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The tumor microenvironment (TME) is reprogrammed by cancer cells and participates in all stages of tumor progression. The contribution of stromal cells to the reprogramming of the TME is not well understood. Here, we provide evidence of the role of the cytokine oncostatin M (OSM) as central node for multicellular interactions between immune and nonimmune stromal cells and the epithelial cancer cell compartment. OSM receptor (OSMR) deletion in a multistage breast cancer model halted tumor progression. We ascribed causality to the stromal function of the OSM axis by demonstrating reduced tumor burden of syngeneic tumors implanted in mice lacking OSMR. Single-cell and bioinformatic analysis of murine and human breast tumors revealed that OSM expression was restricted to myeloid cells, whereas OSMR was detected predominantly in fibroblasts and, to a lower extent, cancer cells. Myeloid-derived OSM reprogrammed fibroblasts to a more contractile and tumorigenic phenotype and elicited the secretion of VEGF and proinflammatory chemokines CXCL1 and CXCL16, leading to increased myeloid cell recruitment. Collectively, our data support the notion that the stromal OSM/OSMR axis reprograms the immune and nonimmune microenvironment and plays a key role in breast cancer progression., This work was funded by Spanish Ministry of Science and Innovation - ISCIII (PI15/00623, PI18/00458, PI21/01208, CP18/00076, and FI19/00193); European Regional Development (FEDER) funds; Basque Department of Health (2017111011); Fundación SEOM (Beca SEOM-Font Vella); Fundación Gangoiti; and Ikerbasque Basque Research Foundation. The group also received funds from the breast cancer patient’s charity Katxalin and from Roche Farma S.A. AMA and AA are funded by Basque Government Doctoral Training Grants. JILV is funded by an AECC PhD Fellowship. FVM is supported by the Career Development Fellowship from the Cancer Institute New South Wales (2019/CDF002). AP’s research is funded by the European Research Council (ERC, ERC-2018-StG 804236-NEXTGEN-IO), and by the Spanish Ministry of Science and Innovation (PID2019-107956RA-I00 and RYC2018-024183-I). AC’s research is supported by the Basque Department of Industry, Tourism and Trade (Elkartek); the MICINN (PID2019-108787RB-I00 [FEDER/EU]; Excellence Network (SAF2016-81975-REDT); European Training Networks Project (H2020-MSCA-ITN-308 2016 721532); the AECC (GCTRA18006CARR), Vencer el Cáncer Foundation; La Caixa Foundation (ID 100010434), under the agreement LCF/PR/HR17/; and the ERC (Consolidator Grant 819242). CIBERONC was cofunded with FEDER funds and funded by ISCIII. DGO is supported by a Cancer Council NSW project grant (RG18-03) and the National Breast Cancer Foundation Elaine Henry Fellowship (IIRS-21-096). FC is funded by Institute of Cancer Research, Spanish Ministry of Science and Innovation (RYC-2016-20352 and RTI2018-096778-A-I00); Asociacion Española Contra el Cancer (LAB-AECC, LABAE19044CALV); and BBVA Leonardo Awards (IN[19]_BBM_BAS_0076).

Epithelial–mesenchymal plasticity (EMP) plays critical roles during embryonic development, wound repair, fibrosis, inflammation and cancer. During cancer progression, EMP results in heterogeneous and dynamic populations of cells with mixed epithelial and mesenchymal characteristics, which are required for local invasion and metastatic dissemination. Cancer development is associated with an inflammatory microenvironment characterized by the accumulation of multiple immune cells and pro-inflammatory mediators, such as cytokines and chemokines. Cytokines from the interleukin 6 (IL-6) family play fundamental roles in mediating tumour-promoting inflammation within the tumour microenvironment, and have been associated with chronic inflammation, autoimmunity, infectious diseases and cancer, where some members often act as diagnostic or prognostic biomarkers. All IL-6 family members signal through the Janus kinase (JAK)–signal transducer and activator of transcription (STAT) pathway and are able to activate a wide array of signalling pathways and transcription factors. In general, IL-6 cytokines activate EMP processes, fostering the acquisition of mesenchymal features in cancer cells. However, this effect may be highly context dependent. This review will summarise all the relevant literature related to all members of the IL-6 family and EMP, although it is mainly focused on IL-6 and oncostatin M (OSM), the family members that have been more extensively studied.

Solanum tuberosum aspartic Proteases (StAPs) show selective plasma membrane permeabilization, inducing cytotoxicity of cancer cells versus normal cells in vitro. Herein, we aimed to evaluate both StAP3 systemic toxicity and antitumoral activity against human melanoma in vivo. The toxicity of a single high dose of StAP3 (10 µg/g body weight, intraperitoneally) was assessed in a Balb/c mice model. Subcutaneous A375 human melanoma xenografts in athymic nude (nu/nu) mice were induced. Once tumors developed (mean larger dimension = 3.8 ± 0.09 mm), mice were StAP3-treated (6 µg/g body weight, subcutaneously under the tumor at a single dose). For both models, controls were treated with physiologic saline solution. StAP3-treated mice showed a significant inhibition of tumor growth (p 0.05) compared with controls. No signs of toxicity were detected in StAP3-treated mice in both models. These results suggest the potential of these plant proteases as anticancer agents.

Objective The purpose of the present study was to investigate the effects of an upper body compression garment (UBCG) on physiologic and perceptual responses while cycling in a hot environment. Methods Twenty recreational road cyclists were pair-matched for age, anthropometric data, and fitness level (VO 2max ) and randomly assigned to a control (CON) group (n=10) of cyclists who wore a conventional t-shirt or to a group (n=10) of cyclists who wore UBCG. Test session consisted of cycling at a fixed load (~50% VO 2max ) for 30 minutes at an ambient temperature of ~40oC (39.9±0.4oC), followed by 10 minutes of recovery. Results Significantly greater ( P = .002) rectal temperature ( T rec ) was observed at the end of exercise in the UBCG group (38.3±0.2oC) versus CON group (37.9±0.3oC). Significantly greater heart rate (HR) was observed in the UBCG group at minute 15 ( P = .01) and at the end of exercise (187±9 vs 173±10 beats/min; P = .004) for UBCG and CON, respectively. Furthermore, participants who wore UBCG perceived a significantly greater ( P = .03) thermal sensation at the end of exercise. During recovery HR and T rec remained significantly greater ( P .05) in the UBCG group. Conclusions The use of an UBCG increased cardiovascular and thermoregulatory strain during cycling in a hot environment and did not aid during recovery.

The efficacy of the use of an upper body compression garment (UBCG) as an ergogenic aid to reduce thermoregulatory strain in older adults remains unknown. The aim of this study was to evaluate the effects of UBCG on thermoregulatory, cardiorespiratory, and perceptual responses during cycling in a temperate environment (~25 °C, 66% rh) in trained older adults. Twelve cyclists aged 66 ± 2 years performed an intermittent 1-hr cycling trial at 50% of the peak power output followed by 10 min of passive recovery. Participants were provided with either commercially available UBCG or a control garment in a randomized order. UBCG increased thermoregulatory strain during exercise, as indicated by a significantly higher core temperature (38.1 ± 0.3 °C vs. 37.9 ± 0.3 °C; p = .04), body temperature (36.9 ± 0.2 °C vs. 36.7 ± 0.2 °C; p = .01), and thermal sensation (8.0 ± 0.4 vs. 7.5 ± 1.0; p = .02). These results suggest that the use of UBCG in trained older adults does not reduce the thermoregulatory strain during moderate exercise.

Leoz-Abaurrea, I, Santos-Concejero, J, Grobler, L, Engelbrecht, L, and Aguado-Jimenez, R. Running performance while wearing a heat dissipating compression garment in male recreational runners. J Strength Cond Res 30(12): 3367-3372, 2016-The aim of this study was to investigate the effects of a heat dissipating compression garment (CG) during a running performance test. Ten male recreational runners (mean ± SD: age 23 ± 3 years; V[Combining Dot Above]O2max 55.8 ± 4.8 ml·kg·min) completed 2 identical sessions wearing either CG or conventional t-shirt (CON). Each trial included a 45-minute run at 60% of the peak treadmill speed (PTS) followed by a time to exhaustion (TTE) run at 80% of the PTS and a 10-minute recovery period. During the tests, thermoregulatory and cardiovascular responses were monitored. Participants wearing the CG displayed an impaired running performance (508 ± 281 vs. 580 ± 314 seconds, p = 0.046; effect size [ES] = 0.24). In addition, a higher respiratory exchange ratio (1.06 ± 0.04 vs. 1.02 ± 0.07, p = 0.01; ES = 0.70) was observed at TTE when wearing the CG in comparison to CON. Changes in core temperature did not differ between garments after the 45-minute run (p = 0.96; ES = 0.03) or TTE (1.97 ± 0.32 vs. 1.98 ± 0.38° C; p = 0.93; ES = 0.02) for CG and CON, respectively. During recovery, significantly higher heart rate and blood lactate values were observed when wearing CG (p ≤ 0.05). These findings suggest that the use of a heat dissipating CG may not improve running performance in male recreational runners during a running performance test to exhaustion.

Summary A histological study of 23 testicular biopsies or surgical specimens from adult cryptorchid testes revealed the presence of multi-vacuolated Leydig cells in 12 cases. These cells showed abundant lipid inclusions and scarce secondary lysosomes as well as lipofuchsin pigment granules. Some of these cells contained crystals of Reinke but others had only microcristal-line inclusions. This Leydig cell alteration may be related either to heat or to congenital lesions. Leydigzellen mit Multi-Vakuolen in den Hoden von Erwachsenen mit Kryptorchismus Zusammenfassung Anhand einer histologischen Studie bei den Hoden von 23 Patienten mit Kryptorchismus konnten in 12 Fallen Multi-Vakuolen nachgewiesen werden. Diese Zellen zeigten reichlich Lipideinschlusse und selten sekundare Lysosome sowie Lipofuscin-Pigment-Granula. Einige dieser Zellen enthielten Reinke-Kristalle, andere wiederum hatten ausschlieslich mikrokristalline Einschlusse. Es wird die Auffassung vertreten, das diese Veranderung der Leydig-Zellen auf Hitzeeinflusse bzw. kongenitale Schaden zuruckgeht.

This paper deals with the characterization and aryl hydrocarbon receptor (AhR) agonist activities of a series of chlorinated, brominated, and mixed bromo/chlorocarbazoles, some of which have been identified in various environmental samples. Attention is directed here to the possibility that halogenated carbazoles may currently be emitted into the environment as a result of the production of carbazole-containing polymers present in a wide variety of electronic devices. We have found that any carbazole that is not substituted in the 1,3,6,8 positions may be lost during cleanup of environmental extracts if a multilayer column is utilized, as is common practice for polychlorinated dibenzo-p-dioxin (dioxin) and related compounds. In the present study, (1)H NMR spectral shift data for 11 relevant halogenated carbazoles are reported, along with their gas chromatographic separation and analysis by mass spectrometry. These characterization data allow for confident structural assignments and the derivation of possible correlations between structure and toxicity based on the halogenation patterns of the isomers investigated. Some halogenated carbazoles exhibit characteristics of persistent organic pollutants and their potential dioxin-like activity was further investigated. The structure-dependent induction of CYP1A1 and CYP1B1 gene expression in Ah-responsive MDA-MB-468 breast cancer cells by these carbazoles was similar to that observed for other dioxin-like compounds, and the magnitude of the fold induction responses for the most active halogenated carbazoles was similar to that observed for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). 2,3,6,7-Tetrachlorocarbazole was one of the most active halogenated carbazoles and, like TCDD, contains 4 lateral substituents; however, the estimated relative effect potency for this compound (compared to TCDD) was 0.0001 and 0.0032, based on induction of CYP1A1 and CYP1B1 mRNA, respectively.

Previous studies have not investigated the effects of a heat dissipating upper body compression garment (UBCG) during cycling in a hot environment. The present study examined the effects of a heat dissipating UBCG on thermoregulatory, cardiorespiratory and perceptual responses (thermal sensation and exertion scales), during cycling at a fixed workload (~50% VO2peak) and during active recovery (~25% VO2peak).Thirteen untrained males (mean±SD; age 21±6 years, VO2peak 53.7±5.0 ml·kg-1·min-1) completed two randomized cycling trials consisting of a 5 min rest on a cycling ergometer, followed by 4 bouts of 14 min at a fixed load + 1 min active recovery. Followed further by 10 min of active recovery. Testing occurred in a hot environment (~40±0.4 ºC, 35±2 % relative humidity, ~2.5 m·s-1 air velocity) and volunteers wore either a UBCG or non-UBCG (CON).Wearing UBCG resulted in significantly smaller reduction in heart rate (31±11 bpm vs. 46±15 bpm) and higher VO2 and VCO2 values (P0.05) during 10 min recovery period. No differences in rectal, skin and body temperature were observed during the trial between garment conditions. Clothing wetness sensation remained significantly higher wearing CON (P0.05) during exercise although no significant differences in weight loss or in sweat rate were observed.These results suggest that wearing heat dissipating UBCG had no thermoregulatory benefits during exercise and it had impaired cardiorespiratory responses during active recovery when exercising in a hot environment.

We have evaluated the level of satisfaction of patients assigned to a social worker whose role was to give information, support, advice, grief and shock counselling; and develop resource strategies for marginal peoples. Six hundred patients were admitted to the study; 300 of them were supervised by a social worker (group A) and the other 300 were not (group B). After the completion of the study, a questionnaire was sent to be filled in by group A and group B for later evaluation. We collected 200 completed questionnaires (33.3%). The most important areas were: 105 patients (94.5%) in group A vs. 73 patients (82%) (p < 0.005) consider the medical care good or very good. The waiting time was assessed as short or acceptable in 91 patients (81.9%) in group A vs. 55 patients (61.8%) in group B (p < 0.001). The psychosocial care was assessed as very good or good in 101 patients group A (90.9%) vs. 73 patients in group B (82%) (p < 0.5).

Prosthetic joint infections are a cause of increasing morbidity and medical expenditure.To determine the incidence and the clinical and the epidemiological characteristics of knee and hip prosthetic infections (PI) in patients undergoing elective surgery in five Catalonian hospitals. To determine the predictive factors of PI.A total of 425 patients operated on between 8 January and 8 July 2001 were prospectively followed for a period of two years. The cumulative incidence, incidence rate and effect measures were determined. Logistic regression was used to identify variables associated with PI.Average age was 71 years and 63.1% were women. Antibiotic prophylaxis with cefazolin was given to 44.7% of the patients, with a mean duration of two days. Prophylaxis was administered during anesthesia induction in 75.6% of the patients. Among the total, 63.4% of the patients were ASA 2. Microbiological confirmation was obtained in all the infected patients; Staphylococcus epidermidis was found in 58%. Fourteen PI were diagnosed, 71% during the first 3 months, with a cumulative incidence of 3.29% and a 3-month incidence rate of 63 patients/10,000 patients/month. Diabetes mellitus was the only variable related to PI in the multivariate analysis: 3.18, 95% CI (1.1-9.9).The cumulative incidence of PI was slightly higher than that seen in other studies. Variations were observed in the antibiotic used for prophylaxis, and the place where it was administered. PI occurred 3.18 times more frequently in diabetic patients.

Medical care to patients with heart failure (HF) entails high needs in health care and social resources. Hospital at home (HH) is a potentially useful care alternative for these patients.Observational study with 110 elderly patients with non complicated HF admitted to an HH unit. Patients were treated with educational support (clinical, dietetic and pharmacologic) and intensive home follow-up. Conventional hospital admissions and visits to the Emergency Department were analyzed during the 90 days before and after HH.After HH, conventional hospital admissions decreased by 86% and visits to the Emergency Department by 91%. The mean Barthel Index changed from 74 to 77 (p0.05, in all cases). Ninety-six percent of patients were satisfied or very satisfied with HH.In elderly patients with non complicated HF, the intervention of an HH unit reduces conventional hospital admissions and the number of visits to the Emergency Department, the personal satisfaction degree is high and the functional capacity does not worsen.

In this study we introduce a new view of hospital infection, to apply time series techniques to it. Our objective is to complement hospital infection's epidemiological surveillance by means of obtaining alert and alarm thresholds that make easy to the epidemiologist the decision of intervention, in case they are exceeded.We have used the classic time series analysis described by Rumeau-Rouquette, and ARIMA (Autoregresive Integrated Moving Average) models developed by Box and Jenkins. The study focus on three hospital units: one intensive care, one long term care and one surgical unit. The nosocomial infection intervals have been calculated with a 68% (1SD) and 95% (2SD) confidence levels.We detect an ascending general trend in the last two units, without the detection of seasonal variations. Two ARIMA (1, 0, 0) models we obtained for surgery and long term care, discarding other better adjusted models, more complex and difficult to obtain, but with no real advantage in prediction power. Confidence intervals were calculated with both methods. We did not find general trend and seasonal variations for intensive care unit. No model was considered valid, because of its high random component. The nosocomial infection intervals have been calculated with mean +/- 1SD and mean +/- 2SD.We think that more precise knowledge of hospital infection, with a high random component in our study, can be in addition useful to assign priority to human and material resources.

Vasa deferentia of 20 human adult males and 8 children were divided into four portions (proximal, middle, distal and terminal) for histological, histochemical and ultra-structural studies. The epithelium of the adult vas deferens was formed of columnar and basal cells. Three types of columnar cells were observed: (1) principal cells with PAS-positive cytoplasmic granules (lysosomes); (2) dark or pencil cells with a dark cytoplasm and nucleoplasm and cytoplasmic lipid vacuoles, and (3) mitochondrion-rich cells with numerous mitochondria similar to those of principal cells. All these cell types showed stereocilia and irregular convoluted nuclei, some of them containing granular, PAS-positive intranuclear inclusions. Principal cells were the most frequent cell type in the proximal portion but their number gradually decreased along the length of the vas deferens, while the proportion of both pencil cells and mitochondrion-rich cells increased. The muscular coat comprised three muscular layers: (1) inner longitudinal, (2) middle oblique (circular in the distal and terminal portions), and (3) outer longitudinal. The functional significance of regional variations is discussed. The infant vas deferens showed a columnar cell type only. However, cells either with numerous lysosomes or with numerous mitochondria were occasionally found. No regional variations were observed in the infant vas.

The prophylactic effect of a short preoperative loading dose of oral neomycin and erythromycin upon infectious complications following elective operations upon the colon and rectum was compared with the prophylactic effect of systemic administration of metronidazole and gentamicin preoperatively and postoperatively. In this randomized prospective clinical study, 45 patients received neomycin-erythromycin while 48 received metronidazole-gentamicin; all patients were prepared mechanically using whole gut irrigation with a mannitol solution. Both groups were comparable in sex, age, clinical diagnosis and type of operation performed. In the neomycin-erythromycin group, 41 of 45 patients had an uncomplicated postoperative course versus 35 of 48 patients in the other group (p less than 0.001) and fewer wound infections (p less than 0.05). We conclude that the better results observed with the neomycin-erythromycin combination is probably an addition of two effects--the decrease in colon flora and the adequate serum levels of antibiotics during the operation.

Testicular biopsy specimens from adult patients affected with cryptorchidism, Klinefelter's syndrome, and Del Castillo's syndrome were examined by light and electron microscopy. The study revealed a high proportion of testes showing seminiferous tubules with hyperplasia of Sertoli cells (from 25 to 45 cells per transverse tubular section). These cells had an immature appearance and showed a pseudostratified distribution. The nucleus was round to ovoid and regular in outline, with a smaller nucleolus than that of mature Sertoli cells. The cytoplasm showed less development of the endoplasmic reticulum as well as of the secondary lysosomes and lipid droplets than that in mature Sertoli cells. Characteristic features of these immature Sertoli cells were abundant cytoplasmic microfilaments, elaborate interdigitations between adjacent cells, and extensive tight junctions, from basement membrane to lumen. In the cryptorchid testes, a more immature sertoli cell was found to constitute the majority of the cells in hypoplastic zones. In Klinefelter's and Del Castillo's syndromes as well as in cryptorchid testes to a lesser degree, a transitional type of cell—from immature to mature—was also observed. These observations suggest that Sertoli cells in these primary testicular disorders reflect a congenital deficiency producing abnormal development.

Examination of testicular biopsy from a patient with 47,XXY Klinefelter's syndrome revealed a diffuse hyalinization of seminiferous tubules as well as absence of mature Leydig cells. Ultrastructural findings showed some immature Leydig cells in the testicular interstitium. Hormone assays revealed low serum FSH and LH levels. The association of both, hormone assays and testicular morphologic pattern, suggests the presence of a Klinefelter's syndrome with hypogonadotropic hypogonadism.

Normal (infant and adult) and pathological testes were examined by electron microscopy in order to study testicular innervation. Nerves composed of non-myelinated fibres were abundant in the tunica vasculosa of the tunica albuginea. These nerves penetrated into the testicular septa reaching the interstitial tissue. This showed numerous non-myelinated nerve fibres running among the Leydig cells and blood vessels. Single axons or small groups of them, partially surrounded by Schwann cells, approached: 1) the Leydig cells, 2) the interstitial blood vessels, and 3) the seminiferous tubules. Single naked axons were also observed primarily in the proximity of the seminiferous tubules. These axons showed varicosities containing both small and large "synaptic" vesicles. The latter were less numerous and contained a central dense core. Small vesicles were agranular. Some varicose axons ran across the myofibroblast layer of the tunica propria reaching the basal lamina of the seminiferous tubules at the level of the Sertoli cells but not at the level of the spermatogonia. The intercellular space between Sertoli cell and axon membrane was about 150-200 nm.

In order to evaluate the changes in the number and form of the Sertoli cell from birth to the onset of puberty, a histometric and ultrastructural study was carried out in normal children. Ultrastructural findings revealed that immature Sertoli cells, present from birth to puberty, show round to elliptical nuclei, with regular outlines and small nucleoli. The cytoplasm exhibits well developed rough endoplasmic reticulum, prominent supranuclear Golgi complexes and vesicles at the luminal face; smooth endoplasmic reticulum was scarce. Histometric study revealed a progressive decrease in the Sertoli cell number per transverse tubular section as well as per unit area of testicular parenchyma, mainly from 3 years onwards. However, this decrease seemed to be the result of the progressive increase in the testicular volume as well as in the length and width of the seminiferous tubules, without change in the total Sertoli cell number per testis. This number may be considered constant, not only for adult testes but also for postnatal developing testes.