Circular Dichroic Power of Chiral Spiro Aromatics. Theoretical Calculation of the CD and UV Spectra of 2,2\u27 -Spirobi [2Hbenzeindene ] Derivatives

The CD and UV spectra of (2S)-2,2\u27-spirobi[2H-benz[e]indene]- 1,1\u27(3H,3\u27H)-dione (2) and (IR,I\u27S,2S)-I,I\u27,3,3\u27-tetrahydro-2,2\u27-spirobi[ 2H -benz[e]indene]-I,I\u27 -diyl diacetate (3) were theoretical1y calculated by the application of the Jt-electron SCF-CI-DV MO method. The shape of component CD and UV bands was approximated by method (A) of the Gaussian distribution, or by method (B) employing the observed band shape of the UV spectra of model compounds. The calculated CD and UV curves were in good agreement with the observed ones. For compound 2, method (A), calcd CD, Aox! = 318.5 nm (As = +5.8), 250.0 (-63.7), 213.7 (+90.8); obsd. CD, J"" = 336.2 nm (1\u2711; = +11.9), 253.2 (-96.1), 214.0 (+ 1\u2712.1). For compound 3, method (A), calcd CD, J,e,! = 279.3 nm (As = +6.5), 224.2 (-590.2), 213.7 (+753.7); obsd. CD, J\u27e" = 285.0 nm (As = +4.4), 230.2 (-961.5), 221.6 (+567.1). The absolute stereostructures of chiral spiro aromatics 2 and have been thus established by the calculation. The mechanism of the widely spread and weak CD Cotton effects of diketone 2 has been also clarified by the calculation. The calculated CD and UV spectral curves of compound 3 obtained by the application of method (B) were in excellent agreement with the observed ones: calcd CD, Ae<t = 282.5 nm (As = +10.2), 231.5 (-1139.5), 221.2 (+474.0); obsd. CD, J,,,! = 285.0 nm (As = + 4.4), 230.2 (-961.5), 221.6 (+ 567.1)

Synergistic effect of combining theophylline and drugs that potentially elevate serum creatine kinase

An increase in the serum creatine kinase (CK) level is one of the side effects of theophylline;on rare occasions, the increase may be followed by rhabdomyolysis. Theophylline is often administered with drugs that potentially elevate the serum CK level (CK-elevating drugs) such as β-agonists and steroids. However, the effects of the combined treatment of theophylline and CK-elevating drugs have not been reported. We, therefore, retrospectively investigated the effects of combined treatment on the serum CK level, in391asthmatic outpatients. In this study, the number and type of the CK-elevating drugs administered, and the serum levels of CK and theophylline, were investigated. The patients were divided into four groups:the theophylline-treated and CK-elevating drug-treated group, the theophylline-treated and non-CK-elevating drug-treated group, the non-theophylline-treated and CK-elevating drug-treated group, and the non-theophylline-treated and non-CK-elevating drug-treated group. The theophylline-treated and CK-elevating drug-treated group showed about 100%higher serum CK levels (225IU/L) than any other group (102-124IU/L), and no increase in the serum theophylline level. This result indicates that there is a synergistic effect of theophylline and CK-elevating drugs on the serum CK level. The combined treatment of theophylline and CK-elevating drugs induces a synergistic increase in the serum CK level, indicating not pharmacokinetic but pharmacodynamic interactions with these drugs

Associations of COVID-19 symptoms with omicron subvariants BA.2 and BA.5, host status, and clinical outcomes in Japan: a registry-based observational study

Background Previous SARS-CoV-2 infection and vaccination, coupled with the rapid evolution of SARS-CoV-2 variants, have modified COVID-19 clinical manifestations. We aimed to characterise the clinical symptoms of COVID-19 individuals in omicron BA.2 and BA.5 Japanese pandemic periods to identify omicron and subvariant associations between symptoms, immune status, and clinical outcomes. Methods In this registry-based observational study, individuals registered in Sapporo’s web-based COVID-19 information system entered 12 pre-selected symptoms, days since symptom onset, vaccination history, SARS-CoV-2 infection history, and background. Eligibility criteria included symptomatic individuals who tested positive for SARS-CoV-2 (PCR or antigen test), and individuals who were not tested for SARS-CoV-2 but developed new symptoms after a household member tested positive for SARS-CoV-2. Symptom prevalence, variables associated with symptoms, and symptoms associated with progression to severe disease were analysed. Findings Data were collected and analysed between April 25 and Sept 25, 2022. For 157 861 omicron-infected symptomatic individuals, cough was the most common symptom (99 032 [62·7%] patients), followed by sore throat (95 838 [60·7%] patients), nasal discharge (69 968 [44·3%] patients), and fever (61 218 [38·8%] patients). Omicron BA.5 infection was associated with a higher prevalence of systemic symptoms than BA.2 in vaccinated and unvaccinated individuals (adjusted odds ratio [OR] for fever: 2·18 [95% CI 2·12–2·25]). Omicron breakthrough-infected individuals with three or more vaccinations or previous infection were less likely to exhibit systemic symptoms (fever 0·50 [0·49–0·51]), but more likely to exhibit upper respiratory symptoms (sore throat 1·33 [1·29–1·36]; nasal discharge 1·84 [1·80–1·89]). Infected older individuals (≥65 years) had lower odds for all symptoms. However, when symptoms were manifest, systemic symptoms were associated with increased odds for severe disease (dyspnoea 3·01 [1·84–4·91]; fever 2·93 [1·89–4·52]), whereas upper respiratory symptoms were associated with decreased odds (sore throat 0·38 [0·24–0·63]; nasal discharge 0·48 [0·28–0·81]). Interpretation Host immunological status, omicron subvariant, and age were associated with a spectrum of COVID-19 symptoms and outcomes. BA.5 produced a higher systemic symptom prevalence than BA.2. Vaccination and previous infection reduced systemic symptom prevalence and improved outcomes but increased upper respiratory tract symptom prevalence. Systemic, but not upper respiratory, symptoms in older people heralded severe disease. Our findings could serve as a practical guide to use COVID-19 symptoms to appropriately modify health-care strategies and predict clinical outcomes for older patients with omicron infections

Case report: Laparoscopic gastrojejunostomy for duodenal atresia with situs inversus and preduodenal portal vein: a report of two cases

Congenital duodenal atresia with situs inversus is occasionally accompanied by a preduodenal portal vein (PDPV), which is incidentally diagnosed during surgery. Duodenoduodenostomy is the most common and effective treatment. However, some patients require other anastomoses. Here, we present two cases of laparoscopic gastrojejunostomy for congenital duodenal atresia with situs inversus and PDPV and describe the reason for selecting gastrojejunostomy. The optimal surgical strategy is patient specific and should be determined based on the patient's general and physical condition

Laparoscopic restorative proctocolectomy with ileal-J-pouch anal canal anastomosis without diverting ileostomy for total colonic and extensive aganglionosis is safe and feasible with combined Lugol's iodine staining technique and indocyanine green fluorescence angiography

BackgroundWe present the surgical technique and outcomes of reduced-port laparoscopic restorative proctocolectomy with ileal-J-pouch anal canal anastomosis (IPACA) without diverting ileostomy for total colonic and extensive aganglionosis (TCA+).MethodsWe retrospectively reviewed TCA+ cases between 2014 and 2022. Preoperative ileostomy was performed when transanal bowel irrigation was ineffective. Radical surgery for TCA+ was performed at approximately 6 kg. The surgery was performed using laparoscopy through a multi-channel trocar with or without an additional 3-mm trocar and IPACA reconstruction with indocyanine green fluorescence angiography (ICG) to assess anastomotic perfusion and Lugol's iodine staining to visualize the surgical anal canal.ResultsTen patients with TCA+ were included. Ileostomy was performed in seven cases. The median operation time and blood loss were 274.5 min and 20 ml, respectively. No significant postoperative complications were found. All patients experienced frequent liquid stools and perianal excoriation in the early postoperative period, requiring anti-flatulence or codeine. The median follow-up period was 3.5 years. Three patients required irrigation management 1 year postoperatively, and the others defecated a median of 3.5 times per day. The median Kelly's clinical score was 5 in 5 patients aged &gt;4 years.ConclusionReduced-port surgery, combined with Lugol's iodine staining and ICG, was safe, feasible, and had cosmetically and clinically acceptable mid-term outcomes

Fetal exposure to bisphenol A as a risk factor for the development of childhood asthma: an animal model study

<p>Abstract</p> <p>Background</p> <p>The prevalence of asthma in industrialized countries has been increasing dramatically and asthma is now the most common chronic disease of children in the United States. The rapidity of the increase strongly suggests that changes in environmental exposures are the likely cause of this epidemic. Further, the early onset of allergic manifestations suggests that these exposures may act on the prenatal development of the immune system. We have focused on the potential effects of bisphenol A (BPA), a chemical pollutant with one of the largest productions, on the development of childhood asthma. We have reported that perinatal BPA exposure promotes the development of allergic asthma in a mouse model. The current study was designed to identify a critical period of BPA exposure and to begin elucidating the mechanisms for this susceptibility.</p> <p>Methods</p> <p>Female BALB/c mice received 10 micro g/ml BPA in their drinking water from one week before pregnancy until the end of the study. Some of the pups were transferred in the first 48 h of life from their BPA-loaded mother to an unexposed mother, or vice versa. Half of the pups were sensitized with a low dose of the experimental allergen ovalbumin (OVA), the rest received PBS as an unsensitized controls. On day 22, the pups were challenged by inhalations of ovalbumin or PBS followed by quantification of eosinophils in and hyperreactivity of their airways, major indicators of experimental asthma in this classical mouse model. Hepatic expression of two isoforms of UDP-glucuronosyltransferase (Ugt) was quantified by quantitative RT-PCR at various ages.</p> <p>Results</p> <p>Pups exposed to BPA in utero and through breast milk, or in utero only, displayed an asthma phenotype in response to their "suboptimal" allergic sensitization, whereas, pups only exposed to BPA postnatally from breast milk, did not. The expression of Ugt2b1, an isoform related to BPA clearance in rats, was not detectable in mouse fetuses and newborn pups, but increased by day 5 and approached adult levels by day 25.</p> <p>Conclusions</p> <p>Prenatal exposures that produce environmentally relevant burdens of BPA, followed by postnatal allergic sensitization and challenges, promote the development of experimental allergic asthma. Delayed expression of BPA-metabolizing enzymes may explain, at least in part, the enhanced fetal susceptibility to this common environmental contaminant.</p

Early-phase changes of extravascular lung water index as a prognostic indicator in acute respiratory distress syndrome patients

Background: The features of early-phase acute respiratory distress syndrome (ARDS) are leakage of fluid into the extravascular space and impairment of its reabsorption, resulting in extravascular lung water (EVLW) accumulation. The current study aimed to identify how the initial EVLW values and their change were associated with mortality. Methods: This was a post hoc analysis of the PiCCO Pulmonary Edema Study, a multicenter prospective cohort study that included 23 institutions. Single-indicator transpulmonary thermodilution-derived EVLW index (EVLWi) and conventional prognostic factors were prospectively collected over 48 h after enrollment. Associations between 28-day mortality and each variable including initial (on day 0), mean, maximum, and Δ (subtracting day 2 from day 0) EVLWi were evaluated. Results: We evaluated 192 ARDS patients (median age, 69 years (quartile, 24 years); Sequential Organ Failure Assessment (SOFA) score on admission, 10 (5); all-cause 28-day mortality, 31%). Although no significant differences were found in initial, mean, or maximum EVLWi, Δ-EVLWi was significantly higher (i.e., more reduction in EVLWi) in survivors than in non-survivors (3.0 vs. ?0.3 mL/kg, p = 0.006). Age, maximum, and Δ-SOFA scores and Δ-EVLW were the independent predictors for survival according to the Cox proportional hazard model. Patients with Δ-EVLWi > 2.8 had a significantly higher incidence of survival than those with Δ-EVLWi ? 2.8 (log-rank test, χ2 = 7.08, p = 0.008). Conclusions: Decrease in EVLWi during the first 48 h of ARDS may be associated with 28-day survival. Serial EVLWi measurements may be useful for understanding the pathophysiologic conditions in ARDS patients. A large multination confirmative trial is required

Magnetic field and energetic particle flux oscillations and high- frequency waves deep in the inner magnetosphere during substorm dipolarization: ERG observations

Using Exploration of energization and Radiation in Geospace (ERG or Arase) spacecraft data, we studied low-frequency magnetic field and energetic particle flux oscillations and high-frequency waves deep in the inner magnetosphere at a radial distance of ~4–5 during substorm dipolarization. The magnetic field oscillated alternately between dipole-like and taillike configuration at a period of 1 min during dipolarization. When the magnetic field was dipole-like, the parallel magnetic component of the Pi2 waves was at trough. Both energetic ion and electron fluxes with a few to tens of kiloelectronvolts enhanced out of phase, indicating that magnetosonic waves were in slow mode. Field-aligned currents also oscillated. These observations are consistent with signatures of ballooning instability. In addition, we found that broadband waves from the Pi1 range to above the electron cyclotron frequency tended to appear intermittently in the central plasma sheet near dipole-like configuration

Association of variations in HLA class II and other loci with susceptibility to EGFR-mutated lung adenocarcinoma

Lung adenocarcinoma driven by somatic EGFR mutations is more prevalent in East Asians (30-50%) than in European/Americans (10-20%). Here we investigate genetic factors underlying the risk of this disease by conducting a genome-wide association study, followed by two validation studies, in 3,173 Japanese patients with EGFR mutation-positive lung adenocarcinoma and 15,158 controls. Four loci, 5p15.33 (TERT), 6p21.3 (BTNL2), 3q28 (TP63) and 17q24.2 (BPTF), previously shown to be strongly associated with overall lung adenocarcinoma risk in East Asians, were re-discovered as loci associated with a higher susceptibility to EGFR mutation-positive lung adenocarcinoma. In addition, two additional loci, HLA class II at 6p21.32 (rs2179920; P =5.1 × 10(-17), per-allele OR=1.36) and 6p21.1 (FOXP4) (rs2495239; P=3.9 × 10(-9), per-allele OR=1.19) were newly identified as loci associated with EGFR mutation-positive lung adenocarcinoma. This study indicates that multiple genetic factors underlie the risk of lung adenocarcinomas with EGFR mutations