Serum biomarkers related to frailty predict negative outcomes in older adults with hip fracture.

PURPOSE: Hip fracture is a public health problem worldwide. Traditional prognostic models do not include blood biomarkers, such as those obtained by proteomics. This study aimed to investigate the relationships between serum inflammatory biomarkers and frailty in older adults with hip fracture as well as adverse outcomes at one and three months after discharge. METHODS: A total of 45 patients aged 75 or older who were admitted for hip fracture were recruited. At admission, a Comprehensive Geriatric Assessment (CGA) was conducted, which included a frailty assessment using the Clinical Frailty Scale (CFS). Blood samples were collected before surgery. Participants were followed up at one and three months after discharge. The levels of 45 cytokines were analyzed using a high-throughput proteomic approach. Binary logistic regression was used to determine independent associations with outcomes, such as functional recovery, polypharmacy, hospital readmission, and mortality. RESULTS: The results showed that IL-7 (OR 0.66 95% CI 0.46-0.94, p = 0.022) and CXCL-12 (OR 0.97 95% CI 0.95-0.99, p = 0.011) were associated with better functional recovery at three months after discharge, while CXCL-8 (OR 1.07 95% CI 1.01-1.14, p = 0.019) was associated with an increased risk of readmission. CONCLUSIONS: These findings suggest that immunology biomarkers may represent useful predictors of clinical outcomes in hip fracture patients.

Metabolic effects of resistance or high-intensity interval training among glycemic control-nonresponsive children with insulin resistance.

BACKGROUND: Little evidence exists on which variables of body composition or muscular strength mediates more glucose control improvements taking into account inter-individual metabolic variability to different modes of exercise training. OBJECTIVE: We examined 'mediators' to the effects of 6-weeks of resistance training (RT) or high-intensity interval training (HIT) on glucose control parameters in physically inactive schoolchildren with insulin resistance (IR). Second, we also determined both training-induce changes and the prevalence of responders (R) and non-responders (NR) to decrease the IR level. METHODS: Fifty-six physically inactive children diagnosed with IR followed a RT or supervised HIT program for 6 weeks. Participants were classified based on ΔHOMA-IR into glycemic control R (decrease in homeostasis model assessment-IR (HOMA-IR) <3.0 after intervention) and NRs (no changes or values HOMA-IR⩾3.0 after intervention). The primary outcome was HOMA-IR associated with their mediators; second, the training-induced changes to glucose control parameters; and third the report of R and NR to improve body composition, cardiovascular, metabolic and performance variables. RESULTS: Mediation analysis revealed that improvements (decreases) in abdominal fat by the waist circumference can explain more the effects (decreases) of HOMA-IR in physically inactive schoolchildren under RT or HIT regimes. The same analysis showed that increased one-maximum repetition leg-extension was correlated with the change in HOMA-IR (ß=-0.058; P=0.049). Furthermore, a change in the waist circumference fully mediated the dose-response relationship between changes in the leg-extension strength and HOMA-IR (ß'=-0.004; P=0.178). RT or HIT were associated with significant improvements in body composition, muscular strength, blood pressure and cardiometabolic parameters irrespective of improvement in glycemic control response. Both glucose control RT-R and HIT-R (respectively), had significant improvements in mean HOMA-IR, mean muscular strength leg-extension and mean measures of adiposity. CONCLUSIONS: The improvements in the lower body strength and the decreases in waist circumference can explain more the effects of the improvements in glucose control of IR schoolchildren in R group after 6 weeks of RT or HIT, showing both regimes similar effects on body composition or muscular strength independent of interindividual metabolic response variability.

Longitudinal association between ideal cardiovascular health status and muscular fitness in adolescents: The LabMed Physical Activity Study.

BACKGROUND AND AIMS: Muscular fitness is an emerging predictor for cardiovascular disease mortality. The ideal cardiovascular health metrics has been inversely related to a subsequent cardiometabolic health in adulthood. However, evidence regarding muscular fitness and ideal cardiovascular health in adolescents is scarce. This study aimed to examine the longitudinal association between ideal cardiovascular health index and muscular fitness. METHODS AND RESULTS: This study cohort consisted of 331 adolescents (183 girls) from the LabMed Physical Activity Study who were followed from 2011 to 2013. Ideal cardiovascular health, as defined by the American Heart Association, was determined as meeting ideal health factors (total cholesterol, blood pressure, and glucose) and behaviors (smoking status, body mass index, physical activity, and diet). Handgrip strength and standing long jump tests assessed muscular fitness and were transformed into standardized values according to age and sex. ANCOVA showed a significant association between the accumulation of ideal cardiovascular health metrics at baseline and muscular fitness indices at follow-up (F(4, 322) = 2.280, p = 0.04). In addition, the higher the number of ideal cardiovascular health metrics accumulated, the higher the likelihood of having a high muscular fitness over a two-year period (p for trend = 0.01), after adjustments for age, sex, pubertal stage and socioeconomic status and muscular fitness at baseline. CONCLUSION: The ideal cardiovascular health status during adolescence was associated with high muscular fitness levels over a two-year period.

Handgrip and knee extension strength as predictors of cancer mortality: A systematic review and meta-analysis.

The specific role of different strength measures on mortality risk needs to be clarified to gain a better understanding of the clinical importance of different muscle groups, as well as to inform intervention protocols in relation to reducing early mortality. The aim of the systematic review and meta-analysis was to determine the relationship between muscular strength and risk of cancer mortality. Eligible cohort studies were those that examined the association between muscular strength, as assessed using validated tests, and cancer mortality in healthy youth and adults. The hazard ratio (HR) estimates obtained were pooled using random effects meta-analysis models. The outcome was cancer mortality assessed using the HR (Cox proportional hazards model). Eleven prospective studies with 1 309 413 participants were included, and 9787 cancer-specific deaths were reported. Overall, greater handgrip (HR = 0.97, 95% CI, 0.92-1.02; P = .055; I2  = 18.9%) and knee extension strength (HR = 0.98, 95% CI, 0.95-1.00; P = .051; I2  = 60.6%) were barely significant associated with reduced risk of cancer mortality. Our study suggests that higher level of muscular strength is not statistically associated with lower risk of cancer mortality.

Interindividual responses to different exercise stimuli among insulin-resistant women.

We aimed to investigate which among 20 cardiometabolic and performance outcomes do and do not respond to high-intensity interval training (HIT), resistance training (RT), or concurrent training (CT) in insulin-resistant adult women. A secondary aim was to report the training-induced changes and the prevalence of non-responders. Forty-five insulin-resistant adult women were randomly assigned to one of the following 4 groups: HIT (39.2 ± 9.5 years [y]; body mass index [BMI], 29.3 ± 3.3; n = 14), RT (33.9 ± 9.3 y; BMI, 29.4 ± 5.5; n = 8), CT (43.3 ± 8.1 y; BMI, 29.1 ± 2.9; n = 10), and a control group (CG, 40.1 ± 11.4 y; BMI, 28.3 ± 3.5; n = 13). Nine body composition, 3 cardiovascular, 3 metabolic, and 5 performance outcomes were assessed at baseline and after 12 weeks of intervention. Considering all outcomes, the lowest number of total non-responses for one or more variables was found in the RT group, followed by the CT and HIT groups. Individuals in the CG group were classified as non-responders for almost all the variables. Moreover, there were several significant changes in body composition and metabolic parameters, including fasting glucose (HIT: -5.7, RT -5.1 mg/d), fasting insulin (HIT: -0.6, RT -0.6 µIU/mL), and HOMA-IR (HIT: -0.3, RT -0.4), in addition to improvements in cardiovascular and performance parameters. Also, there were significant differences among groups in the prevalence of non-responders for the variables where a non-response was detected. Overall, the study suggests that independent of the mode of training including volume and frequency, RT has an important ability to reduce the prevalence of non-response to improve the 20 outcomes of health and performance in insulin-resistant adult women.

Exercise, adipokines and pediatric obesity: a meta-analysis of randomized controlled trials.

BACKGROUND/OBJECTIVE: Adipokines are involved in the etiology of diabetes, insulin resistance, and the development of atherosclerosis and other latent-onset complications. The objective of this meta-analysis was to determine the effectiveness of exercise interventions on adipokines in pediatric obesity. SUBJECTS/METHODS: A computerized search was made using three databases. The analysis was restricted to studies that examined the effect of exercise interventions on adipokines (adiponectin, leptin, resistin and visfatin) in pediatric obesity (6-18 years old). Fourteen randomized controlled trials (347 youths) were included. Weighted mean difference (WMD) and 95% confidence intervals were calculated. RESULTS: Exercise was associated with a significant increase in adiponectin (WMD=0.882 µg ml-1, 95% CI, 0.271-1.493) but did not alter leptin and resistin level. Likewise, exercise intensity and change in body fat; as well as total exercise program duration, duration of the sessions, and change in body fat all significantly influenced the effect of exercise on adiponectin and leptin, respectively. CONCLUSIONS: Exercise seems to increase adiponectin levels in childhood obesity. Our results also suggested that exercise on its own, without the concomitant presence of changes in body composition levels, does not affect leptin levels.

Adiposity as a full mediator of the influence of cardiorespiratory fitness and inflammation in schoolchildren: The FUPRECOL Study.

BACKGROUND AND AIMS: Studies in the paediatric population have shown inconsistent associations between cardiorespiratory fitness and inflammation independently of adiposity. The purpose of this study was (i) to analyse the combined association of cardiorespiratory fitness and adiposity with high-sensitivity C-reactive protein (hs-CRP), and (ii) to determine whether adiposity acts as a mediator on the association between cardiorespiratory fitness and hs-CRP in children and adolescents. METHODS AND RESULTS: This cross-sectional study included 935 (54.7% girls) healthy children and adolescents from Bogotá, Colombia. The 20 m shuttle run test was used to estimate cardiorespiratory fitness. We assessed the following adiposity parameters: body mass index, waist circumference, and fat mass index and the sum of subscapular and triceps skinfold thickness. High sensitivity assays were used to obtain hs-CRP. Linear regression models were fitted for mediation analyses examined whether the association between cardiorespiratory fitness and hs-CRP was mediated by each of adiposity parameters according to Baron and Kenny procedures. Lower levels of hs-CRP were associated with the best schoolchildren profiles (high cardiorespiratory fitness + low adiposity) (p for trend <0.001 in the four adiposity parameters), compared with unfit and overweight (low cardiorespiratory fitness + high adiposity) counterparts. Linear regression models suggest a full mediation of adiposity on the association between cardiorespiratory fitness and hs-CRP levels. CONCLUSIONS: Our findings seem to emphasize the importance of obesity prevention in childhood, suggesting that having high levels of cardiorespiratory fitness may not counteract the negative consequences ascribed to adiposity on hs-CRP.

Muscular fitness, adherence to the Southern European Atlantic Diet and cardiometabolic risk factors in adolescents.

BACKGROUND AND AIM: Muscular fitness and an adherence to the Southern European Atlantic Diet (SEADiet) have been inversely associated with cardiometabolic risk. Our aim was to assess the independent and combined associations of muscular fitness and adherence to the SEADiet on cardiometabolic risk in adolescents. METHODS AND RESULTS: A total of 467 Portuguese adolescents (275 girls) participated in this cross-sectional study. Sum of the Z-Scores of Curl-Up and Push-Up tests was used to create a muscular fitness score. Adherence to SEADiet was obtained using a food frequency questionnaire. A cardiometabolic risk score was computed from sum of Z-score of triglycerides, systolic blood pressure, total cholesterol/HDL ratio, HOMA-IR and waist circumference. Adolescents with low muscular fitness and low adherence to the SEADiet had the poorest cardiovascular profile F(5, 452) = 5.074 (p < 0.001) and the highest odds of having a high cardiometabolic risk score (OR = 4.5; 95% CI: 2.1-14) when compared to those with High muscular fitness/High adherence to the SEADiet after adjustments for age, sex, pubertal stage, socioeconomic status, total energy intake, low-energy reporter and cardiorespiratory fitness. CONCLUSIONS: Our findings seem suggest that improving muscular fitness as well as an adherence to the SEADiet could be an important strategy to reduce clustered cardiometabolic risk in youth.

Cost analysis of sentinel lymph node biopsy in melanoma.

INTRODUCTION AND OBJECTIVE: Sentinel lymph node biopsy (SLNB) is the most useful tool for node staging in melanoma. SLNB facilitates selective dissection of lymph nodes, that is, the performance of lymphadenectomy only in patients with sentinel nodes positive for metastasis. Our aim was to assess the cost of SLNB, given that this procedure has become the standard of care for patients with melanoma and must be performed whenever patients are to be enrolled in clinical trials. Furthermore, the literature on the economic impact of SLNB in Spain is scarce. METHOD: From 2007 to 2010, we prospectively collected data for 100 patients undergoing SLNB followed by transhilar bivalving and multiple-level sectioning of the node for histology. Our estimation of the cost of the technique was based on official pricing and fee schedules for the Spanish region of Murcia. RESULTS: The rate of node-positive cases in our series was 20%, and the mean number of nodes biopsied was 1.96; 44% of the patients in the series had thin melanomas. The total cost was estimated at between €9486.57 and €10471.29. Histopathology accounted for a considerable portion of the cost (€5769.36). DISCUSSION: The cost of SLNB is high, consistent with amounts described for a US setting. Optimal use of SLNB will come with the increasingly appropriate selection of patients who should undergo the procedure and the standardization of a protocol for histopathologic evaluation that is both sensitive and easy to perform.

Oxygen metabolism in human placenta mitochondria.

Due to the high metabolic demands of the placental tissue during gestation, we decide to analyzed the mitochondrial bioenergetic functions in the human term placenta. Different mitochondrial morphological parameters, membrane potential and cardiolipin content were determined by flow cytometry. Oxygen uptake, hydrogen peroxide production and cytochrome P450 content, were also measured. Some apoptotic mitochondrial proteins were also analyzed by western blot. Two isolated mitochondrial fractions were observed: large/heavy and small/light with different functional characteristics. Oxygen uptake showed a respiratory control (RC) of 3.4 ± 0.3 for the heavy mitochondria, and 1.1 ± 0.4 for light mitochondria, indicating a respiratory dysfunction in the light fraction. Good levels of polarization were detected in the heavy fraction, meanwhile the light population showed a collapsed ΔΨm. Increased levels of cytochrome P450, higher levels of hydrogen peroxide, and low cardiolipin content were described for the light fraction. Three pro-apoptotic proteins p53, Bax, and cytochrome c were found increased in the heavy mitochondrial fraction; and deficient in the light fraction. The heavy mitochondrial fraction showed an improved respiratory function. This mitochondrial fraction, being probably from cytotrophoblast cells showed higher content of proteins able to induce apoptosis, indicating that these cells can effectively execute an apoptotic program in the presence of a death stimulus. Meanwhile the light and small organelles probably from syncytiotrophoblast, with a low oxygen metabolism, low level of ΔΨm, and increased hydrogen peroxide production, may not actively perform an apoptotic process due to their deficient energetic level. This study contributes to the characterization of functional parameters of human placenta mitochondria in order to understand the oxygen metabolism during the physiological process of gestation.

Critical consideration of the multiplicity of experimental and organismic determinants of pyrethroid neurotoxicity: a proof of concept.

Pyrethroids (PYR) are pesticides with high insecticidal activity that may disrupt neuronal excitability in target and nontarget species. The accumulated evidence consistently showed that this neurophysiologic action is followed by alterations in motor, sensorimotor, neuromuscular, and thermoregulatory responses. Nevertheless, there are some equivocal results regarding the potency of PYR in lab animals. The estimation of potency is an important step in pesticide chemical risk assessment. In order to identify the variables influencing neurobehavioral findings across PYR studies, evidence on experimental and organismic determinants of acute PYR-induced neurotoxicity was reviewed in rodents. A comprehensive analysis of these studies was conducted focusing on test material and dosing conditions, testing conditions, animal models, and other determinants such as testing room temperature. Variations in the severity of the neurotoxicity, under lab-controlled conditions, was explained based upon factors including influence of animal species and age, test material features such as chemical structure and stereochemistry, and dosing conditions such as vehicle, route of exposure, and dose volume. If not controlled, the interplay of these factors may lead to large variance in potency estimation. This review examined the scope of acute toxicological data required to determine the safety of pesticide products, and factors and covariates that need to be controlled in order to ensure that predictivity and precaution are balanced in a risk assessment process within a reasonable time-frame, using acute PYR-induced neurotoxicity in rodents as an exemplar.

Prevalence of metabolic syndrome in urban Colombian adolescents aged 10-16 years using three different pediatric definitions.

The aim of this study was to evaluate the metabolic syndrome (MetS) prevalence in adolescents using three different definitions for this age group. The evaluated sample consisted of 718 male and 743 female adolescents. Definitions by Cook et al., de Ferranti et al. and International Diabetes Federation (IDF) for adolescents were used to estimate the prevalence of MetS. The prevalence of MetS was 8.5, 2.5 and 1.2% by de Ferranti et al., Cook et al. and IDF definitions, respectively. High fasting glucose component had the lower prevalence whereas high triglycerides levels component was the most prevalent. In obese adolescents, the prevalence of MetS was higher. MetS classification in adolescents strongly depends on the definition chosen. Further research is required for the evaluation of the current definitions (multicentric studies), and for addition or design of new and useful criteria.

Children's lead exposure in the U.S.: Application of a national-scale, probabilistic aggregate model with a focus on residential soil and dust lead (Pb) scenarios.

Lead (Pb) exposures from soil and dust ingestion contribute to children's blood lead levels (BLLs) in the United States. The U.S. Environmental Protection Agency (EPA)'s Strategy to Reduce Lead Exposures and Disparities in U.S. Communities and the Federal Action Plan to Reduce Childhood Lead Exposure describe multi-pronged collaborative approaches. These include reducing multi-media lead exposures nationally using analytical tools such as EPA's Stochastic Human Exposure and Dose Simulation model for lead [SHEDS-Pb; formerly known as SHEDS-IEUBK (Integrated Exposure Uptake Biokinetic model)], which was initially developed and applied with a focus on children's drinking water exposures. In this study we applied SHEDS-Pb to determine what residential soil Pb and dust Pb concentrations (individually and their sum) can keep BLLs of potentially exposed young children in the general U.S. population below specified values, considering aggregate exposures from water, soil, dust, food, and air. We considered two age groups (1 to <2 years and 2 to <6 years), two BLL values (5 µg/dL and 3.5 µg/dL), and two population percentiles (95th and 97.5th). Sensitivity analyses were conducted using several alternative model inputs and data sets, yielding 15 scenarios summarized in the paper. Of those scenarios, we focused on ones with the most recent science and available data. Modeled soil Pb concentrations by age group, population percentile and reference BLL scenarios for the focus scenarios ranged from 70 ppm to 220 ppm; and modeled dust Pb concentrations ranged from 110 ppm to 240 ppm. These results are consistent with current soil and dust Pb concentrations in the U.S. general population and are lower than most of the current U.S. Federal standards. Estimated BLLs compared well with measured BLLs from CDC's NHANES 2009-2016 (0-27 % relative error for focus scenarios). This analysis can be used to inform EPA and other federal Pb efforts.

Tailored Prevention of Functional Decline through a Multicomponent Exercise Program in Hospitalized Oncogeriatric Patients: Study Protocol for a Randomized Clinical Trial.

BACKGROUND: Cancer mostly affects older adults, causing a wide variety of diagnostic and therapeutic dilemmas. One of the most important moments in cancer patients is the hospitalization period, in which older patients usually remain bedridden for many hours and this may lead to the appearance of sarcopenia and disability. METHODS: We present the research protocol for a randomized controlled trial that will analyze whether an intervention applied to older patients (≥ 65 years) who are hospitalized for acute medical conditions in an Oncology Department improves function. A total of 240 hospitalized older patients will be recruited in the Hospital Universitario de Navarra, Pamplona, Spain, and they will be randomized. The intervention consists of a multicomponent exercise training program that will take place for 4 consecutive days (2 sessions/day). The control group will receive usual hospital care, which will include physical rehabilitation when needed. The primary end point will be the change in functional capacity from baseline to hospital discharge, assessed with the Short Physical Performance Battery (SPPB). Secondary end points will be changes in cognitive and mood status, quality of life, fatigue, strength (dynamic and handgrip), pain, nutrition, length of stay, falls, readmission rate and mortality at 3 months after discharge. RESULTS: Basal data of the patients included in the RCT are described. The foreseen recruitment will not be achieved due to the context of the Covid pandemic and the significantly different responses observed during the clinical trial in oncogeriatric patients compared to our previous experience in older adults hospitalized for medical reasons. DISCUSSION: If our hypothesis is correct and shows that a multicomponent, individualized and progressive exercise program is an effective therapy for improving the capacity of acutely hospitalized older patients compared to usual care, a change in the current system of hospitalization may be justified in oncogeriatric patients.

Parameters for pyrethroid insecticide QSAR and PBPK/PD models for human risk assessment.

In this review we have examined the status of parameters required by pyrethroid QSAR-PBPK/PD models for assessing health risks. In lieu of the chemical,biological, biochemical, and toxicological information developed on the pyrethroids since 1968, the finding of suitable parameters for QSAR and PBPK/PD model development was a monumental task. The most useful information obtained came from rat toxicokinetic studies (i.e., absorption, distribution, and excretion), metabolism studies with 14C-cyclopropane- and alcohol-labeled pyrethroids, the use of known chiral isomers in the metabolism studies and their relation to commercial products. In this review we identify the individual chiralisomers that have been used in published studies and the chiral HPLC columns available for separating them. Chiral HPLC columns are necessary for isomer identification and for developing kinetic values (Vm,, and Kin) for pyrethroid hydroxylation. Early investigators synthesized analytical standards for key pyrethroid metabolites, and these were used to confirm the identity of urinary etabolites, by using TLC. These analytical standards no longer exist, and muste resynthesized if further studies on the kinetics of the metabolism of pyrethroids are to be undertaken.In an attempt to circumvent the availability of analytical standards, several CYP450 studies were carried out using the substrate depletion method. This approach does not provide information on the products formed downstream, and may be of limited use in developing human environmental exposure PBPK/PD models that require extensive urinary metabolite data. Hydrolytic standards (i.e., alcohols and acids) were available to investigators who studied the carboxylesterase-catalyzed hydrolysis of several pyrethroid insecticides. The data generated in these studies are suitable for use in developing human exposure PBPK/PD models.Tissue:blood partition coefficients were developed for the parent pyrethroids and their metabolites, by using a published mechanistic model introduced by Poulin and Thiele (2002a; b) and log DpH 7.4 values. The estimated coefficients, especially those of adipose tissue, were too high and had to be corrected by using a procedure in which the proportion of parent or metabolite residues that are unbound to plasma albumin is considered, as described in the GastroPlus model (Simulations Plus, Inc.,Lancaster, CA). The literature suggested that Km values be adjusted by multiplying Km by the substrate (decimal amount) that is unbound to microsomal or CYPprotein. Mirfazaelian et al. (2006) used flow- and diffusion-limited compartments in their deltamethrin model. The addition of permeability areas (PA) having diffusion limits, such as the fat and slowly perfused compartments, enabled the investigators to bring model predictions in line with in vivo data.There appears to be large differences in the manner and rate of absorption of the pyrethroids from the gastrointestinal tract, implying that GI advanced compartmental transit models (ACAT) need to be included in PBPK models. This is especially true of the absorption of an oral dose of tefluthrin in male rats, in which 3.0-6.9%,41.3-46.3%, and 5.2-15.5% of the dose is eliminated in urine, feces, and bile,respectively (0-48 h after administration). Several percutaneous studies with the pyrethroids strongly support the belief that these insecticides are not readily absorbed, but remain on the surface of the skin until they are washed off. In one articular study (Sidon et al. 1988) the high levels of permethrin absorption through the forehead skin (24-28%) of the monkey was reported over a 7- to 14-days period.Wester et al. (1994) reported an absorption of 1.9% of pyrethrin that had been applied to the forearm of human volunteers over a 7-days period.SAR models capable of predicting the binding of the pyrethroids to plasma and hepatic proteins were developed by Yamazaki and Kanaoka (2004), Saiakhov et al. (2000), Colmenarejo et al. (2001), and Colmenarejo (2003). QikProp(Schrodinger, LLC) was used to obtain Fu values for calculating partition coefficients and for calculating permeation constants (Caco-2, MDCK, and logBBB). ADMET Predictor (Simulations Plus Inc.) provided Vm~,x and Km values for the hydroxylation of drugs/pyrethroids by human liver recombinant cytochrome P450 enzymes making the values available for possible use in PBPK/PD models.The Caco-2 permeability constants and CYP3A4 Vmax and Km values are needed in PBPK/PD models with GI ACAT sub models. Modeling work by Chang et al.(2009) produced rate constants (kcat) for the hydrolysis of pyrethroids by rat serumcarboxylesterases. The skin permeation model of Potts and Guy (1992) was used topredict K, values for the dermal absorption of the 15 pyrethroids.The electrophysiological studies by Narahashi (1971) and others (Breckenridgeet al. 2009; Shafer et al. 2005; Soderlund et al. 2002; Wolansky and Harrill 2008)demonstrated that the mode of action of pyrethroids on nerves is to interfere with the changes in sodium and potassium ion currents. The pyrethroids, being highly lipid soluble, are bound or distributed in lipid bilayers of the nerve cell membrane and exert their action on sodium channel proteins. The rising phase of the action potential is caused by sodium influx (sodium activation), while the falling phase is caused by sodium activation being turned off, and an increase in potassium efflux(potassium activation). The action of allethrin and other pyrethroids is caused by an inhibition or block of the normal currents. An equation by Tatebayashi and Narahashi (1994) that describes the action of pyrethroids on sodium channels was found in the literature. This equation, or some variation of it, may be suitable for use in the PD portion of pyrethroid PBPK models.

Infectious diseases among travellers and migrants in Europe, EuroTravNet 2010.

To investigate trends in travel-associated morbidity with particular emphasis on emerging infections with the potential for introduction into Europe, diagnoses of 7,408 returning travellers presenting to 16 EuroTravNet sites in 2010 were compared with 2008 and 2009. A significant increase in reported Plasmodium falciparum malaria (n=361 (6% of all travel-related morbidity) vs. n=254 (4%) and 260 (5%); p<0.001), P. vivax malaria (n=51 (1%) vs. n=31 (0.5%) and 38 (1%); p=0.027) and dengue fever (n=299 (5%) vs. n=127 (2%) and 127 (2%); p<0.001) was observed. Giardia lamblia was identified in 16% of patients with acute diarrhoea, with no significant annual variation. The proportion of acute diarrhoea due to Campylobacter increased from 7% in 2008 to 12% in 2010 (p=0.001). We recorded 121 patients with pulmonary tuberculosis in 2010, a threefold increase in the proportionate morbidity from 2008 to 2010. In 2010, 60 (0.8%) cases of chronic Chagas disease, 151 (2%) cases of schistosomiasis and 112 (2%) cases of cutaneous larva migrans were reported. Illness patterns in sentinel travellers, captured by EuroTravnet, continue to highlight the potential role of travellers in the emergence of infectious diseases of public health concern in Europe and the relevance of offering medical travel advice and enforcing specific and adequate prophylaxis.

[The value of laminin-322 staining in distinguishing between keratoacanthoma, keratoacanthoma with areas of squamous cell carcinoma, and crateriform squamous cell carcinoma]. / Utilidad de la tinción con laminina-332 para diferenciar queratoacantoma, queratoacantoma con áreas de carcinoma epidermoide y carcinoma epidermoide crateriforme.

INTRODUCTION: Keratoacanthoma is a fast-growing crateriform skin tumor. Approximately 25% of such tumors undergo malignant transformation and develop areas of squamous cell carcinoma (SCC). The presence of laminin-322 has been associated with progression to invasive forms of SCC. The aim of this study was to determine whether or not immunohistochemical staining for laminin-322 would be of value in distinguishing between keratoacanthomas, keratoacanthomas with areas of squamous cell carcinoma, and SCCs. MATERIAL AND METHODS: Seventy-four lesions were selected from the pathology archives of our hospital and divided into 4 groups: 20 keratoacanthomas without SCC, 20 keratoacanthomas with areas of squamous cell carcinoma, 20 invasive SCCs (8 with crateriform morphology) unrelated to keratoacanthoma, and 14 problem lesions (keratoacanthomas with areas suggestive of SCC). All 74 lesions were stained for laminin-322. RESULTS: Laminin-322 staining was strongly positive both in areas of SCC in keratoacanthomas with malignant transformation and in invasive SCCs (mostly at the invasive front of the SCC). However, in benign keratoacanthomas, it was only weakly positive and furthermore it was confined to isolated cells or small groups of cells. The 14 problem lesions were reexamined after laminin-322 staining and 8 were diagnosed as keratoacanthomas with incipient SCC and 6 as keratoacanthomas without SCC. CONCLUSIONS: Laminin-322 staining is different in keratoacanthomas and SCCs and would thus be a useful test for differentiating keratoacanthomas from both invasive SCCs and keratoacanthomas with areas of squamous cell carcinoma. It would also be of value in diagnosing keratoacanthomas with areas suggestive of SCC or with incipient SCC.

[Effects of two methods of heat therapy on the acute vascular response and hemodynamics in healthy subjects]. / Efectos de dos métodos de termoterapia sobre la respuesta vascular aguda y parámetros hemodinámicos en un grupo de sujetos sanos.

OBJECTIVE: Recently, non-pharmacological resources to relieve pain like hot packs and ultrasound (US) have become common in clinical practice. However, little experimental evidence is available about the possible mechanisms through which these methods bring about pain relief. We aimed to determine the effects of hot packs and US on the acute vascular response and on hemodynamic parameters in healthy subjects. MATERIALS AND METHODS: We conducted an experimental study in 20 healthy subjects (10 men and 10 women; mean age, 22.54±1.70 years). The two interventions were randomly applied: a) hot packs (n=10): 15min at 60°C and b) US (n=10): 15min at 1Mhz. Before and after each intervention, the following vascular parameters were measured in the brachial artery using Doppler ultrasonography with a 7MHz probe: arterial compliance, elastic modulus, beta stiffness index, systolic and diastolic arterial diameters, systolic flow velocity and diastolic flow velocity, systolic/diastolic ratio, resistance index, and pulsatility index. The following hemodynamic parameters were monitored: heart rate and blood pressure (systolic, diastolic, and mean). RESULTS: After the application of hot packs, we observed changes in diastolic flow velocity and in the pulsatility index (P<05). After the application of US, we observed changes in diastolic flow velocity, systolic/diastolic ratio, resistance index, and arterial compliance (P<05). No changes in hemodynamic parameters were observed after either intervention. CONCLUSIONS: Applying hot packs or US modifies the physiology of the vascular system but does not affect hemodynamic parameters in healthy subjects.

Efficacy of Antiresorptive Treatment in Osteoporotic Older Adults: A Systematic Review and Meta-Analysis of Randomized Clinical Trials.

OBJECTIVES: To investigate concerns surrounding the benefits of antiresorptive drugs in older adults, a systematic review was carried out to evaluate the efficacy of these treatments in the prevention of osteoporotic hip fractures in older adults. DESIGN: a systematic review and meta-analysis of randomized clinical trials. SETTING AND PARTICIPANTS: older adults ≥65 years with osteoporosis, with or without a previous fragility fracture. Studies with cancer-related and corticosteroid-induced osteoporosis, participants <65 years and no reported hip fracture were not included. METHODS: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, ISI Web of Science and Scopus databases were searched. The primary outcome was hip fracture, and subgroup analysis (≥75 years, with different drug types and secondary prevention) and sensitivity analysis was carried out using a GRADE evaluation. Secondary outcomes were any type of fractures, vertebral fracture, bone markers and adverse events. The risk of bias was assessment with the Cochrane risk of bias tool. RESULTS: A total of 12 randomised controlled trials (RCTs) qualified for this meta-analysis, with 36,196 participants. Antiresorptive drugs have a statistically significant effect on the prevention of hip fracture (RR=0.70; 95%CI 0.60 to 0.81), but with a moderate GRADE quality of evidence and a high number needed to treat (NNT) of 186. For other outcomes, there is a statistically significant effect, but with a low to moderate quality of evidence. Antiresorptives showed no reduction in the risk of hip fracture in people ≥75 years. The results for different drug types, secondary prevention and sensitivity analysis are similar to the main analyses and have the same concerns. CONCLUSIONS: Antiresorptive drugs have a statistically significant effect on preventing hip fracture but with a moderate quality (unclear/high risk of bias) and high NNT (186). This small benefit disappears in those ≥75 years, but increases in secondary prevention. More RCTs in very old osteoporotic adults are needed.