Headache onset after vaccination against SARS-CoV-2: a systematic literature review and meta-analysis.
Vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are used to reduce the risk of developing Coronavirus Disease 2019 (COVID-19). Despite the significant benefits in terms of reduced risk of hospitalization and death, different adverse events may present after vaccination: among them, headache is one of the most common, but nowadays there is no summary presentation of its incidence and no description of its main features. We searched PubMed and EMBASE covering the period between January 1st 2020 and August 6th, 2021, looking for record in English and with an abstract and using three main search terms (with specific variations): COVID-19/SARS-CoV-2; Vaccination; headache/adverse events. We selected manuscript including information on subjects developing headache after injection, and such information had to be derived from a structured form (i.e. no free reporting). Pooled estimates and 95% confidence intervals were calculated. Analyses were carried out by vaccine vs. placebo, by first vs. second dose, and by mRNA-based vs. "traditional" vaccines; finally, we addressed the impact of age and gender on post-vaccine headache onset. Out of 9338 records, 84 papers were included in the review, accounting for 1.57 million participants, 94% of whom received BNT162b2 or ChAdOx1. Headache was generally the third most common AE: it was detected in 22% (95% CI 18-27%) of subjects after the first dose of vaccine and in 29% (95% CI 23-35%) after the second, with an extreme heterogeneity. Those receiving placebo reported headache in 10-12% of cases. No differences were detected across different vaccines or by mRNA-based vs. "traditional" ones. None of the studies reported information on headache features. A lower prevalence of headache after the first injection of BNT162b2 among older participants was shown. Our results show that vaccines are associated to a two-fold risk of developing headache within 7 days from injection, and the lack of difference between vaccine types enable to hypothesize that headache is secondary to systemic immunological reaction than to a vaccine-type specific reaction. Some descriptions report onset within the first 24 h and that in around one-third of the cases, headache has migraine-like features with pulsating quality, phono and photophobia; in 40-60% of the cases aggravation with activity is observed. The majority of patients used some medication to treat headache, the one perceived as the most effective being acetylsalicylic acid.


Late rupture of left ventricular true aneurysm after acute myocardial infarction.
Left ventricular (LV) free wall rupture complicated with acute myocardial infarction (AMI) usually occurs in the early phase of AMI. True aneurysm of the LV is sometimes a complication of AMI but rarely ruptures. In our patient, a 72-year-old woman, the LV free wall ruptured on Day 49 after the onset of AMI and the ruptured site was the thinnest wall of large true aneurysm of the LV. The large aneurysmal formation probably was due to corticosteroids used for pericarditis. More attention should be paid to late cardiac rupture and the use of corticosteroids.


[Evaluation of the effectiveness of disinfectants used in several Neapolitan hospitals].
Among the various and complex aspects concerning the etiology of nosocomial infections, a relevant role is played by the indiscriminate and incorrect use of disinfectants: they may change paradoxically from devices used for nosocomial infection prevention into carriers of infections. Critical situations are: a) inadequate cleaning of the container; b) inaccurate concentrations set up; c) use of unsterilized water as a diluent; d) introduction of gauze or cotton flocks into the container; e) disinfectant contact with inactivating substances such as soaps, detergents, and organic substances; f) solution stability; etc.. Therefore, in the light of the experience we acquired in the field of nosocomial infections, we believed interesting to carry out a study in order to detect contamination of disinfectants used in various hospitals in Naples as well as their usage. In the period from January to May 1988, 243 disinfecting solutions routinely used in surgical departments of the 2nd School of Medicine and of three large neapolitan hospitals were tested for microbiological contamination. The analysis was carried out according to Kelsey and Maurer. 13 disinfectants were contaminated. The bacterial count exceeded the value of 5000 col/ml in 6 cases, while for he other disinfectants there were levels between 2500 and 4500 col/ml. 64% of the microorganisms isolated belonged to Pseudomonas spp. (cepacia, aeruginosa, fluorescens, maltophilia), while Acinetobacter calcoaceticus and Staphylococcus epidermidis were found in 21% and 15% of specimens respectively. A major consideration arising out from our study is the little attention played to health problems related to disinfection by hospital staff, together with a lack of knowledge about the proper way of using disinfectants.(ABSTRACT TRUNCATED AT 250 WORDS)


Live Wait Times.
People in North Wales who need treatment for injuries can now obtain up-to-the-minute information on waiting times at the region's minor injuries units and emergency departments.


KDM2 Family Members are Regulated by HIF-1 in Hypoxia.
Hypoxia is not only a developmental cue but also a stress and pathological stimulus in many human diseases. The response to hypoxia at the cellular level relies on the activity of the transcription factor family, hypoxia inducible factor (HIF). HIF-1 is responsible for the acute response and transactivates a variety of genes involved in cellular metabolism, cell death, and cell growth. Here, we show that hypoxia results in increased mRNA levels for human lysine (K)-specific demethylase 2 (KDM2) family members, KDM2A and KDM2B, and also for Drosophila melanogaster KDM2, a histone and protein demethylase. In human cells, KDM2 family member's mRNA levels are regulated by HIF-1 but not HIF-2 in hypoxia. Interestingly, only KDM2A protein levels are significantly induced in a HIF-1-dependent manner, while KDM2B protein changes in a cell type-dependent manner. Importantly, we demonstrate that in human cells, KDM2A regulation by hypoxia and HIF-1 occurs at the level of promoter, with HIF-1 binding to the KDM2A promoter being required for RNA polymerase II recruitment. Taken together, these results demonstrate that KDM2 is a novel HIF target that can help coordinate the cellular response to hypoxia. In addition, these results might explain why KDM2 levels are often deregulated in human cancers.


Applications of Nanotechnology-based Approaches to Overcome Multi-drug Resistance in Cancer.
Cancer is one of the leading causes of death worldwide. Chemotherapy and radiation therapy are the major treatments used for the management of cancer. Multidrug resistance (MDR) is a major hindrance faced in the treatment of cancer and is also responsible for cancer relapse. To date, several studies have been carried out on strategies to overcome or reverse MDR in cancer. Unfortunately, the MDR reversing agents have been proven to have minimal clinical benefits, and eventually, no improvement has been made in therapeutic efficacy to date. Thus, several investigational studies have also focused on overcoming drug resistance rather than reversing the MDR. In this review, we focus primarily on nanoformulations regarded as a novel approach to overcome or bypass the MDR in cancer. The nanoformulation systems serve as an attractive strategy as these nanosized materials selectively get accumulated in tumor tissues, thereby improving the clinical outcomes of patients suffering from MDR cancer. In the current work, we present an overview of recent trends in the application of various nano-formulations, belonging to different mechanistic classes and functionalization like carbon nanotubes, carbon nanohorns, carbon nanospheres, liposomes, dendrimers, etc., to overcome MDR in cancer. A detailed overview of these techniques will help researchers in exploring the applicability of nanotechnologybased approaches to treat MDR.


Recent advances in hGH clinical research.
While hundreds of studies are currently being conducted with growth factors in a variety of areas, there are at least four major areas where significant contributions to medicine and health care of individuals can be accomplished in the future. These areas include the establishment of true benefit and risk for longterm use of hGH therapy for the treatment of short stature in a variety of conditions. They include the identification of medical need for replacement therapy in adults with growth hormone deficiency. The possibility that growth hormone may significantly improve recovery in patients from serious wounds, malnutrition or catabolic states remains to be proven. Finally, the effect of growth hormone therapy on other body systems, such as the reproductive system, the immune system, or bone, is only beginning to be delineated. Clinical investigators are encouraged to maximize their research efforts through well designed and well controlled studies in their areas of interest.


Diffusion coefficient scaling of a free Brownian particle with velocity-dependent damping.
An analytical expression for the diffusion coefficient D of a free Brownian particle with velocity-dependent damping γ(v) is derived from the Green-Kubo formula. A special case of damping that decreases monotonically with velocity is considered. At high temperature T, the diffusion coefficient is found to exhibit two scaling types: (i) for a power-law decrease of damping with the particle's kinetic energy, γ(v)∝1/v^{2α}, it scales as D∝T^{α+1}; (ii) for a Gaussian function γ(v), it diverges at temperatures above a critical value T_{c} and behaves as D∝1/sqrt[T_{c}-T] at T slightly below T_{c}. At T>T_{c}, the particle trajectory contains long flight events, which are not observed at T<T_{c} in case (ii) and at all temperatures in case (i).


A study on enzymatic reaction using a liquid emulsion membrane technique.
An enzymatic reaction using a liquid emulsion membrane technique was studied to investigate the effects of some experimental variables on the stability of liquid membrane, enzyme deactivation, and transport of substrates and products. The hydrolysis of L-phenylalanine methyl ester by alpha-chymotrypsin was selected as a model reaction system. First, a transport mechanism for the substrates and products across the membrane was qualitatively identified. Second, it was found that the pH of the internal phase was one of the most important variables to determine the enzyme activity in a liquid membrane. Third, the effect of membrane phase which consists of surfactant, carrier, and organic solvent on the emulsion stability was investigated. It was found that the properties of the organic solvents greatly affect the emulsion stability. For an optimum condition, it was possible to reuse the emulsion which consists of membrane phase and internal phase without further separation. It was finally concluded that the enzyme in a liquid membrane retained 60% of its native activity in spite of vigorous mixing during the emulsification step.


Degree of conversion and cross-link density within a resin-matrix composite.
The aims of this study were to profile light radiated from two light-curing units (LCUs) and evaluate profile relationship to polymerization patterns within a resin-matrix composite (RMC). Beam profiles of one multiple emission peak light-emitting-diode and one quartz-tungsten-halogen curing-unit were measured using a beam profiler/spectrometer system. A camera-based profiler and an integrating sphere/spectrometer assembly were used to evaluate each LCU beam. Polymerization patterns within a nano-hybrid RMC were investigated using a mapping approach by assessing the degree of conversion utilizing micro-Raman spectroscopy and indirectly estimating cross-link-density by repeated microhardness testing before and after exposure to ethanol (%KH reduction, n = 3). The irradiance received on the top and bottom specimen surfaces from both LCUs was measured using a MARC-RC system. The investigated beam profile area from both LCUs was non-uniform and yielded localized discrepancies in DC (55.7-74.9%) and %KH reduction (26.7-54.1%). The LCU irradiance received at the bottom of the specimens was ∼10% of the top value. This study demonstrated that LCU beam profiles were non-uniform in the area explored. Localized differences in DC and %KH reduction existed throughout the RMC specimens but did not follow a specific pattern. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1496-1504, 2018.


[Molecular characterization of mosquitoes of the Anopheles gambiae complex from Mayotte and Great Comoro].
The mosquitoes of the Anopheles gambiae complex have been characterised at specific and sub-specific levels in two islands of the Comoros archipelago: the island of Mayotte (French departmental collectivity) and the island of Grande Comore (Comoros Union). Results are similar in the two islands and are presented together. The species An. gambiae s.s. was observed alone (determination performed on 149 specimens by PCR product of IGS of rDNA). The molecular form observed alone was S, and corresponds in this geographic area to the chromosomal form Savanna (determination performed on 123 specimens by another PCR product of IGS of rDNA). The haplotype IB was observed alone (determination performed on ten specimens, by sequencing the ITS of rDNA, with special attention at the position 871 of ITS), as previously observed by other authors in East Africa. Finally, in Mayotte and Grande Comore the An. gambiae complex is only composed by An. gambiae s.s. from the molecular form S/type IB.


Janus-Faced Fluorescence Imaging Agent for Malondialdehyde and Formaldehyde in Brains.
Carbonyl stress caused by reactive carbonyl species (RCS) is closely related to various brain diseases. As the highly reactive, highly toxic, and lipophilic RCS, malondialdehyde (MDA) and formaldehyde (FA) could easily cross the blood-brain barrier (BBB) and induce protein dysfunction or cross-linking in the brain. Do MDA and FA coordinately regulate the physio-pathological processes of the brain? To answer the question, first of all, powerful identification and sensing tools are needed. However, competent probes for simultaneously analyzing MDA and FA in living brains are lacking, which originates from the following three challenges: (1) MDA and FA are difficult to distinguish due to their great similarity in structure and reactivity; (2) to achieve simultaneous and discriminable imaging, same excitation and different emissions are preferable; and (3) the detection of MDA and FA in living brains require the materials to pass through the BBB. Thus, we created a two-photon fluorescent agent, TFCH, for MDA/FA. The hydrazine group in TFCH could successfully differentiate MDA/FA at 440/510 nm under same excitation. Moreover, the lipophilic trifluoromethyl group (-CF3) in TFCH prompts it to traverse the BBB, thereby realizing the coinstantaneous visualization of MDA and FA in the living brain. Using TFCH, we observed the excessive production of MDA and FA in living PC12 cells under carbonyl stress and oxidative stress. Notably, for the first time, two-photon fluorescence imaging indicated the synchronous increase of MDA and FA in living brains of mice with depression. Altogether, this work provides a promising tool for revealing the carbonyl stress-related molecular mechanism involved in brain diseases.


Effects of a secondary high amplitude stimulus on the impedance of perforated plates.
High sound pressure levels cause impedance changes in orifices and perforated plates due to vortex shedding and jet formation at the orifices. The effects of an additional high amplitude stimulus, unrelated in terms of frequency and phase, on the impedance of perforated plates received little attention. This work experimentally studies the impedance changes of perforated plates at various primary frequencies when an additional unrelated high-level single tone actuation is applied. It is shown that the impedance, the primary sound field faces, is altered dependent on the particle velocity induced in the orifices by the secondary actuation. Dimensionless quantities correlating the change of impedance with the secondary excitation are identified from the measurements and an empirical model for the change of resistance at quasi-steady flow conditions is derived. The results show that for low amplitude primary sound fields, the change of impedance is completely dependent on the secondary sound field. In case of a high amplitude primary sound field, the impedance is dependent on the particle velocities induced by both sound fields, whereas the larger induced particle velocity is the main contributor to the impedance changes. For unsteady flow conditions, a dependency on the frequency of the secondary actuation is found.


Endoscopic endonasal and transorbital approaches to petrous apex lesions.
The petrous apex (PA) is one of the most challenging areas in skull base surgery because it is surrounded by numerous critical neurovascular structures. The authors analyzed the clinical outcomes of patients who underwent endoscopic endonasal approach (EEA) and transorbital approach (TOA) procedures for lesions involving PA to determine the perspectives and proper applications of these two approaches. The authors included patients younger than 80 years with lesions involving PA who were treated between May 2015 and December 2019 and had regular follow-up MR images available for analysis. Patients with meningioma involving petroclival regions were excluded. The authors classified PA into three regions: superior to the petrous segment of the internal carotid artery (p-ICA) (zone 1); posterior to p-ICA (zone 2); and inferior to p-ICA (zone 3). Demographic data, preoperative clinical and radiological findings, surgical outcomes, and morbidities were reviewed. A total of 19 patients with lesions involving PA were included. Ten patients had malignant tumor (chondrosarcoma, chordoma, and osteosarcoma), and 6 had benign tumor (schwannoma, Cushing's disease, teratoma, etc.). Three patients had PA cephalocele (PAC). Thirteen patients underwent EEA, and 5 underwent TOA. Simultaneous combined EEA and TOA was performed on 1 patient. Thirteen of 16 patients (81.3%) had gross- or near-total resection. Tumors within PA were completely resected from 13 of 16 patients using a view limited to only the PA. Complete obliteration of PAC was achieved in all patients. Postoperative complications included 2 cases of CSF leak, 1 case of injury to ICA, 1 fatality due to sudden herniation of the brainstem, and 1 case of postoperative diplopia. EEA is a versatile surgical approach for lesions involving all three zones of PA. Clival tumor spreading to PA in a medial-to-lateral direction is a good indication for EEA. TOA provided a direct surgical corridor to the superior portion of PA (zone 1). Patients with disease with cystic nature are good candidates for TOA. TOA may be a reasonable alternative surgical treatment for select pathologies involving PA.


Development of a multidisciplinary osteoporosis telehealth program.
Osteoporosis is a disease characterized by low bone mass and changes to bone structure. The optimal treatment requires both pharmacologic and nonpharmacologic treatment including adequate levels of calcium and vitamin D, exercise, and fall prevention. There is currently a shortage of family physicians and specialists in Ontario, which can result in patients not receiving optimal osteoporosis care. In 2005, a multidisciplinary osteoporosis telehealth program, based on an existing outpatient program, was developed at Women's College Hospital in conjunction with NORTH Network (now part of the Ontario Telemedicine Network). The objectives of this study were to determine the feasibility of delivering a multidisciplinary model of care through telehealth and to improve access to specialist care for osteoporosis investigation and management. Patients were referred by family physicians (n = 20). The average length of the consultations was 2 hours. Ninety-two percent of the participants would use it again and would also recommend it to family and friends, 90% increased their knowledge about osteoporosis, and 83% felt completely comfortable discussing their health problems during their consultation. The results demonstrate that it is feasible to deliver an existing outpatient multidisciplinary osteoporosis program via telehealth. In addition, the program increased access to osteoporosis care, for complex patients in particular, highlighting an unmet need in their communities.


Effect of mitoxantrone on MRI in progressive MS: results of the MIMS trial.
To evaluate the effects of mitoxantrone (Mx) in progressive multiple sclerosis (MS) on MRI. A total of 194 patients with worsening relapsing-remitting or secondary progressive MS were treated with Mx 12 mg/m2 (n = 34), Mx 5 mg/m2 (n = 40), or placebo (n = 36) at 3-month intervals IV over a 2-year period. In preselected MRI centers unenhanced and Gd-enhanced MRI scans were performed at month (M) 0, 12, and 24 in a non-randomized subset of 110 patients and non-selected for MRI criteria. The primary MRI outcome measure was the total number of MRI scans with positive Gd enhancement per group. Twelve mg/m2 Mx failed to reach a significant difference from placebo as measured by the primary MRI outcome at month 12 (p = 0.431) and 24 (p = 0.065). Secondary MRI outcome measures: 5 mg/m2 Mx influenced favorably the number of Gd-enhancing lesions only at month 24 (p = 0.004), but not at month 12 (p = 0.095). Twelve mg/m2 Mx reduced the number of T2-weighted lesions at month 24 (p = 0.027) and showed a positive trend at month 12 (p = 0.069), but not 5 mg/m2 Mx. The number of active MR lesions showed a strong trend toward reduction in the 12 mg/m2 Mx group only at month 24 (p = 0.054). All comparisons are vs placebo, and unadjusted for baseline incidence. In the MIMS trial 12 mg/m2 Mx does not reduce the number of MRI scans with positive Gd enhancement at month 12 and 24 vs placebo. Results of secondary MRI outcome measures are suggestive of a positive impact of 12 and 5 mg/m2 Mx on some of the Gd enhanced and unenhanced MRI measures as expected from other Mx MRI studies in the past.


Value of the Jirgl flocculation test in the diagnosis of jaundice.
The Jirgl flocculation test has been compared with the combination of the thymol reactions and serum alkaline phosphatase determination recommended by Maclagan in the investigation of 68 patients with jaundice. The test was found to be of value in distinguishing biliary obstruction from other causes of jaundice, but failed to distinguish between extrahepatic and intrahepatic biliary obstruction. Serum glutamic oxalacetic transaminase and serum glutamic pyruvic transaminase estimations were performed in a number of cases, but were found to be of no value in the diagnosis of jaundice.


Airway pressure changes during one-lung ventilation.
This investigation analyzed the changes in inspiratory airway pressures during transition from two-lung to one-lung ventilation in patients tracheally intubated with a double-lumen endotracheal tube (DLT) using a classical method of intubation without fiberoptic bronchoscopy. All patients were anesthetized in a standardized fashion. Ventilation was accomplished with the Siemens 900 constant-flow mechanical ventilator (Solna, Sweden). Peak (Ppeak) and plateau (Pplateau) inspiratory airway pressures were recorded with an on-line respiratory monitor before and after clamping the tracheal limb of the DLT. The position of the DLTs was evaluated by fiberoptic bronchoscopy with the patient in supine position. Of the 51 intubations, the DLT was malpositioned in 15 cases (29.5%). Ppeak and Pplateau increased significantly when switched from two-lung ventilation to one-lung ventilation in both correctly and incorrectly positioned DLTs. When the DLT was in a correct position, Ppeak increased by a mean of 55.1% and Pplateau increased by a mean of 41.9%. When the DLT was malpositioned, this increase was significantly larger (74.9% and 68.8%, respectively). Three tests commonly used as markers of malpositioned DLTs were evaluated based on the data of this study, and it was established that, although the pressure differences related to position are statistically significant, as a single value, they cannot be used for clinical decision making.


Morphing-Enabled Path Planning for Flying Tensegrity Robots as a Semidefinite Program.
The development of deformable drones is of high importance but presents significant challenges. Such drones can be based on tensegrity structures, which leaves open the questions of configuration-space path planning for such robots. In this paper we propose a method that takes advantage of a simplified encoding of the drone's shape, allowing to turn the path planning into a sequence of semidefinite programs. The mapping from the simplified description and the actual tensegrity configuration is done via a data-driven method, using a pre-computed dataset of statically stable configurations and their outer Löwner-John ellipsoids, as well as eigendecompositions of the ellipsoid matrices. Together it allows rapid containment check, whose computational cost depends linearly on the number of dataset entries. Thus, the proposed method offloads computationally-intensive parts to the offline dataset generation procedure, speeding up the algorithm execution.


A phylogenetic analysis of cordyliformes (Reptilia: Squamata): comparison of molecular and karyological data.
A karyological study and the analysis of two mitochondrial genes were conducted in several species of cordyliformes from Madagascar. Both studies confirmed the monophyly of cordyliformes. The karyological conservatism and small genetic distance among mitochondrial genes observed in these species are in line with the hypothesis that all cordyliformes should be included in a single family. The two studies yielded contrasting results with regard to the relationships between the Malagasy species and the Cordylidae and Gerrhosauridae. Nonetheless, the consistency between the data from mitochondrial gene analysis and those of taxonomic studies based on morphological characters is more in favor of an affinity between Malagasy Zonosaurinae and Gerrhosauridae and suggests that the karyological similarities between the former and the Cordylidae may be due to plesiomorphy. Interesting, though not conclusive, data were also obtained on interspecific relationships among Zono-


Risk factors for poor survival after recurrence of hepatocellular carcinoma after liver transplantation.
This study was designed to analyze the risk factors for poor survival after recurrence of hepatocellular carcinoma after liver transplantation. Patients who underwent liver transplantation for hepatocellular carcinoma during the period of 2007 to 2018 were reviewed and patients who experienced recurrence were included. Multivariable Cox proportional hazard ratios were performed for potential risk factors for survival after recurrence. A total of 151 recipients experienced hepatocellular carcinoma recurrence after liver transplantation. The median of the recurrence-free period was 9.3 months (0.89-97.25 months). The median follow-up after recurrence was 13.4 months (0.59-118.28 months). One-, 3-, and 5-year survival after recurrence were 65.2%, 34.0% and 20.5%, respectively. Multivariable Cox analysis showed that, graft from living donor (hazard ratio [HR], 0.430; 95% confidence interval [CI], 0.210-0.882; P = 0.021), recurrence-free interval of ≥9 months (HR, 0.257; 95% CI, 0.164-0.403; P < 0.001), alphafetoprotein of ≥100 ng/mL at the time of recurrence (HR, 1.689; 95% CI, 1.059-2.695; P = 0.028), and recurrence in bone (HR, 2.304; 95% CI, 1.399-3.794; P = 0.001) and everolimus within 3 months after recurrence (HR, 0.354; 95% CI, 0.141-0.889; P = 0.027) were related to survival after recurrence. Although survival was generally poor after recurrence of hepatocellular carcinoma in liver transplantation recipients, prolonged survival can be achieved in certain patients with better prognostic factors.


Correlation between Retention and Hydrocarbonaceous Area of Non-protein Alicyclic α-Amino Acids in Reversed-phase HPLC.
The retention by reversed-phase HPLC of a homologous series of aliphatic amino acids increased as the size of the apolar moiety increased. By use of the hydrocarbonaceous surface area as the structural descriptor, we found that cyclic amino acids had higher retention indices than the corresponding linear homologues. The retention difference between ring and chain compounds probably arises from the entropy effects.


Rapid virological response is the most important predictor of sustained virological response across genotypes in patients with chronic hepatitis C virus infection.
The probability of response to peginterferon and ribavirin is associated with numerous host and virological factors. Attainment of a rapid virological response (RVR), defined as undetectable HCV RNA at week 4 during treatment with peginterferon and ribavirin, is highly predictive of sustained virological response (SVR). The aim of the present study was to determine the relative importance of the kinetics of antiviral response compared to baseline host and virological factors for predicting SVR. A retrospective analysis of 1383 patients, encompassing genotypes 1-4, treated with peginterferon alfa-2a and ribavirin, was performed. Baseline characteristics were compared across HCV genotypes and pretreatment factors associated with RVR were identified. The relative significance of RVR compared to other baseline factors for predicting SVR was analyzed by multiple logistic regression analysis. RVR was achieved by 16% of patients with genotype 1 and 71% and 60% of those with genotype 2 and 3, respectively. Among patients who achieved RVR, the rate of SVR was high across all genotypes and ranged from 88% to 100% (genotypes 1-4). Baseline factors predictive of RVR included genotype, younger age, lower initial viral load, higher ALT ratio, absence of advanced fibrosis, and younger age. Notably, the presence of RVR generated the highest odds ratio (5.47, 95% confidence interval 3.97-7.52) for predicting SVR in multiple logistic regression analysis of these factors. Attainment of RVR varies by genotype and is associated with several baseline factors. Patients who achieve RVR have the highest rates of SVR, regardless of genotype. These findings have important implications for predicting and managing response-guided combination antiviral therapies.


Threats to life in residential structure fires.
Firefighters are taught that heat, oxygen deprivation, and carbon monoxide (CO) are the primary threats to life in residential structure fires, and they are taught to search for victims on the fire floor first, and then floors above. The objective of this study was to gather data regarding oxygen, CO, and heat conditions inside a realistic house fire, to examine the validity of these teachings. During six live-burn training evolutions in a two-story wood-frame house, metering for oxygen levels, CO levels, and temperature was conducted. Except where noted, all readings were taken 24 inches off the floor, to simulate the location of a crawling victim or firefighter. Readings were hand-recorded on a convenience basis by firefighters stationed outside the building, near the meters. Of the 35 oxygen levels recorded, the lowest was 18.2%, with only 12 readings below 20%. Three of 16 first-floor readings were below 20%, whereas nine of 19 second-floor readings were below 20% (p=0.07). First- and second-floor readings were comparable (mean 20.3% vs. 19.9%, p=0.11). Except for one reading of 1,870 ppm, all CO readings at the ceiling exceeded the 2,000-ppm limit of the meters. Of the 34 CO levels recorded 24 inches off the floor, 29 (76%) exceeded the permissible exposure limit of 50 ppm, with the highest reading being 1,424 ppm, well above the "immediately dangerous to life and health" level of 1,200 ppm. None of the 20 CO levels recorded on the first floor exceeded the 30-minute exposure limit of 800 ppm, whereas seven of 14 second-floor readings exceeded this limit (p<0.001). While ceiling temperatures frequently exceeded the 1,000 degrees F limit of the meters, none of 16 readings taken 24 inches off the floor exceeded 137 degrees F. First- and second-floor temperatures were comparable (mean 88.5 degrees F vs. 90.1 degrees F, p=0.9). In residential structure fires, CO poses a greater threat to victims and firefighters than does oxygen deprivation or heat. Emergency medical services personnel should consider CO toxicity in all fire victims. Conditions on the floor above a fire are at least as adverse as those on the fire floor.


Genetic analysis of trimethylamine N-oxide reductases in the light organ symbiont Vibrio fischeri ES114.
Trimethylamine N-oxide (TMAO) reductases are widespread in bacteria and often function in anaerobic respiration. The regulation and expression of TMAO reductase operons have been well studied in model genera such as Escherichia, Shewanella, and Rhodobacter, although TMAO reductases are present in many other bacteria, including the marine Vibrio species. The genome sequence of Vibrio fischeri revealed three putative TMAO reductase operons, and a previous report identified TMAO reductase activity in symbiotic V. fischeri isolates associated with the light organs of adult Hawaiian bobtail squid, Euprymna scolopes. We examined the roles and regulation of these three operons using mutational analyses and promoter-reporter fusions. We found that the torECA promoter, and to a lesser extent the torYZ and dmsABC promoters, were active during symbiotic colonization of juvenile E. scolopes; however, a V. fischeri strain lacking TMAO reductase activity displays no discernible colonization defect over the first 48 h. Our studies also revealed that torECA has the most active promoter of the putative TMAO reductase operons, and TorECA is the major contributor to TMAO-dependent growth in V. fischeri under the conditions tested. Interestingly, the transcriptional regulation of TMAO reductase operons in V. fischeri appears to differ from that in previously studied organisms, such as Escherichia coli, which may reflect differences in gene arrangement and bacterial habitat. This study lays the foundation for using V. fischeri as a model system for studying TMAO reductases in the Vibrionaceae.


Subacute myelopathy: an unusual paraneoplastic complication of Hodgkin's disease.
We report a case of Hodgkin disease presenting with a subacute myelopathy without evidence of metastatic involvement of the spinal cord. The systemic disease responded to conventional chemotherapy, but the myelopathy only improved after intrathecal dexamethasone was added to the treatment program, beta-2-microglobulin levels in the cerebrospinal fluid were elevated at presentation. Following the use of intrathecal corticosteroids there was a decrease of CSF beta-2-microglobulin levels. The possible significance of these findings is discussed.


Association of Three Single Nucleotide Polymorphisms in MTR and MTRR Genes with Lung Cancer in a Turkish Population.
Folate metabolism plays a critical role in DNA methylation and synthesis. Polymorphisms in folate metabolism may affect enzyme activities and thereby affect the cancer risk. Methionine synthase (MTR) and methionine synthase reductase (MTRR) are critical enzymes for the folate cycle. In this study, possible associations between genetic variabilities in MTR and MTRR and susceptibility to lung cancer (LC) were investigated in a Turkish population. A case-control study with 193 LC cases and 199 noncancerous controls was conducted. DNA was extracted from leukocytes using the high pure polymerase chain reaction (PCR) template preparation kit. The MTR 2756 A>G (rs1805087), MTRR 524 C > T (rs1532268), and MTRR 66 A>G (rs1801394) genotypes were determined using PCR-restriction fragment length polymorphism (PCR-RFLP) assays. The genotype and haplotype analyses of these polymorphisms were performed using SPSS 21 and Haploview 4.2, respectively. An association between the MTRR A66G polymorphism and LC (p = 0.042) was found. In addition, this allele was observed more frequently in smokers compared to nonsmokers (p = 0.030). In contrast, the distribution of the MTR 2756 A>G and the MTRR 524 C > T allele frequencies were similar in the subject cases and controls. In conclusion, the present study suggests an association between the MTRR 66 A>G gene polymorphisms and LC risk in a Turkish population.


In-depth analysis of anisotropic magnetoconductance in Bi2Se3thin films with electron-electron interaction corrections.
A combination of out-of-plane (OOP) and in-plane (IP) magnetoconductance (MC) study in topological insulators (TI) is often used as an experimental technique to probe weak anti-localization (WAL) response of the topological surface states (TSSs). However, in addition to the above WAL response, weak localization (WL) contribution from conducting bulk states are also known to coexist and contribute to the overall MC; a study that has so far received limited attention. In this article, we accurately extract the above WL contribution by systematically analyzing the temperature and magnetic field dependency of conductivity in Bi2Se3films. For accurate analysis, we quantify the contribution of electron-electron interactions to the measured MC which is often ignored in the WAL studies. Moreover, we show that the WAL effect arising from the TSSs with finite penetration depth, for OOP and IP magnetic field can together explain the anisotropic magnetoconductance (AMC) and, thus, the investigated AMC study can serve as a useful technique to probe the parameters like phase coherence length and penetration depth that characterise the TSSs in 3D TIs. We also demonstrate that increase in bulk-disorder, achieved by growing the films on amorphous SiO2substrate rather than on crystalline Al2O3(0001), can lead to stronger decoupling between the top and bottom surface states of the film.


Evaluating exposure of northern fur seals, Callorhinus ursinus, to microplastic pollution through fecal analysis.
Environmental microplastics are widely documented in marine life and bioaccumulation may present risks to marine predators. Investigations of microplastics in marine mammals are increasing, though none have examined animals routinely consumed by humans. Here, we investigate microplastic exposure in the northern fur seal (Callorhinus ursinus), a species consumed by humans, using fecal material. We examined 44 feces (scat) at sites encompassing the seals' eastern Pacific range. Multiple contamination control measures were implemented, including field and laboratory controls. Fragments were the most common microplastic recovered, in 55% (24/44) of scat and no controls (range 1 to 86 fragments/scat, mean 16.6, sd 19.1). Microplastic fibers were recovered from 41% of scats (18/44), though some controls contained fibers confounding fiber results. Fecal analysis documented northern fur seal exposure to microplastics throughout their eastern Pacific range.


Computing the meanings of words in reading: cooperative division of labor between visual and phonological processes.
Are words read visually (by means of a direct mapping from orthography to semantics) or phonologically (by mapping from orthography to phonology to semantics)? The authors addressed this long-standing debate by examining how a large-scale computational model based on connectionist principles would solve the problem and comparing the model's performance to people's. In contrast to previous models, the present model uses an architecture in which meanings are jointly determined by the 2 components, with the division of labor between them affected by the nature of the mappings between codes. The model is consistent with a variety of behavioral phenomena, including the results of studies of homophones and pseudohomophones thought to support other theories, and illustrates how efficient processing can be achieved using multiple simultaneous constraints.


Indications for functional examination in patients with peripheral arteriopathy.
On the basis of personal research with the reactive hyperemia test and of a study of the literature, an attempt is made to adequately define the indications for functional examination of patients with arteriosclerosis obliterans. The question considered is how much extra information is gained by functional examination, compared with the mere determination of ankle/arm systolic blood pressure index at rest, in regard to the following problems: 1 are the symptoms indeed due to arterial insufficiency? 2 how severe is this insufficiency? 3 where are the hemodynamically important lesions situated? It is concluded that functional examination rarely yields additional information in respect of these three questions, and therefore need not be carried out routinely.


Myopathy during statin therapy in the daily practice of an outpatient cardiology clinic: prevalence, predictors and relation with vitamin D.
The mechanism of statin-related myopathy is unknown, while its prevalence is probably underestimated. An association between statin-related myopathy and vitamin D deficiency has been reported. In this pilot study we assessed the prevalence of myopathy in statin users attending the outpatient clinic of the Department of Cardiology of a University Hospital from October 2009 to March 2010. We also searched for predictors of myopathy and investigated whether the myopathy was associated with vitamin D deficiency. Statin-treated patients were asked to complete an assisted structured questionnaire. Serum creatine kinase (CK) and 25-hydroxyvitamin D (25(OH)D) were measured. Patients with rheumatic diseases, muscle diseases, (poly)neuropathy and peripheral arterial disease were excluded from predictor analysis. Percentage of patients with myopathy in the daily clinical practice of an outpatient clinic, serum 25(OH)D, CK, and predictors of myopathy. One hundred and four statin-treated patients completed the questionnaire. Serum 25(OH)D was measured in 93 patients. Twenty patients with confounding comorbidities were excluded from analysis. Of the remaining 84 patients, 33% reported myopathy, 24% had myalgia and 6% myositis. Rhabdomyolysis was not observed. Time spent outdoors during winter (≤6 h/week; OR: 10.61; 95% CI: 1.91-58.88), total number of prescribed drugs (1.39; 1.05-1.83), BMI (1.35; 1.07-1.69), CK (1.02; 1.00-1.03) and consumption of fish (≥1/week; 0.19; 0.04-0.89) were predictors of myopathy in multivariate analysis. Considering the small patient group and a relatively narrow range of vitamin D levels, we arrive at the following statements: 1) one out of three patients reported myopathy; 2) BMI, CK, number of prescription drugs, time spent outdoors and fish consumption were myopathy predictors; and 3) myopathy and 25(OH)D were unrelated.


Quorum protection, growth and survival.
For the growth of a cell culture, one inoculates not with one cell but with a quorum of cells. This most often a requirement, not just a convenience, and most of us take this for granted without question. Here this observation is re-examined to understand why a quorum may be required to grow cells. The importance of quorums may be widespread in the aspects of microbiology they affect. It is very likely that quorums are connected with and have a large impact on the determination of Minimal Inhibitory Concentrations. It is also possible that low cell density may adversely affect cell survival, however, this is an area where even less is known. The need for a quorum might affect other aspects of microbial cell culture, cell isolation and cell preservation. Effects also extend to mammalian cell culture. Here I seek to review studies that have been documented and speculate on how the information might be utilized in the future.


Infections in patients with inherited defects in phagocytic function.
Patients with defects in phagocytic function are predisposed to intracellular microorganisms and typically have early dissemination of the infection. Recognition of the underlying disorder and aggressive antimicrobial therapy has been beneficial for the patients. Improved understanding of the pathophysiology has also affected patient management by allowing specific, targeted immunomodulatory intervention. The disorders described in this review are not common but have had a significant impact on our understanding of the role of phagocytic cells in host defense. Conversely, understanding the role of the neutrophil and macrophage in infection has benefited not just the patients described in this review but also other patients with similar disease processes.


Pioglitazone promotes insulin-induced activation of phosphoinositide 3-kinase in 3T3-L1 adipocytes by inhibiting a negative control mechanism.
Activation of phosphoinositide 3-kinase (PI 3-kinase) is an early event in insulin signal transduction that is blocked completely in adipocytes from insulin-resistant KKAy mice. Treatment of KKAy mice with pioglitazone, an anti-diabetic thiazolidinedione, partially restores insulin-dependent changes in PI 3-kinase. The mechanism of this effect of pioglitazone was investigated, using murine 3T3-L1 cells as an experimental model. Insulin and insulin-like growth factor I (IGF-I) each elicited rapid (within 2 min) and large (2- to 5-fold) increases in PI 3-kinase activity that could be immunoprecipitated using anti-phosphotyrosine (pY) antibodies. Maximal insulin-induced activity of PI 3-kinase in pY-immunoprecipitates was similar in 3T3-L1 adipocytes and mouse adipocytes, but the kinetics of activation differed. Insulin- and IGF-I-induced changes in PI 3-kinase were each half-maximal at 3-5 nM of hormone and were not additive. Increases in both insulin-induced and IGF-I-induced pY-immunoprecipitable PI 3-kinase activity were observed when 3T3-L1 fibroblasts became confluent and when they adopted the adipocyte phenotype. Pioglitazone (10 microM), administered either acutely or chronically to either 3T3-L1 adipocytes or 3T3-L1 fibroblasts, did not alter greatly the kinetics, magnitude or sensitivity of changes in PI 3-kinase elicited by either insulin or IGF-I. In contrast, the attenuation by isoproterenol of insulin-induced changes in PI 3-kinase was prevented in cells pretreated with pioglitazone. This effect of pioglitazone did not involve inhibition of isoproterenol-elicited accumulation of cyclic AMP. Pioglitazone also prevented attenuation of insulin induced changes in PI 3-kinase by cell penetrating analogs of cyclic AMP. Pioglitazone, therefore, has no direct effect on insulin-stimulated PI 3-kinase activity, but interferes with a cyclic AMP-dependent mechanism that normally antagonizes this action of insulin. These data support the proposition that the facilitation of insulin action by pioglitazone involves, at least in part, an inhibition of a negative control mechanism.


Hydrolysis of butteroil by immobilized lipase using a hollow-fiber reactor: IV. Effects of temperature.
A lipase from Aspergillus niger, immobilized by adsorption on microporous polypropylene hollow fibers, was used to effect the hydrolysis of the glycerides of melted butterfat at pH. 7.0 at 40, 50, 55, and 60 degrees C. Mcllvane buffer was pumped upward through the lumen, and melted butterfat was pumped upward through the shell side of a hollow fiber reactor. Nonlinear regression methods were employed to determine the kinetic parameters of models based on combinations of three nested rate expressions for the hydrolysis reaction with three nested rate expressions for thermal deactivation of the enzyme. A rate expression containing four lumped parameters is sufficient to model the release of free fatty acids as a function of reactor space time and time elapsed after immobilization. Nonlinear regression methods were also employed in global fits of the data to rate expressions containing an explicit dependence on temperature. For the reaction conditions used in this research, a 14-parameter rate expression is necessary to accurately model the overall release of free fatty acids as a continuous function of the absolute temperature, initial substrate concentrations, reactor space time, and time elapsed after immobilization of the lipase.


(E)-Ethyl 2-benzoyl-4-(naphthalen-2-yl)-4-oxobut-2-enoate.
The title compound, C(23)H(18)O(4), is a 1,4-enedione compound which contains a naphthalene ring and a benzene ring. The dihedral angle between the ring systems is 74.9 (2)°. In the crystal, the mol-ecules form π-π stacking inter-actions between naphthalene rings of inversion-related mol-ecules, with an inter-planar spacing of 3.499 (2) Å.


Does Proton Therapy Have a Future in CNS Tumors?
Proton therapy is characterized by certain physical properties leading to a reduction in integral dose. As proton therapy becomes more widely available, the ongoing discussion on the real indications for proton therapy becomes more important. In the present article, data on proton therapy for tumors of the central nervous system (CNS) is summarized and discussed in view of modern photon treatments. Still today, no randomized controlled trials are available confirming any clinical benefit of protons in CNS tumors. For certain skull base lesions, such as chordomas and chondrosarcomas, dose escalation is possible with protons thus patients should be referred to a proton center if readily available. For vestibular schwannoma, at present, proton data are inferior to advanced photons. For glioma patients, early data is present for low-grade gliomas, presenting comparable results to photons; dose escalation studies for high-grade gliomas have led to significant side effects, thus strategies of dose-escalation need to rethought. For skull base meningiomas, data from stereotactic series and IMRT present excellent local control with minimal side effects, thus any improvement with protons might only be marginal. The largest benefit is considered in pediatric CNS tumors, due to the intricate radiation sensitivity of children's normal tissue, as well as the potential of long-term survivorship. Long-term data is still lacking, and even recent analyses do not all lead to a clear reduction in side effects with improvement of outcome; furthermore, clinical data seem to be comparable. However, based on the preclinical evidence, proton therapy should be evaluated in every pediatric patient. Protons most likely have a benefit in terms of reduction of long-term side effects, such as neurocognitive sequelae or secondary malignancies; moreover, dose escalation can be performed in radio-resistant histologies. Clinical data with long-term follow-up is still warranted to prove any superiority to advanced photons in CNS tumors. If available, protons should be evaluated for chordoma or chondrosarcoma of the skull base and pediatric tumors. However, many factors are important for excellent oncology care, and no time delay or inferior oncological care should be accepted for the sake of protons only.


Effect of Type 2 Diabetes on the Development of Acute Respiratory Distress Syndrome (ARDS) in Patients with Lung Cancer After Surgery and Its Prognosis.
Type 2 diabetes mellitus (T2DM) is associated with the occurrence of lung cancer. Postoperative lung cancer complications with acute respiratory distress syndrome (ARDS) are characterized by rapid onset and severe disease. This study aimed to analyze the effect of T2DM on the occurrence of ARDS in patients with lung cancer after surgery and its prognosis and further investigate the risk factors of postoperative complications of ARDS. A total of 530 patients who developed lung cancer from December 2016 to December 2021 were retrospectively analyzed. The t- and chi-square tests were used to determine the relationship between whether the patients had combined diabetes and other clinical characteristics. Binary logistic and Cox risk regressions were used to analyze the independent risk factors for the development of ARDS in patients after surgery and the effect of each factor on the survival status of patients, respectively. Fifty-three cases of ARDS occurred after lung cancer surgery, with an incidence of 10%. Binary logistic regression analysis demonstrated that the independent influencing factors that determined the occurrence of ARDS after surgery were the presence or absence of combined diabetes (odds ratio [OR] = 3.888, P<0.001), history of radiotherapy (OR = 2.039, P = 0.024), surgery mode (OR = 2.521, P = 0.002), and so on. Moreover, Cox risk regression analysis demonstrated that the presence or absence of combined diabetes (OR = 1.389, P = 0.039) and occurrence of ARDS (OR = 2.028, P = 0.037) were independent influencing factors on the patient survival time. In lung cancer patients with T2DM, postoperative ARDS is more likely to occur, and both diabetes and postoperative ARDS are risk factors affecting the survival of patients with lung cancer. Preoperative and postoperative glycemic control and improved pulmonary ventilation should be enhanced to minimize the chance of ARDS.


A new look at Crohn's disease: novel imaging techniques.
Imaging the gut provides information on Crohn's disease activity, identifies complications and provides insight into patient symptoms. Imaging can help direct therapy and can predict important patient outcomes. In a rapidly changing, technology-driven field, new imaging applications add novel insights that we are only beginning to appreciate. The purpose of this review is to highlight recent advances in imaging as they are applied to the assessment of patients with Crohn's disease. In the past year, key literature describing cross-sectional imaging techniques, including computed tomography (CT) based imaging, specifically CT enterography (CTE) and magnetic resonance enterography (MRE), transcutaneous ultrasound, and PET-based imaging, has emerged in the field of inflammatory bowel disease. MRI sequences that have been recently applied to Crohn's disease assessment, including diffusion-weighted imaging (DWI) and magnetization transfer imaging (MTI), add important new insights. These new data highlight the current status of available imaging modalities and provide a glimpse into the future of our practice. CTE and MRE are our new standard imaging modalities for small bowel Crohn's disease. PET scanning is promising but currently only used routinely in centers with a strong research presence in this area. Ultrasound is emerging as a useful, potentially less costly, radiation-free technique. New MRI sequences offer future promise for effectively monitoring the natural history of Crohn's disease.


Two divergent catalase genes are differentially regulated during Aspergillus nidulans development and oxidative stress.
Catalases are ubiquitous hydrogen peroxide-detoxifying enzymes that are central to the cellular antioxidant response. Of two catalase activities detected in the fungus Aspergillus nidulans, the catA gene encodes the spore-specific catalase A (CatA). Here we characterize a second catalase gene, identified after probing a genomic library with catA, and demonstrate that it encodes catalase B. This gene, designated catB, predicts a 721-amino-acid polypeptide (CatB) showing 78% identity to an Aspergillus fumigatus catalase and 61% identity to Aspergillus niger CatR. Notably, similar levels of identity are found when comparing CatB to Escherichia coli catalase HPII (43%), A. nidulans CatA (40%), and the predicted peptide of a presumed catA homolog from A. fumigatus (38%). In contrast, the last two peptides share a 79% identity. The catalase B activity was barely detectable in asexual spores (conidia), disappeared after germination, and started to accumulate 10 h after spore inoculation, throughout growth and conidiation. The catB mRNA was absent from conidia, and its accumulation correlated with catalase activity, suggesting that catB expression is regulated at the transcription level. In contrast, the high CatA activity found in spores was lost gradually during germination and growth. In addition to its developmental regulation, CatB was induced by H2O2, heat shock, paraquat, or uric acid catabolism but not by osmotic stress. This pattern of regulation and the protective role against H2O2 offered by CatA and CatB, at different stages of the A. nidulans life cycle, suggest that catalase gene redundancy performs the function of satisfying catalase demand at the two different stages of metabolic and genetic regulation represented by growing hyphae versus spores. Alternative H2O2 detoxification pathways in A. nidulans were indicated by the fact that catA/catB double mutants were able to grow in substrates whose catabolism generates H2O2.


Health sector reform and equity: a study at a family health center affiliated to health insurance organization in Alexandria.
The 1990's witnessed a wave of reform in health systems of many countries. Health sector reform (HSR) initiatives aimed at improving health status, utilizers' satisfaction, as well as equity and accessibility of care. This study aims at exploring the question of whether there is a socioeconomically- based differential access to services provided by a family health center applying HSR. A total of 248 utilizers were randomly selected and interviewed. An access index comprised of eight elements was developed to measure access and its corollary equity. Results demonstrated that the majority belonged to the low middle socio-economic class and one- quarter belonged to the low class. Approximately 9/10 of utilizers had high access to the services offered. Mean access index score for all utilizers was above the 90% mark. ANOVA analysis of mean access index according to socio-economic class revealed that there is no statistically significant disparity among various socio-economic classes regarding their access to care. However, it was demonstrated that higher classes had a higher opinion concerning the completeness of physical examination during the initial visit than lower classes. It was recommended to establish an appropriate policy framework to assure optimal standards of equity, preferably a 100% of high access as measured through the access index devised in this study.


[Chronic alveolar hypoventilation in obstructive sleep apnea syndrome].
Among 30 patients with obstructive sleep (OSA) syndrome in 15% (50%) chronic alveolar hypoventilation developed; chronic hypercapnia was found in patients with mildly (7), moderately (2) and severely (6 patients) impaired lung ventilatory function. All patients with chronic hypercapnia were morbidly obese (BMI 44 +/- 12). Nocturnal polysomnography showed similar mean apnea duration in the groups of hypercapnic and eucapnic patients, longer duration of the longest apneas in hypercapnia (88 +/- 42 s) than in eucapnia (38 +/- 19 s), p < 0.01 and more severe desaturation during sleep (the mean of the lowest SaO2 during apneas 0.46 +/- 0.17 mol/mol) in hypercapnic and 0.71 +/- 0.11 mol/mol in eucapnic patients, p < 0.001). Polycythemia was found in 14 patients, exclusively in hypercapnia. Chronic alveolar hypoventilation develops in some obese patients with impaired-even mildly or moderately-lung ventilatory function and with the most severe OSA syndrome, in which apneas may occasionally be extremely long and lead to very low saturation during sleep. Polycythemia occurs in most patients with chronic alveolar hypoventilation and OSA syndrome.


Significant metabolic improvement by a water extract of olives: animal and human evidence.
Dyslipidemia and impaired glucose metabolism are the main health issues of growing prevalence and significant high healthcare cost, requiring novel prevention and/or therapeutic approaches. Epidemiological and animal studies revealed that olive oil is an important dietary constituent, inducing normolipidemia. However, no studies have specifically investigated the polyphenol-rich water extract of olives (OLWPE), generated during olive oil production. In the present work, we initially examined the effect of OLPWE on animals' metabolic parameters. Rats fed with a high-fat diet were treated with three different doses of OLPWE for 4 months. Additionally, bioavailability was explored. Afterwards, OLWPE's metabolic effect was explored in humans. Healthy volunteers consumed microencapsulated OLWPE for 4 weeks, in a food matrix [one portion (30 g) of a meat product]. High-fat-fed rats developed a metabolic dysfunction, with increased LDL and insulin levels and decreased HDL; this syndrome was significantly impaired when treated with OLWPE. Treated rats had increased total plasma antioxidant capacity, while several phenolic compounds were detected in their blood. These findings were also verified in humans that consumed OLWPE, daily, for 4 weeks. Interestingly, in individuals with elements of cardio-metabolic risk, OLWPE consumption resulted in reduced glucose, insulin, total cholesterol, LDL and oxLDL levels. Our data clearly show that OLWPE can improve glucose and lipid profile, indicating its possible use in the design of functional food and/or therapeutic interventions.


Biomimetic Connection of Transcutaneous Implants with Skin.
Bacterial infection is a crucial complication in implant restoration, in particular in permanent skin-penetrating implants. Therein, the resulting gap between transcutaneous implant and skin represents a permanent infection risk, limiting the field of application and the duration of application. To overcome this limitation, a tight physiological connection is required to achieve a biological and mechanical welding for a long-term stable closure including self-healing probabilities. This study describes a new approach, wherein the implant is connected covalently to a highly porous electrospun fleece featuring physiological dermal integration potential. The integrative potential of the scaffold is shown in vitro and confirmed in vivo, further demonstrating tissue integration by neovascularization, extracellular matrix formation, and prevention of encapsulation. To achieve a covalent connection between fleece and implant surface, self-initiated photografting and photopolymerization of hydroxyethylmethacrylate is combined with a new crosslinker (methacrylic acid coordinated titanium-oxo clusters) on proton-abstractable implant surfaces. For implant modification, the attached fleece is directed perpendicular from the implant surface into the surrounding dermal tissue. First in vitro skin implantations demonstrate the implants' dermal integration capability as well as wound closure potential on top of the fleece by epithelialization, establishing a bacteria-proof and self-healing connection of skin and transcutaneous implant.


COPULATORY BEHAVIOR, GENITAL MORPHOLOGY, AND MALE FERTILIZATION SUCCESS IN WATER STRIDERS.
Recent theoretical and empirical interest in postmating processes have generated a need for increasing our understanding of the sources of variance in fertilization success among males. Of particular importance is whether such postmating sexual selection merely reinforces the effects of premating sexual selection or whether other types of male traits are involved. In the current study, we document large intraspecific variation in last male sperm precedence in the water strider Gerris lateralis. Male relative paternity success was repeatable across replicate females, showing that males differ consistently in their ability to achieve fertilizations. By analyzing shape variation in male genital morphology, we were able to demonstrate that the shape of male intromittent genitalia was related to relative paternity success. This is the first direct experimental support for the suggestion that male genitalia evolve by postmating sexual selection. A detailed analysis revealed that different components of male genitalia had different effects, some affecting male ability to achieve sperm precedence and others affecting male ability to avoid sperm precedence by subsequent males. Further, the effects of the shape of the male genitalia on paternity success was in part dependent on female morphology, suggesting that selection on male genitalia will depend on the frequency distribution of female phenotypes. We failed to find any effects of other morphological traits, such as male body size or the degree of asymmetry in leg length, on fertilization success. Although males differed consistently in their copulatory behavior, copulation duration was the only behavioral trait that had any significant effect on paternity.


Is the 14C-triolein breath test useful in the assessment of malabsorption in clinical practice?
A 14C-triolein breath test was carried out on 49 subjects suffering from chronic pancreatitis or from other digestive diseases, and its results were compared with the daily fecal fat excretion. The 14CO2 peak excretion was abnormal in all the subjects with a fecal fat excretion above 14 g/day, whereas individual values of 14CO2 peak excretion in subjects without steatorrhea and with a fecal fat excretion ranging from 7.1 to 14 g overlapped. The lowest value observed in patients not suffering from steatorrhea was chosen as the lower normal limit of 14CO2 peak excretion. A test sensitivity as high as 64% was attained. The correlation between fecal fat and 14CO2 peak excretion was highly significant (r = 0.802; p less than 0.0001), and it followed a negative exponential function. Therefore, small variations in the 14CO2 peak excretion can be associated with a wide range of fecal fat excretion. Well-compensated diabetes secondary to pancreatitis did not interfere with the results of the test. In conclusion, in our experience this test proved to be a qualitative diagnostic tool with a low sensitivity.


The course of development of mania in patients with recurrent depression.
The authors attempted to assess the extent to which bipolar patients are misdiagnosed as unipolar by evaluating the development of mania in patients who had recognized bipolar illness and by means of follow-up data on patients who had recurrent depressions. Mania occurred early in the course of bipolar illness: almost 80% of the bipolar patients were initially hospitalized for mania. Follow-up data and theoretically based calculations suggest that the chance of a patient with recurrent depressions becoming bipolar is about 5%. Based on these findings, the authors make suggestions for the classification of unipolar patients.


Computational implementation of interfacial kinetic transport theory for water vapour transport in porous media.
A computational framework is developed for applying interfacial kinetic transport theory to predict water vapour permeability of porous media. Modified conservation equations furnish spatially periodic disturbances from which the average flux and, thus, the effective diffusivity is obtained. The equations are solved exactly for a model porous medium comprising parallel layers of gas and solid with arbitrary solid volume fraction. From the microscale effective diffusivity, a two-point boundary-value problem is solved at the macroscale to furnish the water vapour transport rate in membranes subjected to a finite RH differential. Then, the microscale model is implemented using a computational framework (extended finite-element method) to examine the role of particle size, aspect ratio and positioning for periodic arrays of aligned super-ellipses (model particles that pack with high density). We show that the transverse water vapour permeability can be reduced by an order of magnitude only when fibres with a high-aspect ratio cross section are packed in a periodic staggered configuration. Maximum permeability is achieved at intermediate micro-structural length scales, where gas-phase diffusion is enhanced by surface diffusion, but not limited by interfacial-exchange kinetics. The two-dimensional computations demonstrated here are intended to motivate further efforts to develop efficient computational solutions for realistic three-dimensional microstructures.


Coarse and Fine Two-Stage Calibration Method for Enhancing the Accuracy of Inverse Finite Element Method.
The inverse finite element method (iFEM) is a novel method for reconstructing the full-field displacement of structures by discrete measurement strain. In practical engineering applications, the accuracy of iFEM is reduced due to the positional offset of strain sensors during installation and errors in structural installation. Therefore, a coarse and fine two-stage calibration (CFTSC) method is proposed to enhance the accuracy of the reconstruction of structures. Firstly, the coarse calibration is based on a single-objective particle swarm optimization algorithm (SOPSO) to optimize the displacement-strain transformation matrix related to the sensor position. Secondly, as selecting different training data can affect the training effect of self-constructed fuzzy networks (SCFN), this paper proposes to screen the appropriate training data based on residual analysis. Finally, the experiments of the wing-integrated antenna structure verify the efficiency of the method on the reconstruction accuracy of the structural body displacement field.


Development of a native-locus dual reporter system for the efficient screening of the hyper-production of natural products in Streptomyces.
Streptomyces is renowned for its abundant production of bioactive secondary metabolites, but most of these natural products are produced in low yields. Traditional rational network refactoring is highly dependent on the comprehensive understanding of regulatory mechanisms and multiple manipulations of genome editing. Though random mutagenesis is fairly straightforward, it lacks a general and effective strategy for high throughput screening of the desired strains. Here in an antibiotic daptomycin producer S. roseosporus, we developed a dual-reporter system at the native locus of the daptomycin gene cluster. After elimination of three enzymes that potentially produce pigments by genome editing, a gene idgS encoding the indigoidine synthetase and a kanamycin resistant gene neo were integrated before and after the non-ribosomal peptidyl synthetase genes for daptomycin biosynthesis, respectively. After condition optimization of UV-induced mutagenesis, strains with hyper-resistance to kanamycin along with over-production of indigoidine were efficiently obtained after one round of mutagenesis and target screening based on the dual selection of the reporter system. Four mutant strains showed increased production of daptomycin from 1.4 to 6.4 folds, and significantly improved expression of the gene cluster. Our native-locus dual reporter system is efficient for targeting screening after random mutagenesis and would be widely applicable for the effective engineering of Streptomyces species and hyper-production of these invaluable natural products for pharmaceutical development.


Bis{μ(3)-cis-N-(2-carboxyl-ato-5-chloro-phen-yl)-N'-[3-(dimethyl-amino)-prop-yl]oxamidato(3-)}bis-(perchlorato-κO)bis-(N,N,N',N'-tetra-methyl-ethylene-diamine)-tetra-copper(II).
The title complex, [Cu(4)(C(14)H(15)ClN(3)O(4))(2)(ClO(4))(2)(C(6)H(16)N(2))(2)], is a tetra-nuclear copper(II) complex lying about an inversion center wherein a cis-oxamide group is coordinated to both Cu atoms with bite angles of 84.45 (6) and 84.08 (10)°. Both Cu atoms adopt distorted square-pyramidal coordination geometries. The apical position of one Cu atom is occupied by an O atom from a perchlorate group, with a Cu-O bond length of 2.519 (7) Å, while the apical site of the other Cu atom is occupied by a carboxyl-ate O atom with a Cu-O distance of 2.281 (3) Å. The Cu atoms bridged by oxamide and carboxyl-ate-group bridges are separated by 5.204 (6) and 5.603 (2) Å, respectively. The crystal structure is consolidated by weak inter-molecular C-H⋯O inter-actions. Two perchlorate O atoms are disordered with unequal site-occupancy factors.


In vivo osmoregulation of Na/myo-inositol cotransporter mRNA in rat kidney medulla.
myo-Inositol, a major compatible osmolyte in renal medulla, is accumulated in kidney-derived epithelial cells cultured in hypertonic media via Na/myoinositol cotransporter (SMIT). The altered medium osmolality of Madin-Darby canine kidney cells leads to changes in the transcription of the SMIT gene and mRNA abundance. To investigate whether SMIT is regulated by tonicity in vivo, renal medullary myoinositol and SMIT mRNA was measured in rats in hydrated and dehydrated states. Rats were divided into two groups: (1) hydrated rats, free access to 3% sucrose water; (2) dehydrated rats, 3 days of water deprivation. Urine sodium, potassium, urea, and osmolality in dehydrated rats were significantly higher than in hydrated rats. Renal medullary sodium, urea, and myo-inositol in dehydrated rats were significantly higher than in hydrated rats. Northern analysis revealed that there was a message hybridized to SMIT cDNA in the cortex and outer and inner medulla of the kidney. Compared with hydrated rats, SMIT mRNA in dehydrated rats was 2.6-fold higher in the outer medulla and 2.5-fold higher in the inner medulla. These results indicate that there is osmoregulatory SMIT in the outer and inner medulla of the kidney and that myo-inositol accumulation in this region is probably due to the increased expression of the SMIT gene.


Graphene-Roll-Wrapped Prussian Blue Nanospheres as a High-Performance Binder-Free Cathode for Sodium-Ion Batteries.
Sodium iron hexacyanoferrate (Fe-HCF) has been proposed as a promising cathode material for sodium-ion batteries (SIBs) because of its desirable advantages, including high theoretical capacity (∼170 mAh g-1), eco-friendliness, and low cost of worldwide rich sodium and iron resources. Nonetheless, its application faces a number of obstacles due to poor electronic conductivity and structural instability. In this work, Fe-HCF nanospheres (NSs) were first synthesized and fabricated by an in situ graphene rolls (GRs) wrapping method, forming a 1D tubular hierarchical structure of Fe-HCF NSs@GRs. GRs not only provide fast electronic conduction path for Fe-HCF NSs but also effectively prevent organic electrolyte from reaching active materials and inhibit the occurrence of side reactions. The Fe-HCF NSs@GRs composite has been used as a binder-free cathode with a capacity of ∼110 mAh g-1 at a current density of 150 mA g-1 (∼1C), the capacity retention of ∼90% after 500 cycles. Moreover, the Fe-HCF NSs@GRs cathode displays a super high rate capability with ∼95 mAh g-1 at 1500 mA g-1 (∼10C). The results suggest that the 1D tubular structure of 2D GRs-wrapped Fe-HCF NSs is promising as a high-performance cathode for SIBs.


Studies on allergen and allergoid preparations from purified timothy (Phleum pratense) pollen extracts. II. Anaphylaxis studies in rats and histamine release from human leukocytes.
In vivo and in vitro allergenic activities of allergen and allergoid preparations from partially purified timothy pollen extract were measured in three different systems. In heterologous PCA titration, the allergen preparation was found to be 32 times more allergenic than the allergoid preparation. By intravenous chaled that treatment of allergen preparations with formaldehyde led to a preparation with the properties of an allergoid. In addition, it was found that the carbohydrate fraction of the refined allergen preparation of timothy a reduction in blood pressure. Thus, the allergen preparation was at least 50 times more potent in inducing systemic anaphylaxis in sensitized rats than the allergoid preparation. In the histamine release assay of grass-sensitive human leukocytes, approximately 1,000 times more allergoid protein than allergen protein was required to achieve 30% histamine release. Although to different degrees, in all three test systems in could be demonstrated that treatment of allergen preparations with formaldehyde led to a preparation with the properties of an allergoid. In addition, it was found that the carbohydrate fraction of the refined allergen preparation of timothy pollen decreased the blood pressure even in nonsensitized animals. The effect of this carbohydrate fraction on blood pressure was immediate but short-lived and immunologically nonspecific.


Simultaneous acute nephrosis and hepatitis in secondary syphilis.
Simultaneous occurrence of acute nephrosis and hepatitis in secondary syphilis is rare. We report a 24-year-old man who presented with sudden onset of nephrotic syndrome, acute hepatitis, and skin lesions associated with secondary syphilis. A renal biopsy demonstrated electron-dense deposits located in the subepithelial, mesangial and intramembranous areas under electron microscopy. Light microscopy revealed a mild increase in mesangial matrix with normal glomerular cellularity. Immunofluorescent examination showed granular deposition of IgG and IgA along the glomerular capillary basement membrane without deposits of complements. These morphological changes differed from those reported previously. All, the heavy proteinuria, disturbances of liver function, and skin lesions resolved after 4-week treatment.


Strain engineering of two-dimensional multilayered heterostructures for beyond-lithium-based rechargeable batteries.
Beyond-lithium-ion batteries are promising candidates for high-energy-density, low-cost and large-scale energy storage applications. However, the main challenge lies in the development of suitable electrode materials. Here, we demonstrate a new type of zero-strain cathode for reversible intercalation of beyond-Li+ ions (Na+, K+, Zn2+, Al3+) through interface strain engineering of a 2D multilayered VOPO4-graphene heterostructure. In-situ characterization and theoretical calculations reveal a reversible intercalation mechanism of cations in the 2D multilayered heterostructure with a negligible volume change. When applied as cathodes in K+-ion batteries, we achieve a high specific capacity of 160 mA h g-1 and a large energy density of ~570 W h kg-1, presenting the best reported performance to date. Moreover, the as-prepared 2D multilayered heterostructure can also be extended as cathodes for high-performance Na+, Zn2+, and Al3+-ion batteries. This work heralds a promising strategy to utilize strain engineering of 2D materials for advanced energy storage applications.


Safety Assessment of Ultrasound-Assisted Intravesical Chemotherapy in Normal Dogs: A Pilot Study.
Intravesical chemotherapy after transurethral resection is a treatment option in patients with non-muscle invasive bladder cancer. The efficacy of intravesical chemotherapy is determined by the cellular uptake of intravesical drugs. Therefore, drug delivery technologies in the urinary bladder are promising tools for enhancing the efficacy of intravesical chemotherapy. Ultrasound-triggered microbubble cavitation may enhance the permeability of the urothelium, and thus may have potential as a drug delivery technology in the urinary bladder. Meanwhile, the enhanced permeability may increase systemic absorption of intravesical drugs, which may increase the adverse effects of the drug. The aim of this preliminary safety study was to assess the systemic absorption of an intravesical drug that was delivered by ultrasound-triggered microbubble cavitation in the urinary bladder of normal dogs. Pirarubicin, a derivative of doxorubicin, and an ultrasound contrast agent (Sonazoid) microbubbles were administered in the urinary bladder. Ultrasound (transmitting frequency 5 MHz; pulse duration 0.44 μsec; pulse repetition frequency 7.7 kHz; peak negative pressure -1.2 MPa) was exposed to the bladder using a diagnostic ultrasound probe (PLT-704SBT). The combination of ultrasound and microbubbles did not increase the plasma concentration of intravesical pirarubicin. In addition, hematoxylin and eosin staining showed that the combination of ultrasound and microbubble did not cause observable damages to the urothelium. Tissue pirarubicin concentration in the sonicated region was higher than that of the non-sonicated region in two of three dogs. The results of this pilot study demonstrate the safety of the combination of intravesical pirarubicin and ultrasound-triggered microbubble cavitation, that is, ultrasound-assisted intravesical chemotherapy.


Association of Asthma Exacerbation Risk and Physician Time Expenditure With Provision of Asthma Action Plans and Education for Pediatric Patients.
To provide information about factors underlying provision of asthma action plans (AAPs) to a minority of pediatric patients with asthma, assess whether risk of exacerbation acts on provision of AAP and asthma education directly, suggesting targeting to highest-risk patients, or indirectly by influencing physician-patient interaction time. This study was a retrospective cross-sectional analysis of a nationally representative sample of physician office visits that consisted of patients aged 2 to 18 years with asthma. Exacerbation risk comprised proxy indicators of control and severity. Direct and time-mediated effects of exacerbation risk on provision of AAP and education were calculated from logistic regression models. Asthma action plans were provided in 14.3% of visits, education in 23.9%. Total direct effects of exacerbation risk (ORs = 3.88-4.69) far exceeded indirect, time-mediated effects (both ORs = 1.03) on AAPs. Direct effects on education were similar but smaller. After adjusting for risk, physician time expenditure of ≥30 minutes was associated with nearly doubled odds of providing AAP or education (ORs = 1.90-1.99). Visits that included allied health professionals alongside physician care were significantly associated with all 4 outcomes in multivariate analyses (ORs = 3.06-5.28). Exacerbation risk has a strong, direct association with AAP provision in pediatric asthma, even controlling for physician time expenditure. Provision of AAP and education to pediatric patients with asthma may be facilitated by increasing available time for office visits and involving allied health professionals.


Expression of survivin in CIN and invasive squamous cell carcinoma of uterine cervix.
Survivin is a novel member of the inhibitors of apotosis proteins (IAP). To evaluate the possible role of survivin in tumorigenesis of CIN (cervical intraepithelial neoplasia) and invasive squamous cervical carcinoma of the uterine cervix (SCC), the expression of survivin was studied. In 41 CIN and SCC tissues, the expression of survivin, Fas-ligand, Fas and bcl-2 was studied by immunohistochemistry. Survivin expression tended to increase along with tumor progression; low-grade squamous intra-epithelial lesions (HSIL, CIN I), 66.7%, high-grade squamous epithelial lesions (HSIL, CIN II and III), 87.5% and SCC, 100% with a statistical significance (p<0.019). Alteration of Fas-ligand, Fas and bcl-2 expression was detected in 12.5%-25% of HSIL and in 7.7%-30.8% of SCC but no abnormal expression was found in LSIL. Survivin expression seems to be more closely related to the progression of CIN and SCC compared to Fas-ligand, Fas and bcl-2.


External and internal human exposure to PFOA and HFPOs around a mega fluorochemical industrial park, China: Differences and implications.
Hexafluoropropylene oxide dimer and trimer acids (HFPO-DA and HFPO-TA) are used as alternatives to legacy perfluorooctanoic acid (PFOA); however, little is known about their human exposure risks. In this study, the concentrations of PFOA and HFPO were measured in major human exposure matrices and human bio-samples of local residents near a mega fluorochemical industrial park in Shandong, China, to characterize their external and internal exposures. Although HFPO-DA was detected in drinking water and indoor dust, it exhibited a considerably low bioaccumulation potential in animal-origin food and human samples (urine, hair, and serum), implying that it might be a benign alternative to PFOA. Although the estimated daily intake (EDI) of HFPO-TA was comparable to that of PFOA, its concentration in urine was higher than that of PFOA, implying that it might be eliminated faster than PFOA. A simple one-compartment pharmacokinetic model was applied to estimate the serum concentrations of the target compounds and subsequently compare them with the measured concentrations. The predicted concentration of PFOA in serum based on its concentration in urine and half-life was close to the measured value, confirming the distinct internal exposure of PFOA in the local residents. However, the measured concentrations of HFPO in serum were considerably lower than those predicted from the external EDI and urine concentrations, implying that they were eliminated faster than expected in humans. Various perfluoroalkyl substances were detected in human hair, and their compositions were similar to those in human serum, suggesting that hair is a good non-invasive indicator for long-term exposure to legacy long-chain perfluoroalkyl carboxylic acids and HFPOs. This study provided valuable information about the human exposure to legacy PFOA and HFPOs in highly impacted areas near point sources and necessitates studies on the toxicokinetics of HFPOs.


Intra-specific variations in expression of stress-related genes in beech progenies are stronger than drought-induced responses.
Rapidly decreasing water availability as a consequence of climate change is likely to endanger the range of long-lived tree species. A pressing question is, therefore, whether adaptation to drought exists in important temperate tree species like European beech (Fagus sylvatica L.), a wide-spread, dominant forest tree in Central Europe. Here, five beech stands were selected along a precipitation gradient from moist to dry conditions. Neutral genetic markers revealed strong variation within and little differentiation between the populations. Natural regeneration from these stands was transferred to a common garden and used to investigate the expression of genes for abscisic acid (ABA)-related drought signaling [9-cis-epoxy-dioxygenase (NCED), protein phosphatase 2C (PP2C), early responsive to dehydration (ERD)] and stress protection [ascorbate peroxidase (APX), superoxide dismutase (SOD), aldehyde dehydrogenase (ALDH), glutamine amidotransferase (GAT)] that are involved in drought acclimation. We hypothesized that progenies from dry sites exhibit constitutively higher expression levels of ABA- and stress-related genes and are less drought responsive than progenies from moist sites. Transcript levels and stress responses (leaf area loss, membrane integrity) of well-irrigated and drought-stressed plants were measured during the early, mid- and late growing season. Principal component (PC) analysis ordered the beech progenies according to the mean annual precipitation at tree origin by the transcript levels of SOD, ALDH, GAT and ERD as major loadings along PC1. PC2 separated moist and drought treatments with PP2C levels as important loading. These results suggest that phosphatase-mediated signaling is flexibly acclimated to the current requirements, whereas stress compensatory measures exhibited genotypic variation, apparently underlying climate selection. In contrast to expectation, the drought responses were less pronounced than the progeny-related differences and the transcript levels were constitutively lower in beeches from dry than from moist sites. These results imply that beeches from dry origins may have evolved mechanisms to avoid oxidative stress.


Transforming growth factor-β/SMAD Target gene SKIL is negatively regulated by the transcriptional cofactor complex SNON-SMAD4.
The human SKI-like (SKIL) gene encodes the SMAD transcriptional corepressor SNON that antagonizes TGF-β signaling. SNON protein levels are tightly regulated by the TGF-β pathway: whereas a short stimulation with TGF-β decreases SNON levels by its degradation via the proteasome, longer TGF-β treatment increases SNON levels by inducing SKIL gene expression. Here, we investigated the molecular mechanisms involved in the self-regulation of SKIL gene expression by SNON. Bioinformatics analysis showed that the human SKIL gene proximal promoter contains a TGF-β response element (TRE) bearing four groups of SMAD-binding elements that are also conserved in mouse. Two regions of 408 and 648 bp of the human SKIL gene (∼2.4 kb upstream of the ATG initiation codon) containing the core promoter, transcription start site, and the TRE were cloned for functional analysis. Binding of SMAD and SNON proteins to the TRE region of the SKIL gene promoter after TGF-β treatment was demonstrated by ChIP and sequential ChIP assays. Interestingly, the SNON-SMAD4 complex negatively regulated basal SKIL gene expression through binding the promoter and recruiting histone deacetylases. In response to TGF-β signal, SNON is removed from the SKIL gene promoter, and then the activated SMAD complexes bind the promoter to induce SKIL gene expression. Subsequently, the up-regulated SNON protein in complex with SMAD4 represses its own expression as part of the negative feedback loop regulating the TGF-β pathway. Accordingly, when the SNON-SMAD4 complex is absent as in some cancer cells lacking SMAD4 the regulation of some TGF-β target genes is modified.


Assessment of a novel continuous cleaning device using metatranscriptomics in diverse hospital environments.
Despite routine implementation of cleaning and disinfection practices in clinical healthcare settings, high-touch environmental surfaces and contaminated equipment often serve as reservoirs for the transmission of pathogens associated with healthcare-associated infections (HAIs). The current study involved the analysis of high-touch surface swabs using a metatranscriptomic sequencing workflow (CSI-Dx™) to assess the efficacy of cleanSURFACES® technology in decreasing microbial burden by limiting re-contamination. This is a non-human single center study conducted in the Emergency Department (ED) and on an inpatient Oncology Ward of Walter Reed National Military Medical Center that have followed hygienic practices during the COVID-19 pandemic environment. Although there was no difference in observed microbial richness (two-tailed Wilcoxon test with Holm correction, P > 0.05), beta diversity findings identified shifts in microbial community structure between surfaces from baseline and post-intervention timepoints (Day 1, Day 7, Day 14, and Day 28). Biomarker and regression analyses identified significant reductions in annotated transcripts for various clinically relevant microorganisms' post-intervention, coagulase-negative staphylococci and Malassezia restricta, at ED and Oncology ward, respectively. Additionally, post-intervention samples predominantly consisted of Proteobacteria and to a lesser extent skin commensals and endogenous environmental microorganisms in both departments. Findings support the value of cleanSURFACES®, when coupled with routine disinfection practices, to effectively impact on the composition of active microbial communities found on high-touch surfaces in two different patient care areas of the hospital (one outpatient and one inpatient) with unique demands and patient-centered practices.


Barriers and Enablers to Direct Observation of Trainees' Clinical Performance: A Qualitative Study Using the Theoretical Domains Framework.
Direct observation is essential to assess and provide feedback to medical trainees. However, calls for its increased use in medical training persist as learners report that direct observation occurs infrequently. This study applied a theory-driven approach to systematically investigate barriers and enablers to direct observation in residency training. From September 2016 to July 2017, semistructured interviews of faculty and residents at The Ottawa Hospital were conducted and analyzed. An interview guide based on the theoretical domains framework (TDF) was used to capture 14 domains that may influence direct observation. Interview transcripts were independently coded using direct content analysis, and specific beliefs were generated by grouping similar responses. Relevant domains were identified based on the frequencies of beliefs reported, presence of conflicting beliefs, and perceived influence on direct observation practices. Twenty-five interviews (12 residents, 13 faculty) were conducted, representing 10 specialties. Ten TDF domains were identified as influencing direct observation: knowledge, skills, beliefs about consequences, social/professional role and identity, intention, goals, memory/attention/decision processes, environmental context and resources, social influences, and behavioral regulation. Discord between faculty and resident intentions, coupled with social expectations that residents should be responsible for ensuring that observations occur, was identified as a key barrier. Additionally, competing demands identified across multiple TDF domains emerged as a pervasive theme. This study identified key barriers and enablers to direct observation. These influencing factors provide a basis for the development of potential strategies aimed at embedding direct observation as a routine pedagogical practice in residency training.


Human metapneumovirus infection in the Canadian population.
Human metapneumovirus (hMPV), a newly discovered paramyxovirus, has been associated with acute respiratory tract infections (ARIs) ranging from upper ARIs to severe bronchiolitis and pneumonia. Important questions remain on the contribution of hMPV to ARIs and its impact on public health. During the 2001-2002 season, we conducted a collaborative study with four provincial public health laboratories to study the prevalence of this new virus in the Canadian population. A total of 445 specimens were collected from patients of all age groups with ARIs and were tested for the presence of hMPV by reverse transcription-PCR. Of these, 66 (14.8%) tested positive for hMPV. Positive specimens were found in all age groups and in all four provinces studied. Virus activity peaked in February and March. The age range of the patients with hMPV infection was 2 months to 93 years (median age, 25 years), with similar numbers of females (35%) and males (41%). Thirty-three percent (n = 22) of hMPV-infected patients were hospitalized; of these, 27% (n = 6) had rhinitis and pneumonia, 23% (n = 5) had bronchiolitis, and 9% (n = 2) had bronchitis. The hospitalization rates were significantly higher among patients <5 years of age (P = 0.0005) and those >50 years of age (P = 0.0044) than among those 6 to 50 years of age. Phylogenetic analysis of the F gene showed that two hMPV genetic clusters were cocirculating in the 2001-2002 season, and comparison with earlier studies suggests a temporal evolutionary pattern of hMPV isolates. These results provide further evidence of the importance of hMPV in ARIs, particularly in young children and elderly individuals.


Spectroscopic insights into photochemical transformation of effluent organic matter from biological wastewater treatment plants.
The photodegradation of discharged effluent organic matter (EfOM) changes its composition and shifts its impacts on pollutant migration and transformation in receiving waters. However, to date, EfOM photodegradation processes are not well understood due to the complexity and heterogeneity of EfOM. Herein, the spectroscopic analysis including ultra violet-visible (UV-Vis), fluorescence and FTIR spectroscopies coupled with two-dimensional correlation analysis (2D-COS) were used to draw a comprehensive view of EfOM photodegradation and involving mechanisms. Results revealed that the photolability of each component in EfOM followed the order: tannin-like > humic-like > protein-like > carbohydrate-like and aliphatic compounds. The photolability of different components of EfOM were found to be related to the photolability of their functional groups. Specifically, the aromatic, carboxylic, phenolic and quinonoid groups associated with humic or tannin-like compounds were more prone to be photodegraded than amides in proteins or C-OH and C-O-C in carbohydrates. Furthermore, the humic-like components, dominating the light absorption of EfOM, were found to be degraded by direct photolysis. Nevertheless, the photodegradation of tannin-like and protein-like components were mainly due to the indirect photodegradation by ROS and 3OM⁎. Furthermore, results indicated that UV light, rather than visible light, was responsible for the photodegradation of EfOM. The spectroscopic techniques integrated with 2D-COS analysis could serve as a powerful tool with which to clarify complex EfOM photodegradation process as well as to improve our understanding of the fate of discharged EfOM and related environmental processes.


STrack: A Tool to Simply Track Bacterial Cells in Microscopy Time-Lapse Images.
Bacterial growth can be studied at the single cell level through time-lapse microscopy imaging. Technical advances in microscopy lead to increasing image quality, which in turn allows to visualize larger areas of growth, containing more and more cells. In this context, the use of automated computational tools becomes essential. In this paper, we present STrack, a tool that allows to track cells in time-lapse images in a fast and efficient way. We compared it to 3 recently published tracking tools on images ranging over 6 different bacterial strains with various morphologies. STrack showed to be the most consistent tracking tool, returning more than 80% of correct cell lineages on average, in comparison to manually annotated ground-truth. The python implementation of STrack, a docker structure, and a tutorial on how to download and use the tool can be found on the following github page: https://github.com/Helena-todd/STrack. IMPORTANCE Automated image analysis of growing prokaryotic cell populations becomes indispensable with larger data sets, such as derived by time-lapse microscopy. The tracking of the same individual cells and their daughter lineages is cumbersome and prone to errors in image alignment or poor resolution. Here, we present a simplified but highly effective tool for non-specialists to engage in cell tracking. The tool can be downloaded and run as a contained script-structure requiring minimal user input. Run times are fast, in comparison to other equivalent tools, and outputs consist of cell tables that can be subsequently used for lineage analysis, for which we offer examples. By providing open code, training data sets, as well as simplified script execution, we aimed to facilitate wide usage and further tool development for image analysis.