Chemoselective and stereoselective lithium carbenoid mediated cyclopropanation of acyclic allylic alcohols.

The reaction of geraniol with different lithium carbenoids generated from n-BuLi and the corresponding dihaloalkane has been evaluated. The reaction occurs in a chemo and stereoselective manner, which is consistent with a directing effect from the oxygen of the allylic moiety. Furthermore, a set of polyenes containing allylic hydroxyl or ether groups were chemoselectively and stereoselectively converted into the corresponding gem-dimethylcyclopropanes in one single step in moderate to good yields mediated by a lithium carbenoid generated in situ by the reaction of n-BuLi and 2,2-dibromopropane.

The synthesis of 3-hydroxy-2,4,8-trimethyldec-8-enolides and an approach to 3,4-dihydroxy-2,4,6,8-tetramethyldec-8-enolide.

The synthesis of several derivatives of 3-hydroxy-2,4,8-trimethyldec-8-enolide and attempts at the synthesis of 3,4-dihydroxy-2,4,6,8-tetramethyldec-8-enolide (1), a structure which has been assigned to a metabolite of the phytopathogenic fungus, Botrytis cinerea, gave products whose spectroscopic data had significant differences from those reported for the natural product 1. The rare 11-membered lactone rings were constructed by ring-closing metathesis reactions. The increase in conformational restrictions imposed by the substituents has a high influence on the stereochemistry of the ring-closing metathesis reaction and gives rise to a decrease in the yield for the synthesis of 11-membered lactones. The predominant alkene which was obtained was the (Z)-isomer. The observed spectroscopic differences between the synthesized lactones and the natural product and the spectroscopic data of its acetylated derivative 26a allowed us to revise the structure 1 to that of the γ-butyrolactone 26.

Exploring mutasynthesis to increase structural diversity in the synthesis of highly oxygenated polyketide lactones.

The enantioselective synthesis of (2R,3R,4E,8E)-3-hydroxy-2,4,8-trimethyldeca-4,8-dienolide (5) by ring-closing metathesis is described. This compound is an analogue of 3,4-dihydroxy-2,4,6,8-tetramethyldec-8-enolide (4) which is a rare 11-membered lactone produced by the fungus, Botrytis cinerea. Mutasynthetic studies with compound 5 using two mutants of B. cinerea led to the isolation of four new highly oxygenated 11-membered lactones (11-14) in which compound 5 has been stereoselectively epoxidized and hydroxylated at sites that were not easily accessible by classical synthetic chemistry.

Does pilates exercise increase physical activity, quality of life, latency, and sleep quantity in middle-aged people?

This prospective study assessed the effects of a 12-wk. exercise program based on the Pilates method (2 one-hr. sessions per week) on 99 sedentary middle-aged volunteers (M age = 47.6 yr., SD = 0.8), using an accelerometry, the Pittsburgh Sleep Quality Index, and the SF-36 questionnaire to measure changes in physical activity, quality of life, sleep latency, and quantity. The variables (quality of life, sleep latency, and quantity) were compared before and after applying the Pilates program. All of the physical and emotional components of the SF-36 questionnaire showed significant improvement, and the latency and sleep quantity also showed significant increases. The results indicate that Pilates is an accessible, interesting exercise program that can generate important changes in middle age.

Effect of combined electrostimulation and plyometric training on 30 meters dash and triple jump.

AIM: The aim of this paper was to analyze the effects of training combining plyometrics (PT) and neuromuscular electrostimulation (ES) on speed training and triple jump. The study consisted on the application of an electrostimulation protocol and plyometric jumps to four groups of young athletes (Control, G II, G III and G IV). METHODS: Eighty-four young athletes took part in the study (40 girls and 44 boys). All of them were sprinters (100 and 200 meters dash, and 100 and 110 hurdles meters), their mean age, weight and height being 15.9±1.4 years old, 58.53±8.05 kg, and 1.68±0.07 m, respectively. After 8 weeks of training, a 30-meter sprint launched test -time being measured by photoelectric cells - and a triple jump test from static position were completed. Repeated measures ANCOVA were used. RESULTS: The only group that improved significantly in the speed test (P<0.001) relative to the control group was G IV. In the triple jump test, improvements were significant, (P<0.05) and (P<0.01), in G II and G IV, respectively, relative to the control group. The results of ES + PT combined training offered no significant differences in either speed test and triple jump by gender. CONCLUSION: The most effective training aimed at improving the speed of 30 m is simultaneous combined training. Regarding triple jump, the results showed significant improvements in the performance of athletes who used both simultaneous combined training and used ES followed by plyometrics. However, no significant improvement was observed after PT training prior to ES.

Neuroprotective agents: cannabinoids.

Chronic inflammation and neurodegeneration are the main pathological traits of multiple sclerosis that coexist in all stages of the disease course, with complex and still nonclarified relationships. Currently licensed medications have efficacy to control aspects related to inflammation, but have been unable to modify pure progression. Experimental work has provided robust evidence of the immunomodulatory and neuroprotective properties that cannabinoids exert in animal models of multiple sclerosis. Through activation of the CB2 receptor, cannabinoids modulate peripheral blood lymphocytes, interfere with migration across the blood-brain barrier and control microglial/macrophage activation. CB1 receptors present in neural cells have a fundamental role in direct neuroprotection against several insults, mainly excitotoxicity. In multiple sclerosis, several reports have documented the disturbance of the endocannabinoid system. Considering the actions demonstrated experimentally, cannabinoids might be promising agents to target the main aspects of the human disease.

Restless legs syndrome in patients with multiple sclerosis: evaluation of risk factors and clinical impact.

INTRODUCTION: Restless legs syndrome (RLS) is a disorder characterised by an irresistible urge to move the legs, usually accompanied by unpleasant sensations. It is more frequent in patients with multiple sclerosis (MS) than in the general population. OBJECTIVES: To evaluate the prevalence of RLS, defined according to the 4 essential requirements included in the diagnostic criteria proposed by the International Restless Leg Syndrome Study Group, in a cohort of patients with MS; and to identify potential risk factors and the clinical impact of RLS. RESULTS: The sample included 120 patients with MS, with a mean age of symptom onset of 40 years and an average disease duration of 46 months. The prevalence rate of RLS was 23.3%. MS progression time was significantly shorter in patients with RLS (P=.001). A recent relapse, and symptoms of anxiety, depression, and neuropathic pain were significantly associated with risk of RLS (P=.001, P<.001, P<.001, and P=.001, respectively). In addition, patients with RLS had a greater risk of poor sleep quality, fatigue, daytime sleepiness, and poor quality of life than those without RLS (P=.002, P=.017, P=.013, and P=.009, respectively). CONCLUSIONS: RLS should be considered in the neurological evaluation of patients with MS; early diagnosis and treatment would improve the quality of life of patients with MS presenting RLS.

Approximate reinforcement learning to control beaconing congestion in distributed networks.

In vehicular communications, the increase of the channel load caused by excessive periodical messages (beacons) is an important aspect which must be controlled to ensure the appropriate operation of safety applications and driver-assistance systems. To date, the majority of congestion control solutions involve including additional information in the payload of the messages transmitted, which may jeopardize the appropriate operation of these control solutions when channel conditions are unfavorable, provoking packet losses. This study exploits the advantages of non-cooperative, distributed beaconing allocation, in which vehicles operate independently without requiring any costly road infrastructure. In particular, we formulate the beaconing rate control problem as a Markov Decision Process and solve it using approximate reinforcement learning to carry out optimal actions. Results obtained were compared with other traditional solutions, revealing that our approach, called SSFA, is able to keep a certain fraction of the channel capacity available, which guarantees the delivery of emergency-related notifications with faster convergence than other proposals. Moreover, good performance was obtained in terms of packet delivery and collision ratios.

Perioperative and oncologic outcomes of interval colectomy performed by acute care surgeons after stenting as a bridge to surgery for left-sided malignant colonic obstruction are non-inferior to the outcomes of colorectal surgeons in the elective setting: single center experience.

PURPOSE: To analyze if perioperative and oncologic outcomes with stenting as a bridge to surgery (SEMS-BS) and interval colectomy performed by acute care surgeons for left-sided occlusive colonic neoplasms (LSCON) are non-inferior to those obtained by colorectal surgeons for non-occlusive tumors of the same location in the full-elective context. METHODS: From January 2011 to January 2021, patients with LSCON at University Regional Hospital in Málaga (Spain) were directed to a SEMS-BS strategy with an interval colectomy performed by acute care surgeons and included in the study group (SEMS-BS). The control group was formed with patients from the Colorectal Division elective surgical activity dataset, matching by ASA, stage, location and year of surgery on a ratio 1:2. Stages IV or palliative stenting were excluded. Software SPSS 23.0 was used to analyze perioperative and oncologic (defined by overall -OS- and disease free -DFS-survival) outcomes. RESULTS: SEMS-BS and control group included 56 and 98 patients, respectively. In SEMS-BS group, rates of technical/clinical failure and perforation were 5.35% (3/56), 3.57% (2/56) and 3.57% (2/56). Surgery was performed with a median interval time of 11 days (9-16). No differences between groups were observed in perioperative outcomes (laparoscopic approach, primary anastomosis rate, morbidity or mortality). As well, no statistically significant differences were observed in OS and DFS between groups, both compared globally (OS:p < 0.94; DFS:p < 0.67, respectively) or by stages I-II (OS:p < 0.78; DFS:p < 0.17) and III (OS:p < 0.86; DFS:p < 0.70). CONCLUSION: Perioperative and oncologic outcomes of a strategy with SEMS-BS for LSCON are non-inferior to those obtained in the elective setting for non-occlusive neoplasms in the same location. Technical and oncologic safety of interval colectomy performed on a semi-scheduled situation by acute care surgeons is absolutely warranted.

Women's preference for caesarean section: a systematic review and meta-analysis of observational studies.

BACKGROUND: The striking increase in caesarean section rates in middle- and high-income countries has been partly attributed to maternal request. We conducted a systematic review and meta-analysis of women's preferences for caesarean section. OBJECTIVES: To review the published literature on women's preferences for caesarean section. SEARCH STRATEGY: A systematic search of MEDLINE, EMBASE, LILACS and PsychINFO was performed. References of all included articles were examined. SELECTION CRITERIA: We included studies that quantitatively evaluated women's preferences for caesarean section in any country. We excluded articles assessing health providers' preferences and qualitative studies. DATA COLLECTION AND ANALYSIS: Two reviewers independently screened abstracts of all identified citations, selected potentially eligible studies, and assessed their full-text versions. We conducted a meta-analysis of proportions, and a meta-regression analysis to determine variables significantly associated with caesarean section preference. MAIN RESULTS: Thirty-eight studies were included (n = 19,403). The overall pooled preference for caesarean section was 15.6% (95% CI 12.5-18.9). Higher preference for caesarean section was reported in women with a previous caesarean section versus women without a previous caesarean section (29.4%; 95% CI 24.4-34.8 versus 10.1%; 95% CI 7.5-13.1), and those living in a middle-income country versus a high-income country (22.1%; 95% CI 17.6-26.9 versus 11.8%; 95% CI 8.9-15.1). AUTHORS' CONCLUSIONS: Only a minority of women in a wide variety of countries expressed a preference for caesarean delivery. Further research is needed to better estimate the contribution of women's demand to the rising caesarean section rates.

Effects of training frequency on physical fitness in male prepubertal tennis players.

AIM: Aim of the present study was to test if training frequency determines physical fitness and fat mass accumulation in prepubertal male tennis players (TP). METHODS: Body composition scans (DXA), jump performance (SJ and CMJ) and 30 m running speed tests were conducted in 24 TP (10.6 years) and 17 physically active boys. Tennis players were divided into two groups (TP5: playing 5 d/week, n.=14; TP2: playing 2 d/week, n.=10). RESULTS: Compared to TP5 and TP2, controls had more total body fat (+23-28%) and fat mass in the trunk (+42-43%) and legs (+13-19%), respectively (P<0.05). The relative VO2max was higher in TP2 (12%) and TP5 (15%) than in controls (P<0.001). A positive correlation was observed between weekly trainng hours and VO2max (r=0.42, P<0.05, N.=24). Compared to controls, TP5 and TP2 jumped higher in SJ and CMJ (P<0.05) and ran faster in the 30 m test (P<0.05). Similar VO2max, jumping heights and running speed times were observed between TP5 and TP2. After adjustment for the percentage of body fat and age, TPs reached higher VO2max values than controls, while differences in SJ, CMJ and 30 m did not reach statistical significance. CONCLUSION: Playing tennis 2 d/week at prepubertal ages was associated to enhanced aerobic power and reduced total and regional adiposity (trunk and legs) compared to non-active boys. Playing 5 d/week only has a small additional effect. TPs had also higher jumping and sprinting performance than the controls, although these differences were accounted for by the increased fat mass of the control boys.

Role of minor determinants of amoxicillin in the diagnosis of immediate allergic reactions to amoxicillin.

BACKGROUND: Skin testing of subjects with immediate hypersensitivity to amoxicillin is performed using major and minor determinants of benzylpenicillin plus amoxicillin. However, sensitivity is not optimal, and other determinants need to be considered. We assessed the sensitivity of stable, well-characterized minor determinants of amoxicillin in subjects with immediate allergic reactions to amoxicillin to improve skin test sensitivity. METHODS: Amoxicillin, amoxicilloic acid, and diketopiperazine were prepared and characterized by reverse-phase HPLC, tested in vivo by skin testing and in vitro by basophil activation test and RAST inhibition assay. RESULTS: Patients with immediate hypersensitivity to amoxicillin were selected: Group A (n = 32), skin test positive just to amoxicillin; Group B (n = 19), skin test positive to benzylpenicillin determinants; Group C (n = 10), skin test negative and amoxicillin drug provocation test positive. In Group A, 27 subjects (81.8%) were skin test positive to amoxicillin, ten (30.3%) to amoxicilloic acid, two (6.1%) to diketopiperacine, and six (18.2%) negative. In Group B, nine (50%) were positive to amoxicillin, eight (42.1%) to amoxicilloic acid, none to diketopiperacine, and nine (50%) negative. In Group C, skin tests were negative. BAT was positive to amoxicillin in 26 patients (50.9%), to amoxicilloic acid in 15 (29.1%), and diketopiperazine in four (7.8%). RAST inhibition studies showed > 50% inhibition in all sera, with the highest concentration of amoxicillin and amoxicilloic acid. CONCLUSIONS: The combination of minor determinants of amoxicillin, amoxicilloic acid, and diketopiperazine seems to be of no greater value than the use of amoxicillin alone. Further efforts are needed to find new structures to improve sensitivity in the diagnosis of immediate hypersensitivity to betalactams.

The cannabinoid receptor 1 gene (CNR1) and multiple sclerosis: an association study in two case-control groups from Spain.

Different studies point to the implication of the endocannabinoid system in multiple sclerosis (MS) and animal models of MS. The purpose of this study was to evaluate a possible association of MS with polymorphic markers at the CNR1 gene, encoding the cannabinoid 1 (CB(1)) receptor. We have performed a genetic analysis of an AAT repeat microsatellite localized in the downstream region of the CNR1 gene, in two case-control groups of MS patients and healthy controls (HC) from Spain (Madrid and Bilbao). MS patients with primary progressive MS (PPMS) had more commonly long ((AAT) > or = (13)) alleles and genotypes with a significant difference for genotype 7/8 in Madrid (p = 0.043) and in the sum of both groups (p = 0.016); short alleles were less frequently found in PPMS with a significant difference for allele 5 in the analysis of both groups together (p = 0.039). In patients with relapsing MS, no consistent differences in allele and genotype distribution were found. Disease severity and progression was unrelated to AAT repeat variations. In conclusion, long (AAT) > or = (13) CNR1 genotypes could behave as risk factors for PPMS.

Conservative approach versus urgent appendectomy in surgical management of acute appendicitis with abscess or phlegmon.

BACKGROUND: Surgical management of acute appendicitis with appendiceal abscess or phlegmon remains controversial. We studied the results of initial conservative treatment (antibiotics and percutaneous drainage if necessary, with or without interval appendectomy) compared with immediate surgery. METHODS: We undertook an observational, retrospective cohort study of patients with a clinical and radiological diagnosis of acute appendicitis with an abscess or phlegmon, treated in our hospital between January 1997 and March 2009. Patients younger than 14, with severe sepsis or with diffuse peritonitis were excluded. A study group of 15 patients with acute appendicitis complicated with an abscess or phlegmon underwent conservative treatment. A control group was composed of the other patients, who all underwent urgent appendectomy, matched for age and later randomized 1:1. The infectious risk stratification was established with the National Nosocomial Infections Surveillance System (NNIS) index. Dependent variables were hospital stay and surgical site infection. Analysis was with SPSS, with p < 0.05 considered significant. RESULTS: Interval appendectomy was performed in 7 study group patients. Surgical site infection episodes were more frequent in the control group (6 vs. 0, p < 0.001). A greater percentage of high risk patients (NNIS ≥ 2) was identified in the control group (80 vs. 28.7%, p < 0.03), mostly related with contaminated or dirty procedures in this group (p < 0.001). No significant difference between groups was found in hospital stay. CONCLUSION: Initial conservative treatment should be considered the best therapeutic choice for acute appendicitis with abscess or phlegmon.

Multiple sclerosis associates with LILRA3 deletion in Spanish patients.

The genetic susceptibility to multiple sclerosis (MS) is only partially explained, and it shows geographic variations. We analyse here two series of Spanish patients and healthy controls and show that relapsing MS (R-MS) is associated with a gene deletion affecting the hypothetically soluble leukocyte immunoglobulin (Ig)-like receptor A3 (LILRA3, 19q13.4), in agreement with an earlier finding in German patients. Our study points to a gene-dose-dependent, protective role for LILRA3, the deletion of which synergizes with HLA-DRB1(*)1501 to increase the risk of R-MS. We also investigated whether the risk of suffering R-MS might be influenced by the genotypic diversity of killer-cell Ig-like receptors (KIRs), located only approximately 400 kb telomeric to LILRA3, and implicated in autoimmunity and defence against viruses. The relationship of LILRA3 deletion with R-MS is not secondary to linkage disequilibrium with a KIR gene, but we cannot exclude some contributions of KIR to the genetic susceptibility to R-MS.

Adverse effects on the lipid profile of immunosuppressive regimens: tacrolimus versus cyclosporin measured using C2 levels.

Immunosuppression has improved graft and recipient survival in transplantation but is accompanied by several adverse effects like dyslipidemia and cardiovascular disease. Herein, we performed an observational, descriptive study to analyze the relationship of dyslipemia (hypercholesterolemia [hypercho] and hypertriglyceridemia [hypertg]) and cardiovascular disease with two different immunosuppressive regimens in liver transplantation: cyclosporine treatment based upon C2 levels (CsA2) and tacrolimus (Tac), both in combination with steroids. Seventy-four liver transplantation patients were included during a 2-year period: 35 with CsA2 and 39 with Tac. The mean follow-up was 40 months. There were no significant differences between the groups in terms of age, gender, Model for End-stage Liver Disease Score, Child stage, and indication for transplantation. The distribution of patients with HyperCho and HyperTg was independent of the immunosuppressive agent (P = NS), both in a global and in a stratified analysis at 6, 12, 24, and 60 months. The analysis of cardiovascular events revealed no differences between the groups (CsA2 14.3%; Tac 18.9%; P = NS). We suggest that CsA monitoring using C2 levels shows a safety profile similar to that of Tac with regard to the development of dyslipidemia and cardiovascular events.

Restless legs syndrome in patients with multiple sclerosis: evaluation of risk factors and clinical impact. / Síndrome de piernas inquietas en esclerosis múltiple: evaluación de factores de riesgo y repercusión clínica.

INTRODUCTION: Restless legs syndrome (RLS) is a disorder characterised by an irresistible urge to move the legs, usually accompanied by unpleasant sensations. It is more frequent in patients with multiple sclerosis (MS) than in the general population. OBJECTIVES: To evaluate the prevalence of RLS, defined according to the 4 essential requirements included in the diagnostic criteria proposed by the International Restless Leg Syndrome Study Group, in a cohort of patients with MS; and to identify potential risk factors and the clinical impact of RLS. RESULTS: The sample included 120 patients with MS, with a mean age of symptom onset of 40 years and an average disease duration of 46 months. The prevalence rate of RLS was 23.3%. MS progression time was significantly shorter in patients with RLS (P = 0.001). A recent relapse, and symptoms of anxiety, depression, and neuropathic pain were significantly associated with risk of RLS (P = 0.001, P < 0.001, P < 0.001, and P = 0.001, respectively). In addition, patients with RLS had a greater risk of poor sleep quality, fatigue, daytime sleepiness, and poor quality of life than those without RLS (P = 0.002, P = 0.017, P = 0.013, and P = 0.009, respectively). CONCLUSIONS: RLS should be considered in the neurological evaluation of patients with MS; early diagnosis and treatment would improve the quality of life of patients with MS presenting RLS.

Determination of progesterone in saliva using an electrochemical immunosensor and a COTS-based portable potentiostat.

This paper describes the reliable determination of progesterone (P4) in undiluted saliva making use of a disposable amperometric immunosensors implemented on low-cost and portable device/potentiostat constructed with commercial-off-the-shelf (COTS) components. The immunosensor allows the fast (45 min), selective and sensitive determination (5 pg mL-1 LOD) of P4 using amperometry in stirred solutions. The immunosensor was coupled to the COTS-based potentiostat and amperometry was made into drops of quiescent solutions. No significant differences were apparent between the analytical performance achieved with the immunosensor for P4 using both a conventional and the COST-based potentiostats. The practical applicability of the immunosensor coupled with the COTS-based potentiostat was demonstrated by determining the endogenous P4 content in different undiluted saliva samples with highly variable endogenous contents of the target hormone. The obtained results were in good agreement with those provided by the conventional ELISA methodology and with the contents reported in the literature for samples with similar characteristics. This validated the combined device for the reliable and minimally invasive determination of the target hormone involving a very simple protocol and taking only 45 min.

Recent advances in analytical determination of thalidomide and its metabolites.

Thalidomide, a racemate, is coming into clinical use as immuno-modulating and anti-inflammatory drug. Thalidomide was approved by the FDA in July 1998 for the treatment of erythema nodusum leprosum associated with leprosy. Recently, thalidomide is proving to be a promising drug in the treatment of a number of cancers and inflammatory diseases, such as multiple myeloma, inflammatory bowel disease (Crohn's disease), HIV and cancer associated cachexia. These effects may chiefly be exerted by S-thalidomide, but the enantiomers are inter-converted in vivo. Thalidomide is given orally, although parenteral administration would be desirable in some clinical situations. Thalidomide has been determined in formulations and, principally in biological fluids by a variety of methods such as high-performance liquid chromatography with ultraviolet detection and liquid chromatography coupled with tandem mass spectrometry. The overview includes the most relevant analytical methodologies used in its determination.