High performance liquid chromatography and UV detection for the separation and quantitation of prostaglandins.
A fast and reliable method for the separation and quantitation of arachidonic acid metabolites PGF1 alpha, PGF2 alpha, PGD2, PGE1, PGE2, PGB2, PGA2, 6-keto PGE1, 6-keto PGF1 alpha, TxB2 and 15-keto PGE2 by high-performance liquid chromatography has been developed. Utilizing a single reverse-phase column and a UV spectrophotometer, sensitivity as little as 30 nanograms of each of these prostaglandins can be separated and subsequently detected. Although this study was performed using standards, it is highly promising for future application to biological fluids.


Deformability and cell membrane properties of erythrocytes in Duchenne muscular dystrophy.
In many investigations of the hypothesis of a membrane defect in Duchenne muscular dystrophy, the erythrocyte has been the cell of choice, but reported abnormalities in the Duchenne erythrocyte are disputed. Techniques of microsieving, cell surface staining and measurement of cell water diffusion turnover rate have been used in this investigation to examine erythrocyte properties. Measurements of pressure drop-velocity relations were carried out in a capillary pore rheometer using pure erythrocyte suspensions. The study showed that Duchenne erythrocytes do not behave differently from normal, results which are in substantial agreement with similar microsieving studies. A nuclear magnetic resonance method was used to measure cell water diffusion efflux which, using our cell surface data, could be related to cell membrane permeability. Under normal conditions and conditions of chemical interference with the membrane protein, the results revealed that the membrane pathways involved in water diffusion in Duchenne erythrocytes are unaltered.


Improvement of L-lactic acid production by osmotic-tolerant mutant of Lactobacillus casei at high temperature.
L-Lactic acid production by Lactobacillus casei was used as a model to study the mechanism of substrate inhibition and the strategy for enhancing L-lactic acid production. It was found that the concentration of cell growth and L-lactate decreased with the increase of glucose concentration and fermentation temperature. To enhance the osmotic stress resistance of the strain at high temperature, a mutant G-03 was screened and selected with 360 g/L glucose at 45°C as the selective criterion. To further increase the cell growth for lactic acid production, 3 g/L of biotin was supplemented to the medium. As a result, L: -lactate concentration by the mutant G-03 reached 198.2 g/L (productivity of 5.5 g L(-1) h(-1)) at 41°C in a 7-L fermentor with 210 g/L glucose as carbon source. L: -Lactate concentration and productivity of mutant G-03 were 115.2% and 97.8% higher than those of the parent strain, respectively. The strategy for enhancing L: -lactic acid production by increasing osmotic stress resistance at high temperature may provide an alternative approach to enhance organic acid production with other strains.


Myeloid-derived suppressor cells at diagnosis may discriminate between benign and malignant ovarian tumors.
The behavior of the immune system as a driver in the progression of ovarian cancer has barely been studied. Our knowledge is mainly limited to the intra-tumoral adaptive immune system. Because of the widespread metastases of ovarian cancer, an assessment of the circulating immune system seems more accurate.To demonstrate the presence of immune cells in blood samples of patients with ovarian neoplasms. In this exploratory prospective cohort study, peripheral blood mononuclear cells were collected at diagnosis from 143 women, including 62 patients with benign cysts, 13 with borderline tumor, 41 with invasive ovarian cancer, and 27 age-matched healthy controls. Immune profile analyses, based on the presence of CD4 (cluster of differentiation), CD8, natural killer cells, myeloid-derived suppressor cells, and regulatory T cells, were performed by fluorescence activated cell sorting. In a multivariable analysis, six immune cells (activated regulatory T cells, natural killer cells, myeloid-derived suppressor cells, monocytic myeloid-derived suppressor cells, exhausted monocytic myeloid-derived suppressor cells, and total myeloid cells) were selected as independent predictors of malignancy, with an optimism-corrected area under the receiver operating characteristic curve (AUC) of 0.858. In contrast, a profile based on CD8 and regulatory T cells, the current standard in ovarian cancer immunology, resulted in an AUC of 0.639. Our immune profile in blood suggests an involvement of innate immunosuppression driven by myeloid-derived suppressor cells in the development of ovarian cancer. This finding could contribute to clinical management of patients and in selection of immunotherapy.


Vasoactive peptides in experimental renal hypertension.
1. Blood pressure is controlled by both integrated neurogenic and humoral vasoactive mechanisms. 2. Both vasopressor (angiotensin and vasopressin) and vasodepressor (bradykinin) hormonal peptides have been identified. 3. In acute experimental renal hypertension in the rat plasma renin, angiotensin and vasopressin have all been shown to be elevated. 4. Associated with this increase in vasopressor hormonal peptides, urinary kallikrein excretion has been demonstrated to be reduced during the development of renal hypertension. 5. The level of blood pressure achieved in experimental renal hypertension is probably a summation of these vasoactive peptides as well as other factors.


Impact of high-flow nasal cannula oxygen therapy on intensive care unit patients with acute respiratory failure: a prospective observational study.
The purpose of this study was to determine the impact of high-flow nasal cannula oxygen (HFNC) on patients with acute respiratory failure (ARF) in comparison with conventional oxygen therapy. This was a prospective observational study. Patients with persistent ARF despite oxygen with conventional facemask without indication for immediate intubation were treated with HFNC oxygen. Clinical respiratory parameters and arterial blood gases were compared under conventional and HFNC oxygen therapy. Twenty patients, aged 59 years (38-75 years) and SAPS2 (simplified acute physiology score) 33 (26.5-38), were included in the study. Etiology of ARF was mainly pneumonia (n = 11), sepsis (n = 3), and miscellaneous (n = 6). Use of HFNC enabled a significant reduction of respiratory rate, 28 (26-33) vs 24.5 (23-28.5) breath per minute (P = .006), and a significant increase in oxygen saturation, oxygen saturation as measured by pulse oximetry 93.5% (90-98.5) vs 98.5% (95.5-100) (P = .0003). Use of HFNC significantly increased Pao(2) from 8.73 (7.13-11.13) to 15.27 (9.66-25.6) kPa (P = .001) and moderately increased Paco(2), 5.26 (4.33-5.66) to 5.73 (4.8-6.2) kPa (P = .005) without affecting pH. Median duration of HFNC was 26.5 (17-121) hours. Six patients were secondarily intubated, and 3 died in the intensive care unit. Use of HFNC in patients with persistent ARF was associated with significant and sustained improvement of both clinical and biologic parameters.


The mycotoxins deoxynivalenol and nivalenol show in vivo synergism on jejunum enterocytes apoptosis.
The mycotoxins deoxynivalenol (DON) and nivalenol (NIV), worldwide cereal contaminants, raise concerns for human and animal gut health, following exposure through contaminated food and feed. The aim of this work was to analyze the effects of DON and NIV, alone or associated, on the intestinal pig mucosa. Jejunal loops were used for testing DON and NIV individually and in combination (1:1) after a single exposure, for 24 h. For repeated exposure, piglets received a natural contaminated feed, with DON or with DON + NIV for 28 days. Histological investigations, proliferation and apoptosis assessments were conducted. Both experiments were concordant for the total-cell proliferation decreased at the villus tips after DON or DON + NIV at 10 μM acutely, or repeatedly, by 30-35% and 20-25%, respectively. In loops model, apoptotic enterocytes at villus tips increased dose-dependently after DON, NIV alone or DON + NIV in combination. The combination in loops at 10 μM showed higher effects on proliferation and apoptosis than DON alone, and synergism was shown for villus apoptotic enterocyte. These results are to be considered for NIV consumer risk assessment. Our results demonstrate the in vivo disruption of the intestinal balance proliferation/apoptosis explaining, at least partly, the disruption of intestinal barrier by these mycotoxins.


Authorities and foundation of an orthopaedic school in Germany in the nineteenth century: Part I: Conrad Johann Martin Langenbeck; Georg Friedrich Louis Stromeyer; Bernhard Rudolf Conrad von Langenbeck; Johann Friedrich August von Esmarch.
The rapid development of surgery in Germany in the nineteenth century occurred for many reasons, particularly political and economic changes and cultural and scientific progress. This paper analyses the progress of orthopaedic surgery from an historical point of view. After Napoleon's defeat, a peace conference was held in Vienna (1814-1815). Prussia took a portion of Saxony, Austria and territories along the Rhine. The unification of Germany continued in 1850 and 1880; several wars occurred in the unification process, including against Denmark, Austria and France. These wars caused an urgent request for army surgeons and cooperation between civil and military practice. The increase in the number of faculty institutes in surgery, the unification of different surgical organisations, and the organisation of scientific societies participated in this development. C. Langenbeck, G. Stromeyer, B. von Langenbeck and J.F. von Esmach were the most proactive surgeons of this period Improvements in war surgery, percutaneous tenotomy, the foundation of the German Society of Surgery and bloodless surgical techniques for limbs were the most important innovations.


Metagenomic insight into the distribution of metal resistance genes within cascade reservoir waters: Synergic impacts of geographic variation and anthropogenic pollution.
Metal resistance genes (MRGs) are potential bio-indicators to diagnose contamination stress on riverine ecosystems. Within reservoir systems, river damming weakens hydrodynamic condition and enriches metal contaminants. But, little is known about the synergic impacts of geographic variation and anthropogenic pollution on MRGs. In this study, the abundance, composition and microbes of MRGs in four cascade reservoirs along the Jinsha River, southwestern China were investigated via high-throughput metagenomics. The results showed significant enrichment of chromium, cadmium and lead in Ludila and Xiluodu reservoirs with moderate ecological risks based on the criteria of drinking water quality and aquatic life protection. Nevertheless, at watershed scale, these metals played little role in up-regulating MRGs abundance owing to the limited toxic stress on microbes. Accordingly, geographic variation showed stronger impacts on MRGs composition than metals as revealed by the distance-decay relationship (Pearson correlation, rgeo = 0.24-0.57, rmetal = 0.10-0.41) and co-occurrence network (Node degree to MRGs subtype, ngeo = 180, nmetal = 6). River damming, as an artificial isolation of geographic space, significantly affected MRGs composition. The longer operation history, smaller storage capacity and higher regulation frequency caused the higher dissimilarity of MRGs composition between the reservoir's upstream and downstream areas. In conclusion, the metal pollution level is a prerequisite regulating MRGs; while under the lowly-polluted conditions, geographic variation had stronger impacts on MRGs than metal pollution via altered assembly of microbial communities. This study provides an important guidance for the future environmental management and ecological protection of river-reservoir ecosystems.


Identification of adenosine receptor in rat pineal gland: evidence for A-2 selectivity.
We have examined the binding of the adenosine agonist radioligands [3H]cyclohexyladenosine [( 3H]CHA), R-N6-[3H]phenylisopropyladenosine [( 3H]R-PIA), and 5'-N-ethylcarboxamido[3H]adenosine [( 3H]NECA) to membranes prepared from rat pineal gland. The results showed that the A-1-selective ligands (CHA and R-PIA) had less than or equal to 10% specific binding. By contrast, [3H]NECA, a nonselective A-1/A-2 ligand, gave 72% specific binding of the total binding. This specific binding was insensitive to cyclopentyladenosine (50 nM) or R-PIA (50 microM). To characterize this binding, we used the N-ethylmaleimide pretreatment method. Under these conditions, this binding was of high affinity with a KD of 51 +/- 10 nM and an apparent Bmax of 1,060 +/- 239 fmol/mg of protein. Specific binding was unaffected by the presence of MgCl2 (10 mM) but was sensitive to guanylylimidodiphosphate (100 microM) (-25%), a result suggesting the involvement of an N-protein mechanism in the coupling of the adenosine receptor labeled by [3H]NECA to other components of the receptor complex. The rank of activity of adenosine analogues in displacing specific [3H]NECA binding was NECA greater than 2-chloroadenosine greater than S-adenosyl-L-homocysteine greater than CHA. Binding was also displaced by 3-isobutyl-1-methylxanthine (IC50 = 23.6 microM). These findings are consistent with the selective labeling by [3H]NECA of an A-2-type adenosine receptor in rat pineal membranes.


The Clinicopathological Study of Benign Lesions of Vocal Cords.
Benign vocal lesions are non-malignant growths of abnormal tissue on the vocal cords. The common benign lesions of vocal cord are singer's nodule, polyps, papilloma, polypoidal degeneration and cysts. The aim of this study was to analyze the demographics such as age, sex, occupation, symptomatology, site of involvement. An objective evaluation of voice handicap was done pre and postoperatively using VHI-10 scale to see improvement in patient's symptoms. In this prospective study, a total of 50 cases were selected with benign lesions in regional hospital of India. The pre and post operative assessment for voice handicap was assessed by VHI-10. Chi square test (SPSS 20.0 version) used to analyze result; value of p < 0.05 was taken significant. In this study of 50 patients, the benign lesions were most common in 20-29 age group. Male (70%) outnumbered females (30%). Most common was Vocal polyp (56%), followed by nodule (32%), cyst (10%) and papilloma (2%) respectively. All patients showed improvement after phonosurgery and postoperative speech therapy, being assessed by VHI-10 scale. The benign lesions of vocal cords produces symptoms which can vary from hoarseness to stridor, affect social functioning, work performance. Speech therapy following microlaryngeal surgery forms an essential part of treatment, to avoid recurrence. VHI-10 scale as found to be a useful and convenient tool in measuring patient voice handicap and to see improvement after surgery.


Prognostic significance of proliferative activity, DNA-ploidy, p53 and Ki-ras point mutations in colorectal liver metastases.
Paired colorectal liver metastases (CLM) and normal tissue samples from a consecutive series of 36 patients were studied prospectively. MIB-1 expression was studied by immunohistochemistry on paraffin-embedded sections. DNA ploidy and S-phase fraction (SPF) measurements were performed by flow cytometry on frozen tissues. Mutations within the p53 (exons 5-8) and c-Ki-ras (codons 12 and 13) genes were detected by PCR single-strand conformation polymorphism analysis followed by sequencing. A high correlation was observed between the MIB-1 LI and SPF value (rho=0.81; P<0.01). Moreover, p53 gene mutations were associated with either high MIB-1 LI and high SPF. In univariate analysis, SPF and MIB-1 levels were related to risk of death. The association between overall survival and DNA-ploidy or p53 mutations did not reach statistical significance, but a slightly better survival was observed for patients either with DNA-diploid tumours or without mutations (P=0.05 and P=0.06, respectively). SPF was shown by multivariate Cox model analysis to be an independent prognostic variable and thus it might be a useful prognostic factor in patients with CLM.


Effect of peripheral axotomy on expression of neuropeptide Y receptor mRNA in rat lumbar dorsal root ganglia.
Using in situ hybridization, the expression of the mRNA for a neuropeptide Y (NPY) receptor, was studied in lumbar (L) 4 and 5 dorsal root ganglia (DRGs) of normal rats and at various intervals after unilateral sciatic nerve transection. Twenty percent of all normal DRG neurons were NPY receptor mRNA-positive, and the majority of these neurons were of the small type, with only a few labelled medium-sized and large neurons. In L5 normal ganglia NPY receptor mRNA colocalized with substance P, calcitonin gene-related peptide and galanin mRNAs in small neurons, but not in medium-sized or large neurons containing these peptides. NPY receptor mRNA was not observed in somatostatin or nitric oxide synthase mRNA-positive neurons. Sciatic nerve transection induced a marked decrease in NPY receptor mRNA levels. However, in parallel there was a transient increase in the number of NPY receptor mRNA-positive small neuron profiles, but the intensity of labelling was mostly very low, although a few strongly labelled, small neuron profiles were also encountered. In addition, axotomy caused a marked increase in the number of NPY receptor mRNA-positive large neuron profiles in the ipsilateral DRGs, and they constituted 15-20% of counted DRG neuron profiles and 45-65% of counted large neuron profiles, 7-28 days after axotomy. In L5 DRGs, ipsilateral to the axotomy, NPY receptor mRNA colocalized with NPY mRNA in many large and some medium-sized neuron profiles, with galanin mRNA in some small, medium-sized and large neuron profiles and with vasoactive intestinal polypeptide mRNA in some small and medium-sized neuron profiles and a few large profiles. Occasionally, NPY receptor mRNA was observed in nitric oxide synthase mRNA-positive small neurons. In the dorsal horn, NPY receptor mRNA-positive small neurons were concentrated in lamina II at L4 and L5 levels, and were scattered in deeper laminae. No marked changes were observed ipsilateral to the axotomy. No NPY receptor mRNA-positive cells were found in the normal rat gracile nucleus, or in this nucleus after axotomy. These results show that a NPY receptor may be a prejunctional receptor in primary afferent neurons and play a role in the modulation of somatosensory information, both in normal and lesioned primary afferent DRG cells. However, axotomy induced a distinct shift in NPY receptor mRNA expression from small to large neurons, indicating that sensitivity to NPY is switched from one modality to another.(ABSTRACT TRUNCATED AT 400 WORDS)


Suicidal ideation and risk factors in primary care patients with anxiety disorders.
The presence of an anxiety disorder is associated with greater frequency of suicidal thoughts and behaviors. Given the high personal and societal costs of suicidal behaviors, suicide prevention is a priority. Understanding factors present within individuals with anxiety disorders that increase suicide risk may inform prevention efforts. The aims of the present study were to examine the prevalence of suicidal ideation and behaviors, as well as factors associated with suicide risk in patients with anxiety disorders in primary care. Data from a large scale randomized controlled study were analyzed to assess prevalence of suicidal thoughts and behaviors, as well as factors associated with suicide risk. Results revealed that suicidal ideation and behaviors were relatively common in this group. When examining mental and physical health factors jointly, presence of depression, mental health-related impairment, and social support each uniquely accounted for variance in suicide risk score. Methodological limitations include cross-sectional data collection and lack of information on comorbid personality disorders. Moreover, patients included were from a clinical trial with exclusion criteria that may limit generalizability. Results highlight the complex determinants of suicidal behavior and the need for more nuanced suicide assessment in this population, including evaluation of comorbidity and general functioning.


Normal imaging findings after ascending aorta prosthesis implantation on 18F-Fluorodeoxyglucose Positron Emission Tomography with computed tomography.
To diagnose abnormal 18F-Fluorodeoxyglucose (18F-FDG) uptake in suspected endocarditis after aortic root and/or ascending aorta prosthesis (ARAP) implantation, it is important to first establish the normal periprosthetic uptake on positron emission tomography with computed tomography (PET/CT). Patients with uncomplicated ARAP implantation were prospectively included and underwent 18F-FDG-PET/CT at either 12 (± 2) weeks (group 1) or 52 (± 8) weeks (group 2) after procedure. Uptake on three different locations of the prosthesis ("cranial anastomosis (CA)," "prosthetic heart valve (PHV)," "ascending aorta prosthesis (AAP)") was scored visually (none/low/intermediate/high) and quantitatively (maximum standardized uptake value (SUVmax) and target-to-background ratio (SUVratio). In total, 20 patients (group 1: n = 10, group 2: n = 10) (mean age 64±7 years, 70% male) were included. Both groups had similar visual uptake intensity for all measured areas (CA: mostly low-intermediate (16/20 (80%)), p = .17; PHV: low-intermediate (16/20 (80%)), p = .88; AAP: low-intermediate (19/20 (95%)), p = .48). SUVmax for CA was 5.6 [4.1-6.1] and 3.8 [3.1-5.9] (median [IQR], p = .19), and around PHV 5.0 [4.1-5.7] and 6.3 [4.6-7.1] (p = .11) for groups 1 and 2, respectively. SUVratio for CA was 2.8 [2.3-3.2] and 2.0 [1.7-2.6] (median [IQR], p = .07) and around PHV 2.5 [2.4-2.8] and 2.9 [2.3-3.5] (median [IQR], p = .26) for groups 1 and 2, respectively. No significant differences were observed between PET/CT findings at 3 months and 1 year after ARAP implantation, warranting caution in interpretation of PET/CT in the first year after implantation.


Nuclear Receptors and Transcription Factors in Obesity-Related Kidney Disease.
Both obesity and chronic kidney disease are increasingly common causes of morbidity and mortality worldwide. Although obesity often co-exists with diabetes and hypertension, it has become clear over the past several decades that obesity is an independent cause of chronic kidney disease, termed obesity-related glomerulopathy. This review defines the attributes of obesity-related glomerulopathy and describes potential pharmacologic interventions. Interventions discussed include peroxisome proliferator-activated receptors, the farnesoid X receptor, the Takeda G-protein-coupled receptor 5, and the vitamin D receptor.


[Interaction of the lymph node and splenic lymphocytes of mice in inactivation of allogeneic hematopoietic stem cells].
A study was made of interaction of mouse spleen and lymph node lymphocytes in inactivation of allogeneic stem cells. It was established that T lymphocytes of the lymph nodes and spleen lymphocytes do not interact on combined administration; their action is of additive nature. B lymphocytes of the lymph nodes have a regulating activity both in respect to T lymphocytes of the lymph nodes and lymphocytes of the spleen. The stem cells serve as target. Depending on the stem cells/B lymphocytes ratio B lymphocytes are capable of exerting either helper or suppressor action.


Theoretical analysis of T-wave polarity based on a model of cardiac electrical activity.
The effect of the gradient of transmembrane action potential duration through the ventricular wall on T-wave polarity and QRS-T angle was investigated using a mathematical model of the electrical activity of the heart which incorporates the characteristic electrophysiological properties of the left ventricular wall. Two models, a rectangular solid model and a concave model, were constructed to simulate a part of the left ventricular wall. The ventricular gradient was defined as a linear decrease (beta msec/cm) of the action potential duration from the endocardium to epicardium. The theoretically-obtained relationship between the QRS-T angle and the ventricular gradient revealed that the transmural gradient (beta) was 10--40 msec/cm when the QRS-T angle was within the normal range. The positive T wave was obtained at the observation point which would correspond to the precordial lead when the transmural gradient was more than 30 msec/cm. The amplitude of the simulated T-wave increased with the ventricular gradient. Thus, our mathematical models can provide the quantitative relationship between the transmural ventricular gradient and T-wave polarity and are compatible with further simulation study for various pathological conditions.


Position of Biphenyl Group Turning the Structure and Photophysical Property of D-π- π -A Prototype Fluorescent Material.
Three novel D-π-π-A prototype compounds, namely, (E)-2-(3-([1,1'-biphenyl]-2-yl)-1-(9H-fluoren-2-yl)allylidene)malononitri-le (2-BAM), (E)-2-(3-([1,1'-biphenyl]-3-yl)-1-(9H-fluoren-2-yl)allylidene)malononitri-le (3-BAM), and (E)-2-(3-([1,1'-biphenyl]-4-yl)-1-(9H-fluoren-2-yl)allylidene)malononitri-le (4-BAM) were synthesized. Furthermore, the structures and photophysical properties of three compounds were compared. Molecules of 2-BAM were packed into a 1D column structure with H-aggregation. However, both of 3-BAM and 4-BAM were packed into 3D layer structures with J-aggregation, respectively. Although all three compounds showed highly twisted molecular geometries, their respective molecular packing and intermolecular interactions were different. Because of the differences in electronic structures of molecules, three compounds displayed different emission behaviors in solid and dilute solution states. This study indicated that changing the position of biphenyl groups is an effective way for turning the structures and photophysical properties of such D-π-π-A prototype fluorescent materials.


Long and short isoforms of c-FLIP act as control checkpoints of DED filament assembly.
The assembly of the death-inducing signaling complex (DISC) and death effector domain (DED) filaments at CD95/Fas initiates extrinsic apoptosis. Procaspase-8 activation at the DED filaments is controlled by short and long c-FLIP isoforms. Despite apparent progress in understanding the assembly of CD95-activated platforms and DED filaments, the detailed molecular mechanism of c-FLIP action remains elusive. Here, we further addressed the mechanisms of c-FLIP action at the DISC using biochemical assays, quantitative mass spectrometry, and structural modeling. Our data strongly indicate that c-FLIP can bind to both FADD and procaspase-8 at the DED filament. Moreover, the constructed in silico model shows that c-FLIP proteins can lead to the formation of the DISCs comprising short DED filaments as well as serve as bridging motifs for building a cooperative DISC network, in which adjacent CD95 DISCs are connected by DED filaments. This network is based on selective interactions of FADD with both c-FLIP and procaspase-8. Hence, c-FLIP proteins at the DISC control initiation, elongation, and composition of DED filaments, playing the role of control checkpoints. These findings provide new insights into DISC and DED filament regulation and open innovative possibilities for targeting the extrinsic apoptosis pathway.


[Role of the duodenum in rapid adaptive reorganizations of saccharose hydrolysis and transport].
After isolation of the chick duodenum from the lower parts of the intestine, no adaptation of the sucrose activity or hexose transport occurred. The data suggest that the adaptive factor is formed in the duodenum under the influence of sugars.


The longitudinal NIHR ARC North West Coast Household Health Survey: exploring health inequalities in disadvantaged communities.
The Household Health Survey (HHS) was developed to understand the socioeconomic determinants of mental and physical health, and health inequalities in health and social care. This paper aims to provide a detailed rationale of the development and implementation of the survey and explore socio-economic variations in physical and mental health and health care. This comprehensive longitudinal public health survey was designed and piloted in a disadvantaged area of England, comprising questions on housing, physical health, mental health, lifestyle, social issues, environment, work, and finances. After piloting, the HHS was implemented across 28 neighbourhoods - 10 disadvantaged neighbourhoods for learning (NfLs), 10 disadvantaged comparator sites, and eight relatively advantaged areas, in 2015 and 2018. Participants were recruited via random sampling of households in pre-selected neighbourhoods based on their areas of deprivation. 7731 residents participated in Wave 1 (N = 4319) and 2 (n = 3412) of the survey, with 871 residents having participated in both. Mental health, physical health, employment, and housing quality were poorer in disadvantaged neighbourhoods than in relatively advantaged areas. This survey provides important insights into socio-economic variations in physical and mental health, with findings having implications for improved care provision to enable residents from any geographical or socio-economic background to access suitable care.


Removal of doxycycline hydrochloride from aqueous solution by rice husk ash using response surface methodology and disposability study.
The huge demand and consumption of DOX, its incomplete metabolism, and complex behavior in atmosphere are causing a great ecological issue, which needs to be solved. In the present study, the suitability of rice husk ash (RHA) for the greater sorption efficiency of DOX antibiotic was investigated. Furthermore, disposability study of exhausted RHA was performed using solidification technique and leachate had undergone toxicity test to evaluate the DOX encapsulation ability. The central composite design under RSM was employed for the design of experiment and optimization of adsorption parameters. RHA was characterized using various techniques such as XRD, SEM (EDX), FTIR, BET, and zeta potential analysis. The influence of various adsorption parameters, like initial DOX concentration (C0), RHA dosage (m), incubation-time period (t), and pH were examined on the performance in terms of DOX elimination % (X1) and adsorptive capacity (mg/g) (X2). At optimized conditions, the obtained X1 and X2 were 98.85% and 17.74 mg/g, respectively. Moreover, the kinetics data suited well to the pseudo-second-order model. Freundlich, Langmuir, and Redlich-Peterson (R-P) isotherm models were applied, out of which Langmuir model best performed under optimized conditions; m = 5 g/L, t = 85.85 min, DOX concentration = 89.73 mg/L, and pH = 6. The bacterial toxicity test of leachate confirmed complete encapsulation of DOX by solidification technique.


Serial passage of murine K-papovavirus in primary cultures of mouse embryo cells. Brief report.
Murine K-papovavirus was serially passaged 10 times in primary cultures of mouse embryo cells, using cell suspensions and media from infected cultures to inoculate fresh flasks at each passage level. Titers of K virus infectivity in cell suspensions and media rose during serial passage, but viral hemagglutinating activity was not detected in cells or media before the 10th passage. Although the infectivity of K virus for mouse embryo cultures was enhanced by serial passage, lethality of the virus for suckling mice was lost. The present study represents the first successful serial transmission of K virus infection in vitro.


Incidence of antibiotic resistance genotypes of Vibrio species recovered from selected freshwaters in Southwest Nigeria.
Vibrio species are classified as potent hazards because of their tendency to effect serious diseases like cholera and other gastrointestinal ailments in humans, as well as vibriosis in fish. A total of 144 freshwater samples were aseptically collected monthly across four rivers (Asejire, Ona, Dandaru and Erinle rivers) over a 12-month period from which Vibrio spp. were isolated using culture procedures, confirmed by means of biochemical test as well as Polymerase Chain Reaction (PCR) assay and further characterized for their phenotypic antibiotic susceptibilities and relevant antimicrobial resistant determinants by PCR. Three hundred and fifteen (58%) isolates confirmed across the sampled sites (Asejire = 75, Dandaru = 87, Eleyele = 72, Erinle = 81) showed high resistance against erythromycin-95%, Sulphamethoxazole-94%, rifampicin-92%, doxycycline-82%, tetracycline-75%, amoxicillin-45%, cephalothin-43% and varied susceptibilities to other antibiotics. The multiple antibiotic resistance indices of 97% of the Vibrio isolates were above the 0.2 threshold limit with MAR phenotype pattern E-SUL-RF-TET-DOX (0.38) found to be the most prevalent pattern among the isolates. The distributions of resistance determinant of the tested antibiotics were revealed as follows: sulII 33%, sulI 19% (sulfonamides); blaOXA 27%, ampC 39%, blapse 11% (beta-lactams); tetA 28%, tetE 20%, tet39 8%, (tetracyclines) and strA 39%. aacC2 24%, aphA1 14% (aminoglycosides). Strong positive associations were observed among tetA, sulI, tetE and sulII. This study raises concerns as these selected rivers may contribute to the environmental spread of waterborne diseases and antibiotic resistance genes. Therefore, we recommend environmental context-tailored strategies for monitoring and surveillance of resistance genes so as to safeguard the environment from becoming reservoirs of virulent and infectious Vibrio species.


Variation in the coat protein sequence of British isolates of Turnip yellow mosaic virus and comparison with previously published isolates. Brief report.
Isolates of Turnip yellow mosaic virus (TYMV) were collected from wild cabbage (Brassica oleracea) on a 400 m stretch of Dorset coastline. The coat protein genes of four isolates showed high homology in nucleotide sequence (0.970-1.000, mean 0.987). Lower levels of homology where found to previously published sequences of Australian isolates [10] (0.725-0.775, mean 0.741). The amino acid composition of the Dorset isolates showed high levels of homology (0.964-1.000, mean 0.986). Numerous amino acid substitutions occurred between the Dorset and Australian isolates (0.705-0.819, mean 0.742). Comparison with other isolates showed large genetic distances between the Dorset isolates and both European and Australian isolates.


Common trends in elements? Within- and between-tree variations of wood-chemistry measured by X-ray fluorescence - A dendrochemical study.
Element composition of annually resolved tree-rings constitutes a promising biological proxy for reconstructions of environmental conditions and pollution history. However, several methodological and physiological issues have to be addressed before sound conclusions can be drawn from dendrochemical time series. For example, radial and vertical translocation processes of elements in the wood might blur or obscure any dendrochemical signal. In this study, we tested the degree of synchronism of elemental time series within and between trees of one coniferous (Pinus sylvestris L.) and one broadleaf (Castanea sativa Mill.) species growing in conventionally managed forests without direct pollution sources in their surroundings. Micro X-ray fluorescence (μXRF) analysis was used to establish time series of relative concentrations of multiple elements (Mg, Al, P, Cl, K, Ca, Cr, Mn, Fe and Ni) for different stem heights and stem exposures. We found a common long-term (decadal) trend for most elements in both species, but only little coherence in the high frequency domain (inter-annual variations). Aligning the element curves by cambial age instead of year of ring formation reduced the standard deviations between the single measurements. This points at an influence of age on longer term trends and would require a detrending in order to extract any environmental signal from dendrochemical time series. The common signal was stronger for pine than for chestnut. In pine, many elements show a concentration gradient with higher values towards the tree crown. Mobility of elements in the stem leading to high within- and between-tree variability, as well as a potential age-trend apparently complicate the establishment of reliable dendrochemical chronologies. For future wood-chemical studies, we recommend to work with element ratios instead of single element time series, to consider potential age trends and to analyze more than one sample per tree to account for internal variability.


Adding MEMS feedback to behavioral smoking cessation therapy increases compliance with bupropion: a replication and extension study.
This study was conducted to replicate and extend initial positive findings on the usefulness of a Medication Event Monitoring System (MEMS) to assess pill-taking behavior and enhance compliance with bupropion for smoking cessation. Participants (N=55) received MEMS bottles containing bupropion-SR (150 mg) to be taken twice daily for 7 weeks. For participants randomly assigned to the Enhanced Therapy group (n=27), weekly individual smoking cessation therapy sessions included an additional 10 min of MEMS feedback and compliance enhancement counseling using CBT techniques. The Usual Care group (n=28) received weekly individual smoking cessation sessions only. Compliance outcomes included total doses taken and number of doses taken within the prescribed time interval. Results indicated significantly higher compliance over time for the Enhanced Therapy group. Smoking abstinence rates did not differ between the two groups, although results from the pooled sample analysis showed a significant association between level of medication compliance and abstinence status at treatment weeks 3 and 6. Incorporating MEMS-based compliance interventions into smoking pharmacotherapy trials is recommended.


A consistent pattern of minor immunodeficiency and subtle enteropathy in children with multiple food allergy.
Although immunoglobulin (Ig)E-mediated allergies are readily identifiable, non-IgE-mediated allergies present more diagnostic difficulty. We performed a formal retrospective analysis to determine whether there is a recognizable clinical pattern in children. We studied 121 children (mean age, 17.3 months) with multiple food allergies who were recruited on the basis of adequate immunological assessment by using case notes and parental questionnaire. Group 1 (n=44) had rapid reactions to dietary antigens, of whom 41 also showed delayed reactions. Group 2 (n=77) had delayed reactions only. Mean IgE was increased in group 1 but both groups otherwise shared a pattern of increased IgG1, decreased IgG2/4, and low-normal IgA. Lymphocyte subsets were skewed, with an increased percentage of CD4 and CD19 and decreased CD8 and natural killer cells. Gastroesophageal reflux, esophagitis, subtle enteropathy, and constipation were frequent in both groups. Of 55 exclusively breast-fed infants, 44 sensitized before weaning. Twenty-one of the mothers suffered from autoimmunity. There appears to be a recognizable pattern of immune deviation and minor enteropathy in children with multiple food allergy, irrespective of the speed of reactions. Disturbed gut motility is particularly common, as is a maternal history of autoimmunity.


Prediction and control of food rewards modulate endogenous pain inhibitory systems.
Tail-flick latencies were measured in food-deprived rats submitted to various schedules of food reinforcement with experimental and yoked animals differing by the possibility of either predicting the occurrence of food by means of a pre-food signal, controlling its delivery by lever-pressing or developing adjunctive activities (schedule-induced drinking). In the first two cases, yoked animals that could not predict or control food deliveries displayed higher tail-flick latencies at the end of sessions than did experimental animals. In the polydipsia experiment, rats that did not develop schedule-induced drinking had higher tail-flick latencies from the start of the experiment than rats that did develop drinking and for these latter animals, drinking was accompanied by a significant reduction in tail-flick latencies. These results demonstrate that prediction and control over external events modulate the activation of endogenous pain-suppressing systems.


Actin filament elongation in Arp2/3-derived networks is controlled by three distinct mechanisms.
Spatial and temporal control of actin filament barbed end elongation is crucial for force generation by actin networks. In this study, genetics, cell biology, and biochemistry were used to reveal three complementary mechanisms that regulate actin filament barbed end elongation in Arp2/3-derived networks. Aip1 inhibits elongation of aged ADP-actin filaments decorated with cofilin and, together with capping protein (CP), maintains a high level of assembly-competent actin species. We identified Abp1 and Aim3 as two additional proteins that work together to inhibit barbed end elongation. Abp1/Aim3 collaborates with CP to control elongation of newly assembled ATP-actin filaments to organize filament polarity within actin networks. Thus, three distinct mechanisms control filament elongation in different regions of Arp2/3 networks, maintaining pools of assembly-competent actin species while ensuring proper filament polarity and facilitating force production.


STRO-1, HOP-26 (CD63), CD49a and SB-10 (CD166) as markers of primitive human marrow stromal cells and their more differentiated progeny: a comparative investigation in vitro.
There is widespread interest in the use of bone marrow stromal cells (BMSC) for tissue reconstruction and repair and for gene therapy. BMSC represent the differentiated progeny of CFU-F, which however comprise a developmentally heterogeneous population as is reflected in the cellular heterogeneity of the cell populations to which they give rise. We have compared the efficacy of monoclonal antibodies recognising a series of stromal antigens, viz. STRO-1, HOP-26, CD49a and SB-10/CD166, as tools for the enrichment of CFU-F prior to culture and as developmental markers for culture-expanded BMSC. In freshly isolated bone marrow mononuclear cells (BMMNC), the proportion of antigen-positive cells was 27%, 46%, 5% and 19% for STRO-1, HOP-26, CD49a and CD166, respectively. All CD49a(+) cells co-expressed STRO-1. The degree of CFU-F enrichment obtained with anti-CD49a (approximately 18-fold) by a one-pass immunoselection strategy was significantly greater than that of all other antibodies tested. BMSC expressed higher levels of all antigens investigated (except for HOP-26) compared with BMMNC. Expression of STRO-1 and CD49a remained restricted to a subset of BMSC, whereas all BMSC were SB-10/CD166 positive. Treatment with dexamethasone (10 nM), which promotes the differentiation and further maturation of cells of the osteogenic lineage in this cell culture system, increased the expression of CD49a and HOP-26. The CD49a(+) and HOP-26(+) fractions of BMSC were further subdivided by dual-labelling with anti-STRO-1 and B4-78 (an antibody recognising the B/L/K isoform of the enzyme alkaline phosphatase), respectively. By using a variety of criteria, the HOP-26 antigen was identified as CD63, a member of the tetraspanin family of proteins thought to modulate integrin compartmentalisation and signalling.


Persistent cloaca presenting with a perineal cyst: Prenatal ultrasound and magnetic resonance imaging findings.
A 40-year-old, primigravid woman presented at 23 weeks of gestation for evaluation of an extra-abdominal echogenic cystic mass of the fetus. Amniocentesis revealed a karyotype of 46,XX. Prenatal ultrasound showed a two-vessel umbilical cord, hydrocolpos, and distended bladder, urethra, and colon, and a perineal cystic mass. The kidneys and amniotic fluid amount were normal. Fetal magnetic resonance imaging revealed ascites, hydrocolpos, distended urinary bladder and colon, high rectum, and a perineal cyst. The fetus postnatally manifested persistent cloaca. The perineum was distended and smooth, without patent anal, vaginal, and urethral openings. The external genitalia were ambiguous with no labia majora, labia minora, or clitoris. The perineal cyst had a very small single orifice. We suggest that cloacal anomalies be considered in any female fetus with hydrocolpos, distended bladder and colon, ascites, and a perineal cyst.


Statins enhance the effects of corticosteroids on the balance between regulatory T cells and Th17 cells.
Plasticity of CD4(+) lymphocyte Th17/regulatory T cell (Treg) subsets is involved in the pathogenesis of chronic airway inflammatory diseases, such as asthma. Reversal of Th17/Treg cell balance towards Treg cells may be beneficial for the suppression of chronic Th2 cell-mediated inflammatory diseases, such as asthma. However, the effect of the combination of corticosteroids and a statin on the ratio of Treg/Th17 cells is unknown. We investigated the in vitro effects of the combination of simvastatin and fluticasone propionate (FP) on the numbers of Treg and Th17 cells in asthmatic patients after co-incubation with monocyte-derived DCs (mDCs), and explored the underlying signalling pathways involved. Using flow cytometry, we determined the effects of FP and simvastatin on Treg/Th17 balance after co-incubation of asthmatic CD4(+) T cells with mDCs. We also measured the relevant Treg and Th17-polarizing cytokines released from mDCs and also investigated the role of indoleamine 2, 3-dioxygenase (IDO) in this response. The combination of simvastatin and FP significantly increased Treg and concomitantly reduced Th17 cell numbers to a greater extent than FP or statin treatment alone. The enhancing effects of simvastatin on FP effects were mediated through the up-regulation of indoleamine 2, 3-dioxygenase and interleukin (IL)-10, together with down-regulation of IL-6 and IL-23 expression in mDCs. On the basis of this in vitro model of asthma, we suggest that the combination of a statin and a corticosteroid could augment the Treg/Th17 cell ratio and thus more effectively suppress airway inflammation in asthma patients. This may be particularly relevant in the treatment of severe asthma where Th17 cells are activated and linked to neutrophilic inflammation.


Overexpression of GRP78 protects glial cells from endoplasmic reticulum stress.
Endoplasmic reticulum (ER) stress induces apoptotic cell death by causing the accumulation of structurally abnormal proteins. The 78-kDa glucose-regulated protein (GRP78) is an ER chaperone that regulates protein folding in the ER and has been suggested to contribute to cell survival. Using the rat C6 glioma cell line and flow cytometry, we assessed GRP78 expression following tunicamycin- and glutamate-induced ER stress. The results showed that GRP78 expression is upregulated following ER stress and has protective effects on injured glial cells. Annexin V and propidium iodide labeling revealed cells transiently expressing GRP78 prior to injury were protected against high-concentrations of tunicamycin and glutamate within 72 h. Our findings support the hypothesis that GRP78 inhibits cell death associated with ER stress.


[Interrater reliability of amp symptoms (author's transl)].
Two psychiatrists examined 48 patients (25 depressed and 23 schizophrenic). Each documented the symptoms on AMP sheets 3 (psychopathologic symptoms) and 4 (somatic signs, first column only). The study deals with 139 AMP symptoms. Seventy could be judged concerning symptom exists/does not exist. Of these 70 symptoms, 45 showed a good or moderate interrater reliability. Specific symptoms had a better reliability than nonspecific. Symptoms described by the patients had a better reliability than those judged by the doctor alone. The results indicate that expanded use of the AMP system in its present form is problematic. Work on a new version of the AMP system has already begun.


Characteristics of health-related quality of life in different types of chronic middle ear disease.
Different types of chronic middle ear disease (CMED) present with differing severity of single symptoms, such as discharge, vertigo or hearing loss, which impair health-related quality of life (HRQoL). Here, we aimed to (i) investigate characteristics of HRQoL and (ii) evaluate the association between HRQoL and hearing among different types of CMED. In this prospective longitudinal cohort study, we included adult patients undergoing surgical treatment for CMED. Primary outcomes included HRQoL assessed by the Zurich Chronic Middle Ear Inventory (ZCMEI-21) and hearing assessed by pure-tone audiometry. In the included 108 patients (51% females), CMED were chronic otitis media (COM) with (n = 46) or without (n = 22) cholesteatoma, persistent mastoid cavity (with [n = 15] or without [n = 10] recurrent cholesteatoma), revision ossiculoplasty for hearing restoration (n = 14), and postinflammatory meatal fibrosis (n = 1). Preoperatively, the mean ZCMEI-21 score showed statistically significant differences among different types of CMED (p = 0.007) with persistent mastoid cavity without cholesteatoma exhibiting the highest score (34.1, SD 7.7) indicating poor HRQoL. At a mean follow-up period of 183 days, no statistically significant differences in the ZCMEI-21 scores among different types of CMED were observed (p = 0.67). This study objectifies differences in HRQoL among different types of CMED. In patients with indication for functional surgery only, e.g., persistent mastoid cavity without cholesteatoma, the worst HRQoL was observed. Yet, in these types of CMED, HRQoL guides decision for treatment. Moreover, differences in HRQoL among different types of CMED were not closely associated with hearing, but largely depended on other symptoms, such as discharge or vertigo.


Similarities and differences in progesterone and androgens in modulation of LH, FSH and PRL release: unexpected properties of flutamide.
The purpose of this study was to determine if the similarity of effect of progesterone and androgens on antagonism of estrogen-induced prolactin release also applied to the regulation of LH and FSH release. An additional objective was to examine the effect of the antiandrogen, flutamide, upon the ability of progesterone to induce gonadotropin secretion. Using the ovariectomized estrogen-primed immature rat, testosterone propionate suppressed LH and FSH secretion, whereas dihydrotestosterone only suppressed serum LH levels. In contrast, progesterone significantly elevated both serum LH and FSH levels. Thus, with respect to regulation of gonadotropin secretion, the effects of androgens and progesterone were dissimilar. In the estrogen-primed ovariectomized immature rat, flutamide was found to suppress LH, FSH and PRL secretion. Progesterone (0.8 mg/kg body wt) was incapable of overcoming this suppressive effect of flutamide. The effect of flutamide on gonadotropin secretion required estrogen priming. The effect of flutamide in suppressing LH, FSH and PRL release was not through suppression of an adrenal steroid as shown by adrenalectomy or the use of RU486. In the PMSG primed immature rat, flutamide had no effect on basal gonadotropin levels or ovulation. However, flutamide antagonized progesterone and triamcinolone acetonide-induced gonadotropin surges and blocked their ability to facilitate ovulation. These studies demonstrate that in the ovariectomized estrogen-primed immature rat flutamide has potent neuroendocrine regulatory ability leading to suppression of LH, FSH and PRL release. Flutamide also blocked progesterone and triamcinolone acetonide induced gonadotropin surges and ovulation in PMSG-primed immature female rats.


Morphological and molecular characterization of a new member of the phylum Rhodelphidia.
Rhodelphidia is a recently discovered phylum within the supergroup Archaeplastida, comprising only two known representatives (Rhodelphis marinus and Rhodelphis limneticus). Despite its close phylogenetic relatedness to red algae, Rhodelphidia differ markedly by being nonphotosynthetic eukaryotrophic flagellates with gene- and intron-rich genomes. Here, we describe a new freshwater Rhodelphidia species, Rhodelphis mylnikovi sp. n., strain Rhod-M. It shows clear morphological differences with the two other Rhodelphis species, including larger cell body size, presence of two contractile vacuoles, short and blunt pseudopodia, absence of cysts, and tendency to cannibalism. 18S rRNA-based phylogenetic analysis placed it sister to the freshwater species R. limneticus.


The metacognitive model of depression: An empirical test in a large Norwegian sample.
The aim of the current study was to test the metacognitive model of depression in a large Norwegian sample. We hypothesized that metacognitions and rumination would explain variance in depressive symptoms as suggested by the metacognitive model. A total of 1433 participants were included using a cross-sectional study design. Participants answered scales assessing positive beliefs about rumination, rumination, negative beliefs about rumination, and symptoms of depression. Metacognitive beliefs and rumination in their hypothesized order explained significant variance in depressive symptoms. The results replicate previous studies and provide further support for a metacognitive model of depression.


Multi-objective Bayesian algorithm automatically discovers low-cost high-growth serum-free media for cellular agriculture application.
In this work, we applied a multi-information source modeling technique to solve a multi-objective Bayesian optimization problem involving the simultaneous minimization of cost and maximization of growth for serum-free C2C12 cells using a hyper-volume improvement acquisition function. In sequential batches of custom media experiments designed using our Bayesian criteria, collected using multiple assays targeting different cellular growth dynamics, the algorithm learned to identify the trade-off relationship between long-term growth and cost. We were able to identify several media with >100% more growth of C2C12 cells than the control, as well as a medium with 23% more growth at only 62.5% of the cost of the control. These algorithmically generated media also maintained growth far past the study period, indicating the modeling approach approximates the cell growth well from an extremely limited data set.


A sharp lithosphere-asthenosphere boundary imaged beneath eastern North America.
Plate tectonic theory hinges on the concept of a relatively rigid lithosphere moving over a weaker asthenosphere, yet the nature of the lithosphere-asthenosphere boundary remains poorly understood. The gradient in seismic velocity that occurs at this boundary is central to constraining the physical and chemical properties that create differences in mechanical strength between the two layers. For example, if the lithosphere is simply a thermal boundary layer that is more rigid owing to colder temperatures, mantle flow models indicate that the velocity gradient at its base would occur over tens of kilometres. In contrast, if the asthenosphere is weak owing to volatile enrichment or the presence of partial melt, the lithosphere-asthenosphere boundary could occur over a much smaller depth range. Here we use converted seismic phases in eastern North America to image a very sharp seismic velocity gradient at the base of the lithosphere-a 3-11 per cent drop in shear-wave velocity over a depth range of 11 km or less at 90-110 km depth. Such a strong, sharp boundary cannot be reconciled with a purely thermal gradient, but could be explained by an asthenosphere that contains a few per cent partial melt or that is enriched in volatiles relative to the lithosphere.


The role of amino acids in ApoB100 synthesis and catabolism in human HepG2 cells.
The object of this study was to examine the effects of extracellular amino acids on hepatic apoB100 metabolism using a transformed human liver cell line (HepG2) as a hepatocyte model. The data demonstrate that reduced extracellular amino acids resulted in marked increases in apoB100 concentrations in the medium (87 +/- 10% increase; p < 0.002). These data contrast with the effects of amino acids on secretion of total hepatic protein into the medium, which increased by 541 +/- 83% at 5.5 mg/ml amino acids compared to the low (0.5 mg/ml) amino acid medium (p < 0.01), pointing to a positive relationship between the concentration of amino acids in the medium and overall secretion of protein by the HepG2 cells. No significant effect of medium amino acid concentration on intracellular synthesis of cholesterol ester, cholesterol, triglyceride, or apoA1 secretion was evident. Amino acids also affected the activity of the low density lipoprotein pathway: at lower medium amino acid concentration, specific cell-associated radioactivity and cellular degradation were increased (117 +/- 24 and 233 +/- 13% at 0.5 versus 5.5 mg/ml amino acids, respectively). Pulse-chase analysis demonstrated that there was no difference in secretion efficiency of apoB (36 +/- 6 versus 46 +/- 8% in low versus high amino acid medium, respectively), but that the initial amount of [3H]apoB synthesized was greater in the low amino acid medium (10.5 +/- 3.8 versus 5.7 +/- 1.7 x 10(3) dpm [3H]apoB/mg of cell protein; p < 0.05). In contrast, the initial amount of [3H]albumin synthesized was much greater in the high amino acid medium (26.6 +/- 5.0 versus 54.6 +/- 19.0 x 10(3) dpm [3H]albumin/mg of cell protein in low versus high amino acid medium, respectively; p < 0.05). Slot blot analysis of apoB mRNA was 87 +/- 22% higher in lower amino acid medium as compared to the high amino acid medium (p < 0.01). These results demonstrate that amino acids have a profound negative regulatory effect on apoB synthesis and secretion and may shed light on the pathogenesis of some clinical dyslipidemias such as the increased plasma apoB levels in patients treated with continuous ambulatory peritoneal dialysis.


Ultrastructural localization of neurophysin-like immunoreactivity in the rat posterior pituitary. An alternative method using frozen-dried tissue fixed with OsO4 vapor.
Electron microscopic identification of elements containing neurophysin-like immunoreactivity can be accomplished in rat posterior pituitary that has been frozen-dried and fixed with OsO4 vapor. Alternating serial ultrathin sections are placed on grids and glass slides. The sections on the slides are stained for neurophysin using immunofluorescence histochemistry, and the resultant images are superimposed on electron micrographs from the adjacent sections. The method provides several advantages for the localization of neuropeptide immunoreactivity in nervous tissue.


The Evolving Theory of Evolutionary Radiations.
Evolutionary radiations have intrigued biologists for more than 100 years, and our understanding of the patterns and processes associated with these radiations continues to grow and evolve. Recently it has been recognized that there are many different types of evolutionary radiation beyond the well-studied adaptive radiations. We focus here on multifarious types of evolutionary radiations, paying special attention to the abiotic factors that might trigger diversification in clades. We integrate concepts such as exaptation, species selection, coevolution, and the turnover-pulse hypothesis (TPH) into the theoretical framework of evolutionary radiations. We also discuss other phenomena that are related to, but distinct from, evolutionary radiations that have relevance for evolutionary biology.


Enhancement of sample loadings for the analysis of oligosaccharides isolated from Pseudomonas aeruginosa using transient isotachophoresis and capillary zone electrophoresis - electrospray - mass spectrometry.
The analysis of underivatized core oligosaccharides arising from mild acid hydrolysis of lipopolysaccharides from Pseudomonas aeruginosa serotype 05 was achieved using a transient isotachophoretic preconcentration method coupled to capillary zone electrophoresis-electrospray-mass spectrometry (tCITP-CZE-ES-MS). The combination of a tCITP preconcentration step provided a 10- to 50-fold enhancement of sample loading and a corresponding improvement in sensitivity compared to the conventional zone electrophoresis format. Electrophoretic conditions, enabling the separation of these anionic analytes, were developed to determine possible sites of heterogeneity on either the core or the O-chain structures. The tCITP-CZE-ES-MS technique provided unparalleled resolution of the different core glycoforms and oligosaccharides obtained from the acid cleavage of the native endotoxins whether isolated following conventional gel permeation chromatography or obtained from direct hydrolysis of the bacterial isolates. These investigations also highlighted the highly phosphorylated nature of these complex cell membrane components, where the heptose residues of the core oligosaccharide can bear up to six phosphate groups.


Predicting response to systemic treatments: learning from the past to plan for the future.
Therapeutic effects of adjuvant therapies for breast cancer have been assessed "across the board" and implemented using the principle that if a treatment is effective "on average" then it is effective "for all patients." Exploration and improved understanding of the biological basis for predicting response to available adjuvant therapies is essential to enhance patient care. As illustration, we consider the effects of chemotherapy and tamoxifen in two International Breast Cancer Study Group (IBCSG) trials for postmenopausal women. The level of estrogen receptor (ER) expression in the primary tumor is a powerful predictor of response to adjuvant therapy. Absence of ER identifies a chemosensitive cohort for which concurrent tamoxifen significantly blunts the large chemotherapy effect. High levels of ER expression are associated with good results using tamoxifen alone; adding chemotherapy provides little additional benefit. By contrast, adding chemotherapy to tamoxifen provides additional benefit for patients with node-positive disease and tumors expressing intermediate levels of ER. Identification of chemosensitive targets, e.g., absence of PgR, in tumors with intermediate ER expression is required to further tailor, adding chemotherapy within this otherwise endocrine-responsive cohort. Age is not a therapeutic target. Thus, the biological bases for treatment responsiveness must be defined. All findings from clinical trials and meta-analyses should be presented primarily according to steroid hormone receptor status and future studies should be designed as tailored treatment investigations.


Information and learning in processing adjective inflection.
We investigated the processing of inflected Serbian adjective forms to bring together quantitative linguistic measures from two frameworks - information theory and discrimination learning. From each framework we derived several quantitative descriptions of an inflectional morphological system and fitted two separate regression models to the processing latencies that were elicited by inflected adjectival forms presented in a visual lexical decision task. The model, which was based on lexical distributional and information theory revealed a dynamic interplay of information. The information was sensitive to syntagmatic and paradigmatic dimensions of variation; the paradigmatic information (formalized as respective relative entropies) was also modulated by lemma frequency. The discrimination learning based model revealed an equally complex pattern, involving several learning-based variables. The two models revealed strikingly similar patterns of results, as confirmed by the very high proportion of shared variance in model predictions (85.83%). Our findings add to the body of research demonstrating that complex morphological phenomena can arise as a consequence of the basic principles of discrimination learning. Learning discriminatively about inflectional paradigms and classes, and about their contextual or syntagmatic embedding, sheds light on human language-processing efficiency and on the fascinating complexity of naturally emerged language systems.


Is CD38 involved in Ca2+ signalling elicited by activation of T cell receptors?
A recent publication proposes that T cell receptor activation elicits formation of the Ca2+ releasing messenger NAADP from NAADPH, catalysed by the NADPH oxidase DUOX. This is in contrast to the hitherto prevailing view that CD38 is critical for NAADP formation. Is it time to reassess the role of CD38?


Antibacterial brush polypeptide coatings with anionic backbones.
Preventing initial colonization of bacteria on biomaterial surfaces is crucial to address the medical device-associated infection issues. Antimicrobial peptide (AMP) or cationic polymer modified surfaces have shown promising potentials to inhibit the initial colonization of bacteria by contact killing. However, their development has been impeded because of bacterial adhesion and high cytotoxicity. Herein, we report a series of brush polypeptide coatings with anionic backbones and cationic AMP mimetic side-chains that displayed superior bactericidal activity, antibacterial adhesion property, and biocompatibility. The cationic side-chain density played an important role in the bioactivities of the brush polypeptide modified surfaces. Brush polypeptide coating with low side-chain density exhibited improved bactericidal activity and antibacterial adhesion property, ascribing to the cooperative effects of adjacent side-chains and backbones/side-chains, respectively. It also showed negligible hemolysis/cytotoxicity in vitro and potent anti-infection property (≥99.9% bactericidal efficacy) in vivo. Brush polymers with anionic backbones and cationic side-chains can be used as a promising design motif to potentiate both antibacterial property and biocompatibility of coatings for combating device-associated infections. STATEMENT OF SIGNIFICANCE: Device-associated infections (DAIs) have led to increased medical cost, pain, and even mortality of patients. Antimicrobial peptide and cationic polymer coatings provide an important strategy to combat DAIs by preventing initial colonization of bacteria on biomaterial surfaces. Nevertheless, they have suffered bacterial adhesion and cytotoxicity issues. Herein, we developed a brush polypeptide coating with anionic backbones and cationic side-chains. The brush polypeptide coating showed superior bactericidal and antibacterial adhesion properties outperforming conventional antibacterial coatings based on antimicrobial peptide (i.e., melittin), lysozyme (i.e., lysostaphin), cationic polymer, anionic polymer, and the blends of cationic/anionic polymers. It also showed good biocompatibility and potent anti-infection property, making it a promising candidate to combat the DAIs.


Novel concept on antiviral strategies to dengue.
Recent evidence has revealed that asymptomatic and/or persistent dengue virus (DENV) infections play a role in the cycling pattern of dengue outbreaks. These findings add a new dimension to the continually evolving search for effective prevention strategies in dengue. Disappointing outcomes of clinical trials in anti-dengue modalities have become commonplace. These failures may result from confounding variables and/or unresolved scientific issues that surround dengue, including the replication cycle of DENV in a natural setting, the target cells and reservoir for viral replication in vivo, and the effect of asymptomatic/persistent carriers in the dissemination of dengue. This article sets forth to address these issues using the most updated information available in the literature and to propose a novel antiviral strategy for the prevention and control of dengue.


Measurement invariance of assessments of depression (PHQ-9) and anxiety (GAD-7) across sex, strata and linguistic backgrounds in a European-wide sample of patients after Traumatic Brain Injury.
The Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder (GAD-7) are two widely used instruments to screen patients for depression and anxiety. Comparable psychometric properties across different demographic and linguistic groups are necessary for multiple group comparison and international research on depression and anxiety. We examine measurement invariance for the PHQ-9 and GAD-7 by: (a) the sex of the participants, (b) recruitment stratum, and (c) linguistic background. This study is based on non-randomized observational data six months after Traumatic Brain Injury (TBI) that were collected in 18 countries. We used multiple methods to detect Differential Item Functioning (DIF) including Item Response Theory, logistic regression, and the Mantel-Haenszel method. At the 6-month post-injury, 2137 (738 [34.5%] women) participants completed the PHQ-9 and GAD-7 questionnaires: 885 [41.4%] patients were primarily admitted to the Intensive Care Unit (ICU), 805 [37.7%] were admitted to hospital ward, and 447 [20.9%] were evaluated in the Emergency Room and discharged. Results supported the invariance of PHQ-9 and GAD-7 across sex, patient strata and linguistic background. For different strata three PHQ-9 items and one GAD-7 item and for different linguistic groups only two GAD-7 items were flagged as showing differences in two out of four DIF tests. However, the magnitude of the DIF effect was negligible. Despite high number of participants from ICU, patients have mostly mild TBI. The findings demonstrate adequate psychometric properties for PHQ-9 and GAD-7, allowing direct multigroup comparison across sex, strata, and linguistic background.


A comparative trial of praziquantel, metrifonate and niridazole against Schistosoma haematobium.
Praziquantel administered in a single oral dose of 30 mg kg-1 to subjects infected with Schistosoma haematobium produced minimal side effects and was more effective than established regimes of niridazole and metrifonate. Praziquantel should prove a major tool in schistosomiasis control programmes.


Antibiotic therapeutic drug monitoring in intensive care patients treated with different modalities of extracorporeal membrane oxygenation (ECMO) and renal replacement therapy: a prospective, observational single-center study.
Effective antimicrobial treatment is key to reduce mortality associated with bacterial sepsis in patients on intensive care units (ICUs). Dose adjustments are often necessary to account for pathophysiological changes or renal replacement therapy. Extracorporeal membrane oxygenation (ECMO) is increasingly being used for the treatment of respiratory and/or cardiac failure. However, it remains unclear whether dose adjustments are necessary to avoid subtherapeutic drug levels in septic patients on ECMO support. Here, we aimed to evaluate and comparatively assess serum concentrations of continuously applied antibiotics in intensive care patients being treated with and without ECMO. Between October 2018 and December 2019, we prospectively enrolled patients on a pneumological ICU in southwest Germany who received antibiotic treatment with piperacillin/tazobactam, ceftazidime, meropenem, or linezolid. All antibiotics were applied using continuous infusion, and therapeutic drug monitoring of serum concentrations (expressed as mg/L) was carried out using high-performance liquid chromatography. Target concentrations were defined as fourfold above the minimal inhibitory concentration (MIC) of susceptible bacterial isolates, according to EUCAST breakpoints. The final cohort comprised 105 ICU patients, of whom 30 were treated with ECMO. ECMO patients were significantly younger (mean age: 47.7 vs. 61.2 years; p < 0.001), required renal replacement therapy more frequently (53.3% vs. 32.0%; p = 0.048) and had an elevated ICU mortality (60.0% vs. 22.7%; p < 0.001). Data on antibiotic serum concentrations derived from 112 measurements among ECMO and 186 measurements from non-ECMO patients showed significantly lower median serum concentrations for piperacillin (32.3 vs. 52.9; p = 0.029) and standard-dose meropenem (15.0 vs. 17.8; p = 0.020) in the ECMO group. We found high rates of insufficient antibiotic serum concentrations below the pre-specified MIC target among ECMO patients (piperacillin: 48% vs. 13% in non-ECMO; linezolid: 35% vs. 15% in non-ECMO), whereas no such difference was observed for ceftazidime and meropenem. ECMO treatment was associated with significantly reduced serum concentrations of specific antibiotics. Future studies are needed to assess the pharmacokinetic characteristics of antibiotics in ICU patients on ECMO support.


Modal approximation for plasmonic resonators in the time domain: the scalar case.
We study the electromagnetic field scattered by a metallic nanoparticle with dispersive material parameters in a resonant regime. We consider the particle placed in a homogeneous medium in a low-frequency regime. We define modes for the non-Hermitian problem as perturbations of electro-static modes, and obtain a modal approximation of the scattered field in the frequency domain. The poles of the expansion correspond to the eigenvalues of a singular boundary integral operator and are shown to lie in a bounded region near the origin of the lower-half complex plane. Finally, we show that this modal representation gives a very good approximation of the field in the time domain. We present numerical simulations in two dimensions to corroborate our results.


A Systematic Review on the Timing of Surgical Intervention for Benign Prostatic Enlargement (BPE).
Surgical intervention for benign prostatic enlargement (BPE) is typically reserved for those who fail medical therapy (i.e., α-blocker or 5-α reductase inhibitor treatment). We conducted a systematic review to determine whether timing of surgical intervention for BPE affects patient outcomes. The studies we reviewed suggested that patients who undergo surgical intervention for BPE after failing medical therapy may have worse outcomes. Increased age, worsened bladder function, and worse overall health may contribute to worsened outcomes. To date, there are few high-quality studies on the timing of surgical intervention for BPE in the literature. Further prospective trials are needed to determine ideal timing for intervention.


Increased production of hydrogen with in situ CO2 capture through the process of water splitting using magnetic core/shell structures as novel photocatalysts.
One of the chief challenges in hydrogen production through the photocatalytic splitting of water is to employ an efficient photocatalyst that has an absorption edge at the range of long wavelengths. In this study, composite structures made of different Ag-based shells over the core of Fe2O3 nanoparticles were utilized as novel magnetic photocatalysts for hydrogen generation from water. Specifically, Ag nanoparticles, Ag/(3-aminopropyl) triethoxysilane (APTS), and Ag/polyethyleneimine (PEI) were capped on the surface of the hematite core to produce three visible light-effective photocatalysts. Structural and textural properties of the synthesized photocatalysts were confirmed by Fourier transform infrared (FTIR), X-ray diffraction (XRD), energy dispersive X-ray spectroscopy (EDS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). Additionally, their thermal stability and optical properties were respectively studied using thermogravimetric analysis (TGA) and UV reflectance. Photocatalytic activities of the presented core/shells were planned either as a function of the magnetic force or composition of the shell layer. It could be noted that the incorporation of organic or polymer layer could significantly increase the electronic density at the metal centers. Thus, the ability of iron oxide to catalyze the water-splitting process could be enhanced. Hence, the variation of shell structure could show a key-role in the photocatalytic potential of the presented structures in terms of manipulating the composition of produced gases. On the other hand, the magnetic nature of hematite could also positively affect the photocatalytic activity of these structures by minimizing the scattering of light irradiation during the splitting process. Particularly, shifting the way of photocatalysts dispersion from magnetic to mechanical (during water splitting) had in turn reduced hydrogen productivity from 540 to 485 mmol h-1 g-1. This obviously confirms the relationship between the level of hydrogen production by the presented photocatalysts and their magnetic nature which results in quenching of irradiation scattering.


Neurotoxic effects, molecular responses and oxidative stress biomarkers in Nile tilapia, Oreochromis niloticus (Linnaeus, 1758) exposed to verapamil.
Pharmaceutical drugs and their metabolites are detected in aquatic ecosystems and have been reported to cause ecotoxicological consequences to resident aquatic organisms. The study investigated the effects of acute and long-term exposure to verapamil on activities of acetylcholinesterase and antioxidant enzymes as well as mRNA expression of stress-related genes in brain and muscle tissues of Nile tilapia, Oreochromis niloticus. The 96h LC50 of verapamil to O. niloticus was 2.29mgL-1. Exposure to sub-lethal concentrations of verapamil (0.14, 0.29 and 0.57mgL-1) for period of 15, 30, 45 and 60days, led to inhibition of acetylcholinesterase activities in the brain and muscle of the fish. The activities of the oxidative enzymes such as the catalase, superoxide dismutase and glutathione peroxidase were also inhibited in both the tissues while there was an increase in the activities of glutathione-S-transferase and reduced glutathione in the muscle after 15 days at 0.29mgL-1. Lipid peroxidation and carbonyl protein showed elevated level, indicating a positive correlation with both time and concentration. The activities of energy-related biomarker (Na+-K+-ATPase) in both the tissues were significantly inhibited (p<0.05) compared with the control. Transcription of catalase (cat), superoxide dismutase (sod) and heat shock proteins 70 (hsp70) were up-regulated in both the tissues after the study period. Prolonged exposure to sub-lethal verapamil can result in oxidative stress, up-regulation of stress-related genes and neurotoxicity in O. niloticus.


Pharmacist's recommendations of over-the-counter treatments for the common cold - analysis of prospective cases in Poland.
Common cold is a frequent illness in northern hemisphere between late autumn and early spring. Patients suffering from it frequently turn to pharmacists instead of physicians in order to receive medical advice and treatment. We studied its treatment advised by pharmacists in Poland, as well as evidence for the efficacy of their recommendations by utilizing a self-developed questionnaire and a study of existing literature. The data were collected by 27 pharmacists who worked in four large network community pharmacies in Lodz, Poland. The study took place from December 2019 to February 2020. Data were recorded only if the patient asked for pharmacy counselling for over-the counter (OTC) products due to common cold self-diagnosis and a product was sold. Pharmacists' recommendations were compared with the results of a literature review of best evidence to determine appropriateness of the pharmacists' decisions. In four out of five cases the pharmacists recommended products contained paracetamol. In addition, in one out of three patient encounters they advised nasal decongestant, inosines and/or OTC mucolytics. There was a significant relationship between fever and recommendation frequency of some analgesics, inosines, mucolytics and sore throat products (OR > 1, p < 0.05); rhinorrhea and recommendation frequency of paracetamol, inosines, anti-histamines and alpha-mimetics (OR > 1, p < 0.05); cough and recommendation frequency of paracetamol, inosines, mucolytics and sore throat products (OR > 1, p < 0.05); and fatigue and recommendation frequency of paracetamol, acetylsalicylic acid, inosines and sore throat products (OR > 1, p < 0.05). The pharmacist recommendations were based on patients' symptoms, product price, pharmaceutical company promotion and the financial incentive. In many cases their recommendations were not in line with current best practice recommendations. Our study suggests that the most common rationale for pharmacist recommendation on anti-common cold treatment was to take a "shotgun" approach. Pharmacists commonly made recommendations for products that lack strong evidence for efficacy (i.e. anti-viral agents) and are potentially unnecessary, based on presentation of the symptom. Reasons for this situation include lack of training, lack of time to evaluate the patient, lack of awareness of evidence as well as drug company marketing and financial incentives (i.e. fulfilling sale plans and target sale bonuses). The study was a non-interventional, observational research trial. The study registration was not required.


Resistance of Acanthamoeba to classic DNA extraction methods used for the diagnosis of corneal infections.
Sensitive diagnosis of Acanthamoeba infections may prevent the clinical condition from becoming worse. In order to improve the diagnosis tool performances, we studied the implication of the DNA extraction procedures on the detection of Acanthamoeba by real-time PCR. Acanthamoeba cysts mixed with a tag virus were processed according to different DNA preparation procedures: heat, Proteinase K (ProtK), alkali lysis, QIAmp kit, MagNA Pure (DNA Mini kit, MagNA Pure Nucleic Acid isolation kit), ProtK+QIAmp and ProtK+MagNA Pure. Parasite-DNA loads were assessed by real-time PCR. The results show that the structures of Acanthamoeba cysts are resistant to reagents releasing the DNA from other cells and viruses. Heat, NaOH or ProtK did not allow the DNA extraction yields to be assessed or the inhibitors to be eliminated The QIAmp and the MagNA Pure partially improved the sensitivity of the PCR and eliminated the inhibitors. A significant increase in positive results was obtained with a ProtK treatment before commercial extraction kits. ProtK+MagNA Pure yielded the highest rates of positivity. To minimise false negative results, the nucleic-acid based Acanthamoeba diagnosis requires, first, the efficient lysis of cysts (without affecting the DNA) to make the DNA available for extraction and amplification, and, second, the elimination of PCR inhibitors. A significant increase in the detection rates is obtained by adding a ProtK treatment (10 min at 56 degrees C) before the commercial procedures. ProtK+MagNA Pure yielded the best results in 30 min, followed by ProtK+QIAmp (150 min).


KLF5 promotes cell proliferation and tumorigenesis through gene regulation and the TSU-Pr1 human bladder cancer cell line.
KLF5 is a transcription factor that plays important roles in multiple physical and pathological processes, including cell growth, cell cycle regulation, and angiogenesis. To better characterize KLF5 function in bladder carcinogenesis, we established stable TSU-Pr1 cell clones expressing different levels of KLF5. These clones were then characterized for cell growth, cell cycle progression, tumorigenesis, and alteration in gene expression. Overexpression of KLF5 promoted tumorigenesis of the TSU-Pr1 cancer cells in mice. Consistently, KLF5 increased G1 to S phase transition, which was accompanied by the upregulation of cyclin D1, phosphorylation of MAPK and Akt, and reduced protein levels for CDK inhibitors p27 and p15. Microarray analysis combined with expression verification in different cell systems identified a number of additional genes that are potentially regulated by KLF5, including HBP17, ITGA6, and RAIG1. These findings suggest that the KLF5 transcription factor plays an oncogenic role in the TSU-Pr1 bladder cancer cell line through the regulation of a subset of genes.


Measurement issues related to upper limb interventions in persons who have tetraplegia.
Measurement of upper limb function in persons with tetraplegia poses significant issues for clinicians and researchers. It is crucial that measures detect the small but significant improvements in hand function that may or may not occur as a result of our interventions. Before determining how we measure changes from upper limb interventions, we must establish what outcomes are of greatest interest, and for whom. Many issues have an impact on both the measurement and interpretative process.


Reoperation rate and implants' position variation features of displaced femoral neck fractures with sliding compression or length-stable fixation in young and middle-aged population.
Sliding compression fixation and length-stable fixation are two basic internal fixation concepts in the treatment of displaced femoral neck fractures. In this study, we aimed to compare the reoperation rates for different methodologies of internal fixation for femoral neck fractures in young and middle-aged population. This a retrospective study. A total of 215 patients with displaced femoral neck fractures treated with cannulated screw fixation were enrolled and divided into the sliding compression and length-stable groups according to the fixation pattern. The occurrence of and reason for revision surgery within one year were recorded. Forty-five patients with complete CT data (including CT scanning on the first postoperative day and at the last follow up) were selected from the total sample. A newly established computerized image processing method was used to evaluate variations in the spatial location of screws. The reoperation rate was significantly higher in the length-stable group (23.8%) than in the sliding compression group (7.3%). The rate of revision surgery due to nonunion was also higher in the length-stable group (11.4%) than in the sliding compression group (1.8%). However, no significant difference was observed in terms of joint penetration or soft tissue irritation. The sliding compression group (6.58 ± 3.18 mm) showed higher femoral neck shortening than length-stable group (4.16 ± 3.65 mm). When analyzing the spatial variations, a significantly greater screw withdrawal distance was observed in the sliding compression group than in the length-stable group, but with a smaller rotation angle. Length-stable internal fixation of displaced femoral neck fractures may lead to an increased reoperation rate in young and middle-aged population. Name of the registry: Chinese Clinical Trial Registry. ChiCTR2000032327. Trial registration date: 2020-4-26.


Duration and method of tissue storage alters placental morphology - implications for clinical and research practice.
We assessed whether placental morphology is affected by placental storage before fixation. Fresh tissue from uncomplicated pregnancies (n = 10) was fixed immediately and further samples were stored dry, in PBS or culture medium for 24, 48 or 72 h at 4 °C. Placental morphology quantified using image analysis software found no difference in syncytial nuclear aggregates, cytokeratin 7, CD45 or Ki67 immunostaining irrespective of duration or mode of storage. The number of blood vessels per villus (CD31) was reduced in all conditions after 72 h (p < 0.05). Distal villous hypoplasia increased after 72 h (p < 0.05). Ideally, storage time should be minimised to ≤48 h prior to morphological or qualitative analysis.


The Association Between On-treatment Ambulatory Central Blood Pressure and Left Ventricular Reverse Remodeling in Heart Failure With Reduced Ejection Fraction.
Compared to office blood pressure (OBP), central blood pressure (CBP) and ambulatory blood pressure (BP) are known to be better markers for predicting cardiovascular events. We evaluated the association between left ventricular reverse remodeling (LVRR) and ambulatory CBP in heart failure with reduced ejection fraction (HFrEF). This study retrospectively analyzed 93 patients who performed ambulatory CBP and brachial BP (BBP) monitoring from 2018 to 2020 within 1 year after diagnosis of HFrEF at a single tertiary center. We analyzed the association between on-treatment ambulatory BPs and LVRR on follow-up echocardiography. The mean age of participants was 59 years; 65.6% were men; mean LVEF was 29%. Ambulatory BP and follow-up echocardiography were done at 143 days (interquartile range [IQR], 64-267) and 454 days (IQR, 281-600) after diagnosis of HF, respectively. Baseline OBP was not different between 2 groups, but ambulatory systolic CBP was significantly higher in the LVRR group than the non-LVRR group (p=0.005). Systolic OBP (odds ratio [OR], 1.029; confidence interval [CI], 1.004-1.055; p=0.026), 24-hour ambulatory systolic CBP (OR, 1.048; CI, 1.015-1.082; p=0.004), and 24-hour ambulatory systolic BBP (OR, 1.049; CI,1.017-1.082; p=0.003) were associated with LVRR. Compared to ambulatory systolic CBP of 110-119 mmHg, 90-99 mmHg showed lower OR for LVRR. Low on-treatment ambulatory systolic CBP was closely related to a lower likelihood of LVRR in HFrEF than the normal range. Ambulatory CBP measured during treatment of patients with HFrEF appears to be useful in predicting outcomes.


Disseminated fungal infection in a patient receiving zanubrutinib.
We report a case of fatal disseminated aspergillosis in the setting of administration of zanubrutinib, a second-generation Bruton's tyrosine kinase inhibitor thought to have a lower rate of immunosuppression-related side effects.


Endo-robotic resection of the submandibular gland in a cadaver model.
By means of a prospective, nonrandomized investigation, we evaluated the feasibility of performing endo-robotic resection of the submandibular gland in a cadaver model and compared the results of robotically enhanced endoscopic surgery with those from a conventional endoscopic technique. Procedural times were recorded in a consecutive series of 11 endoscopic submandibular gland resections using the daVinci Surgical System (Intuitive Surgical, Sunnyvale, CA) and a modified endoscopic surgical approach previously developed in a porcine model. The presence of neurovascular injury was assessed postoperatively, and the specimens were examined histologically. Eleven endo-robotic submandibular gland resections were successfully performed in six cadavers (no conversions to open resection were necessary). The median duration of the procedures was 48 minutes (range, 33-82 minutes). Creation of the operative pocket took an average (+/-SD) of 12.2 +/- 5.3 minutes, assembly of the robot required 9.3 +/- 4.1 minutes, and the mean time for submandibular gland resection was 29.4 +/- 8.9 minutes. The time required for robotic assembly was offset by the reduced operative time necessary compared with conventional endoscopic resection. Histologic examination confirmed the presence of normal glandular architecture, without evidence of excessive mechanical or thermal injury. There were no cases of apparent neurovascular injury. Robotically enhanced endoscopic surgery in the neck is feasible and offers a number of compelling advantages over conventional endoscopic neck surgery. Clinical trials will be necessary to determine whether these advantages can be achieved in clinical practice.


Image Reconstruction in Light-Sheet Microscopy: Spatially Varying Deconvolution and Mixed Noise.
We study the problem of deconvolution for light-sheet microscopy, where the data is corrupted by spatially varying blur and a combination of Poisson and Gaussian noise. The spatial variation of the point spread function of a light-sheet microscope is determined by the interaction between the excitation sheet and the detection objective PSF. We introduce a model of the image formation process that incorporates this interaction and we formulate a variational model that accounts for the combination of Poisson and Gaussian noise through a data fidelity term consisting of the infimal convolution of the single noise fidelities, first introduced in L. Calatroni et al. (SIAM J Imaging Sci 10(3):1196-1233, 2017). We establish convergence rates and a discrepancy principle for the infimal convolution fidelity and the inverse problem is solved by applying the primal-dual hybrid gradient (PDHG) algorithm in a novel way. Numerical experiments performed on simulated and real data show superior reconstruction results in comparison with other methods.


Comparison between the lengths of individual osteoid seams and resorption cavities in human iliac crest cancellous bone.
The current concept of bone remodelling is based on the belief that bone resorption and formation are coupled both in time and space; this implies that the surface extent of bone eroded in a bone remodelling unit would approximate to the surface extent of the osteoid seam formed subsequently. The greater total surface extent of osteoid as opposed to erosion is generally attributed to the longer life-span of bone formation, but no comparison of the length of eroded surface and osteoid seam within individual bone remodelling units has been reported. In this study we have compared the length of individual osteoid seams, resorption cavities and bone structural units in iliac crest trabecular bone obtained from normal subjects and from patients with renal osteodystrophy. Values for osteoid seam and bone packet length were significantly greater than resorption cavity length in both the normal and patient groups (P < 0.001), the ratio of osteoid seam and eroded length being similar in the two groups (1:0.44 and 1:0.40, respectively). These results indicate that the discrepancy between total osteoid and eroded surface extent cannot be wholly explained on the basis of a longer formation life-span. Possible additional explanations include underestimation of eroded surface by light microscopic techniques, initiation of bone formation within a cavity before the completion of resorption, the presence of arrested resorption cavities, non-random distribution of resorption cavities on the trabecular surface and bone formation on quiescent bone surfaces.


Automated prediction of 15N, 13Calpha, 13Cbeta and 13C' chemical shifts in proteins using a density functional database.
A database of peptide chemical shifts, computed at the density functional level, has been used to develop an algorithm for prediction of 15N and 13C shifts in proteins from their structure; the method is incorporated into a program called SHIFTS (version 4.0). The database was built from the calculated chemical shift patterns of 1335 peptides whose backbone torsion angles are limited to areas of the Ramachandran map around helical and sheet configurations. For each tripeptide in these regions of regular secondary structure (which constitute about 40% of residues in globular proteins) SHIFTS also consults the database for information about sidechain torsion angle effects for the residue of interest and for the preceding residue, and estimates hydrogen bonding effects through an empirical formula that is also based on density functional calculations on peptides. The program optionally searches for alternate side-chain torsion angles that could significantly improve agreement between calculated and observed shifts. The application of the program on 20 proteins shows good consistency with experimental data, with correlation coefficients of 0.92, 0.98, 0.99 and 0.90 and r.m.s. deviations of 1.94, 0.97, 1.05, and 1.08 ppm for 15N, 13Calpha, 13Cbeta and 13C', respectively. Reference shifts fit to protein data are in good agreement with 'random-coil' values derived from experimental measurements on peptides. This prediction algorithm should be helpful in NMR assignment, crystal and solution structure comparison, and structure refinement.


Chemical mitophagy modulators: Drug development strategies and novel regulatory mechanisms.
Maintaining mitochondrial homeostasis is a potential therapeutic strategy for various diseases, including neurodegenerative diseases, cardiovascular diseases, metabolic disorders, and cancer. Selective degradation of mitochondria by autophagy (mitophagy) is a fundamental mitochondrial quality control mechanism conserved from yeast to humans. Indeed, small-molecule modulators of mitophagy are valuable pharmaceutical tools that can be used to dissect complex biological processes and turn them into potential drugs. In the past few years, pharmacological regulation of mitophagy has shown promising therapeutic efficacy in various disease models. However, with the increasing number of chemical mitophagy modulator studies, frequent methodological flaws can be observed, leading some studies to draw unreliable or misleading conclusions. This review attempts (a) to summarize the molecular mechanisms of mitophagy; (b) to propose a Mitophagy Modulator Characterization System (MMCS); (c) to perform a comprehensive analysis of methods used to characterize mitophagy modulators, covering publications over the past 20 years; (d) to provide novel targets for pharmacological intervention of mitophagy. We believe this review will provide a panorama of current research on chemical mitophagy modulators and promote the development of safe and robust mitophagy modulators with therapeutic potential by introducing high methodological standards.


Noninflammatory myopathies.
The noninflammatory myopathies are a diverse group of diseases, some of which may mimic the autoimmune-mediated idiopathic inflammatory myopathies in their clinical presentation. They include certain metabolic, toxic, and infectious myopathies, as well as muscular dystrophies. In addition to muscle weakness, these forms of myopathy may present with exercise intolerance and muscle pain. Special testing techniques are often required to establish the diagnosis. This review focuses on those noninflammatory myopathies that should be included in the differential diagnosis of idiopathic inflammatory myopathy.