Health services, suicide, and self-harm: patient distress and system anxiety.
Patients often become distressed in health settings, and provision of emotional support is a routine part of clinical care. However, in some situations, patient distress can become disturbing to both clinicians and patients, and can affect ordinary therapeutic engagement. We argue that health systems that support people presenting with suicidal acts and self-harm are particularly at risk of providing maladaptive responses, which we have termed dysregulation. If health systems become dysregulated, staff and patients might find it difficult to think clearly and respond adaptively. We describe some common characteristics of dysregulation, including negative feelings about patients, an inappropriately narrow focus on diagnosis and risk assessment, and ad-hoc, abrupt, and inconsistent decision making. These dysregulated responses might impair more adaptive responses such as containment of distress, safety planning, and negotiated responsibility with patients and carers. We discuss the main drivers of dysregulation and the implications for clinical practice in the management of self-harm and suicide risk.


Use of plasmid profiles and restriction endonuclease digest in environmental studies of Listeria spp. from raw milk.
Forty-eight isolates of Listeria spp. (19 L. monocytogenes, 27 L. innocua, 2 L. welshimeri) from bulk raw milk were screened for plasmid DNA. These isolates were collected over a period of 1 year. Only L. innocua harboured plasmids (8/27 strains) which ranged in size 10-44 megadaltons. The plasmid bearing strains could be arranged into three groups 10 Md, 44 Md and 44 + 10 Md. In two farms where Listeria innocua were persistent in bulk raw milk different plasmids profiles were found (farm 1 and 3). In species carrying similar plasmid profiles (44 Md) isolated from the same bulk tank raw milk samples over a period of 2-4 months (farm 2) no similarities in restriction endonuclease digest patterns of the plasmids were observed. This study suggests there may be a constant influx of Listeria spp. into raw milk supplies on the farm.


Nondestructive measurement of bone mineral in femurs from ovariectomized rats.
One hundred ninety-eight rats were ovariectomized (OX) or sham-ovariectomized (shOX) at 100 days of age. Groups were killed at 35, 70, 100, 125, 180, 270, 360, and 540 days postsurgery. Bone mineral content (BMC) of the right femur was assayed on a dual photon absorptiometer (DPA) optimized for human spine and whole body measurements. Three regions were studied: the distal measuring 0.8 cm, the proximal measuring 0.88 cm, and the diaphysis, the remainder. The DPA technique accurately showed the ash content (r = 0.96), with a precision error of 3-5%. Whole femoral BMC was 4.3-11.1% lower in OX than shOX rats, with significant differences from 35-180 days. By 35 days, distal femoral BMC declined 6% in OX rats and rose 12% in shOX rats. Distal femoral BMC was 11.3-17.5% lower in OX than shOX rats, with significant differences at all times except 540 days. Femoral diaphyseal BMC of OX and shOX rats did not differ at any time. The relative distal femoral osteopenia which appeared by 35 days in OX rats did not worsen during the next 17 months. A DPA suited for human BMC studies is also accurate for BMC determination in bones with 250-500 mg of mineral. It is less precise for this purpose than dedicated instruments using single photon absorptiometry. However, enough precision exists to monitor the development of relative osteopenia in OX rats. Osteopenia in OX rats is confined to a region containing appreciable cancellous bone. Its self-limiting nature suggests the existence of an estrogen-dependent quantum of cancellous bone in female rats. The adult rat model is accurate for cancellous bone of the adult human, but inaccurate for cortical bone.


Relationship between surface area for adhesion and tensile bond strength--evaluation of a micro-tensile bond test.
The purpose of this study was to test the null hypothesis that there is no relationship between the bonded surface area of dentin and the tensile strength of adhesive materials. The enamel was removed from the occlusal surface of extracted human third molars, and the entire flat surface was covered with resin composite bonded to the dentin to form a flat resin composite crown. Twenty-four hours later, the bonded specimens were sectioned parallel to the long axis of the tooth into 10-20 thin sections whose upper part was composed of resin composite with the lower half being dentin. These small sections were trimmed using a high speed diamond bur into an hourglass shape with the narrowest portion at the bonded interface. Surface area was varied by altering the specimen thickness and width. Tensile bond strength was measured using custom-made grips in a universal testing machine. Tensile bond strength was inversely related to bonded surface area. At surface areas below 0.4 mm2, the tensile bond strengths were about 55 MPa for Clearfil Liner Bond 2 (Kuraray Co., Ltd.), 38 MPa for Scotchbond MP (3M Dental Products), and 20 MPa for Vitremer (3M Dental Products). At these small surface areas all of the bond failures were adhesive in nature. This new method permits measurement of high bond strengths without cohesive failure of dentin. It also permits multiple measurements to be made within a single tooth.


Could the New BA.2.75 Sub-Variant Cause the Emergence of a Global Epidemic of COVID-19? A Scoping Review.
With over 58 million cases and 6 million deaths by August 2022, the Coronavirus disease 2019 (COVID-19), causing severe acute respiratory syndrome coronavirus 2 (SARs-CoV-2), has had an insurmountable impact on the world's population. This is one of the worst health crises since 1918's influenza pandemic. There are four subvariants of Omicron; BA.1, BA.1.1, BA.2 and BA.3. As a result of new mutations in its spike protein, most of which occur in its receptor binding site, the Omicron variant appears to be more transmissible and less resistant to vaccination and antibody response. Understanding Omicron's virology and mutations is essential to developing diagnostic and therapeutic methods. A thorough assessment of control measures, as well as timely adjustment of control measures, requires addressing such issues as re-infection risk, vaccine response, booster vaccine doses, and the increased rate of Omicron infections. This review article aims to look at the current information about the different types of SARs-CoV-2, focusing on the new subtype BA.2.75.


Bioluminescent whole-cell reporter gene assays as screening tools in the identification of antimicrobial natural product extracts.
We describe novel tools, bioluminescent whole-cell reporter gene assays, for facilitating the use of natural products in antimicrobial drug discovery. As proof-of-concept, a plant extract library was screened and follow-up experiments were carried out. Primary results can be obtained in 2-4h with high sensitivity, leading to significant improvements of the process.


Gentamicin drug monitoring for peritonitis patients by using a CMOS-BioMEMS-based microcantilever sensor.
We developed a Complementary Metal-Oxide-Semiconductor Bio-Microelectromechanical Systems (CMOS-BioMEMS) based piezoresistive microcantilever sensor for detecting gentamicin, a peritonitis therapeutic small-molecule drug. In recent years, the patient-centric concept has been emphasized. In such a trend, therapeutic drug monitoring (TDM) is especially crucial for patients with peritonitis to avoid adverse reactions from a high concentration of gentamicin in the blood. With the aid of a commercialized semiconductor manufacturing process, the microcantilever sensing platform can serve as a portable, low-cost device and offer real-time detection. With chemical surface modification and capture antibody immobilization, the sensor can detect the small-molecule (< 2 kDa) gentamicin directly. We also modified the pH value of the buffer solution and applied an external electric field to promote sensor sensitivity. Comparing the change of the signals in a non-electric field of antibody immobilization and a 60-volt electric field of antibody immobilization showed that the average signal response increased 1.8 times. In the detection of gentamicin with different concentrations of 10-200 μg/mL, the limit of detection (LOD) of the sensor was 9.44 µg/mL. Finally, the detecting result of a microrcantilever sensor was compared with the one measured by a common instrument in hospital, and the high correlation was expressed between them in gentamicin detection. The CMOS-BioMEMS-based piezoresistive microcantilever sensor has been demonstrated to have great potential as a point-of-care (POC) device for real-time drug concentration monitoring.


Patient blood management (PBM) in pregnancy and childbirth: literature review and expert opinion.
Patient blood management [PBM] has been acknowledged and successfully introduced in a wide range of medical specialities, where blood transfusions are an important issue, including anaesthesiology, orthopaedic surgery, cardiac surgery, or traumatology. Although pregnancy and obstetrics have been recognized as a major field of potential haemorrhage and necessity of blood transfusions, there is still little awareness among obstetricians regarding the importance of PBM in this area. This review, therefore, summarizes the importance of PBM in obstetrics and the current evidence on this topic. We review the current literature and summarize the current evidence of PBM in pregnant women and postpartum with a focus on postpartum haemorrhage (PPH) using PubMed as literature source. The literature was reviewed and analysed and conclusions were made by the Swiss PBM in obstetrics working group of experts in a consensus meeting. PBM comprises a series of measures to maintain an adequate haemoglobin level, improve haemostasis and reduce bleeding, aiming to improve patient outcomes. Despite the fact that the WHO has recommended PBM early 2010, the majority of hospitals are in need of guidelines to apply PBM in daily practice. PBM demonstrated a reduction in morbidity, mortality, and costs for patients undergoing surgery or medical interventions with a high bleeding potential. All pregnant women have a significant risk for PPH. Risk factors do exist; however, 60% of women who experience PPH do not have a pre-existing risk factor. Patient blood management in obstetrics must, therefore, not only be focused on women with identified risk factor for PPH, but on all pregnant women. Due to the risk of PPH, which is inherent to every pregnancy, PBM is of particular importance in obstetrics. Although so far, there is no clear guideline how to implement PBM in obstetrics, there are some simple, effective measures to reduce anaemia and the necessity of transfusions in women giving birth and thereby improving clinical outcome and avoiding complications. PBM in obstetrics is based on three main pillars: diagnostic and/or therapeutic interventions during pregnancy, during delivery and in the postpartum phase. These three main pillars should be kept in mind by all professionals taking care of pregnant women, including obstetricians, general practitioners, midwifes, and anaesthesiologists, to improve pregnancy outcome and optimize resources.


Identification of a short PIASx gene promoter that directs male germ cell-specific transcription in vivo.
PIASx gene encodes two SUMO E3 ligases that are highly expressed in the testis. We have isolated and analyzed the promoter of the murine PIASx gene. Electrophoretic mobility shift assays with testicular nuclear extracts showed that the proximal promoter forms a major DNA-protein complex containing Sp1, Sp2, and Sp3 transcription factors. Reporter gene assays in cultured cells indicated that a fragment comprising nucleotides from -168 to +76 relative to transcription start site is sufficient for basal promoter activity in cultured cells, but these in vitro assays failed to reveal clear differences in promoter activity between testis- and non-testis-derived cell lines. Interestingly, however, the proximal promoter encompasses the elements necessary for a testis-specific transcription in vivo, as it directed beta-galactosidase expression exclusively to male germ cells in transgenic mice. In conclusion, we have characterized the minimal PIASx promoter that can be used for highly specific targeting of transgene expression to male germ cells.


The re-emergence of dengue in China.
The number of reports in the literature on dengue outbreaks in various parts of south China is increasing. This trend is likely contributed to by multiple factors, chief among which is the increase in trade and human movement in and out of China from the Southeast Asian region where dengue is firmly endemic. However, a holistic picture of dengue in China and how the public health authorities are responding to this global health challenge has been missing. In a research article published in BMC Medicine, Lai et al. have now filled this gap in knowledge by analysing statutorily mandated national dengue surveillance data from 1990 till 2014. They also conducted time series analyses to identify key drivers of dengue transmission in south China as well as from south China to the other parts of this vast and populous country. Their findings, as well as the description of surveillance and disease control activities in China, highlight urgent steps that need to be taken if China wishes to prevent itself from becoming another country that experiences large and frequent cycles of epidemic dengue.


Development of Simplified Heterocyclic Acetogenin Analogues as Potent and Selective Trypanosoma brucei Inhibitors.
Neglected tropical diseases caused by parasitic infections are an ongoing and increasing concern. They are a burden to human and animal health, having the most devastating effect on the world's poorest countries. Building upon our previously reported triazole analogues, in this study we describe the synthesis and biological testing of other novel heterocyclic acetogenin-inspired derivatives, namely 3,5-isoxazoles, furoxans, and furazans. Several of these compounds maintain low-micromolar levels of inhibition against Trypanosoma brucei, whilst having no observable inhibitory effect on mammalian cells, leading to the possibility of novel lead compounds for selective treatment.


Compensation of skeletal Class III malocclusion by isolated extraction of mandibular teeth: Part 2: Skeletal, dentoalveolar and soft tissue parameters in comparison with nonextraction Class III therapies.
To retrospectively compare two compensatory approaches taken in skeletal Class III patients during the main treatment stage, including a study group of multiband treatment plus isolated extraction of mandibular teeth and a control group of multiband treatment without extraction of teeth. The extraction group included 22 (12 female, 10 male) patients receiving compensatory multiband treatment for a mean of 3.47 ± 1.14 years and 16.22 ± 1.92 years old at debonding. The nonextraction group included 24 (14 female, 10 male) patients undergoing multiband treatment for 2.76 ± 1.28 years and 15.38 ± 1.46 years old at debonding. Lateral cephalograms obtained at baseline and upon completion of active treatment were traced for skeletal, dentoalveolar, and soft tissue parameters. Welch and Wilcoxon tests were used to analyze intergroup differences (initial values, final values, initial-to-final changes) and within-group differences (p < 0.05). Upon completion of active treatment, the only significant intergroup differences were noted for U1NA and L1ML. Significant within-group changes over the courses of treatment were seen for SNB, MLNL, U1NA, U1NL, L1NB, L1ML, H-angle, ULipEL, and LLipEL (extraction group) or for SNB, ANB, individual ANB, Wits appraisal, U1NA, U1NL, H-angle, Naslab-a, ULipEL, and LLipEL (nonextraction group). Parameters that changed by significantly different amounts in both groups included Wits appraisal, L1NB, L1ML, and LLipEL. The added value of isolated extraction therapy basically lies in increasing the potential for retruding the lower incisor inclinations, so that compensatory treatment becomes an option even in selected patients presenting with adverse occlusal situations that would otherwise require orthognathic surgery. Given the successful outcomes in both groups, which had been established by Peer Assessment Rating (PAR) scores, it was possible to define the skeletal, dentoalveolar, and soft tissue characteristics of successful treatment more precisely than before.


Identifying sources of phthalate exposure with human biomonitoring: results of a 48h fasting study with urine collection and personal activity patterns.
Human biomonitoring studies measuring phthalate metabolites in urine have shown widespread exposure to phthalates in the general population. Diet is thought to be a principle route of exposure to many phthalates. Therefore, we studied urinary phthalate metabolite patterns over a period of strict fasting and additionally recorded personal activity patterns with a diary to investigate non-dietary routes of exposure. Five individuals (3 female, 2 male, 27-47 years of age) fasted on glass-bottled water only over a 48-h period. All urine void events were captured in full, and measured for metabolites of the high molecular weight (HMW) di-(2-ethylhexyl) phthalate (DEHP), di-isononyl phthalate (DINP) and di-isodecyl phthalate (DiDP), and the low molecular weight (LMW) di-n-butyl phthalate (DnBP), di-iso-butyl phthalate (DiBP), butylbenzyl phthalate (BBzP), dimethyl phthalate (DMP), and diethyl phthalate (DEP). In all, 21 metabolites were measured in a total of 118 urine events, including events before and after the fasting period. At the onset of the study all phthalate metabolite concentrations were consistent with levels found in previous general population studies. Metabolites of the HMW phthalates (DEHP, DiNP and DiDP) showed a rapid decline to levels 5-10 times lower than initial levels within 24h of the fast and remained low thereafter. After food consumption resumed, levels rose again. By contrast, metabolites of the LMW phthalates including DMP, DEP, BBzP, DnBP and DiBP showed a cyclical pattern of rising and declining concentrations suggestive of ongoing non-food exposures. Furthermore, metabolites of most of the LMW phthalates (BBzP, DnBP and DiBP) tracked each other remarkably well, suggesting concurrent exposures. Diary entries could not help explain exposure sources for these phthalates, with one exception: rises in MEP concentrations around males' showers suggest personal care products as a major source of DEP. Exposure to HMW phthalates in this cohort appears to be driven by dietary intake, while non-dietary routes such as use of personal care products and ubiquitous sources including dust and indoor air appear to explain exposure to LMW phthalates.


Treatment with sodium butyrate inhibits the complete condensation of interphase chromatin.
The effects of histone hyperacetylation on chromatin fiber structure were studied using direct observations with the electron microscope. Histone hyperacetylation was induced in HeLa cells by treatment with sodium butyrate, and the ultrastructure of control and of acetylated chromatin fibers examined after fixation at different stages of compaction. No differences between control and acetylated chromatin were seen when the fibers were partially unfolded (10 mM NaCl, 20 mM NaCl, 50 mM NaCl), but in 100 mM NaCl, control chromatin showed further compaction to the "30 nm" fiber, while hyperacetylated chromatin failed to undergo this final compaction step. These results strongly suggest that histone acetylation causes a moderate "relaxation" rather than complete decondensation of interphase chromatin fibers. The relationship of these findings to the increased DNase I sensitivity of acetylated chromatin, and to transcription and replication, is discussed.


Folding of a three-stranded coiled coil.
Coiled coils consist of two or more amphipathic a-helices wrapped around each other to form a superhelical structure stabilized at the interhelical interface by hydrophobic residues spaced in a repeating 3-4 sequence pattern. Dimeric coiled coils have been shown to often form in a single step reaction in which association and folding of peptide chains are tightly coupled. Here, we ask whether such a simple folding mechanism may also apply to the formation of a three-stranded coiled coil. The designed 29-residue peptide LZ16A was shown previously to be in a concentration-dependent equilibrium between unfolded monomer (M), folded dimer (D), and folded trimer (T). We show by time-resolved fluorescence change experiments that folding of LZ16A to D and T can be described by 2M (k1)<==>(k(-1)) D and M + D (k2)<==>(k(-2)) T. The following rate constants were determined (25 degrees C, pH 7): k1 = 7.8 x 10(4) M(-1) s(-1), k(-1) = 0.015 s(-1), k2 = 6.5 x 10(5) M(-1) s(-1), and k(-2) = 1.1 s(-1). In a separate experiment, equilibrium binding constants were determined from the change with concentration of the far-ultraviolet circular dichroism spectrum of LZ16A and were in good agreement with the kinetic rate constants according to K(D) = k1/2k(-1) and K(T) = k2/k(-2). Furthermore, pulsed hydrogen-exchange experiments indicated that only unfolded M and folded D and T were significantly populated during folding. The results are compatible with a two-step reaction in which a subpopulation of association competent (e.g., partly helical) monomers associate to dimeric and trimeric coiled coils.


The priming effect of glucose on insulin release does not involve redistribution of secretory granules within the pancreatic B-cell.
Short-term stimulation of the pancreatic B-cell with glucose produces a time-dependent potentiation of this cell, which markedly enhances the insulin response to a renewed stimulation with the hexose. To study if a redistribution of the B-cell secretory granules to a location close to the B-cell plasma membrane could underlie the priming effect of glucose, an investigation by ultrastructural morphometry was performed. After exposure of perfused rat pancreas to non-priming or priming concentrations of glucose, pale and dark B-cell secretory granules were distinguished and analysed both within a central and a peripheral zone of the B-cell. The pale secretory granules comprised 30-40% of the total granule population in the B-cell. Whereas no difference in diameter of the granules was observed, there was evidence for a greater numerical density of dark granules in the central than in the peripheral part of the B-cell. This finding may be in line with observations implying that newly synthesized insulin is released preferentially to older insulin. The present experiments did, however, not reveal any significant priming effect of glucose on the intracellular distribution of secretory granules in the pancreatic B-cell. The lack of morphological changes in the B-cell by glucose priming of insulin release should, rather, direct increased attention to the biochemical aspects of the priming phenomenon.


Association of changes in lipid levels with changes in vitamin D levels in a real-world setting.
In clinical trials, vitamin D supplementation has been reported to reduce serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG) but not high-density lipoprotein cholesterol (HDL-C). In this cohort study we evaluated the association between changes in vitamin D (25-hydroxyvitamin D) and changes in lipid levels in a real-world setting. Changes in lipid levels over a 1-year period were evaluated among individuals whose vitamin D levels increased (group 1) or decreased (group 2) by ≥ 10 ng/mL in year 2018 versus 2017 (cohort 1; n = 5580), in 2019 versus 2018 (cohort 2, n = 6057), or in 2020 versus 2019 (cohort 3, n = 7249). In each cohort, levels of TC, LDL-C, and TG decreased in group 1 and increased in group 2. Between-group differences in average changes in the 3 cohorts ranged from 10.71 to 12.02 mg/dL for TC, from 7.42 to 8.95 mg/dL for LDL-C, and from 21.59 to 28.09 mg/dL for TG. These differences were significant after adjusting for age, sex, race, education, body mass index, blood pressure, smoking status, geographical location, and baseline levels of vitamin D and lipids (P < 0.001). Changes in vitamin D levels were not significantly associated with changes in HDL-C levels.


Local graft-versus-host-reaction in mice specifically inhibited by anti-receptor antibodies.
The local graft-versus-host (GVH) reaction provoked by parental spleen cells in F1 mice was shown to be T-cell-dependent. GVH reactions were suppressed in F1 hybrid mice immunized with parental T lymphocytes of the same genotype, but not in F1 mice immunized with parental B cells. In some cases this immunity could be passively transferred by serum into normal F1 mice. The specific activity of such sera could be removed by absorption with either parental T or B cells. Some of the F1 antisera were specificlly cytotoxic for parental GVH-reactive lymphocytes.


Polysomnographic measures of disturbed sleep are associated with reduced quality of life in multiple sclerosis.
The relationship of objective sleep parameters with health-related quality of life (HRQoL) in multiple sclerosis (MS) has not been studied. To evaluate the relationship between polysomnographic (PSG) parameters and HRQoL in MS. Ambulatory MS patients without a known sleep disorder completed the Short Form (36) Health Survey (SF-36), pain visual analog scale, and two consecutive overnight PSGs. HRQoL was assessed using SF-36 Physical and Mental Component Summary (PCS, MCS) scores. Standard objective PSG measures of sleep quality were determined. The relationship between objective sleep parameters and HRQoL was evaluated with multivariate linear regression, adjusting for age, sex, body mass index, disability, and pain. 62 MS patients were included. PSG measures of sleep disruption including stage changes, awakenings, time in N1 sleep, and apnea-hypopnea and total arousal indices were negatively associated (p<0.05) with MCS scores (lower scores indicating poorer HRQoL). PSG parameters reflective of better sleep quality including total sleep time, sleep efficiency, and time in REM sleep were positively associated with MCS scores. PSG parameters were not significantly associated with PCS scores. PSG-documented sleep disruption negatively impacts, while better objective sleep quality positively impacts on the mental domain of HRQoL in MS.


25(OH)D-but not 1,25(OH)2D-Is an independent risk factor predicting graft loss in stable kidney transplant recipients.
Vitamin D deficiency (VDD) or vitamin D insufficiency is common in kidney transplant recipients (KTRs). The impact of VDD on clinical outcomes in KTRs remain poorly defined and the most suitable marker for assessing vitamin D nutritional status in KTRs is unknown so far. We conducted a prospective study including 600 stable KTRs (367 men, 233 women) and a meta-analysis to pool existing evidence to determine whether 25(OH)D or 1,25(OH)2D predicted graft failure and all-cause mortality in stable KTRs. Compared with a higher 25(OH)D concentration, a low concentration of 25(OH)D was a risk factor for graft failure (HR 0.946, 95% CI 0.912-0.981, p = 0.003), whereas 1,25 (OH)2D was not associated with the study end-point graft loss (HR 0.993, 95% CI 0.977-1.009, p = 0.402). No association was found between either 25(OH)D or 1,25 (OH)2D and all-cause mortality. We furthermore conducted a meta-analysis including 8 studies regarding the association between 25(OH)D or 1,25(OH)2D and graft failure or mortality, including our study. The meta-analysis results were consistent with our study in finding that lower 25(OH)D levels were significantly associated with the risk of graft failure (OR = 1.04, 95% CI: 1.01-1.07), but not associated with mortality (OR = 1.00, 95% CI: 0.98-1.03). Lower 1,25(OH)2D levels were not associated with the risk of graft failure (OR = 1.01, 95% CI: 0.99-1.02) and mortality (OR = 1.01, 95% CI: 0.99-1.02). Baseline 25(OH)D concentrations but not 1,25(OH)2D concentrations were independently and inversely associated with graft loss in adult KTRs.


Reconstruction Using a Fibular Autograft for Lumbosacral Spinal Deformity in Neurofibromatosis Type 1: A Report of 2 Cases.
We present 2 cases (19- and 40-year-old women) of lumbosacral spinal deformity with sacroiliac joint destruction. Reconstruction surgery using a fibular strut autograft was performed in both patients, and spinal reconstruction and fusion were successfully maintained without bone resorption for at least 7 years. This is the first report of reconstructive surgery using a fibular strut bone graft for lumbosacral deformity with destruction of the sacroiliac joint in patients with neurofibromatosis type 1 (NF-1). These findings suggest that reconstruction with a fibular strut autograft is useful for lumbosacral spinal deformity that includes destruction of the sacroiliac joints in NF-1.


Prevalence and genotype of hepatitis C virus infection in pregnant women and blood donors in Ghana.
The seroprevalence of hepatitis C virus was evaluated in blood donors and antenatal clinic attenders in Kumasi, Ghana and seropositive subjects were tested for hepatitis C virus ribonucleic acid by the polymerase chain reaction (PCR). The overall seroprevalence among Ghanaians was 2.8% but there was a significantly higher prevalence in males (4.6%) than in females (1.0%). No risk factor for infection was identified by a questionnaire. Among those who showed evidence of active infection with a positive PCR, the most common genotype was type 2 but the subtype could not be specifically determined; these type 2 hepatitis C viruses may be indigenous to Africa.


Neutron scattering observation of quasi-free rotations of water confined in carbon nanotubes.
The translational and orientational dynamics of water in carbon nanotubes has been studied by quasi-elastic neutron scattering from 300 down to 10 K. Results show that, reducing temperature below 200 K, part of this water behaves as a quasi-free rotor, that is, the orientational energy of such molecules becomes comparable to the rotational energy of water in the gas phase. This novel and unique dynamic behavior is related to the appearance of water molecules characterized by a coordination number of about two, which is promoted by sub-nanometer axial confinement. This peculiar molecular arrangement allows water to show an active rotational dynamics even at temperatures as low as 10 K. The translational mobility shows a behavior compatible with the rotational one.


Diurnal pattern of choline concentrations in serum of pigs as influenced by dietary choline or lecithin intake.
Athletes especially experience a significant decrease in plasma choline concentrations during exercise which can be compensated in part by consumption of lecithin, a natural source of choline. In addition, the effect of lecithin on plasma choline concentrations in humans is obviously considerably greater and more prolonged than that of an equivalent amount of choline salts. Serum choline acts as a precursor for the synthesis of acetylcholine, which, in turn, acts as a neurotransmitter. The effect of dietary choline derived from either choline chloride or lecithin on the diurnal pattern of free choline concentrations in serum was studied using the pig as a potential model for humans. Six barrows, average initial body weight 120 kg, were fitted with permanent catheters in the jugular vein to determine the diurnal pattern of serum choline concentrations as affected by dietary choline or lecithin intake. The pigs were fed two semi-purified diets twice daily (1,500 g each meal) that contained corn, casein and a mineral-vitamin premix supplemented with equal amounts of choline (480 mg/kg) from either choline chloride or lecithin (BIOFOSFATIN). The diets supplemented with choline were fed at 08.00 h in the morning and the experiment was carried out according to a 3 x 2 cross-over design. All pigs received the basal diet that contained 450 mg/kg choline at the evening feeding (20.00 h). Following an adaptation period of 6 d, blood was collected on d 7; 0.5 h before the morning feeding and 1, 2, 4, 6, 8, 10 and 12 h postprandially. The determination of serum choline concentrations was carried out by tandem-mass spectroscopy. There were no differences (p > 0.05) between the two diurnal patterns of the serum choline concentrations. Both diurnal patterns showed a postprandial peak at 0.5 h (2.71 mg/l for choline chloride and 2.35 mg/l for lecithin supplementation) and decreased after 2 h postprandially to the preprandial concentrations. In conclusion, there were no differences (p > 0.05) in the diurnal patterns of serum choline concentrations in pigs after consumption of dietary choline chloride or lecithin, which is in contrast to corresponding studies in humans.


The Mechanisms of Systemic Inflammatory and Immunosuppressive Acute-on-Chronic Liver Failure and Application Prospect of Single-Cell Sequencing.
Acute-on-chronic liver failure (ACLF) is a complex clinical syndrome, and patients often have high short-term mortality. It occurs with intense systemic inflammation, often accompanied by a proinflammatory event (such as infection or alcoholic hepatitis), and is closely related to single or multiple organ failure. Liver inflammation begins when innate immune cells (such as Kupffer cells (KCs)) are activated by binding of pathogen-associated molecular patterns (PAMPs) from pathogenic microorganisms or damage-associated molecular patterns (DAMPs) of host origin to their pattern recognition receptors (PRRs). Activated KCs can secrete inflammatory factors as well as chemokines and recruit bone marrow-derived cells such as neutrophils and monocytes to the liver to enhance the inflammatory process. Bacterial translocation may contribute to ACLF when there are no obvious precipitating events. Immunometabolism plays an important role in the process (including mitochondrial dysfunction, amino acid metabolism, and lipid metabolism). The late stage of ACLF is mainly characterized by immunosuppression. In this process, the dysfunction of monocyte and macrophage is reflected in the downregulation of HLA-DR and upregulation of MER tyrosine kinase (MERTK), which weakens the antigen presentation function and reduces the secretion of inflammatory cytokines. We also describe the specific function of bacterial translocation and the gut-liver axis in the process of ACLF. Finally, we also describe the transcriptomics in HBV-ACLF and the recent progress of single-cell RNA sequencing as well as its potential application in the study of ACLF in the future, in order to gain a deeper understanding of ACLF in terms of single-cell gene expression.


Hepatic extraction, metabolism and biliary excretion of doxorubicin in the isolated perfused rat liver.
The hepatic extraction, metabolism, and biliary excretion of doxorubicin (DX) were studied in the isolated perfused rat liver. Three doses of DX equivalent to 2, 20, and 100 mg/kg in rats were studied over a period of 3 h after bolus injection into the reservoir. DX and metabolites concentration in perfusate, bile, and liver were determined by high-pressure liquid chromatography. The hepatic extraction ratio was low (less than 0.24) and decreased progressively over the 3 h. The hepatic extraction and clearance were significantly lower at the highest dose. Doxorubicinol (DX-OL) was the only metabolite detected in the perfusate, accounting for less than 4% of the total AUC. Thirty-one to thirty-three percent of the dose was excreted into bile over 3 h as unchanged DX. This was reduced to 22% at the highest dose. Only 0.35%-1.33% of the dose was excreted as DX-OL. DX aglycones were found only in the liver, where they represented 20%-30% of the total fluorescence at 3 h. In conclusion, in this model DX has a low extraction ratio, is poorly metabolized and extensively excreted into bile.


School- and class-level variation in self-harm, suicide ideation and suicide attempts in Danish high schools.
Strong associations have been found between being exposed to self-harm in family and friends and own self-harm in adolescence. Therefore, self-harm and suicide behaviour might tend to cluster within school and school classes. The aim of this study was to describe the prevalence, frequency and type of self-harm, suicide ideation and suicide attempts within Danish high schools and to test whether self-harm and suicide behaviour cluster in schools and school classes. Data came from the Danish National Youth Study 2014, a national survey. The respective study included 66,284 high-school students nested in 117 schools and 3146 school classes. The prevalence and clustering of self-harm behaviour, ever and within the last year, type of self-harm (e.g. cutting, burning, scratching and hitting) and suicide ideation and suicide attempts were investigated. Multi-level logistic regression was applied to quantify clustering among participants within the same class and school. In total, 12,960 (20%) reported self-harm ever and 5706 (8.6%) within the last year. Prevalence was higher among girls than boys. Among girls, cutting (15%) and scratching (13%) was the most common type of self-harm, whereas among boys, hitting (6.7%) was most prevalent. The degree of clustering of self-harm and suicide behaviour was low, with school-level intra-class correlation coefficients (ICC) ranging from 0.8-1.8% and school class level ICC's from 4.3-6.8%. This study shows that self-harm was common, especially in girls. The degree of clustering of self-harm and suicide behaviour in school and school classes was low.


Abnormal/normal metaphase ratio and prognosis in chronic B-lymphocytic leukemia.
Cytogenetic analysis was performed in B-cell mitogen-stimulated leukemic cell cultures from 55 patients with chronic B-lymphocytic leukemia. Clonal chromosomal aberrations were found in the cells of 33 patients, whereas 10 patients were cytogenetically normal. For 12 patients, too few metaphases were found to enable proper evaluation of the karyotype. The patients were subdivided into four groups according to the ratio between the number of metaphases with abnormal and normal chromosome patterns: AA, patients with only abnormal (A) metaphases; A/N high, patients with both abnormal and normal (NN metaphases and an A/N ratio greater than 0.5; A/N low, patients with an A/N ratio less than 0.5; NN, patients with only normal metaphases. In a log rank analysis, increasing A/N ratio was significantly associated with poor survival (p = 0.025). Four AA patients had a median survival of 6 months, whereas the 5-year probability of survival was 0.62 for the A/N high group, 0.92 for the A/N low group, and 1.0 for the NN group.


Algal biofuels.
The world is facing energy crisis and environmental issues due to the depletion of fossil fuels and increasing CO2 concentration in the atmosphere. Growing microalgae can contribute to practical solutions for these global problems because they can harvest solar energy and capture CO2 by converting it into biofuel using photosynthesis. Microalgae are robust organisms capable of rapid growth under a variety of conditions including in open ponds or closed photobioreactors. Their reduced biomass compounds can be used as the feedstock for mass production of a variety of biofuels. As another advantage, their ability to accumulate or secrete biofuels can be controlled by changing their growth conditions or metabolic engineering. This review is aimed to highlight different forms of biofuels produced by microalgae and the approaches taken to improve their biofuel productivity. The costs for industrial-scale production of algal biofuels in open ponds or closed photobioreactors are analyzed. Different strategies for photoproduction of hydrogen by the hydrogenase enzyme of green algae are discussed. Algae are also good sources of biodiesel since some species can make large quantities of lipids as their biomass. The lipid contents for some of the best oil-producing strains of algae in optimized growth conditions are reviewed. The potential of microalgae for producing petroleum related chemicals or ready-make fuels such as bioethanol, triterpenic hydrocarbons, isobutyraldehyde, isobutanol, and isoprene from their biomass are also presented.


Clinical and Autonomic Profile, and Modified Calgary Score for Children and Adolescents with Presumed Vasovagal Syncope Submitted to the Tilt Test.
In the pediatric population, syncope is mainly from vasovagal (VVS) origin. Its evaluation must be done by clinical methods, and the tilt test (TT) can contribute to the diagnosis. To analyze the clinical profile, Calgary and modified Calgary scores, response to TT and heart rate variability (HRV) of patients aged ≤ 18 years with presumed VVS. To compare the variables between patients with positive and negative responses to TT. Observational and prospective study, with 73 patients aged between 6 and 18 years, submitted to clinical evaluation and calculation of scores without previous knowledge of the TT. It was done at 70º under monitoring for HRV analysis. P-value < 0.05 was the statistical significance criterion. Median age was 14.0 years; 52% of participants were female, 72 had Calgary ≥ -2 (mean 1.80), and 69 had modified Calgary ≥ -3 (mean 1.38). Prodromes were observed in 59 patients, recurrence in 50 and trauma in 19. The response to TT was positive in 54 participants (49 vasovagal, with 39 vasodepressor responses), with an increase in the low frequency (LF) component and a decrease in the high frequency (HF) component (p < 0,0001). In the supine position, LF was 33.6 in females and 47.4 in normalized units for males (p = 0.02). When applying the operating characteristic curve for positive TT, there was no statistical significance for HRV and scores. Most children and adolescents with a presumed diagnosis of VVS presented a typical clinical scenario, with a Calgary score ≥ -2, and a predominant vasodepressor response to TT. Greater sympathetic activation was observed in the supine position in males. Calgary scores and sympathetic activation did not predict the response to TT.


Prenatal smoke exposure, DNA methylation, and childhood atopic dermatitis.
The biological mechanisms of how prenatal smoke exposure leading to atopic disorders remain to be addressed. Whether prenatal smoke exposure affects DNA methylation leading to atopic disorders is not clear. As most children suffering from atopic dermatitis (AD) continue to develop asthma later in life, we explored whether prenatal smoke exposure induces cord blood DNA methylation. Methylation differences associated with smoke exposure were screened by Illumina Infinium 27K methylation arrays for 14 children from the Taiwan birth panel study cohort initially. Information about development of atopic dermatitis (AD) and risk factors was collected. Cord blood cotinine levels were measured to represent prenatal smoke exposure. CpG loci that demonstrated a statistically significant difference in methylation were validated by methylation-dependent fragment separation (MDFS). Differential methylation in three genes (TSLP, GSTT1, and CYB5R3) was identified through the screen. Among these, only thymic stromal lymphopoietin (TSLP) gene displayed significant difference in promoter methylation percentage after being validated by MDFS (p = 0.018). TSLP gene was further investigated in a larger sample of 150 children from the cohort who completed the follow-up study. Methylation status of the TSLP 5'-CpG island (CGI) was found to be significantly associated with prenatal smoke exposure (OR = 3.17, 95% CI = 1.63-6.19) and with AD (OR = 2.32, 95% CI = 1.06-5.11). The degree of TSLP 5'CGI methylation inversely correlated with TSLP protein expression levels (r = -0.45, P = 0.001). The effect of prenatal tobacco smoke exposure on the risk for AD may be mediated through DNA methylation.


A rare chromosome 5 heterochromatic variant derived from insertion of 9qh satellite 3 sequences.
A rare chromosome 5 heterochromatic variant not linked to any clinical sign was identified in a three-generation family. After performing conventional cytogenetics characterization, fluorescence in situ hybridization of D9Z1 indicated that the unusually large qh region of chromosome 5 originated from 9qh, whereas the centromere of the variant chromosome was 5-specific as demonstrated by primed in situ DNA labelling. FISH of probes targeting satellite 3 and beta-satellite sequences of 9qh showed that only satellite 3 sequences were present in the variant 5qh region.


Follicular aspiration: a comparison of an ultrasonic endovaginal transducer with fixed needle guide and other retrieval methods.
Ultrasonic techniques have been developed as alternatives to conventional laparoscopic aspiration for oocyte retrieval for in vitro fertilization (IVF). Given the advantages (less risk, lower cost, and greater patient acceptance) of these alternative techniques, it is appropriate to assess their efficacy compared with traditional laparoscopic retrieval. This article examines the recovery rate of oocytes and their subsequent fertilization rate with the use of an ultrasonic endovaginal transducer with fixed needle guide and compares these results with other retrieval methods. Comparisons were made between laparoscopic harvesting (n = 71, group I), ultrasonic transabdominal transvesical (n = 21, group II), and ultrasonic vaginal transducer (n = 76, group III). The data demonstrate comparable success using an ultrasonic endovaginal transducer with fixed needle guide. The authors believe this technique to be the procedure of choice for all routine oocyte retrievals during IVF treatment.


The theoretical basis for nursing at the community level: a comparison of three models.
Although literature on community health nursing identifies a nursing role at the community level, there is a lack of clarity about the elements and expected outcomes of this role. In this paper three models of community health practice are presented and discussed in terms of their effectiveness as a basis for nursing practice at the community level. These models are (1) the public health model, (2) community participation model, and (3) community change model. Factors that affect the effectiveness of nursing to work at the community level are also discussed and questions for reflection and debate raised.


Labedipinedilol-C: a third-generation dihydropyridine-type calcium channel antagonist displaying K+ channel opening, NO-dependent and adrenergic antagonist activities.
Intravenous and oral labedipinedilol-C showed a dose-dependent long-lasting hypotension and a decrease of heart rate in normotensive and conscious spontaneously hypertensive rats (SHR). In isolated Wistar rat and guinea pig tissues, labedipinedilol-C competitively antagonized (-)isoproterenol-induced cardiac stimulation, tracheal relaxation, and phenylephrine-, CaCl2-, and high-K-induced aorta contractions in a concentration-dependent manner. The estimated pA2 and pKCa values were 8.22+/-0.04 and 7.11+/-0.52, respectively. [H]CGP-12177 binding to ventricle and lung tissues as well as [H]prazosin and [H]nitrendipine binding to brain membranes were inhibited by labedipinedilol-C with Ki values of 2.86, 9.03, 0.39, and 0.05 muM, respectively. The vasorelaxant effects of labedipinedilol-C on phenylephrine (10 microM)-induced contractions were attenuated by removing endothelium, by pretreatment with soluble guanylyl cyclase (sGC) inhibitors ODQ (10 microM) and methylene blue (10 microM), a NOS inhibitor L-NAME (100 microM), a K channel blocker TEA (10 mM), a KATP channel blocker glibenclamide (1 microM), and Ca-dependent K channel blockers apamin (1 microM) and charybdotoxin (0.1 microM). In human umbilical vein endothelial cells (HUVECs), labedipinedilol-C increased NO release, which was significantly inhibited by L-NAME. The Western blot analysis on HUVECs indicated that labedipinedilol-C increased the expression of eNOS. These results indicate that hypotension effects of labedipinedilol-C result from alpha-adrenoceptor and Ca entry-blocking activities and release of NO or NO-related substance from vascular endothelium. The endothelium-independent relaxation of vascular smooth muscle is probably linked to K channel opening and alpha-adrenoceptor-blocking activities.


[Analysis of a population of Cannabis sativa L. originating from Mexico and cultivated in France (author's transl)].
Cannabinoid content of a population of Cannabis sativa L. originating from Mexico and cultivated in France is studied. The statistical analysis of results shows how difficult it is to obtain homogenous and representative samples. This problem is correlated to genetic heterogeneity of seeds.


Several microRNAs could predict survival in patients with hepatitis B-related liver cancer.
MicroRNAs as biomarkers play an important role in the tumorigenesis process, including hepatocellular carcinomas (HCCs). In this paper, we used The Cancer Genome Atlas (TCGA) database to mine hepatitis B-related liver cancer microRNAs that could predict survival in patients with hepatitis B-related liver cancer. There were 93 cases of HBV-HCC and 49 cases of adjacent normal controls included in the study. Kaplan-Meier survival analysis of a liver cancer group versus a normal control group of differentially expressed genes identified eight genes with statistical significance. Compared with the normal liver cell line, hepatocellular carcinoma cell lines had high expression of 8 microRNAs, albeit at different levels. A Cox proportional hazards regression model for multivariate analysis showed that four genes had a significant difference. We established classification models to distinguish short survival time and long survival time of liver cancers. Eight genes (mir9-3, mir10b, mir31, mir519c, mir522, mir3660, mir4784, and mir6883) were identified could predict survival in patients with HBV-HCC. There was a significant correlation between mir10b and mir31 and clinical stages (p < 0.05). A random forests model effectively estimated patient survival times.


A review of the main methods for composite adsorbents characterization.
Adsorption is a promising technology for removing several contaminants from aqueous matrices. In the last years, researchers worldwide have been working on developing composite adsorbents to overcome some limitations and drawbacks of conventional adsorbent materials, which depend on various factors, including the characteristics of the adsorbents. Therefore, it is essential to characterize the composite adsorbents to describe their properties and structure and elucidate the mechanisms, behavior, and phenomenons during the adsorption process. In this sense, this work aimed to review the main methods used for composite adsorbent characterization, providing valuable information on the importance of these techniques in developing new adsorbents. In this paper, we reviewed the following methods: X-Ray diffraction (XRD); spectroscopy; scanning electron microscopy (SEM); N2 adsorption/desorption isotherms (BET and BJH methods); thermogravimetry (TGA); point of zero charge (pHPZC); elemental analysis; proximate analysis; swelling and water retention capacities; desorption and reuse.


Di-chlorido-(pyridine-κN)[2,3,5,6-tetra-kis-(pyridin-2-yl)pyrazine-κ3 N 2,N 1,N 6]nickel(II).
In the title complex, [NiCl2(C5H5N)(C24H16N6)], the NiII ion is six-coordinated in a distorted octa-hedral coordination environment defined by three N atoms of the tridentate 2,3,5,6-tetra-2-pyridyl-pyrazine ligand, one N atom of the pyridine ligand and two Cl- anions, with the latter being mutually trans. The complex is disposed about a twofold rotation axis along the a axis. The complex molecules are connected in the crystal via C-H⋯Cl, C-H⋯N and π-π [closest inter-centroid separation = 3.7446 (14) Å between pyridyl rings].


VE1 immunohistochemistry accurately detects BRAF V600E mutations in colorectal carcinoma and can be utilized in the detection of poorly differentiated colorectal serrated adenocarcinoma.
Serrated adenocarcinoma (SAC) is a recently defined subtype of colorectal carcinoma (CRC). However, in cases where an adjacent serrated adenoma is absent and the differentiation is poor, the diagnosis of SAC can be challenging. BRAF V600E mutation is a characteristic molecular change for the serrated route, but the utility of the newly described BRAF V600E-specific immunohistochemistry in the recognition of SAC is unclear. In this study, we conducted immunohistochemical determination of BRAF V600E mutation and correlated the results to BRAF mutation status and the histological features of SAC in a cohort of 147 CRC patients. There were 13 (8.8 %) BRAF-mutated CRCs confirmed by DNA sequencing. The sensitivity of immunohistochemistry in detecting BRAF V600E mutation was 100 % (13/13) and the specificity was 99.3 % (133/134). Three evaluators independently analyzed the immunohistochemical sections and the correlation between all the evaluators was perfect (κ = 1). In histologic examination, 33 (22.4 %) of the CRCs were classified as SACs. Twelve of 13 (92.3 %) BRAF-mutated CRCs were evaluated to represent serrated type growth pattern. One of 13 (7.7 %) showed poor differentiation not enabling convincing classification. In conclusion, we found immunohistochemistry to be accurate in the detection of the BRAF V600E mutation, with potential applications in the recognition of the BRAF-mutated SACs. Especially in cases where the adjacent adenoma is absent and the tumor is poorly differentiated, BRAF immunohistochemistry could be utilized as an aid to detect SACs.


Association of metals with geochemical phases in wetland soils of a Ramsar site in India.
Mobilization of metals in wetland ecosystems is a function of the behaviour of a specific metal species and is dependent largely on the prevailing micro-environmental conditions. Apparently, five different chemical forms of metals are known with varying affinity to binding sites, mobility, bioavailability and toxicity. Quantification of these forms of metals in the soils is imperative in predicting their biogeochemical fate and toxicity. In this context, we examined the association of Cu, Pb and Zn, with various geochemical phases in the soil profile of wetland system of Keoladeo National Park, a Ramsar site in India. The assessment covered the soil profile until 100 cm depth at every 25-cm intervals. Different operationally defined geochemical phases in the soil at different depths were examined during the study for respective metal concentrations. Hydrous oxides of Fe-Mn were the major carrier for all the three metals and the fraction associated with exchangeable phase was the least. The low organic matter content in the soil seems to be influencing the metal association with the organic matter (OM-S) phase, which was also a less preferred carrier for metals. For Cu (5.8-78.4%) and Pb (33.5-88.5%), Fe-Mn hydroxide phase was an important binding site and for Zn (31.02-79.03%), it was the silicate mineral matrix (RES phase). This suggests the importance of micro-environmental conditions in the wetland bed such as redox and pH in mobilization of metals. As metals such as Pb have high eco-toxicological potential, an assessment of fractional concentrations of metals provides insights into their mobility and bioavailability in aquatic ecosystems. This aids wetland managers to develop appropriate strategy to maintain quality of inflow water, the single most crucial factor for a wetland ecosystem, and thus controls the micro-environmental conditions.


The giant panda is cryptic.
The giant panda (Ailuropoda melanoleuca) is an iconic mammal, but the function of its black-and-white coloration is mysterious. Using photographs of giant pandas taken in the wild and state-of-the-art image analysis, we confirm the counterintuitive hypothesis that their coloration provides camouflage in their natural environment. The black fur blends into dark shades and tree trunks, whereas white fur matches foliage and snow when present, and intermediate pelage tones match rocks and ground. At longer viewing distances giant pandas show high edge disruption that breaks up their outline, and up close they rely more on background matching. The results are consistent across acuity-corrected canine, feline, and human vision models. We also show quantitatively that the species animal-to-background colour matching falls within the range of other species that are widely recognised as cryptic. Thus, their coloration is an adaptation to provide background matching in the visual environment in which they live and simultaneously to afford distance-dependent disruptive coloration, the latter of which constitutes the first computational evidence of this form of protective coloration in mammals.


Temporal and spatial analysis of traffic - Related pollutant under the influence of the seasonality and meteorological variables over an urban city in Peru.
A four yearlong air monitoring data (since 2015 to 2018) was collected to assess the impact of meteorological parameters such as temperature, relative humidity, wind speed and wind direction on the spatial and temporal variability of CO (carbon monoxide), NO2 (nitrogen oxide), O3 (ozone), SO2 (sulfur dioxide), PM10 and PM2.5 (particulate matter with diameter aerodynamic less than 2.5 μm and 10 μm respectively) in Lima Metropolitan Area (LMA). Data from eight air quality monitoring stations, currently under the supervision of the National Meteorological and Hydrological Service (SENAMHI), was used to capture traffic - related pollutants concentrations under various local traffic conditions. Effects on meteorological events on seasonal traffic-related pollutants concentration variability were identified. Using average data from the eight stations, it was found that the monthly mean traffic-related pollutants since 2015 to 2018 were higher in spring and winter and lower in autumn and summer. Low-wind speed was associated with events that contribute to elevated seasonal PM2.5 levels. Correlation coefficients between PM2.5 concentrations and meteorological variables fluctuated significaly across different seasons. High PM2.5 concentrations were associated with low relative humidity and high wind conditions in spring. Results suggest that there exist a seasonal variation of PM2.5 concentration, and set the need of future work on the understanding of the air pollution effects on human health.


Mucosal Melanoma of the Oral Cavity: What is the Role of Elective Neck Dissection?
Mucosal melanoma (MM) is a rare malignancy that can present in the head and neck (H&N). The Oral cavity is the second most common primary site in the H&N after sinonasal mucosa. This study investigates the impact of demographic and clinical factors on survival in oral cavity MM. Further, it investigates the outcomes and utility of elective neck dissections (END) in the management of oral MM. The National Cancer Database was used to evaluate 432 patients with oral cavity MM from 2004 to 2016. Kaplan-Meir and Cox regression analyses were used to determine variables associated with survival. The mean age was 64.0 ± 16.0 years. Most patients were white (85.1%) and male (60.0%). Gingiva (37.6%) and hard palate (36.1%) were the most common primary subsites in the oral cavity. Five-year overall survival was 31.0%. Age (Hazards Ratio [95% Confidence Interval], 1.03 [1.01-1.06]), N-stage (1.94 [1.10-3.42]), M-stage (10.13 [3.33-30.86]), male sex (1.79 [1.06-3.03]), and African-American race (2.63 [1.14-6.11]) were significantly associated with worse survival. 199 patients (46.9%) underwent neck dissection including 118 with lymph node yield (LNY) ≥ 18. The rate of occult nodal positivity was 45.4% for LNY ≥ 18 and 28.3% for LNY ≥ 1. ENDs were not associated with improved outcomes. However, occult lymph node involvement was associated with worse overall survival (p = 0.004). Oral cavity MM has a poor prognosis. Lymph node involvement, distant metastasis, age, race, and male sex are associated with worse outcomes. Performing an END did not improve survival. However, END may have a prognostic role and help select patients for treatment intensification. 4 Laryngoscope, 133:317-326, 2023.


Treatment of old cervical bilateral facet dislocation: Case report and literature review.
Late diagnosis of cervical bilateral facet dislocation is rare and contributes to concerns in the management of these patients. We present a case of a 44-year-old woman presented 8 months after a trauma with persistent neck pain, without neurological deficits. A bilateral C5-C6 facet dislocation was identified. The patient was treated with a combined C5-C6 approach: posterior facet joints release, anterior discectomy and fusion, bilateral posterior fixation. Surgery was performed under intraoperative neurophysiological monitoring. The postoperative period was uneventful, and the patient presented functional improvement. Late surgical treatment of bilateral cervical facet dislocation is safe and feasible. Combined procedures are needed for proper reduction and stabilization of the spine. Intraoperative neurophysiological monitoring adds value to this technique contributing to good outcomes.


Multiple RNA- and DNA-binding proteins exhibit direct transfer of polynucleotides with implications for target-site search.
We previously demonstrated that the polycomb repressive complex 2 chromatin-modifying enzyme can directly transfer between RNA and DNA without a free-enzyme intermediate state. Simulations suggested that such a direct transfer mechanism may be generally necessary for RNA to recruit proteins to chromatin, but the prevalence of direct transfer capability is unknown. Herein, we used fluorescence polarization assays and observed direct transfer for several well-characterized nucleic acid-binding proteins: three-prime repair exonuclease 1, heterogeneous nuclear ribonucleoprotein U, Fem-3-binding factor 2, and MS2 bacteriophage coat protein. For TREX1, the direct transfer mechanism was additionally observed in single-molecule assays, and the data suggest that direct transfer occurs through an unstable ternary intermediate with partially associated polynucleotides. Generally, direct transfer could allow many DNA- and RNA-binding proteins to conduct a one-dimensional search for their target sites. Furthermore, proteins that bind both RNA and DNA might be capable of readily translocating between those ligands.


Cognitive impairment of rats caused by oxidative stress and aging, and its prevention by vitamin E.
In order to verify whether brain damage caused by chronic oxidative stress induces the impairment of cognitive function, the ability of learning and memory was assessed using the water maze and the eight-arm radial maze tasks. Young rats showed significantly greater learning ability before the stress than the old and vitamin E-deficient rats. At five days after subjection to oxidative stress, the memory function of the young declined toward the level of that in the aged rats maintained under normal condition. This phenomenon is supported by the findings that the delayed-type apoptosis appeared in the CA1 region of the hippocampus of the young at five to seven days after the stress. Vitamin E supplementation to the young accelerated significantly their learning functions before the stress and prevented the deficit of memory caused by the stress. When rats were subjected to stress, thiobarbituric acid-reactive substance (TBARS), lipid hydroperoxides, and protein carbonyls were significantly increased in synaptic plasma membranes. It was found that zeta-potential of the synaptic membrane surface was remarkably decreased. These phenomena were also observed in the aged and vitamin E-deficient rats maintained under normal condition. These results suggest that oxidative damage to the rat synapse in the cerebral cortex and hippocampus during aging may contribute to the deficit of cognitive functions.


Efficient Health Information Management Based on Patient-Generated Digital Data.
Technology has been a growing part of healthcare for decades. The patient experience is going digital, and consumers are leading the way by accessing EHRs and using digital tools, such as wearables and apps, to manage their health. Patient-generated health data (PGHD) are health-related data created, recorded, or gathered by or from patients (or family members or other caregivers) to help address a health concern. PGHD may have several reported patient engagement and empowerment benefits, but lingering issues may prohibit providers from actually using patients' data. In this paper we review the main recent PGHD uses, challenges and opportunities.


The incisural fracture.
A case report is presented on two adolescent patients with fracture of the distal tibial articular surface that is different than the Tillaux, Wagstaffe-Le Fort, and Chaput fractures.


Behavior of medically-derived 131I in the tidal Potomac River.
Iodine-131 (t1/2=8.04 d) is administered to patients for treatment of thyroid disorders, excreted by patients and discharged to surface waters via sewage effluent. Radionuclides generally behave like their stable analogs; therefore, medically-derived (131)I is useful as a transport-reaction tracer of anthropogenic inputs and the aquatic biogeochemistry of iodine. Iodine-131 was measured in Potomac River water and sediments in the vicinity of the Blue Plains Water Pollution Control Plant (WPCP), Washington, DC, USA. Concentrations measured in sewage effluent from Blue Plains WPCP and in the Potomac River suggest a relatively continuous source of this radionuclide. The range of (131)I concentrations detected in surface water was 0.076±0.006 to 6.07±0.07 Bq L(-1). Iodine-131 concentrations in sediments ranged from 1.3±0.8 to 117±2 Bq kg(-1) dry weight. Partitioning in the sewage effluent from Blue Plains and in surface waters indicated that (131)I is associated with colloidal and particulate organic material. The behavior of medically-derived (131)I in the Potomac River is consistent with the nutrient-like behavior of natural iodine in aquatic environments. After discharge to the river via sewage effluent, it is incorporated into biogenic particulate material and deposited in sediments. Solid phase sediment profiles of (131)I indicated rapid mixing or sedimentation of particulate debris and diagenetic remineralization and recycling on short time scales.


Motor unit activity and surface electromyogram power spectrum during increasing force of contraction.
Twelve male subjects were tested to determine the relationship between motor unit (MU) activities and surface electromyogram (EMG) power spectral parameters with contractions increasing linearly from zero to 80% of maximal voluntary contraction (MVC). Intramuscular spike and surface EMG signals recorded simultaneously from biceps brachii were analyzed by means of a computer-aided intramuscular MU spike amplitude-frequency (ISAF) histogram and an EMG frequency power spectral analysis. All measurements were made in triplicate and averaged. Results indicate that there were highly significant increases in surface EMG amplitude (71 +/- 31.3 to 505 +/- 188 microV, p less than 0.01) and mean power frequency (89 +/- 13.3 to 123 +/- 23.5 Hz, p less than 0.01) with increasing force. These changes were accompanied by progressive increases in the firing frequency of MU's initially recruited, and of newly recruited MU's with relatively larger spike amplitudes. The group data in the ISAF histograms revealed significant increases in mean spike amplitude (412 +/- 79 to 972 +/- 117 microV, p less than 0.01) and mean firing frequency (17.8 +/- 5.4 to 24.7 +/- 4.1 Hz, p less than 0.01). These data suggest that surface EMG spectral analysis can provide a sensitive measure of the relative changes in MU activity during increasing force output.


A study of the separate effects of influence factors and their coupled interactions on cryoinjury of human erythrocytes.
The separate effects of five influence factors and their coupled interactions on cryoinjury of human erythrocytes were investigated experimentally and statistically. The five factors, each having three levels, were as follows: (1) cooling rate: -0.5, -140, and -800 degrees C/min; (2) warming rate: +0.5, +25, and +200 degrees C/min; (3) hematocrit: 2, 11, and 60%; (4) concentration of cryoprotectant (glycerol): 1, 2, and 4 M in PBS; and (5) holding temperature at which the frozen samples were kept: no hold, -75 degrees C for 1.5 hr, and -196 degrees C for 1.5 hr. Twenty-seven special tests, which were chosen from the 243 possible tests by using the Fractional Factorial Design Technique, an optimum seeking technique, were performed. The conclusions are: (1) the cooling rate is the most significant or sensitive factor causing cryoinjury to the cells; (2) the main effects of the hematocrit and the concentration of cryoprotectant, the interaction between the cooling rate and the warming rate, and the interaction between the cooling rate and the concentration of cryoprotectant are next most significant; (3) the main effect of warming rate, and the interaction between the holding temperature and the cooling rate are less significant; (4) the holding temperature below -75 degrees C, and the remaining interactions between two factors are relatively not significant; and (5) in the present study, the optimal combination of the five factors for the survival of the cells is: cooling at -0.5 degrees C/min, warming at +0.5 degrees C/min, hematocrit at 11%, glycerol concentration at 4 M in PBS, and holding temperature below -75 degrees C.


What do residents do when not working or sleeping? A multispecialty survey of 36 residency programs.
To determine how residents spend their time when not working or sleeping, and to examine correlates of these outside activities. In 2009, the authors surveyed 36 internal medicine, surgery, pediatrics, and obstetrics-gynecology programs. Residents answered questions about their recently completed first and second residency years, including, "During your past year of residency, outside of working hours, about how often did you…," followed by 10 listed activities and a four-point rating scale (1 = "less than once a week"; 4 = "almost daily"). The most frequent activity reported across all 634 respondents was using the Internet, followed by watching television and doing household tasks. The lowest reported activity was moonlighting, followed by seeing a movie. K-cluster analyses divided residents into three clusters: (1) "Friend Focused," reporting higher means for time with friends, Internet use, physical exercise, and watching television, (2) "Family Focused," reporting higher means for time with family, Internet use, household tasks, and watching television, and (3) "Low Activity," reporting the lowest ratings for all activities. Comparisons among these three clusters showed the Low Activity residents to have significantly higher scores on validated depression, anxiety, and sleepiness scales; higher stress; more reported work hours and sleep deprivation; and lower ratings for satisfaction, time with attendings, and learning. Scores for Friend-Focused and Family-Focused clusters were similar to each other. These data provide new information about the residency experience and suggest that activities outside of work and sleep hours correlate highly with residents' mood, learning, and satisfaction.


P-Chirogenic Diphosphazanes with Axially Chiral Substituents and Their Use in Rh-Catalyzed Asymmetric Hydrogenation.
A convenient synthesis of enantiopure P-chirogenic diphosphazanes incorporating bulky bisphenol and 1,1'-bi-2-naphthol-derived substituents via the functionalization of a readily accessible enantiopure lithium phosphinoamide with chlorophosphoridites was developed. Since the product requires no subsequent deprotection, the protocol provides an easy, convenient synthesis of P-chirogenic ligands on the gram scale. The ligands were applied in the Rh-catalyzed asymmetric hydrogenation of benchmark substrates furnishing enantiomeric excess values up to 96%.


Intrinsic Age-Dependent Changes and Cell-Cell Contacts Regulate Nephron Progenitor Lifespan.
During fetal development, nephrons of the metanephric kidney form from a mesenchymal progenitor population that differentiates en masse before or shortly after birth. We explored intrinsic and extrinsic mechanisms controlling progenitor lifespan in a transplantation assay that allowed us to compare engraftment of old and young progenitors into the same young niche. The progenitors displayed an age-dependent decrease in proliferation and concomitant increase in niche exit rates. Single-cell transcriptome profiling revealed progressive age-dependent changes, with heterogeneity increasing in older populations. Age-dependent elevation in mTor and reduction in Fgf20 could contribute to increased exit rates. Importantly, 30% of old progenitors remained in the niche for up to 1 week post engraftment, a net gain of 50% to their lifespan, but only if surrounded by young neighbors. We provide evidence in support of a model in which intrinsic age-dependent changes affect inter-progenitor interactions that drive cessation of nephrogenesis.


[Clinical and electroencephalographic characteristics of specific language impairment in children and an evaluation of the efficacy of cerebrolysin].
To study different forms of specific language impairment in children and to evaluate the efficacy of cerebrolysin in clinical and electroencephalographic aspects. Authors examined 60 children, aged 5-7 years, with a specific language impairment (SLI). The study showed the significantly higher severity of speech disorders, a higher degree of asthenia and dyspraxia/dysgnosia in a group of children with a disorder of receptive language (SLI-R) compared to children with a disorder of expressive speech (SLI-E). A comparative analysis of the EEG power spectra showed large values of slow theta-band EEG in children with SLI compared with healthy children. Children with SLI-R were characterized by the increase in theta rhythm power in the occipital region compared with children with SLI-E. The high efficacy of cerebrolysin in the treatment of this disease (an improvement was obtained in 73.3% of cases) was demonstrated, with the best effect in children with SLI-E (80.0% of cases).


Introduction of the Exocelinacasuarina-group, with a key to its representatives and descriptions of 19 new species from New Guinea (Coleoptera, Dytiscidae, Copelatinae).
Nineteen new species of Exocelina Broun, 1886 from New Guinea are described herein: E.adelbertensis sp. n., E.ambua sp. n., E.bewani sp. n., E.cyclops sp. n., E.ibalimi sp. n., E.keki sp. n., E.kumulensis sp. n., E.mendiensis sp. n., E.menyamya sp. n., E.okapa sp. n., E.piusi sp. n., E.pseudofume sp. n., E.pseudopusilla sp. n., E.pusilla sp. n., E.sima sp. n., E.simbaiensis sp. n., E.simbaijimi sp. n., E.sumokedi sp. n., and E.yoginofi sp. n. All of them, together with five already described species, have been united into the newly defined casuarina-group, a polyphyletic complex of related species with similar shape of the median lobe and paramere setation. An identification key to all known species of the group is provided, and important diagnostic characters (habitus, color, male protarsomeres 4-5, median lobes, and parameres) are illustrated. Data on the distribution of the species are given, showing that most of the species occur in the central, mountain part of Papua New Guinea.


Alterations in cyclin-dependent kinase 2 function during differentiation of primary human keratinocytes.
Terminal differentiation of epithelial cells is intimately linked to cell-cycle withdrawal. The tight coupling of these two processes is critical to maintenance of epidermal tissue homeostasis and is frequently disrupted in squamous cell carcinoma. To identify possible molecular targets of epithelial carcinogenesis, we investigated the regulatory pathways that couple cellular differentiation and proliferation in primary cultures of human keratinocytes and found that the cyclin-dependent kinase inhibitors (CKIs) p21cip1/waf1 and p27kip1 were induced early during differentiation of human keratinocytes, whereas p15ink4B was induced later in differentiation. The induction of p21c1/waf1 was mediated by both transcriptional and non-transcriptional mechanisms, and the activities of cyclin A/cyclin-dependent kinase (cdk) 2 and cyclin E/cdk2 complexes were specifically inhibited during keratinocyte differentiation. In contrast, p21cip1/wafl did not associate with cdk4, and the activities of cdk4 complexes remained unchanged. Hence, our results support the model that multiple CKIs participate in linking cellular proliferation and differentiation in human keratinocytes by specific modulation of cdk2 activity.


Three new compounds from the dried root bark of Wikstroemia indica and their cytotoxicity against HeLa cells.
Three new compounds (1-3) and twelve known compounds (4-15) were isolated from the n-butanol extraction of the 70% ethanol extract of the dried root barks of Wikstroemia indica. The structures of new compounds were identified by chemical evidence and extensive analysis of spectroscopic data (HR-ESI-MS, 1 D and 2 D NMR) and ECD calculations. All isolated compounds were evaluated for their cytotoxicity against HeLa cells using MTT assay and the results showed that daphnoretin (compound 5) owned the highest cytotoxicity against HeLa cells (IC50=28.89 μmol/L).


Carcinosarcoma of the renal pelvis.
An unusual heterologous carcinosarcoma of the renal pelvis is reported. The differential diagnosis, problems related to nomenclature and histogenetic implications of this rare neoplasm are discussed.


Titanium dioxide nanofibers integrated stainless steel filter for photocatalytic degradation of pharmaceutical compounds.
A photocatalytically active stainless steel filter (P-SSF) was prepared by integrating electrospun TiO2 nanofibers on SSF surface through a hot-press process where a poly(vinylidene fluoride) (PVDF) nanofibers interlayer acted as a binder. By quantifying the photocatalytic oxidation of cimetidine under ultraviolet radiation and assessing the stability of TiO2 nanofibers integrated on the P-SSF against sonication, the optimum thickness of the TiO2 and PVDF layer was found to be 29 and 42 μm, respectively. At 10L/m(2)h flux, 40-90% of cimetidine was oxidized when the thickness of TiO2 layer increased from 10 to 29 μm; however, no further increase of cimetidine oxidation was observed as its thickness increased to 84 μm, maybe due to limited light penetration. At flux conditions of 10, 20, and 50 L/m(2) h, the oxidation efficiencies for cimetidine were found to be 89, 64, and 47%, respectively. This was attributed to reduced contact time of cimetidine within the TiO2 layer. Further, the degradation efficacy of cimetidine was stably maintained for 72 h at a flux of 10 L/m(2) h and a trans-filter pressure of 0.1-0.2 kPa. Overall, our results showed that it can potentially be employed in the treatment of effluents containing organic micropollutants.


[Immune and autoimmune reactions in the mechanism of action of drug substances, their detoxication and the development of habituation to them].
It has been shown that rausedyl administration is followed by enhanced synthesis of autoantibodies to serotonine and adrenaline. Meanwhile bucarban enhances the synthesis of autoantibodies to endogenous insulin and ACTH to hydrocortisone and testosterone. Activation of the autoimmune system of regulating the balance of endogenous compounds was shown by an increased number of specific antibody-producing cells in the organs and tissues and by the growth of the titer of circulating antibodies in the blood.


Psychopharmacological study with K 8409, a 1H-naphtho[2,1-b]pyran 3-dialkylamino substituted derivative.
A 1H-naphtho[2,1-b]pyran derivative (K 8409) has undergone pharmacological investigation for psychotropic activity. The results show potential antidepressant action quantitatively similar to that of imipramine and amitriptyline, but due rather to MAO inhibition than to imipramine-like activity; interestingly enough, anti-MAO activity was particularly selective for the serotonin-converting enzyme, both centrally and peripherally. The outcome of the other tests suggests that the incidence of untoward effects is likely to be limited.


TRP channel functions in the gastrointestinal tract.
Transient receptor potential (TRP) channels are predominantly distributed in both somatic and visceral sensory nervous systems and play a crucial role in sensory transduction. As the largest visceral organ system, the gastrointestinal (GI) tract frequently accommodates external inputs, which stimulate sensory nerves to initiate and coordinate sensory and motor functions in order to digest and absorb nutrients. Meanwhile, the sensory nerves in the GI tract are also able to detect potential tissue damage by responding to noxious irritants. This nocifensive function is mediated through specific ion channels and receptors expressed in a subpopulation of spinal and vagal afferent nerve called nociceptor. In the last 18 years, our understanding of TRP channel expression and function in GI sensory nervous system has been continuously improved. In this review, we focus on the expressions and functions of TRPV1, TRPA1, and TRPM8 in primary extrinsic afferent nerves innervated in the esophagus, stomach, intestine, and colon and briefly discuss their potential roles in relevant GI disorders.


Yeast mitochondrial DNA mutators with deficient proofreading exonucleolytic activity.
The MIP1 gene which encodes yeast mitochondrial DNA polymerase possesses in its N-terminal region the three motifs (Exo1, Exo2 and Exo3) which characterize the 3'-5' exonucleolytic domain of many DNA polymerases. By site directed mutagenesis we have substituted alanine or glycine residues for conserved aspartate residues in each consensus sequence. Yeast mutants were therefore generated that are capable of replicating mitochondrial DNA (mtDNA) and exhibit a mutator phenotype, as estimated by the several hundred-fold increase in the frequency of spontaneous mitochondrial erythromycin resistant mutants. By overexpressing the mtDNA polymerase from the GAL1 promoter as a major 140 kDa polypeptide, we showed that the wild-type enzyme possesses a mismatch-specific 3'-5' exonuclease activity. This activity was decreased by approximately 500-fold in the mutant D347A; in contrast, the extent of DNA synthesis was only slightly decreased. The wild-type mtDNA polymerase efficiently catalyses elongation of singly-primed M13 DNA to the full-length product. However, the mutant preferentially accumulates low molecular weight products. These data were extended to the two other mutators D171G and D230A. Glycine substitution for the Cys344 residue which is present in the Exo3 site of several polymerases generates a mutant with a slightly higher mtDNA mutation rate and a slightly lower 3'-5' exonucleolytic activity. We conclude that proofreading is an important determinant of accuracy in the replication of yeast mtDNA.


Circulating microRNAs as potential biomarkers for genetic generalized epilepsies: a three microRNA panel.
Genetic generalized epilepsies (GGEs) encompass a group of syndromes of mainly genetic causes, characterized by the involvement of both hemispheres. MicroRNAs (miRNAs) are small non-coding RNAs with a critical role in the regulation of neuronal biological processes through gene expression modulation. Dysregulated miRNA expression has been shown in epilepsy. Due to their stability in biological fluids like serum, miRNAs have assumed a prominent role in biomarker research. Our aim was to evaluate circulating levels of three miRNAs in GGE patients and assess their putative diagnostic value. MiR-146a, miR-155 and miR-132 were quantified by real-time polymerase chain reaction in the serum of 79 GGE patients (47 women, 32 men, 35.1 ± 12.4 years) and 67 healthy individuals (41 women, 26 men, 42.4 ± 10.1 years). Relative expression values were calculated using the 2-ΔΔCt method. Receiver operating characteristic curve analysis was performed to assess diagnostic value. MiRNA expression was correlated with clinicopathological features. Serum levels of miR-146a and miR-155 were significantly upregulated in GGE patients relative to controls (3.13 and 6.05, respectively). Combined miR-146a, miR-155 and miR-132 serum levels performed well as a diagnostic biomarker, discriminating GGE patients from controls with an area under the curve of 0.85, 80% specificity and 73% sensitivity. Our results indicate that miR-146a, miR-155 and miR-132 may partake in GGE epileptogenesis. A panel of three circulating miRNAs with potential value as a GGE biomarker is reported for the first time. Novel biomarkers may help to identify new treatment targets and contribute to improved patients' quality of life through earlier diagnosis and a more precise prognosis.


[Reduced emotional reactivity to negative stimuli in multiple sclerosis, preliminary results].
Charcot first described emotional deficits in multiple sclerosis (MS) in the XIXth century. Despite this early description, there are very few studies about emotions and MS. This study aimed at better understanding the emotional process in MS and more specifically recognition of facial emotions and emotional experience. Thirteen women with remittent MS (R-MS), with a mean EDSS score of 2, were compared with thirteen healthy control subjects, matched for age (mean age of 42±2), sex and educational level. The Beck Depression Inventory (BDI), the Hamilton Anxiety Scale and the brief repeatable battery of neuropsychological tests for MS (BCcogSEP) were administered. Recognition of faces and facial expression of emotion were assessed by the Benton facial recognition test and recognition of facial emotions was assessed by Ekman's facial expression test. We have also presented 12 different sounds and pictures from the International Affective Digitized Sounds and Picture System (IADS and IAPS) in order to study the emotional experience by using criteria of valence and arousal. No deficit of facial emotion recognition was found in MS in this small population. Nevertheless, patients who had difficulty recognizing faces were the least able to recognize facial expressions. No significant difference was observed between the patient and control group for the experience of emotional valence. However, independently of their mood and cognitive status, the self-assessment of the MS patient population suggested that the patients were less reactive to negative sounds (P=0.005) and negative pictures (P=0.002) as compared with the control group, pointing to lesser sensitivity towards aversive stimuli. These data suggest disorders in emotional processes in R-MS, mainly a poor reactivity to negative stimuli which may have an impact on everyday life. A larger population should be studied to confirm these modifications of emotion.


Thermoosmosis through charged membranes. Theoretical analysis of concentration dependence.
A theoretical equation for thermoosmosis through charged membranes in electrolyte solutions is derived from nonequilibrium thermodynamics. The theory shows that the volume flux through the membrane is proportional to the temperature difference across the membrane. The proportionality constant, i.e., the thermoosmotic coefficient is a function of electrolyte concentration. The electrolyte concentration dependence of the thermoosmotic coefficient calculated is compared with our previous experimental results. Agreement between theory and experiments is satisfactory.


Targeted inactivation of the hrcA repressor gene in cyanobacteria.
To determine if the CIRCE/HrcA system operates in cyanobacteria, we have inactivated the hrcA repressor gene in Synechocystis sp. PCC 6803 by gene targeting. In the hrcA mutant, the groESL1 operon and the groEL2 gene, both of which have the CIRCE operator in their upstream regions, were derepressed at 30 degrees C without affecting expression of other major heat-shock genes. However, expression of these groE genes in the mutant was not fully derepressed. Their transcription increased further upon heat shock, and was initiated from the same sites as those used under normal conditions. This suggests that their expression is regulated by at least two different mechanisms, a negative one controlled by HrcA and an unknown positive one. The heat-induced expression of clpB1 and htpG was greatly repressed by the absence of HrcA. The hrcA mutant which constitutively overexpressed GroEL displayed improved cellular thermotolerance and also reduced photobleaching of phycocyanin under heat stress conditions.


Overlapping and non-overlapping Ptch2 expression with Shh during mouse embryogenesis.
In Drosophila, patched encodes a negative regulator of Hedgehog signaling. Biochemical experiments have demonstrated that vertebrate patched homologues might function as a Sonic hedgehog (Shh) receptor. In mice, two patched homologues, Ptch and Ptch2, have been identified. Sequence comparison have suggested that they might possess distinct properties in Shh signaling. In the developing tooth, hair and whisker, Shh and Ptch2 are co-expressed in the epithelium while Ptch is strongly expressed in the mesenchymal cells. We report here the chromosomal localization of Ptch2 and further analysis of Ptch2 expression. Throughout mouse development, the level of Ptch2 expression is significantly lower than that of Ptch. In early mouse embryos, Ptch and Ptch2 were found to be co-expressed in regions adjacent to Shh-expressing cells in the developing CNS. Similar to other epidermal structures, Shh and Ptch2 also show overlapping expression in the developing nasal gland and eyelids. Thus, during mouse development, Ptch2 is expressed in both Shh-producing and -nonproducing cells.


In situ dynamics of Vibrio parahaemolyticus and Vibrio vulnificus in water, sediment and triploid Crassostrea virginica oysters cultivated in floating gear.
To understand spatial-temporal distribution of Vibrio parahaemolyticus and Vibrio vulnificus in triploid Crassostrea virginica in off-bottom aquaculture. Oysters, sediments and water were seasonally collected in Georgia, USA. V. parahaemolyticus and V. vulnificus were quantified with tlh/tdh/trh and vvhA genes, respectively. No tdh/trh genes were detected. Highest concentrations of tlh gene were observed in summer sediments > oysters > water (105 /g, 104 /g, 103 /ml). VvhA concentrations were similar in sediments and oysters but never exceeded ≥3 × 101 /ml in water. Concentrations of tlh and vvhA genes correlated to temperature and turbidity, respectively, which along with their different spatial distribution indicated different environmental drivers. In oysters, ratios of the tlh and vvhA to 16S rRNA gene have increased from 0 to 10-1 and 10-2 in summer, while these ratios in water and sediments were lower by 2-3 orders of magnitude. Dynamics of tlh and vvhA concentrations and abundances suggested enrichment of V. parahaemolyticus and V. vulnificus by off-bottom triploid oysters in summer resulting in their abundance by far exceeding that in water. This first report on enrichment of Vibrio pathogens in triploid oysters with no direct contact to sediments reveals a threat to human health suggesting their monitoring in triploid off-bottom C. virginica aquaculture.


Local treatment options for ipsilateral breast tumour recurrence.
In case of ipsilateral breast tumour recurrence (IBTR), radical mastectomy represents the treatment option frequently proposed. A second conservative treatment (2ndCT) has been proposed using either lumpectomy alone or associated with a re-irradiation of the tumor bed. However, in both clinical situations, the proof level of such therapeutic approaches remains low, based on cased-series or retrospective studies (level C). In order to assess the different strategies of local treatment proposed in case of IBTR, a PubMed literature review was performed using the following keywords: breast cancer, ipsilateral recurrence, mastectomy, radiation therapy, brachytherapy. Four different salvage options were analyzed: (a) salvage mastectomy alone; (b) salvage mastectomy with postoperative re-irradiation; (c) 2ndCT with surgery alone; (d) 2ndCT with re-irradiation. The rate of second local recurrence is about 10% [3-32%], about 25% [7-36%] and about 10% [2-26%], after salvage mastectomy, salvage lumpectomy alone or combined with a re-irradiation of the tumor bed respectively. However, the 5-year overall survival rates after salvage mastectomy and 2ndCT seem to be equivalent (≈75%) mainly influenced by distant metastatic progression. In terms of Evidence Based Medicine, different options can be discussed such as Phase III or II randomized trials comparing salvage mastectomy versus 2ndCT, retrospective studies based on a matched-pair analysis or observatory studies. Those study designs need to be carefully analyzed to be able to propose new treatment options for women who experience an IBCR.


Pressure to produce=pressure to reduce accident reporting?
Each year, more than 4 million U.S. workers are injured on the job - several thousand die (Bureau of Labor Statistics, 2008). Despite these staggering numbers, research suggests that they are gross underestimates of the true volume of workplace related illnesses and injuries due to accident under-reporting. Although accident under-reporting has been well-documented, less is known regarding why this occurs. The current study suggests that under-reporting may in part be due to high levels of perceived production pressure. Specifically, this study tested the hypotheses that production pressure would be related to more experienced accidents overall and more negative attitudes toward reporting accidents. Further, we expected that production pressure would exacerbate the under-reporting of accidents. Survey data were collected from a sample of 212 copper mining workers located in the southwestern United States. The survey measured employee perceptions regarding production pressure, attitudes toward reporting accidents, perceived consequences of reporting accidents, and actual reporting behaviors (e.g., types and numbers of accidents experienced vs. reported). As predicted, the average number of experienced accidents per employee was significantly higher (M=2.84) than the number of reported accidents (M=.49). In addition, production pressure was related to more negative reporting attitudes. Individuals who had positive reporting attitudes were injured less frequently; however, when an incident occurred, they were more likely to report it. Finally, higher levels of production pressure were related to greater accident under-reporting. Additionally, employees who perceived high levels of production pressure not only experienced more accidents overall, they also reported fewer of them to the organization. Implications for occupational safety initiatives--particularly in the current economic climate--are discussed, as are methodological challenges of conducting research in this area.


Individual and joint performance of DNA methylation profiles, genetic risk score and environmental risk scores for predicting breast cancer risk.
DNA methylation patterns in the blood, genetic risk scores (GRSs), and environmental risk factors can potentially improve breast cancer (BC) risk prediction. We assessed the individual and joint predictive performance of methylation, GRS, and environmental risk factors for BC incidence in a prospective cohort study. In a cohort of 5462 women aged 50-75 from Germany, 101 BC cases were identified during 14 years of follow-up and were compared to 263 BC-free controls in a nested case-control design. Three previously suggested methylation risk scores (MRSs) based on methylation of 423, 248, and 131 cytosine-phosphate-guanine (CpG) loci, and a GRS based on the risk alleles from 269 recently identified single nucleotide polymorphisms were constructed. Additionally, multiple previously proposed environmental risk scores (ERSs) were built based on environmental variables. Areas under the receiver operating characteristic curves (AUCs) were estimated for evaluating BC risk prediction performance. MRS and ERS showed limited accuracy in predicting BC incidence, with AUCs ranging from 0.52 to 0.56 and from 0.52 to 0.59, respectively. The GRS predicted BC incidence with a higher accuracy (AUC = 0.61). Adjusted odds ratios per standard deviation increase (95% confidence interval) were 1.07 (0.84-1.36) and 1.40 (1.09-1.80) for the best performing MRS and ERS, respectively, and 1.48 (1.16-1.90) for the GRS. A full risk model combining the MRS, GRS, and ERS predicted BC incidence with the highest accuracy (AUC = 0.64) and might be useful for identifying high-risk populations for BC screening.


Formation of mutagenic activity from amino acids heated at cooking temperatures.
To investigate the formation of aromatic amine-like mutagenic activity in cooked grain foods, amino acids were heated alone or in binary combinations at either 150 or 210 degrees C. About half of the binary mixtures of arginine heated with other amino acids produced potent mutagenic responses in the Ames/Salmonella assay, but only cysteine produced mutagenic products when heated alone. One-to-one molar ratios of arginine heated with threonine, valine, cystine, cysteine or tryptophan produced reaction products that gave 1200-3200 revertants/mmol in Salmonella strain TA98 with metabolic activation. 1-Methylguanidine, a fragment of arginine, produced a mutagenic response when heated alone or in binary mixtures with all amino acids tested. Analysis of reaction product extracts by solid-phase extraction and HPLC failed to find the known heterocyclic amines commonly found in cooked meats that would explain the measured mutagenic activity. As judged by biological and chemical characterization, several new aromatic amine mutagens are formed by heating some simple amino acids combined with arginine, and these reactants may be the source of the mutagenic products detected in the extracts of some cooked grain-based foods.