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Background: \ud The SARS-CoV-2 delta (B.1.617.2) variant was first detected in England in March, 2021. It has since rapidly become the predominant lineage, owing to high transmissibility. It is suspected that the delta variant is associated with more severe disease than the previously dominant alpha (B.1.1.7) variant. We aimed to characterise the severity of the delta variant compared with the alpha variant by determining the relative risk of hospital attendance outcomes.\ud \ud Methods: \ud This cohort study was done among all patients with COVID-19 in England between March 29 and May 23, 2021, who were identified as being infected with either the alpha or delta SARS-CoV-2 variant through whole-genome sequencing. Individual-level data on these patients were linked to routine health-care datasets on vaccination, emergency care attendance, hospital admission, and mortality (data from Public Health England's Second Generation Surveillance System and COVID-19-associated deaths dataset; the National Immunisation Management System; and NHS Digital Secondary Uses Services and Emergency Care Data Set). The risk for hospital admission and emergency care attendance were compared between patients with sequencing-confirmed delta and alpha variants for the whole cohort and by vaccination status subgroups. Stratified Cox regression was used to adjust for age, sex, ethnicity, deprivation, recent international travel, area of residence, calendar week, and vaccination status.\ud \ud Findings: \ud Individual-level data on 43 338 COVID-19-positive patients (8682 with the delta variant, 34 656 with the alpha variant; median age 31 years [IQR 17–43]) were included in our analysis. 196 (2·3%) patients with the delta variant versus 764 (2·2%) patients with the alpha variant were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2·26 [95% CI 1·32–3·89]). 498 (5·7%) patients with the delta variant versus 1448 (4·2%) patients with the alpha variant were admitted to hospital or attended emergency care within 14 days (adjusted HR 1·45 [1·08–1·95]). Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients with the delta variant versus the alpha variant (adjusted HR for hospital admission 1·94 [95% CI 0·47–8·05] and for hospital admission or emergency care attendance 1·58 [0·69–3·61]) were similar to the HRs for unvaccinated patients (2·32 [1·29–4·16] and 1·43 [1·04–1·97]; p=0·82 for both) but the precision for the vaccinated subgroup was low.\ud \ud Interpretation: \ud This large national study found a higher hospital admission or emergency care attendance risk for patients with COVID-19 infected with the delta variant compared with the alpha variant. Results suggest that outbreaks of the delta variant in unvaccinated populations might lead to a greater burden on health-care services than the alpha variant.\ud \ud Funding: \ud Medical Research Council; UK Research and Innovation; Department of Health and Social Care; and National Institute for Health Research.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections were rising during early summer 2021 in many countries as a result of the Delta variant. We assessed reverse transcription polymerase chain reaction swab positivity in the Real-time Assessment of Community Transmission–1 (REACT-1) study in England. During June and July 2021, we observed sustained exponential growth with an average doubling time of 25 days, driven by complete replacement of the Alpha variant by Delta and by high prevalence at younger, less-vaccinated ages. Prevalence among unvaccinated people [1.21% (95% credible interval 1.03%, 1.41%)] was three times that among double-vaccinated people [0.40% (95% credible interval 0.34%, 0.48%)]. However, after adjusting for age and other variables, vaccine effectiveness for double-vaccinated people was estimated at between ~50% and ~60% during this period in England. Increased social mixing in the presence of Delta had the potential to generate sustained growth in infections, even at high levels of vaccination.

The five-coordinate iron porphyrin carbene complexes [Fe(TPP) (CCl2)] (TPP = tetraphenylporphyrin), [Fe(TTP) (CCl2)] (TTP = tetratolylporphyrin) and [Fe(TFPP) (CPh2)] (TFPP = tetra(pentafluorophenyl)porphyrin), utilizing two types of carbene ligands (CCl2 and CPh2), have been investigated by single crystal X-ray, XANES (X-ray absorption near edge spectroscopy), Mossbauer, NMR and UV–vis spectroscopies. The XANES suggested the iron(II) oxidation state of the complexes. The multitemperature and high magnetic field Mossbauer experiments, which show very large quadrupole splittings (QS, ΔEQ), determined the S = 0 electronic configuration. More importantly, combined structural and Mossbauer studies, especially the comparison with the low spin iron(II) porphyrin complexes with strong diatomic ligands (CS, CO and CN–) revealed the covalent bond nature of the carbene ligands. A correlation between the iron isomer shifts (IS, δ) and the axial bond distances is established for the first time for these donor carbon ...

Background Devastating morbidity and mortality can result when patients with undiagnosed sleep apnea syndrome (SAS) undergo bariatric surgery. We evaluated the prevalence of SAS and its rate of nondiagnosis in bariatric patients at a university hospital. Methods The demographic, anthropomorphic, and co-morbidity data were collected from 1368 patients evaluated for bariatric surgery. All patients were screened for symptoms of SAS, and symptomatic patients were evaluated with polysomnography. Results At the time of this report, 834 patients (61%) had completed the preoperative evaluation. Of these patients, 210 (25%) presented with previously diagnosed SAS. An additional 174 patients (21%) exhibited symptoms of SAS and underwent polysomnography. Most patients tested (127, 73%) had SAS that required treatment, 11 patients (6%) had mild SAS not requiring treatment, and 36 (21%) tested negative for SAS. Thus, symptom screening for SAS had a positive predictive value of 79% for predicting the presence of SAS and 73% for identifying patients who required SAS treatment. The patients with SAS tended to be older and male and have a greater body mass index ( P Conclusion Overall, SAS that required treatment with an oral appliance was prevalent (40%) in patients who presented for bariatric surgery. However, many of these patients with significant SAS (38%) were previously undiagnosed, despite exhibiting clear symptoms of the disease. Symptom screening appears to be effective in identifying patients who should be evaluated by polysomnography. To avoid the potential perils of undiagnosed SAS during the perioperative period, patients who undergo bariatric surgery should be screened, tested, and treated for this co-morbidity.

Background The present study was performed at a tertiary care university hospital. The present study examined the incidence of internal hernia (IH) in our series of laparoscopic Roux-en-Y gastric bypass (LRYGB) with retrocolic, retrogastric routing of the alimentary limb accompanied by routine secure closure of all mesenteric defects. Methods During a 4-year period, 847 patients underwent LRYGB. Our operative technique included retrocolic, retrogastric placement of the alimentary limb. The enteroenterostomy mesenteric defect, mesocolic defect, and Petersen defect were routinely closed in running fashion with nonabsorbable suture. Results The study population had a mean age of 42.4 ± 9.3 years and a mean preoperative body mass index of 45.3 ± 5.6 kg/m 2 . The mean operative time was 154 ± 25 minutes. The mean excess body weight loss at 1 year was 70%. The incidence of IH among this large study population was 0%. A total of 11 patients (1.3%) presented with symptoms concerning for IH, most commonly nausea, vomiting, and crampy abdominal pain, from 1 month to 6 years after the initial surgery. On re-exploration, 4 patients had adhesive small bowel obstruction, 4 had adhesions without obstruction, 1 had small bowel intussusception, and 2 patients had negative findings. Conclusion IH is a serious complication of LRYGB that can lead to catastrophic morbidity and mortality. We advocate vigilant screening for this complication and laparoscopic exploration for patients with worrisome symptoms. Our data have indicated that a routine and consistent technique to securely close the mesenteric defects can significantly reduce the risk of IH associated with retrocolic, retrogastric placement of the alimentary limb during LRYGB.

Previous outcome research in bariatric surgery has been unable to document quantitative changes in co-morbidities associated with obesity owing to a lack of a standardized instrument to grade the severity. We report a detailed description of the early resolution of the metabolic syndrome using our novel scheme for assessing co-morbidities. This study was performed at a tertiary care university hospital.Co-morbidity data were prospectively collected for 827 patients who underwent laparoscopic Roux-en-Y gastric bypass during a 4-year period using the Assessment of Obesity-Related Co-morbidities (AORC) scale. This scale assigns a score of 0-5 for the major medical conditions associated with obesity. The co-morbid conditions of obesity and biochemical markers of the metabolic syndrome were examined preoperatively and at the follow-up visits.Of the 827 patients who underwent laparoscopic Roux-en-Y gastric bypass, 72 (8.7%) met the AORC criteria for the metabolic syndrome (AORC score2 for diabetes mellitus [DM], hypertension [HTN], and dyslipidemia [DYS]). Overall, 75% of patients with DM, 69.4% of patients with HTN, and 76.4% of patients with DYS showed improvement in these co-morbidities (decrease from the preoperative AORC score) within 2 months after surgery. Within this period, DM, HTN, and DYS resolved in 65.3%, 51.4%, and 73.6% of patients, respectively. Concurrent decreases in hemoglobin A1c, serum lipids, and blood pressure were observed (P.05). Patients exhibited a modest excess body weight loss of 27.7% during this period. However, the mean AORC score for the whole group decreased significantly for DM, DYS, and HTN (P.001) before significant weight loss occurred.We have demonstrated a new and novel approach to categorize and more accurately define the magnitude of improvement in co-morbidities after laparoscopic Roux-en-Y gastric bypass. This improvement preceded the weight loss effects on the metabolic syndrome.

Telestration is an important teaching tool in minimally invasive surgery (MIS). While robotic surgery offers the added benefit of three-dimensional (3-D) visualization, telestration technology does not currently exist for this modality. This project aimed to develop a video algorithm to accurately translate a mentor's two-dimensional (2-D) telestration into a 3-D telestration in the da Vinci visual field.A prototype 3-D telestration system was constructed to translate 2-D telestration from a mentor station into 3-D graphics for the trainee at the robotic console. This system uses fast image correlation algorithms to allow 2-D images to be placed over the same anatomic location in the two separate video channels of the stereoscopic robotic visualization system. Three subjects of varying surgical backgrounds, blinded to the mode of telestration (2-D vs. 3-D), were tested in the laboratory, using a simulated robotic task.There were few technologic errors (2), only one of which resulted in a task error, in 99 total trials. Only the experienced MIS staff surgeon had a significantly faster task time in 2-D than in 3-D (P0.05). The MIS fellow recorded the fastest task times in 2-D and 3-D (P0.05). There were nine task errors, six of which were committed by the MIS fellow. The nonsurgeon trainee had the least number of errors but also had the slowest times.Robotic telestration in 3-D is feasible and does not negatively impact performance in laboratory tasks. We plan to refine the prototype and investigate its use in vivo.

Background: The purpose of this study was to evaluate the natural history of patients undergoing Rouxen-Y gastric bypass (RYGBP) with known asymptomatic cholelithiasis in whom prophylactic cholecystectomy was not performed at the time of surgery. Methods: The records of 144 consecutive patients from a single year experience in RYGBP surgery at the University of California, Davis Medical Center were reviewed. Patients undergoing RYGBP were routinely screened for cholelithiasis by ultrasound. Patients who did not have cholecystectomy were managed with ursodiol for 6 months postoperatively. Results: 13 males (9.0%) and 131 females (91%) underwent RYGBP. The mean age was 43 years (SD 8.55), and mean BMI was 46 kg/m 2 (SD 6.5). The comorbidities of our patient population included diabetes (14%), hypertension (48%), gastroesophageal reflux disease (50%), dyslipidemia (35%), obstructive sleep apnea (31%), and musculoskeletal complaints (69%). 22 patients were diagnosed with cholelithiasis by ultrasonography preoperatively. 9 of these patients (41%) were symptomatic and underwent concurrent cholecystectomy and RYGBP. The remaining 13 patients (59%) had asymptomatic cholelithiasis preoperatively but did not undergo cholecystectomy at the time of surgery. Only one of these asymptomatic patients eventually developed symptoms necessitating cholecystectomy at up to 1 year follow-up. Conclusions: Our data suggest that it may not be absolutely indicated to perform prophylactic cholecystectomy at the time of RYGBP surgery for asymptomatic cholelithiasis. We believe that this phenomenon needs to be further studied in a randomized trial.

Urethane-protected tripeptides are synthesized in solution, without isolation or purification of intermediates, using urethane-protected N-carboxyanhydrides as coupling reagents and hydrogenation for removal of N-protection.

Esterification of 4-Alkoxybenzyl alcohol resin (Wang resin) is accomplished rapidly in high yield and with no detectable racemization when FMOC-histidine(N im -trityl)-NCA is the condensing reagent.

Two hydroxyl-containing resins (Wang and Rink resins) were esterified using 9-fluorenylmethyloxycarbonyl α-amino acid N-carboxyanhydrides (Fmoc-NCAs) efficiently with high levels of substitution. The solvent of choice for this procedure was toluene. With varying amounts of N-methylmorpholine (NMM) as the base and reaction time, the level of racemization was remarkably low. For maximum substitution efficiency and low racemization, the following conditions gave the best results: toluene 15 min and NMM (1.0 equiv.) for the Wang resin and toluene 1.5 h and NMM (1.0 equiv.) for the Rink resin.

The adipocyte hormone, leptin has been demonstrated to have profibrogenic actions in vitro and in animal models. However, no correlation was found between plasma leptin levels and fibrosis stage in humans. Thus, our aim was to study whether soluble leptin receptor (SLR) or free leptin index (FLI; calculated as the ratio of leptin to SLR), may correlate better with the features of metabolic syndrome and with the histological grade and stage of nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH). We studied a population (n = 104) of morbidly obese patients undergoing bariatric surgery. Data including BMI, type 2 diabetes mellitus, hypertension, and hyperlipidemia were obtained. Plasma fasting leptin and SLR, fasting glucose and insulin were measured, and homeostasis model of assessment insulin resistance (HOMA(IR)) index and FLI were calculated. All patients had intraoperative liver biopsies. Leptin levels correlated with the BMI. The multiple regression analysis indicated that increasing HOMA and decreasing FLI were predictors of steatosis in the liver (P < 0.0003). SLR levels were positively correlated with the presence of diabetes mellitus and the stage of fibrosis. In conclusion, increased SLR levels in morbidly obese patients with diabetes are correlated with the stage of liver fibrosis, and may reflect progressive liver disease.

Urethane-protected tripeptides are synthesized in solution, without isolation or purification of intermediates, using urethane-protected N-carboxyanhydrides as coupling reagents and hydrogenation for removal of N-protection.

Depression is prevalent among bariatric surgical patients, and previous studies have suggested a link between depression and quality of life. Our objective was to examine the relationship between depression and other co-morbidities of obesity at a university hospital in the United States.Data were collected from 1368 consecutive patients evaluated for bariatric surgery. The demographic and co-morbidity profiles of these patients were compared between the depressed and nondepressed individuals. Depression was defined as an Assessment of Obesity-Related Co-morbidities score ofor = 3, signifying that the patient required medical treatment for (score of 3) or had complications of (score of 4-5) depression.The prevalence of depression among these patients was 36%. The mean age of the patients with depression was older (44.3 + or - 9.4 versus 42.2 + or - 9.6, P.05), but the mean body mass index was similar. Depression was more prevalent among the female patients (37.4% versus 29.6%, P.05). Diabetes mellitus, hypertension, polycystic ovarian syndrome, idiopathic intracranial hypertension, and obesity hypoventilation syndrome occurred with similar frequency and severity in persons with and without depression. The analysis revealed a significantly greater prevalence and severity of dyslipidemia (P.05), gastroesophageal reflux disease (P.05), back pain (P.0001), joint pain (P.05), sleep apnea (P.01), stress incontinence (P.01), and hernia (P.05) among patients with depression. Overall, patients with depression had more co-morbidities per patient (5.46 versus 4.55) and a greater likelihood of severe or complicated co-morbidities (2.67 versus 1.89 per patient).This report has characterized a link between depression and other co-morbidities in bariatric surgical patients. This association was independent of the body mass index. Although a causal relationship could not yet be identified, our findings indicate that depression, in this patient population, is associated with a greater prevalence and increased severity of medical co-morbidities that express distinct physical symptoms.

This study was performed at a tertiary care university hospital. We hypothesized that weight loss before laparoscopic Roux-en-Y gastric bypass (LRYGB) is feasible, does not diminish the expected postoperative weight loss, and might enhance overall weight loss and maintenance.A population of 351 consecutive patients, who had undergone LRYGB, was divided into 4 groups depending on the percentage of body weight loss achieved before surgery (group 1, none or gain; group 2,5%; group 3, 5-10%; and group 4,10%). Data were collected regarding the demographics, body mass index (BMI) change, and excess weight loss and analyzed by analysis of variance and Fisher's exact test at the alpha = 0.05 level.All groups were demographically similar in age and were predominantly women. The maximal follow-up was 36 months. Groups 3 and 4 had significantly greater initial excess weight and BMI (P.05) but these became similar after the preoperative weight loss. Most patients (74%) were able to lose weight before surgery, with 36% losing5% body weight. Preoperative weight loss did not decrease the magnitude of the expected postoperative weight loss. Patients who lost weight preoperatively demonstrated more excess weight loss and BMI change (from their initial weight) that was sustained far into the postoperative period and reached statistical significance at several points (P.05).The results of this study have demonstrated that obese patients are capable of losing weight before LRYGB and that this weight loss does not negatively affect their expected postoperative weight loss. Furthermore, preoperative weight loss combined with LRYGB might result in better long-term excess weight loss and BMI change than surgery alone.

In Western society, morbid obesity has become an increasingly costly public health issue, in terms of the serious medical illnesses that are associated with this condition and the number of dollars that are spent on treatment. Currently, the number of overweight individuals in the world is estimated at 1.7 billion [1]. In the United States, the problem is at epidemic proportions. It has been estimated that up to two thirds of the population of the United States is overweight, and that half of these individuals can be classified as obese [1]. The spread of obesity has been well-documented since 1980, with significant increases occurring in the adolescent population and in individuals who are 18 to 29 years old [2–4]. Currently, 15 million individuals in the United States can be characterized as morbidly obese (Body Mass Index [BMI] O 35 kg/m 2 ) [5]. The condition seems to be particularly prevalent in populations with the least access to medical care, such as ethnic minorities, as well as in poorly-educated and impoverished populations; this stresses the potential for huge burdens on the health care system from this treatable condition [6].

Cyanoacetylene (I) is one of the major nitrogen-containing products of the action of an electric discharge on a mixture of nitrogen and methane. Hence we believe it may have been important in prebiotic chemistry. Cyanoacetylene undergoes hydrolysis in dilute alkali to give cyanoacetaldehyde which may then form the aldol dimer (IV). In the reaction of cyanoacetylene with cyanate, cytosine is formed mainly in a reaction sequence involving the stable intermediate cyanovinylurea. Cyanogen or cyanoformamide can replace cyanate in this synthesis. Since cytosine hydrolyzes quite readily to uracil, these reactions constitute a prebiotic synthesis of the pyrimidines. The concentrations of reactants required to give reasonable cytosine yields are quite low. However, the instability of cyanate and cyanoacetylene restricts severely the range of prebiotic environments in which such a synthesis could have occurred.

The purine nucleosides (adenosine, guanosine, inosine, xanthosine) are formed when the corresponding purine bases and D-ribose are heated together in the presence of certain salts and minerals. The salts remaining after the evaporation of seawater are particularly effective in these syntheses. The relevance of these reactions for prebiological evolution is discussed.

La reaction de Hofmann de Z-Asp(Bzl)-Ala-NH 2 conduit a l'amino-1' ethylamide-1 et ester benzyle-4 de Z-Asp-OH; l'acylation par des chlorures d'acyle (essentiellement cyclanecarbonyle) conduit a des dipeptides retro inverso correspondants aux acylamino-1' ethylamides-1 de l'acide aspartique

We have identified propiololdehyde as a product of the action of an electric discharge on mixtures of methane and water or methane, nitrogen, and water. The aldehyde reacts with cyanoacetaldehyde and ammonia (other "prebiological molecules") to yield nicotinonitrile. This substance can be hydrolyzed to nicotinamide and nicotinic acid.