[Treatment of pediatric genital condyloma].
Condyloma, also known as venereal warts, are caused by human papillomavirus (HPV). Conventional wart therapies destroy infected keratinocytes rather than directly inhibiting viral infection or replication. No available drug therapy effectively eliminates HPV. Treatments are often disappointing for the patient, the family and the physician due to the duration of the disease and the frequency of recurrences in spite of treatment.


Endogenous opioid mediation of somatostatin inhibition of arginine vasopressin release evoked by insulin-induced hypoglycemia in man.
In order to establish whether endogenous opioids play a role in the control of arginine vasopressin (AVP) response to insulin-induced hypoglycemia by interacting with somatostatin (SRIH), seven normal men were submitted to an insulin (0.15 U/kg) tolerance test (ITT) in the presence or absence of naloxone (10 mg in an i.v. bolus), SRIH (4.1 micrograms/min x 90 min) or the combination of the two substances. Plasma AVP concentrations rose significantly during ITT. The AVP response remained unchanged in the presence of naloxone, whereas it was significantly reduced by the treatment with SRIH. When both SRIH and naloxone were given, the hypoglycemia induced AVP rise was similar to that observed in the control test. These results indicate the involvement of naloxone sensitive endogenous opioids in the mechanism underlying SRIH inhibitory action, but not in the mediation of the AVP response to hypoglycemia.


rs11895168 C allele and the increased risk of breast cancer in Isfahan population.
Some of the single nucleotide polymorphisms in EebB4 gene have been studied to date in order for finding their relevance to the risk of breast cancer. However, no study has been conducted to investigate the importance of rs11895168, a microRNA-related SNP located in ErbB4 3'UTR, in breast tumors. In this paper, we investigated the frequency and association between rs11895168 and breast cancer. The rs11895168 was genotyped in 364 samples collected from 172 breast cancer patients and 192 healthy participants, using Tetra-primer ARMS PCR. The frequency of genotypes was analyzed to find the association between rs11895168 and breast cancer risk and also clinicopathological characteristics of patients. our in silico studies suggested that different alleles at rs11895168 affect the binding strength of miR-1276, a potential tumor suppressor. Statistical analysis showed a significant association between rs11895168 C allele-harboring genotypes and increased breast cancer risk. rs11895168 C allele is strongly and significantly associated with the increased risk of breast cancer and positivity of ER/PR tumor cells.


Opinion survey of health care providers towards psychogenic non epileptic seizures.
Psychogenic non epileptic seizures (PNES) are challenging conditions to diagnose and manage. Previous workers have investigated the opinion of health care providers towards PNES; still several lacunae remain to be stressed. Amongst health care professionals, opinion of nurses has not been adequately explored. We attempted to identify areas which need more emphasis to provide optimal care to the patients. We approached 417 health care providers (HCP; primary care, neurology and in-patient nurses) with a questionnaire regarding their opinion of PNES. Total 115 respondents responded to our survey. We found one-thirds of respondent favoured "non-epileptic seizure" as the preferred diagnostic term. Although majority (61%) of responders felt that PNES were involuntary, 48% of nurses felt that PNES are 'fake' and patients have voluntary control over them. Neurologists and nurses expressed high level of confidence in managing patients of PNES. About 1/3rd (35%) of responders did not feel video EEG (vEEG) to be always required for the diagnosis of PNES. Only a minority (15%) of healthcare providers favor unrestricted driving by patients of PNES in setting of ongoing seizures. Our findings highlight areas where more emphasis needs to be placed regarding PNES amongst HCPs. More emphasis needs to be placed on the involuntary nature of these episodes within the HCP community. It might be necessary to more strongly address the education of nurses and residents for this condition.


Bilateral Radial Head Fractures in a Young Patient: A Rare and Unique Presentation.
Bilateral radial head fractures are a unique and rare presentation. Few studies are available in the literature documenting these type of injuries. We present a rare case of bilateral radial head fractures (Mason type 1) and managed conservatively with full functional recovery. A 20-year-old male sustained bilateral radial head fractures (Mason type 1) following a roadside accident. The patient was managed conservatively with above elbow slab for 2 weeks followed by range of motion exercises. The patient had uneventful follow-up with full range of motion at elbow. Bilateral radial head fractures in a patient are a discreet clinical entity. A high index of suspicion, meticulous history, clinical examination, and appropriate imaging is essential in patients with history of fall on outstretched hands to avoid missing diagnosis. Early diagnosis, proper management, and appropriate physical rehabilitation lead to complete functional recovery.


α-Lipoic acid alleviates myocardial injury and induces M2b macrophage polarization after myocardial infarction via HMGB1/NF-kB signaling pathway.
Myocardial infarction (MI) is a serious cardiovascular disease with a poor prognosis. Macrophages are the predominant immune cells in patients with MI and macrophage regulation during the different phases of MI has important consequences for cardiac recovery. Alpha-lipoic acid (ALA) plays a critical role in MI by modulating the number of cardiomyocytes and macrophages. MI mice were generated by ligating the left anterior descending coronary artery. Macrophages were exposed to hypoxia to establish a hypoxia model and M1 polarization was induced by LPS and IFN-γ. Different groups of macrophages and MI mice were treated with ALA. The cardiomyocytes were treated with various macrophage supernatants and the cardiac function, cytokine levels, and pathology were also analyzed. Factors related to apoptosis, autophagy, reactive oxygen species (ROS), and the mitochondrial membrane potential (MMP) were assessed. Finally, the HMGB1/NF-κB pathway was identified. ALA promoted M2b polarization in normal cells and suppressed inflammatory cytokines during hypoxia. ALA inhibited ROS and MMP production in vitro. Supernatants containing ALA inhibited apoptosis and autophagy in hypoxic cardiomyocytes. Moreover, ALA suppressed the HMGB1/NF-κB pathway in macrophages, which may be a potential mechanism for attenuating MI. ALA alleviates MI and induces M2b polarization via the HMGB1/NF-κB pathway, impeding inflammation, oxidation, apoptosis, and autophagy, and might be a potential strategy for MI treatment.


Heart Failure in Breast Cancer Survivors: Focus on Early Detection and Novel Biomarkers.
Breast cancer survival rate has greatly improved in the last two decades due to the emergence of next-generation anti-cancer agents. However, cardiotoxicity remains a significant adverse effect arising from traditional and emerging chemotherapies as well as targeted therapies for breast cancer patients. In this review, we will discuss cardiotoxicities of both traditional and emerging therapies for breast cancer. We will discuss current practices to detect cardiotoxicity of these therapies with the focus on new and emerging biomarkers. We will then focus on 'omics approaches, especially the use of epigenetics to discover novel biomarkers and therapeutics to mitigate cardiotoxicity. Significant cardiotoxicities of conventional chemotherapies remain and new and unpredictable new forms of cardiac and/or vascular toxicity emerge with the surge in novel and targeted therapies. Yet, there is no clear guidance on detection of cardiotoxicity, except for significant left ventricular systolic dysfunction, and even then, there is no uniform definition of what constitutes cardiotoxicity. The gold standard for detection of cardiotoxicity involves a serial echocardiography in conjunction with blood-based biomarkers to detect early subclinical cardiac dysfunction. However, the ability of these tests to detect early disease remains limited and not all forms of toxicity are detectable with these modalities. There is an unprecedented need to discover novel biomarkers that are sensitive and specific for early detection of subclinical cardiotoxicity. In that space, novel echocardiographic techniques, such as strain, are becoming more common-place and new biomarkers, discovered by epigenetic approaches, seem to become promising alternatives or adjuncts to conventional non-specific cardiac biomarkers.


MicroRNA-Offset RNA Alters Gene Expression and Cell Proliferation.
MicroRNA-offset RNAs (moRs) were first identified in simple chordates and subsequently in mouse and human cells by deep sequencing of short RNAs. MoRs are derived from sequences located immediately adjacent to microRNAs (miRs) in the primary miR (pri-miR). Currently moRs are considered to be simply a by-product of miR biosynthesis that lack biological activity. Here we show for the first time that a moR is biologically active. We demonstrate that endogenous or over-expressed moR-21 significantly alters gene expression and inhibits the proliferation of vascular smooth muscle cells (VSMC). In addition, we find that miR-21 and moR-21 may regulate different genes in a given pathway and can oppose each other in regulating certain genes. We report that there is a "seed region" of moR-21 as well as a "seed match region" in the target gene 3'UTR that are indispensable for moR-21-mediated gene down-regulation. We further demonstrate that moR-21-mediated gene repression is Argonaute 2 (Ago2) dependent. Taken together, these findings provide the first evidence that microRNA offset RNA alters gene expression and is biologically active.


Efficiency of food utilization during fat deposition in the long-distance migratory garden warbler, Sylvia borin.
1 Intake of food, fat, protein and carbohydrates and their fecal output were recorded during the annual body weight cycle of the garden warbler, and old-world longdistance migratory bird species, and the efficiencies of food and nutrient utilization, defined as the ratio (intake-fecal output)/intake, were calculated. 2. Gross food intake and food and nutrient utilization differed significantly between different phases of the birds' body weight cycle. 3. During premigratory fattening, both in "autumn" and "spring", food intake and utilization of fat, protein and carbohydrates were significantly higher than during the low body weight prefattening periods. 4. The increase in efficiency of nutrient utilization accounted for about 1/3 and the increase in gross food intake about 2/3 of all surplus energy for hyperlipogenesis in the premigratory periods of the garden warbler. 5. The seasonal changes in efficiency of food and nutrient utilization seem to be driven by a circannual timing mechanism.


Staining MIF in Cells for Confocal Microscopy.
Confocal microscopy is a powerful technique for immunofluorescence imaging of cells and tissues. The technique allows for detailed analysis of intracellular localization of molecules, as well as three-dimensional representation and analysis of samples, and can be used as a gateway to more advanced techniques, including FLIM-FRET and super-resolution microscopy. Relatively few studies have used confocal microscopy to study intracellular localization of macrophage migration inhibitory factor (MIF) in detail. This chapter outlines basic protocols and tips for staining MIF in fixed cells for confocal analysis.


Animal models of primary biliary cirrhosis.
Primary biliary cirrhosis (PBC) is well known as a disease that predominantly affects women and has been hitherto only described in humans. The absence of an animal model has significantly impaired research into both etiology and treatment. However, in the past 2 years, several spontaneous and two induced models of PBC were described. This article reviews the data on these animal models and places it in the perspective of human PBC and generic autoimmunity.


The effect of stem cell mobilization by granulocyte-colony stimulating factor on neointimal hyperplasia and endothelial healing after vascular injury with bare-metal versus paclitaxel-eluting stents.
The goal of this study was to investigate the effect of mobilized stem cells by granulocyte-colony stimulating factor (G-CSF) on neointimal growth, the biologic impact on vascular healing process, and the utility of paclitaxel-eluting stent (PES) in this circumstance. Questions have been raised on the safety of stem cell mobilization because of the tendency of neointimal overgrowth in a recent clinical trial, despite improvement of cardiac function. Rabbits underwent iliac artery injury with bare-metal stent (BMS) or PES and then received rhG-CSF or placebo for 6 days. Morphometric analysis and scanning electron microscopy for re-endothelialization were performed. The characteristics of mobilized peripheral blood mononuclear cells were determined in vitro, and the fate of these cells was evaluated by re-infusion with tagging in vivo. At day 60 after stenting, neointimal overgrowth was observed at BMS with G-CSF. The tendency of neointimal overgrowth was substantially reduced on PES. Intriguingly, the delayed endothelial recovery on PES was restored to normal after G-CSF treatment. The G-CSF increased not only the endothelial progenitor cells, but also putative smooth muscle progenitor cells. Paclitaxel, at working concentration, preferentially inhibited proliferation of smooth muscle lineage cells rather than endothelial lineage cells. Our findings demonstrate that G-CSF mobilizes putative vascular progenitor cells in peripheral blood, which induces neointimal overgrowth at stented vasculature. Unique differential action of paclitaxel results in the enhanced endothelial healing with reduced neointimal growth after G-CSF treatment, suggesting that drug-eluting stents might be the optimal modality for revascularization in cytokine-based stem cell therapy.


USP7, negatively regulated by miR-409-5p, aggravates hypoxia-induced cardiomyocyte injury.
Hypoxia-induced apoptosis is linked to the pathogenesis of myocardial infarction (MI) and heart failure. Ubiquitin-specific peptidase 7 (USP7) is related to catabolic/pro-apoptotic signaling. However, its role in cardiomyocyte injury is unclear. In this study, we aimed to investigate the role and the underlying regulatory mechanism of USP7 in MI. H9c2 cardiomyocytes were cultured in hypoxia to establish an in vitro model of myocardial hypoxic/ischemic injury. Sprague-Dawley (SD) rats were used to establish animal models with MI. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assays were performed to evaluate the expression levels of miR-409-5p, USP7, and p53, respectively. After USP7 and miR-409-5p were selectively regulated in H9c2 cells, the inflammatory response, apoptosis, and cell viability were detected by ELISA, flow cytometry, and MTT assay, respectively. The interaction between USP7 and miR-409-5p was determined by bioinformatics analysis, qRT-PCR, Western blot, and dual-luciferase reporter assay. LVEF, LVIDd, and LVIDs of rats after MI were also measured. USP7 expression was markedly elevated while miR-409-5p expression was significantly down-regulated in H9c2 cells under hypoxic culture. Augmentation of USP7 expression led to a dramatic promotion of hypoxia-induced apoptosis of cardiomyocytes, accompanied by an increase in the secretion of the cytokines IL-1β, TNF-α, and IL-6. Myocardial injury markers LDH, cTnI, and CK-MB expressions were also increased. Besides, overexpression of USP7 aggravated left ventricular remodeling and decreased left ventricular function of the rats. Conversely, the up-regulation of miR-409-5p expression protected H9c2 cells from apoptosis and inhibited the release of cytokines and myocardial injury. Left ventricular remodeling and left ventricular function were also improved by miR-409-5p overexpression. Furthermore, USP7 was identified as a target of miR-409-5p and the overexpression of miR-409-5p reversed the effects of USP7 on H9c2 cells. USP7 exacerbates myocardial ischemic injury by promoting inflammation and apoptosis of cardiomyocytes, and the up-regulation of its expression is partly caused by the down-regulation of miR-409-5p expression.


Characteristics of gut microbiota in patients with metabolic associated fatty liver disease.
Metabolic associated fatty liver disease (MAFLD) is rising in incidence and is an increasingly common cause of cirrhosis and hepatocellular carcinoma (HCC). Alterations in the gut microbiota have been shown to correlate with the development and progression of MAFLD. However, little is known regarding differences in the gut microbiomes of MAFLD patients and healthy cohorts, and subgroups at the abnormal activity of hepatic enzymes in China. In this study, we enrolled 81 MAFLD patients and 25 healthy volunteers. The fecal microbiota was assessed using 16S rRNA gene sequencing and metagenomic sequencing. The results suggested that Ruminococcus obeum and Alistipes were most enriched in healthy individuals when compared with MAFLD patients. Microbe-set Enrichment Analysis (MSEA) results showed Dorea, Lactobacillus and Megasphaera are enriched in MAFLD group. We also found that Alistipes has negatively related to serum glucose (GLU), gamma-glutamyl transferase (GGT), and alanine aminotransferase (ALT). Moreover, the abundance of Dorea was found to be significantly overrepresented in the MAFLD patients and the degree of enrichment increased with the increasing abnormal liver enzyme. An increase in Dorea, combined with decreases in Alistipes appears to be characteristic of MAFLD patients. Further study of microbiota may provide a novel insight into the pathogenesis of MAFLD as well as a novel treatment strategy.


Long-term motor and sensory outcomes after surgery for the nonaccommodative component of partially refractive accommodative esotropia.
To report long-term motor and sensory outcomes after surgery for the nonaccommodative component of partially refractive accommodative esotropia (PRAET). The medical records of consecutive patients ≤11 years old operated for the nonaccommodative component of PRAET and followed postoperatively for at least 10 years were retrospectively reviewed. A total of 47 patients were included (median age, 3.0 years). The mean postoperative follow-up was 12.15 ± 2.05 years (range, 10.00-17.50 years). Overall, 23 patients (49%) had surgical success; 10 (21%), decompensation; and 7 (15%), esotropia with a high ratio of accommodative convergence to accommodation (AC/A) or consecutive exotropia. The median age at surgery, mean cycloplegic refraction, median near and distance deviation, presence of binocular vision, and amblyopia did not predict decompensation, a high AC/A ratio esotropia, and consecutive exotropia. Eight patients (18%) achieved stereopsis. Patients with an older age at onset (2.87 ± 1.31 years) and a shorter duration of strabismus (≤4 years) achieved better stereopsis. Nearly half of our patients with PRAET achieved a successful ocular alignment after surgery for the nonaccommodative component. Some developed decompensation, a high AC/A ratio esotropia, or consecutive exotropia. Few patients achieved stereopsis. Older age at onset and a shorter duration of strabismus predicted a better stereopsis outcome.


A phylogenetic analysis of Legionella.
Four species of Legionella, L. pneumophila NCTC 11192, L. bozemanii NCTC 11368, L. micdadei NCTC 11371 and L. jordanis ATCC 33623 have been characterized by oligonucleotide cataloguing of their 16S ribosomal RNA. All four species are phylogenetically closely related, while no specific relationship could be detected with any other group of organisms investigated so far with respect to this method. At a low level of relationship legionellae are members of the broad group of purple photosynthetic bacteria and their non-phototrophic relatives, in which Legionella form an independent line of descent.


Quality evaluation of the classical prescription, Danggui Jianzhong decoction, using ultra-high-performance liquid chromatography fingerprint, chemical pattern recognition, and network pharmacology.
Danggui Jianzhong decoction is a classical prescription that has been widely used for thousands of years. However, the quality of this formula is difficult to control owing to its complex chemical component system. In this study, a simple and efficient method comprising ultra-high-performance liquid chromatography fingerprint, chemical pattern recognition, and network pharmacology was established to evaluate the quality of this decoction. A total of 20 common peaks were obtained by fingerprint analysis and 19 chemicals were identified. The fingerprint similarity of 15 batch samples ranged from 0.963 to 0.991. Chemical pattern recognition analysis could clearly classify 15 batches of Danggui Jianzhong decoction into three groups. Further, seven chemical markers were screened out. A herbs-active components-targets-disease network was constructed and enrichment analyses were performed, which indicated that these 19 chemical components are the medicinal substances of Danggui Jianzhong decoction. Further, the mechanism employed by this formula to treat primary dysmenorrhea may be related to the regulation of inflammatory response. In conclusion, this combination approach enables accurate evaluation and prediction of the quality of Danggui Jianzhong decoction, and lays the foundation for studies on the material basis and exploration of the mechanism of Danggui Jianzhong decoction in the treatment of primary dysmenorrhea.


Mixed-mode chromatography characteristics of chiralpak ZWIX(+) and ZWIX(-) and elucidation of their chromatographic orthogonality for LC × LC application.
Two-dimensional liquid chromatography requires orthogonal columns and/or separation principles in the first and second separation dimension. It is sometimes not straightforward to achieve. Chiral columns could expand the toolbox for 2D-LC, but are rarely exploited for this purpose, not least due to missing understanding of retention principles under non-chiral application conditions. To gain more insight, in this study Chiralpak ZWIX(+) and ZWIX(-), based on zwitterionic quinine and quinidine carbamate selectors, were carefully characterized by molecular dynamics simulations, lipophilicity/hydrophilicity measurements of selectors, pH-dependent ζ-potential determinations, and chromatographic characterization in RPLC and HILIC modes combined with unsupervised principal component analysis to extract classification of these columns in comparison to a number of commercial benchmarks (RP, HILIC and mixed-mode columns). The results showed that these chiral columns can be classified as mixed-mode chromatography phases with balanced lipophilic-hydrophilic surface character, excess of negative net charge due to sulfonic acid groups (in spite of weakly basic quinuclidine and quinoline rings), and multimodal applicability (RP, HILIC and polar organic elution modes). Orthogonality mapping in comparison to a number of modern HILIC and mixed-mode columns revealed that Poroshell HILIC-Z (with a zwitterionic ligand on 2.7 μm core-shell particles) can be beneficially combined as second dimension with the ZWIX column for comprehensive LC × LC. The online hyphenation of this 2D-LC system with complementary detection modalities including UV (DAD for chromophoric substances), charged aerosol detection (for universal detection and calibration of non-volatile analytes) and high-resolution mass spectrometry (ESI-QTOF-MS/MS for identification) provided an advanced method for comprehensive impurity profiling, applicable for instance for amino acid pharmaceutical products.


Longitudinal analysis of alcohol use and intimate partner violence perpetration among men with HIV in northern Vietnam.
Alcohol use is a known risk factor for male-perpetrated intimate partner violence (IPV), although few studies have been conducted globally and among men with HIV (MWH). We estimated the longitudinal effects of alcohol use on IPV perpetration among MWH. This study is a secondary analysis of randomized controlled trial data among male and female antiretroviral treatment patients with hazardous alcohol use in Thai Nguyen, Vietnam. Analyses were restricted to male participants who were married/cohabitating (N = 313). Alcohol use was assessed as proportion days alcohol abstinent, heavy drinking, and alcohol use disorder (AUD) using the Timeline Followback and Mini International Neuropsychiatric Interview questionnaire. Multilevel modeling was used to estimate the effects of higher versus lower average alcohol use on IPV perpetration (between-person effects) and the effects of time-specific deviations in alcohol use on IPV perpetration (within-person effects). Participants with higher average proportion days alcohol abstinent had decreased odds of IPV perpetration (adjusted Odds Ratio [aOR] = 0.43, p = 0.03) and those with higher average heavy drinking and AUD had increased odds of IPV perpetration (Heavy drinking: aOR = 1.05, p = 0.002; AUD: aOR = 4.74, p < 0.0001). Time-specific increases in proportion days alcohol abstinent were associated with decreased odds of IPV perpetration (aOR = 0.39, p = 0.02) and time-specific increases in AUD were associated with increased odds of IPV perpetration (aOR = 2.95, p = 0.001). Within-person effects for heavy drinking were non-significant. Alcohol use is associated with IPV perpetration among Vietnamese men with HIV. In this context, AUD and frequent drinking are stronger correlates of IPV perpetration as compared to heavy drinking.


Experimental investigation on sucrose/alumina catalyst coated converter in gasoline engine exhaust gas.
In this study, a modified catalytic converter was employed to treat the harmful exhaust gas pollutants of a twin-cylinder, four-stroke spark-ignition engine. This research mainly focuses on the emission reduction of unburnt hydrocarbons, carbon monoxide, and nitrogen oxides at low light-off temperatures. A sucrolite catalyst (sucrolite) was coated over the metallic substrate present inside the catalytic converter, and exhaust gas was allowed to pass through it. A scanning electron microscope, X-ray diffraction, and Fourier transform infrared spectroscopy were used to investigate the changes in morphology, chemical compounds, and functional group elements caused by the reactions. Catalytic reactions were studied by varying the engine loads and bed temperatures, and the results were compared with those of the commercial catalytic converter. The results show that sucrose present in the catalyst was suitable at low temperatures while alumina was suitable for a wide range of temperatures. In the case of the modified catalytic converter, the maximum catalytic conversion efficiencies achieved for oxidizing CO and HC were 70.73% and 85.14%, respectively, and for reduction reaction at NOx was 60.22% which is around 42% higher than in commercial catalytic converter. As a result, this study claims that sucrolite catalyst is effective for low-temperature exhaust gas.


Changes in QRS segments during exercise in relation to scintigraphic myocardial perfusion defects: a multivariate analysis.
The relation between QRS changes during exercise and ischemic heart disease is controversial. The present investigation addressed whether exercise QRS changes are related 1) to myocardial ischemia or necrosis, 2) to possibly confounding factors such as baseline QRS size and changes in heart rate and ST magnitude during exercise, and 3) to the location of scintigraphic defects. Advanced computerized vectorcardiography (MIDA1000, Ortivus Medical AB, Sweden) was recorded in 71 consecutive patients referred for 201TI exercise myocardial scintigraphy. Maximal exercise tests were performed in the sitting position on a bicycle ergometer. Planar scintigraphic images were obtained immediately after exercise and 4 hours later in three projections, and were evaluated blindly. Exercise QRS changes correlated to baseline QRS size (X, Y, and Z leads; P < 0.005), change in heart rate (X and Y leads; P < 0.01), and ST change at J + 20 ms (X, Y, and Z leads; P < 0.0001). Increased QRS magnitudes in the Y and Z leads correlated to late perfusion defects (P < 0.0001). These correlations remained after correction for baseline QRS size and changes in heart rate and ST magnitude at J+20 ms during exercise (P < 0.0001). No consistent relationships were observed between the location of myocardial perfusion defects and the stress-induced alterations in QRS. Baseline QRS size and changes in heart rate and ST magnitude may have important confounding effects on the QRS response to exercise. However, even after consideration of these factors, the QRS response to exercise was related to late (4 h) scintigraphic myocardial perfusion defects. The findings suggest that the presence of myocardial infarctions or long-lasting ischemia after exercise is associated with increased QRS magnitudes during exercise.


[Decrease of the contraction force of skeletal muscle in mammals by the potassium channel activator, SR 44866].
The ATP-sensitive K channel opener, SR 44866, was applied to intact extensor digitorum muscle of the mouse. Electrically stimulated maximal twitch contractions of the muscle were decreased by SR 44866 with a KD of 7.4 microM and a Hill coefficient of 1.2 at 34 degrees C. The effect of SR 44866 was antagonized by glibenclamide and reduced at 24 degrees C. We suggest that these results represent the consequence of activation of ATP-sensitive K channels in mammalian skeletal muscle.


Semi-supervised WCE image classification with adaptive aggregated attention.
Accurate abnormality classification in Wireless Capsule Endoscopy (WCE) images is crucial for early gastrointestinal (GI) tract cancer diagnosis and treatment, while it remains challenging due to the limited annotated dataset, the huge intra-class variances and the high degree of inter-class similarities. To tackle these dilemmas, we propose a novel semi-supervised learning method with Adaptive Aggregated Attention (AAA) module for automatic WCE image classification. Firstly, a novel deformation field based image preprocessing strategy is proposed to remove the black background and circular boundaries in WCE images. Then we propose a synergic network to learn discriminative image features, consisting of two branches: an abnormal regions estimator (the first branch) and an abnormal information distiller (the second branch). The first branch utilizes the proposed AAA module to capture global dependencies and incorporate context information to highlight the most meaningful regions, while the second branch mainly focuses on these calculated attention regions for accurate and robust abnormality classification. Finally, these two branches are jointly optimized by minimizing the proposed discriminative angular (DA) loss and Jensen-Shannon divergence (JS) loss with labeled data as well as unlabeled data. Comprehensive experiments have been conducted on the public CAD-CAP WCE dataset. The proposed method achieves 93.17% overall accuracy in a fourfold cross-validation, verifying its effectiveness for WCE image classification. The source code is available at https://github.com/Guo-Xiaoqing/SSL_WCE.


Ribosomal protein S19 deficiency leads to reduced proliferation and increased apoptosis but does not affect terminal erythroid differentiation in a cell line model of Diamond-Blackfan anemia.
Diamond-Blackfan anemia (DBA) is a congenital red-cell aplasia in which 25% of the patients have a mutation in the ribosomal protein (RP) S19 gene. It is not known how the RPS19 deficiency impairs erythropoiesis and proliferation of hematopoietic progenitors. To elucidate molecular mechanisms in RPS19-deficient DBA, we analyzed the effects of RPS19 deficiency on erythropoietin (EPO)-induced signal transduction, cell cycle, and apoptosis in RPS19-deficient TF-1 cells. We did not find any abnormality in EPO-induced signal transduction. However, RPS19-deficient TF-1 cells showed G0/G1 arrest (82% vs. 58%; p < .05) together with accumulation of p21 and p27. The fraction of apoptotic cells detected by Annexin V analysis also increased compared with control cells (13% vs. 3.1%; p < .05). Western blot analysis of apoptosis-related proteins showed that the level of bcl-2 and Bad was decreased and Bax was increased in RPS19-deficient TF-1 cells. Moreover, primary CD34-positive cells from DBA patients detected by Annexin V analysis also generated a higher number of apoptotic cells compared with normal CD34-positive cells during in vitro culture (38% vs. 8.9%; n = 5; p < .001). Finally, we show that although RPS19 silencing reduces EPO-induced development of erythroid progenitors expressing glycophorin A (GPA), RPS19 silencing in cells already expressing GPA does not affect GPA expression. These findings indicate that RPS19 deficiency causes apoptosis and accelerated loss of erythroid progenitors in RPS19-deficient DBA.


A new 5-HT2 antagonist (ritanserin) in the treatment of chronic headache with depression. A double-blind study vs amitriptyline.
The exact relationship between depression and chronic headache remains unclear. Considerable clinical and pharmacological evidence suggests the existence of a common biological terrain. Many antidepressant drugs are effective in the treatment of migraine and chronic headache disorders. Ritanserin, a new very selective serotonin-2 (5-HT2) antagonist, has recently shown both analgesic and antidepressant properties. The present study compares in a double-blind design, the effectiveness of ritanserin and amitriptyline, a well-known antidepressant extensively used in migraine prophylaxis. Thirty-eight patients (30 females and 8 males ranging in age from 20 to 50 yrs) were classified according to the International Headache Society criteria as: patients with chronic tension-type headache (CTH) (11 cases) and patients with coexisting migraine and CTH (MCTH) (27 cases). Only patients with a score equal to or higher than 18 on the Hamilton Rating Scale for Depression (HRSD) were included. Ritanserin was highly effective in reducing Pain Total Index and analgesic consumption in chronic headache, and its activity was similar to that observed during amitriptyline treatment. A significant improvement of HRSD and HRSA (Hamilton Rating Scale for Anxiety) scores was observed during both treatments. The main results of our study concern the demonstration of antiheadache and antidepressive properties of ritanserin. To better define the profile of the patients and their clinical responsiveness to the treatment, dexamethasone suppression test, clonidine test and nociceptive flexion reflex were investigated in our patients. Our data confirm the usefulness of these methods as markers of chronic headache with depression.


The role of surgery in primary osteomyelitis of the chest wall.
Seven patients with primary osteomyelitis of the chest wall are described. All patients presented with pain at the site of infection, and four patients had a tumor-like mass that could easily be confused with a neoplastic process. All were heroin addicted and pseudomonas was the most common organism cultured. Conservative management with antibiotics for a minimum of 4 weeks is recommended with operation assuming a secondary role, namely, to assist in the initial diagnosis or in the form of limited resection of residual sinuses. Primary wide resection is discouraged.


A Randomized Double-Blind Placebo-Controlled Clinical Study to Evaluate the Effect on the Weight of a Medical Device with Polyglucosamine L112 in a Group of Overweight and Obese Subjects.
Overweight and obesity have reached epidemic proportions and safe treatments are needed to heal these diseases. The objective of this study is to examine the activity of a medical device based on polyglucosamine polymers (PG) on body weight (BW) reduction, insulin resistance, and the serum levels of fat-soluble vitamins and glucosamine. A double-blind placebo-controlled interventional study comparing PG and a placebo (PL) was conducted. One hundred and fifty overweight or obese cases were treated, divided into two groups for a period of 90 days at the dosage of 3 g/day. One hundred and nineteen cases (58 with PG and 61 with PL, respectively) concluded the treatment. PG was more effective than the PL on the reduction of BW and insulin resistance. No modification of fat-soluble vitamins (Vit A, E, D3, K1) and glucosamine levels was shown. Total cholesterol levels were significantly more reduced in the PG group compared to the PL group as it was for subjects with a BW decrease of >5%. PG acts as a safe medical device, is not absorbed, and binds lipids in the upper gastrointestinal tract, reducing their availability, with a significant activity on the reduction of BW, insulin resistance, and cholesterol levels without the modification of fat-soluble vitamins.


Exploring fragment-based target-specific ranking protocol with machine learning on cathepsin S.
Cathepsin S (CatS), a member of cysteine cathepsin proteases, has been well studied due to its significant role in many pathological processes, including arthritis, cancer and cardiovascular diseases. CatS inhibitors have been included in D3R-GC3 for both docking pose prediction and affinity ranking, and in D3R-GC4 for binding affinity ranking. The difficulties posed by CatS inhibitors in D3R mainly come from three aspects: large size, high flexibility and similar chemical structures. We have participated in GC4; our best submitted model, which employs a similarity-based alignment docking and Vina scoring protocol, yielded Kendall's τ of 0.23 for 459 binders in GC4. In our further explorations with machine learning, by curating a CatS specific training set, adopting a similarity-based constrained docking method as well as an arm-based fragmentation strategy which can describe large inhibitors in a locality-sensitive fashion, our best structure-based ranking protocol can achieve Kendall's τ of 0.52 for all binders in GC4. In this exploration process, we have demonstrated the importance of training data, docking approaches and fragmentation strategies in inhibitor-ranking protocol development with machine learning.


The peroxisome: an update on mysteries 2.0.
Peroxisomes are key metabolic organelles, which contribute to cellular lipid metabolism, e.g. the β-oxidation of fatty acids and the synthesis of myelin sheath lipids, as well as cellular redox balance. Peroxisomal dysfunction has been linked to severe metabolic disorders in man, but peroxisomes are now also recognized as protective organelles with a wider significance in human health and potential impact on a large number of globally important human diseases such as neurodegeneration, obesity, cancer, and age-related disorders. Therefore, the interest in peroxisomes and their physiological functions has significantly increased in recent years. In this review, we intend to highlight recent discoveries, advancements and trends in peroxisome research, and present an update as well as a continuation of two former review articles addressing the unsolved mysteries of this astonishing organelle. We summarize novel findings on the biological functions of peroxisomes, their biogenesis, formation, membrane dynamics and division, as well as on peroxisome-organelle contacts and cooperation. Furthermore, novel peroxisomal proteins and machineries at the peroxisomal membrane are discussed. Finally, we address recent findings on the role of peroxisomes in the brain, in neurological disorders, and in the development of cancer.


Stroke Following Coronavirus Disease 2019 Vaccination: Evidence Based on Different Designs of Real-World Studies.
We aimed to evaluate whether coronavirus disease 2019 (COVID-19) vaccination was associated with stroke. We conducted a systematic meta-analysis of studies using cohort, self-controlled case series (SCCS), and case-crossover study (CCOS) designs to evaluate incidence risk ratios (IRRs) and 95% confidence intervals (CIs) of ischemic stroke (IS), hemorrhagic stroke (HS), and cerebral venous sinus thrombosis (CVST) following COVID-19 vaccination. Risks of stroke were pooled among subpopulations categorized by vaccine type, dose, age, and sex. Sensitivity analysis was performed by different defined risk periods. Fourteen studies involving 79 918 904 individuals were included. Cohort studies showed decreased risks of IS (IRR, 0.82 [95% CI, .75-.90]) and HS (IRR, 0.75 [95% CI, .67-.85]) postvaccination, but not CVST (IRR, 1.18 [95% CI, .70-1.98]). SCCS identified increased risks 1-21 days postvaccination (IRRIS, 1.05 [95% CI, 1.00-1.10]; IRRHS, 1.16 [95% CI, 1.06-1.26]) or 1-28 days postvaccination (IRRIS, 1.04 [95% CI, 1.00-1.08]; IRRHS, 1.37 [95% CI, 1.15-1.64]), similar to CVST (IRR, 1.58 [95% CI, 1.08-2.32]). CCOS reported an increased risk of CVST after ChAdOx1 vaccination (IRR, 2.9 [95% CI, 1.1-7.2]). Although different study designs yielded inconsistent findings, considering the relatively low background incidence of stroke and benefits of vaccination, even a potentially increased risk of stroke postvaccination should not justify vaccine hesitancy.


Prognostic significance of several biomarkers in epithelial ovarian cancer: a meta-analysis of published studies.
Abnormal expression of several biomarkers might predict disease prognosis and response to chemotherapy in patients with epithelial ovarian cancer (EOC). However, the published data are inconsistent. Eligible studies that investigated the association between survival or response to platinum-based chemotherapy in EOC and the expression status of Bcl-2, EGFR, GST, LRP, p16, p21, P-gp and TNF-α were identified by an electronic search of PubMed and Embase. The measures of interest were hazard ratio (HR) for survival or risk ratio for chemotherapy response. A meta-analysis was performed using the fixed-effect or random-effect models. The number of eligible studies analyzed was 27 for Bcl-2, 22 for EGFR, 29 for GST, 12 for LRP, 16 for p16, 22 for p21, 27 for P-gp and three for TNF-α. A meta-analysis showed that high EGFR and P-gp expression was associated with poor overall survival (OS) (pooled adjusted HR = 1.826 and HR = 1.822). Only high GST expression was associated with improved OS (HR = 0.780). Furthermore, high p16 and P-gp expression was associated with poor progression-free survival (PFS) (HR = 1.550 and HR = 2.136). High GST expression was associated with improved PFS (HR = 0.689). Among these factors, only LRP, P-gp and TNF-α were associated with response to platinum-based chemotherapy. The markers we analyzed are unlikely to be useful as predictors of prognosis and response to platinum-based chemotherapy in EOC patients in clinical practice.


Cross-sectional and pulsed Doppler echocardiography of the atrioventricular junction of hearts with univentricular atrioventricular connexion.
The atrioventricular junction of 52 consecutive patients with univentricular atrioventricular connexion was examined by cross-sectional and pulsed Doppler echocardiography. The echocardiographic features were then compared with catheterisation and cineangiographic findings. In the diagnosis of the mode of atrioventricular connexion, cross-sectional echocardiography was superior to cineangiography in differentiating single inlet with absence of one atrioventricular connexion from double inlet with a common atrioventricular valve. Straddling atrioventricular valves were diagnosed by echocardiography alone. Using pulsed Doppler echocardiography, the diagnostic sensitivity of atrioventricular valvar regurgitation was 92.6% and the specificity 100%. By mapping the regurgitant jet with pulsed Doppler echocardiography, an index was derived to evaluate the severity of atrioventricular valvar regurgitation. The indices obtained correlated well with cineangiographic grading on a three-point scale (Spearman rank correlation coefficient: rs = 0.9). Thus, cross-sectional echocardiography coupled with a range-gated Doppler system provide accurate anatomical details of the atrioventricular junction and reliable assessment of atrioventricular valvar regurgitation in patients with univentricular atrioventricular connexion.


Bipolar II disorder family history using the family history screen: findings and clinical implications.
Psychiatric family history of bipolar II disorder is understudied. The aims of the current study were to find the psychiatric family history of bipolar II patients using a new structured interview, the Family History Screen by Weissman et al (2000), and to find bipolar disorders family history predicting power for the diagnosis of bipolar II. One hundred sixty-four consecutive unipolar major depressive disorder (MDD) and 241 consecutive bipolar II major depressive episode (MDE) outpatients were interviewed with the Structured Clinical Interview for DSM-IV (SCID). The Family History Screen was used. Sensitivity and specificity of predictors of the diagnosis of bipolar II (bipolar [type I and II] family history, bipolar II family history, atypical depression, depressive mixed state, many MDE recurrences, early onset) were studied. Bipolar II subjects had significantly more bipolar I, more bipolar II (50.7%), more MDE, and more social phobia in first-degree relatives than did unipolar subjects. Bipolar II subjects had many more first-degree relatives with bipolar II than with bipolar I. Among the predictors of the diagnosis of bipolar II, bipolar II family history had the highest specificity (82.8%), while early onset had the highest sensitivity. Discriminant analysis of predictor variables found that bipolar II family history and early onset were highly significant predictors. In conclusion, bipolar II family history was common in bipolar II patients, and it had high specificity for predicting bipolar II. If detected, it could reduce bipolar II misdiagnosis by inducing careful probing for a history of hypomania.


Cerebellar ependymoma with overlapping features of clear-cell and tanycytic variants mimicking hemangioblastoma: a case report and literature review.
Imaging and histology of clear-cell ependymoma and cerebellum-based hemangioblastoma are similar; distinguishing between them is a diagnostic challenge. A 62-year-old Chinese woman presented with an intermittent headache of 8 years' duration. Computed tomography and magnetic resonance imaging revealed a mass in the cerebellum. Neurological imaging suggested hemangioblastoma (HB). Histologically, the tumor included cellular and paucicellular areas, in which cells were arranged in nests or diffusely distributed; and a highly vascular area, in which tumor cells were arranged in clusters and separated by capillaries. At low magnification, the tumor mimicked cellular HB, but at high magnification, tumor cells showed clear cytoplasm instead of the vacuolated cytoplasm typically observed in HB. Moreover, spindly, bipolar elements resembling tanycytes were observed within the nest structures. Although these features indicated the possibility of ependymoma, neither true ependymal rosettes nor an ependymal-lined profile was observed. The tumor was characterized by prominent vascularity, but glomeruloid formation was absent. We saw pleomorphism in foci of some tumor giant cells, but pathologic mitosis and palisaded necrosis were absent. Most tumor cells were positive for glial fibrillary acidic protein and S100. Epithelial membrane antigen was expressed with a paranuclear dot-like or a ring-like pattern. The Ki-67 index was approximately 2%. Considering the patient's symptom, neurological imaging, and pathological findings, she was diagnosed as cerebellar ependymoma (WHO grade II). Here, we report a case of ependymoma with overlapping clear-cell and tanycytic features, and review the literature to evaluate its real incidence. Pathologists should consider this rare diagnosis when confronted with a similar presentation.


Surgical treatment of congenital hyperinsulinism.
A multidisciplinary approach to patients with congenital hyperinsulinism (HI) can distinguish focal from diffuse HI, localize focal lesions, and permit partial pancreatectomy with cure in almost all focal patients. Surgery does not cure diffuse disease but can help prevent severe hypoglycemia and brain damage. Surgery can be curative for insulinoma and for some cases of atypical HI.


Specific gravity test strips used in monitoring urine concentrations of urolithiasis patients.
Current therapy for urolithiasis patients includes instructions to increase water intake and 24-hour urine output. Previous studies have measured changes in the 24-hour urine volume to evaluate the efficacy of fluid therapy in each patient. We used paper test strips to monitor urine pH and specific gravity in 22 of our stone clinic patients: 10 were instructed to increase water intake just before the study (group 1) and 12 were not so instructed (group 2). Mean specific gravities of 1.0222 (1.0238 corrected for pH) for group 1 and 1.0197 (1.0220 corrected for pH) for group 2 did not differ significantly. Urine specific gravities also were compared for 3 intervals: 1 to 9 a.m., 9 a.m. to 5 p.m. and 5 p.m. to 1 a.m. Of the 22 patients 10 (3 from group 1 and 7 from group 2) had significant diurnal variations in the urine specific gravities, corrected and uncorrected, among these 3 periods. In addition, both groups had a significantly higher mean specific gravity from 1 to 9 a.m. (1.0234 uncorrected and 1.0248 corrected) than from 9 a.m. to 5 p.m. (1.0194 uncorrected and 1.0218 corrected). The 5 p.m. to 1 a.m. (mean of 1.0220 uncorrected and 1.0239 corrected) specific gravity did not differ significantly in either group. If 1.015 is the highest acceptable specific gravity of urine in stone patients, the findings suggest inadequate dilution of urine in these patients, whether or not they were instructed to increase water intake. Also, the significant diurnal variation in urine specific gravity would allow a nighttime triggering event at these hours of higher urine concentration.


Gene Expression in Bronchial Epithelial Cell Responses to Vanadium Exposure.
Vanadium exposure has the adverse effect on lung function in human, whereas the detailed mechanisms of vanadium exposure-induced pulmonary toxicity are limited. Hence, the present study aimed to investigate the hub genes and signaling pathways related to sodium metavanadate (SMV)-induced pulmonary toxicity. The transcript expression profile GSE36684 downloaded from Gene Expression Omnibus contained eight human bronchial epithelial cell (HBEC) samples including five SMV-treated and three control HBEC samples. Totally 455 differentially expressed genes (DEGs) were screened, especially 201 and 254 genes were up- and down-regulated in the HBECs treated with SMV. Gene ontology analysis suggested that the DEGs were mainly involved in signal transduction, the response to drug, cell proliferation, adhesion, and migration. Pathway analysis demonstrated that the DEGs were primarily participated in NF-κB, Wnt, MAPK, and PI3K-Akt signaling pathways. Moreover, the hub genes, including ITGA5, ITGB3, ITGA2, LAMC2, MMP2, and ITGA4, might contribute to SMV-induced pulmonary toxicity. Our study improves the understanding of the molecular mechanisms by which SMV induced the pulmonary toxicity.


Diet and carcinogenesis: historical perspectives.
Some 40-50 years ago, experiments with animals began to provide conclusive evidence that diet can significantly influence carcinogenesis. Underfeeding or severe restriction of caloric intake to between one-half and two-thirds of normal had a general inhibitory effect on development of tumors of various types. On the other hand, high fat diets were found to enhance tumor yields relative to low fat diets. The effect of dietary fat was shown to be independent of caloric intake and was more selective for certain types of tumors. Both dietary fat and caloric restriction appear to exert their effects mainly at the promotional stage of carcinogenesis, although the exact mechanisms are not known. Interest in the role of diet in carcinogenesis has been revived in recent years by epidemiologic data that show correlations between certain dietary constituents, such as dietary fat, and cancer incidence at particular sites in the body and mortality. These epidemiologic observations have, in turn, led to an increase in research on effects of diet on carcinogenesis in animal models.


Biochemical characterization of a T-lymphoma-specific 90,000 molecular weight disulfide linked dimeric glycoprotein.
The biochemical features of a membrane antigen detected by a mouse monoclonal antibody (A1) raised against the murine thymoma cell line EL4 are described. This reagent detected a novel disulfide-linked 90,000 mol. wt dimeric membrane glycoprotein composed of two chains of approx 45,000 mol. wt. Endo-beta-N-acetylglucosaminidase F digestion generated a single 28,000 polypeptide, thus suggesting that the A1 molecule is a homodimer. No structural homology between the A1 molecule and the human T 90/44 protein (9.3 antigen) could be revealed by peptide mapping analysis. In view of the fact that three polypeptides of mol. wts 28,000-30,000, 21,000 and 15,000 respectively co-precipitated with the A1 antigen, the possible relationship of the A1 molecular complex to other known T-cell surface antigens including the antigen receptor is discussed.


Production of artificial fingermarks. Part I - Synthetic secretions formulation.
Fingermark variability is a critical parameter. To mitigate the effects of this variability, synthetic secretions in the form of simple mixtures of target compounds found in eccrine sweat have been described in the literature, but they are usually reactive towards only a minimal range of detection techniques. If this approach is acceptable for the production of single-technique test strips, such artificial secretions cannot be considered as reliable fingermark simulants because they do not reproduce the complex matrix that makes up real secretions. Research has shown that sebaceous and eccrine compounds are probably present simultaneously in fingermark residue in the form of an emulsion. This paper is the first part of a research project that aims at producing realistic artificial fingermarks containing an extensive range of eccrine and sebaceous compounds. This first study aimed to reproduce and compare two synthetic fingermark residues formulations and assess their potential to be used as fingermark simulants. Spot tests of the artificial secretions were deposited on paper substrates, and their reactivity with four common detection techniques was tested: 1,2-indanedione-zinc, ninhydrin, oil red O, and physical developer. Both formulations showed very good results when processed with the two amino acid reagents, as well as oil red O, and no obvious differences were observed between the two versions. The results obtained with the physical developer were inconsistent and demonstrated that the fundamental working principle of physical developer needs to be further understood. The results were extremely promising as they showed the potential of such reproducible artificial secretions to be used to assess an extensive range of detection techniques, which would be highly beneficial to guarantee better research and quality control in fingermark detection. The use of spot tests to deposit the simulant was shown to be unreliable and a more controllable and reproducible deposition method using an inkjet printer will be presented in the second part of this research.


Data in support of DPF2 regulates OCT4 protein level and nuclear distribution.
DPF2, also named ubi-d4/requiem (REQU), interacts with a protein complex containing OCT4. This paper provides data in support of the research article entitled "DPF2 regulates OCT4 protein level and nuclear distribution". The highlights include: (1) Denature-immunoprecipitation assay revealed ubiquitination of OCT4 in pluripotent H9 cells, which was enhancedby MG132, a proteasome inhibitor. (2) Well colocalization of ectopic OCT4 and FLAG-Ub was found in HeLa cells, which was also increased by MG132. (3) MG132 treatment decreased DPF2 cytoplasmic expression in vivo. These data give insights into how proteasome inhibition contributes to studying ubiquitnation of OCT4.


[The patient's team and the responsible doctor as a condition for efficient patient courses].
In the healthcare system in The North Denmark Region the patient's team has been implemented in order to create and ensure efficient patient courses. Each patient has his or her own team, which is responsible for the entire patient course. As part of the team there is one doctor, who has the ultimate responsibility for the patient's treatment and pathway within the healthcare system. The patient's team is implemented in 2015-2017 in the healthcare system in The North Denmark Region.


"Dermal dendritic cells" comprise two distinct populations: CD1+ dendritic cells and CD209+ macrophages.
A key cell type of the resident skin immune system is the dendritic cell (DC), which in normal skin is located in two distinct microanatomical compartments: Langerhans cells (LCs), mainly in the epidermis, and dermal DCs (DDCs), in the dermis. Here, the lineage of DDCs was investigated using monoclonal antibodies and immunohistology. We provide evidence that "DDC" comprise at least two major phenotypic populations of dendritic-appearing cells, immature DC expressing CD1, CD11c and CD208; and macrophages expressing CD209, CD206, CD163, and CD68. These data suggest that dermal dendritic-appearing macrophages comprise a novel part of the innate immune response in the resident skin immune system.


A technique to reconstruct the anal sphincters following iatrogenic stretching related to a pull-through for Hirschsprung disease.
Soiling and fecal incontinence are troubling complications which can occur after a pull-through for Hirschsprung disease. They can usually be improved with proper medical management, but in some cases are the result of an anatomic defect related to overstretching of the sphincters and/or damage of the anal canal. For such patients the treatment of this true fecal incontinence is limited to a structured bowel management program with ante- or retrograde enemas to achieve social continence. Herein we report two such patients with overstretched sphincters and loss of the dentate line after an initial pull-through and describe a sphincter tightening technique to improve bowel control.


Cost effectiveness of hepatitis A/B versus hepatitis B vaccination for US prison inmates.
Hepatitis B immunization is provided in many US prison systems. We examined the cost effectiveness of substituting bivalent hepatitis A/B vaccine in this setting, considering regional variation in hepatitis A risks and the potential for disease transmission by former prisoners. Where hepatitis A rates are >200, 100-200, and <100% the national average, declines in hepatitis A treatment costs would offset 137, 88, and 40% of the bivalent vaccine's added cost. In the three regions considered, cost effectiveness would be US$ <0, 2131, and 22,819 per life-year saved, respectively. Prison-based hepatitis A/B immunization would meet accepted standards of cost effectiveness throughout the US.


Non-communicable disease prevention in Kosovo: quantitative and qualitative assessment of uptake and barriers of an intervention for healthier lifestyles in primary healthcare.
Smoking, physical inactivity, low fruit and vegetable consumption, and obesity are common in Kosovo. Their prevention is a priority to relieve the health system of from costly non-communicable disease treatments. The Accessible Quality Healthcare project is implementing a primary healthcare intervention that entails nurse-guided motivational counselling to facilitate change in the domains of smoking, diet, alcohol consumption and physical inactivity for at-risk patients. This study quantitatively assesses the uptake of motivational counselling and the distribution of health behaviours and stages of health behaviour change of the participants according to the intervention, as well as qualitatively describes experiences and perceived benefits of motivational counselling. Study participants (n = 907) were recruited consecutively in 2019 from patients visiting the Main Family Medical Centres in 12 municipalities participating in the Kosovo Non-Communicable Disease Cohort study as part of the Accessible Quality Healthcare project. For the quantitative study, we used baseline and first follow-up data on smoking status, physical inactivity, obesity, fruit and vegetable as well as alcohol consumption, uptake of counselling, and stages for behavioural change. For the qualitative study, in-depth interviews were conducted with a subset of 26 cohort participants who had undergone motivational counselling. Motivational counselling was obtained by only 22% of the eligible participants in the intervention municipalities. Unhealthy behaviours are high even in persons who underwent counselling (of whom 13% are smokers; 86% physically inactive; 93% with inadequate fruit and vegetable consumption; and 61% are obese); only the rate of smoking was lower in those who obtained counselling. Among smokers, over 80% were still in the pre-contemplation phase of behaviour change. More advanced stages of behaviour change were observed among the highly prevalent group of inactive persons and participants with poor dietary habits, among the 5 intervention municipalities. According to the qualitative study results, the participants who obtained motivational counselling were very satisfied with the services but requested additional services such as group physical activity sessions and specialized services for smoking cessation. More tailored and additional primary health care approaches in accordance with patients' views need to be considered for the motivational counselling intervention to reach patients and efficiently facilitate lifestyle behaviour change.


Neurogenic astrocytes transplanted into the adult mouse lateral ventricle contribute to olfactory neurogenesis, and reveal a novel intrinsic subependymal neuron.
Spatially and temporally restricted populations of neurogenic astrocytes can generate multipotent neurospheres in vitro. To examine the ability of neurogenic astrocytes to respond to in vivo differentiation cues within a germinal matrix, we provided cultured neonatal cerebellar astrocytes access to the subependymal zone (SEZ) by grafting them directly into the lateral ventricle of adult mice. Here we report three events that follow such transplants. 1) Donor cells attach to periventricular structures, and form "neoplastic-like" spheres that penetrate the ventricular wall. These attached spheres can persist for months, as they give rise to "clones" of cells that infiltrate forebrain parenchyma. 2) Many donor cells enter the rostral migratory stream and migrate into the olfactory bulb where a small percentage differentiates as olfactory interneurons. 3) Finally, within the SEZ, some donor cells formed cell clusters that appear to interact with the SEZ neuronal precursor chains, and some donor cells differentiate into distinctive neurons with extensive, beady projections precisely confined between the ependymal layer and the striatum. Further analysis of normal SEZ anatomy reveals indigenous neurons with identical morphologies--some of which are contacted by 5-HT+ fibers--that we propose represent a heretofore uncharacterized, intrinsic SEZ neuron of unknown function. These results suggest that cultured astrocytes derived from non-SEZ brain regions can respond in different ways to in vivo cues provided by the adult lateral ventricle and SEZ by differentiating into neurons that eventually inhabit both the olfactory bulb and SEZ proper.


Community-acquired Klebsiella pneumoniae meningitis in an alcoholic patient with an infected pancreatic pseudocyst; a case report and review of literature.
We report a case of a 49-year-old male with a history of chronic alcoholism and evidence of a pancreatic pseudocyst on CT scanning. He presented with a 3-days history of fever, loss of appetite and upper abdominal pain. Blood cultures grew Klebsiella pneumoniae and he improved clinically with a seven-day course of intravenous co-amoxiclav and metronidazole. Two weeks later he was readmitted to hospital with impaired consciousness and septic shock, and died three days later in intensive care. Post mortem examination revealed bacterial meningitis and an infected pancreatic pseudocyst. Klebsiella pneumoniae was isolated from the pancreas and meninges.


Phase I study of pegylated liposomal doxorubicin, paclitaxel, and cisplatin in patients with advanced solid tumors.
The combination of doxorubicin, paclitaxel, and cisplatin has activity in gynecologic malignancies but requires colony stimulating factor (G-CSF) support. Moreover, there is concern about cardiotoxicity with doxorubicin/paclitaxel combinations. Pegylated liposomal doxorubicin may result in less myelosuppression and cardiac toxicity than free doxorubicin. The purpose of this study was to determine the maximal tolerated dose of pegylated liposomal doxorubicin with fixed doses of paclitaxel and cisplatin without using G-CSF support in advanced solid malignancies. Twenty-three patients were enrolled; none of the patients had received prior doxorubicin. Patients received paclitaxel (90 mg/m2 for dose level one, escalating to 135 mg/m2 for all subsequent dose levels), with a fixed dose of cisplatin (60 mg/m2), followed by escalating doses of pegylated liposomal doxorubicin every 21 days. A total of 73 cycles was administered. Grade 4 neutropenia was seen after cycle one in two of eight patients receiving 30 mg/m2 of pegylated liposomal doxorubicin and three of seven patients receiving 40 mg/m2 of pegylated liposomal doxorubicin when combined with 135 mg/m2 of paclitaxel and 60 mg/m2 of cisplatin. Two additional patients at the 40 mg/m2 dose level developed grade 4 neutropenia following cycles 2 and 5. The mean decline in left ventricular ejection fraction (LVEF) after 2 cycles was 5 percentage points (P = 0.012). The combination of pegylated liposomal doxorubicin, paclitaxel and cisplatin is feasible without G-CSF support.


Quantitation of leukotaxis in agarose by three different methods.
The agarose method for measuring chemotaxis has been rigorously examined by a variety of quantitative approaches, including measurements of the distance of cell migration ('leading front'), counts of total numbers of migrated cells, and counts of migrated cells in single planes. These methodologies are described in detail. It is demonstrated for the first time that the results are dependent on the concentration of chemotactic factor. Results obtained by the three quantitative methods are similar. Measurement of cells migrating in a single plane is preferable because this method is reliable and relatively simple. The assay conforms to a pattern determined by checkerboard analysis that confirms a true chemotactic response.


Growth-associated protein 43 is down-regulated in cultured astrocytes.
Growth-associated protein 43 (GAP-43: other designations--pp46, F1, B-50, p-57) is an abundant, neural, membrane-associated protein involved in synaptic plasticity and regeneration. We recently reported that GAP-43 is present in plasma membranes of cultured rat astrocytes. In the present study the level of astrocytic GAP-43 was assessed by indirect immunofluorescence labeling of cells with a specific anti-GAP-43 serum and immunoblotting of plasma membrane proteins. The results indicate that all astrocytes from 1-day-old cortex contained GAP-43 and those differentiated in culture did not. Furthermore, GAP-43 decreased dramatically during 3 weeks in culture. These results are consistent with the developmental down-regulation of GAP-43 in vivo.


Diagnosis of herpesvirus infections: correlation of Tzanck preparations with viral isolation.
Evaluation of Giemsa-stained smears of scrapings from the base of vesicles or ulcers ( Tzanck preparation) for the presence of multinucleated giant cells and/or intracellular inclusions were diagnostic for herpesvirus in 18 of 21 cases (86%) of culturally proved herpesvirus infections. Smears from four patients with varicella-zoster infection also revealed cytologic alterations characteristic of herpesvirus.


Acceptance and importance of clinical pharmacists' LIMM-based recommendations.
The objective of this study was to evaluate the quality of the clinical pharmacy service in a Swedish hospital according to the Lund Integrated Medicine Management (LIMM) model, in terms of the acceptance and clinical significance of the recommendations made by clinical pharmacists. The clinical significance of the recommendations made by clinical pharmacists was assessed for a random sample of inpatients receiving the clinical pharmacy service in 2007. Two independent physicians retrospectively ranked the recommendations emerging from errors in the patients' current medication list and actual drug-related problems according to Hatoum, with rankings ranging between 1 (adverse significance) and 6 (extremely significant). The random sample comprised 132 patients (out of 800 receiving the service). The clinical significance of 197 recommendations was assessed. The physicians accepted and implemented 178 (90%) of the clinical pharmacists' recommendations. Most of these recommendations, 170 (83%), were ranked 3 (somewhat significant) or higher. This study provides further evidence of the quality of the LIMM model and confirms that the inclusion of clinical pharmacists in a multi-professional team can improve drug therapy for inpatients. The very high level of acceptance by the physicians of the pharmacists' recommendations further demonstrates the effectiveness of the process.


[The dynamic hematological indices in alcoholic intoxication in relation to the ecological situation].
Comparative investigations of conventional male rat red blood with modelling of chronic alcohol-toxic influence of different types were carried out. Even a short alcohol intoxication developing against the background of ecologically unfavourable factors of the environment was shown to cause rapid development of decompensation of the blood system protective mechanisms. In these cases hematologic picture resembled that after long and hard alcohol abuse.


Estimation of molecular averages and equilibrium fluctuations in lipid bilayer systems from the excess heat capacity function.
It is demonstrated that the bilayer partition function can be numerically obtained from scanning calorimetric data without assuming a particular model for the gel-liquid crystalline transition. From this partition function, the enthalpy, entropy and volume changes accompanying the transition can be calculated. In the limit of very large systems, the method of the grand partition function allows calculation of cluster model distribution functions from which average sizes of gel and liquid-crystal clusters, cluster densities and equilibrium fluctuations are obtained. These results indicate that the main transition in phospholipid bilayers proceeds through the formation of clusters and that these clusters are not static domains but highly fluctuating entities. These fluctuations in cluster size are approximately equal to the average cluster size and give rise to localized density and volume fluctuations. The magnitude of these fluctuations is affected by the radius of curvature of the bilayer and by the addition of small molecular weight compounds to the system.


Fusion between uninfected cells in retrovirus-induced fusion-from-within.
We previously examined Moloney murine leukemia virus-induced fusion-from-within (FFWI) and fusion-from-without (FFWO) of SC-1 mouse cells. FFWI and FFWO can be distinguished by their stimulation by ionophores and polycations, respectively. FFWI is caused by infected cells. Normally, fusion between an infected cell and uninfected cells (heterofusions) is described, but we have surprisingly found that the infected cells also caused homofusion between uninfected cells in their vicinity (named neighbor homofusions). It was shown that neighbor homofusions were not induced by free virus particles (by FFWO). Transfectants expressing envelope proteins only induced heterofusions, indicating that virus production is necessary for the formation of neighbor homofusions. Both plasma membrane fragments and easily removable material from the surface of infected cells were able to induce fusion with the same stimulation pattern as FFWI and neighbor homofusion. These materials, especially the latter, have properties in common with virions, and it is discussed whether immature virions are involved in the formation of the neighbor homofusions.


Studying the impact of translational genomic research: Lessons from eMERGE.
Two major goals of the Electronic Medical Record and Genomics (eMERGE) Network are to learn how best to return research results to patient/participants and the clinicians who care for them and also to assess the impact of placing these results in clinical care. Yet since its inception, the Network has confronted a host of challenges in achieving these goals, many of which had ethical, legal, or social implications (ELSIs) that required consideration. Here, we share impediments we encountered in recruiting participants, returning results, and assessing their impact, all of which affected our ability to achieve the goals of eMERGE, as well as the steps we took to attempt to address these obstacles. We divide the domains in which we experienced challenges into four broad categories: (1) study design, including recruitment of more diverse groups; (2) consent; (3) returning results to participants and their health care providers (HCPs); and (4) assessment of follow-up care of participants and measuring the impact of research on participants and their families. Since most phases of eMERGE have included children as well as adults, we also address the particular ELSI posed by including pediatric populations in this research. We make specific suggestions for improving translational genomic research to ensure that future projects can effectively return results and assess their impact on patient/participants and providers if the goals of genomic-informed medicine are to be achieved.


Preoperative prediction and risk assessment of microvascular invasion in hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is one of the most common and highly lethal tumors worldwide. Microvascular invasion (MVI) is a significant risk factor for recurrence and poor prognosis after surgical resection for HCC patients. Accurately predicting the status of MVI preoperatively is critical for clinicians to select treatment modalities and improve overall survival. However, MVI can only be diagnosed by pathological analysis of postoperative specimens. Currently, numerous indicators in serology (including liquid biopsies) and imaging have been identified to effective in predicting the occurrence of MVI, and the multi-indicator model based on deep learning greatly improves accuracy of prediction. Moreover, several genes and proteins have been identified as risk factors that are strictly associated with the occurrence of MVI. Therefore, this review evaluates various predictors and risk factors, and provides guidance for subsequent efforts to explore more accurate predictive methods and to facilitate the conversion of risk factors into reliable predictors.


Sensitivity for Change Analyses of the Patient-Reported Outcomes in Obesity (PROS) Questionnaire: A Prospective Cohort Study.
Many patients seeking bariatric surgery experience reduced health-related quality of life (HRQOL). A simple clinical tool, the Patient-Reported Outcomes in Obesity (PROS), was developed to address patients' HRQOL concerns during clinical consultations and facilitate meaningful dialogue. The present study aims to explore its sensitivity to change. A prospective study of patients undergoing bariatric surgery was conducted. The patients responded to items on the PROS and the Obesity-related Problems Scale (OP) before surgery and three, 12 and 24 months after surgery. Longitudinal mixed-effects models were applied to estimate the change in PROS and OP scores over time. Thirty-eight patients were included. A significant change over time was detected for the PROS with the largest effect size at 24 months (effect size -1.34, p ˂ 0.001), while the corresponding effect size for the OP was -1.32 (p ˂ 0.001). In all items of the PROS, the majority of patients responded not bothered at 24 months. The items physical activity, pain, sleep and self-esteem showed the largest change in the percentage of patients reporting not bothered from baseline to 24 months after surgery. The PROS is sensitive to change over time and may be used as a brief, easy to administer tool to facilitate a conversation about obesity-specific quality of life in clinical consultations.


Mast cells infiltration and decreased E-cadherin expression in ketamine-induced cystitis.
Ketamine is a controlled substance and often illegally used as a recreational drug primarily by young adults. Increasing ketamine abusers associated with lower urinary tract symptoms have been reported at hospitals in recent years. Here we used a murine model to explore the changes of bladder in order to elucidate its pathogenesis. ICR mice were randomly distributed into control and ketamine groups and received daily intraperitoneal injection of saline and ketamine (30 mg/kg), respectively. The bladders were excised and processed for histology at 4, 8 and 12 weeks. Tryptase and E-cadherin were investigated by immunohistochemistry in bladder tissues from ketamine-treated and control mice to assess the mast cell activation and junction protein expression. After ketamine treatment, the bladder changed to be hyperemic, inflamed, and with more fissures in mucosa. Compared with control group, the number of tryptase-positive mast cells significantly increased, which was 6.98 ± 2.89 and 23.00 ± 6.48 cells per field (100×) at 8 and 12 weeks, respectively (P = 0.016 and P = 0.003, respectively). Additionally, the expression of E-cadherin in ketamine-treated mice bladder tissue was significantly lower than that in the control tissues, P < 0.001. Increased mast cells in bladder wall and downregulated expression of E-cadherin junction protein in epithelial cells were probably associated with interstitial inflammation and fissures in mucosa. It implied that ketamine induced an interstitial cystitis.


Cysteamine selectively enhances neuropeptide Y2 receptor binding activity.
Affinity labeling of [125I]NPY to the bovine hippocampal NPY receptor has revealed a 50 kDa specific binding protein, the Y2 receptor. Cysteamine (10 microM - 10 mM) specifically enhanced NPY specific labeling of the Y2 receptor without affecting cross-linking efficiency. Several structurally related agents, including reduced glutathione, cysteine, beta-mercaptoethanol and ethanolamine, were without effect on receptor binding. The enhancement of binding by cysteamine could be reversed by washing the membranes. These studies suggest that cysteamine may change the conformation of the NPY Y2 receptor and increase its binding activity.


Characterization of secondary ultrasonic waves radiated by two oscillating bubbles.
A bubble oscillating under an ultrasonic wave produces an interference sound field with the incident ultrasonic wave, forming fringe patterns of trapped microbubbles. We discuss secondary ultrasonic waves radiated by two oscillating bubbles in the incident ultrasonic wave in terms of both theory and experimental conditions. Two oscillating bubbles produce an inherent secondary wave field that varies with the distance between the two bubbles and the phases of these waves. Here we discuss the Bjerknes force derived for two bubbles and microbubble trapping around the bubbles. The experiments were carried out using microbubbles produced with an ultrasonic contrast agent (Levovist). The microbubble-trapping pattern observed around the bubbles in the experiment closely agrees with the numerical simulation.


Differential regulation of alpha 2u globulin gene expression in liver, lachrymal gland, and salivary gland.
The alpha 2u globulins, products of a highly homologous multigene family, are synthesized in the liver and submaxillary salivary glands of the rat. Although their precise function has not been ascertained, they are of interest because of the complex developmental and hormonal regulation of their tissue levels. We now report that alpha 2u globulin is synthesized in a third tissue of the rat, the extraorbital lachrymal gland. Immunocytochemical studies indicate that the distribution of alpha 2u globulin is more homogeneous in the lachrymal gland than in the liver or submaxillary gland. In situ hybridization to alpha 2u globulin RNA reveals specific signal only over the acinar cells of the lachrymal gland. Several different isoelectric forms of alpha 2u globulin are encoded by lachrymal gland mRNA. The major lachrymal and salivary gland isoforms are indistinguishable from one another, but more acidic than the hepatic isoforms. In addition, analysis of double-stranded cDNAs with a diagnostic restriction-enzyme pair detects no differences between the alpha 2u globulin mRNAs of lachrymal and salivary gland, but clearly distinguishes these from their hepatic counterparts. In spite of the similarity between the lachrymal and salivary gland alpha 2u globulin gene products, we find that the hormonal and developmental regulation of alpha 2u globulin expression differs markedly in these two tissues. In the liver, where a different subset of alpha 2u globulin genes is expressed, a third regulatory phenotype is observed.


Biomechanical pathogenesis of fragility fractures in vertebrae and femur.
The causes of fragility fractures in vertebrae and femur are reviewed, and the possibility of both surgical and pharmacological treatment to prevent their occurrence is indicated.


Metabolome shifts triggered by chlorine sanitisation induce Escherichia coli on fresh produce into the viable but nonculturable state.
Facing the increasing occurrence of "big six" Escherichia coli outbreaks linked to fresh produce, chlorine-based sanitisers are widely used for fresh produce decontamination in recent years. However, latest finding that chlorine may induce E. coli cells into a viable not nonculturable (VBNC) state is bringing a new challenge to the fresh produce industry. VBNC cells are undetectable by the plate count test, and yet they retain pathogenicity and are more antibiotic-resistant than culturable cells. As a result, their eradication is critical to ensure the safety of fresh produce. Understanding VBNC cells at the metabolic level may provide a breakthrough for their eradication. Therefore, this study was carried out to collect the VBNC pathogenic E. coli (O26:H11, O121:H19, and O157:H7) cells from chlorine-treated pea sprouts and characterise them using NMR-based metabolomics. From the globally increased metabolite contents detected in the VBNC E. coli cells as compared to the culturable cells, mechanisms underlying E. coli's VBNC induction were elucidated. These include rendering the energy generation scheme to become more compatible with the lowered energy needs, disaggregating protein aggregates to release amino acids for osmoprotection and later resuscitation, as well as increasing cAMP content to downregulate RpoS. These identified metabolic characteristics can inspire future development of targeted measures for VBNC E. coli cell inhibition. Our methods can also be applied to other pathogens to help lower the risk of overall foodborne diseases.


Behavioural development of conspecific odour preferences in bank voles, Clethrionomys glareolus.
Biological odours of conspecifics are known to have strong influences on behavioural interaction in bank voles Clethrionomys glareolus. This experiment tested two hypotheses. (1) Olfactory cues from familiar and unfamiliar mature opposite-sex conspecifics differ in their attractiveness to males and females, and their behavioural reactions change with age. (2) A genetically based mechanism is involved in female recognition of kin.In a two-choice preference test, prepubertal males and females were more attracted to familiar than to unfamiliar odours of opposite-sex conspecifics, as manifested by more time spent sniffing familiar voles. As the young reached sexual maturity they shifted their odour preferences. Mature males and females preferred the novel odour of unrelated opposite-sex conspecifics to that of relatives. The results of experiments testing the second hypothesis indicate that females use a genetically based mechanism to recognise their kin. Young and mature females were able to recognise the odour of their biological but socially unknown fathers, and showed the same pattern of behaviour as females in previous experiments.The possible biological functions of kin recognition in bank voles are discussed.


Extracorporeal shock wave lithotripsy-induced perirenal hematomas.
Subcapsular or perirenal bleeding is the most commonly experienced adverse effect directly attributable to externally applied shock waves. The first consecutive 3,620 extracorporeal shock wave lithotripsy treatments with the HM3 Dornier lithotriptor at our institution resulted in 24 hematomas in 21 patients, for an incidence of 0.66 per cent. Various factors associated with treatment were examined. The number of shock waves (up to 2,000) and voltage up to 24 kv. did not correlate with the development of hematoma. Coagulation studies were normal in all patients with hematomas. There was no correlation of patients size and weight, or stone size, number or location with the occurrence rate of perinephric hematoma. Patients with pre-existing hypertension, particularly those with unsatisfactory control of hypertension, had a significantly increased incidence of perinephric hematoma. The incidence of hematoma in hypertensive patients was 2.5 per cent and it increased to 3.8 per cent in patients with unsatisfactory control of hypertension. Therefore, pre-existing hypertension is a significant risk factor in the occurrence of post-extracorporeal shock wave lithotripsy bleeding. The incidence of perinephric hematoma also was increased in patients with pre-treatment urinary tract infection and those who underwent simultaneous bilateral treatment. Management of post-extracorporeal shock wave lithotripsy bleeding generally is conservative although a third of the patients required transfusion.


Treatment of seven cases of chronic granulomatous disease with sulfamethoxazole-trimethoprim (SMX-TMP).
Seven male Japanese children with chronic granulomatous disease were given sulfamethoxazole-trimethoprim (SMX-TMP) for recurrent pyogenic infections, most of which had proved difficult to control with other antibiotics. With continous treatment the children remained free of infections severe enough to necessitate hospitalization, except on one occasion. Serious complications, including hematological disorders, never occurred during therapy and there were no changes in leukocyte function during therapy. These results indicate that SMX-TMP should be considered in the treatment of bacterial infections associated with chronic granulomatous disease.


Gender representation amongst editorials boards in United Kingdom surgical specialty journals.
Females remain under-represented in surgery in the United Kingdom and around the globe. Gender representation on journal editorial boards is one of the key metrics of gender representation within academic surgery. The aim of this study was to quantify gender representation within the editorial leadership of journals affiliated with UK surgical specialties. A web-based search for each of the UK surgical specialty associations was conducted, followed by identification of the endorsed journals for each one. As of August 2022, data on the gender of the editor-in-chief and other journal leadership positions, including associate, section, and deputy editors, were collated. Gender classification was completed using first-name recognition, verified by a web search using the name and institution provided. Managing editors without clinical backgrounds were excluded. Ten journals were identified for the following surgical specialties: General Surgery, Trauma and Orthopaedics, Neurosurgery, Cardiothoracic, Urology, Paediatric Surgery, Ear Nose and Throat, Oral and Maxillofacial, Plastic and Reconstructive Surgery, and Vascular Surgery. In total, 242 editorial positions were identified: 207 were held by males (82.8%) and 35 by females (17.2%). There were no female editors-in-chief. The average female proportion of editorial leadership per journal was 18.8%. One journal had no female editorial leadership representation. Overall, the number of females in editorial leadership positions is comparable to the current proportion of UK female consultant surgeons (13.7%). Journals with an under-representation of females in senior editorial leadership positions compared with the parent specialty should consider initiatives that will encourage diversity, promote greater gender parity, and champion female representation.


Hexa-aquadodeca-μ2-chlorido-octa-hedro-hexa-niobium diiodide.
The title compound, [Nb6Cl12(H2O)6]I2, consists of the niobium cluster cation [Nb6Cl12(H2O)6]2+ and two non-coordinating, charge-balancing iodide ions. The edges of the Nb6 octa-hedron are bridged by chlorido ligands. Each Nb atom is further coordinated by a water ligand. The cluster cation has a charge of +2, which is balanced by that of two iodide anions.


Antipyretic studies on some indigenous Pakistani medicinal plants.
Significant oral antipyretic activity in rabbits was exhibited by hexane-, chloroform- and water-soluble extracts of Artemisia absinthium, Viola odorata, Melia azadirachta and Fumaria parviflora comparable in potency aspirin. Pyresis was induced by subcutaneous yeast injections. Antipyretic activity was more prominent in the hexane-soluble portions of these plants. Insignificant to no antipyretic effects were produced by extracts of Butea frondosa, Berberis lycium and Sisymbrium irio. No obvious toxic effects were noted for any of the plant extracts up to doses of 1.6 g/kg.


Following specific podocyte injury captopril protects against progressive long term renal damage.
Angiotensin converting enzyme inhibitors (ACEi) reduce proteinuria and preserve kidney function in proteinuric renal diseases. Their nephroprotective effect exceeds that attributable to lowering of blood pressure alone. This study examines the potential of ACEi to protect from progression of injury after a highly specific injury to podocytes in a mouse model. We created transgenic (Podo-DTR) mice in which graded specific podocyte injury could be induced by a single injection of diphtheria toxin. Transgenic and wild-type mice were given the ACEi captopril in drinking water, or water alone, commencing 24h after toxin injection. Kidneys were examined histologically at 8 weeks and injury assessed by observers blinded to experimental group. After toxin injection, Podo-DTR mice developed acute proteinuria, and at higher doses transient renal impairment, which subsided within 3 weeks to be followed by a slow glomerular scarring process. Captopril treatment in Podo-DTR line 57 after toxin injection at 5ng/g body weight reduced proteinuria and ameliorated glomerular scarring, matrix accumulation and glomerulosclerosis almost to baseline (toxin: 17%; toxin + ACEi 10%, p<0.04; control 7% glomerular scarring). Podocyte counts were reduced after toxin treatment and showed no recovery irrespective of captopril treatment (7.1 and 7.3 podocytes per glomerular cross section in water and captopril-treated animals compared with 8.2 of wild-type controls, p<0.05). Observations in Podo-DTR mice support the hypothesis that continuing podocyte dysfunction is a key abnormality in proteinuric disease. Our model is ideal for studying strategies to protect the kidney from progressive injury following podocyte depletion. Demonstrable protective effects from captopril occur, despite indiscernible preservation or restoration of podocyte counts, at least after this degree of relatively mild injury.


Activation of K+ channels and Na+/K+ ATPase prevents aortic endothelial dysfunction in 7-day lead-treated rats.
Seven day exposure to a low concentration of lead acetate increases nitric oxide bioavailability suggesting a putative role of K+ channels affecting vascular reactivity. This could be an adaptive mechanism at the initial stages of toxicity from lead exposure due to oxidative stress. We evaluated whether lead alters the participation of K+ channels and Na+/K+)-ATPase (NKA) on vascular function. Wistar rats were treated with lead (1st dose 4 μg/100 g, subsequent doses 0.05 μg/100g, im, 7 days) or vehicle. Lead treatment reduced the contractile response of aortic rings to phenylephrine (PHE) without changing the vasodilator response to acetylcholine (ACh) or sodium nitroprusside (SNP). Furthermore, this treatment increased basal O₂⁻ production, and apocynin (0.3 μM), superoxide dismutase (150 U/mL) and catalase (1000 U/mL) reduced the response to PHE only in the treated group. Lead also increased aortic functional NKA activity evaluated by K+-induced relaxation curves. Ouabain (100 μM) plus L-NAME (100 μM), aminoguanidine (50 μM) or tetraethylammonium (TEA, 2 mM) reduced the K+-induced relaxation only in lead-treated rats. When aortic rings were precontracted with KCl (60 mM/L) or preincubated with TEA (2 mM), 4-aminopyridine (4-AP, 5 mM), iberiotoxin (IbTX, 30 nM), apamin (0.5 μM) or charybdotoxin (0.1 μM), the ACh-induced relaxation was more reduced in the lead-treated rats. Additionally, 4-AP and IbTX reduced the relaxation elicited by SNP more in the lead-treated rats. Results suggest that lead treatment promoted NKA and K+ channels activation and these effects might contribute to the preservation of aortic endothelial function against oxidative stress.


Unusual case of porocarcinoma of the foot with no clinically evident dermatologic manifestations.
Eccrine poromas are solitary nodules that predilect the soles of the foot. Rarely, malignancies may arise within these tumors. When this occurs, the growth is classified as a malignant eccrine poroma, or porocarcinoma. A case of a 39-year-old woman who originally presented with an incidental plantar skin lesion that was later diagnosed as a porocarcinoma is reported. The patient underwent local excision of the lesion and a sentinel node biopsy. At 18 months postoperative there were no signs of recurrence. This case has been presented to demonstrate that skin lesions with minimal abnormalities of skin texture or color, and slight elevation as the only dermatologic manifestation, can represent a malignancy.


CD204⁺ tumor-associated macrophages are associated with clinical outcome in canine pulmonary adenocarcinoma and transitional cell carcinoma.
Tumor-associated macrophages are abundant infiltrating cells in the tumor microenvironment (TME). Macrophages can be classified into several types of subsets based on their immune responses. Among those subsets, M2 macrophages contribute to anti-inflammatory responses and create an immunosuppressive environment that promotes tumor cell proliferation. In a previous study, human cancer patients with high M2 macrophages showed a worse prognosis for many types of tumors. However, studies examining the relationship between M2 macrophages and clinical outcomes in canine tumors are limited. In the previous human and canine studies, CD204 has been used as the marker for detecting M2 macrophages. Then we evaluated CD204+ and total macrophages infiltration and its association with clinical outcomes in canine solid tumors. In this study, we examined dogs with oral malignant melanoma (OMM), pulmonary adenocarcinoma (PA), hepatocellular carcinoma (HCC), and transitional cell carcinoma (TCC). Compared to healthy tissues, CD204+ and total macrophages were increased in OMM, PA, and TCC, but not in HCC. High CD204+ macrophage levels were significantly associated with lung metastasis in TCC (P = 0.030). Kaplan-Meier analysis revealed that high CD204+ macrophage levels were associated with shorter overall survival (OS) in canine patients with PA (P = 0.012) and TCC (P = 0.0053). These results suggest that CD204+ macrophages contribute to tumor progression and could be a prognostic factor in dogs with PA and TCC.


A glassy carbon electrode modified with nitrogen-doped reduced graphene oxide and melamine for ultra-sensitive voltammetric determination of bisphenol A.
A composite was prepared at room temperature from nitrogen-doped reduced graphene oxide (N-rGO) and melamine via π-interaction. An ultra-sensitive electrochemical sensor for the determination of trace levels of bisphenol A (BPA) was obtained by coating a glassy carbon electrode (GCE) with the composite. The structure and morphology of composite were characterized by FTIR, Raman, XRD, XPS, SEM and TEM. Because of the synergetic effects of N-rGO and melamine, the modified GCE displays considerably enhanced sensitivity to BPA. The voltammetric response, typically measured at a peak of 0.48 V (vs. SCE) is linear in the 0.05 to 20 μM BPA concentration range, and the detection limit is 0.8 nM (at S/N = 3). The sensor is reproducible, stable and selective. It was applied to analyze baby bottles, drinking cups, mineral water bottles and shopping receipts that were spiked with BPA, and the recoveries reached 99.1-101.4%. Graphical abstract Illustration of fabricating the electrochemical sensor for detecting BPA. N-G/M: nitrogen-doped reduced graphene oxide and melamine composite; GCE: glassy carbon electrode.


Machine Learning for Optical Scanning Probe Nanoscopy.
The ability to perform nanometer-scale optical imaging and spectroscopy is key to deciphering the low-energy effects in quantum materials, as well as vibrational fingerprints in planetary and extraterrestrial particles, catalytic substances, and aqueous biological samples. These tasks can be accomplished by the scattering-type scanning near-field optical microscopy (s-SNOM) technique that has recently spread to many research fields and enabled notable discoveries. Herein, it is shown that the s-SNOM, together with scanning probe research in general, can benefit in many ways from artificial-intelligence (AI) and machine-learning (ML) algorithms. Augmented with AI- and ML-enhanced data acquisition and analysis, scanning probe optical nanoscopy is poised to become more efficient, accurate, and intelligent.