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Latinx populations are underrepresented in DNA-based research, and risk not benefiting from research if underrepresentation continues. Latinx populations are heterogenous; reflect complex social, migration, and colonial histories; and form strong global diasporas. We conducted a global study using a survey tool (Amazon’s Mechanical Turk portal) to ascertain willingness to participate in genetic research by Latin America birth-residency concordance. Participants in the global study identified as Latinx (n=250) were classified as the following: (1) born/live outside of Latin America and the Caribbean (LAC), (2) born within/live outside LAC, and (3) born/live within LAC. Latinx were similarly likely to indicated they would participate DNA-based research as their non-Latinx counterparts (52.8% vs. 56.2%, respectively). Latinx born and living in LAC were significantly more willing to participate in DNA-based research than Latinx born and living outside of LAC (OR: 2.5; 95% CI: 1.3, 4.9, p

The identification of LSN3318839, a positive allosteric modulator of the glucagon-like peptide-1 receptor (GLP-1R), is described. LSN3318839 increases the potency and efficacy of the weak metabolite GLP-1(9-36)NH2 to become a full agonist at the GLP-1R and modestly potentiates the activity of the highly potent full-length ligand, GLP-1(7-36)NH2. LSN3318839 preferentially enhances G protein-coupled signaling by the GLP-1R over β-arrestin recruitment. Ex vivo experiments show that the combination of GLP-1(9-36)NH2 and LSN3318839 produces glucose-dependent insulin secretion similar to that of GLP-1(7-36)NH2. Under nutrient-stimulated conditions that release GLP-1, LSN3318839 demonstrates robust glucose lowering in animal models alone or in treatment combination with sitagliptin. From a therapeutic perspective, the biological properties of LSN3318839 support the concept that GLP-1R potentiation is sufficient for reducing hyperglycemia.

GIP receptor (GIPR) agonism enhances the reduction of food intake and weight loss induced by GLP-1 receptor (GLP-1R) agonism. Recently, GLP-1R agonists have been described that exhibit biased agonism as determined using cells engineered to facilitate measuring the two canonical signaling pathways engaged upon binding the GLP-1R. Such “biased agonists” retain the ability to activate the G alpha S/cyclic AMP (cAMP) pathway to a similar magnitude as native GLP-1 but exhibit markedly weaker ability to induce receptor recruitment of beta-arrestin. The prototype biased GLP-1R agonist Exendin-Phe1 (Ex-Phe1) is reported to exhibit greater weight and glucose control in diet-induced obese (DIO) mice than its unbiased parent Exendin-4 (Ex4). Herein, we investigated whether the enhanced weight loss of Ex-Phe1 erodes the ability of GIPR agonism to further enhance the efficacy of GLP-1R agonism. The peptides were first characterized in vitro to validate the biased nature of Ex-Ph1. In cells expressing either the human or murine GLP-1R, Ex-Phe1 activated cAMP signaling to a similar magnitude as GLP-1 and Ex4 but with approximately 5-fold lower potency than Ex4. The maximum effect of Ex-Phe1 upon human or mouse GLP-1R recruitment of beta-arrestin was 20% compared with full efficacy for Ex4 relative to GLP-1. In this assay Ex-Phe1 was marginally less potent than Ex4. In a 14-day osmotic minipump DIO mice study, Ex4 and Ex-Phe1 each dose dependently reduced food intake and lowered body weight. Ex-Phe1 was 10-fold more potent than Ex4, and at the maximum dose, delivered superior weight loss. Combination treatment with d-Ala-GIP resulted in similar additional body weight loss to that achieved by either Ex-Phe1 or Ex4 alone by enhancing food intake reduction and increasing energy expenditure. D-Ala-GIP alone had no effect on body weight. These findings indicate that GIPR agonism enhances GLP-1R agonism mediated weight loss irrespective of the pathway bias nature of the latter. Disclosure M. P. Coghlan: Employee; Self; Eli Lilly and Company. K. Sloop: Employee; Self; Eli Lilly and Company. T. Coskun: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. L. O’farrell: None. A. D. Showalter: None. D. B. Wainscott: Employee; Self; Eli Lilly and Company, Employee; Spouse/Partner; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company, Stock/Shareholder; Spouse/Partner; Eli Lilly and Company. C. Stutsman: None. G. Cardona: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. O. Cabrera: None. J. Alsina-fernandez: None. F. S. Willard: Employee; Self; Eli Lilly and Company. Funding Eli Lilly and Company

Background Postpartum Care is a strategy to improve survival of women and newborns, especially in low- and middle-income countries. Early post-partum care can promote healthy behaviors and the identification of risk factors associated with poorer pregnancy-related outcomes. The objective of this study was to assess the association of perceived social support with attendance to post-partum care in women from three Latin-American and Caribbean countries: Costa Rica, Dominican Republic and Honduras. Methods Women aged 18+ who completed a pregnancy in the past 5 years were interviewed in local healthcare and community settings in each country. Perceived social support (PSS) was the primary explanatory variable and the primary outcome was self-reported attendance to post-partum care. Odds Ratios (OR) with 95% confidence intervals derived from logistic regression documented the association between variables. Adjusted Odds Ratios (AOR) were calculated, controlling for social and pregnancy-related confounders. Hosmer– Lemeshow’s Goodness-of-Fit statistic was computed to assess model fit. Results Our cohort of 1199 women across the three Latin-American and Caribbean countries showed relatively high attendance to post-partum care (82.6%, n = 990). However, 51.7% (n = 581) of women reported lower levels of total PSS. Women were more likely to attend postpartum care if they had mean and higher levels of PSS Family subscale (OR: 1.9, 95%CI: 1.4, 2.7), Friends subscale (OR 1.3, 95%CI: 0.9,1.8), Significant Other subscale (OR 1.8, 95%CI: 1.3, 2.4) and the Total PSS (OR 1.8, 95%CI: 1.3, 2.5). All associations were statistically significant at p Conclusions Women with higher perceived social support levels were more likely to attend to post-partum care. From all countries, women from Dominican Republic had lower perceived social support levels and this may influence attendance at post-partum care for this subgroup. Societal and geographic factors can act as determinants when evaluating perceived social support during pregnancy.

Background: Severe cutaneous adverse reactions to drugs (SCARs) are associated with high morbidity and mortality and with sequelae. Objective: To characterize patients with SCARs in 8 health care institutions in Latin America. Methods: We performed a cross-sectional, descriptive, multicenter study of patients diagnosed with SCARs in Latin America between January 2009 and December 2018. The analysis was carried out using a database in BD Clinic. Results: We collected 70 patients, of whom 42 (60%) were women. Mean age was 38.7 years. Forty-two patients (60%) had DRESS-DIHS, 12 (17.1%) TEN, 5 (7.1%) SJS, 6 (8.5%) AGEP, 4 (5.7%) other reactions not classified as SCARs, and 1 (1.4%) overlapping SJS-TEN. The main causative drugs were aromatic anticonvulsants in 31 cases (44.3%), ß-lactam antibiotics in 11 cases (15.7%), and non–ß-lactam antibiotics in 6 cases (8.6%). In all of the cases, the suspected drug was withdrawn at the first sign of a SCAR. Sixty-six patients (94.2%) received anti-inflammatory treatment, mostly systemic corticosteroids. Complications occurred in 53 cases (75.7%), and 3 patients died (4.3%). Thirteen patients (18.6%) had sequelae. Conclusions: This is the first multicenter report on SCARs in Latin America. DRESS-DIHS was the most frequently reported clinical entity, and anticonvulsants were the main triggers. Most of the patients received systemic corticosteroids. Complications were frequent, and 3 patients died.

As a part of our program to identify potent GPR40 agonists capable of being dosed orally once daily in humans, we incorporated fused heterocycles into our recently disclosed spiropiperidine and tetrahydroquinoline acid derivatives 1, 2, and 3 with the intention of lowering clearance and improving the maximum absorbable dose (Dabs). Hypothesis-driven structural modifications focused on moving away from the zwitterion-like structure. and mitigating the N-dealkylation and O-dealkylation issues led to triazolopyridine acid derivatives with unique pharmacology and superior pharmacokinetic properties. Compound 4 (LY3104607) demonstrated functional potency and glucose-dependent insulin secretion (GDIS) in primary islets from rats. Potent, efficacious, and durable dose-dependent reductions in glucose levels were seen during glucose tolerance test (GTT) studies. Low clearance, volume of distribution, and high oral bioavailability were observed in all species. The combination of enhanced pharmacology and pharmacokinetic properties supported further development of this compound as a potential glucose-lowering drug candidate.

Impingement and penetration of the anterior cortex of the femur have been reported as complications after cephalomedullary nailing. The purpose of this study was to determine factors related to nail impingement in our population of Hispanic patients. A non-matched case–control study was carried out and 156 patients who underwent cephalomedullary nailing from 2010 and 2013 were included; 78 cases with anterior cortical impingement and 78 control cases without impingement were documented. Demographic variables and specifications of the nails such as manufacture and radius of curvature were recorded. The presence of impingement, angle of incidence on radiographs—indirect measurement of the femoral bow on the sagittal plane—and nail entry site were determined. Bivariate and multivariate logistic regression analyses were performed to identify the factors associated with cortical impingement. The distribution by sex corresponded to 87 females (56 %) and 69 males (44 %) with a mean age of 75 years [SD 18.2]. Cortical impingement was presented in 78 cases (50 %) and 6 (3.8 %) patients evidenced penetration of the anterior cortex of the femur. On the bivariate analysis the posterior nail start site is highlighted, which showed a positive association with impingement (OR 4.3; 95 % CI 1.1–36 and p = 0.04). After the multivariate analysis, the factors associated with anterior cortical impingement included female gender (OR 2.2; 95 % CI 1.1–4.6 and p ≤ 0.038), straight nails—short nails—(OR 4.9; 95 % CI 2.2–10 and p ≤ 0.001) and angle of incidence ≥7° (OR 4.9; 95 % CI 2.2–10 and p ≤ 0.001), the latter showing a likelihood of 57 % for impingement, increasing to 90 % with an angle of incidence of 11°. Posterior entry site should be avoided and an anterior site should be used. Female gender, straight nails and greater angle of incidence of the femur were associated with cortical impingement. A specific intramedullary nail design is needed for the Hispanic population due to high impingement and anterior cortical penetration rates seen with conventional nails. Short curved nails and long nails with a lower radius of curvature are required.

Purpose Caring Letters entails sending brief caring messages to patients following psychiatric hospitalisation. The purpose of this multi-site randomised controlled trial is to test a caring emails intervention to determine if it is effective in preventing suicide and re-hospitalisation rates. This in-progress trial fills an important gap in the evidence base for the Caring Letter intervention through a methodologically rigorous research design. This reports preliminary data on the follow-up assessment portion of the intervention. Methods Participants are recruited from inpatient psychiatry units and randomised to either a group that receives email letters (Caring Letters) or a group that does not receive letters (Usual Care). In the Caring Letters (CL) group, participants are emailed ‘letters’ on a planned schedule. The emails are simple expressions of care and include contact information for crisis intervention resources. The participants in the Usual Care (UC) group do not receive the emails. Both groups are contacted for follow-up assessment after two years. The follow-up assessment evaluates suicidal behaviours, service utilisation, suicidal ideation, acquired capability for lethal self-injury, and measure feelings of thwarted belongingness and perceived burdensomeness. Mortality rates will also be assessed upon study completion. Results At VA Palo Alto, 341 participants were retained in the study after two years (n=182 UC, n=159 CL). To date, 185 participants completed the final surveys. During the Follow-up Assessment, 12 participants expressed distress or emotional crises. The treatment team was immediately alerted and all participants were reconnected to care. Conclusion Both groups (CL and UC) benefited from the Follow-up Assessment. The study’s low-cost caring emails and follow-up assessments (either by phone or by mail) demonstrate effective means of providing human interaction that support at-risk individuals in times of crises. Communicating care and concern and creating a sense of connexion may prevent suicide and avert crisis among discharged psychiatric patients.

Background Hospital de la Familia was established to serve the indigent population in the western highlands of Guatemala and has a full-time staff of Guatemalan primary care providers supplemented by short-term missions of surgical specialists. The reasons for patients seeking surgical care in this setting, as opposed to more consistent care from local institutions, are unclear. We sought to better understand motivations of patients seeking mission-based surgical care. Methods Patients presenting to the obstetric and gynecologic, plastic, ophthalmologic, general, and pediatric surgical clinics at the Hospital de la Familia from July 27 to August 6, 2015 were surveyed. The surveys assessed patient demographics, surgical diagnosis, location of home, mode of travel, and reasons for seeking care at this facility. Results Of 252 patients surveyed, 144 (59.3%) were female. Most patients reported no other medical condition (67.9%, n = 169) and no consistent income (83.9%, n = 209). Almost half (44.9%, n = 109) traveled >50 km to receive care. The most common reasons for choosing care at this facility were reputation of high quality (51.8%, n = 130) and affordability (42.6%, n = 102); the least common reason was a lack of other options (6.4%, n = 16). Conclusions Despite long travel distances and the availability of other options, reputation and affordability were primarily cited as the most common reasons for choosing to receive care at this short-term surgical mission site. Our results highlight that although other surgical options may be closer and more readily available, reputation and cost play a large role in choice of patients seeking care.

Background: Allergic diseases are very common, with the estimated cumulative prevalence in Colombia for asthma and allergic rhinitis being 22.7% and 31.3% respectively, and with a clear upward trend. A major social as well as economic impact associated with allergic disease has been described. Because in Colombia there are no studies that assess the Health-Related Quality of Life (HRQOL) in allergic respiratory diseases, our aim is to describe the HRQOL in subjects with respiratory allergy and its association with clinical control variables. Methods: A prospective descriptive study was conducted among 76 Colombian subjects with rhinitis and asthma/allergic rhinitis. In order to evaluate the HRQOL, the instruments Kidscreen27 and SF-36 were applied. The scores obtained in the HRQOL fields were correlated with the following clinical variables: peak expiratory flow (PEF) and peak nasal inspiratory flow (PNIF). Results: In children, the better HRQL domain is present in the school environment (55.9) and the worst in psychological well-being (39.9). For adults the worst HRQL was found in the emotional function domain (55.6) while the physical function (81.7) had the best. There were no statistical differences between groups of asthma/allergic rhinitis and allergic rhinitis. Subjects with allergic asthma showed a strong correlation between the mental health domain and PEF values (r = −0717, p = 0.046). Conclusion: Mental health is more affected than physical health in Colombian subjects with respiratory allergy. There was a strong correlation between the mental health domain and the values of PEF in patients with asthma/allergic rhinitis COL0007121 COL0059567

The G protein-coupled receptor 40 (GPR40) also known as free fatty acid receptor 1 (FFAR1) is highly expressed in pancreatic, islet β-cells and responds to endogenous fatty acids, resulting in amplification of insulin secretion only in the presence of elevated glucose levels. Hypothesis driven structural modifications to endogenous FFAs, focused on breaking planarity and reducing lipophilicity, led to the identification of spiropiperidine and tetrahydroquinoline acid derivatives as GPR40 agonists with unique pharmacology, selectivity, and pharmacokinetic properties. Compounds 1 (LY2881835), 2 (LY2922083), and 3 (LY2922470) demonstrated potent, efficacious, and durable dose-dependent reductions in glucose levels along with significant increases in insulin and GLP-1 secretion during preclinical testing. A clinical study with 3 administered to subjects with T2DM provided proof of concept of 3 as a potential glucose-lowering therapy. This manuscript summarizes the scientific rationale, medicinal chemistry, preclinical, and early development data of this new class of GPR40 agonists.

The design, synthesis, and structure activity relationships for a novel series of indoles as potent, selective, thyroid hormone receptor β (TRβ) agonists is described. Compounds with >50× binding selectivity for TRβ over TRα were generated and evaluation of compound 1c from this series in a model of dyslipidemia demonstrated positive effects on plasma lipid endpoints in vivo.

OBJECTIVE: The acute decrease in iodide organification in the thyroid in response to excess iodide is termed the acute Wolff-Chaikoff effect and normal organification resumes in spite of continued high plasma iodide concentrations (escape from the acute Wolff-Chaikoff effect). We have recently reported that large doses of iodide given to rats chronically decrease the sodium/iodide symporter (NIS) mRNA and protein, suggesting that escape is due to a decrease in NIS and subsequent iodide transport. We have now studied the effect of excess iodide on NIS in FRTL-5 cells to further explore the mechanisms whereby excess iodide decreases NIS. DESIGN: FRTL-5 cells were employed and were incubated in the presence or absence of various concentrations of iodide. NIS mRNA and protein and the turnover of NIS were assessed. METHODS: NIS mRNA was measured by Northern analysis, NIS protein by Western analysis and NIS turnover by pulse-chase labeling experiments. RESULTS: Iodide (10(-) mol/l) had no effect on NIS mRNA in FRTL-5 cells at 24 and 48 h compared with cells cultured in the absence of iodide. However, excess iodide decreased NIS protein by 50% of control values at 24 h and by 70% at 48 h. This effect of iodide was dose dependent. Pulse-chase experiments demonstrated that there was no effect of iodide on new NIS protein synthesis and that the turnover of NIS protein in the presence of iodide was 27% faster than in the absence of added iodide. CONCLUSIONS: Excess iodide does not decrease NIS mRNA in FRTL-5 cells but does decrease NIS protein, suggesting that in this in vitro thyroid cell model iodide modulates NIS, at least in part, at a post-transcriptional level. This iodide-induced decrease in NIS protein appears to be due, at least partially, to an increase in NIS protein turnover.

Thyroid hormones influence both bone formation and bone resorption. Clinical data and animal studies provide evidence of skeletal site heterogeneity (hip vs. spine) of bone responses to thyroid hormones. In vitro studies also demonstrate direct effects of thyroid hormones on cells of the osteoblast lineage. Transcriptional regulation by thyroid hormone is mediated by ligand-dependent transcription factors called thyroid hormone receptors (TRs). Two genes, c-ErbAalpha and c-ErbAbeta, generate at least four TR isoforms in the rat: TRalpha(1), c-erbAalpha(2), TRbeta(1), and TRbeta(2). Although functional TRs have been identified in cells of the osteoblast lineage, it is still not known if TR isoform expression in bone differs depending upon which skeletal site is examined. We have used ribonuclease protection assay and Northern blot analysis to simultaneously examine the expression of TR isoform mRNAs in adult rat femoral and vertebral bone. TRalpha(1), c-erbAalpha(2), and TRbeta(1) are expressed in both femur and vertebra whole bone. Bone marrow cells from both skeletal sites were also cultured under conditions whereby the osteoprogenitors differentiated into osteoblasts and formed a mineralized extracellular matrix. TRalpha(1), c-erbAalpha(2), and TRbeta(1) mRNAs are each expressed in both femoral and vertebral osteoblast cultures. The presence of TRalpha(1), c-erbAalpha(2), and beta(1) proteins was confirmed by Western analysis of nuclear protein extracts from femoral and vertebral cell cultures. These results indicate that the three predominant TR isoforms are highly expressed in bone and osteoblasts from femurs and vertebrae. Whether there are distinct mechanisms of thyroid hormone action mediated by TRalpha(1), c-erbAalpha(2), and TRbeta(1) at these separate skeletal sites remain to be shown.

In 1948, Wolff and Chaikoff reported that organic binding of iodide in the thyroid was decreased when plasma iodide levels were elevated (acute Wolff-Chaikoff effect), and that adaptation or escape from the acute effect occurred in approximately 2 days, in the presence of continued high plasma iodide concentrations. We later demonstrated that the escape is attributable to a decrease in iodide transport into the thyroid, lowering the intrathyroidal iodine content below a critical inhibitory threshold and allowing organification of iodide to resume. We have now measured the rat thyroid sodium/iodide symporter (NIS) messenger RNA (mRNA) and protein levels, in response to both chronic and acute iodide excess, in an attempt to determine the mechanism responsible for the decreased iodide transport. Rats were given 0.05% NaI in their drinking water for 1 and 6 days in the chronic experiments, and a single 2000-μg dose of NaI ip in the acute experiments. Serum was collected for iodine and hormone measurements, an...

Resumen: La lipodistrofia generalizada congénita o síndrome de Berardinelli-Seip es una entidad rara con herencia autosómica recesiva que se caracteriza por una ausencia congénita de tejido adiposo y secundariamente un defecto en la síntesis de leptina. Los sujetos afectos presentan un fenotipo clásico con rasgos acromegaloides, atrofia generalizada del tejido graso subcutáneo, apariencia musculada, acantosis nigricans, hepatomegalia y abdomen prominente. Desde el punto de vista metabólico, y como consecuencia del déficit de la leptina son características la hipertrigliceridemia marcada, que suele conllevar esteatosis hepática y la resistencia a la insulina. Presentamos el caso de dos sujetos de distintas familias afectos de lipodistrofia generalizada congénita que durante su evolución desarrollaron diabetes mellitus con mal control que fueron tratados con dosis elevadas de insulina y que presentaron precozmente complicaciones microvasculares. Se constató la existencia de mutación para el gen LMNA en uno de los sujetos. Abstract: Generalized congenital lipodystrophy or Berardinelli-Seip Syndrome is a rare autosomal recessive condition characterized by the absence of adipose tissue and eventually a defect in leptin synthesis. Affected subjects tend to show a classical phenotype with acromegaloid appearance, generalized atrophy of subcutaneous adipose tissue with muscular hypertrophy, acanthosis nigricans, hepatomegaly and prominent abdomen. From metabolic point of view and as a consequence of leptin absence, hypertriglyceridemia leading to hepatic steatosis and insulin resistance may appear. Two cases of unrelated subjects affected of generalized congenital lipodystrophy are presented. Both developed difficult-to-manage diabetes mellitus and were treated with high doses of insulin. In both cases early microvascular complications were present. A mutation for LMNA gene was found in one of the subjects.

Rat pituitary cDNAs encoding the full peptide coding sequence of the rat gonadotropin-releasing hormone receptor were isolated and characterized. The deduced amino acid sequence encodes a protein of 327 residues with seven putative transmembrane domains characteristic of the family of G-protein coupled receptors. It is 95% identical at the amino acid level with the mouse gonadotropin-releasing hormone receptor. An mRNA of 4.5 Kb was identified in the rat pituitary, ovary, and testis, and in murine αT3 cells. In addition, a larger mRNA species of 5.0–5.5 Kb was present in these rat tissues, and a smaller mRNA species of 1.8 Kb was present in the rat pituitary and ovary, and in αT3 cells. The receptor mRNA levels were increased in the female rat pituitary after ovariectomy compared to levels in intact female rats.

Intra-aortic balloon pumping (IABP), a minimally invasive method of left ventricular support, has become a staple of management in the intensive care setting. Indications range from cardiogenic shock and its antecedents to unstable angina, percutaneous transluminal coronary angioplasty in high-risk patients, and perioperative support for heart surgery patients, as well as for cardiac patients undergoing general surgery. Complications are chiefly vascular or infectious and are predominantly minor. The technique is straightforward and rapidly initiated. Accurate synchronous phasing of balloon to heart action, the sine qua non of effective IABP, promises to be simplified and enhanced with the advent of new generation IABP systems.

A new generation, closed loop, fully automatic intraaortic balloon pump (CL-IABP) system continuously optimizes diastolic augmentation by adjusting balloon pump parameters beat by beat without operator intervention. In dogs in sinus rhythm and with experimentally induced arrhythmias, the new CL-IABP system provided safe, effective augmentation. To investigate the system's suitability for clinical use, 10 patients meeting standard indications for IABP were studied. The patients were pumped by the fully automatic IABP system for an average of 20 hr (range, 1-48 hr). At start-up, the system optimized pumping parameters within 7-20 sec. Evaluation of 186 recordings made at hourly intervals showed that inflation began within 20 msec of the dicrotic notch 99% of the time. In 100% of the recordings, deflation straddled the first half of ventricular ejection. Peak pressure across the balloon membrane averaged 55 mmHg and, in no case, exceeded 100 mmHg. Examination of the data showed that as soon as the system was actuated it provided consistently beneficial diastolic augmentation without any further operator intervention. Eight patients improved and two died (one of irreversible cardiogenic shock and one of ischemic cardiomyopathy). No complications were attributable to the investigational aspects of the system. A fully automated IABP is feasible in the clinical setting, and it may have advantages relative to current generation IABP systems.

SUMMARY Routine screening has been shown to reduce the mortality from breast cancer in asymptomatic women. All women should be instructed in breast self-examination, and should begin a program of screening mammography and breast physical examination on an annual basis beginning at the age of 40. Most early breast cancers can be adequately treated without ablative surgery.

In unilateral total knee replacement (TKR), perioperative blood loss, low transfusion thresholds and short hospital stay result in patients being discharged with low haemoglobin (Hb). We assessed the effects of perioperative administration of intravenous iron, with or without erythropoietin, plus a restrictive transfusion threshold (Hb < 80 g L(-1)) both on transfusion rate and recovery from post-operative anaemia. TRK patients received iron sucrose (2 x 200 mg per 48 h, iv) (Group IVI, n = 129). Patients with admission Hb < 130 g L(-1), also received erythropoietin (1 x 40 000 IU, sc) (Group EPO, n = 19). Perioperative clinical and laboratory data were obtained. Mean Hb loss was 36 g L(-1), but only seven patients were transfused (5%). Pre-operatively, 66 (45%) patients did not have enough stored iron to compensate Hb loss. At post-operative day 30, only 15% were anaemic, 70% of Hb loss and 92% of pre-operative Hb were recovered and ferritin increased by 73 microg L(-1) (P < 0.01), although erythropoietic response was higher in patients receiving erythropoietin (P < 0.05). No adverse effects of iron sucrose or erythropoietin were witnessed. This protocol seems to reduce allogeneic blood transfusion rate and may hasten the recovery from post-operative anaemia in TKR patients, without depleting iron stores. Further studies are needed to ascertain which patients may benefit of extended intravenous iron and/or erythropoietin administration.

The individual lifetimes of three low-lying states in the proton-decaying well-deformed rotational band in the second minimum of the N = Z nucleus Cu-58 were determined. Doppler-shift attenuated gamma -ray lineshapes were analyzed following the fusion-evaporation reaction C-40,(Mg-24,1 alpha 1p1n)Cu-58 and using the EUROBALL gamma -ray spectrometer coupled to ancillary detector systems. The deduced transitional quadrupole moments confirm the predicted increase of deformation towards the bottom of the band. The gamma decay-out strength hints towards a nonstatistical pattern.

Thyroid hormone receptors (TRs) are ligand-dependent transcription factors that regulate target gene transcription. The conserved carboxy-terminal region of the ligand-binding domain (AF-2) has been thought to play a critical role in mediating ligand-dependent transactivation by the interaction with coactivator(s). Using bacterially-expressed TR as a probe, far-Western-based expression cDNA library screening identified cDNAs that encode, in part, the recently reported partial steroid receptor coactivator-1 (SRC-1) sequence. Additional work, including 5' RACE, has characterized a full-length cDNA that encodes a approximately 160 kD protein as a putative thyroid hormone receptor coactivator (F-SRC-1). In vitro binding studies show that F-SRC-1 binds to a variety of nuclear hormone receptors in a ligand-dependent manner, along with TBP and TFIIB, suggesting that F-SRC-1 may play a role as a bridging molecule between nuclear hormone receptors and general transcription factors. Interestingly, AF-2 mutants also retain ligand-dependent interaction with F-SRC-1. Although F-SRC-1 recognizes the ligand-induced conformational changes of nuclear hormone receptors, our observations suggest that F-SRC-1 may bind directly with subregion(s) in nuclear hormone receptors other than the AF-2 region.

The mechanical auxiliary ventricle (MAV) is an avalvular prosthesis that is permanently implanted in the descending thoracic aorta. It is counterpulsated like the intraaortic balloon pump (IABP); however, the MAV, with its larger pumping chamber, can provide greater hemodynamic effects than the IABP. The IABP is an accepted therapy for alleviating acute pharmacologically refractory congestive heart failure (CHF). The beneficial actions of the MAV in advanced CHF have been documented, using an earlier version of the system [Kantrowitz A, Krakauer JS, Zorzi G, Rubenfire M, Freed PS, Phillips S, Lipsius M, Titone C, Cascade P, Jaron D (1971) Current status of the intraaortic balloon pump and initial clinical experience with an aortic patch mechanical auxiliary ventricle. Transplant Proc 3:1459] These studies also confirmed that the MAV, because of the small surface area of artificial material in contact with the blood, is minimally thrombogenic, allowing the system to be turned off at will and permitting the patient to be untethered when physiologically appropriate. However, these studies also demonstrated that the MAV’s percutaneous access device had led to infection. The MAV system was therefore redesigned, necessitating in vitro and in vivo studies to determine the reliability of the reconfigured prosthesis. In this report, the results of in vivo tests of biochemical and hematological studies of four calves with long-term, intermittently activated, MAVs are presented. Four animals were pumped intermittently for 2-h sessions, 5 days a week, for 22, 26, 60, and 112 weeks, respectively. In the aggregate, the four animals were pumped for 3790 h. During this time, the blood pumps were activated for more than 20 million cycles and were restarted after inactivation of hours or days more than 1700 times. No aberrations of clinical significance were discovered. The results of other tests, including an exhaustive search for thromboemboli and other pathological responses to the MAV, also proved negative. These results provide evidence that turning the MAV ‘Off’ and ‘On’ does not activate the host’s hemostatic mechanism. In clinical application, with the MAV ‘Off,’ the patient can be free of any external connection, or have the option of a standby wearable drive unit weighing

Today, almost a quarter century since its first trial in patients, the intraaortic balloon pump is the most commonly used cardiac assist device.1 Indeed, intraaortic balloon pumping (IABP) has become standard in coronary care and cardiac surgery facilities, where it has established its role in the management of acute left ventricular (LV) dysfunction. In this chapter, we outline the theoretical concept of diastolic augmentation and summarize early experimental studies that supported the concept and enabled advances toward clinical implementations of cardiac assistance based on this principle. We then discuss the hemodynamic effects of IABP. A critical review of knowledge as to the determinants of the efficacy of IABP follows, setting the stage for consideration of the capabilities and limitations of currently available IABP apparatus.

Background: In the past decade, cryptorchidism has generally been treated in the first 36 months of life using an inguinal approach, in the case of palpable testis, or using laparoscopy, in the case of nonpalpable testis. Nevertheless, before this period some children were managed incorrectly. This case report shows how laparoscopy and the collaboration between pediatric surgeons and urologists may lead to optimal results. Case report: A 19-year-old male was referred to our unit following routine medical examination for enrollment in the military service with a diagnosis of right cryptorchidism. The clinical history showed the anamnesis of right cryptorchidism diagnosed at birth as a right nonpalpable testis, confirmed at 2 years of age with clinical examination and computer tomography. The patient came to our attention to again undergo a clinical examination, ultrasonography, computed tomography, and magnetic resonance imaging. We found a left, well-positioned testis of 20 ml in volume and an empty right scrotum; all the instrumental examinations were negative. The patient was thus scheduled for a diagnostic laparoscopy. A pediatric surgeon with extensive experience in this pathology performed the procedure. The 10-mm 30° optics introduced through the umbilicus showed a closed right inguinal ring, with no evidence of either vas deferens or inner spermatic vessels at the level of the inguinal region or pelvis. Two more trocars were introduced and a testis of 15 ml in volume was found under the ascending colon 10 cm away from the cecum. An orchiectomy was performed via laparoscopy. Conclusion: This case clearly shows that some males with nonpalpable testis may have been treated incorrectly in the prelaparoscopic era and may now have an intraabdominal testis. In addition, our experience shows that intraabdominal testis may sometime be in an unusual location, and a laparoscopic surgeon with experience in this pathology is fundamental to finding the testis. In the case of adults with nonpalpable testis, when echography, computed tomography, and magnetic resonance imaging are not useful, the only effective diagnostic procedure is laparoscopy.

The herbicide 2,4,5-T is actively transported by renal cortical slices of dogs and rats, suggesting that the compound should be rapidly eliminated from the body via the kidneys. The prolonged plasma half-life of 2,4,5-T in the dog (77 hr) indicates that factors other than secretion into the urine are important determinants of elimination in the dog. This study was designed to determine the renal handling of 2,4,5-T in anaesthetized dogs, and an attempt was made to increase excretion of the herbicide with sodium acetate. Injection of 2,4,5-T decreased clearance of p -aminohippurate in a dose-dependent manner, suggesting that the compound was actively secreted. The clearance of the herbicide, however, was exceedingly low, being less than 1% of inulin clearance. The clearance of 2,4,5-T was increased by sodium acetate and by acetazolamide. Additional studies with mannitol, sodium bicarbonate and ammonium chloride demonstrated that clearance of 2,4,5-T was related to urinary pH, but only when the pH exceeded 6, and was not affected by changes in urine volume. Addition of plasma inhibited the transport of 2,4,5-T by renal cortex slices in vitro , suggesting that the low clearance in vivo was due to very tight binding of the herbicide to plasma protein.

Professionals de la salut; Formació mèdica continuada; Atenció primària Profesionales de la salut; Formación médica continuada; Atención primaria Healthcare professionals; Continuing medical education; Primary care BACKGROUND The planning and execution of continuous education in an organization that provides health services is a complex process. The objectives, learning sequences, and implementation strategies should all be oriented to improving the health of the population. The aim of this study was to analyse the expectations and perceptions of continuous educations by primary healthcare professionals (physicians and nurses) and identify aspects that hinder or encourage the process. METHODS A qualitative study with 5 focus groups made up of 25 primary healthcare professionals from the Catalan Health Institute, Barcelona (Catalonia, Spain). The focus groups were audio-recorded and the results transcribed. The analysis involved: a) Reading of the data looking for meanings b) Coding of the data by themes and extracting categories c) Reviewing and refining codes and categories d) Reconstruction of the data providing an explanatory framework for the meanings e) Discussion about the interpretations of the findings and f) Discussed with relevant professionals from PHC (physicians and nurses)"Data regarding thematic content were analyzed with the support of Atlasti 5.1 software. RESULTS The health needs of the population were often at the core of the learning processes but the participants' views did not always spontaneously refer to improvements in these issues. Common themes that could hinder learning and where identified, including contextual aspects such as work constraints (timetables, places being covered during training) and funding policies. New learning strategies to improve the effectiveness of continuous education were proposed such as the exchange of knowledge, the activation of personal commitment to change, and the improvement of organizational aspects. CONCLUSIONS The primary healthcare professionals in our study viewed continuous education as a professional necessity and would like to translate the knowledge acquired to improving the health of the population. Nevertheless, professional, structural, and organizational issues impede the process.