Morphometric analysis of nerve fibers in neural leprosy.
The present study assesses the contributions of axonal degeneration and demyelination in leprosy nerve damage. New clinical strategies can emerge from an in-depth understanding of the pathogenesis of neural leprosy (NL). Morphometric analysis of myelinated nerve fibers was performed on 44 nerve biopsy samples collected from leprosy patients. Measures of density, diameter distribution, g-ratios, and the counting of axonal ovoids on the myelinated fibers were taken and compared to those in the control group. The proportion of small myelinated fibers increased in the leprosy group while large fiber frequency decreased. Indicative of axonal atrophy, the g-ratio was lower in the leprosy group. The frequency of axonal ovoids was identical to that found in the non-leprosy neuropathies. Axonal atrophy, Wallerian degeneration, and demyelination coexist in NL. Axonal degeneration predominates over demyelination in the chronic course of the disease; however, this may change during leprosy reactive episodes. This study regards demyelination and axon degeneration as concurrent mechanisms of damage to nerve fibers in leprosy. It also calls into question the view that demyelination is the primary and predominant mechanism in the complex pathogeny of NL.


The effects of glycosaminoglycans, pyrophosphate and allopurinol treatment on urease-induced crystallization in vitro.
Previous studies have found that human urine inhibits urease-induced crystallization in synthetic urine. To identify the inhibitory components the effects of chondroitin sulphate, heparin and pyrophosphate on urease-induced crystallization were studied and the inhibitory capacity of human urine collected during and before/after allopurinol treatment compared. None of the substances studied nor allopurinol treatment was found to influence the urease-induced crystallization. These findings do not support the idea that glycosaminoglycans or pyrophosphate are responsible for the inhibitory effect detected in human urine.


Endosomal Acid-Base Homeostasis in Neurodegenerative Diseases.
Neurodegenerative disorders are debilitating and largely untreatable conditions that pose a significant burden to affected individuals and caregivers. Overwhelming evidence supports a crucial preclinical role for endosomal dysfunction as an upstream pathogenic hub and driver in Alzheimer's disease (AD) and related neurodegenerative disorders. We present recent advances on the role of endosomal acid-base homeostasis in neurodegeneration and discuss evidence for converging mechanisms. The strongest genetic risk factor in sporadic AD is the ε4 allele of Apolipoprotein E (ApoE4), which potentiates pre-symptomatic endosomal dysfunction and prominent amyloid beta (Aβ) pathology, although how these pathways are linked mechanistically has remained unclear. There is emerging evidence that the Christianson syndrome protein NHE6 is a prominent ApoE4 effector linking endosomal function to Aβ pathologies. By functioning as a dominant leak pathway for protons, the Na+/H+ exchanger activity of NHE6 limits endosomal acidification and regulates β-secretase (BACE)-mediated Aβ production and LRP1 receptor-mediated Aβ clearance. Pathological endosomal acidification may impact both Aβ generation and clearance mechanisms and emerges as a promising therapeutic target in AD. We also offer our perspective on the complex role of endosomal acid-base homeostasis in the pathogenesis of neurodegeneration and its therapeutic implications for neuronal rescue and repair strategies.


A new staging method versus TNM staging in children with posterior fossa primitive neuroectodermal tumor (medulloblastoma).
Prognostic factors were evaluated in 30 children with primitive neuroectodermal tumors of the posterior fossa (classical medulloblastoma or differentiated medulloblastoma). The preoperative TNM (Tumor, Node, Metastasis) staging system has been applied to estimate prognosis of patients with central nervous system tumors, but this system was not applicable in assessing the postoperative status of the tumor. To fill this need, a postoperative staging system was developed known as MAPS (Metastasis, Age, Pathology, Surgery), and in this report its efficacy is compared with that of the TNM system. The predictive values of MAPS staging in these 30 children were better than those obtained using the TNM method (MAPS r2 = -0.90; TNM r2 = 0.73; P less than 0.05).


Carbon tetrachloride and trichloroethylene toxicities to rat hepatocytes in primary monolayer culture: its relationship to the level of cytochrome P-450.
The effects of carbon tetrachloride (CCl4) and trichloroethylene (TCE) on the synthesis and the secretion of triacylglycerols (TGs) in primary cultured rat hepatocytes were investigated in relation to the level of cellular cytochrome P-450 (P-450). Pretreatment of rats with phenobarbital (PB) and plating the hepatocytes in the presence of metyrapone attained a marked preservation of P-450 during the preparation of monolayer. CCl4 was able to cause the accumulation of cellular TG in the hepatocytes when the content of P-450 was retained at the level equivalent to that in the liver in vivo.


FDG-PET in carcinoma of the uterine cervix with endometrial extension.
The authors wished to determine whether pretreatment pathologic evidence of endometrial invasion correlated with fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) findings and outcomes in patients with carcinoma of the uterine cervix. Pretreatment whole body FDG-PET was performed in 58 patients with cervical carcinoma who also underwent pathologic evaluation of the endometrium by biopsy or dilation and curettage. FDG-PET lymph node status, disease free survival, and overall survival were evaluated. Thirty seven (64%) patients had pathologic evidence of endometrial invasion. Pelvic lymph node metastases were three times more frequent in patients with evidence of endometrial invasion compared with those without endometrial invasion (70% vs. 23%, P < 0.001). Patients with endometrial invasion also had a significantly increased risk of paraaortic and supraclavicular lymph node metastases at presentation (30% vs. 0% P = 0.006). Endometrial invasion was associated with a decreased 2-year disease-free survival (78% vs. 58%, P = 0.046) and overall survival (92% vs. 65%, P = 0.047). Endometrial extension in cervical cancer correlated strongly with risk of FDG-PET detected lymph node metastases in this study's population and was associated with a poor prognosis.


The effects of dietary cholesterol upon the hypercholesterolemia of pregnancy.
The hypercholesterolemia which accompanies the normal human pregnancy is not known to be influenced by diet or other factors. The present experiment in fourteen pregnant women was designed to document this phenomenon under controlled metabolic conditions and to study the effect of dietary cholesterol upon this usual increase in serum cholesterol. The subjects included twelve normal subjects, one juvenile diabetic, and one type II familial hypercholesterolemic subject. They were fed controlled, nutritionally adequate diets which were equivalent except for the cholesterol content, which was cholesterol-free or 600-1000 mg from egg yolk daily. Calories were adjusted to permit weight gain of 1.4 kg per mo. The cholesterol-free diet lowered th mean serum cholesterol level in the 12 normal pregnant women from 234-187 mg/dl, a 20% decrease (-47 +/- 37 S.D.) (p less than 0.005). The addition of cholesterol to the diet invariably elevated the mean serum cholesterol concentrations to 223 mg/dl, a 19% increase (+36 +/- 12) (p less than 0.001). The mean serum triglyceride levels increased steadily throughout pregnancy regardless of diet, up to 198 +/- 43 (S.D.) mg/dl at term. Both serum cholesterol and triglyceride concentrations decreased strikingly 1 wk after parturition. These serum cholesterol and triglyceride responses occurred similarly in the familial hypercholesterolemic and the diabetic women. The increased serum cholesterol levels during the high cholesterol diets occurred largely in the low density lipoprotein (LDL) fraction. Despite the inevitable alterations of cholesterol and lipoprotein homeostasis which occur in pregnancy, the results of this study indicated that the usual hypercholesterolemia of pregnancy in women eating the general American diet was greatly ameliorated by a very low cholesterol, nutritionally adequate diet.


The rs113883650 variant of SLC7A5 (LAT1) gene may alter brain phenylalanine content in PKU.
Functional alteration of the LAT1 amino acid transporter may be responsible for interindividual differences in cerebral phenylalanine content and the lack of intellectual disability in some patients with untreated phenylketonuria. We assessed the effect of the common variant rs113883650 of the SLC7A5 (LAT1) gene on brain phenylalanine content, as measured with use of magnetic resonance spectroscopy. Our results suggest that the presence of this variant could influence the amount of phenylalanine in the brain.


[Statement of the surgical working group for liver, gall bladder and pancreatic diseases (CALGP) of the German Society for General and Visceral Surgery (DGAV) on rapid report V19-03: association between volume of cases and quality in complex pancreatic surgery].
The Institute for Quality and Efficiency in Health Care (IQWiG) was commissioned by the Federal Joint Committee (G‑BA) to carry out a systematic literature search and assessment of the evidence for the association between the hospital and surgeon volume of cases and the quality of the treatment results in complex pancreatic surgery. The results are presented in the rapid report V19-03. The report confirms an association between the number of cases and the quality of the treatment results in favor of hospitals and surgeons with high volume case numbers; however, a statement with respect to the minimum numbers of complex pancreatic interventions is not given. The surgical working group for liver, gall bladder and pancreatic diseases (CALGP) of the German Society for General and Visceral Surgery (DGAV) comments on these conclusions.


Novel LRAP-binding partner revealing the plasminogen activation system as a regulator of cementoblast differentiation and mineral nodule formation in vitro.
Amelogenin isoforms, including full-length amelogenin (AMEL) and leucine-rich amelogenin peptide (LRAP), are major components of the enamel matrix, and are considered as signaling molecules in epithelial-mesenchymal interactions regulating tooth development and periodontal regeneration. Nevertheless, the molecular mechanisms involved are still poorly understood. The aim of the present study was to identify novel binding partners for amelogenin isoforms in the cementoblast (OCCM-30), using an affinity purification assay (GST pull-down) followed by mass spectrometry and immunoblotting. Protein-protein interaction analysis for AMEL and LRAP evidenced the plasminogen activation system (PAS) as a potential player regulating OCCM-30 response to amelogenin isoforms. For functional assays, PAS was either activated (plasmin) or inhibited (ε-aminocaproic acid [aminocaproic]) in OCCM-30 cells and the cell morphology, mineral nodule formation, and gene expression were assessed. PAS inhibition (EACA 100 mM) dramatically decreased mineral nodule formation and expression of OCCM-30 differentiation markers, including osteocalcin (Bglap), bone sialoprotein (Ibsp), osteopontin (Spp1), tissue-nonspecific alkaline phosphatase (Alpl) and collagen type I (Col1a1), and had no effect on runt-related transcription factor 2 (Runx2) and Osterix (Osx) mRNA levels. PAS activation (plasmin 5 µg/µl) significantly increased Col1a1 and decreased Bglap mRNA levels (p < .05). Together, our findings shed new light on the potential role of plasminogen signaling pathway in the control of the amelogenin isoform-mediated response in cementoblasts and provide new insights into the development of targeted therapies.


Comparative Chloroplast Genomes of Six Magnoliaceae Species Provide New Insights into Intergeneric Relationships and Phylogeny.
Magnoliaceae plants are industrial tree species with high ornamental and medicinal value. We published six complete chloroplast genomes of Magnoliaceae by using Illumina sequencing. These showed a typical quadripartite structure of angiosperm and were 159,901−160,008 bp in size. A total of 324 microsatellite loci and six variable intergenic regions (Pi > 0.01) were identified in six genomes. Compared with five other genomes, the contraction and expansion of the IR regions were significantly different in Manglietia grandis. To gain a more thorough understanding of the intergeneric relationships in Magnoliaceae, we also included 31 published chloroplast genomes of close relative species for phylogenetic analyses. New insights into the intergeneric relationships of Magnoliaceae are provided based on our results and previous morphological, phytochemical and anatomical information. We suggest that the genus Yulania should be separated from the genus Michelia and its systematic position of should be restored; the genera Paramichelia and Tsoongiodendron should be merged into the genus Michelia; the genera Pachylarnax and Parakmeria should be combined into one genus. These findings will provide a theoretical basis for adjusting the phylogenetic position of Magnoliaceae at the molecular level.


The role of interleukin-17A in the pathogenesis of kidney diseases.
Being a member of the IL-17 family, comprising six structurally related ligands, IL-17A is a cytokine, produced by multiple cell types, such as CD4+αβ T cells, γδ T cells, natural killer cells, neutrophils, macrophages, dendritic cells, lymphoid tissue inducer cells, mast cells and plasma cells. IL-17A participates in tissue inflammation by inducing the expression of chemokines, proinflammatory cytokines and matrix metalloproteases. Besides its role in host defence against infectious diseases, IL-17A is involved in different autoimmune and inflammatory diseases. In this review, we will highlight the role of IL-17A in the pathogenesis of acute and chronic kidney diseases. Due to its pleiotropic character, IL-17A is involved in the development of atherosclerosis, hypertension, diabetic nephropathy, ischaemia-reperfusion injury, fibrosis, glomerulonephritis, nephrotic syndrome, minimal change disease and acute renal allograft rejection. In addition, inhibition of IL-17A may be a promising therapeutic target to prevent end-stage renal disease.


Infrared thermography and ulcer prevention in the high-risk diabetic foot: data from a single-blind multicentre controlled clinical trial.
To assess the usefulness of monthly thermography and standard foot care to reduce diabetic foot ulcer recurrence. People with diabetes (n = 110), neuropathy and history of ≥ 1 foot ulcer participated in a single-blind multicentre clinical trial. Feet were imaged with a novel thermal imaging device (Diabetic Foot Ulcer Prevention System). Participants were randomized to intervention (active thermography + standard foot care) or control (blinded thermography + standard foot care) and were followed up monthly until ulcer recurrence or for 12 months. Foot thermograms of participants from the intervention group were assessed for hot spots (areas with temperature ≥ 2.2°C higher than the corresponding contralateral site) and acted upon as per local standards. After 12 months, 62% of participants were ulcer-free in the intervention group and 56% in the control group. The odds ratios of ulcer recurrence (intervention vs control) were 0.82 (95% CI 0.38, 1.8; P = 0.62) and 0.55 (95% CI 0.21, 1.4; P = 0.22) in univariate and multivariate logistic regression analyses, respectively. The hazard ratios for the time to ulcer recurrence (intervention vs control) were 0.84 (95% CI 0.45, 1.6; P = 0.58) and 0.67 (95% CI 0.34, 1.3; P = 0.24) in univariate and multivariate Cox regression analyses, respectively. Monthly intervention with thermal imaging did not result in a significant reduction in ulcer recurrence rate or increased ulcer-free survival in this cohort at high risk of foot ulcers. This trial has, however, informed the design of a refined study with longer follow-up and group stratification, further aiming to assess the efficacy of thermography to reduce ulcer recurrence.


Effects of aging and food restriction on the trigeminal ganglion: a morphometric study.
A quantitative morphometric study of the rat trigeminal ganglion was conducted to determine the changes that occur with aging. All measurements were tracked from young to old age in two rat groups simultaneously. One group was fed ad libitum, the other was maintained on restricted food intake from 6 weeks on. Immunocytochemical and radioimmunoassay techniques were used to study the neuron group that produces the peptide, CGRP and to compare it with the CGRP-negative neuron group. We observed that in the trigeminal ganglion, soma diameters and nucleus diameters of all neurons, whether CGRP positive or negative, increased modestly with age; so did total ganglion weight. Food restriction delayed, but did not prevent the increases in neuron diameters. No significant changes occurred as a function of age in the total number of neurons per ganglion, the ratio of CGRP positive to CGRP negative neurons and ganglion content of CGRP. Food restriction did not affect the parameters that remained constant with age. These findings are in contrast to the marked inhibitory effect of food restriction on age-related increase in thyroid calcitonin, a hormone that is encoded by the same gene as CGRP.


[Mitochondrial reorganization after HCG stimulation of Leydig cells from hypophysectomized hogs].
One to three months after hypophysectomy, porcine Leydig cells contain numerous dense bodies surrounded by a single membrane and crowded with dense rods geometrically arranged. In organotypic culture with HCG they undergo a striking evolution which leads first to intermediate bodies looking like peroxysomes and then to mitochondrial structures. This evolution is quantitatively reduced in a medium without HCG.


Blood flow and electrolytes in spinal cord ischemia.
The contribution of reoxygenation-reperfusion injury to ischemic brain damage has been clearly demonstrated but not in the spinal cord. To evaluate this phenomenon in spinal cord ischemia, we measured spinal cord blood flow (SCBF) by [14C]iodoantipyrine and electrolytes in rabbits after 10 or 40 min ischemia followed by 30 min or 4 days recirculation. Ischemia for 10 or 40 min reduced blood flow in the lower lumbar segments L5-L7 (30 ml/100 g/min) to 5 and 10% of control. After 30 min of recirculation moderate hyperemia (25-40% above control) was observed in segments L5-L7 which was not related to the degree of functional impairment. Na+, water, and Ca2+ increased and K+ decreased after 40 min ischemia, but were unchanged after 10 min ischemia. Recirculation for 30 min after 40 min of ischemia resulted in a progressive rise in Ca2+ which correlated with irreversible spinal cord injury.


Cowden's disease: clinical and molecular genetic findings in a patient with a novel PTEN germline mutation.
We report a 54-year-old woman with Cowden's disease (CD) who was found to carry a novel germline mutation in the PTEN gene. The mutation (c.334C-->G) introduced a splice donor site within exon 5 that caused the expression of an aberrant transcript lacking 159 nucleotides corresponding to codons 112-164. Clinically, the patient showed multiple benign hamartomatous lesions of the skin, papillomatosis of the lips and oral mucosa, polyposis coli and bilateral fibrocystic disease of the breast. In addition, she developed different types of malignant neoplasms, including bilateral carcinomas of the breast and malignant melanomas of the skin. Molecular genetic analysis of a benign skin hamartoma and an invasive ductal breast carcinoma revealed loss of heterozygosity (LOH) at microsatellite markers on chromosome 10 in the carcinoma but not in the hamartoma. The breast carcinoma additionally carried a somatic TP53 point mutation (c.466C-->G; R156G) that was associated with LOH on 17p and nuclear p53 protein accumulation. Taken together, our findings indicate that benign hamartomas in CD may develop without loss of the second (wild-type) PTEN allele, whereas the pathogenesis of malignant tumours, such as breast carcinomas, appears to require the complete inactivation of Pten as well as further alterations such as the loss of p53-dependent growth control.


Comparison of acid/base status in conscious and anaesthetized rats during acute hypothermia.
Acute hypothermia was surface-induced in unrestrained conscious rats at two different levels, moderate (30 degrees C TB) and severe (20 degrees C TB). Data reflecting the acid/base status were determined. The values obtained for moderate hypothermia were compared with the acid/base pattern observed during hypothermia induced by two different anaesthetics, sodium pentobarbital and urethane, at room temperature. Conscious, hypothermic animals developed an apparent respiratory alkalosis, with an increase in pHa (from 7.476 to 7.546 in moderate hypothermia and from 7.484 to 7.563 in severe hypothermia) correlated with a decrease in arterial bicarbonate levels (from 22.9 to 16.8 mmol l-1 and from 20.7 to 14.9 mmol l-1 respectively). Lactate increased slightly in conscious, severely hypothermic rats (1.02 mmol l-1). This acid/base pattern was clearly different from that seen in sodium pentobarbital (mild respiratory acidosis) and urethane-induced hypothermia (metabolic acidosis). These results suggest that conscious rats follow a pattern closer to that underlying the relative alkalinity shown by many poikilotherms than to that underlying the constant pH shown in hibernating mammals. This latter pattern, nevertheless, approaches that observed during moderate pentobarbital hypothermia and the acid/base pattern during shallow hypothermia in birds. Anaesthesia may interfere with the development of the processes that lead to the acid/base pattern observed in conscious animals.


Pyridinium aldoxime analysis by HPLC: the method for studies on pharmacokinetics and stability.
Reversed-phase separation of various pyridinium aldoximes requires a certain concentration of ion-pairing agent, as their chemical structures contain two quaternary amines in the pyridinium ring. Adequate mobile phase is scouted on the basis of retention of pyridinium aldoxime (using the graph of k' versus concentration of an ion-pairing agent) compared to the chromatogram of the background peaks originated from the homogenate. Change in the ion-pairing agent concentration was more expressed for the elution of K-203 than that of the background peaks from the serum, brain and cerebrospinal fluid. Stability of K-203 was investigated using HPLC. Determination of K-203 in tissue samples requires homogenization using either trichloroacetic acid or perchloric acid. Fast degradation takes place at acidic pH. Adjusting pH to neutral in the possible shortest time frame helps to avoid degradation. Degradation of K-203 was easily followed by HPLC separation and monitoring the elution with an ultraviolet absorbance detector at 276 nm. Amperometric detection indicates only the decrease of K-203 content.


The directional effects of passive eye movement on the directional visual responses of single units in the pigeon optic tectum.
We have investigated the visual responses of 184 single units located in the superficial layers of the optic tectum (OT) of the decerebrate, paralysed pigeon. Visual responses were similar to those reported in non-decerebrate preparations; most units responded best to moving visual stimuli, 18% were directionally selective (they had a clear preference for a particular direction of visual stimulus movement), 76% were plane-selective (they responded to movement in either direction in a particular plane). However, we also found that a high proportion of units showed some sensitivity to the orientation of visual stimuli. We examined the effects of extraocular muscle (EOM) afferent signals, induced by passive eye movement (PEM), on the directional visual responses of units. Visual responses were most modified by particular directions of eye movement, although there was no unique relationship between the direction of visual stimulus movement to which an individual unit responded best and the direction of eye movement that caused the greatest modification of that visual response. The results show that EOM afferent signals, carrying information concerning the direction of eye movement, reach the superficial layers of the OT in the pigeon and there modify the visual responses of units in a manner that suggests some role for these signals in the processing of visual information.


Neurosteroid modulation of arterial baroreflex function in the rostral ventrolateral medulla.
Through both genomic and nongenomic actions, ovarian hormones and their metabolites have significant effects on the central nervous system to modulate a variety of regulatory systems, including the cardiovascular system. The major metabolite of progesterone, 3α-hydroxy-dihydroprogesterone, is the most potent endogenous positive modulator of GABA(A) receptors known and central nervous system levels of this progesterone metabolite fluctuate with the ovarian cycle and are elevated in pregnant animals. Pregnancy is associated with attenuated arterial baroreflex sympathoexcitation and increased tonic GABAergic inhibition of the rostral ventrolateral medulla (RVLM) likely contributes. The current experiments were performed to determine if the effects of pregnancy on arterial baroreflex control of renal sympathetic nerve activity could be mimicked by microinjection of the neuroactive progesterone metabolite into the RVLM. Compared to control values, 15 min after microinjection of 3α-hydroxy-dihydroprogesterone into the RVLM (n=10), baseline renal sympathetic nerve activity was decreased to 82% of baseline, and the range (157±10 to 131±11%) and maximum nerve activity (164±9 to 136±12%) for the arterial baroreflex curves were decreased. In contrast, microinjection of the inactive isomer, 3β-hydroxy-dihydroprogesterone into the RVLM (n=9), had no effect on baseline nerve activity or the arterial baroreflex nerve activity range or maximum. Thus, although multiple mechanisms likely contribute to pregnancy associated changes in baroreflex function, these experiments suggest that increased levels of 3α-hydroxy-dihydroprogesterone in the RVLM might contribute.


Investigation of Elekta AQUA software for kilovoltage to megavoltage radiation isocenter coincidence.
Elekta AQUA v2.02 software (Gantry Runout isocenter test) was investigated as a tool for verification of kilovoltage to megavoltage gantry radiation isocenter coincidence. AQUA reported megavoltage (6 MV) isocenter was independent of field size over the range 5 cm × 5 cm to 20 cm × 20 cm. For the 10 cm × 10 cm field size, standard deviation in AQUA reported 3D megavoltage (6MV) isocenter over ten consecutive deliveries was less than 0.04 mm for any axis. Compared to the full AQUA test delivery (Gantry Runout), the shorter AQUA test version (Gantry Runout short) gave a root mean square MV isocenter (± 1 SD) difference of 0.18 mm ± 0.08. Across 7 machines, root mean square differences between AQUA and PIPS PRO reported MV isocenter (for 6 MV and 6 MV FFF beams) was 0.1 mm ± 0.1 mm, with most of the difference observed in the gun-target (Y-axis). AQUA 6 MV isocentre position was offset to gantry relative to Elekta XVI customer acceptance test (CAT) workflow by 0.25 mm to 0.52 mm. For 6 MV FFF beams, AQUA reported an MV isocenter of between 0.27 and 0.39 mm offset to target relative to Elekta CAT.


Noninvasive MRI and multilineage differentiation capability of ferritin-transduced human mesenchymal stem cells.
Molecular imaging can be a breakthrough tool for the investigation of the behavior and ultimate feasibility of transplanted human mesenchymal stem cells (hMSCs) inside the body, and for the development of guidelines and recommendations based on the treatment and evaluation of stem cell therapy for patients. The goals of this study were to evaluate the multilineage differentiation ability of hMSCs expressing an MRI reporter, human ferritin heavy chain (FTH) and to investigate the feasibility of using FTH-based MRI to provide noninvasive imaging of transplanted hMSCs. The transduction of FTH and green fluorescence protein (GFP) did not influence the expression of the mesenchymal stem cell surface markers (CD29+/CD105+/CD34-/CD45-) or the self-renewal marker genes [octamer-binding transcription factor 4 (OCT-4) and SRY (sex determining region Y)-box 2 (Sox-2)], cell viability, migration ability and the release of cytokines [interleukin-5 (IL-5), IL-10, IL-12p70, tumor necrosis factor-α (TNF-α)]. FTH-hMSCs retained the capacity to differentiate into adipogenic, chondrogenic, osteogenic and neurogenic lineages. The transduction of FTH led to a significant enhancement in cellular iron storage capacity and caused hypointensity and a significant increase in R2 * values of FTH-hMSC-collected phantoms and FTH-hMSC-transplanted sites of the brain, as shown by in vitro and in vivo MRI performed at 9.4 T, compared with control hMSCs. This study revealed no differences in biological characteristics between hMSCs and FTH-hMSCs and, therefore, these cells could be used for noninvasive monitoring with MRI during stem cell therapy for brain injury. Our study suggests the use of FTH for in vivo long-term tracking and ultimate fate of hMSCs without alteration of their characteristics and multidifferentiation potential.


Element Effects on High-Entropy Alloy Vacancy and Heterogeneous Lattice Distortion Subjected to Quasi-equilibrium Heating.
We applied Simmons-Balluffi methods, positron measurements, and neutron diffraction to estimate the vacancy of CoCrFeNi and CoCrFeMnNi high-entropy alloys (HEAs) using Cu as a benchmark. The corresponding formation enthalpies and associated entropies of the HEAs and Cu were calculated. The vacancy-dependent effective free volumes in both CoCrFeNi and CoCrFeMnNi alloys are greater than those in Cu, implying the easier formation of vacancies by lattice structure relaxation of HEAs at elevated temperatures. Spatially resolved synchrotron X-ray measurements revealed different characteristics of CoCrFeNi and CoCrFeMnNi HEAs subjected to quasi-equilibrium conditions at high temperatures. Element-dependent behavior revealed by X-ray fluorescence (XRF) mapping indicates the effect of Mn on the Cantor Alloy.


[Cytotoxicity of human T-lymphocytes sensitized by Epstein-Barr virus. Role of HLA antigens at the surface of target cells infected by the virus].
Peripheral T-lymphocytes from patients with infectious mononucleosis are cytotoxic towards target cells from Epstein-Barr virus-genome carrying human lumphoblastoid lines. Thus, these T-cells appear to be sensitized to viral coded determinants. Daudi cells, that carry EBV-genome, but lack HLA antigens are resistant to specific cytolysis in this model. These results suggest direct HLA involvement in the target structure recognized by birus-sensitized cytolytic T-lymphocytes in human.


Finite-size effect on magnetic ordering temperatures in long-period antiferromagnets: holmium thin films.
The thickness dependence of the helical antiferromagnetic ordering temperature T(N) was studied for thin Ho metal films by resonant magnetic soft x-ray and neutron diffraction. In contrast with the Curie temperature of ferromagnets, T(N) was found to decrease with film thickness d according to [T(N)(infinity)-T(N)(d)]/T(N)(d) proportional variant (d-d(0))(-lambda(')), where lambda(') is a phenomenological exponent and d(0) is of the order of the bulk magnetic period L(b). These observations are reproduced by mean-field calculations that suggest a linear relationship between d(0) and L(b) in long-period antiferromagnets.


Anaphylactic reaction and unrelated, subsequent, known side effects during therapy with thiethylperazine.
We report the first case presenting with successive anaphylactic reaction and extra-pyramidal syndrome after treatment with thiethylperazine maleate (thiethylperazine). Both reactions were caused due to this anti-emetic drug, but an additive effect of clemastine fumarate, prescribed to treat the anaphylactic reaction, is suggested by the sequence of events. We discuss the importance of knowing the pharmacological similitudes of common prescribed drugs in order to avoid the occurrence of side effects.


Machine learning for clinical decision support in infectious diseases: a narrative review of current applications.
Machine learning (ML) is a growing field in medicine. This narrative review describes the current body of literature on ML for clinical decision support in infectious diseases (ID). We aim to inform clinicians about the use of ML for diagnosis, classification, outcome prediction and antimicrobial management in ID. References for this review were identified through searches of MEDLINE/PubMed, EMBASE, Google Scholar, biorXiv, ACM Digital Library, arXiV and IEEE Xplore Digital Library up to July 2019. We found 60 unique ML-clinical decision support systems (ML-CDSS) aiming to assist ID clinicians. Overall, 37 (62%) focused on bacterial infections, 10 (17%) on viral infections, nine (15%) on tuberculosis and four (7%) on any kind of infection. Among them, 20 (33%) addressed the diagnosis of infection, 18 (30%) the prediction, early detection or stratification of sepsis, 13 (22%) the prediction of treatment response, four (7%) the prediction of antibiotic resistance, three (5%) the choice of antibiotic regimen and two (3%) the choice of a combination antiretroviral therapy. The ML-CDSS were developed for intensive care units (n = 24, 40%), ID consultation (n = 15, 25%), medical or surgical wards (n = 13, 20%), emergency department (n = 4, 7%), primary care (n = 3, 5%) and antimicrobial stewardship (n = 1, 2%). Fifty-three ML-CDSS (88%) were developed using data from high-income countries and seven (12%) with data from low- and middle-income countries (LMIC). The evaluation of ML-CDSS was limited to measures of performance (e.g. sensitivity, specificity) for 57 ML-CDSS (95%) and included data in clinical practice for three (5%). Considering comprehensive patient data from socioeconomically diverse healthcare settings, including primary care and LMICs, may improve the ability of ML-CDSS to suggest decisions adapted to various clinical contexts. Currents gaps identified in the evaluation of ML-CDSS must also be addressed in order to know the potential impact of such tools for clinicians and patients.


Dietary management of acute childhood diarrhea: optimal timing of feeding and appropriate use of milks and mixed diets.
Several recent clinical trials have examined the optimal timing of feeding and the appropriate foods for use in the dietary management of acute childhood diarrhea. Important methodologic issues relevant to these trials, such as the composition and masking of study diets, measurement of outcome variables, and assessment of nutritional status, are discussed. Available data suggest that feeding should be continued during diarrhea, although a small subgroup of patients receiving nonhuman milk exclusively may have an excess rate of complications. These children should be closely supervised or provided with alternative diets. By contrast, children receiving human milk, nonmilk formulas, and mixed diets are generally able to tolerate these foods and to benefit nutritionally from continued feeding.


Cell forces meet cell metabolism.
Epithelial cells form energetically costly cell-cell adhesions in response to mechanical forces. How cells obtain their energy during this event is unclear. Activity of a key regulator of cell metabolism, the AMP-activated protein kinase (AMPK), is now shown to be mechanoresponsive, and thus can bridge adhesion mechanotransduction and energy homeostasis.


Child passenger fatalities and restraint use in Auckland.
To determine the proportion of children killed as passengers in car crashes who were unrestrained and to estimate the reduction in mortality that might result from increasing child restraint utilisation. All children killed as passengers in car crashes, over the period 1980-90, were identified from the Auckland coroners records. Data were recorded on sex, age, use and type of restraint, position within the motor vehicle, pattern of injuries and place of death. There were 49 children (25 male, 24 female) killed as passengers in car crashes over the study period (2.14/100,000/year). The median age was eight years (range 0-14 years). Of the 38 children for whom restraint use could be determined, 31 (81.6%) were unrestrained and seven (18.4%) were restrained. None of the children aged 0-2 years were restrained. Thirty-five children (71.4%) died at the scene of the crash, three (6.2%) died during transport to hospital, and 11 (22.4%) died in hospital. Based on overseas reports of the efficacy of child restraints, close to half (49%) of all child passenger deaths in Auckland could have been prevented with appropriate child restraint use.


Characterization of the effect of sample quality on high density oligonucleotide microarray data using progressively degraded rat liver RNA.
The interpretability of microarray data can be affected by sample quality. To systematically explore how RNA quality affects microarray assay performance, a set of rat liver RNA samples with a progressive change in RNA integrity was generated by thawing frozen tissue or by ex vivo incubation of fresh tissue over a time course. Incubation of tissue at 37 degrees C for several hours had little effect on RNA integrity, but did induce changes in the transcript levels of stress response genes and immune cell markers. In contrast, thawing of tissue led to a rapid loss of RNA integrity. Probe sets identified as most sensitive to RNA degradation tended to be located more than 1000 nucleotides upstream of their transcription termini, similar to the positioning of control probe sets used to assess sample quality on Affymetrix GeneChip(R) arrays. Samples with RNA integrity numbers less than or equal to 7 showed a significant increase in false positives relative to undegraded liver RNA and a reduction in the detection of true positives among probe sets most sensitive to sample integrity for in silico modeled changes of 1.5-, 2-, and 4-fold. Although moderate levels of RNA degradation are tolerated by microarrays with 3'-biased probe selection designs, in this study we identify a threshold beyond which decreased specificity and sensitivity can be observed that closely correlates with average target length. These results highlight the value of annotating microarray data with metrics that capture important aspects of sample quality.


The osteocalcin gene promoter provides a molecular blueprint for regulatory mechanisms controlling bone tissue formation: role of transcription factors involved in development.
Characterization of regulatory sequences and their cognate binding factors in the bone-specific osteocalcin (OC) gene promoter has provided insight into mechanisms that control expression of the gene under diverse biological conditions. We present evidence for AP-1 motifs and two multipartite conserved regulatory sequences, the OC Box I (nt-99 to-76) and a site designated OC Box II (nt-136 to-130) in contributing to developmental and tissue-specific expression of osteocalcin. OC Box I is characterized by a homeodomain binding site and OC Box II is a recognition sequence for AML-1 (also called PEBP2 alpha), a runt homology-related DNA binding protein. Functional activity of the elements was established in osseous and non-osseous cell lines and is in part related to the binding of osteoblast-specific complexes which enhance OC transcription. The contribution of several elements and binding of multiple classes of transcription factors to independent elements in both these domains serve to illustrate the complexity of control required for tissue-specific OC expression.


Screening clinical breast examination: how often does it miss lethal breast cancer?
Although most American women regularly receive screening clinical breast examination (CBE), little is known about CBE accuracy in community practice. We sought to estimate the rate of cancer detection (sensitivity) of screening CBE performed by community-based clinicians on women who ultimately died of breast cancer, as well as to identify factors associated with accurate detection. We evaluated CBE accuracy among asymptomatic female health plan enrollees in five states (WA, OR, CA, MA, and MN) who received a CBE within 1 year of breast cancer diagnosis and who died of breast cancer within 15 years of diagnosis (N = 485). Sensitivity was estimated as the proportion whose exam was abnormal. Bivariate and logistic regression analyses identified patient characteristics associated with cancer detection. An abnormality was noted on screening CBE in one of five women who ultimately succumbed to breast cancer (sensitivity = 21.6%; 95% confidence interval [CI] = 18.1% to 25.6%). The odds of a true-positive screening CBE (sensitivity) were decreased among women using estrogen (odds ratio [OR] = 0.23; 95% CI = 0.07 to 0.80), receiving a Pap smear during the same visit as CBE (OR = 0.45; 95% CI = 0.27 to 0.72), and with increasing chronic disease comorbidity (P(trend) = .08). Screening CBE as performed in the community may be insufficiently sensitive to detect most lethal breast cancers. Low sensitivity of screening CBE in community practice may be partly attributable to its performance alongside time-consuming clinical tasks such as Pap smear screening or chronic illness care.


What are the rates and validity of French authors' conflicts of interest disclosures in Orthopaedics & Traumatology: Surgery & Research? Analysis of the year 2017 with comparison versus the Transparence.sante.gouv.fr database.
Authors are responsible for their own Disclosure of Interests in submitting to Orthopaedics & Traumatology: Surgery & Research (OTSR). Disclosure may be incomplete or false, by deliberate or unintended omission. Omission may impact the analysis of results or at least the reader's perception of it. The rate of validity of disclosure in OTSR is not known, and we therefore conducted a bibliometric study on articles published in 2017, in order to: 1) determine the proportion of articles in which authors disclose interests; and 2), when interests are disclosed, to assess their validity by comparison against the Transparence.gov.fr database. Disclosure rates exceed 75%. We analyzed all articles published in OTSR in 2017, and extracted those with at least one French author. We also analyzed data from the Transparence.gouv.fr corporate declaration database, for comparison with the authors' own disclosures in each article. Significant interest was defined by a €1000 threshold, although higher thresholds (>€5000, >€10,000 and >€100,000) were also investigated. In 2017, 337 articles were published in OTSR, 210 of which had at least 1 French author. Of these, 201 (95.7%) had at least 1 author with significant interest (>€1000) according to the Transparence data. In 189 of these 201 articles (94%), authors had failed to disclose at least 1 direct or indirect conflict of interest. This omission rate fell to 22/45 (48.9%) for more substantial interests, which were more faithfully disclosed. At the €1000 threshold, in only 8/201 articles (4%) did authors disclose all their interests with perfect validity, but this rate increased up to 25/45 (55.5%) at higher thresholds. At the €1000 threshold, 66 of the 201 articles cited the trade-name of interest, resulting in 54/66 (82%) correct disclosure of direct interest; this rate increased up to 25/26 (96%) at higher thresholds. At a threshold of €1000, the rate of complete and valid disclosure was 4% and the rate of omission 94%. At higher thresholds, rates were better, with just 48.9% omission and, above all, 55.5% validity, even if these rates were lower than hypothesized (75%). Authors and editors need to take greater care. Disclosures were often made, but incompletely, and authors need reminding that they must disclose not only interests related to the article in question but also all interests that might directly or indirectly influence their interpretation of the results reported, allowing readers to make up their own minds. IV; systematic retrospective study.


A phase I dose escalation study of the pharmacokinetics and tolerability of ZK 304709, an oral multi-targeted growth inhibitor (MTGI), in patients with advanced solid tumours.
The toxicities, pharmacokinetics and recommended dose of oral once daily ZK 304709, a novel multi-targeted growth inhibitor (MTGI) with activity against cell-cycle progression and angiogenesis, was investigated in patients by administration for 14 consecutive days followed by 14 days recovery. Patients with solid tumours resistant to standard treatments were enrolled in an accelerated titration design. Thirty-seven patients received ZK 304709 from 15 to 285 mg daily. The most common drug-related adverse events were vomiting, diarrhoea and fatigue. Systemic exposure to ZK 304709 increased with dose up to 90 mg daily but plateaued thereafter, with high inter-individual variability at all doses. Thirteen patients had stable disease as best response as per RECIST criteria. There was no increase in exposure to ZK 304709 with dose escalation above 90 mg, and the MTD was not determined. This study illustrates the importance of phase I pharmacokinetic data to guide dose escalation and drug development.


P-chloromercuribenzene sulfonate blocks and reverses the effect of amiloride on sodium transport across rabbit colon in vitro.
The addition of 10(-3) M p-chloromercuribenzene sulfonate (PCMBS) to the solution bathing the mucosal surface of rabbit colon has no effect on the rate of active Na transport but blocks or reverses the inhibitory action of amiloride. The tissue must be exposed to PCMBS for 20-30 min for a complete blocking effect, and removal of PCMBS from the mucosal solution after this period of exposure does not restore the sensitivity of the tissue to amiloride. The slow time-courses of the blocking and reversal effects suggest that PCMBS does not irreversibly interact with groups directly involved in the binding of amiloride.


1-Year Results From the RANGER II SFA Randomized Trial of the Ranger Drug-Coated Balloon.
This study sought to evaluate the safety and effectiveness of the Ranger drug-coated balloon (DCB) (paclitaxel dose density 2 μg/mm2) for treating superficial femoral artery or proximal popliteal artery lesions. Paclitaxel-coated balloon treatment prevents reinterventions, but dose and coating characteristics differ among balloons and necessitate discrete confirmation of safety and effectiveness. Patients with symptomatic lower limb ischemia (Rutherford classification 2 to 4) were randomized 3:1 to treatment with the Ranger DCB or standard percutaneous transluminal angioplasty (PTA). Twelve-month primary target lesion patency, freedom from major adverse events (i.e., target lesion revascularization, major amputations, death within 1 month of the index procedure), and patient outcomes were analyzed. Mean lesion length was 82.5 ± 48.9 mm for the Ranger DCB group (n = 278) and 79.9 ± 49.3 mm for the control group (n = 98). Ranger DCB was superior to PTA (82.9% [n = 194 of 234] vs. 66.3% [n = 57 of 86]) with observed 12-month primary patency rates yielding a difference of 16.6% (95% confidence interval: 5.5% to 27.7%; p = 0.0013). Noninferior freedom from major adverse events (94.1% [n = 241 of 256] vs. 83.5% [n = 76 of 91]) was demonstrated with a difference of 10.6% (95% confidence interval: 2.5% to 18.8%; noninferiority p < 0.0001). Primary patency rate curves showed significant separation by Kaplan-Meier analysis (log-rank p = 0.0005), with rates of 89.8% and 74.0% estimated at day 365 for the Ranger DCB and PTA cohorts, respectively. The low-dose Ranger DCB demonstrated significantly better effectiveness than standard PTA through 1 year and a good safety profile. (Ranger™ Paclitaxel Coated Balloon vs Standard Balloon Angioplasty [RANGER II SFA]; NCT03064126).


Superior Graft-versus-Host Disease-Free Relapse-Free Survival in Matched Unrelated Donor Hematopoietic Stem Cell Transplantation with Anti-Thymocyte Globulin (ATG) Compared to Matched Related Donor without ATG.
The use of anti-T cell globulin (ATG) in allogeneic stem cell transplantation with matched unrelated donors (MUDs) is considered standard of care in many transplant centers, as these patients are at higher risk of developing acute and chronic graft-versus-host disease (GVHD). Several publications have reported reduced incidence of chronic GVHD compared to matched related donors (MRDs). This may support the idea of introducing ATG in prospective clinical trials, also in MRDs, in an effort to reduce the long-term complications with moderate and severe GVHD. We retrospectively analyzed 169 patients, in whom ATG was given to patients who underwent transplantation with MUDs (n = 124) and not MRDs (n = 45). The incidence acute GVHD II to IV and III to IV was significantly lower in the MUD group compared to the MRD group (28.2% versus 51.3% and 8.1% versus 24.7%). Extensive chronic GVHD incidence was 5% versus 40%. Our results further support the rationale for examining the efficacy of ATG in MRDs in prospective randomized trials.


Biochar addition supports high digestion performance and low membrane fouling rate in an anaerobic membrane bioreactor under low temperatures.
The enhancement effects of biochar to an anaerobic membrane bioreactor (AnMBR) treating sewage at low temperatures was investigated in this study through analyzing organics removal, digestion performance, mixed liquor properties, membrane resistance, and foulant compositions. The chemical oxygen demand (COD) removal efficiency and the COD converted to methane rate increased by more than 12.5% at 10 °C, mainly because of the promotion of biochar to volatile fatty acids degradation. Although biochar caused higher dissolved organic matter (DOM) concentration in the AnMBR, it improved the filtration property of the bulk sludge and absorbed the hydrophobic DOM. The decreased filtration resistance assisted by biochar leads to a prolonged membrane operation duration over 200%. Surface foulants, especially cake foulants, were largely mitigated by the enhanced scouring intensity of mixed liquor at the membrane surface, and hence, decreasing the cake/gel foulants ratio.


B-cell receptor repertoire sequencing: Deeper digging into the mechanisms and clinical aspects of immune-mediated diseases.
B cells play an essential role in adaptive immunity and are intimately correlated with pleiotropic immune-mediated diseases. Each B cell occupies a unique B cell receptor (BCR), and all BCRs throughout our body form "BCR repertoire." With the development of sequencing technology and coupled bioinformatics, accumulating evidence indicates that BCR repertoire largely varies under physiological and pathological conditions. Therefore, comprehensive grasp of BCR repertoire will provide new insights into the pathogenesis of immune-mediated diseases and help exploit efficient diagnostic and treatment strategies. In this review, we start with an overview of BCR repertoire and related sequencing technologies and summarize their current applications in immune-mediated diseases. We also underscore the challenges of this emerging field and propose promising future directions in advancing BCR repertoire exploration.


Statistical optimization of media components for production of extracellular lipase from edible mushroom Cantharellus cibarius.
Cantharellus cibarius is a wild edible mushrooms and considered as a plethora of compounds with potential biotechnological applications. This study highlighted the utilization of C. cibarius mushroom in the production of extracellular lipase under submerged fermentation, representing the first report on lipase production by this mushroom. Various physicochemical factors were optimized via one-factor-at-a time (OFAT) method. Maximum enzyme production was recorded when the mushroom mycelium was grown at 30 °C on pH 6.0 for 96 h in the medium supplemented with 1% [(v/v)] olive oil. Productivity of enzyme was affected by variation in the nitrogen sources, carbon sources, metal ions and NaCl salt. Glucose and peptone significantly enhanced enzyme production as carbon and nitrogen sources, respectively. Stimulatory and inhibitory effects were found by Ca2+ and Zn2+ ions, respectively. Furthermore, Box-Behnken Design (BBD) of Response Surface Methodology (RSM) was employed to optimize the interactive effects of specific media components like glucose, olive oil and CaCl2. The regression model was significant with a coefficient of determination (R2) value of 0.9483. Statistically optimized design (RSM) resulted approximately two-fold increase (23.5-42.283 UmL-1) of lipase production than classical optimization method (OFAT), confirmed the validation of model. The kinetic parameters for p-nitrophenyl palmitate hydrolysis, Km and Vmax were 5.24 mM and 0.768 mmol/min/mg respectively, established a high affinity for the substrate.


Effect of incident angle on weld microstructure and mechanical properties of laser beam welded nitronic -50 austenitic stainless steel joints.
3 mm thick nitronic-50 stainless steel sheets were successfully butt-joined using a 2 kW fiber laser beam welding. Three weld joints were fabricated for different incident angles, namely, 70°, 80° and 90° for the other constant welding process parameters. The effect of incident angle on the weld bead geometry, microstructure evolution, and strength of the laser beam welded joints was studied in detail. The incident angle significantly affected the bead geometry and its orientation. Lowering the incident angle beyond a limit caused the beam shift near the weld root of the joint, where the bead was formed away from the joint line resulting in improper fusion and a defective weld occurred. The microstructure transformed from columnar to an equiaxed dendritic structure at the center of the weld nugget for lower incident angles. Skeletal and lathy ferrite was observed in the joints' weld zone. However, the fraction of lathy ferrite was higher at lower incident angles due to a faster cooling rate. A higher weld joint strength of 1010 MPa (97% of the base metal UTS) was achieved at an 80° incident angle, owing to the formation of more equiaxed dendritic grains and the absence of the secondary phases. All of the tensile test samples showed evidence of ductile failure, and overall, an acceptable level of elongation was achieved.


ZW800-PEG: A Renal Clearable Zwitterionic Near-Infrared Fluorophore for Potential Clinical Translation.
Near-infrared (NIR) fluorescence imaging has advanced medical imaging and image-guided interventions during the past three decades. Despite tremendous advances in imaging devices, surprisingly only a few dyes are currently available in the clinic. Previous fluorophores, ZW800-1A and ZW800-1C, significantly improved the poor performance of the FDA-approved indocyanine green. However, ZW800-1A is not stable in serum and ZW800-1C induces severe stacking in aqueous media. To solve such dilemmas, ZW800-PEG was designed by introducing a flexible yet stable thiol PEG linker. ZW800-PEG shows high solubility in both aqueous and organic solvents, thus improving renal clearance with minimal binding to serum proteins during systemic circulation. The sulfide group on the meso position of the heptamethine core improves serum stability and physicochemical properties including the maximum emission wavelength shift to 800 nm, enabling the use of ZW800-PEG for image-guided interventions and augmenting photothermal therapy.


Serotyping of pneumococci: evaluation of the genetic approach and performance with clinical samples.
Determination of pneumococcal serotypes depends on a successful culture and the Quellung's reaction. However, in 2006, the capsular sequences of 90 different pneumococcal capsular loci were published, thus making "genetic" serotyping via PCR possible. We wanted to determine the reliability of the published primers for the 13 serotypes included in pneumococcal conjugated vaccine 13 (PCV13) with pneumococcal isolates from Germany. We used a multiplex PCR approach and agarose gel detection of amplicons. Three hundred ninety well-characterized strains of Streptococcus pneumoniae and 46 clinical samples were used in the study. A 100% concordance was achieved between PCR and Quellung's reaction. In 7 clinical samples with a PCR positive for S. pneumoniae, we could determine a serotype included in PCV13.


Symptomatic and asymptomatic abnormalities in patients with lumbosacral radicular syndrome: Clinical examination compared with MRI.
To determine the frequency of symptomatic and asymptomatic herniated discs and root compression in patients with lumbosacral radicular syndrome (LRS) and to correlate clinical localization with MRI findings. Fifty-seven patients with unilateral LRS were included in the study. Using the visual analogue scale, two physicians independently localized the most likely lumbar level of complaints. These clinical predictions of localizations were correlated with the MRI findings. MRI showed abnormalities on the symptomatic side in 42 of 57 patients (74%). In 30% of the patients, MRI confirmed an abnormality at the exact same level as determined after clinical examination. On the asymptomatic side, MRI showed abnormalities in 19 of 57 patients (33%), 13 (23%) of these patients had asymptomatic root compression. In more than two-thirds of the patients with unilateral LRS there was no exact match between the level predicted by clinical examination and MRI findings. These discrepancies complicate the decision whether or not to operate.


Predicting early recovery of consciousness after cardiac arrest supported by quantitative electroencephalography.
To determine the ability of quantitative electroencephalography (QEEG) to improve the accuracy of predicting recovery of consciousness by post-cardiac arrest day 10. Unconscious survivors of cardiac arrest undergoing daily clinical and EEG assessments through post-cardiac arrest day 10 were studied in a prospective observational cohort study. Power spectral density, local coherence, and permutation entropy were calculated from daily EEG clips following a painful stimulus. Recovery of consciousness was defined as following at least simple commands by day 10. We determined the impact of EEG metrics to predict recovery when analyzed with established predictors of recovery using partial least squares regression models. Explained variance analysis identified which features contributed most to the predictive model. 367 EEG epochs from 98 subjects were analyzed in conjunction with clinical measures. Highest prediction accuracy was achieved when adding QEEG features from post-arrest days 4-6 to established predictors (area under the receiver operating curve improved from 0.81 ± 0.04 to 0.86 ± 0.05). Prediction accuracy decreased from 0.84 ± 0.04 to 0.79 ± 0.04 when adding QEEG features from post-arrest days 1-3. Patients with recovery of command-following by day 10 showed higher coherence across the frequency spectrum and higher centro-occipital delta-frequency spectral power by days 4-6, and globally-higher theta range permutation entropy by days 7-10. Adding quantitative EEG metrics to established predictors of recovery allows modest improvement of prediction accuracy for recovery of consciousness, when obtained within a week of cardiac arrest. Further research is needed to determine the best strategy for integration of QEEG data into prognostic models in this patient population.


Myocytes from congenital myotonic dystrophy display abnormal Na+ channel activities.
Na(+) currents were measured in myocytes from a fetus with congenital myotonic dystrophy type 1 (DM1) using the patch-clamp whole-cell technique. Steady-state activation and inactivation properties of Na(+) channels were not substantially different between these cells and age-matched control cells. However, a decrease in Na(+) channel density and a faster rate of recovery from inactivation were found in myocytes from congenital DM1 suggesting that changes in functional Na(+) channels may affect cell excitability of muscle cells of patients with this disorder.


The Malaysian HEalth and WellBeing AssessmenT (MyHEBAT) Study Protocol: An Initiation of a National Registry for Extended Cardiovascular Risk Evaluation in the Community.
Cardiovascular disease (CVD) has been a burden to many developing countries for decades, including Malaysia. Although various steps have been taken to prevent and manage CVD, it remains the leading cause of morbidity and mortality. The rising prevalence of CVD risk factors such as hypertension, hypercholesterolaemia, diabetes, overweight and obesity is the main driving force behind the CVD epidemic. Therefore, a nationwide health study coined as the Malaysian Health and Wellbeing Assessment (MyHEBAT) was designed. It aimed to investigate the prevalence of CVD and the associated risk factors in the community across Malaysia. The MyHEBAT study recruited participants (18-75 years old) through community health screening programmes from 11 states in Malaysia. The MyHEBAT study was further divided into two sub-studies, namely, the Cardiovascular Risk Epidemiological Study (MyHEBAT-CRES) and the MyHEBAT Familial Hypercholesterolaemia Study (MyHEBAT-FH). These studies assessed the prevalence of CVD risk factors and the prevalence of FH in the community, respectively. The data garnered from the MyHEBAT study will provide information for healthcare providers to devise better prevention and clinical practice guidelines for managing CVD in Malaysia.


Novel glycoproteins inhibiting the binding of colorectal cancer cells to E-selectin.
Novel glycoproteins carrying sialyl-LeA (SLeA) antigens (SL-GP) were isolated from ascites fluid from a patient with colorectal cancer by immunoaffinity chromatography. Their characteristics, including binding capacity to E-selectin, were investigated. SL-GP showed a typical mucin type amino acid composition in which Ser, Thr and Pro together accounted for greater than 50% of the total amino acid residues. A large amount of carbohydrate (about 80%) was present in SL-GP. The number of O-glycans carrying SLeA antigens comprised about 9% of the total number of O-glycosidic chains. SL-GP could bind to IL-1 beta treated HUVEC, and the binding was inhibited by anti-E-selectin and anti-SLeA monoclonal antibodies. The binding of colorectal cancer cells, LS 180, to HUVEC was assayed in the presence of SL-GP, oligosaccharides prepared from SL-GP and human milk SLeA hexasaccharide. SL-GP inhibited the binding most effectively, whereas equivalent amounts of the SL-GP oligosaccharides and milk SLeA hexasaccharide inhibited it only slightly. These results constitute direct evidence that a unique arrangement of SLeA antigens on the polypeptide chain, probably a cluster, is essential for the binding to E-selectin.


The office of the future: Operational energy consumption in the post-pandemic era.
As a result of COVID-19 and in order to combat the spread of the virus, work-from-home and remote working has become a widely accepted practice in professional settings globally. It is widely known that we are currently experiencing a highly transient period in terms of how we define work. Office work is progressively becoming more collaborative, modern workforce more mobile, and office occupancy more dynamic. As flexible working evolves, it becomes apparent that the role of workspace is also changing. So will the occupancy patterns and operation of office building. Using a mixed-method approach, this paper explores the future of offices, considering flexible working model and investigates the operational energy consumption of UK office buildings in the post-pandemic era. Previous research has shown that office buildings are one of the five largest sectors in the building stock in terms of energy consumption. The results of this study demonstrate that by embracing emerging transitions in hybrid working model and activity-based workspace environments, the energy demand in the office building sector could fall below pre-COVID-19 levels, with significant energy savings reaching up to 50% energy reduction in comparison to the pre-pandemic situation.


Patient Education for Patellofemoral Pain: A Systematic Review.
To evaluate the effect of education interventions compared with any type of comparator on managing patellofemoral pain (PFP). Intervention systematic review. PROSPERO identifier: CRD42018088671. MEDLINE, Embase, CINAHL, and Web of Science were searched for studies evaluating the effect of education on clinical and functional outcomes in people with PFP. Two reviewers independently assessed studies for inclusion and quality. We included randomized controlled trials on PFP where at least 1 group received an education intervention (in isolation or in combination with other interventions). Available data were synthesized via meta-analysis where possible; data that were not appropriate for pooling were synthesized qualitatively. Interpretation was guided by the Grading of Recommendations Assessment, Development and Evaluation approach. Nine trials were identified. Low-credibility evidence indicated that health education material alone was inferior to exercise therapy for pain and function outcomes. Low- and very low-credibility evidence indicated that health professional-delivered education alone produced outcomes similar to those of exercise therapy combined with health professional-delivered education for pain and function, respectively. Health professional-delivered education may produce similar outcomes in pain and function compared to exercise therapy plus health professional-delivered education in people with PFP. J Orthop Sports Phys Ther 2020;50(7):388-396. Epub 29 Apr 2020. doi:10.2519/jospt.2020.9400.


Description of the nationally implemented National Health Service digital diabetes prevention programme and rationale for its development: mixed methods study.
The National Health Service (NHS) Digital Diabetes Prevention Programme (DDPP) is a behaviour change programme for adults in England who are at high risk of developing type 2 diabetes. Four independent providers deliver the NHS-DDPP following a competitive tendering process. Although providers work to a single service specification, there is potential for some variation in the service across providers. This study (1) assesses fidelity of the structural features of the design of the NHS-DDPP compared to the service specification, (2) describes the structural features of delivery of the NHS-DDPP as implemented (3) reports developers' views on how the structural components of the NHS-DDPP were developed and why changes were made following implementation. Using mixed methods, we conducted a document review of providers' NHS-DDPP design and delivery documentation, and extracted information using the Template for Intervention Description and Replication checklist, which was adapted to capture features of digital delivery. Documentation was supplemented by content analysis of interviews with 12 health coaches involved in delivering the NHS-DDPP. Semi-structured interviews were also conducted with 6 programme developers employed by the digital providers. Provider plans for the NHS-DDPP show relatively high fidelity to the NHS service specification. Despite this, there was wide variation in structural features of delivery of the NHS-DDPP across providers, particularly for delivery of 'support' (e.g. use, dose and scheduling of health coaching and/or group support). Interviews with developers of the programmes showed that much of this variation is likely to be attributable to the origin of each provider's programme, which was usually a pre-existing programme that was adapted to conform to the NHS-DDPP service specification. The NHS-DDPP is continually improved and developed based on user experience feedback and research conducted by the providers. Indirect evidence suggests that variation in delivery of support could affect effectiveness of the NHS-DDPP. A priority for future research is ascertaining whether the variation in delivery of the NHS-DDPP across providers is related to any differences in health outcomes. It is recommended that future rounds of commissioning the NHS-DDPP pre-specify the type of support participants should receive, including expected dose and scheduling.


Prevalence, causes and consequences of compassion satisfaction and compassion fatigue in emergency care: a mixed-methods study of UK NHS Consultants.
To estimate prevalence and explore potential causes and consequences of compassion satisfaction and compassion fatigue in UK emergency medicine consultants. A sequential mixed-methods design. Cross-sectional e-survey to all UK NHS emergency medicine consultants (n=1317) including Professional Quality of Life (ProQOL) (compassion satisfaction/fatigue), followed by interviews with consultants scoring above (n=6) and below (n=6) predefined ProQOL thresholds. 681 (52%) consultants responded. Most (98%) reported at least 'average' compassion satisfaction. Higher scores were associated with type of workplace (designated trauma centres faring better) and number of years worked as a consultant (gradually worsen over time, except 20 years onwards when it improves). Consultants with lower (worse) compassion satisfaction scores were more likely to report being irritable with patients or colleagues and reducing their standards of care (a third reported these behaviours at least monthly) and were more likely to intend to retire early (59% had such plans). Key features distinguishing 'satisfied' from 'fatigued' interviewed consultants included having strategies to deal with the high work intensities associated with their role and having positive views of the team within which they worked. The degree of variety in their roles and the ability to maintain empathy for their patients were also distinguishing features between these groups. Findings support an urgent review of workforce and resources in emergency medicine and suggest that a multifactorial approach to identification, prevention and treatment of occupational stress in the workforce is required that considers individual, job and organisational factors, particularly those that impact on perceived control and support at work.


Modified radical neck dissection for metastatic carcinoma of the thyroid. A reappraisal.
From January 1958 through December 1983, 56 modified radical neck dissections were performed on 47 patients with metastases to the cervical nodes from differentiated carcinomas of the thyroid. In nine patients, a second modified radical neck dissection was performed either simultaneously or at a later date. Lymph node clearance was performed on all but one surgical specimen. The number of nodes in each specimen ranged from 10 to 96, and the number of involved nodes ranged from 1 to 20. Thirty-eight of the 56 neck specimens contained four or more positive nodes. Seventeen patients were followed for 10 to 26 years, 18 patients for 5 to 9 years, and 5 patients for less than 5 years. Seven other patients died, three from other causes and four from lung metastases. There were no recurrences in the neck sides that would have been cleared if standard radical neck dissection had been performed. This reappraisal with long-term follow-up supports our initial impression that a modified radical neck dissection sparing the spinal accessory nerve, the sternocleidomastoid muscle, the internal jugular vein, or any combination thereof is an effective procedure for differentiated cancer of the thyroid, with preservation of good shoulder function and improvement in the cosmetic appearance of the neck.


Effect of renin-angiotensin system inhibitors on prevention of peritoneal fibrosis in peritoneal dialysis patients.
Long-term peritoneal dialysis (PD) may lead to peritoneal fibrosis and ultrafiltration failure. It had been demonstrated that the renin-angiotensin system (RAS) plays a key role in the regulation of peritoneal function in rats on PD. We investigated the effects of angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) on long-term PD patients. We analyzed data from 66 patients treated with PD therapy at our centre for at least 12 months retrospectively, during which time at least two peritoneal equilibration tests (PET) were performed. Thirty-eight patients were treated with ACE/angiotensin II (AII) inhibitors (ACE/ARB group); the other 28 received none of the above drugs during the entire follow up (control group). The expression of fibronectin, transforming growth factor-beta1 (TGF-beta1), Aquaporin1 (AQP1) and vascular endothelial growth factor (VEGF) in the overnight effluent were examined by enzyme-linked immunosorbent assay. The demographic data of the two groups showed no difference during the study. No difference between the groups was found with respect to residual renal function (RRF) at the start for both groups by the end of follow up, decreased in the vast majority of patients from both groups (P = 0.014). After 12 months, a significant difference in ultrafiltration was found between the two groups: in the control group it had decreased, while it had not changed in the ACE/ARB group (P < 0.05). In comparison with the baseline level, expression of fibronectin, TGF-beta1 and VEGF in dialysate effluent were significantly increased except for AQP1 in the control group (P < 0.05), but not in the ACE/ARB group (P > 0.05). The findings suggest that ACE/AII inhibitors appeared to have a slower rate of decline in ultrafiltration and RRF, effectively protect against peritoneal fibrosis in long-term peritoneal dialysis. Long-term follow up seems to be required to draw more conclusions.


Measles vaccination in the presence of maternal antibodies primes for a balanced humoral and cellular response to revaccination.
Early or low dose antigen exposure can prime the immune system for subsequent responses; the so-called "prime-boost" effect. In the context of a Sudanese measles vaccine trial, we assessed whether or not such early exposure could influence the response to revaccination. Children received either Connaught high titer vaccine (CN: n = 53; 10(4.7)pfu) or meningococcal A + C vaccine as a placebo (MEN: n = 58) at 5 months of age. At 9 months of age, all received standard titer Schwarz vaccine (SCH: 10(3.9)pfu). Neutralizing antibodies were measured before initial vaccination and at 9 months of age (plaque reduction neutralization assay (PRN)) and again at 5 years of age (syncytium inhibition assay (SIA)). Lymphoproliferative responses to measles virus (MV) antigens were evaluated at 5 years of age. Eleven of the 53 CN-SCH children (21%) had sub-protective neutralizing antibody titers prior to revaccination (log PRN 1.5 +/- 0.03 versus 2.9 +/- 0.07 in the remaining 42 children; P < 0.004). Maternal antibody titers at the time of initial vaccination in these 11 were high (PRN 2.44 +/- 0.12 versus 1.9 +/- 0.04; P < 0.0001). At 5 years of age, neutralizing antibodies were comparable in the 11 CN-SCH poor responders (log SIA 2.1 +/- 0.09), the remaining CN-SCH children (2.2 +/- 0.06) and the MEN-SCH group vaccinated only once at 9 months of age (2.25 +/- 0.06). In contrast, 7/11 of the CN-SCH poor responders (64%) had stimulation indices (SI) > 3 in response to MV antigens at 5 years of age (SI 3.1 +/- 0.6) compared with only 14% in the remaining children of the CN-SCH group (2.0 +/- 0.3; P = 0.05) and 8% in the MEN-SCH group (1.4 +/- 0.2; P < 0.0003). These data suggest that early measles vaccination in the presence of maternal antibodies can sometimes prime for a balanced humoral and cellular immune response to subsequent revaccination.


Estimation of contact time and diffusing capacity for oxygen in the chorioallantoic vascular plexus.
The contact time of erythrocyte in the chorioallantioc capillaries of chicken embryos was estimated by referring to the oxygenation rate measured with a microphotometer. The chorioallantioc membrane was excised from an incubated egg and the SO2 of blood in it's capillary was changed by varying the gas composition around the membrane from the venous blood PO2 level to the air space gas. The oxygenation time (te) required to attain the level of arterialized blood SO2 was measured as the contact time (tc) in the capillaries, which resulted in 0.87, 0.74, 0.57, 0.49 and 0.36 sec for 10, 12, 14, 16 and 18 days of incubation, respectively. The obtained te value coincided with the contact time calculated from the CO diffusing capacity referring to the reaction rate of CO with oxygenated erythrocyte. Using the te value, the diffusing capacity for O2 in the chorioallantoic capillary was calculated; 1.1, 2.2, 4.4, 6.0 and 6.6 x 10(-3) ml-min-1 - mm Hg-1 for the same incubation days as above. The capillary blood volume (Vc) was also estimated, which increased from about 16 to 35 mul during development from 10 to 18 days. The values of DO2 and Vc converted per kg weight of embryo at the days near hatching were similar to those per kg body weight estimated in human lung.


Echinococcus canadensis, E. borealis, and E. intermedius. What's in a name?
The phylogenetic relationships of the G6, G7, G8, and G10 genotypes of Echinococcus granulosus are well defined, but their taxonomic status is currently unresolved. We apply an evolutionary species concept to infer that the G6 and G7 genotypes represent a single species that is different to both the G8 and G10 genotypes, and that the G8 and G10 genotypes are also on different evolutionary trajectories and, therefore, should be regarded as separate species. The names Echinococcus intermedius, Echinococcus canadensis, and Echinococcus borealis have been previously proposed for these three taxa (G6/7, G10 and G8, respectively) and we argue that it may be appropriate to resurrect these names. The correct delimitation and formal recognition of species of Echinococcus may have important veterinary and public health consequences.


Polygon reduction of 3D objects using Stokes' theorem.
Surface over volume rendering can be useful for many applications. However, the tremendously large number of polygons composing the surface primitives should be reduced to a manageable size so as to utilize the capability of low cost hardware and software rendering engines, a standard Internet protocol and VRML format. In this paper, we propose a novel algorithm that deletes several vertices simultaneously by forming a closed arbitrary shaped boundary. The Stokes' theorem, used in electro-magnetic field analysis, was newly adapted to extract the arbitrary shaped boundary. The simultaneous deletion procedure provides a computational gain and increases the reduction ratio without sacrificing the topological distortion of the original mesh. Numerically synthesized polygonal objects and real CT data were tested to evaluate the performance of the new algorithm and to demonstrate the possibility of a medical rendering application. The new algorithm outperforms the conventional decimation algorithm in both computational and reduction efficiency.


e-Health solution for home patient telemonitoring in early post-acute TIA/Minor stroke during COVID-19 pandemic.
When it comes to critical early post-acute TIA/stroke phase, there is a lack of a comprehensive multi-parametric telemonitoring system. The COVID-19 emergency, its related global mobility restrictions and fear of hospitalization further highlighted the need of a comprehensive solution. We aimed to design and test a pragmatic e-Health system based on multiparametric telemonitoring to support of TIA/stroke patients in sub-acute phase during the COVID-19 pandemic. We proposed a telemonitoring system and protocol for TIA/minor stroke patients during COVID-19 pandemic for patients at risk of stroke recurrence. This system involves the use of portable devices for BP/HR/SpO2/temperature sensing, panic-button, gateway, and a dedicated ICT platform. The protocol is a 14-day multiparametric telemonitoring, therapy, and emergency intervention based on vital sign alteration notifications. We conducted a proof-of-concept validation test on 8 TIA/minor stroke patients in the early post-acute phase (< 14 days from ischemic event). The proposed solution allowed to promptly and remotely identify vital sign alterations at home during the early post-acute phase, allowing therapy and behavioral intervention adjustments. Also, we observed a significant improvement of quality of life, as well as a significant reduction of anxiety and depression status. TUQ showed ease of use, good interface quality and high user satisfaction of the proposed solution. The 3-month follow-up showed total adherence of prescribed therapy and no stroke/TIA recurrence or other emergency department admissions. The proposed e-Health solution and telemonitoring protocol may be highly useful for early post-acute remote patient management, thus supporting constant monitoring and patient adherence to the treatment pathway, especially during the COVID-19 emergency.


Circulating and Adipose Tissue Adiponectin Level and Outcomes in Incident Peritoneal Dialysis Patients.
Cardiovascular disease is the major cause of mortality and morbidity in peritoneal dialysis (PD) patients. Adiponectin, a key adipokine, is related to obesity and insulin resistance. We determined the clinical and prognostic value of plasma adiponectin level and its adipose tissue messenger RNA (mRNA) expression in new PD patients. Retrospective analysis of a prospective observational study. 152 new PD patients from a single center; 6 adults undergoing abdominal surgeries without kidney disease served as controls. Plasma adiponectin level and its adipose tissue mRNA expression. Body build and composition, patient and technique survival. Adiponectin level and mRNA expression were grouped in quartiles for correlation analysis for body build and Cox regression for survival analysis. The median plasma adiponectin level was 31.98 μg/mL (IQR, 16.81-49.49 μg/mL), and adiponectin mRNA expression in adipose tissue was 1.65 times higher than in controls (IQR, 0.98-2.63). There was a modest but statistically significant correlation between plasma adiponectin and its adipose tissue mRNA expression (r = 0.40, P < 0.001). Plasma adiponectin level inversely correlated with body mass index, waist-hip ratio, mid-arm circumference, adipose tissue mass, plasma triglyceride (r = -0.39, -0.38, -0.41, -0.38, and -0.30, respectively; P < 0.001 for all), as well as serum insulin level (r = -0.24, P = 0.005). Similar correlations were present but less marked with adipose tissue adiponectin mRNA level. Neither plasma adiponectin level nor adipose tissue adiponectin mRNA level predicted patient or technique survival. Observational study, single center, single baseline measurement. Plasma adiponectin level correlated with the degree of adiposity in new PD patients. However, neither plasma adiponectin level nor its adipose tissue mRNA expression was an independent prognostic indicator in kidney failure patients newly started on PD.


Less approach, more avoidance: Response inhibition has motivational consequences for sexual stimuli that reflect changes in affective value not a lingering global brake on behavior.
Response inhibition negatively impacts subsequent hedonic evaluations of motivationally relevant stimuli and reduces the behavioral incentive to seek and obtain such items. Here we expand the investigation of the motivational consequences of inhibition by presenting sexually appealing and nonappealing images in a go/no-go task and a subsequent image-viewing task. Each initially obscured image in the viewing task could either be made more visible or less visible by repeatedly pressing different keys. Fewer key presses were made to obtain better views of preferred-sex images when such images had previously been inhibited as no-go items than when previously encountered as noninhibited go items. This finding replicates prior results and is consistent with the possibility that motor-response suppression has lingering effects that include global reductions in all behavioral expression. However, for nonpreferred images, prior inhibition resulted in more key presses to obscure their visibility than when such images had not been inhibited. This novel finding suggests that the motivational consequences of response inhibition are not due to a global brake on action but are instead linked to negative changes in stimulus value that induce corresponding increases in avoidance and decreases in approach.


Combination of ablative fractional laser and daylight-mediated photodynamic therapy for actinic keratosis in organ transplant recipients - a randomized controlled trial.
Topical photodynamic therapy (PDT) for actinic keratoses (AK) is hampered by pain during illumination and inferior efficacy in organ-transplant recipients (OTR). We assessed ablative fractional laser (AFL)-assisted daylight photodynamic therapy (PDT) (AFL-dPDT) compared with daylight PDT (dPDT), conventional PDT (cPDT) and AFL alone (AFL) in field treatment of AK in OTR. In each patient, four areas in the same region were randomized to one treatment with AFL-dPDT, dPDT, cPDT and AFL. AFL was delivered with a 2940-nm AFL at 2·3 mJ per pulse, 1·15 W, two stacks, 50-μs pulse-duration, 2·4% density. In dPDT and AFL-dPDT, methyl aminolaevulinate (MAL) was applied for 2·5 h without occlusion during daylight exposure. For cPDT, MAL was occluded for 3 h followed by red-light (630 nm) irradiation at 37 J cm(-2). The primary end-point was complete response (CR) 3 months post-treatment. Sixteen patients with 542 AK (grades I-III) in field-cancerized skin of the scalp, chest and extremities were treated during August and September 2012. After 3 months, CR (AK I-III) rates were 74% after AFL-dPDT, 46% after dPDT, 50% after cPDT and 5% after AFL (P < 0·001). CR rates in AFL-dPDT, dPDT and cPDT were also significantly different (P = 0·004). Median maximal pain scores differed significantly during AFL-dPDT (0), dPDT (0), AFL (0) and cPDT (5) (P < 0·001). Erythema and crusting were more intense following AFL-dPDT than dPDT and cPDT, but only transient hypopigmentation was observed. AFL-dPDT is a novel PDT modality that enhances CR with excellent tolerability compared with dPDT and cPDT in difficult-to-treat AK in OTR.


Posterior ankle arthroscopy for posterior ankle synovitis with an enlarged posterior talar process caused by a cat bite or scratch: A case report.
Legs are sometimes infected and swollen by cat bite or scratch. However, there is no report of synovitis with an enlarged talar posterior process in the posterior ankle caused by a cat bite or scratch which was treated by removal of the enlarged process and synovectomy with release of the flexor hallucis longus tendon via posterior ankle arthroscopy. The patient was a 58-year-old woman who had started keeping a cat 7 months earlier. She subsequently sustained cat bite and scratch wounds to her lower legs, which gradually became increasingly swollen. On presentation, there was left lower leg swelling, particularly on the posterior aspect of the ankle. Imaging revealed bone marrow edema in the enlarged posterior talar process and inflammation of the adjacent soft tissue. We excised the enlarged posterior talar process, performed synovectomy, and released the flexor hallucis longus tendon using a posterior arthroscopic technique via standard posterolateral and posteromedial portals. Microbial culture was negative. The patient returned to daily activities approximately 3 weeks after arthroscopic debridement. There was no recurrence at the 1-year follow-up visit. To our knowledge. We report a rare case of posterior ankle synovitis with an enlarged posterior talar process caused by a cat bite or scratch which was treated successfully by posterior ankle arthroscopic debridement.


Generation of versatile ss-dsDNA hybrid substrates for single-molecule analysis.
Here, we describe a rapid and versatile protocol to generate gapped DNA substrates for single-molecule (SM) analysis using optical tweezers via site-specific Cas9 nicking and force-induced melting. We provide examples of single-stranded (ss) DNA gaps of different length and position. We outline protocols to visualize these substrates by replication protein A-enhanced Green Fluorescent Protein (RPA-eGFP) and SYTOX Orange staining using commercially available optical tweezers (C-TRAP). Finally, we demonstrate the utility of these substrates for SM analysis of bidirectional growth of RAD-51-ssDNA filaments. For complete details on the use and execution of this protocol, please refer to Belan et al. (2021).


Epidemiology and Related Risk Factors of Preterm Labor as an obstetrics emergency.
Preterm birth is still a major health problem throughout the world, which results in 75% of neonatal mortality. Preterm labor not only inflicts financial and emotional distress, it may also lead to permanent disability. The present study was conducted to determine the related risk factors and preventive measures of preterm labor. This retrospective cross-sectional study assessed all preterm labors, as well as an equal number of term labors, during seven years, at an educational hospital. Probable risk factors of preterm labor were collected using medical profiles of participants by the aid of a pre-designed checklist. Significant related factors of preterm labor were used for multivariate logistic regression analysis with SPSS 21.0. 810 cases with the mean age of 28.33 ± 6.1 years were evaluated (48.7% preterm). Multipartite; fetal anomaly; prenatal care; smoking; not consuming folic acid and iron supplements; in vitro fertilization; history of infertility, caesarian section, trauma, systemic disease, and hypertension; amniotic fluid leak; rupture of membranes; cephalic presentation; vaginal bleeding; placenta decolman; oligohydramnios; pre-eclampsia; chorioamnionitis; uterine abnormalities; cervical insufficiency; intercourse during the previous week; short time since last delivery; and mother's weight significantly correlated with preterm labor. Based on the results of the present study, intercourse during the previous week, multipartite, short time from last delivery, preeclampsia, fetal anomaly, rupture of membranes, hypertension, and amniotic fluid leak, respectively, were risk factors for preterm labor. On the other hand, iron consumption, cephalic presentation, systematic disease, history of caesarian section, prenatal care, and mother's weight could be considered as protective factors.


Corticosteroids and Outcomes in Solid Organ Transplant Recipients Infected With Severe Acute Respiratory Syndrome Coronavirus 2.
To examine outcomes in organ transplant and nontransplant patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during the initial 22 months of the pandemic. We used Optum electronic health records to compare outcomes between an adult transplant group and a propensity-matched nontransplant group that tested positive for SARS-CoV-2 from February 1, 2020, to December 15, 2021. Baseline characteristics, hospitalization, intensive care unit admission, mechanical ventilation, renal replacement therapy, inpatient, and 90-day mortality were compared between the transplant and nontransplant groups and among specific transplant recipients. Cox proportional analysis was used to examine hospitalization and mortality by organ transplant, medical therapy, sex, and the period of the pandemic. We identified 876,959 patients with SARS-CoV-2 infection, of whom 3548 were organ transplant recipients. The transplant recipients had a higher risk of hospitalization (30.6% vs 25%, respectively; P<.001), greater use of mechanical ventilation (7.8% vs 5.6%, respectively; P<.001), and increased inpatient mortality (6.7% vs 4.7%, respectively; P<.001) compared with the nontransplant patients. The initiation of mechanical ventilation was significantly more frequent in the transplant group. After adjustment for baseline characteristics and comorbidities, the transplant group had a higher risk of hospitalization (odds ratio, 1.38; 95% confidence interval, 1.19-1.59), without a difference in mortality. In the transplant group, lung transplant recipients had the highest inpatient mortality (11.6%). Among patients with SARS-CoV-2 infection, the transplant recipients were at a higher risk of hospitalization and inpatient mortality; however, mortality was mainly driven by advanced age and comorbidities rather than by transplant status or immunosuppressive medications. Lung transplant recipients had the greatest inpatient and 90-day mortality.


Cheiro-oral-pedal syndrome due to brainstem hemorrhage.
Cheiro-oral-pedal syndrome is characterized by specific sensory disturbance around the corner of the mouth, in the hand and in the foot on the same side. Lesions responsible for causing this syndrome vary. We report two cases of cheiro-oral-pedal syndrome due to midbrain and pontine hemorrhage, respectively. Pontine hemorrhage producing cheiro-oral-pedal syndrome has been reported in three cases, but this is the first case that midbrain hematoma exhibits this syndrome. Damage in the sensory pathway can cause cheiro-oral-pedal syndrome. Difference in the threshold may explain the specific sensory pattern in this syndrome. Cheiro-oral-pedal syndrome is caused by lacunar infarction in majority of the cases. However, it should be kept in mind that hematomas can cause cheiro-oral-pedal syndrome.


Value management and model pluralism in climate science.
Non-epistemic values pervade climate modelling, as is now well documented and widely discussed in the philosophy of climate science. Recently, Parker and Winsberg have drawn attention to what can be termed "epistemic inequality": this is the risk that climate models might more accurately represent the future climates of the geographical regions prioritised by the values of the modellers. In this paper, we promote value management as a way of overcoming epistemic inequality. We argue that value management can be seriously considered as soon as the value-free ideal and inductive risk arguments commonly used to frame the discussions of value influence in climate science are replaced by alternative social accounts of objectivity. We consider objectivity in Longino's sense as well as strong objectivity in Harding's sense to be relevant options here, because they offer concrete proposals that can guide scientific practice in evaluating and designing so-called multi-model ensembles and, in fine, improve their capacity to quantify and express uncertainty in climate projections.


Tophus resolution in patients with chronic refractory gout who have persistent urate-lowering responses to pegloticase.
Pegloticase is a recombinant mammalian uricase conjugated to polyethylene glycol approved in the United States for treatment of chronic refractory gout. It can profoundly decrease serum urate to < 1 mg/dl. In patients receiving pegloticase who did not generate high-titer antidrug antibodies (responders), the serum urate remained low for the duration of therapy, 6 months in the phase III clinical trials plus the open-label extension. The objective of this study was to assess the velocity of tophus resolution in subjects treated with pegloticase. Data from two randomized controlled trials of pegloticase in chronic refractory gout were analyzed. Tophi were assessed by computer-assisted measurements of standardized digital photographs. Subjects were designated as responders and nonresponders based on maintenance of serum urate < 6 mg/dl at months 3 and 6 of treatment. The projected time of complete resolution of all tophi was determined by linear regression analysis. The mean total tophus area at baseline was 585.8 mm2 for responders, 661.5 mm2 for nonresponders, and 674.4 mm2 for placebo-treated patients. Complete resolution at 6 months of at least one tophus was achieved by 69.6% of 23 responders, 27.9% of 43 nonresponders, and 14.3% of 21 patients who received placebo. Complete resolution of all photographed tophi was achieved by 34.8% of biochemical responders, 11.6% of nonresponders, and 0% of placebo-treated patients. The mean velocity of resolution of all tophi was 60.1 mm2/month in responders with a mean projected time of complete resolution of 9.9 months (4.6-32.6 months). There was a significant inverse correlation between serum urate AUC and tophus resolution velocity (r = - 0.40, P = 0.0002), although considerable heterogeneity in the velocity of resolution was noted. The only patient characteristic that correlated with the velocity of tophus resolution was the baseline tophus area. Pegloticase treatment caused a rapid resolution of tophi in responders that correlated with the serum urate lowering associated with this therapy.