Recombinant CD5 and CD6 Ectodomains Induce Antiparasitic and Immunomodulatory Effects in Secondary Cystic Echinococcosis.

Scavenger receptors participate in a wide range of biological functions after binding to multiple non-self or altered self-ligands. Among them, CD5 and CD6 are lymphocyte scavenger receptors known to interact with different microbial-associated molecular patterns, and the administration of the recombinant soluble ectodomains of human CD5 (rshCD5) and/or CD6 (rshCD6) has shown therapeutic/prophylactic potential in experimental models of fungal, bacterial and echinococcal infections. The latter is a zoonosis caused by the larval stage of the cestode parasite Echinococcus granulosus sensu lato, which in humans can induce secondary cystic echinococcosis (CE) after the spillage of protoscoleces contained within fertile cysts, either spontaneously or during surgical removal of primary hydatid cysts. Herein, we have analysed the mechanisms behind the significant protection observed in the mouse model of secondary CE following prophylactic administration of rshCD5 or rshCD6. Our results show that both molecules exhibit intrinsic antiparasitic activities in vitro, as well as immunomodulatory functions during early secondary CE, mainly through Th1/Th17 cytokine bias and promotion of peritoneal polyreactive antibodies. These data support the relevance of the parasite components bound by rshCD5 and rshCD6, as well as the potential of their prophylactic administration as a useful strategy to reduce secondary CE in patients.

Two Adverse Early Life Events Induce Differential Changes in Brain CRH and Serotonin Systems in Rats along with Hyperphagia and Depression.

BACKGROUND: Different types of stress inflicted in early stages of life elevate the risk, among adult animals and humans, to develop disturbed emotional-associated behaviors, such as hyperphagia or depression. Early-life stressed (ELS) adults present hyperactivity of the hypothalamus-pituitary-adrenal (HPA) axis, which is a risk factor associated with mood disorders. However, the prevalence of hyperphagia (17%) and depression (50%) is variable among adults that experienced ELS, suggesting that the nature, intensity, and chronicity of the stress determines the specific behavioral alteration that those individuals develop. METHODS: We analyzed corticosterone serum levels, Crh, GR, Crhr1 genes expression in the hypothalamic paraventricular nucleus, amygdala, and hippocampus due to their regulatory role on HPA axis in adult rats that experienced maternal separation (MS) or limited nesting material (LNM) stress; as well as the serotonergic system activity in the same regions given its association with the corticotropin-releasing hormone (CRH) pathway functioning and with the hyperphagia and depression development. RESULTS: Alterations in dams' maternal care provoked an unresponsive or hyper-responsive HPA axis function to an acute stress in MS and LNM adults, respectively. The differential changes in amygdala and hippocampal CRH system seemed compensating alterations to the hypothalamic desensitized glucocorticoids receptor (GR) in MS or hypersensitive in LNM. However, both adult animals developed hyperphagia and depression-like behavior when subjected to the forced-swimming test, which helps to understand that both hypo and hypercortisolemic patients present those disorders. CONCLUSION: Different ELS types induce neuroendocrine, brain CRH and 5-hydroxytriptamine (5-HT) systems' alterations that may interact converging to develop similar maladaptive behaviors.

Transparency as a Means to Analyse the Impact of Inertial Sensors on Users during the Occupational Ergonomic Assessment: A Systematic Review.

The literature has yielded promising data over the past decade regarding the use of inertial sensors for the analysis of occupational ergonomics. However, despite their significant advantages (e.g., portability, lightness, low cost, etc.), their widespread implementation in the actual workplace has not yet been realized, possibly due to their discomfort or potential alteration of the worker's behaviour. This systematic review has two main objectives: (i) to synthesize and evaluate studies that have employed inertial sensors in ergonomic analysis based on the RULA method; and (ii) to propose an evaluation system for the transparency of this technology to the user as a potential factor that could influence the behaviour and/or movements of the worker. A search was conducted on the Web of Science and Scopus databases. The studies were summarized and categorized based on the type of industry, objective, type and number of sensors used, body parts analysed, combination (or not) with other technologies, real or controlled environment, and transparency. A total of 17 studies were included in this review. The Xsens MVN system was the most widely used in this review, and the majority of studies were classified with a moderate level of transparency. It is noteworthy, however, that there is a limited and worrisome number of studies conducted in uncontrolled real environments.

Impact of extrinsic incubation temperature on natural selection during Zika virus infection of Aedes aegypti and Aedes albopictus.

Arthropod-borne viruses (arboviruses) require replication across a wide range of temperatures to perpetuate. While vertebrate hosts tend to maintain temperatures of approximately 37°C-40°C, arthropods are subject to ambient temperatures which can have a daily fluctuation of > 10°C. Temperatures impact vector competence, extrinsic incubation period, and mosquito survival unimodally, with optimal conditions occurring at some intermediate temperature. In addition, the mean and range of daily temperature fluctuations influence arbovirus perpetuation and vector competence. The impact of temperature on arbovirus genetic diversity during systemic mosquito infection, however, is poorly understood. Therefore, we determined how constant extrinsic incubation temperatures of 25°C, 28°C, 32°C, and 35°C control Zika virus (ZIKV) vector competence and population dynamics within Aedes aegypti and Aedes albopictus mosquitoes. We also examined fluctuating temperatures which better mimic field conditions in the tropics. We found that vector competence varied in a unimodal manner for constant temperatures peaking between 28°C and 32°C for both Aedes species. Transmission peaked at 10 days post-infection for Aedes aegypti and 14 days for Aedes albopictus. Conversely, fluctuating temperature decreased vector competence. Using RNA-seq to characterize ZIKV population structure, we identified that temperature alters the selective environment in unexpected ways. During mosquito infection, constant temperatures more often elicited positive selection whereas fluctuating temperatures led to strong purifying selection in both Aedes species. These findings demonstrate that temperature has multiple impacts on ZIKV biology, including major effects on the selective environment within mosquitoes.

New Efforts to Demonstrate the Successful Use of TRH as a Therapeutic Agent.

Thyrotropin-releasing hormone (TRH) is a tripeptide that regulates the neuroendocrine thyroid axis. Moreover, its widespread brain distribution has indicated that it is a relevant neuromodulator of behaviors such as feeding, arousal, anxiety, and locomotion. Importantly, it is also a neurotrophic peptide, and thus may halt the development of neurodegenerative diseases and improve mood-related disorders. Its neuroprotective actions on those pathologies and behaviors have been limited due to its poor intestinal and blood-brain barrier permeability, and because it is rapidly degraded by a serum enzyme. As new strategies such as TRH intranasal delivery emerge, a renewed interest in the peptide has arisen. TRH analogs have proven to be safe in animals and humans, while not inducing alterations in thyroid hormones' levels. In this review, we integrate research from different approaches, aiming to demonstrate the therapeutic effects of TRH, and to summarize new efforts to prolong and facilitate the peptide's actions to improve symptoms and the progression of several pathologies.

Cardamom (Elettaria cardamomum (L.) Maton) Seeds Intake Increases Energy Expenditure and Reduces Fat Mass in Mice by Modulating Neural Circuits That Regulate Adipose Tissue Lipolysis and Mitochondrial Oxidative Metabolism in Liver and Skeletal Muscle.

Cardamom seed (Elettaria cardamomum (L.) Maton; EC) is consumed in several countries worldwide and is considered a nutraceutical spice since it exerts antioxidant, anti-inflammatory, and metabolic activities. In obese individuals, EC intake also favors weight loss. However, the mechanism for these effects has not been studied. Here, we identified that EC modulates the neuroendocrine axis that regulates food intake, body weight, mitochondrial activity, and energy expenditure in mice. We fed C57BL/6 mice with diets containing 3%, 6%, or 12% EC or a control diet for 14 weeks. Mice fed the EC-containing diets gained less weight than control, despite slightly higher food intake. The lower final weight of EC-fed mice was due to lesser fat content but increased lean mass than control. EC intake increased lipolysis in subcutaneous adipose tissue, and reduced adipocyte size in subcutaneous, visceral, and brown adipose tissues. EC intake also prevented lipid droplet accumulation and increased mitochondrial content in skeletal muscle and liver. Accordingly, fasting and postprandial oxygen consumption, as well as fasting fat oxidation and postprandial glucose utilization were higher in mice fed with EC than in control. EC intake reduced proopiomelanocortin (POMC) mRNA content in the hypothalamic arcuate nucleus, without an impact on neuropeptide Y (NPY) mRNA. These neuropeptides control food intake but also influence the hypothalamic-pituitary-thyroid (HPT) and hypothalamic-pituitary-adrenal (HPA) axes. Thyrotropin-releasing hormone (TRH) mRNA expression in the hypothalamic paraventricular nucleus (PVN) and circulating triiodothyronine (T3) were lower in EC-fed mice than in control. This effect was linked with decreased circulating corticosterone and weight of adrenal glands. Our results indicate that EC modulates appetite, increases lipolysis in adipose tissue and mitochondrial oxidative metabolism in liver and skeletal muscle, leading to increased energy expenditure and lower body fat mass. These metabolic effects were ascribable to the modulation of the HPT and HPA axes. LC-MS profiling of EC found 11 phenolic compounds among which protocatechuic acid (23.8%), caffeic acid (21.06%) and syringic acid (29.25%) were the most abundant, while GC-MS profiling showed 16 terpenoids among which costunolide (68.11%), ambrial (5.3%) and cis-α-terpineol (7.99%) were identified. Extrapolation of mice-to-human EC intake was performed using the body surface area normalization equation which gave a conversion equivalent daily human intake dose of 76.9-308.4 mg bioactives for an adult of 60 kg that can be obtained from 14.5-58.3 g of cardamom seeds (18.5-74.2 g cardamom pods). These results support further exploration of EC as a coadjuvant in clinical practice.

Changes in Perioperative Platelet Lymphocyte Ratio Predict Survival in Oesophago-Gastric Adenocarcinoma.

BACKGROUND: Platelet to lymphocyte ratio (PLR) is associated with survival in oesophageal cancer. We explored whether PLR changes during different stages of treatment correlate with survival outcomes. METHODS: A retrospective single-centre study was performed. Consecutive patients who received neoadjuvant chemotherapy followed by surgery for oesophageal adenocarcinoma were identified. Changes in PLR were calculated during two time periods: the first spanning the neoadjuvant period (T1); the second the perioperative period (T2). Differences in PLR were calculated for clinicopathological variables during both T1 and T2 and for variables with regards to their association with median overall survival (OS). Variables found to be significant on univariate analysis were included in a multivariate Cox regression model. Using ROC analysis, optimal cut-offs for PLR changes were identified and plotted on a Kaplan-Meir curve. RESULTS: Of the 370 patients identified, 110 (29.7%) were included in the analysis. During T1 a positive correlation was noted between higher positive lymph node ratio and PLR change. During T2, PLR change was positively higher in patients who suffered major postoperative complications. Median survival for the cohort as a whole was 42.3 months and 5-year OS was 57.3%. Survival at 5 years was associated with lower PLR changes during T2. On univaraite analysis, median OS was significantly less for patients with a tumour size > 3 cm, poor differentiation and change in PLR ≥ 43.4 during T2. The latter two variables remained significant on multivariate analysis. Using the same PLR threshold, the survival curve comparing changes in PLR during T2 remained statistically significant. CONCLUSION: Perioperative PLR changes are highly prognostic of survival outcomes in patients treated for oesophageal adenocarcinoma.

The unreachable doorbells of South Texas: community engagement in colonias on the US-Mexico border for mosquito control.

Mosquitoes and the diseases they transmit continue to place millions of people at risk of infection around the world. Novel methods of vector control are being developed to provide public health officials with the necessary tools to prevent disease transmission and reduce local mosquito populations. However, these methods will require public acceptance for a sustainable approach and evaluations at local settings. We present our efforts in community engagement carried out in colonias of the Lower Rio Grande Valley in south Texas for mosquito surveillance, control, and ecological projects. Along the US-Mexico border the term colonia refers to impoverished communities that are usually inhabited by families of Hispanic heritage. The different engagements were carried out from September 2016 to February 2019; during this time, we had three distinct phases for community engagement. In Phase 1 we show the initial approach to the colonias in which we assessed security and willingness to participate; in Phase 2 we carried out the first recruitment procedure involving community meetings and house-to-house recruitment; and in Phase 3 we conducted a modified recruitment procedure based on community members' input. Our findings show that incorporating community members in the development of communication materials and following their suggestions for engagement allowed us to generate culturally sensitive recruitment materials and to better understand the social relationships and power dynamics within these communities. We were able to effectively reach a larger portion of the community and decrease the dropout rate of participants. Progress gained with building trust in the communities allowed us to convey participant risks and benefits of collaborating with our research projects. Community engagement should be viewed as a key component of any local vector control program as well as for any scientific research project related to vector control. Even in the face of budgetary constraints, small efforts in community engagement go a long way.

Role of the thyrotropin-releasing hormone of the limbic system in mood and eating regulation.

Thyrotropin-releasing hormone (TRH) and its receptors are expressed in the hypothalamus and limbic regions. Brain thyrotropin-releasing hormone actions are exerted directly through its receptors and indirectly by modulating the effects of neurotransmitters such as glutamate, gamma-aminobutyric acid, acetylcholine, and dopamine. The thyrotropin-releasing hormone has been implicated in eating and mood regulation. We integrate studies that analyze the role of limbic thyrotropin-releasing hormone on displaying depressive- and anxiety-like behaviors and anorexia or hyperphagia. Since the decade of 1970s, different efforts have been made to identify some of the thyrotropin-releasing hormone effects and its analogs in feeding regulation or to ameliorate symptoms in patients diagnosed with mood disorders, and to correlate anxious or depressive parameters with thyrotropin-releasing hormone levels in the cerebrospinal fluid or its expression in postmortem brain areas of affected patients. Pharmacological studies where the thyrotropin-releasing hormone is administered to animals by different routes and to distinct brain areas have elucidated its actions in behavioral changes of mood and feeding parameters. In addition, a variety of animal models of depression, anxiety, or anorexia and hyperphagia has suggested the association between the hypothalamic and limbic TRHergic system and the regulation of mood and feeding alterations. Different approaches employ the administration of anti-depressant, anxiolytic or anorectic agents to animals and describe changes in thyrotropin-releasing hormone content or expression in hypothalamic or limbic regions. The different effects on mood that result from modulating thyrotropin-releasing hormone expression may be beneficial to treat patients diagnosed with eating disorders.

Surface roughness and oxygen inhibited layer control in bulk-fill and conventional nanohybrid resin composites with and without polishing: in vitro study.

BACKGROUND: It has been demonstrated that dental restorations with rough surfaces can have several disadvantages such as pigment retention or plaque accumulation, which can facilitate caries formation, color variation, loss of brightness, degradation of restoration, among others. The present study aimed to assess surface roughness in bulk fill and conventional nanohybrid resins with and without polishing, controlling the oxygen inhibited layer. METHODS: This in vitro and longitudinal experimental study consisted of 120 resin blocks of 6 mm diameter and 4 mm depth, divided into two groups: Bulk Fill (Tetric® N-Ceram Bulk-fill, Opus Bulk Fill APS, Filtek™ Bulk Fill) and conventional nanohybrid (Tetric® N-Ceram, Opallis EA2, Filtek™ Z250 XT). Each resin group was divided into two equal parts, placing glycerin only on one of them, in order to control the oxygen inhibited layer. Subsequently, the surface roughness was measured before and after the polishing procedure with Sof-Lex discs. The data were analyzed with the T-test for related measures, and for comparison between groups before and after polishing, the non-parametric Kruskal Wallis test with the Bonferroni post hoc was used, considering a significance level of p < 0.05. RESULTS: Before polishing, the resin composites with the lowest surface roughness were Opus Bulk Fill APS (0.383 ± 0.186 µm) and Opallis EA2 (0.430 ± 0. 177 µm) with and without oxygen inhibited layer control, respectively; while after polishing, those with the lowest surface roughness were Opus Bulk Fill APS (0.213 ± 0.214 µm) and Tetric N-Ceram (0.097 ± 0.099 µm), with and without oxygen inhibited layer control, respectively. Furthermore, before and after polishing, all resins significantly decreased their surface roughness (p < 0.05) except Opus Bulk Fill APS resin with oxygen inhibited layer control (p = 0.125). However, when comparing this decrease among all groups, no significant differences were observed (p < 0.05). CONCLUSION: The Opus Bulk Fill APS resin with oxygen inhibited layer control presented lower surface roughness both before and after polishing, being these values similar at both times. However, after polishing the other bulk fill and conventional nanohybrid resins with and without oxygen inhibited layer control, the surface roughness decreased significantly in all groups, being this decrease similar in all of them.

ERAS 2.0: Continued Refinement of an Established Enhanced Recovery Protocol for Esophagectomy.

BACKGROUND: We have previously demonstrated that implementing an enhanced recovery protocol (ERP) improved outcomes after esophagectomy. We sought to examine if, after a decade of an established ERP, further improvements in postoperative outcomes could be made after continually optimizing and revising the pathway. METHODS: Patients undergoing esophagectomy for cancer from January 2019 to January 2020 were compared with our early-experience group within the initial ERP (June 2010-May 2011) and pre-ERP traditional care (June 2009-May 2010). The original ERP was initiated on June 2010 and underwent several revisions from 2014 to 2018, incorporating the following, amongst other elements: shorten the planned length of stay from 7 to 6 days, elimination of nasogastric tubes, use of soft closed-suction chest drains, and increased application of minimally invasive esophagectomy (MIE). Thirty-day outcomes (complications, length of stay, readmission) were compared for patients undergoing esophagectomy during the initial and most recent ERPs. RESULTS: Overall, 175 patients were identified; 47 underwent esophagectomy before ERP implementation (traditional care), 59 patients underwent esophagectomy after implementation of the original ERP, and 69 patients underwent esophagectomy after the most recent ERP (ERP 2.0). The groups were similar with respect to age, sex, and diagnosis. There were three times more MIEs in the ERP 2.0 group with a shorter median length of stay (7 [6-9] vs. 8 [7-17] vs. 10 [9-17]; p < 0.001) without impacting postoperative morbidity or readmission rate. CONCLUSION: Continued evaluation of institutional outcomes after esophagectomy should be performed to identify target areas for optimization and revision of established enhanced recovery protocols. ERPs are dynamic processes that can be further refined to yield greater improvements in outcomes.

Polyreactive antibodies as potential humoral biomarkers of host resistance to cystic echinococcosis.

Polyreactive antibodies (pAb) bind to a broad range of unrelated structures, providing hosts with functional components able to rapidly recognize and protect against different pathogens. However, their roles against helminth parasites are still unexplored. Here, pAb profiles were analysed in cystic echinococcosis (CE), a zoonosis caused by the cestode Echinococcus granulosus sensu lato. Levels of anti-DNP (2,4-dinitrophenyl-hapten) antibodies were measured as a surrogate parameter of pAb in different biological settings. Firstly, levels of serum and peritoneal pAb were measured during early experimental secondary CE, using both high (Balb/c) and low (C57Bl/6) susceptible mouse strains. Serum pAb mostly differed in normal mice, being pAb levels of IgG subclasses with poor anti-parasite activities predominant in Balb/c animals. Conversely, peritoneal pAb isotypes/subclasses with efficient anti-parasite activities predominated in normal and infected C57Bl/6 mice. Secondly, sera from potentially resistant patients, susceptible individuals and healthy donors were analysed, showing higher pAb levels of the IgA and IgG-particularly IgG1-isotypes in potentially resistant individuals compared to control groups. Finally, since remarkable differences were observed in pAb profiles according to the intrinsic host susceptibility to the infection, we proposed here that pAb might be considered as potential humoral biomarkers for host resistance to CE.

The association between household food insecurity and obesity in Mexico: a cross-sectional study of ENSANUT MC 2016.

OBJECTIVE: To examine the association between household food insecurity and overweight, obesity and abdominal obesity in Mexican adults. DESIGN: Cross-sectional study. SETTING: We analysed data from the Mexican Halfway National Health and Nutrition Survey 2016, a nationally representative survey that accounted for rural and urban areas in four regions of Mexico: North, Centre, Mexico City and South. PARTICIPANTS: Adults from 20 to 59 years old (n 5456, which represents 45 804 210 individuals at the national level). RESULTS: 70·8 % of the Mexican adults had some degree of household food insecurity. This situation showed larger proportions (P < 0·05) among indigenous people, those living in a rural area, in the Southern region or the lowest socio-economic quintiles. The prevalence of obesity and abdominal obesity was higher in female adults (P < 0·001), with the highest proportions occurring among those experiencing severe household food insecurity. Among women, mean BMI and waist circumference were higher as household food insecurity levels increased (P < 0·001). According to multivariate logistic regression models, severe household food insecurity showed to be positively associated with obesity (OR: 2·36; P = 0·001) in Mexican adult females. CONCLUSIONS: Our findings confirm the association between household food insecurity and obesity among Mexican women. Given the socio-demographic characteristics of the food-insecure population, it is alarming that prevailing socio-economic inequalities in the country might also be contributing to the likelihood of obesity. Therefore, it is crucial to maintain and bolster surveillance systems to track both problems and implement adequate policies and interventions.

The Lymphocytic Scavenger Receptor CD5 Shows Therapeutic Potential in Mouse Models of Fungal Infection.

Invasive fungal diseases represent an unmet clinical need that could benefit from novel immunotherapeutic approaches. Host pattern recognition receptors (e.g., Toll-like receptors, C-type lectins, or scavenger receptors) that sense conserved fungal cell wall constituents may provide suitable immunotherapeutic antifungal agents. Thus, we explored the therapeutic potential of the lymphocyte class I scavenger receptor CD5, a nonredundant component of the antifungal host immune response that binds to fungal ß-glucans. Antifungal properties of the soluble ectodomain of human CD5 (shCD5) were assessed in vivo in experimental models of systemic fungal infection induced by pathogenic species (Candida albicans and Cryptococcus neoformans). In vitro mechanistic studies were performed by means of fungus-spleen cell cocultures. shCD5-induced survival of lethally infected mice was dose and time dependent and concomitant with reduced fungal load and increased leukocyte infiltration in the primary target organ. Additive effects were observed in vivo after shCD5 was combined with suboptimal doses of fluconazole. Ex vivo addition of shCD5 to fungus-spleen cell cocultures increased the release of proinflammatory cytokines involved in antifungal defense (tumor necrosis factor alpha and gamma interferon) and reduced the number of viable C. albicans organisms. The results prompt further exploration of the adjunctive therapeutic potential of shCD5 in severe invasive fungal diseases.

Cell fusing agent virus (Flavivirus) infection in Aedes aegypti in Texas: seasonality, comparison by trap type, and individual viral loads.

South Texas has experienced local transmission of Zika virus and of other mosquito-borne viruses such as chikungunya virus and dengue virus in the last decades. Using a mosquito surveillance program in the Lower Rio Grande Valley (LRGV) and San Antonio, TX, from 2016 to 2018, we detected the presence of an insect-specific virus, cell fusing agent virus (CFAV), in the Aedes aegypti mosquito population. We tested 6,326 females and 1,249 males from the LRGV and 659 females from San Antonio for CFAV by RT-PCR using specific primers. Infection rates varied from 0 to 261 per 1,000 mosquitoes in the LRGV and 115 to 208 per 1,000 in San Antonio depending on the month of collection. Infection rates per 1,000 individuals appeared higher in females collected from BG Sentinel 2 traps compared to Autocidal Gravid Ovitraps, but the ratio of the percentage of infected pools did not differ by trap type. The natural viral load in individual males ranged from 1.25 x 102 to 5.50 x 106 RNA copies and in unfed females from 5.42 x 103 to 8.70 x 106 RNA copies. Gravid females were found to harbor fewer viral particles than males and unfed females.

Ranitidine Impairs Bone Healing and Implant Osseointegration in Rats' Tibiae.

PURPOSE: Ranitidine has been found to have an impact on bone metabolism by suppressing osteoclastogenesis. We hypothesized that the use of ranitidine would impair bone healing and implant osseointegration. This study investigated the effect of postoperative administration of ranitidine on bone healing and osseointegration in rats. MATERIALS AND METHODS: Twenty-two Sprague-Dawley rats underwent surgery to create a unicortical bone defect in each tibia. A titanium implant was placed on the right tibial defect, whereas the contralateral defect was left unfilled. After surgery, the rats were randomly divided into 2 groups receiving a daily dose of ranitidine or saline solution for 14 days and then euthanized for assessment of bone healing and osseointegration using micro-computed tomography (CT) and histomorphometry. RESULTS: Micro-CT analysis of the bone defect showed a larger bone defect volume in the ranitidine group (0.82 ± 0.13 µL vs 0.66 ± 0.16 µL, P = .034), thinner cortical thickness (0.54 ± 0.07 mm vs 0.63 ± 0.11 mm, P = .026), and less bone regeneration at the defect site (40% ± 12% vs 57% ± 11%, P = .003). Implant-site micro-CT analysis showed less osseointegration in the ranitidine group (34.1% ± 2.7% vs 43.5% ± 2.1%, P = .014), and implant-site histologic analysis showed less medullary (P = .021), cortical (P = .001), and total (P = .003) bone-implant contact and less peri-implant bone volume-tissue volume (P = .002) in the ranitidine group. Histologic analysis for osteoclastic activity showed a lower number of osteoclasts in the ranitidine group (4.8 ± 2.4 mm-2 vs 9.1 ± 2.1 mm-2, P = .026). CONCLUSIONS: The postoperative use of ranitidine impaired bone healing and osseointegration.

Defective bone repair in diclofenac treated C57Bl6 mice with and without lipopolysaccharide induced systemic inflammation.

Bone repair after trauma or surgical intervention involves a tightly regulated cascade of events that starts with hemostasis and an inflammatory response, which are critical for successful healing. Nonsteroidal anti-inflammatory drugs (NSAID) are routinely prescribed for pain relief despite their potential inhibitory effect on bone repair. The goal of this study was to determine the impact of administration of the non-selective NSAID diclofenac in the inflammatory phase of bone repair in mice with or without lipopolysaccharide-induced systemic inflammation. Repair of femoral window defects was characterized using micro computed tomography imaging and histological analyses at 2 weeks postoperative. The data indicate (a) impaired bone regeneration associated with reduced osteoblast, osteoclast, and macrophage activity; (b) changes in the number, activity, and distribution of mast cells in regenerating bone; and (c) impaired angiogenesis due to a direct toxic effect of diclofenac on vascular endothelial cells. The results of this study provide strong evidence to support the conjecture that administration of NSAIDs in the first 2 weeks after orthopaedic surgery disrupts the healing cascade and exacerbates the negative effects of systemic inflammation on the repair process.

Mosquito-Borne Viruses and Insect-Specific Viruses Revealed in Field-Collected Mosquitoes by a Monitoring Tool Adapted from a Microbial Detection Array.

Several mosquito-borne diseases affecting humans are emerging or reemerging in the United States. The early detection of pathogens in mosquito populations is essential to prevent and control the spread of these diseases. In this study, we tested the potential applicability of the Lawrence Livermore Microbial Detection Array (LLMDA) to enhance biosurveillance by detecting microbes present in Aedes aegypti, Aedes albopictus, and Culex mosquitoes, which are major vector species globally, including in Texas. The sensitivity and reproducibility of the LLMDA were tested in mosquito samples spiked with different concentrations of dengue virus (DENV), revealing a detection limit of >100 but <1,000 PFU/ml. Additionally, field-collected mosquitoes from Chicago, IL, and College Station, TX, of known infection status (West Nile virus [WNV] and Culex flavivirus [CxFLAV] positive) were tested on the LLMDA to confirm its efficiency. Mosquito field samples of unknown infection status, collected in San Antonio, TX, and the Lower Rio Grande Valley (LRGV), TX, were run on the LLMDA and further confirmed by PCR or quantitative PCR (qPCR). The analysis of the field samples with the LLMDA revealed the presence of cell-fusing agent virus (CFAV) in A. aegypti populations. Wolbachia was also detected in several of the field samples (A. albopictus and Culex spp.) by the LLMDA. Our findings demonstrated that the LLMDA can be used to detect multiple arboviruses of public health importance, including viruses that belong to the Flavivirus, Alphavirus, and Orthobunyavirus genera. Additionally, insect-specific viruses and bacteria were also detected in field-collected mosquitoes. Another strength of this array is its ability to detect multiple viruses in the same mosquito pool, allowing for the detection of cocirculating pathogens in an area and the identification of potential ecological associations between different viruses. This array can aid in the biosurveillance of mosquito-borne viruses circulating in specific geographical areas.IMPORTANCE Viruses associated with mosquitoes have made a large impact on public and veterinary health. In the United States, several viruses, including WNV, DENV, and chikungunya virus (CHIKV), are responsible for human disease. From 2015 to 2018, imported Zika cases were reported in the United States, and in 2016 to 2017, local Zika transmission occurred in the states of Texas and Florida. With globalization and a changing climate, the frequency of outbreaks linked to arboviruses will increase, revealing a need to better detect viruses in vector populations. With the capacity of the LLMDA to detect viruses, bacteria, and fungi, this study highlights its ability to broadly screen field-collected mosquitoes and contribute to the surveillance and management of arboviral diseases.

Health-Related Quality of Life and Satisfaction With Health Care: Relation to Clinical Stage in Mexican Patients With Multiple Myeloma.

Multiple myeloma (MM) is characterized by bone pain, pathologic fractures, bone destruction, and secondary hypercalcemia, all these conditions impact on health-related quality of life of patients. The objective was to evaluate the global health state and health-related quality of life in a group of patients with MM who attended a tertiary health-care center of the Instituto Mexicano del Seguro Social in Mexico, through the questionnaires designed by European Organization for Research and Treatment of Cancer (EORTC) quality of life group. Exploratory cross-sectional study in patients with MM treated in a Department of Hematology in a High-Specialty Medical Unit was conducted. Patients older than 18 years of age, men and women, were selected, and their informed written consent was obtained. We included all consecutive cases treated from January 2012 to December 2014. Questionnaires EORTC QLQ-C30, EORTC QLQ-MY20, and EORTC IN-PATSAT-32 were used. We studied 37 patients, 19 (51%) men and 18 women. The mean age was 61.9 years. Twenty-two (59.46%) patients presented with clinical stage III. The mean time for diagnosis was 33.11 months. The most used first-line treatment schedule was melphalan/prednisone/thalidomide (15; 40%). The global health median was 66.67, and symptoms showed a median score of 22.22. Treatment side effects score was 16.67; for general satisfaction, the median score was 75. In conclusion, the patients showed an advanced clinical stage and poor prognosis but had scores higher than 50 in functional scales and lower than 50 for symptom scales. The scores for symptom scales were related to age, renal failure, and disease-free survival. Identification of quality of life and satisfaction of care markers allow for early therapeutic intervention and efficiency and enable a change in quality of life and perception of care in Health Services.

[General characteristics of medical education in Mexico. A look from medical schools]. / Características generales de la educación médica en México. Una mirada desde las escuelas de medicina.

OBJECTIVE: To know the characteristics of medical education and identify its strengths and weaknesses. MATERIALS AND METHODS: A transversal and quantitative study of the characteristics of medical education in 29 medical schools in Mexico was carried out, between April and September 2017. Questionnaire with Likert scale was applied to explore context, regulation, structure, process, results and impact of medical education. Bivariate analysis was performed with a Chi square test and the significance level was equal to or less than 0.05. RESULTS: The political context obtained 64%, economical context 10% and mechanisms of regulation 31%. The educational structure was 61% and the social impact was 93%. CONCLUSIONS: Public policies, regulatory mechanisms and public investment must be strengthened to improve the quality of medical education.

OBJETIVO: Conocer las características de la educación médica e identificar sus fortalezas y debilidades. MATERIAL Y MÉTODOS: Se realizó un estudio transversal y cuantitativo para conocer las características de la educación médica en 29 escuelas de medicina en México, entre abril y septiembre de 2017. Se utilizó un cuestionario con escala tipo Likert para explorar el contexto, la regulación, la estructura, el proceso, los resultados y el impacto de la educación médica. Se realizó un análisis bivariado con ji cuadrada y una significancia estadística de p igual o menor a 0.05. RESULTADOS: El contexto político obtuvo 64%, el contexto económico 10%, los mecanismos de regulación 31%, la estructura educativa 61% y el impacto social 93%. CONCLUSIONES: Se requiere fortalecer las políticas públicas, la regulación y la inversión pública, para mejorar la calidad de la educación médica.