[FTIR Noise Calibration in Quantitative Estimate of VOCs Concentration].
The Classical Least Square regression (CLS) is one of the most popular regression methods in FTIR quantitative estimation. However, CLS is the best unbiased estimator only under the assumption that error (noise) in the spectrum has equal variance, which usually is not the case in FTIR. This paper proposed a noise calibration method for FTIR spectrum analysis. Based on measured variance of noise in the FTIR spectrum by computer, the Weighted Least Square regression (WLS) method is used in quantitative estimation. The experiment results showed that the WLS performs much better than CLS in quantitative estimation of VOCs pollution.


Changes in PMN leukocyte migration activity and complement C3d levels in RA patients with high disease activity during steroid treatment.
We have investigated chemotaxis of polymorphonuclear granulocytes (PMN) from 7 well characterized RA patients with intense disease activity, before and after steroid treatment. Increased spontaneous and directed granulocyte migration was observed in 6 out of 7 patients before steroid treatment. In 5 patients these parameters were reduced after treatment. In contrast to this, decreased chemotaxis of polymorphonuclear granulocytes (PMN) from patients with Rheumatoid Arthritis (RA), have been reported earlier. This has been suggested as a partial explanation of the increased morbidity of these patients. Plasma levels of Complement C3d were initially increased in all patients and were slightly reduced following treatment. PMN migration in highly active RA cases is increased and responds markedly to steroid treatment, in contrast to the complement activation. The mainly unaffected, increased levels of plasma C3d might, in part, explain the early recurrence of symptoms often seen when steroid medication is withdrawn. Our results contrast with earlier findings and need to be confirmed in further studies.


The Russian registry of primary hyperparathyroidism, latest update.
Until recently no major epidemiological research of primary hyperparathyroidism (PHPT) has been conducted in the Russian Federation, this led to the creation of the Russian online registry. The objective of this study is to estimate the clinical and biochemical profile, classical and non-classical complications, surgical intervention and medical therapy of the patients with different forms of PHPT in the Russian Federation. The cross-sectional, observational, continuous study was conducted at the Endocrinology Research Centre (Moscow). The present study explored retrospective data from 6003 patients submitted to the Registry between 12.12.2016 and 25.10.2022 from 81 regions of the Russian Federation (http://pgpt.clin-reg.ru/). The median age was 59 [60; 66] years with a female:male ratio of 11.7:1. Symptomatic PHPT was observed in 74.3% while asymptomatic form - only in 25.7% of cases. Bone pathology was the predominant clinical manifestation in 62.5% of cases (n=2293), mostly in combination with visceral complications 45.7% (n=1676). The majority of patients (63.3%) had combined visceral disorders including kidney damage in 51.8% and gastroduodenal erosions/ulcers in 32.3% of patients. Symptomatic patients were older (60 [53; 67] vs. 54 [45; 62] years, p<0.001) and had more severe biochemical alterations of calcium-phosphorus metabolism. Cardiovascular disease (СVD) was recorded in 48% of patients, among them the most frequent was arterial hypertension (up to 93.9%). A genetic test was conducted in 183 cases (suspicious for hereditary PHPT) revealing the mutations in MEN1, CDC73, RET genes in 107, 6 and 2 cases, respectively. Surgery was performed in 53.4% of patients with remission achievement in 87%, the relapse/persistence were recorded in 13% of cases. Histological examination revealed carcinoma in 4%, atypical adenoma in 2%, adenoma in 84% and hyperplasia in 11% of cases. Drug therapy was prescribed in 54.0% of cases, most often cholecalciferol. The detection rate of PHPT has increased in the Russian Federation in recent years. This increase is associated with the start of online registration. However, the majority of patients remain symptomatic with significant alterations of phosphorus-calcium metabolism that indicates delayed diagnosis and requires further modifications of medical care.


One-dose immunization against paralytic poliomyelitis using a noninfectious vaccine.
Recent advances in production and standardization of noninfectious poliovirus vaccine now make it feasible to induce durable immunity against paralytic poliomyelitis with one dose of a suitably standardized vaccine. A single dose of a vaccine containing 40, 8, and 32 D-antigen units of type 1, 2, and 3, respectively, administered to six-month-old infants, was observed to induce antibody levels of greater than or equal to 1:4 in greater than 90% and immunologic memory in all. Since protection against paralysis is associated with the presence of either type-specific serum antibody or type-specific immunologic memory, and since immunologic memory once induced is irreversible, then lifelong immunity to paralytic poliomyelitis can be induced with a single dose of a suitably standardized vaccine administered at five to seven months of age. In areas of the world where exposure to poliovirus can occur before this age, vaccine should be administered earlier. Until the influence of age and/or maternal antibody has been further studied, infants immunized before the age of six months should receive a second dose after six months of age.


A Situation Assessment of Community Health Workers' Preparedness in Supporting Health System Response to COVID-19 in Kenya, Senegal, and Uganda.
Coronavirus disease (COVID-19) caused socio-economic disruptions across the globe. The pandemic disrupted the health system (HS) calling for reengineering in response to high infection rates, deaths, and resultant containment measures. To deal with COVID-19 and promote resilience, community health workers (CHWs) were engaged across countries. Assess the preparedness of CHWs in supporting health system response in prevention and management of COVID-19 in Kenya, Senegal, and Uganda. A mixed methods design study involving national and subnational jurisdictions in the 3 countries. Key informant interviews were conducted with policy actors (16) and health care workers (24) while in-depth interviews involved CHWs (14) and community members (312) subjected to survey interviews. Most (>50%) households survived on <USD 100/month during COVID-19 announced in March 2020 through national TV (57%), FM (42%), and radio station (27%). Community members interactions with CHWs increased during the pandemic through home visits as health educators, basic counseling providers and distributors of pandemic information tools, personal protective equipments, and social support commodities. The CHWs faced challenges during pandemic prevention and management including lack of: protective gear, salary, refresher courses, and identification tools; limited supervision and training; hostile reception during home visits; misconception and politicking about the pandemic. To effectively support prevention and manage of COVID-19, priority needs for CHWs were identified namely: provision of resources, protective gear, transport reimbursement, stipends, identification cards, and tools for recording and reporting; empowerment with adequate skills, trainings on provision of psychosocial support, first aid, and sensitization on policies. COVID-19 linked disruptions to optimal functioning of HS necessitated engagement of CHWs in the pandemic prevention and management. Findings underscore the important role CHWs play in supporting HS during crisis like COVID-19 to mitigate disruptions and stabilize the system for effective response. The CHWs can improve resilience of social and HS during unplanned disruptions for optimal functioning and attainment of universal health care. Policy makers should develop structured mechanisms for engaging CHWs while committing resources to address challenges that affect seamless synergy between health and CHWs Systems.


Antibody responses of raccoons naturally exposed to influenza A virus.
An investigation was performed to describe the responses of naturally acquired antibodies to influenza A virus in raccoons (Procyon lotor) over time. Seven wild raccoons, some of which had been exposed to multiple subtypes of influenza A virus, were held in captivity for 279 days, and serum samples were collected on 10 occasions during this interval. Serum samples from 9 of 10 bleeding occasions were tested using an epitope-blocking enzyme-linked immunosorbent assay for the presence of antibodies to influenza A virus. Although titer declines were noted in most animals over time, all animals maintained detectable antibodies for the duration of the study. These data indicate that naturally acquired antibodies to influenza A virus can remain detectable in raccoons for many months, with the actual duration presumably being much longer because all animals had been exposed to influenza A virus before this study commenced. This information is important to surveillance programs because the duration of naturally acquired antibodies to influenza A virus in wildlife populations is largely unknown.


Robot-assisted pyeloplasty for ureteropelvic junction obstruction: initial experience with the novel avatera system.
This pilot study was designed to interpret the technically specific features of the avatera robotic system and present our initial experience with this novel platform in robot-assisted pyeloplasty (RAP). A single-center prospective study was conducted including all patients who underwent RAP with the avatera robotic system from June 2022 to October 2022 in our Department. Transperitoneal robot-assisted dismembered pyeloplasty was performed in all cases. The trocar placement and the surgical technique were similar in all patients. The successful completion of the procedures, operation time (including draping, docking and console time), decrease in hemoglobin postoperatively, and presence of any complications were the study's primary endpoints. In total, nine patients underwent RAP using the avatera system. All procedures were successfully completed. The draping of the robotic unit was completed in a median time of 10 min (range 7-15), while the median docking time was 17 min (range 10-24). The median console time was 88 min (range 78-116) and no complications were noticed. The median hemoglobin drop was calculated to 0.7 g/dL (range 0.4-1). During the mean follow-up of 9.33 ± 2.78 months, no late postoperative complications were noticed. The early outcomes of the use of the novel avatera system in RAP are presented. All operations were successfully completed with safety and efficacy, without complications or significant blood loss.


Insights on resistance to reverse transcriptase: the different patterns of interaction of the nucleoside reverse transcriptase inhibitors in the deoxyribonucleotide triphosphate binding site relative to the normal substrate.
It is presently known that the long-term failure in the treatment of AIDS with the currently available nucleotide reverse transcriptase inhibitors (NRTIs) is related to the development of resistance by reverse transcriptase (RT) at the binding or incorporation level or both, or subsequent to the nucleotide incorporation (excision). To achieve greater insight on the differential interactions of two NRTIs that are mainly discriminated by different mechanisms, 2',3'-didehydro-2',3'-dideoxythymidine-5'-triphosphate (d4TTP, that is, phosphorylated stavudine) and 2',3'-dideoxycytidine-5'-triphosphate (ddCTP, that is, phosphorylated zalcitabine), with the primer/template (p/t) and with the N binding site of reverse transcriptase (RT) in relation to the normal substrate (dNTP), we have conducted a series of molecular dynamics (MD) simulations. We propose that the different resistance profiles arise from the different conformations adopted by the inhibitors at the N site. d4TTP adopts an ideal conformation for catalysis because it forms an ion-dipole intramolecular interaction with the beta-phosphate oxygen of the triphosphate, as does the normal substrate. In ddCTP, the lack of this essential interaction results in a different, noncatalytic conformation.


Negative Conversion of Progesterone Receptor Status after Primary Systemic Therapy Is Associated with Poor Clinical Outcome in Patients with Breast Cancer.
Alteration of biomarker status after primary systemic therapy (PST) is occasionally found in breast cancer. This study was conducted to clarify the clinical implications of change of biomarker status in breast cancer patients treated with PST. The pre-chemotherapeutic biopsy and post-chemotherapeutic resection specimens of 442 breast cancer patients who had residual disease after PST were included in this study. The association between changes of biomarker status after PST and clinicopathologic features of tumors, and survival of the patients, were analyzed. Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) status changed after PST in 18 (4.1%), 80 (18.1%), and 15 (3.4%) patients,respectively. ER and PR mainly underwent positive to negative conversion,whereas HER2 status underwent negative to positive conversion. Negative conversion of ER and PR status after PST was associated with reduced disease-free survival. Moreover, a decline in the Allred score for PR in post-PST specimens was significantly associated with poor clinical outcome of the patients. HER2 change did not have prognostic significance. In multivariate analyses, negative PR status after PST was found to be an independent adverse prognostic factor in the whole patient group, in the adjuvant endocrine therapy-treated subgroup, and also in pre-PST PR positive subgroup. ER and HER2 status changed little after PST, whereas PR status changed significantly. In particular, negative conversion of PR status was revealed as a poor prognostic indicator, suggesting that re-evaluation of basic biomarkers is mandatory in breast cancer after PST for proper management and prognostication of patients.


The epidemiology of St. Louis encephalitis in Dallas, Texas, 1966.
An epidemic of St. Louis encephalitis (SLE) occurred in Dallas, Texas, in the summer of 1966. A total of 545 suspected cases within Dallas city and county were reported, of which 145 were laboratory-confirmed as SLE virus infection. The greatest concentration of cases occurred in lower socioeconomic areas of the central part of the city in black populations. The attack rate and mortality rate increased markedly with age. The overall attack rate was 15.2 per 100,000, with a case fatality rate of 9.7%. During the course of the epidemic, most of the county was sprayed aerially with an ultra-low volume (ULV), high-concentration malathion mist. The effects of this treatment cannot be adequately assessed from the human epidemiologic aspect alone, but the spraying clearly reduced the number and infection rate of the vector mosquitoes.


Fibrolipomatous hamartomas not only on the soles.
Fibrolipomatous hamartomas are asymptomatic, subcutaneous lumps usually located on the infant's heels. There is wide heterogeneity in the naming of and management of this condition. Ultrasound examination permits a clear distinction from other disorders. We report herein a case of palmoplantar fibrolipomatous hamartomas.


Diagnosis and endoscopic resection of early gastric cancer.
The overall prognosis of gastric cancer is generally poor due to late presentation and diagnosis. When detected early, the prognosis for gastric cancer is excellent, and curative endoscopic resection may be possible, without the need for surgery. Careful endoscopic examination is important so as to avoid missed lesions. Endoscopic resection, especially with the technique of endoscopic submucosal dissection, is a viable alternative to surgery for the curative treatment of early gastric cancer, with similar long term results, as long as strict inclusion criteria are adhered to.


Phosphoinositide 3-kinase-dependent inhibition of dendritic cell interleukin-12 production by Giardia lamblia.
Dendritic cell interactions with pathogenic microbes initiate and direct the development of subsequent adaptive responses. The protozoan pathogen Giardia lamblia infects the mammalian small intestine, leading to nutrient malabsorption and diarrhea but rarely causing inflammation. In order to begin to understand how the innate immune system responds to this parasite and shapes the eventual adaptive response, we examined the interaction between parasites and murine bone marrow-derived dendritic cells (DCs). DCs incubated with live parasites or parasite extracts displayed enhanced levels of CD40. The expression of CD80 and CD86 also increased, but less than was seen with lipopolysaccharide-activated DCs. Small amounts of interleukin-6 (IL-6) and tumor necrosis factor alpha were secreted by these DCs, whereas no IL-10 or IL-12 could be detected. Coincubation of DCs with parasite extracts along with known Toll-like receptor (TLR) ligands resulted in enhanced secretion of IL-10 and reduced secretion of IL-12. The levels of major histocompatibility complex class II, CD80, and CD86 were also reduced compared to DCs stimulated with TLR ligands alone. Finally, studies with an extracellular signal-regulated kinase 1/2 pathway inhibitor, a phosphoinositide 3-kinase (PI3K) inhibitor, and anti-IL-10 receptor antibody revealed that the PI3K pathway is the dominant mechanism of inhibition in DCs incubated with both lipopolysaccharide and Giardia. These data suggest that this parasite actively interferes with host innate immunity, resulting in an immune response able to control the infection but devoid of strong inflammatory signals.


[Doppler color ultrasonography of maternal-fetal circulation in HELLP syndrome].
The authors investigated the blood flow velocity waveforms of the mothers uterine arteries and fetal middle cerebral, renal and umbilical arteries in cases of HELLP syndrome by color Doppler ultrasonography. The elevated velocimetry indices in the uterine and umbilical arteries were the result of utero-placental and fetoplacental vascular lesions with resultant decrease in blood flow. These laid to the centralization of fetal circulation with increased blood flow in cerebral and decreased in renal arteries. All women were delivered small for gestational age infants.


Interpreting Cis-Regulatory Interactions from Large-Scale Deep Neural Networks for Genomics.
The rise of large-scale, sequence-based deep neural networks (DNNs) for predicting gene expression has introduced challenges in their evaluation and interpretation. Current evaluations align DNN predictions with experimental perturbation assays, offering a limited perspective of the DNN's capabilities within the studied loci. Moreover, existing model explainability tools mainly focus on motif analysis, which becomes complex to interpret for longer sequences. Here we introduce CREME, an in silico perturbation toolkit that interrogates large-scale DNNs to uncover rules of gene regulation that it has learned. Using CREME, we investigate Enformer, a prominent DNN in gene expression prediction, revealing cis-regulatory elements (CREs) that directly enhance or silence target genes. We explore the relationship between CRE distance from transcription start sites and gene expression, as well as the intricate complexity of higher-order CRE interactions. This work advances the ability to translate the powerful predictions of large-scale DNNs to study open questions in gene regulation.


Thienylsilane-modified indium tin oxide as an anodic interface in polymer/fullerene solar cells.
The generation and characterization of a robust thienylsilane molecular layer on indium tin oxide substrates was investigated. The molecular layer was found to reduce the oxidation potential required for the electrochemical polymerization of 3,4-ethylenedioxythiophene. The resulting electrochemically prepared poly(3,4-ethylenedioxythiophene):poly(p-styrenesulfonate) (ePEDOT:PSS) films were found to be more uniform in coverage with lower roughness and higher conductivity than analogous films fabricated with bare ITO. A relative improvement in the efficiency of 2,5-diyl-poly(3-hexylthiophene) (P3HT)/[6,6]-phenyl-C(61)-butyric acid methyl ester (PCBM) bulk heterojunction solar cells was observed when devices were formed on thienylsilane-modified ITO electrodes, rather than unmodified ITO control electrodes.


[Current status of clinical trials of HPV therapeutic vaccines].
Cervical cancer mainly caused by human papillomavirus (HPV) infection has become a public health issue, which seriously threatens women 's health. To prevent HPV infection, the currently used prophylactic vaccines mainly induce a humoral immune response in the host, thereby generating neutralizing antibodies. In contrast, the design goal of therapeutic HPV vaccines is to induce a cell-mediated immune response in the host, primarily driven by Th1 cells, aiming to clear existing viral infections and slow down or inhibit tumor progression. Currently, several therapeutic HPV vaccines based on different mechanisms and techniques have entered clinical trials. This review will summarize the progress of these clinical trials, providing reference for the research and development of therapeutic HPV vaccines.


Acoustic neuroma identified after electroconvulsive therapy in a patient with recurrent major depression and undifferentiated somatoform disorder.
Little is known about the safety of electroconvulsive therapy (ECT) in patients with brain tumors, especially in patients with acoustic neuroma, which is difficult to diagnose early. For patients with somatoform disorder, physicians may alter the sensitivity to the somatic complaints, making it even more difficult to make an early diagnosis of "silent" brain tumors. This report describes a rare case involving treatment of refractory major depression and somatoform disorder that developed into increased intracranial pressure after ECT, possibly due to an undiagnosed acoustic neuroma. It is suggested that for patients with refractory major depression with somatoform disorders, the threshold of suspicion for silent tumors should be lowered and pre-ECT brain imaging study should be performed, specifically when the pattern of symptoms of the central nervous system-related somatoform syndrome changes.


Ultrasonographic measurement of fetal nasal bone length in the second trimester in Korean population.
To establish the reference range of fetal nasal bone length (NBL) in the second trimester in the Korean population and to determine its clinical value in screening for trisomy 21. A total of 3019 consecutive fetuses at 16-28 weeks of gestation underwent ultrasonographic measurement of NBL at Asan Medical Center from October 2003 to August 2005. Fetal profile was successfully examined in 95.6% (2885/3019) of the fetuses. NBL increased linearly with advanced gestation (R(2) = 0.4337, p < 0.001). During this period, 23 fetuses with chromosomal abnormalities (including nine with trisomy 21, two with trisomy 18, and three with Turner syndrome) were detected. In trisomy 21, hypoplastic nasal bone (<2.5th percentile) was seen in 3/9 fetuses, and the NBL of one fetus was between the 2.5th and 5th percentile. Hypoplastic nasal bone was seen in 3.1% (89/2833) of fetuses with normal chromosomal or postnatal examination findings. We present the normal range of NBL in the second trimester in the Korean population and also their linear relationship with gestational age (GA). The NBL appears to be shorter in Korean fetuses than Caucasian and Chinese fetuses. This indicates that the normal range would vary between races and that a relative percentile is a more reliable screening criterion than an absolute value.


Zinc and Macular Degeneration.
A zinc metalloenzyme of the lysosomal apparatus of the retinal pigment epithelium of humans has been shown to lose activity with age. Zinc supplements may retard the rate of loss of visual acuity in subjects with age-related macular degeneration.


Ovarian reserve tests for predicting fertility outcomes for assisted reproductive technology: the International Systematic Collaboration of Ovarian Reserve Evaluation protocol for a systematic review of ovarian reserve test accuracy.
The presence of a wide range of tests of ovarian reserve suggests that no single test provides a sufficiently accurate result. Many tests are used without reference to an evidence base. So far, individual studies conducted on these tests are too small to give precise estimates of prognostic accuracy. To systematically assess the accuracy of the available tests of ovarian reserve in terms of prediction of fertility outcomes. The search will be conducted using the name of the respective index test being studied (as listed on the MESH database), if more than 2000 citations are listed, 'ovary' and or 'ovarian', 'fertility' and or 'reserve' will be combined with the original search term as required. Studies of the accuracy of tests of ovarian reserve will be obtained without language restrictions from 1980 to 2005 using the following electronic databases and Ovid software: MEDLINE, EMBASE, PUBmed, Biological extracts, Pascal, Cochrane Library (CDSR, DARE, CCTR, HTA), Best Evidence databases, SCISEARCH, Conference Proceedings (ISI Proceedings, Healthstar, Current Contents, Science Citation Index, Cancerlit and Econlit and NHS Economic Evaluation database. The National Research Register, the Medical Research Council's Clinical Trials Register, MEDION, DARE, and the US Clinical Trials register. Studies will be selected if accuracy of tests are compared with a reference standard and include data that can be abstracted into a two-by-two table to calculate sensitivity and specificity. The studies to be included in this review will examine one of the following index 'tests' within a study population of women undergoing assisted reproductive technology: * Clinical variables--age, history of cancelled cycles. * Basal blood tests--follicle-stimulating hormone (FSH), lutenising hormone (LH), FSH:LH ratios, estradiol (E(2)), inhibin A and B, progesterone (P(4)), P(4):E(2) ratios, antimullerian hormone, testosterone, vascular endothelial growth factor, insulin-like growth factor-1:insulin-like growth factor binding protein-1 ratios. * Dynamic tests--clomiphene citrate challenge test, gonadotropin analogue stimulating test, exogenous FSH ovarian reserve test. * Ultrasound tests-antral follicle count, ovarian volume, ovarian stromal peak systolic velocity, including waveform and pulsatility index, ovarian follicular vascularity. * Histology--ovarian biopsy. Data collection and analysis Two independent reviewers will perform quality assessment and data extraction. Prognostic accuracy will be determined by calculating positive and negative likelihood ratios for the following outcomes or reference standards: live birth, ongoing pregnancy, clinical pregnancy, biochemical pregnancy, embryos available for transfer, eggs obtained at oocyte retrieval, cycles cancelled prior to oocyte retrieval. Main results and conclusions N/A.


Mechanisms of pancreatic beta-cell destruction in type I diabetes.
The pathogenetic mechanisms leading to beta-cell destruction and insulin-dependent diabetes mellitus (IDDM) are major histocompatibility complex (MHC) nonrestricted and are MHC associated and beta-cell specific. The macrophage peptide hormone interleukin 1 (IL-1) may be the primary MHC-nonrestricted beta-cell-destructive molecule. Beta-Cell death most likely results from free radical induction by IL-1. Thus, islet cell-specific antibodies and cytotoxic T-lymphocytes are secondary in importance and time. The potentiation of IL-1 effects on beta-cells by tumor necrosis factor alpha (TNF), another macrophage hormone controlled by a gene in the HLA region on chromosome 6, may account for the MHC association of IDDM. In the experimental model of IDDM etiopathogenesis described, release of beta-cell antigen, processed and presented by macrophages to helper T-lymphocytes, initiates a self-perpetuating and self-limiting circuit of cytokine production of which IL-1 is beta-cell cytotoxic. As postulated, the IL-1 effect is potentiated by TNF, whereas IL-1 and/or TNF production is controlled in a quantitative way by HLA-D genes.


Haemolysis complicating acute viral hepatitis in patients with normal or deficient glucose-6-phosphate dehydrogenase activity.
Haemolytic anaemia as a complication of acute hepatitis has been reported in up to 23% of patients. However, the incidence may rise up to 70-87% in patients who have glucose-6-phosphate dehydrogenase (G6PD) deficiency. Massive intravascular haemolysis with renal failure, hepatic encephalopathy and even death have been reported. In our retrospective study of patients with acute viral hepatitis, the overall incidence of acute haemolysis was 4% (17/434). Only 53% (9/17) of them had G6PD deficiency. Patients with acute haemolysis had a significantly higher peak bilirubin level and required more prolonged hospitalization. Since hepatitis A virus vaccination, unlike hepatitis B virus vaccination, is not yet recommended for routine immunization, we suggest subjects who are G6PD-deficient should be vaccinated against hepatitis A. In endemic areas of hepatitis A virus infection, universal immunization remains the definitive answer.


Detection of HeLa cell contamination--presence of human papillomavirus 18 DNA as HeLa marker in JTC-3, OG and OE cell lines.
There are warnings of the contamination of cell cultures with HeLa cells in many laboratories in the world. The cell lines JTC-3, OG and OE that were established in Okayama in 1959, 1969 and 1971, respectively, were examined for human papillomavirus (HPV) 18 DNA by Southern blot hybridization. The HPV 18 DNA detected in these three cell lines showed hybridization patterns characteristic of the HPV 18 DNA in the HeLa cell line established in 1951. Southern hybridization patterns of HPV 18 DNA in the cellular DNA of the C4-II cervical cancer cell line that was established in the USA in 1962 was different from that of HeLa cells. These results suggest that the JTC-3, OG and OE cell lines have been contaminated by HeLa cells.


Musculoskeletal attenuation of impact shock in response to knee angle manipulation.
Shock waves resulting from the foot-ground impact are attenuated by biological tissues within the body. It has been suggested that the primary site for shock attenuation is the knee joint. The purpose of this study was to determine if knee flexion affects the filtering characteristics of the musculoskeletal system in response to impacts. Impacts were delivered to 10 participants during inline skating on a treadmill at 2.0 m/s. Four knee angle conditions (0, 10, 20, and 30 degrees) were investigated using real-time visual feedback of motion capture data. Shock attenuation between the leg and head was determined using accelerometry. The cutoff frequency of the body was determined by progressive filtering of the leg acceleration until differences between head acceleration and filtered leg acceleration were minimized. A nonlinear increase in shock attenuation (p < .001) and a nonlinear decrease in the cutoff frequency of the body (p < .001) were observed as the knee became more flexed. These results suggest that the knee joint acts as a low-pass filter allowing greater shock attenuation with increased knee flexion. Flexing the knee may shift the shock-attenuating responsibilities away from passive biological tissue toward active muscular contraction.


Is Gorlin-Chaudhry-Moss syndrome associated with aortopathy?
Gorlin-Chaudhry-Moss syndrome (GCMS) is a rare disorder consisting of craniofacial dysostosis, hypertrichosis, underdeveloped genitalia, and ocular and dental anomalies. Recently, GCMS has been reclassified together with Fontaine syndrome as Fontaine progeroid syndrome (FPS), after a common genetic basis was found. It was previously thought that GCMS/FPS was not associated with aortopathy, but in recent years 3 patients with aortic disease have been described. We describe the fourth case, who is the oldest patient with GCMS/FPS reported in the medical literature: a 45-year-old patient who presented with acute aortic dissection. We therefore recommend screening patients previously diagnosed with GCMS/FPS for aortic pathology to aid early detection and avoid patient presentation in an acute setting.


Novel use of flow diversion for the treatment of aneurysms associated with arteriovenous malformations.
The use of flow-diverting stents for intracranial aneurysms has become more prevalent, and flow diverters are now routinely used beyond their initial scope of approval at the proximal internal carotid artery. Although flow diversion for the treatment of cerebral aneurysms is becoming more commonplace, there have been no reports of its use to treat flow-related cerebral aneurysms associated with arteriovenous malformations (AVMs). The authors report the cases of 2 patients whose AVM-associated aneurysms were managed with flow diversion. A 40-year-old woman presented with a history of headaches that led to the identification of an unruptured Spetzler-Martin Grade V, right parietooccipital AVM associated with 3 aneurysms of the ipsilateral internal carotid artery. Initial attempts at balloon-assisted coil embolization of the aneurysms were unsuccessful. The patient underwent placement of a flow-diverting stent across the diseased vessel; a 6-month follow-up angiogram demonstrated complete occlusion of the aneurysms. In the second case, a 57-year-old man presented with new-onset seizures, and an unruptured Spetzler-Martin Grade V, right frontal AVM associated with an irregular, wide-necked anterior communicating artery aneurysm was identified. The patient underwent placement of a flow-diverting stent, and complete occlusion of the aneurysm was observed on a 7-month follow-up angiogram. These 2 cases illustrate the potential for use of flow diversion as a treatment strategy for feeding artery aneurysms associated with AVMs. Because of the need for dual antiplatelet medications after flow diversion in this patient population, however, this strategy should be used judiciously.


An efficient and high-order convergence mode solver for solving graphene and phosphorene-based waveguides.
Guided modes of two-dimensional (2D) material-based plasmonic waveguides are applied in photonic devices because of their strong light-matter interaction within atomically thin layers and unique optical characteristics. Numerical simulations and experiments both play crucial roles in exploring unexpected phenomena at the sub-nanoscale of these materials. To efficiently and precisely compute mode characteristics, a multi-domain pseudospectral method (MPM) exhibiting high accuracy and fast convergence is proposed to study 2D material-based plasmonic waveguides in this study to alleviate the highly computational load of the widely used finite difference time domain or finite element method, as they demand extremely fine grid points or meshes around 2D materials. Models of graphene- and black phosphorus-based waveguides demonstrate that the MPM preserves exponential accuracy at relatively low computational cost, compared with the analytical characteristic equation and FEM, respectively. We believe that the proposed MPM offers a highly efficient and accurate approach to the study of 2D material-based photonics devices.


The differential role of CR3 (CD11b/CD18) and CR4 (CD11c/CD18) in the adherence, migration and podosome formation of human macrophages and dendritic cells under inflammatory conditions.
CR3 and CR4, the leukocyte specific β2-integrins, involved in cellular adherence, migration and phagocytosis, are often assumed to have similar functions. Previously however, we proved that under physiological conditions CR4 is dominant in the adhesion to fibrinogen of human monocyte-derived macrophages (MDMs) and dendritic cells (MDDCs). Here, using inflammatory conditions, we provide further evidence that the expression and function of CR3 and CR4 are not identical in these cell types. We found that LPS treatment changes their expression differently on MDMs and MDDCs, suggesting a cell type specific regulation. Using mAb24, specific for the high affinity conformation of CD18, we proved that the activation and recycling of β2-integrins is significantly enhanced upon LPS treatment. Adherence to fibrinogen was assessed by two fundamentally different approaches: a classical adhesion assay and a computer-controlled micropipette, capable of measuring adhesion strength. While both receptors participated in adhesion, we demonstrated that CR4 exerts a dominant role in the strong attachment of MDDCs. Studying the formation of podosomes we found that MDMs retain podosome formation after LPS activation, whereas MDDCs lose this ability, resulting in a significantly reduced adhesion force and an altered cellular distribution of CR3 and CR4. Our results suggest that inflammatory conditions reshape differentially the expression and role of CR3 and CR4 in macrophages and dendritic cells.


Akt inhibition promotes ABCA1-mediated cholesterol efflux to ApoA-I through suppressing mTORC1.
ATP-binding cassette transporter A1 (ABCA1) plays an essential role in mediating cholesterol efflux to apolipoprotein A-I (apoA-I), a major housekeeping mechanism for cellular cholesterol homeostasis. After initial engagement with ABCA1, apoA-I directly interacts with the plasma membrane to acquire cholesterol. This apoA-I lipidation process is also known to require cellular signaling processes, presumably to support cholesterol trafficking to the plasma membrane. We report here that one of major signaling pathways in mammalian cells, Akt, is also involved. In several cell models that express ABCA1 including macrophages, pancreatic beta cells and hepatocytes, inhibition of Akt increases cholesterol efflux to apoA-I. Importantly, Akt inhibition has little effect on cells expressing non-functional mutant of ABCA1, implicating a specific role of Akt in ABCA1 function. Furthermore, we provide evidence that mTORC1, a major downstream target of Akt, is also a negative regulator of cholesterol efflux. In cells where mTORC1 is constitutively activated due to tuberous sclerosis complex 2 deletion, cholesterol efflux to apoA-I is no longer sensitive to Akt activity. This suggests that Akt suppresses cholesterol efflux through mTORC1 activation. Indeed, inhibition of mTORC1 by rapamycin or Torin-1 promotes cholesterol efflux. On the other hand, autophagy, one of the major pathways of cholesterol trafficking, is increased upon Akt inhibition. Furthermore, Akt inhibition disrupts lipid rafts, which is known to promote cholesterol efflux to apoA-I. We therefore conclude that Akt, through its downstream targets, mTORC1 and hence autophagy, negatively regulates cholesterol efflux to apoA-I.


Effects of hepatitis C virus infection and its recurrence after liver transplantation on functional performance and health-related quality of life.
Our aim was to examine the effects of hepatitis C virus (HCV) infection, a leading cause of end-stage liver disease, and its recurrence after liver transplantation on functional performance and health-related quality of life. Functional performance, liver function, and HCV recurrence were assessed longitudinally in 75 adult transplant recipients (28 with HCV). Quality of life was reported once after transplantation. Functional performance improved through year 2 (P < 0.001) and then declined in those with HCV, whereas the others remained stable (P = 0.05). Time had a positive effect (beta = 0.22, P = 0.05) and HCV infection had a negative effect (beta = -0.28, P = 0.01) on post-transplant functional performance. Educational level (beta = 0.24, P < 0.05) and recent functional performance (beta = 0.31, P = 0.01) had positive effects on quality of life. HCV recurrence was associated with relatively poorer pretransplant functional performance, a greater rate of improvement through month 3 (P < 0.05), and abnormal transaminase values between years 1 and 2 (P < 0.001). Rehospitalization for recurrent HCV was associated with reduced functional performance (P < 0.05). Functional performance improves with time following liver transplantation, but HCV infection exerts an opposing and comparably strong effect. Post-transplant functional performance, in turn, directly affects post-transplant quality of life. Severe, recurrent HCV illness is associated with reduced functional performance.


Impact of errors in recorded compressed breast thickness measurements on volumetric density classification using volpara v1.5.0 software.
Mammographic density has been demonstrated to predict breast cancer risk. It has been proposed that it could be used for stratifying screening pathways and recommending additional imaging. Volumetric density tools use the recorded compressed breast thickness (CBT) of the breast measured at the x-ray unit in their calculation; however, the accuracy of the recorded thickness can vary. The aim of this study was to investigate whether inaccuracies in recorded CBT impact upon volumetric density classification and to examine whether the current quality control (QC) standard is sufficient for assessing mammographic density. Raw data from 52 digital screening mammograms were included in the study. For each image, the clinically recorded CBT was artificially increased and decreased in increments of 1 mm to simulate measurement error, until ±15% from the recorded CBT was reached. New images were created for each 1 mm step in thickness resulting in a total of 974 images which then had volpara density grade (VDG) and volumetric density percentage assigned. A change in VDG was observed in 38.5% (n = 20) of mammograms when applying ±15% error to the recorded CBT and 11.5% (n = 6) was within the QC standard prescribed error of ±5 mm. The current QC standard of ±5 mm error in recorded CBT creates the potential for error in mammographic density measurement. This may lead to inaccurate classification of mammographic density. The current QC standard for assessing mammographic density should be reconsidered.


[Clinical observation on treating diabetic macular edema with intravitreal triamcinolone acetonide and laser].
To evaluate the effect of intravitreal injection of triamcinolone acetonide(IVTA) combining with retinal laser treating for diabetic macular edema(DME). Twenty five patients(32 eyes) with DME who has microangioma in macula lutea were randomly divided into group A, B,C and D(8 eyes each group). Eyes in group A were treated with laser photocoagulation. Eyes in group B were treated with multiplier-532 laser photocoagulation and transpupillary thermotherapy. Eyes in group C were treated with multiplier-532 laser photocoagulation and intravitreal triamcinolone acetonide. Eyes in group D were treated with multiplier-532 laser, transpupillary thermotherapy plus triamcinolone acetonide injection. Intravitreal injection of 4 mg triamcinolone acetonide was done 1 week after laser photocoagulation in group C and D. The visual acuity, intraocular pressure, macular thickness (foveal thickness) of the eyes in 4 groups were observed before and 1, 3 and 6 months after treatment. The visual acuity, intraocular pressure and foveal thickness of the 4 groups before treatment showed no significant difference(p> ). The visual acuity, intraocular pressure, macular thickness of eyes in group A, B were better than those of group C, D at 1, 3 and 6 months after treatment, and they had significant difference(p<0.05), while they didn't show significant difference between group A and B, group C and D(p>0.05). The effect of laser photocoagulation and intravitreal triamcinolone acetonide, laser photocoagulation combining with transpupillary thermotherapy plus triamcinolone acetonide injectionvisual treating for DME was better than laser photocoagulation alone, laser photocoagulation combining with transpupillary thermotherapy.


MRI-Targeted or Standard Biopsy in Prostate Cancer Screening.
High rates of overdiagnosis are a critical barrier to organized prostate cancer screening. Magnetic resonance imaging (MRI) with targeted biopsy has shown the potential to address this challenge, but the implications of its use in the context of organized prostate cancer screening are unknown. We conducted a population-based noninferiority trial of prostate cancer screening in which men 50 to 74 years of age from the general population were invited by mail to participate; participants with prostate-specific antigen (PSA) levels of 3 ng per milliliter or higher were randomly assigned, in a 2:3 ratio, to undergo a standard biopsy (standard biopsy group) or to undergo MRI, with targeted and standard biopsy if the MRI results suggested prostate cancer (experimental biopsy group). The primary outcome was the proportion of men in the intention-to-treat population in whom clinically significant cancer (Gleason score ≥7) was diagnosed. A key secondary outcome was the detection of clinically insignificant cancers (Gleason score 6). Of 12,750 men enrolled, 1532 had PSA levels of 3 ng per milliliter or higher and were randomly assigned to undergo biopsy: 603 were assigned to the standard biopsy group and 929 to the experimental biopsy group. In the intention-to-treat analysis, clinically significant cancer was diagnosed in 192 men (21%) in the experimental biopsy group, as compared with 106 men (18%) in the standard biopsy group (difference, 3 percentage points; 95% confidence interval [CI], -1 to 7; P<0.001 for noninferiority). The percentage of clinically insignificant cancers was lower in the experimental biopsy group than in the standard biopsy group (4% [41 participants] vs. 12% [73 participants]; difference, -8 percentage points; 95% CI, -11 to -5). MRI with targeted and standard biopsy in men with MRI results suggestive of prostate cancer was noninferior to standard biopsy for detecting clinically significant prostate cancer in a population-based screening-by-invitation trial and resulted in less detection of clinically insignificant cancer. (Funded by the Swedish Research Council and others; STHLM3-MRI ClinicalTrials.gov number, NCT03377881.).


Prognostic significance of limited resection in pathologic stage I lung adenocarcinoma with spread through air spaces.
Tumor spread through air spaces (STAS) is now recognized as tumor invasion. However, the association between STAS and procedure-specific outcomes (limited resection and lobectomy) in patients with pathologic stage I lung adenocarcinoma (ADC) is still under investigation. To investigate whether limited resection predicts poorer survival in such patients, we retrospectively analyzed the clinicopathologic features of a large cohort of 1,566 patients with stage I ADC from 2017 to 2020 and classified them according to STAS status and surgical method. Kaplan-Meier, Cox hazard proportional regression, and propensity score matching (PSM) were adopted for prognostic evaluation. STAS-positive patients had worse recurrence-free survival (RFS) (P<0.001). There was no significant difference in RFS and overall survival (OS) between limited resection and lobectomy, neither for the STAS-negative nor STAS-positive group before matching. After matching, limited resection was found to achieve comparable RFS to lobectomy in STAS-positive patients with pathologic I, IA, or IB stage tumor, (P=0.816, P=0.576, P=0.281, respectively), but worse OS in stage I and stage IB patients (P=0.029, P=0.010, respectively). Furthermore, in multivariable analysis, limited resection was not an independent prognostic factor of RFS or OS. Instead, the high-grade histological subtype was the only independent prognostic factor for RFS (P=0.001). In the subgroup analysis, adjuvant chemotherapy (ACT) did not improve the outcomes of stage IB STAS-positive patients. Limited resection was associated with worse survival than lobectomy in stage I STAS-positive patients, but not in stage IA STAS-positive patients.


Primary non-Hodgkin's lymphoma of the maxillary sinus.
Primary non-Hodgkin's lymphoma of the maxillary sinus is a rare lesion. We studied nine patients with malignant lymphoma involving the maxillary sinus, treated between 1980 and 1994 in the Kyushu University Hospital. All lymphomas had a diffuse pattern; five were the large-cell type, two the mixed type, and one the small lymphatic and small cleaved type. Immunohistologically, all tumors were B-cell type. Using the Ann Arbor staging system, six patients were classified as stage I, two stage II, and one stage IV. Two patients received only radiotherapy because of advanced age; the remaining seven received a combination of radiotherapy and chemotherapy (CHOP or VEPA). The tumor doses ranged from 30 to 51 Gy (mean, 46.7). The mean follow-up was 51 months. Only one patient (stage IV) died of disease, and eight stage I-II patients were rendered disease-free. The 5-year survival rate was 80%, suggesting that primary lymphoma of the maxillary sinus has a relatively good prognosis.


Future drug discovery in renin-angiotensin-aldosterone system intervention.
Renin-angiotensin-aldosterone system inhibitors (RAASIs), including angiotensin-converting enzyme inhibitors, angiotensin AT1 receptor blockers and mineralocorticoid receptor antagonists (MRAs), are the cornerstone for the treatment of cardiovascular and renal diseases. Areas covered: The authors searched MEDLINE, PubMed and ClinicalTrials.gov to identify eligible full-text English language papers. Herein, the authors discuss AT2-receptor agonists and ACE2/angiotensin-(1-7)/Mas-receptor axis modulators, direct renin inhibitors, brain aminopeptidase A inhibitors, biased AT1R blockers, chymase inhibitors, multitargeted drugs, vaccines and aldosterone receptor antagonists as well as aldosterone synthase inhibitors. Expert opinion: Preclinical studies have demonstrated that activation of the protective axis of the RAAS represents a novel therapeutic strategy for treating cardiovascular and renal diseases, but there are no clinical trials supporting our expectations. Non-steroidal MRAs might become the third-generation of MRAs for the treatment of heart failure, diabetes mellitus and chronic kidney disease. The main challenge for these new drugs is that conventional RAASIs are safe, effective and cheap generics. Thus, the future of new RAASIs will be directed by economical/strategic reasons.


[Phenotypic and genetic analysis of a child featuring multiple malformations due to chromosome 14q deletion].
To analyze a child with mental retardation, growth retardation and language development disorders. Conventional G-banding analysis was performed on chromosomes cultivated from peripheral blood samples derived from the child and her parents. Array-comparative genomic hybridization (aCGH) was performed to detect minor structural chromosomal abnormalities, and the result was confirmed by short tandem repeats (STR) analysis. For the child and her parents, no karyotypic abnormality was detected. However, aCGH analysis has identified a 14q22.1 deletion in the child. The microdeletion, with a size of 2.9 Mb was confirmed by STR analysis. The 2.9 Mb chromosomal microdeletion probably underlies the mental retardation, growth retardation and language development disorders in the child.


The Effect of Unilateral Spinal Anaesthesia and Psoas Compartment with Sciatic Block on the Postoperative Pain Management in Total Knee Artroplastic Surgery.
Purpose. This study was designed to investigate the effects of peripheral nerve block methods, applied through unilateral spinal anaesthesia on elderly patients to undergo total knee arthroplasty, on perioperative hemodynamic parameters and postoperative analgesia period. Materials and Method. 60 patients were randomly divided into two groups in the study. In group USA spinal anaesthesia was performed. In group PCS it was applied on psoas compartment block and sciatic nerve block. Results. Significantly higher intraoperative 60th and 90th minute mean arterial pressure values were ascertained in the PCS group compared to the USA group. The decrease observed in the 5th, 10th, and 20th minute MAP values in the USA group was statistically significant according to the control MAP value. Concerning within group comparisons, the decrease in 5th, 10th, and 20th minute heart rate values in the USA group was statistically significant compared with the control measurement value. The mean beginning time of sensory and motor blocks in the PCS group was found to be at a significantly advanced level compared with that in the USA group. Conclusions. The PCS block technique using bupivacaine hydrochloride ensured a higher haemodynamic efficiency in the perioperative period in high-risk elderly patients undergoing total knee arthroplasty. This trial is registered with ClinicalTrials.gov Identifier: NCT03021421.


Realization of a Test Tool for Diagnosis of Contact Resistance and Measurement of Selected Types of Conductive Materials.
Contact connections in electrical machines and apparatus are important elements in the whole power supply network and a high level of reliability is expected there. Contact resistance is a fundamental criterion in the design of an electrical contact or contact system. The contact resistance should be as low as possible to minimize losses due to the current passage and the related heating of the contact connection. The value of the contact resistance depends on the material used, the value of the applied force, the type of contact, and, last but not least, the quality of the surface and chemical layers. In this paper, an initial diagnosis of the contact material is performed based on the determination of the sample's specific resistivity by the four-wire method and the evaluation of the measurement uncertainty. The work is followed by the design of a testing device that uses crossed bars to measure the change in contact resistance as a function of the magnitude of the applied force. An analysis of the sample mounting method is performed here using FEM simulations of the current field and shows the interaction between the holder and the sample in terms of current line transfer. The proposed system is then used for experimental measurements of the material-dependent coefficient KC for verification of existing or newly developed materials in electrical engineering, where the values of the KC coefficient are not known. Finally, the paper also deals with the measurement of fritting voltage for individual contact pairs having surface quality corresponding to brushing.


[Vaccination for HIV positive travelers].
People with HIV+ travelling around the world comprise a unique group regarding immunological disorders which can be intensified due to, e.g. climatic and time zones. Increased exposure of vulnerable tourists to various biological factors (viruses, bacteria, fungi, and parasites) is hazardous to their health. Travellers are advised to active prophylaxis as far as endemic diseases of particular globe regions are concerned. Limitations in vaccine use in HIV+ travellers are due to the kind of biological material contained in preparations. Live vaccines in those with impaired immunity are limited as it is widely known. It is absolutely contraindicated to vaccinate patients with AIDS against tuberculosis, typhoid fever, and yellow fever. Killed vaccines are considered safe and recombined ones are recommended. Vaccines against HBV, HAV, Haemophilus influenzae b (Hib), influenza, and pneumococcus are indicated. However, the kind of prophylaxis should be individualized, decided by a managing physician in concord with an appropriate referential center.


Concordance of P450 2D6 (debrisoquine hydroxylase) phenotype and genotype: inability of dextromethorphan metabolic ratio to discriminate reliably heterozygous and homozygous extensive metabolizers.
Debrisoquine-hydroxylase (P450 2D6) not equal to phenotype was determined in 116 individuals using dextromethorphan as the substrate probe. Polymerase chain reaction and restriction fragment length polymorphism analyses were used to detect inactivating mutations in the CYP2D6 gene and assign genotype in all 116 individuals. Using a urinary metabolic ratio (DM/DT) of > or = 0.3 to define poor metabolizer (PM) phenotypes, 96 subjects were extensive metabolizers (EM) and 20 were PMs. The CYP2D6(B) mutation was the most common mutation, present in 18% of phenotypic EM alleles and 66% of the alleles in PM phenotypes. The CYP2D6(A) mutation (8% of PM alleles) and the CYP2D6 gene deletion (2.6% of PM alleles) were found less frequently. Seven different variants of the CYP2D6 gene were found. In subjects with two mutant alleles, genotype correctly predicted the PM phenotype in 100% (n = 13). Overall, genotype agreed with phenotype assignments in 109 of 116 (94%) subjects. Seven subjects with a wild-type allele at the CYP2D6(A) and CYP2D6(B) loci were phenotypic PMs, representing the only discrepant results. These discrepancies could be due to the imprecision of phenotype assignment or to as yet unknown mutations in CYP2D6. Although the median urinary metabolic ratio was significantly lower in homozygous EMs compared with heterozygous EMs, there was extensive overlap in metabolic ratios in these two groups, indicating that the DM/DT metabolic ratio cannot reliably discriminate homozygous EMs from heterozygous EMs.


Evidence for nonhydrogen bonded compound II in cyclic reaction of hemoglobin I from Lucina pectinata with hydrogen peroxide.
Studies that elucidate the behavior of the hemoglobins (Hbs) and myoglobins upon reaction with hydrogen peroxide are essential to the development of oxygen carrier substitutes. Stopped-flow kinetics and resonance Raman data show that the reaction between hydrogen peroxide and oxygenated and deoxygenated ferric Hb I (oxy- and deoxy-HbI) from Lucina pectinata produce compound I and compound II ferryl species. The rate constants ratio (k23/k41) between the formation of compound II from compound I (k23) and the oxidation of the ferrous HbI (k41, i.e., 25 M(-1) s(-1)) of 12 x 10(-4) M suggests that HbI has a peroxidative capacity for removing H2O2 from solution. Resonance Raman presents the formation of both, met-aquo-HbI and compound II ferryl species in the cyclic reaction of HbI with H2O2. The ferric HbI species is maintained by the presence of H2O2; it can produce HbI compound I, or it can be reduced to a deoxy-HbI derivative to form HbI compound II upon reaction with H2O2. The compound II ferryl vibration frequency appears at 805 and 769 cm(-1) for HbIFe(IV)=(16)O and HbIFe(IV)=(18)O species, respectively. This ferryl mode indicates the absence of hydrogen bonding between the carbonyl group of the distal Q64 and the HbIFe(IV)=O ferryl moiety. The observation suggests that both the trans-ligand effect and the polarizabilty of the HbI heme pocket are responsible for the observed ferryl oxo vibrational energy. The vibrational mode also suggests that the carbonyl group of the distal Q64 is oriented toward the iron of the heme group, increasing the distal pocket electron density.


Pre‑treatment with Chrysanthemum indicum Linné extract protects pyramidal neurons from transient cerebral ischemia via increasing antioxidants in the gerbil hippocampal CA1 region.
Chrysanthemum indicum Linné extract (CIL) is used in herbal medicine in East Asia. In the present study, gerbils were orally pre‑treated with CIL, and changes of antioxidant enzymes including superoxide dismutase (SOD) 1 and SOD2, catalase (CAT) and glutathione peroxidase (GPX) in the hippocampal CA1 region following 5 min of transient cerebral ischemia were investigated and the neuroprotective effect of CIL in the ischemic CA1 region was examined. SOD1, SOD2, CAT and GPX immunoreactivities were observed in the pyramidal cells of the CA1 region and their immunoreactivities were gradually decreased following ischemia‑reperfusion and barely detectable at 5 days post‑ischemia. CIL pre‑treatment significantly increased immunoreactivities of SOD1, CAT and GPX, but not SOD2, in the CA1 pyramidal cells of the sham‑operated animals. In addition, SOD1, SOD2, CAT and GPX immunoreactivities in the CA1 pyramidal cells were significantly higher compared with the ischemia‑operated animals. Furthermore, it was identified that pre‑treatment with CIL protected the CA1 pyramidal cells in the CA1 region using neuronal nuclei immunohistochemistry and Fluoro‑Jade B histofluorescence staining; the protected CA1 pyramidal cells were 67.5% compared with the sham‑operated animals. In conclusion, oral CIL pre‑treatment increased endogenous antioxidant enzymes in CA1 pyramidal cells in the gerbil hippocampus and protected the cells from transient cerebral ischemic insult. This finding suggested that CIL is promising for the prevention of ischemia‑induced neuronal damage.


Methods of analysis for chemicals that promote/disrupt cellular signaling.
Methods of analysis were presented for chemicals that promote or disrupt cellular signaling pathways. The developed analytical methods are based not only on receptor binding, but also on the following known molecular-level processes involved in signal transduction along signaling pathways, reconstituted in vitro or taken in part in living cells. The methods were discussed in relation to receptor binding assay and/or bioassay. Examples include: (1) Insulin signaling pathways; (1-i) Chemical selectivity of agonists for insulin signaling pathways based on agonist-induced phosphorylation of a target peptide; (1-ii) An SPR-based screening method for agonist selectivity for insulin signaling pathways based on the binding of phosphotyrosine to its specific binding protein; (1-iii) A fluorescent indicator for tyrosine phosphorylation-based insulin signaling pathways; (2) An optical method for evaluating ion selectivity for calcium signaling pathways in the cell; (3) Assay and screening of chemicals that disrupt cellular signaling pathways, potential endocrine disruptors in particular; (4) Protein conformational changes, and (5) A screening method for antigen-specific IgE using mast cells, based on intracellular calcium signaling.


Histological and ultrastructural studies of secondary neurulation in mouse embryos.
The histological and ultrastructural features of secondary neurulation in C57BL/6 mouse embryos were examined as a first step in the analysis of how this process occurs in mammalian embryos. Secondary neurulation involves two major events in mouse embryos: (1) formation of the medullary rosette (9.5- to 10-day embryos) or plate (11- to 12-day embryos), and (2) cavitation. These two events occur simultaneously. The medullary rosette consists of elongated tail bud cells, radially arranged around a central lumen formed by cavitation. The secondary portion of the neural tube forms in 9.5- to 10-day embryos by progressive enlargement of the central lumen and addition (by cell recruitment or mitosis) of tail bud cells to the rosette. The medullary plate likewise consists of elongated tail bud cells, but these cells do not surround a central cavity. Instead, cells of the medullary plate extend ventrad from the basal aspect of the dorsal surface ectoderm to a slit-like cavity formed by cavitation. Formation of the secondary neural tube occurs in 11- to 12-day embryos, principally by the recruitment of more lateral and ventral tail bud cells into the medullary plate. Free cells and cellular debris are frequently encountered in the forming lumen of the secondary neural tube, but cells exhibiting signs of necrosis were absent in cavitating regions. Numerous small intercellular junctions form at the inner ( juxtaluminal ) ends of tail bud cells as the medullary rosette or plate is forming and cavitation is occurring. These observations suggest that cavitation per se (i.e., formation of a lumen) during secondary neurulation is a relatively passive phenomenon, which results principally from neighboring cells becoming polarized apicobasally and incorporated into a primitive neuroepithelium. The latter constitutes the walls of the forming secondary neural tube.


Magnetic-field-induced control of breather dynamics in a single plaquette of Josephson junctions.
We present a theoretical study of inhomogeneous dynamic (resistive) states in a single plaquette consisting of three Josephson junctions. Resonant interactions of such a breather state with electromagnetic oscillations manifest themselves by resonant current steps and voltage jumps in the current-voltage characteristics. An externally applied magnetic field leads to a variation of the relative shift between the Josephson current oscillations of two resistive junctions. By making use of the rotation wave approximation analysis and direct numerical simulations we show that this effect allows to effectively control the breather instabilities, e.g., to increase (decrease) the height of the resonant steps and to suppress the voltage jumps in the current-voltage characteristics.


[Factors predicting failure in empirical antibiotic treatment].
Infections are one of the main causes of morbidity and mortality in the population. The choice of empirical treatment is one of the most common decisions facing the physician. This first decision has consequences in the prognosis of the patient and the costs associated with the process. This review attempts to summarize the aspects that can lead to failure of antibiotic treatment by considering microbiological and pharmacological aspects, patient profile and infectious focus control. In addition, a series of recommendations are established to minimize this risk, from the point of view of diagnostic accuracy, adequate severity stratification of the patient, knowledge of the pharmacokinetic and pharmacodynamic aspects of antibiotics and control of the infectious focus.


Embryo sac chromosome doubling in Populus alba × P. glandulosa induced by high temperature exposure to produce triploids.
To determine the effects of the hours after pollination and the treatment durations on triploid production and reveal the effective stages of embryo sac chromosome doubling by high temperature exposure. At least three catkins were sampled, and 80 ovules were used for the determination of the embryo sac developmental process. Catkins (2-74 h after pollination) were treated to induce embryo sac chromosome doubling. Cytological observations revealed that the embryo sac development was a consecutive and asynchronous process. Fertilization occurred 50 h after pollination. In the offspring seedlings, 167 triploids were detected and the highest efficiency of triploid production was 87.0%. Among all the induced triploids, the most effective treatment period of inducing embryo sac chromosome doubling is from 26 to 50 h after pollination, and 121 triploids were obtained, representing 72.46% of the sum of all triploids. GLM-Univariate analysis indicated significant differences among the hours after pollination (F = 4.516, p = 0.045). However, the differences between the treatment durations (F = 0.077, p = 0.791) were not significant. Correlation analysis between the proportion of each embryo sac's developmental stage and the percentage of triploid production indicated that the third mitotic division may be the most effective stage for 2n female gamete induction.


[Inhibition of N/OFQ on transient outward potassium currents in acutely dissociated rat cerebral parietal cortical neurons].
To study the effect of Nociceptin/orphanin FQ (N/OFQ) on transient outward potassium (I(A)) in rat cerebral cortical neurons and its kinetic mechanism. The effects of N/OFQ on I(A) were investigated by using the whole cell patch clamp technique in acutely dissociated rat cerebral cortical neurons. (1) At the voltage of + 60 mV, 0.1 micromol/L N/OFQ made I(A) decreased from (5356.1 +/- 361.6) pA to (4113.3 +/- 312.7) pA (P < 0.01, n = 10) and the percent inhibition was 23.2% +/- 2.2%. (2) (N/OFQ made I-V curve of I(A) decreased significantly (P < 0.01, n = 10).(3) 0.1 micromol/L N/OFQ shifted the activation curve of I(A) to positive potential from (-9.2 +/- 2.5)mV to (30.6 +/- 3.7) mV (P < 0.01, n = 8) and changed the slope factor(kappa) of the activation curve from (20.4 +/- 2.3) mV to (22.6 +/- 2.1) mV (P > 0.05, n = 8). (4) 0.1 micromol/L N/OFQ caused a significant hyperpolarizing shift of the inactivation curve from (-64.1 +/- 3.2) mV to (-55.9 +/- 1.9) mV (P < 0.05, n = 5), without significant effect on kappa of the inactivation curve. 0.1 micromol/L N/OFQ has a significant inhibition on I(A) and shift the activation and inactivation curve to depolarization in cerebral parietal cortical neurons of rats.


Risk factors of gastric cancer specific for tumor location and histology in Cali, Colombia.
To examine histology- and tumor-location specific risk factors of gastric cancer (GC). This was a case-control study. The study subjects were 216 GC patients newly diagnosed during the period 2000-2002 and 431 controls selected from non-cancer patients matching in age, gender, and hospital. We obtained information on lifestyles, dietary habits, and others by a questionnaire. The subjects who were not eldest among his/her siblings were at a slightly elevated GC risk (OR 1.3; 95% CI 0.8-2.0). Salting meals before tasting was related to an increased GC risk (OR 3.5; 95% CI 1.6- 7.3). Frequent consumptions of fruits (OR 0.3; 95% CI 0.1-1.0) and vegetables (OR 0.3; 95% CI 0.1-1.0) were related to decreased GC risks. On the other hand, frying foods (OR 1.9; 95% CI 1.0-3.6) and cooking with coal (OR 1.8; 95% CI 1.3-2.6) were related to increased GC risks. Neither Laurenos histological classification (intestinal and diffuse types) nor tumor location significantly affected those associations except birth order. The subjects who were not eldest among his/her siblings had an increased risk of GCs in the distal and middle thirds, and their ORs were 1.7 (95% CI 1.0-2.8) and 1.9 (95% CI 0.8-4.3), respectively. The corresponding OR in the upper third stomach was 0.3 (95% CI 0.1-0.9). The differences of those three ORs were statistically significant (P = 0.010). The present study shows that birth order, salt intake, consumption of fruits and vegetables, the type of cooking, and cigarette smoking are related to GC risk. In histology and tumor-location specific analyses, non-eldest person among their siblings is related to an increased GC risk in the distal and middle thirds of the stomach, and is related to a decreased GC risk in the cardia.


Management studies using a combination of D-dimer test result and clinical probability to rule out venous thromboembolism: a systematic review.
While the number of patients with suspected venous thromboembolism (VTE) referred to hospital emergency units increases, the proportion in whom the diagnosis can be confirmed is decreasing. A more efficient but safe diagnostic strategy is needed. To evaluate the safety of withholding anticoagulant therapy in patients suspected of VTE based on a diagnostic work-up that combines a clinical decision rule (CDR) with a D-dimer test result without performing additional diagnostic tests. We searched Medline (January 1996-December 2004)-related articles and reference lists of studies in English for prospective clinical studies that managed consecutive patients suspected of VTE and used a D-dimer assay combined with an explicit CDR or implicit clinical judgment. We identified 11 studies in which 6837 consecutive outpatients suspected of VTE were included. In the combined management studies, the overall rate of thromboembolic events was nine out of 2056 patients (0.44 %, 95% CI 0.2%-0.83%) in whom anticoagulants were withheld based on the D-dimer result and a low clinical score. Similar results were obtained with qualitative and quantitative D-dimer tests and with different decision rules. The rate of exclusion varied between 30% and 50% and was highest with a low incidence of VTE among those referred. Withholding anticoagulant treatment in patients suspected of VTE on the basis of a work-up consisting of a low clinical probability combined with either a qualitative or quantitative D-dimer test result is safe.


Takotsubo Cardiomyopathy in a Patient with Preexisting Hypertrophic Cardiomyopathy.
Takotsubo cardiomyopathy (TCM) is a condition characterized by transient left ventricular dysfunction and apical ballooning, best seen on an echocardiogram or left ventriculogram. It mimics acute myocardial infarction but without evidence of coronary artery disease on an angiogram. Hypertrophic cardiomyopathy (HCM) is an autosomal dominant heart muscle disease that is significant with hypertrophy of the left ventricle with various morphologies. We hereby report a case of TCM in a male patient with a known history of HCM. The patient's hemodynamic findings were challenging because the TCM produced an increased left ventricular outflow tract (LVOT) gradient that was previously not seen on his prior echocardiogram or cardiac catheterizations. Assessment and continuous monitoring are warranted in such a rare case. Supportive care afterward with beta blockers, along with echocardiogram surveillance, are the mainstay of management of such a patient.


Use of an improved Watusi collar to manage pediatric neck burn contractures.
Burns to the neck present a serious challenge to the pediatric burn team. Even when full neck range of motion is maintained, scarring may lead to banding and a loss of the neck's natural contour. Conventional thermoplastic neck conformers have been used to maintain neck position and provide pressure to maturing scars, but they are rigid and limit functional mobility. This is of particular concern in the pediatric population where limiting neck mobility can disrupt the development of sensory and motor patterns that are essential to normal developmental progression. The Multi-Ring Watusi collar is a flexible neck orthosis that allows mobility and provides circumferential pressure to the neck. We modified this collar to improve its comfort, cosmetic appearance and ease in donning/doffing. The improved Watusi collar is a flexible splint that supports neck position, provides circumferential pressure, and allows for functional neck mobility.


Optical quality of the cornea after overnight orthokeratology.
To review changes in the optical quality of the cornea induced by overnight orthokeratology for myopia. Sixty-four eyes of 39 patients who underwent overnight orthokeratology for myopia were prospectively examined. Inclusion criteria were uncorrected visual acuity of 20/20 or better after treatment and a minimum follow-up of 3 months. To quantitatively assess changes in corneal regular and irregular astigmatism, videokeratography data were decomposed into spherical component, regular astigmatism, asymmetry, and higher-order irregularity using Fourier analysis. In addition, corneal wavefront aberrations were calculated by expanding anterior corneal height data from videokeratography into a set of orthogonal Zernike polynomials. Although orthokeratology significantly reduced manifest refraction and improved uncorrected visual acuity, the asymmetry component, which is one of the features of irregular astigmatism, increased significantly from 0.35 +/- 0.22 to 0.64 +/- 0.40 D after treatment (P < 0.0001, paired t test). The increases in the asymmetry component significantly correlated with the amount of myopic correction (Pearson correlation coefficient, R = 0.40, P = 0.0009). Furthermore, the root-mean-square of third-order (coma-like) and fourth-order (spherical-like) aberrations significantly increased after orthokeratology (P < 0.0001, paired t test), and these increases showed significant positive correlations with the amount of myopic correction (Pearson correlation coefficient, R = 0.452, P = 0.0001 and R = 0.381, P = 0.0017, respectively). Corneal irregular astigmatism and higher-order aberrations significantly increased even in clinically successful orthokeratology, and the increases correlated with the magnitude of myopic correction. A large myopic correction by orthokeratology should be avoided to not decrease corneal optical quality.


Delay optimization of multipoint pacing increases the cardiac index and narrows the QRS width.
The benefits of MPP delay optimization on hemodynamics and ventricular contraction synchronicity can be quantified with cardiac index (CI) and QRS width. A delay with the maximum CI and minimum QRS width may be the optimized settings for multipoint pacing (MPP). Twelve patients with advanced heart failure who received cardiac resynchronization therapy defibrillation with MPP at the Third People's Hospital of Chengdu from March 2016 to April 2019 were included. Interventricular and intraventricular delays were optimized through noninvasive cardiac output monitoring and a 12 lead ECG. According to CI, the optimized left ventricular- left ventricular - right ventricular delay setting was mainly 25 ms-25 ms and 40 ms-40 ms. And the delay with the minimum QRS width was mainly in 5 ms-5 ms, 25 ms-25 ms, and 40 ms-25 ms. The optimal MPP configuration increased CI compared to the MPP setting that produced the minimum CI (4.5 ± 1.3 vs. 2.8 ± 1.0 L/min/m2, P < 0.001). The QRS width of the optimized MPP was narrower than the MPP setting that produced the maximum QRS width (127 ± 20 vs. 160 ± 29 ms, P < 0.001). Delay optimization improves hemodynamic response and ventricular contraction synchronicity. The delay of 25 ms-25 ms may be the optimal setting for most MPP patients.


The role of dietary n-6 fatty acids in the prevention of cardiovascular disease.
n-6 Fatty acids, like n-3 fatty acids, play essential roles in many biological functions. Because n-6 fatty acids are the precursors of proinflammatory eicosanoids, higher intakes have been suggested to be detrimental, and the ratio of n-6 to n-3 fatty acids has been suggested by some to be particularly important. However, this hypothesis is based on minimal evidence, and in humans higher intakes of n-6 fatty acids have not been associated with elevated levels of inflammatory markers. n-6 Fatty acids have long been known to reduce serum total and low-density lipoprotein cholesterol, and increases in polyunsaturated fat intake, mostly as n-6 fatty acids, were a cornerstone of dietary advice during the 1960s and 1970s. In the United States, for example, intake of n-6 fatty acids doubled and coronary heart disease (CHD) mortality fell by 50% over a period of several decades. In a series of relatively small, older randomized trials, in which intakes of polyunsaturated fat were increased (even up to 20% of calories), rates of CHD were generally reduced. In a more recent detailed examination of fatty acid intake within the Nurses' Health Study, greater intake of linoleic acid, up to about 8% of energy, has been strongly related to lower incidence of myocardial infarction or CHD death. Because n-3 fatty acids were also related inversely to risk of CHD, the ratio was unrelated to risk. n-6 Fatty acids reduce insulin resistance, probably by acting as a ligand for peroxisome proliferator-activated receptors-gamma, and intakes have been inversely related to risk of type 2 diabetes. Adequate intakes of both n-6 and n-3 fatty acids are essential for good health and low rates of cardiovascular disease and type 2 diabetes, but the ratio of these fatty acids is not useful. Reductions of linoleic acid to "improve" this ratio would likely increase rates of cardiovascular disease and diabetes.


Rethinking the definition of rate-induced tipping.
The current definition of rate-induced tipping is tied to the idea of a pullback attractor limiting in forward and backward time to a stable quasi-static equilibrium. Here, we propose a new definition that encompasses the standard definition in the literature for certain scalar systems and includes previously excluded N-dimensional systems that exhibit rate-dependent critical transitions.


Theoretical and computational methods for the noninvasive detection of gastric electrical source coupling.
The ability to study the pathology of the stomach noninvasively from magnetic field measurements is important due to the significant practical advantages offered by noninvasive methods over other techniques of investigation. The inverse biomagnetic problem can play a central role in this process due to the information that inverse solutions can yield concerning the characteristics of the gastric electrical activity (GEA). To analyze gastrointestinal (GI) magnetic fields noninvasively, we have developed a computer implementation of a least-squares minimization algorithm that obtains numerical solutions to the biomagnetic inverse problem for the stomach. In this paper, we show how electric current propagation and the mechanical coupling of gastric smooth muscle cells during electrical control activity can be studied using such solutions. To validate our model, two types of numerical simulations of the GEA were developed and successfully used to demonstrate the ability of our computer algorithm to detect and accurately analyze these two phenomena. We also describe our analysis of experimental, noninvasively acquired gastric biomagnetic data as well as the information of interest that our numerical method can yield in clinical studies. Most importantly, we present experimental evidence that the coupling of gastric electrical sources can be observed using noninvasive techniques of measurement, in our case with the use of a superconducting quantum interference device magnetometer. We discuss the relevance and implications of our achievement to the future of GI research.


Evaluation of the immunosuppressive effect of cyclophosphamide and dexamethasone in mice with visceral toxocariasis.
Visceral toxocariasis is a serious public health problem with a cosmopolitan distribution. Children are susceptible due to their immature immune system and high risks of infection. Nevertheless, the few completed studies about immunosuppression have had controversial results. To evaluate the effect of two immunosuppressive drugs on the larval burden of Toxocara canis, four groups of ten Swiss strain mice each were inoculated on day 0 with 1,200 embryonated T. canis eggs. Fifteen days before the experimental infection, group 1 (control) was treated via intraperitoneal injection (IP) with sterile distilled water and groups 2 and 3 were treated with dexamethasone (DEX) at 1 and 5 mg/kg/day, respectively. Additionally, group 4 was treated IP with cyclophosphamide (CY) at 50 mg/kg at two times per week for 2 weeks. Sixty days following infection, the mice were euthanised to recover the larvae by means of the tissue digestion technique. The levels of antibodies detected by indirect ELISA were not associated with the larval burden. Administration of CY (50 mg/kg) and DEX (5 mg/kg) resulted in an increase of the larval burden of 162.1% and 50.8%, respectively, in relation to the control group. These two treatments, especially CY (50 mg/kg), promoted immunosuppression and the establishment of a significant larval burden, supporting its further utilisation in studies related to immunosuppression in visceral toxocariasis.


A novel splice variant of human gene NPL, mainly expressed in human liver, kidney and peripheral blood leukocyte.
From the human fetal brain cDNA library constructed by our lab, a novel variant cDNA of a human gene was successfully cloned and identified. Because the gene has been named N-acetylneuraminate pyruvate lyase (NPL), accordingly we term our splice variant NPL_v2. The cDNA of NPL_v2 has a full-length open reading frame (ORF) from the nucleotide position 320 to 1225 that encodes a protein comprising 301 amino acids. SMART analysis showed that our hypothetical protein has one dihydrodipicolinate synthase (DHDPS) domain. Phosphorylation analysis of the deduced protein show that there are five phosphorylation sites including three "serine" and two "threonine" at the region that are not found in other splice variant. RT-PCR experiment revealed that our splice variant of the gene is mainly expressed in human placenta, liver, kidney, pancreas, spleen, thymus, ovary, small intestine and peripheral blood leukocyte.


Polymerase chain reaction identification of three members of the Anopheles sundaicus (Diptera: Culicidae) complex, malaria vectors in Southeast Asia.
Anopheles sundaicus s.l., a major malaria vector taxon, occurs primarily along coastal areas and on islands in Southeast Asia. Our previous studies using cytochrome oxidase I, cytochrome-b, and internal transcribed spacer 2 markers discriminated three allopatric species: An. sundaicus s.s. in northern Borneo, An. epiroticus in Southeast Asia, and An. sundaicus E on Sumatra and Java, Indonesia. Morphological comparisons of three developmental stages did not reveal unique diagnostic characters that could reliably distinguish the three species. Therefore, we developed a multiplex polymerase chain reaction (PCR) assay based on two mitochondrial DNA markers to unambiguously identify them. This PCR was tested on 374 specimens from 24 different geographical populations, expanding our knowledge of the distribution of these species.


On-Line Restricted Access Molecularly Imprinted Solid-Phase Extraction of Selective Serotonin Reuptake Inhibitors Directly from Untreated Human Plasma Samples Followed by HPLC-UV Analysis.
In this article, we proposed a new restricted access molecularly imprinted polymer coated with bovine serum albumin (RAMIP-BSA) to be used in a multidimensional chromatographic system applied for the analysis of six selective serotonin reuptake inhibitors (SSRIs) directly from untreated human plasma samples. Fluoxetine, methacrylic acid and ethylene glycol dimethacrylate were used as the template, functional monomer and cross-linker, respectively. The imprinted polymer was covered with a bovine serum albumin (BSA) layer via the interconnections between the amine groups of the BSA using glutaraldehyde as a cross-linker. The obtained RAMIP-BSA was able to extract the SSRIs directly from the human plasma, while ∼100% of the proteins were excluded from the sample. Selectivity coefficients were calculated for fluoxetine (template) in comparison with venlafaxine, duloxetine, citalopram, fluvoxamine, paroxetine and sertraline, and the values were >1 in all cases, attesting to the presence of binding sites in the imprinted polymer. The method presented analytical ranges from 20 to 500 µg/L and correlation coefficients >0.99 for all of the SSRIs (fluoxetine, venlafaxine, duloxetine, citalopram, fluvoxamine and sertraline). Precision and accuracy presented variation coefficients and relative errors <14.5% and within the range of -19.18 to 3.8%, respectively. In all cases, the apparent recoveries were >85%. The proposed method was able to analyze three samples per hour, and each column was used at least 50 times without any significant changes in its performance.


Hospital Dermatology, Introduction.
Inpatient dermatology is emerging as a distinct dermatology subspecialty where dermatologists specialize in caring for patients hospitalized with skin disease. While the main focus of inpatient dermatology is the delivery of top-quality and timely dermatologic care to patients in the hospital setting, the practice of hospital-based dermatology has many additional components that are critical to its success.


Pd-Catalyzed C-H Alkylation of Arenes Using PyrDipSi, a Transformable and Removable Silicon-Tethered Directing Group.
An efficient Pd-catalyzed ortho-C-H alkylation reaction of arenes using a transformable and removable Si-tethered pyridyldiisopropylsilyl (PyrDipSi) directing group has been developed. In addition, the PyrDipSi directing group allows for an efficient sequential double-fold C-H alkylation/oxygenation of arenes to produce meta-alkylated phenols. This directing group can easily be removed or converted into valuable functionalities, such as aryl, iodo, boronic ester, or phenol.


Comparative efficacy of handwashing agents against cytomegalovirus.
Conscientious handwashing is often recommended as an important method for limiting transmission of cytomegalovirus (CMV) from infected individuals to health, education, and child care professionals. To assess the efficacy of handwashing, fingertips of radiation-sterilized latex gloves were inoculated with 0.2 mL of ten different CMV strains. Virus in each inoculum was quantitated by plaque assay. After five minutes, viral inocula were allowed to remain (control), or were washed away by dropwise application of 10 mL of distilled water (DI), 5 mL of 0.08% soap followed by 5 mL of DI, 5 mL of 0.01% chlorhexidine gluconate followed by 5 mL of DI, or 5 mL of 0.025% povidone-iodine solution followed by 5 mL of DI. Separate glove fingertips were sampled 5, 15, 30, 60, 120 and 240 minutes after washing and cultured in duplicate for CMV. Similar studies were performed using human cadaver skin. Ordinary soap was as effective at preventing CMV recovery as other more expensive agents. For inocula with less than 5 log10 pfu CMV/mL, washing with water alone was as effective as other agents. This was confirmed in similar studies with human hands using five CMV stains. Handwashing is probably an effective method for removing CMV from contaminated hands.


BioActivities of Coturnix japonica (quail) egg yolk and albumen against physiological stress.
Cold and immobilization stressors can generate oxidative stress as well as skeletal muscle fatigue. Free radicals cause oxidative degradation of lipids, proteins, nucleic acids, and carbohydrates molecules thereby compromising cell integrity and function. Coturnix japonica (quail) egg had been described as being very functional biochemically, due to the essential biomolecules it contains in very regulated quantity. This study was designed to evaluate the in vitro antioxidant activity of extracts of quail egg yolk and the albumen. The assessment of the antioxidant potentials was typified using the total antioxidant capacity, and ABTS, DPPH (1-diphenyl-2-picrylhydrazyl) and hydroxyl radicals scavenging activities. Others are reducing power, metal chelating and lipid peroxidation inhibition activities. The antistress activities of quail egg yolk and albumen were evaluated on hepatopathic enzymes as well as endogenous antioxidant enzymes. The total antioxidant activities of the yolk extract (YE) and the albumen extracts (AE) were, respectively, 186.57 ± 6.441 mg/g and 172 ± 10.690 mg/g AAE (Ascorbic Acid Equivalent). The YE exhibited significant, potent and appreciable antioxidant activities than AE in a concentration-dependent manner. The study confirmed that quail egg yolk contained highly antioxidative bioactive compounds not present in albumen, contributing to its (yolk) overall antioxidant and anti-inflammatory (antistress) properties, thus necessitating their (albumen and yolk) beneficial effects in the management of oxidative and inflammatory conditions.


The common transcriptional subnetworks of the grape berry skin in the late stages of ripening.
Wine grapes are important economically in many countries around the world. Defining the optimum time for grape harvest is a major challenge to the grower and winemaker. Berry skins are an important source of flavor, color and other quality traits in the ripening stage. Senescent-like processes such as chloroplast disorganization and cell death characterize the late ripening stage. To better understand the molecular and physiological processes involved in the late stages of berry ripening, RNA-seq analysis of the skins of seven wine grape cultivars (Cabernet Franc, Cabernet Sauvignon, Merlot, Pinot Noir, Chardonnay, Sauvignon Blanc and Semillon) was performed. RNA-seq analysis identified approximately 2000 common differentially expressed genes for all seven cultivars across four different berry sugar levels (20 to 26 °Brix). Network analyses, both a posteriori (standard) and a priori (gene co-expression network analysis), were used to elucidate transcriptional subnetworks and hub genes associated with traits in the berry skins of the late stages of berry ripening. These independent approaches revealed genes involved in photosynthesis, catabolism, and nucleotide metabolism. The transcript abundance of most photosynthetic genes declined with increasing sugar levels in the berries. The transcript abundance of other processes increased such as nucleic acid metabolism, chromosome organization and lipid catabolism. Weighted gene co-expression network analysis (WGCNA) identified 64 gene modules that were organized into 12 subnetworks of three modules or more and six higher order gene subnetworks. Some gene subnetworks were highly correlated with sugar levels and some subnetworks were highly enriched in the chloroplast and nucleus. The petal R package was utilized independently to construct a true small-world and scale-free complex gene co-expression network model. A subnetwork of 216 genes with the highest connectivity was elucidated, consistent with the module results from WGCNA. Hub genes in these subnetworks were identified including numerous members of the core circadian clock, RNA splicing, proteolysis and chromosome organization. An integrated model was constructed linking light sensing with alternative splicing, chromosome remodeling and the circadian clock. A common set of differentially expressed genes and gene subnetworks from seven different cultivars were examined in the skin of the late stages of grapevine berry ripening. A densely connected gene subnetwork was elucidated involving a complex interaction of berry senescent processes (autophagy), catabolism, the circadian clock, RNA splicing, proteolysis and epigenetic regulation. Hypotheses were induced from these data sets involving sugar accumulation, light, autophagy, epigenetic regulation, and fruit development. This work provides a better understanding of berry development and the transcriptional processes involved in the late stages of ripening.


[Electrophysiological impairment profile of patients with Wilson's disease].
In addition to hepatic and extrapyramidal motor clinical symptoms, Wilson's disease patients also exhibit subclinical disorders of other central nervous pathways. In this study, an impairment profile is described by means of eight electrophysiological tests (EAEP, MSEP, TSEP, T-VEP, MEP, EEG, heart frequency variability, and SSR) for 37 patients (28 with neurological, nine with tnon-neurological form) undergoing long-term drug therapy. The occurrence in 64.3% of a delayed wave III and/or IPL III-V prolongation in patients with the neurological form makes pathological FAEP the most common form of the disorder, followed by disorders in MSEP, TSEP, MEP, and T-VEP. Patients with the non-neurological form usually have normal values, although latency prolongations occur in isolated cases. The range of evoked potential findings is characterised primarily by latency prolongations, i.e. a demyelinising impairment type, and significant losses of potential hardly occur (except in the MEP). The electrophysiological impairment profile does not include EEG changes or vegetative disorders.


Palladium-Catalyzed Direct α-Arylation of Indane-1,3-dione to 2-Substituted Indene-1,3-diones.
A straightforward and feasible palladium-catalyzed direct α-arylation of indane-1,3-dione to 2-substituted aryl/heteroaryl indene-1,3-diones has been disclosed for the first time. Optimization of reaction conditions identified tBu-XPhos as a preferred ligand for the bis(acetonitrile)dichloropalladium(II) catalyst. A broad spectrum of aryl iodides and aryl triflates containing electron-donating, electron-withdrawing, and sterically hindered substituents gave an excellent yield for the quick access α-arylated 1,3-diones library.


Cholesterol 7 alpha-hydroxylase: evidence for transcriptional regulation by cholesterol or metabolic products of cholesterol in the rat.
Cholesterol 7 alpha-hydroxylase, the rate-determining enzyme in the bile acid biosynthesis pathway, is regulated in a negative feedback manner by hydrophobic bile salts returning to the liver via the portal circulation. The role of cholesterol in the regulation of cholesterol 7 alpha-hydroxylase and the interrelationship between the cholesterol and bile acid biosynthesis pathways remain controversial. The objective of the present study was to define the role of cholesterol in the regulation of cholesterol 7 alpha-hydroxylase and determine the molecular level of its control. In order to avoid intestinal or intravenous administration of cholesterol, we manipulated the flow of cholesterol within the hepatocytes by decreasing cholesterol synthesis with lovastatin in bile fistula rats (bile acid synthesis is up-regulated), or by increasing cholesterol supply by administering mevalonate, a precursor of cholesterol, to rats with intact enterohepatic circulation (bile acid synthesis is normal). In the first series of studies, lovastatin was administered as a single intravenous bolus (10 mg/kg) to rats with chronic bile fistula and to rats with intact enterohepatic circulation (cholesterol and bile acid synthesis is normal). Three hours after lovastatin administration, cholesterol 7 alpha-hydroxylase specific activity, enzyme mass, mRNA, and gene transcriptional activity were decreased by 35%, 32%, 56%, and 34%, respectively, in rats with chronic bile fistula. In rats with intact enterohepatic circulation, lovastatin administration resulted in a similar decrease (34%) of cholesterol 7 alpha-hydroxylase specific activity.(ABSTRACT TRUNCATED AT 250 WORDS)