Effect of the association of continuous shortwave diathermy and Pilates-based exercises on pain, depression, and anxiety in chronic non-specific low back pain: a randomized clinical trial.

Chronic nonspecific low back pain (CNLBP) is the most common musculoskeletal condition, which can be influenced by nociceptive, psychosocial, cognitive, and affective aspects, causing vulnerabilities and impairing the individual's ability to manage pain. The association of continuous shortwave diathermy (CSWD) with Pilates-based exercises may contribute to reduce pain, depression, and anxiety in patients with CNLBP. A single-blind randomized clinical trial was performed in which 36 patients with CNLBP were divided into a control group that received placebo CSWD and an intervention group that received active CSWD. Both groups received 12 sessions of Pilates-based exercises. Pain, depression, and anxiety variables were evaluated using the McGill questionnaire, the Beck Depression Inventory, and the Visual Analog Anxiety Scale. Assessments were performed at baseline, after three and six weeks of treatment, and at the three-month follow-up. The Shapiro-Wilk test, Student's t-test, Mann-Whitney U test, chi-squared test, and repeated measures ANOVA, with α=0.05, were used to compare the outcomes, and indicated that active CSWD did not present additional improvement in the assessed variables in CNLBP patients compared to the placebo group. Both groups improved pain and depression at follow-up and reduced anxiety only during Pilates-based exercises. Therefore, only Pilates-based exercises seemed sufficient to manage patients with CNLBP.

Somatosensory and motor representations following bilateral transplants of the hands: A 6-year longitudinal case report on the first pediatric bilateral hand transplant patient.

A vascularized composite tissue allotransplantation (VCA) was performed at the Children's Hospital of Philadelphia (CHOP), on an 8-year-old patient in 2015, six years after bilateral hand and foot amputation. Hand VCA resulted in reafferentation of the medial, ulnar, and radial nerves serving hand somatosensation and motor function. We used magnetoencephalography (MEG) to assess somatosensory cortical plasticity following the post-transplantation recovery of the peripheral sensory nerves of the hands. Our 2-year postoperative MEG showed that somatosensory lip representations, initially observed at "hand areas", reverted to canonical, orthotopic lip locations with recovery of post-transplant hand function. Here, we continue the assessment of motor and somatosensory responses up to 6-years post-transplant. Magnetoencephalographic somatosensory responses were recorded eight times over a six-year period following hand transplantation, using a 275-channel MEG system. Somatosensory tactile stimuli were presented to the right lower lip (all 8 visits) as well as right and left index fingers (visits 3-8) and fifth digits (visits 4-8). In addition, left and right-hand motor responses were also recorded for left index finger and right thumb (visit 8 only).During the acute recovery phase (visits 3 and 4), somatosensory responses of the digits were observed to be significantly larger and more phasic (i.e., smoother) than controls. Subsequent measures showed that digit responses maintain this atypical response profile (evoked-response magnitudes typically exceed 1 picoTesla). Orthotopic somatosensory localization of the lip, D2, and D5 was preserved. Motor beta-band desynchrony was age-typical in localization and response magnitude; however, the motor gamma-band response was significantly larger than that observed in a reference population.These novel findings show that the restoration of somatosensory input of the hands resulted in persistent and atypically large cortical responses to digit stimulation, which remain atypically large at 6 years post-transplant; there is no known perceptual correlate, and no reports of phantom pain. Normal somatosensory organization of the lip, D2, and D5 representation remain stable following post-recovery reorganization of the lip's somatosensory response.

Effect of the association of continuous shortwave diathermy and Pilates-based exercises on pain, depression, and anxiety in chronic non-specific low back pain: a randomized clinical trial

Chronic nonspecific low back pain (CNLBP) is the most common musculoskeletal condition, which can be influenced by nociceptive, psychosocial, cognitive, and affective aspects, causing vulnerabilities and impairing the individual's ability to manage pain. The association of continuous shortwave diathermy (CSWD) with Pilates-based exercises may contribute to reduce pain, depression, and anxiety in patients with CNLBP. A single-blind randomized clinical trial was performed in which 36 patients with CNLBP were divided into a control group that received placebo CSWD and an intervention group that received active CSWD. Both groups received 12 sessions of Pilates-based exercises. Pain, depression, and anxiety variables were evaluated using the McGill questionnaire, the Beck Depression Inventory, and the Visual Analog Anxiety Scale. Assessments were performed at baseline, after three and six weeks of treatment, and at the three-month follow-up. The Shapiro-Wilk test, Student's t-test, Mann-Whitney U test, chi-squared test, and repeated measures ANOVA, with α=0.05, were used to compare the outcomes, and indicated that active CSWD did not present additional improvement in the assessed variables in CNLBP patients compared to the placebo group. Both groups improved pain and depression at follow-up and reduced anxiety only during Pilates-based exercises. Therefore, only Pilates-based exercises seemed sufficient to manage patients with CNLBP.

Incorporation of 45S5 bioglass via sol-gel in ß-TCP scaffolds: Bioactivity and antimicrobial activity evaluation.

In this work, ß-TCP (ß-tricalcium phosphate) bioresorbable scaffolds were prepared by the gel casting method. Then, they were impregnated with a 45S5 bioglass sol gel solution to improve biocompatibility and promote bioactivity and antimicrobial activity. The ß-TCP scaffolds had an apparent porosity of 72%, and after the incorporation of the bioglass, this porosity was maintained. The elements of the bioglass were incorporated into ß-TCP matrix and there was a partial transformation from the ß-TCP phase to the α-TCP (α-tricalcium phosphate) phase, besides the formation of bioactive calcium and sodium­calcium silicates. The scaffolds ß-TCP with 45S5 bioglass incorporated (ß-TCP/45S5) did not show a reduction in their values of mechanical strength and Weibull modulus, despite the partial transformation to the α-TCP phase. Bioactivity, cell viability, and antimicrobial activity improved significantly for the ß-TCP/45S5 scaffold comparing to the scaffold without the bioglass. The mineralization of carbonated hydroxyapatite was verified in Simulated Body Fluid (SBF). The cell viability, evaluated by the reduction of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide - MTT in MG63 cells, increased by 178%, and ß-TCP/45S5 scaffold also enhanced cell activity and osteoblast differentiation observed by means of total protein contend and alkaline phosphatase activity, respectively. The formation of growth inhibition zones was also observed in the disk diffusion assay for three tested microorganisms: Staphylococcus aureus, Escherichia coli and Candida albicans. To conclude, the vacuum impregnation method in 45S5 bioglass sol gel solution was effective in penetrating all the interconnected macroporosity of the scaffolds and covering the surface of the struts, which improved their biological properties in vitro, bioactivity and antibacterial activity, without reducing mechanical strength and porosity values. Thus, the ß-TCP/45S5 scaffolds are shown as potential candidates for use in tissue engineering, mainly in bone tissue regeneration and recovery.

Four of five tuberculosis patients experience catastrophic costs related to TB diagnosis and care in Timor-Leste.

SETTING: Seventeen health care facilities that report to the national tuberculosis (TB) programme in Timor-Leste. Participants were TB patients.OBJECTIVE: To determine the proportion of TB patients who experienced catastrophic costs due to their TB diagnosis and care, and the magnitude and composition of these costs.DESIGN: This was a cross-sectional health facility-based survey, conducted in 17 DOTS centres between October 2016 and March 2017. TB patients were interviewed by trained nurses using a standardised questionnaire.RESULTS: Among the 457 TB patients who participated (response rate 96.6%), the median age was 32 years; 39.2% were from the capital, Dili. The patient was the main income earner in 26.3% of households. Annual individual and household incomes before and after TB diagnosis decreased by respectively 30.4% and 31.1%. Using a cut-off of 20% of annual household income, 83.0% of patients experienced catastrophic costs related to their TB diagnosis and care. Income loss and nutritional supplementation accounted for respectively 40.7% and 37.9% of these costs.CONCLUSION: Four of five TB patients in Timor-Leste experienced catastrophic costs related to TB diagnosis and care. Financial and social protection to mitigate against these costs are urgently needed, in addition to universal health coverage.

Can Antidiabetic Drugs Improve Male Reproductive (Dys)Function Associated with Diabetes?

The alarming increase in the number of diabetic patients worldwide raises concerns regarding the impact of the disease on global health, not to mention on social and economic aspects. Furthermore, the association of this complex metabolic disorder with male reproductive impairment is worrying, mainly due to the increasing chances that young individuals, at the apex of their reproductive window, could be affected by the disease, further contributing to the disturbing decline in male fertility worldwide. The cornerstone of diabetes management is glycemic control, proven to be effective in avoiding, minimizing or preventing the appearance or development of disease-related complications. Nonetheless, the possible impact of these therapeutic interventions on male reproductive function is essentially unexplored. To address this issue, we have made a critical assessment of the literature on the effects of several antidiabetic drugs on male reproductive function. While the crucial role of insulin is clear, as shown by the recovery of reproductive impairments in insulin-deficient individuals after treatment, the same clearly does not apply to other antidiabetic strategies. In fact, there is an abundance of controversial reports, possibly related to the various study designs, experimental models and compounds used, which include biguanides, sulfonylureas, meglitinides, thiazolidinediones/glitazones, bile acid sequestrants, amylin mimetics, as well as sodiumglucose co-transporter 2 (SGLT2) inhibitors, glucagon-like peptide 1 (GLP1), α-glucosidase inhibitors and dipeptidyl peptidase 4 (DPP4) inhibitors. These aspects constitute the focus of the current review.

Raman micro-spectroscopy analysis of different sperm regions: a species comparison.

STUDY QUESTION: Is Raman micro-spectroscopy a valid approach to assess the biochemical hallmarks of sperm regions (head, midpiece and tail) in four different species? SUMMARY ANSWER: Non-invasive Raman micro-spectroscopy provides spectral patterns enabling the biochemical characterization of the three sperm regions in the four species, revealing however high similarities for each region among species. WHAT IS KNOWN ALREADY: Raman micro-spectroscopy has been described as an innovative method to assess sperm features having the potential to be used as a non-invasive selection tool. However, except for nuclear DNA, the identification and assignment of spectral bands in Raman-profiles to the different sperm regions is scarce and controversial. STUDY DESIGN SIZE, DURATION: Raman spectra from head, midpiece and tail of four different species were obtained. Sperm samples were collected and smeared on microscope slides. Air dried samples were subjected to Raman analysis using previously standardized procedures. PARTICIPANTS/MATERIALS, SETTING, METHODS: Sperm samples from (i) two donors attending the infertility clinic at the Centre of Reproductive Medicine and Andrology; (ii) two C57BL/6 -TgN (ACTbEGFP) 1Osb adult mice; (iii) two adult Cynomolgus monkeys (Macaca fascicularis) and (iv) two sea urchins (Arbacia punctulata) were used to characterize and compare their spectral profiles. Differences and similarities were confirmed by principal component analysis (PCA). MAIN RESULTS AND THE ROLE OF CHANCE: Several novel region-specific peaks were identified. The three regions could be differentiated by distinctive Raman patterns irrespective of the species. However, regardless of the specie, their main spectral pattern remains mostly unchanged. These results were corroborated by the PCA analysis and suggest that the basic constituents of spermatozoa are biochemically similar among species. LIMITATIONS REASONS FOR CAUTION: Further research should be performed in live sperm to validate the detected spectral bands and their use as markers of distinctive regions. WIDER IMPLICATIONS OF THE FINDINGS: Raman peaks that have never been described in the sperm cell were detected. Particularly important are those that are unique to the midpiece as they might be a reference to the identification of sperm mitochondria, whose function is highly correlated with that of sperm. In the future, Raman micro-spectroscopy has the potential to be applied in assessment of male fertility. LARGE SCALE DATA: N/A. STUDY FUNDING AND COMPETING INTEREST(S): This work was supported by BMBF project 'Sperm Ident' (FKZ:13N13024) and the DAAD-CRUP bilateral exchange program (AI A06/16-57213087). S.A. is a recipient of a fellowship from the Portuguese foundation for science and technology (FCT-SFRH/BPD/110160/2015) and R.DC. is a recipient of a DAAD PhD stipend (91590556). There is no competing interest.

Antidiabetic therapies and male reproductive function: where do we stand?

Diabetes mellitus has been increasing at alarming rates in recent years, thus jeopardizing human health worldwide. Several antidiabetic drugs have been introduced in the market to manage glycemic levels, and proven effective in avoiding, minimizing or preventing the appearance or development of diabetes mellitus-related complications. However, and despite the established association between such pathology and male reproductive dysfunction, the influence of these therapeutic interventions on such topics have been scarcely explored. Importantly, this pathology may contribute toward the global decline in male fertility, giving the increasing preponderance of diabetes mellitus in young men at their reproductive age. Therefore, it is mandatory that the reproductive health of diabetic individuals is maintained during the antidiabetic treatment. With this in mind, we have gathered the available information and made a critical analysis regarding the effects of several antidiabetic drugs on male reproductive function. Unlike insulin, which has a clear and fundamental role on male reproductive function, the other antidiabetic therapies' effects at this level seem incoherent. In fact, studies are highly controversial possibly due to the different experimental study approaches, which, in our opinion, suggests caution when it comes to prescribing such drugs to young diabetic patients. Overall, much is still to be determined and further studies are needed to clarify the safety of these antidiabetic strategies on male reproductive system. Aspects such as the effects of insulin levels variations, consequent of insulin therapy, as well as what will be the impact of the side effect hypoglycemia, common to several therapeutic strategies discussed, on the male reproductive system are still to be addressed.

The kidney allocation system does not appropriately stratify risk of pediatric donor kidneys: Implications for pediatric recipients.

Kidney Allocation System (KAS) was enacted in 2014 to improve graft utility, while facilitating transplantation of highly-sensitized patients and preserving pediatric access to high-quality kidneys. Central to this system is the Kidney Donor Profile Index (KDPI), a metric intended to predict transplant outcomes based on donor characteristics but derived using only adult donors. We posited that KAS had inadvertently altered the profile and quantity of kidneys made available to pediatric recipients. This question arose from our observation that most pediatric donors carry a KDPI over 35 and have therefore been rendered relatively inaccessible to pediatric recipients under KAS. Here we explore early trends in pediatric transplantation following KAS, including: (i) use of pediatric donors, (ii) use of Public Health System (PHS) high infectious risk donors, (iii) wait time, and (iv) living donor transplantation. We note some concerning preliminary changes following KAS implementation, including the allocation of fewer deceased donor pediatric kidneys to children and stagnation in pediatric wait times. Moreover, the poor predictive power of the KDPI for adult donors appears to be even worse when applied to pediatric donors. These early trends warrant further observation and consideration of changes in pediatric kidney allocation if they persist.

Spermatogonial stem cell organization in felid testis as revealed by Dolichos biflorus lectin.

Spermatogonial stem cells are being exploited in many species as a tool to recover fertility, but may also be used to manipulate the genetic pool. Whatever the purpose, these cells must be fully characterized and easily identifiable, and our goal was to improve this procedure in the domestic cat, used as an animal model for endangered felid species and for some human diseases/physiological processes. We have therefore screened several markers that might be used to distinguish and study the undifferentiated spermatogonia population in situ and in vitro via immunohistochemistry applied to tissue sections and whole mounts of the domestic cat seminiferous tubules. Our results show that, although they label the cytoplasm and nucleus of gonocytes and spermatogonia in pre-pubertal animals, PGP9.5 and FoxO1 cannot be considered markers of undifferentiated spermatogonia in adult animals, as almost all spermatogonia, namely type A and B, express these proteins. Nonetheless, the Dolichos biflorus agglutinin (DBA lectin) was able to label the cell surface and cytoplasm of a small type A spermatogonial population in the adult animals. Analysis of the number and distribution of the DBA-labeled cells showed they were present in low number, which did not vary with epithelium seminiferous stage. Morphometric analysis revealed that DBA-labeled cells present tropism to a peculiar area of the seminiferous tubules, namely the area in direct contact with Leydig cells. Whole mounts of DBA-stained seminiferous tubules revealed the arrangement of DBA-stained cells in small clones up to eight cells. Noteworthy, the clonal cells presented variable staining intensity suggesting the existence of asymmetric distribution of O-glycosylated proteins within each clone. Our results strongly suggest that the DBA lectin is a marker of undifferentiated spermatogonia in domestic cat, and illustrate the peculiar characteristics of spermatogonial stem cell development and organization in this species.

Microturbellarians (Platyhelminthes and Acoelomorpha) in Brazil: invisible organisms? / Microturbelários (Platyhelminthes e Acoelomorpha) no Brasil: organismos invisíveis?

Abstract Microturbellarians typically belong to the benthos and may occur in a wide variety of environments. They are abundant in freshwater and marine ecosystems and may occur in moist terrestrial habitats. However, turbellarians are seldom taken into account in studies of biodiversity. Most studies on Brazilian microturbellarians had taxonomical purposes and were done in the years 1940-1950. Thus, information on their occurrence and ecological aspects are dispersed throughout several papers. We intend here to summarize the biogeographical distribution and ecological aspects of microturbellarians recorded for Brazil, indicating the main gaps in their knowledge and possible actions to enhance studies on this group. There are 239 species of microturbellarians registered for Brazil, with records distributed in 12 states. However, just three states located in southern Brazil have records of 94% of microturbellarian species. Thus, knowledge on the systematics and geographical distribution of Brazilian microturbellarians clearly reflect the scientific activity over many years or decades in two states of southeastern and southern Brazil. Considering the scant information on this group in Brazil, which is also the situation of the Neotropical microturbellarians in general, some actions should be proposed. First, it would be necessary to sample in the diverse biomes, as well as in the various river and sea basins, based on standardized sampling protocols. Second, it would be necessary to encourage diverse research groups to include microturbellarians and/or turbellarians in general into biodiversity inventories and studies on community structure of invertebrates. Third, it is necessary to increase the number of research groups on microturbellarians, in order to augment the studies on their morphology, systematics, and ecology. Considering their abundance, species richness and ecological importance in aquatic environments, despite some peculiarities regarding their sampling, sorting and identification procedures, the challenge to study microturbellarians and enhance knowledge about them in Brazilian ecosystems should be faced.

Resumo Microturbelários são tipicamente bentônicos e podem ocorrer em uma ampla variedade de ambientes. São abundantes em ecossistemas marinhos e de água doce, podendo ocorrer em ambientes terrestres úmidos. Entretanto, turbelários raramente são considerados em estudos de diversidade. A maioria dos estudos sobre microturbelários brasileiros tiveram propósito taxonômico e foram realizados nos anos 1940-1950. Assim, informações sobre ocorrência e aspectos ecológicos estão dispersos em diversos artigos. O objetivo deste trabalho é sumarizar a distribuição biogeográfica e aspectos ecológicos dos microturbelários registrados para o Brasil, indicando as principais lacunas do conhecimento e possíveis ações para ampliar estudos sobre esse grupo. Há 239 espécies de microturbelários registradas no Brasil, com registros distribuídos em 12 estados. No entanto, 94% das espécies de microturbelários foram registradas em apenas três estados localizados no sul e sudeste do Brasil. Assim, o conhecimento sobre a sistemática e distribuição geográfica dos microturbelários claramente reflete as atividades científicas realizadas por muitos anos ou mesmo décadas em dois estados do sudeste e sul do Brasil. Considerando as escassas informações existentes sobre esse grupo no Brasil, assim como a situação dos microturbelários neotropicais em geral, algumas ações devem ser propostas. Primeiramente, é necessário realizar amostragens em diversos biomas, assim como nas várias bacias e regiões hidrográficas marinhas, baseadas em protocolos de amostragem padronizados. Em segundo lugar, faz-se necessário incentivar diversos grupos de pesquisa a incluir microturbelários e/ou turbelários em geral em inventários da biodiversidade e estudos de estrutura de comunidades de invertebrados. Em terceiro lugar, é necessário ampliar o número de grupos de pesquisa em microturbelários, para aumentar os estudos sobre sua morfologia, sistemática e ecologia. Considerando sua abundância, riqueza de espécies e importância ecológica em ambientes aquáticos, apesar de suas peculiaridades de amostragem, triagem e identificação, o desafio de estudar e ampliar o conhecimento sobre microturbelários em ecossistemas brasileiros deve ser enfrentado.

Mitochondrial Functionality and Chemical Compound Action on Sperm Function.

During the last decade, several studies have shown that mitochondrial parameters, such as integrity, respiratory activity, membrane potential and ROS production are intimately linked with sperm quality. Given the limitations of conventional semen analyses in terms of predicting male fertility, an increasing number of studies are focusing on the characterization of sperm mitochondria in order to more accurately assess sperm functionality. Moreover, mitochondria from several organs, such as the liver, have been described as a powerful screening tool for drug safety, being an easy in vitro model to assess the toxicity of distinct families of compounds. Given that mitochondrial functionality is intimately related to sperm homeostasis, it has become important to understand how compounds, ranging from dietary supplements, environmental pollutants, dependency-inducing drugs to pharmacological agents (such as erectile dysfunction-targeted drugs and male contraceptives) affect sperm mitochondrial function. In this review, we discuss studies describing the effects of various chemical agents on spermatozoa, with particular emphasis on mitochondrial function. From the extensive literature analyzed, we conclude that in some cases the role of sperm mitochondria as putative predictors of sperm functionality is very obvious, while in others further studies are needed to clarify this issue.

Microturbellarians (Platyhelminthes and Acoelomorpha) in Brazil: invisible organisms?

Microturbellarians typically belong to the benthos and may occur in a wide variety of environments. They are abundant in freshwater and marine ecosystems and may occur in moist terrestrial habitats. However, turbellarians are seldom taken into account in studies of biodiversity. Most studies on Brazilian microturbellarians had taxonomical purposes and were done in the years 1940-1950. Thus, information on their occurrence and ecological aspects are dispersed throughout several papers. We intend here to summarize the biogeographical distribution and ecological aspects of microturbellarians recorded for Brazil, indicating the main gaps in their knowledge and possible actions to enhance studies on this group. There are 239 species of microturbellarians registered for Brazil, with records distributed in 12 states. However, just three states located in southern Brazil have records of 94% of microturbellarian species. Thus, knowledge on the systematics and geographical distribution of Brazilian microturbellarians clearly reflect the scientific activity over many years or decades in two states of southeastern and southern Brazil. Considering the scant information on this group in Brazil, which is also the situation of the Neotropical microturbellarians in general, some actions should be proposed. First, it would be necessary to sample in the diverse biomes, as well as in the various river and sea basins, based on standardized sampling protocols. Second, it would be necessary to encourage diverse research groups to include microturbellarians and/or turbellarians in general into biodiversity inventories and studies on community structure of invertebrates. Third, it is necessary to increase the number of research groups on microturbellarians, in order to augment the studies on their morphology, systematics, and ecology. Considering their abundance, species richness and ecological importance in aquatic environments, despite some peculiarities regarding their sampling, sorting and identification procedures, the challenge to study microturbellarians and enhance knowledge about them in Brazilian ecosystems should be faced.

High glucose concentrations per se do not adversely affect human sperm function in vitro.

Diabetes mellitus (DM) represents one of the greatest concerns to global health and it is associated with diverse clinical complications, including reproductive dysfunction. Given the multifactorial nature of DM, the mechanisms that underlie reproductive dysfunction remain unclear. Considering that hyperglycemia has been described as a major effector of the disease pathophysiology, we used an in vitro approach to address the isolated effect of high glucose conditions on human sperm function, thus avoiding other in vivo confounding players. We performed a complete and integrated analysis by measuring a variety of important indicators of spermatozoa functionality (such as motility, viability, capacitation status, acrosomal integrity, mitochondrial superoxide production and membrane potential) in human sperm samples after incubation with d- and l-glucose (5, 25, or 50 mM) for 24 and 48 h. No direct effects promoted by 25 or 50 mM d-glucose were found for any of the parameters assessed (P>0.05), except for the acrosome reaction, which was potentiated after 48 h of exposure to 50 mM d-glucose (P<0.05). Interestingly, non-metabolizable l-glucose drastically increased superoxide production (P<0.05) and suppressed sperm motility (P<0.05) and capacitation (P<0.05) after 24 h of treatment, whereas mitochondrial membrane potential (P<0.05), acrosomal integrity (P<0.01) and viability (P<0.05) were later decreased. The overall results suggest that high glucose levels per se do not influence human sperm function in vitro, which stresses the importance of other factors involved in DM pathology. Nevertheless, the absence of metabolizable glucose contributes to a severe impairment of sperm function and thus compromises male fertility.

Aerobic training prevents dexamethasone-induced peripheral insulin resistance.

This study investigated how proteins of the insulin signaling cascade could modulate insulin resistance after dexamethasone (Dexa) treatment and aerobic training. Rats were distributed into 4 groups: sedentary control (SC), sedentary+Dexa (SD), trained control (TC), and trained+Dexa (TD), and underwent aerobic training for 70 days or remained sedentary. Dexa was administered during the last 10 days (1 mg · kg(-1) per day i. p.). After 70 days, an intraperitoneal glucose tolerance test (ipGTT) was performed. Protein levels of IRS-1, AKT, and PKC-α in the tibialis anterior (TA) muscle were identified using Western blots. Dexa treatment increased blood glucose and the area under the curve (AUC) of ipGTT. Training attenuated the hyperglycemia and the AUC induced by Dexa. Dexa reduced IRS-1 (- 16%) and AKT (- 43%) protein level with no changes in PKC-α levels. Moreover, these effects on IRS-1 and AKT protein level were prevented in trained animals. These results show for the first time that aerobic exercise prevented reductions of IRS-1 and AKT level induced by Dexa in the TA muscle, suggesting that aerobic exercise is a good strategy to prevent Dexa-induced peripheral insulin resistance.

IL-33 targeting attenuates intestinal mucositis and enhances effective tumor chemotherapy in mice.

Intestinal damage and severe diarrhea are serious side effects of cancer chemotherapy and constrain the usage of most such therapies. Here we show that interleukin-33 (IL-33) mediates the severe intestinal mucositis in mice treated with irinotecan (CPT-11), a commonly used cancer chemotherapeutic agent. Systemic CPT-11 administration led to severe mucosal damage, diarrhea, and body weight loss concomitant with the induction of IL-33 in the small intestine (SI). This mucositis was markedly reduced in mice deficient in the IL-33R (ST2(-/-)). Moreover, recombinant IL-33 exacerbated the CPT-11-induced mucositis, whereas IL-33 blockade with anti-IL-33 antibody or soluble ST2 markedly attenuated the disease. CPT-11 treatment increased neutrophil accumulation in the SI and adhesion to mesenteric veins. Supernatants from SI explants treated with CPT-11 enhanced transmigration of neutrophils in vitro in an IL-33-, CXCL1/2-, and CXCR2-dependent manner. Importantly, IL-33 blockade reduced mucositis and enabled prolonged CPT-11 treatment of ectopic CT26 colon carcinoma, leading to a beneficial outcome of the chemotherapy. These results suggest that inhibition of the IL-33/ST2 pathway may represent a novel approach to limit mucositis and thus improve the effectiveness of chemotherapy.

Revisiting multi-organ transplantation in the setting of scarcity.

In the setting of organ scarcity, the ethics of multi-organ transplantation (MOT) deserve new examination. MOT offers substantial benefits to certain recipients, including avoiding serial surgeries. However, MOT candidates in the United States commonly receive priority for their nonprimary organ over many individuals who need that organ, which may undermine equity. The absence of standard criteria for MOT eligibility also enables large and unfair regional variation in MOT, such as simultaneous liver-kidney transplantation. Unfortunately, MOT may also undermine utility (optimal patient and graft survival) in circumstances where providing multiple organs to one person fails to achieve the greater collective benefit attained by providing transplants to multiple people. Policy reforms should include the adoption of minimal clinical criteria for MOT candidacy with the attendant goal of decreasing regional variation in MOT. In the future, these minimal criteria can be revised to accommodate new research about which patients derive the most benefit from MOT. Incentives to perform MOT should also be reduced, such as by including MOT outcomes in center-specific reports. These reforms run the risk that the transplant community could be perceived as abandoning MOT candidates, but offer an opportunity to align transplant practice and ethical principles.

UVB irradiation as a tool to assess ROS-induced damage in human spermatozoa.

One of the consequences of oxygen metabolism is the production of reactive oxygen species (ROS) which in a situation of imbalance with antioxidants can damage several biomolecules, compromise cell function and even lead to cellular death. The particularities of the sperm cell make it particularly vulnerable to ROS attack compromising its functionality, mirrored in terms of fertility outcome and making the study of the origin of sperm ROS, as well as the alterations they cause very important. In the present work, we used UVB irradiation, an easy experimental approach known as a potent inducer of ROS formation, to better understand the origin of ROS damage without any confounding effects that usually exist in disease models in which ROS are reported to play a role. To address these issues we evaluated sperm mitochondrial ROS production using the Mitosox Red Probe, mitochondrial membrane potential using the JC-1 probe, lipid peroxidation through BODIPY probe and vitality using PI. We observed that UVB irradiation leads to an increase in sperm mitochondrial ROS production and lipid peroxidation that occur previously to an observable mitochondrial dysfunction. We concluded that sperm UVB irradiation appears to be a good and easily manipulated in vitro model system to study mitochondria-induced oxidative stress in spermatozoa and its consequences, which may be relevant in terms of dissecting the action pathways of many other pathologies, drugs and contaminants, including endocrine disruptors.