point of view. In conclusion, the results suggest that 4×30 s and 4×4 min promote anabolic processes more than HVT, due to higher increases of hGH, testosterone, and the T/C ratio. It can be speculated that the acute hormonal increase and the metabolic perturbations might play a positive role in optimizing training adaptation and in eliciting health benefits as it has been shown by previous long term training studies using similar exercise protocols.

The IGFBP7 homolog Imp-L2 promotes insulin signaling in distinct neurons of the Drosophila brain.

In Drosophila, Insulin-like peptide 2 (Dilp-2) is expressed by insulin-producing cells in the brain, and is secreted into the hemolymph to activate insulin signaling systemically. Within the brain, however, a more local activation of insulin signaling may be required to couple behavioral and physiological traits to nutritional inputs. We show that a small subset of neurons in the larval brain has high Dilp-2-mediated insulin signaling activity. This local insulin signaling activation is accompanied by selective Dilp-2 uptake and depends on the expression of the Imaginal morphogenesis protein-late 2 (Imp-L2) in the target neurons. We suggest that Imp-L2 acts as a licensing factor for neuronal IIS activation through Dilp-2 to further increase the precision of insulin activity in the brain.