Advantage of ostarine over raloxifene and their combined treatments for muscle of estrogen-deficient rats.

PURPOSE: Selective androgen (ostarine, OST) and estrogen (raloxifene, RAL) receptor modulators with improved tissue selectivity have been developed as alternatives to hormone replacement therapy. We investigated the combined effects of OST and RAL on muscle tissue in an estrogen-deficient rat model of postmenopausal conditions. METHODS: Three-month-old Sprague Dawley rats were divided into groups: (1) untreated non-ovariectomized rats (Non-OVX), (2) untreated ovariectomized rats (OVX), (3) OVX rats treated with OST, (4) OVX rats treated with RAL, (5) OVX rats treated with OST and RAL. Both compounds were administered in the diet. The average dose received was 0.6 ± 0.1 mg for OST and 11.1 ± 1.2 mg for RAL per kg body weight/day. After thirteen weeks, rat activity, muscle weight, structure, gene expression, and serum markers were analyzed. RESULTS: OST increased muscle weight, capillary ratio, insulin-like growth factor 1 (Igf-1) expression, serum phosphorus, uterine weight. RAL decreased muscle weight, capillary ratio, food intake, serum calcium and increased Igf-1 and Myostatin expression, serum follicle stimulating hormone (FSH). OST + RAL increased muscle nucleus ratio, uterine weight, serum phosphorus, FSH and luteinizing hormone and decreased body and muscle weight, serum calcium. Neither treatment changed muscle fiber size. OVX increased body and muscle weight, decreased uterine weight, serum calcium and magnesium. CONCLUSION: OST had beneficial effects on muscle in OVX rats. Side effects of OST on the uterus and serum electrolytes should be considered before using it for therapeutic purposes. RAL and RAL + OST had less effect on muscle and showed endocrinological side effects on pituitary-gonadal axis.

Treatment of osteoporosis using a selective androgen receptor modulator ostarine in an orchiectomized rat model.

PURPOSE: The selective androgen receptor modulator ostarine has been shown to have advantageous effects on skeletal tissue properties, reducing muscle wasting and improving physical function in males. However, data on effects in male osteoporosis remain limited. In this study, the effects of ostarine on osteoporotic bone were evaluated in a rat model of male osteoporosis and compared with those of testosterone treatments. METHODS: Eight-month-old male Sprague-Dawley rats were either non-orchiectomized to serve as a healthy control (Non-Orx, Group 1) or orchiectomized (Orx, Groups 2-6) and then grouped (n = 15/group): (1) Non-Orx, (2) Orx, (3) Ostarine Therapy, (4) Testosterone Therapy, (5) Ostarine Prophylaxis and (6) Testosterone Prophylaxis. Prophylaxis treatments started directly after orchiectomy and continued for 18 weeks, whereas Therapy treatments were initiated 12 weeks after Orx. Ostarine and Testosterone were applied orally at daily doses of 0.4 and 50 mg/kg body weight, respectively. The lumbar vertebral bodies and femora were analyzed using biomechanical, micro-CT, ashing, and gene expression analyses. RESULTS: Ostarine Prophylaxis showed positive effects in preventing osteoporotic changes in cortical and trabecular bone (femoral trabecular density: 26.01 ± 9.1% vs. 20.75 ± 1.2% in Orx and in L4: 16.3 ± 7.3% vs 11.8 ± 2.9% in Orx); biomechanical parameters were not affected; prostate weight was increased (0.62 ± 0.13 g vs 0.18 ± 0.07 g in Orx). Ostarine Therapy increased solely the cortical density of the femur (1.25 ± 0.03 g/cm3 vs. 1.18 ± 0.04 g/cm3 in Orx); other bone parameters remained unaffected. Testosteron Prophylaxis positively influenced cortical density in femur (1.24 ± 0.05 g/cm3 vs. 1.18 ± 0.04 g/cm3 in Orx); Test. Therapy did not change any bony parameters. CONCLUSION: Ostarine Prophylaxis could be further investigated as a preventative treatment for male osteoporosis, but an androgenic effect on the prostate should be taken into consideration, and combination therapies with other anti-osteoporosis agents could be considered.

Multi-source datasets acquired over Toulouse (France) in 2021 for urban microclimate studies during the CAMCATT/AI4GEO field campaign.

The CAMCATT-AI4GEO extensive field experiment took place in Toulouse, a city in the southwest of France, from 14th to 25th June 2021 (with complementary measurements performed on the 6 September 2021). Its main objective was the acquisition of a new reference dataset on an urban site to support the development and validation of data products from the future thermal infrared (TIR) satellite missions such as TRISHNA (CNES/ISRO), LSTM (ESA) and SBG (NASA). With their high spatial (between 30-60m) and temporal (2-3 days) resolutions, the future TIR satellite data will allow a better investigation of the urban climate at the neighbourhood scale. However, in order to validate the future products of these missions such as LST, air temperature, comfort index and Urban Heat Island (UHI), there is a need to accurately characterise the organisation of the city in terms of 3D geometry, spectral optical properties and both land surface temperature and emissivity (LST and LSE) at several scales. In this context, the CAMCATT-AI4GEO field campaign provides a set of airborne VISNIR-SWIR (Visible Near InfraRed - ShortWave InfraRed) hyperspectral imagery, multispectral thermal infrared (TIR) imagery and 3D LiDAR acquisitions, together with a variety of ground data collected, for some of them, simultaneously to the flight. The ground dataset includes surface reflectance measured spectrally with ASD spectroradiometers and in six spectral bands spreading from shortwave to thermal infrared and for two viewing angles with a SOC410-DHR handheld reflectometer. It is completed with LST and LSE retrieved from thermal infrared radiance acquired in six spectral bands with CIMEL radiometers. It also includes meteorological data coming from four radio soundings (one of which was taken during the flight), data routinely collected at the Blagnac airport reference station as well as air temperature and humidity acquired using instrumented cars following two different itineraries. In addition, a link is provided to access the data routinely collected by the network of weather stations set up by Toulouse Metropole in the city and its surroundings. This data paper describes this new reference urban dataset which can be useful for many applications such as calibration/validation of at-surface radiance, LST and LSE data products as well as higher level products such as air temperature or comfort index. It also provides valuable opportunities for other applications in urban climate studies, such as supporting the validation of microclimate models.

Changes of the subchondral bone microchannel network in early osteoarthritis.

OBJECTIVE: We have identified a 3D network of subchondral microchannels that connects the deep zone of cartilage to the bone marrow (i.e., cartilage-bone marrow microchannel connectors; CMMC). However, the pathological significance of CMMC is largely unknown. Here, we quantitatively evaluated how the CMMC microarchitecture is related to cartilage condition, as well as regional differences in early idiopathic osteoarthritis (OA). METHODS: Two groups of cadaveric female human femoral heads (intact cartilage vs early cartilage lesions) were identified, and a biopsy-based high-resolution micro-CT imaging was employed. Subchondral bone (SB) thickness, CMMC number, maximum and minimum CMMC size, and the CMMC morphology were quantified and compared between the two groups. The effect of joint's region and cartilage condition was examined on each dependent variable. RESULTS: The CMMC number and morphology were affected by region of the joint, but not by cartilage condition. On the other hand, the minimum and maximum CMMC size was changed by both the location on the joint, as well as the cartilage condition. The smallest CMMC were consistently detected at the load-bearing region (LBR) of the joint. Compared to non-pathological subjects, the size of the microchannels was enlarged in early OA, most noticeably at the non-load-bearing region (NLBR) and the peripheral rim (PR) of the femoral head. Furthermore, subchondral bone thinning was observed in early OA as a localized occurrence linked with areas of partial chondral defect. CONCLUSION: Our data point to an enlargement of the SB microchannel network, and a collective structural deterioration of SB in early idiopathic OA.

A combined treatment with selective androgen and estrogen receptor modulators prevents bone loss in orchiectomized rats.

PURPOSE: Enobosarm (EN), a selective androgen receptor modulator and raloxifene (RAL), a selective estrogen receptor modulator, have been shown to improve bone tissue in osteoporotic males. The present study evaluated the effects of a combination therapy of EN and RAL on bone properties in orchiectomized rats compared to the respective single treatments. METHODS: Eight-month-old male Sprague-Dawley rats were either left intact (Non-Orx) or orchiectomized (Orx). The Orx rats were divided into four groups (n = 15 each): 1) Orx, 2) EN treatment (Orx + EN), 3) RAL treatment (Orx + RAL), 4) combined treatment (Orx + EN + RAL). EN and RAL (0.4 mg and 7 mg/kg body weight/day) were applied immediately after Orx with a soy-free pelleted diet for up to 18 weeks. The lumbar spine and femora were examined by micro-CT, biomechanical, histomorphological, ashing, and gene expression analyses. RESULTS: EN exhibited an anabolic effect on bone, improving some of its parameters in Orx rats, but did not affect biomechanical properties. RAL exhibited antiresorptive activity, maintaining the biomechanical and trabecular parameters of Orx rats at the levels of Non-Orx rats. EN + RAL exerted a stronger effect than the single treatments, improving most of the bone parameters. Liver weight increased after all treatments; the kidney, prostate, and levator ani muscle weights increased after EN and EN + RAL treatments. BW was reduced due to a decreased food intake in the Orx + RAL group and due a reduced visceral fat weight in the Orx + EN + RAL group. CONCLUSION: The EN + RAL treatment appeared to be promising in preventing male osteoporosis, but given the observed side effects on liver, kidney, and prostate weights, it requires further investigation.

Combination of selective androgen and estrogen receptor modulators in orchiectomized rats.

PURPOSE: Selective androgen and estrogen receptor modulators, ostarine (OST) and raloxifen (RAL), reportedly improve muscle tissue and offer therapeutic approaches to muscle maintenance in the elderly. The present study evaluated the effects of OST and RAL and their combination on musculoskeletal tissue in orchiectomized rats. METHODS: Eight-month-old Sprague Dawley rats were analyzed. Experiment I: (1) Untreated non-orchiectomized rats (Non-ORX), (2) untreated orchiectomized rats (ORX), (3) ORX rats treated with OST during weeks 0-18 (OST-P), (4) ORX rats treated with OST during weeks 12-18 (OST-T). Experiment II: 1) Non-ORX, (2) ORX, 3) OST-P, (4) ORX rats treated with RAL, during weeks 0-18 (RAL-P), 5) ORX rats treated with OST + RAL, weeks 0-18 (OST + RAL-P). The average daily doses of OST and RAL were 0.4 and 7 mg/kg body weight (BW). Weight, fiber size, and capillarization of muscles, gene expression, serum markers and the lumbar vertebral body were analyzed. RESULTS: OST-P exerted favorable effects on muscle weight, expression of myostatin and insulin growth factor-1, but increased prostate weight. OST-T partially improved muscle parameters, showing less effect on the prostate. RAL-P did not show anabolic effects on muscles but improved body constitution by reducing abdominal area, food intake, and BW. OST + RAL-P had an anabolic impact on muscle, reduced androgenic effect on the prostate, and normalized food intake. OST and RAL improved osteoporotic bone. CONCLUSIONS: The OST + RAL treatment appeared to be a promising option in the treatment of androgen-deficient conditions and showed fewer side effects than the respective single treatments.

Sympathectomy aggravates subchondral bone changes during osteoarthritis progression in mice without affecting cartilage degeneration or synovial inflammation.

OBJECTIVE: Osteoarthritis (OA) pathogenesis involves the interaction of articular cartilage with surrounding tissues, which are innervated by tyrosine hydroxylase-positive (TH+) sympathetic nerve fibers suggesting a role of the sympathetic nervous system (SNS) during OA progression. We analyzed the effects of sympathectomy (Syx) in a murine OA model. METHODS: Peripheral Syx was generated by 6-hydroxydopamine (6-OHDA) injections in male C57BL/6 mice. OA was induced in wild-type (WT) and Syx mice by destabilization of the medial meniscus (DMM). TH+ fibers and splenic NE were analyzed to evaluate Syx efficiency. OA progression was examined by OARSI and synovitis scores and micro-CT. Expression of TH, α2A- and ß2-adrenergic receptors (AR), and activity of osteoblasts (ALP) and osteoclasts (TRAP) was investigated by stainings. RESULTS: Syx resulted in synovial TH+ fiber elimination and splenic NE decrease. Cartilage degradation and synovitis after DMM were comparably progressive in both WT and Syx mice. Calcified cartilage (CC) and subchondral bone plate (SCBP) thickness and bone volume fraction (BV/TV) increased in Syx mice due to increased ALP and decreased TRAP activities compared to WT 8 weeks after DMMWT and Syx mice developed osteophytes and meniscal ossicles without any differences between the groups. AR numbers decreased in cartilage but increased in synovium and osteophyte regions after DMM in both WT and Syx mice. CONCLUSION: Peripheral dampening of SNS activity aggravated OA-specific cartilage calcification and subchondral bone thickening but did not influence cartilage degradation and synovitis. Therefore, SNS might be an attractive target for the development of novel therapeutic strategies for pathologies of the subchondral bone.

Root deformation affects mineral nutrition but not leaf gas exchange and growth of Genipa americana seedlings during the recovery phase after soil flooding / A deformação de raízes afeta a nutrição mineral mas não as trocas gasosas foliares e o crescimento de mudas de Genipa americana durante a fase de recuperação após o alagamento do solo

Root deformation (RD) caused by errors in the pricking out process are irreversible and very difficult to detect in container-grown seedlings at the time of planting in the field. The objective of this study was to evaluate the effects of RD on leaf gas exchange, growth, biomass allocation and mineral nutrition of G. americana seedlings during the recovery phase after soil flooding. Four-months-old seedlings, with and without RD, were flooded for 42 days and their recovery was evaluated 28 days after soil drainage. There were no significant interactions between RD and soil flooding for all leaf gas exchange, growth and mineral nutrition after soil drainage, with the exception of leaf P concentrations. In plants with no RD, the P concentration in leaves of non-flooded plants was significantly higher than that of plants with RD. Soil flooding and RD did not influence leaf or root N concentrations or whole-plant N content. RD increased the K concentration in the roots, but not in the leaves. Changes in the nutrient concentrations in leaves and roots indicate that RD may affect physiological performance of seedlings after planting in the field.

A deformação da raiz (RD) causada por erros no processo de repicagem é irreversível e difícil de detectar em mudas produzidas em embalagens no momento do plantio no campo. O objetivo deste estudo foi avaliar os efeitos do RD nas trocas gasosas foliares, crescimento, alocação de biomassa e nutrição mineral de mudas de G. americana na fase de recuperação após o alagamento do solo. Mudas com quatro meses de idade, com e sem RD, foram alagadas por 42 dias e a sua recuperação foi avaliada 28 dias após a drenagem do solo. Não houve interação significativa entre RD e alagamento do solo nas trocas gasosas foliares, crescimento e nutrição mineral após a drenagem, com exceção das concentrações de P foliar. Em plantas sem RD, a concentração de P nas folhas de plantas não alagadas foi significativamente maior que a das plantas com RD. O alagamento do solo e a RD não influenciaram as concentrações de N nas folhas e raízes, e no conteúdo de N na planta inteira. A RD aumentou a concentração de K nas raízes, mas não nas folhas. Alterações nas concentrações de nutrientes nas folhas e raízes indicam que a RD pode afetar o desempenho fisiológico das mudas após o plantio no campo.

Root deformation affects mineral nutrition but not leaf gas exchange and growth of Genipa americana seedlings during the recovery phase after soil flooding / A deformação de raízes afeta a nutrição mineral mas não as trocas gasosas foliares e o crescimento de mudas de Genipa americana durante a fase de recuperação após o alagamento do solo

Root deformation (RD) caused by errors in the pricking out process are irreversible and very difficult to detect in container-grown seedlings at the time of planting in the field. The objective of this study was to evaluate the effects of RD on leaf gas exchange, growth, biomass allocation and mineral nutrition of G. americana seedlings during the recovery phase after soil flooding. Four-months-old seedlings, with and without RD, were flooded for 42 days and their recovery was evaluated 28 days after soil drainage. There were no significant interactions between RD and soil flooding for all leaf gas exchange, growth and mineral nutrition after soil drainage, with the exception of leaf P concentrations. In plants with no RD, the P concentration in leaves of non-flooded plants was significantly higher than that of plants with RD. Soil flooding and RD did not influence leaf or root N concentrations or whole-plant N content. RD increased the K concentration in the roots, but not in the leaves. Changes in the nutrient concentrations in leaves and roots indicate that RD may affect physiological performance of seedlings after planting in the field.

A deformação da raiz (RD) causada por erros no processo de repicagem é irreversível e difícil de detectar em mudas produzidas em embalagens no momento do plantio no campo. O objetivo deste estudo foi avaliar os efeitos do RD nas trocas gasosas foliares, crescimento, alocação de biomassa e nutrição mineral de mudas de G. americana na fase de recuperação após o alagamento do solo. Mudas com quatro meses de idade, com e sem RD, foram alagadas por 42 dias e a sua recuperação foi avaliada 28 dias após a drenagem do solo. Não houve interação significativa entre RD e alagamento do solo nas trocas gasosas foliares, crescimento e nutrição mineral após a drenagem, com exceção das concentrações de P foliar. Em plantas sem RD, a concentração de P nas folhas de plantas não alagadas foi significativamente maior que a das plantas com RD. O alagamento do solo e a RD não influenciaram as concentrações de N nas folhas e raízes, e no conteúdo de N na planta inteira. A RD aumentou a concentração de K nas raízes, mas não nas folhas. Alterações nas concentrações de nutrientes nas folhas e raízes indicam que a RD pode afetar o desempenho fisiológico das mudas após o plantio no campo.

Root deformation affects mineral nutrition but not leaf gas exchange and growth of Genipa americana seedlings during the recovery phase after soil flooding

Abstract Root deformation (RD) caused by errors in the pricking out process are irreversible and very difficult to detect in container-grown seedlings at the time of planting in the field. The objective of this study was to evaluate the effects of RD on leaf gas exchange, growth, biomass allocation and mineral nutrition of G. americana seedlings during the recovery phase after soil flooding. Four-months-old seedlings, with and without RD, were flooded for 42 days and their recovery was evaluated 28 days after soil drainage. There were no significant interactions between RD and soil flooding for all leaf gas exchange, growth and mineral nutrition after soil drainage, with the exception of leaf P concentrations. In plants with no RD, the P concentration in leaves of non-flooded plants was significantly higher than that of plants with RD. Soil flooding and RD did not influence leaf or root N concentrations or whole-plant N content. RD increased the K concentration in the roots, but not in the leaves. Changes in the nutrient concentrations in leaves and roots indicate that RD may affect physiological performance of seedlings after planting in the field.

Resumo A deformação da raiz (RD) causada por erros no processo de repicagem é irreversível e difícil de detectar em mudas produzidas em embalagens no momento do plantio no campo. O objetivo deste estudo foi avaliar os efeitos do RD nas trocas gasosas foliares, crescimento, alocação de biomassa e nutrição mineral de mudas de G. americana na fase de recuperação após o alagamento do solo. Mudas com quatro meses de idade, com e sem RD, foram alagadas por 42 dias e a sua recuperação foi avaliada 28 dias após a drenagem do solo. Não houve interação significativa entre RD e alagamento do solo nas trocas gasosas foliares, crescimento e nutrição mineral após a drenagem, com exceção das concentrações de P foliar. Em plantas sem RD, a concentração de P nas folhas de plantas não alagadas foi significativamente maior que a das plantas com RD. O alagamento do solo e a RD não influenciaram as concentrações de N nas folhas e raízes, e no conteúdo de N na planta inteira. A RD aumentou a concentração de K nas raízes, mas não nas folhas. Alterações nas concentrações de nutrientes nas folhas e raízes indicam que a RD pode afetar o desempenho fisiológico das mudas após o plantio no campo.

Root deformation affects mineral nutrition but not leaf gas exchange and growth of Genipa americana seedlings during the recovery phase after soil flooding.

Root deformation (RD) caused by errors in the pricking out process are irreversible and very difficult to detect in container-grown seedlings at the time of planting in the field. The objective of this study was to evaluate the effects of RD on leaf gas exchange, growth, biomass allocation and mineral nutrition of G. americana seedlings during the recovery phase after soil flooding. Four-months-old seedlings, with and without RD, were flooded for 42 days and their recovery was evaluated 28 days after soil drainage. There were no significant interactions between RD and soil flooding for all leaf gas exchange, growth and mineral nutrition after soil drainage, with the exception of leaf P concentrations. In plants with no RD, the P concentration in leaves of non-flooded plants was significantly higher than that of plants with RD. Soil flooding and RD did not influence leaf or root N concentrations or whole-plant N content. RD increased the K concentration in the roots, but not in the leaves. Changes in the nutrient concentrations in leaves and roots indicate that RD may affect physiological performance of seedlings after planting in the field.

[Reducing tinnitus intensity : Pilot study to attenuate tonal tinnitus using individually spectrally optimized near-threshold noise]. / Reduktion der Tinnituslautstärke : Pilotstudie zur Abschwächung von tonalem Tinnitus mit schwellennahem, individuell spektral optimiertem Rauschen.

BACKGROUND: Around 15% of the general population is affected by tinnitus, but no real cure exists despite intensive research. Based on our recent causal model for tinnitus development, we here test a new treatment aimed at counteracting the perception. This treatment is based on the stochastic resonance phenomenon at specific auditory system synapses that is induced by externally presented near-threshold noise. OBJECTIVE: This pilot study will investigate whether individually spectrally adapted noise can successfully reduce chronic tonal/narrow-band tinnitus during stimulation. MATERIALS AND METHODS: Hearing loss (HL) as well as tinnitus pitch (TP) and loudness (TL) were audiometrically measured in 22 adults (46.6±16.3 years; 4 women) with tinnitus. Based on these measurements, up to eight different noise stimuli with five intensities (-20 to +20 dB SL) were generated. These were presented for 40 s each via audiologic headphones in a soundproof chamber. After each presentation, the change in TL was rated on a five-level scale (-2 to +2). RESULTS: We found patients (n = 6) without any improvement in their TL perception as well as patients with improvement (n = 16), where stimulation around the TP was most effective. The groups differed in post-hoc analysis of their audiograms: the effectiveness of our new therapeutic strategy obviously depends on the individual HL, and was most effective in normal-hearing tinnitus patients and those with mild HL. CONCLUSION: Subjective TL could be reduced in 16 out of 22 patients during stimulation. For a possible success of a future therapy, the HL seems to be of relevance.

Analysis of low-dose estrogen on callus BMD as measured by pQCT in postmenopausal women.

BACKGROUND: Osteoporosis affects elderly patients of both sexes. It is characterized by an increased fracture risk due to defective remodeling of the bone microarchitecture. It affects in particular postmenopausal women due to their decreased levels of estrogen. Preclinical studies with animals demonstrated that loss of estrogen had a negative effect on bone healing and that increasing the estrogen level led to a better bone healing. We asked whether increasing the estrogen level in menopausal patients has a beneficial effect on bone mineral density (BMD) during callus formation after a bone fracture. METHODS: To investigate whether estrogen has a beneficial effect on callus BMD of postmenopausal patients, we performed a prospective double-blinded randomized study with 76 patients suffering from distal radius fractures. A total of 31 patients (71.13 years ±11.99) were treated with estrogen and 45 patients (75.62 years ±10.47) served as untreated controls. Calculated bone density as well as cortical bone density were determined by peripheral quantitative computed tomography (pQCT) prior to and 6 weeks after the surgery. Comparative measurements were performed at the fractured site and at the corresponding position of the non-fractured arm. RESULTS: We found that unlike with preclinical models, bone fracture healing of human patients was not improved in response to estrogen treatment. Furthermore, we observed no dependence between age-dependent bone tissue loss and constant callus formation in the patients. CONCLUSIONS: Transdermally applied estrogen to postmenopausal women, which results in estrogen levels similar to the systemic level of premenopausal women, has no significant beneficial effect on callus BMD as measured by pQCT, as recently shown in preclinical animal models. TRIAL REGISTRATION: Low dose estrogen has no significant effect on bone fracture healing measured by pQCT in postmenopausal women, DRKS00019858 . Registered 25th November 2019 - Retrospectively registered. Trial registration number DRKS00019858 .

Effect of alendronate or 8-prenylnaringenin applied as a single therapy or in combination with vibration on muscle structure and bone healing in ovariectomized rats.

Bisphosphonate alendronate (ALN), phytoestrogen 8-prenylnaringenin (8-PN) and the whole body vibration exert a favorable effect on osteoporotic bone. However, the impact of these treatments and the combination of pharmacological therapies with biomechanical stimulation on muscle and bone has not yet been explored in detail. The effect of ALN and 8-PN and their combination with the vibration (Vib) on skeletal muscle and bone healing was investigated in ovariectomized (Ovx) rats. Three-month old rats were Ovx (n = 78), or left intact (Non-Ovx; n = 12). Five weeks after Ovx, all rats were treated according to the group assignment (n = 12/13): 1) Non-Ovx; 2) Ovx; 3) Ovx + Vib; 4) Ovx + ALN; 5) Ovx + ALN + Vib; 6): Ovx + 8-PN; 7) Ovx + 8-PN + Vib. Treatments with ALN (0.58 mg/kg BW, in food), 8-PN (1.77 mg/kg BW, daily s.c. injections) and/or with vertical vibration (0.5 mm, 35 Hz, 1 g, 15 min, 2×/day, 5×/week) were conducted for ten weeks. Nine weeks after Ovx, all rats underwent bilateral tibia osteotomy with plate osteosynthesis and were sacrificed six weeks later. Vibration increased fiber size and capillary density in muscle, enlarged callus area and width, and decreased callus density in tibia, and elevated alkaline phosphatase in serum. ALN and ALN + Vib enhanced capillarization and lactate dehydrogenase activity in muscle. In tibia, ALN slowed bone healing, ALN + Vib increased callus width and density, enhanced callus formation rate and expression of osteogenic genes. 8-PN and 8-PN + Vib decreased fiber size and increased capillary density in muscle; callus density and cortical width were reduced in tibia. Vibration worsened 8-PN effect on bone healing decreasing the callus width and area. Our data suggest that Vib, ALN, 8-PN, or 8-PN + Vib do not appear to aid bone healing. ALN + Vib improved bone healing; however application is questionable since single treatments impaired bone healing. Muscle responds to the anti-osteoporosis treatments and should be included in the evaluation of the drugs.

Propofol use in children with allergies to egg, peanut, soybean or other legumes.

Propofol is the most commonly administered intravenous agent for anaesthesia in children. However, there are concerns that the emulsified preparation may not be safe in children with an allergy to egg, peanut, soybean or other legumes. We conducted a retrospective study of children with immunologically confirmed egg, peanut, soybean or legume allergy and who underwent general anaesthesia at Princess Margaret Hospital for Children between 2005 and 2015. We extracted details regarding allergy diagnosis, each anaesthetic administered and any adverse events or signs of an allergic reaction in the peri-operative period. A convenience sample of patients without any known food allergies was identified from our prospective anaesthesia research database and acted as a control group. We identified 304 food-allergic children and 649 procedures where propofol was administered. Of these, 201 (66%) had an egg allergy, 226 (74%) had a peanut allergy, 28 (9%) had a soybean allergy and 12 (4%) had a legume allergy. These were compared with 892 allergy-free patients who were exposed to propofol. In 10 (3%) allergy patients and 124 (14%) allergy-free patients, criteria for a possible allergic reaction were met. In nine of the food-allergic children and in all the controls valid non-allergic explanations for the clinical symptoms were found. One likely mild allergic reaction was experienced by a child with a previous history of intralipid allergy. We conclude that genuine serious allergic reaction to propofol is rare and is not reliably predicted by a history of food allergy.

Heat flowing from cold to hot without external intervention by using a "thermal inductor".

The cooling of boiling water all the way down to freezing, by thermally connecting it to a thermal bath held at ambient temperature without external intervention, would be quite unexpected. We describe the equivalent of a "thermal inductor," composed of a Peltier element and an electric inductance, which can drive the temperature difference between two bodies to change sign by imposing inertia on the heat flowing between them, and enable continuing heat transfer from the chilling body to its warmer counterpart without the need of an external driving force. We demonstrate its operation in an experiment and show that the process can pass through a series of quasi-equilibrium states while fully complying with the second law of thermodynamics. This thermal inductor extends the analogy between electrical and thermal circuits and could serve, with further progress in thermoelectric materials, to cool hot materials well below ambient temperature without external energy supplies or moving parts.

[Models of tinnitus development : From cochlea to cortex]. / Modelle der Tinnitusentstehung : Von der Cochlea zum Kortex.

The development of subjective tinnitus is still not mechanistically understood and existing models are controversially discussed. In this overview, the authors discuss three of the main models, all of which propose damage to the cochlea as the initial step in tinnitus development. Based on these models, a possible manifestation of tinnitus-related neuronal activity at the perceptually relevant level of the auditory pathway, the auditory cortex, is presented. Furthermore, it is demonstrated that one of the models offers a new view on the phenomenon, which could potentially help patients to better cope with their condition.

Evaluation of ostarine as a selective androgen receptor modulator in a rat model of postmenopausal osteoporosis.

Selective androgen receptor modulators (SARMs) have shown beneficial effects on muscle wasting, general physical function and bone properties in male mammals. However, data on the effects of SARMs in postmenopausal osteoporotic bone are scarce. We evaluated the effects of the SARM drug ostarine on postmenopausal osteoporotic bone in a rat osteoporosis model. Ovariectomy was performed on 46 of 56 3-month-old female Sprague-Dawley rats. Eight weeks after ovariectomy, ostarine was orally administered daily for 5 weeks in dosages of 0.04 (low, OVX + Ost. 0.04), 0.4 (intermediate, OVX + Ost. 0.4), and 4 mg/kg (high, OVX + Ost. 4) body weight. Another ovariectomized group received no ostarine. Lumbar vertebrae and femora were removed for biomechanical, gene expression, ashing, and computer tomography analyses. Low dose showed no effects. The effects of intermediate and high doses were comparable overall. Improvements were mainly seen in structural properties such as bone mineral density and bone volume density. However, the effects in femora were superior to effects in vertebrae. Ostarine treatment for 5 weeks did not improve significantly biomechanical properties. mRNA expression of the receptor activator of NF-κB ligand decreased after treatment, and uterine weight increased. Serum levels of phosphorus increased following ostarine treatment in intermediate and high-dose groups. Short-term treatment of osteoporotic bone with ostarine leads to improvement of several microstructural bone indices. While we did not observe changes in biomechanics, it is conceivable that longer treatment may also improve biomechanical properties. Further studies are needed to characterize longer time effects and side effects of ostarine in osteoporosis.

Increased levels of sodium chloride directly increase osteoclastic differentiation and resorption in mice and men.

To better understand the association between high salt intake and osteoporosis, we investigated the effect of sodium chloride (NaCl) on mice and human osteoclastogenesis. The results suggest a direct, activating role of NaCl supplementation on bone resorption. INTRODUCTION: High NaCl intake is associated with increased urinary calcium elimination and parathyroid hormone (PTH) secretion which in turn stimulates the release of calcium from the bone, resulting in increased bone resorption. However, while calciuria after NaCl loading could be shown repeatedly, several studies failed to reveal a significant increase in PTH in response to a high-sodium diet. Another possible explanation that we investigated here could be a direct effect of high-sodium concentration on bone resorption. METHODS: Mouse bone marrow macrophage and human peripheral blood mononuclear cells (PBMC) driven towards an osteoclastogenesis pathway were cultivated under culture conditions mimicking hypernatremia environments. RESULTS: In this study, a direct effect of increased NaCl concentrations on mouse osteoclast differentiation and function was observed. Surprisingly, in a human osteoclast culture system, significant increases in the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts, calcitonin receptor (CTR)-positive osteoclasts, nuclear factor-activated T cells c1 (NFATc1) gene expression, and areal and volumetric resorptions were observed for increasing concentrations of NaCl. This suggests a direct, activating, cell-mediated effect of increased concentrations of NaCl on osteoclasts. CONCLUSIONS: The reported that enhanced bone resorption after high-sodium diets may not only be secondary to the urinary calcium loss but may also be a direct, cell-mediated effect on osteoclastic resorption. These findings allow us to suggest an explanation for the clinical findings independent of a PTH-mediated regulation.

Regression models for estimating leaf area of seedlings and adult individuals of Neotropical rainforest tree species / Modelos de regressão para estimativa da área foliar de indivíduos jovens e adultos de espécies arbóreas de floresta neotropical

Abstract Individual leaf area (LA) is a key variable in studies of tree ecophysiology because it directly influences light interception, photosynthesis and evapotranspiration of adult trees and seedlings. We analyzed the leaf dimensions (length – L and width – W) of seedlings and adults of seven Neotropical rainforest tree species (Brosimum rubescens, Manilkara maxima, Pouteria caimito, Pouteria torta, Psidium cattleyanum, Symphonia globulifera and Tabebuia stenocalyx) with the objective to test the feasibility of single regression models to estimate LA of both adults and seedlings. In southern Bahia, Brazil, a first set of data was collected between March and October 2012. From the seven species analyzed, only two (P. cattleyanum and T. stenocalyx) had very similar relationships between LW and LA in both ontogenetic stages. For these two species, a second set of data was collected in August 2014, in order to validate the single models encompassing adult and seedlings. Our results show the possibility of development of models for predicting individual leaf area encompassing different ontogenetic stages for tropical tree species. The development of these models was more dependent on the species than the differences in leaf size between seedlings and adults.

Resumo Área foliar individual (AF) é uma variável chave em estudos sobre a ecofisiologia de arbóreas, porque influencia diretamente a interceptação de luz, a fotossíntese e a evapotranspiração das árvores adultas e das mudas. Foram analisadas as dimensões foliares (comprimento - C e largura - L) de indivíduos adultos e de mudas de sete espécies arbóreas de florestas neotropicais (Brosimum rubescens, Manilkara maxima, Pouteria caimito, Pouteria torta, Psidium cattleyanum, Symphonia globulifera e Tabebuia stenocalyx), com o objetivo de testar a viabilidade de modelos de regressão linear para estimar a AF de indivíduos adultos e mudas. No sul da Bahia, Brasil, um primeiro conjunto de dados foi coletado entre março e outubro de 2012. A partir das sete espécies analisadas, apenas duas (P. cattleyanum e T. stenocalyx) apresentaram relações muito semelhantes entre e AF e CL, em ambos os estádios ontogenéticos. Para estas duas espécies, um segundo conjunto de dados foi coletado em agosto de 2014, a fim de validar os modelos únicos que englobam folhas de indivíduos adultos e mudas. Nossos resultados mostram a possibilidade de desenvolvimento de modelos para a predição da área foliar, abrangendo diferentes estádios ontogenéticos para espécies arbóreas tropicais. O desenvolvimento destes modelos foi mais dependente das espécies do que das diferenças entre o tamanho das folhas de mudas e de indivíduos adultos.