25-gauge transconjunctival diagnostic vitrectomy in suspected cases of intraocular lymphoma: a case series and review of the literature.
To report the cytology results of 25-gauge transconjunctival (25G-TSV) diagnostic vitrectomy in cases suspicious for intraocular lymphoma (IOL), and compare the results to those reported in the literature. Clinical and cytopathological records of 18 vitreous biopsy specimens obtained via 25G-TSV diagnostic vitrectomy in 12 patients suspicious for IOL were reviewed retrospectively. A review of the literature in regards to the diagnostic yields of vitreous specimens obtained via 25-gauge and 20-gauge diagnostic vitrectomy in suspected cases of IOL was performed. Eighteen eyes from 12 patients with clinical suspicion of IOL underwent diagnostic 25G-TSV. The cytopathological investigations demonstrated IOL in 15 eyes (83.3%). Vitreous analysis was non-diagnostic in 3 eyes (16.7%). Twenty-five-gauge diagnostic vitrectomy yields adequate sample for cytological evaluation of the vitreous in cases suspicious for IOL. The diagnostic results of the 25G-TSV in the current study are superior to those reported for 20-gauge vitrectomy but equivalent to those reported for 25G-TSV in the published literature.


Isolation of Lactic Acid Bacteria from Intestine of Freshwater Fishes and Elucidation of Probiotic Potential for Aquaculture Application.
Probiotics play significant roles in enhancing systemic immunity, improving intestinal balance and feed value, enhancing enzymatic digestion, and inhibiting pathogenic microorganisms of freshwater fish. Probiotics from an identical organism's gastrointestinal system promote effective colonization and provide greater benefits than other sources. This study aimed to evaluate the usefulness of probiotic bacteria isolated from the intestines of freshwater fishes for a dietary supplement of freshwater aquaculture. A total of 120 isolates were collected from freshwater fishes of Channa striata, Puntius filamentosus, Oreochromis mossambicus, Cirrhinus mrigala, and Rasbora daniconius. Seven of these isolates exhibited antagonistic activity against fish pathogens: Aeromonas hydrophila, Staphylococcus epidermidis, Staphylococcus aureus, Bacillus cereus, Escherichia coli, and Pseudomonas aeruginosa. Using 16S rRNA gene sequencing analysis, the isolates were identified as Enterococcus sp., Lactococcus lactis, Weissella cibaria, and Limosilactobacillus fermentum. Of these tolerates, L. fermentum URLP18 isolated from C. mrigala exhibited high tolerance to low acidic (pH 2.0) and high bile salt (2%) concentrations, exhibiting a significant hydrophobicity and extracellular enzyme secretions like amylase, protease, and lipase. In vitro evaluations on intestinal mucus indicate that L. fermentum URLP18 have strong adherence capacity, and its survival rate increased after being administered to Artemia nauplii. The results suggest that L. fermentum URLP18 has high probiotic potential and is an effective dietary supplement for freshwater aquaculture.


Moisture retention and consumer acceptability of chocolate bar cookies prepared with okra gum as a fat ingredient substitute.
Low dietary fat intake may reduce the risk of developing atherosclerosis. This study determined the feasibility of using okra gum as a fat replacer in chocolate bar cookies. Fat-free cookies were prepared with okra gum (OK) or applesauce (AP), replacing margarine and egg yolk in high-fat cookies (CTL). The moisture content of cookies was determined by using a drying oven. The moisture contents of fresh OK (28.3+/-0.4%) and AP (27.6+1.1%) cookies were higher than CTL (8.5+/-0.3%) and remained higher after 48 hours (P<.001)(n=3). Fifty-two consumers evaluated the quality of cookies using a hedonic scale. Sensory scores for color, smell, flavor, aftertaste, moistness, and overall acceptability for fresh cookies were acceptable, yet lower for flavor and aftertaste in fat-free cookies than CTL (P<.01). After 48 hours, moistness ratings for fat-free cookies were acceptable and higher than CTL (P<.01). Okra gum is an acceptable fat replacer in chocolate bar cookies.


Influence of in situ TiB reinforcements and role of heat treatment on mechanical properties and biocompatibility of β Ti-alloys.
The effect of heat treatment on the mechanical properties of Ti-35Nb-5.7Ta-7.2Zr (TNZT) and Ti-35Nb-5.7Ta-7.2Zr-0.5B (TNZTB) alloys has been investigated. In the case of TNZT alloy, the presence of ω phase in the matrix has a greater effect on strength and hardness than the presence of secondary α precipitates. The TNZTB alloy shows higher hardness and tensile strength than the TNZT alloy due to the formation of hard TiB precipitates in the matrix of the former. However, the boron free alloy offers higher ductility than the boron containing alloy. Presence of TiB precipitates in the matrix increases the strength of the TNZTB alloy when ω precipitates are present in the matrix. However, the boride precipitates have no substantial influence on the strength of the TNZTB alloy when ω phase in the matrix is replaced by the α phase. The elastic modulus of the TNZT samples shows a very small variation with different heat treatment conditions. The TNZT alloy samples containing β and ω phases show higher elastic modulus than the samples containing β and α phases. The elastic modulus of the TNZTB alloy is higher than that of the TNZT alloy due to the formation of high modulus TiB particles in the matrix. Both the alloys show better cell adhesion and spreading than the control material (polystyrene). However, the boron free Ti-alloy shows better cell attachment than the boron containing Ti-alloy.


No effect of gestational diabetes or pre-gestational obesity on 6-year offspring left ventricular function-RADIEL study follow-up.
We aimed to investigate associations between pre-pregnancy obesity, gestational diabetes (GDM), offspring body composition, and left ventricular diastolic and systolic function in early childhood. This is an observational study, including 201 mother-child pairs originating from the Finnish Gestational Diabetes Prevention Study (RADIEL; 96 with GDM, 128 with pre-pregnancy obesity) with follow-up from gestation to 6-year postpartum. Follow-up included dyads anthropometrics, body composition, blood pressure, and child left ventricular function with comprehensive echocardiography (conventional and strain imaging). Offspring left ventricular diastolic and systolic function was not associated with gestational glucose concentrations, GDM, or pregravida obesity. Child body fat percentage correlated with maternal pre-pregnancy BMI in the setting of maternal obesity (r = 0.23, P = 0.009). After adjusting for child lean body mass, age, sex, systolic BP, resting HR, maternal lean body mass, pre-gestational BMI, and GDM status, child left atrial volume increased by 0.3 ml (95% CI 0.1, 0.5) for each 1% increase in child body fat percentage. No evidence of foetal cardiac programming related to GDM or maternal pre-pregnancy obesity was observed in early childhood. Maternal pre-pregnancy obesity is associated with early weight gain. Child adiposity in early childhood is independently associated with increased left atrial volume, but its implications for long-term left ventricle diastolic function and cardiovascular health remain unknown.


Identification of MDM2, YTHDF2 and DDX21 as potential biomarkers and targets for treatment of type 2 diabetes.
Type 2 diabetes (T2D) is a multifactorial and polygenetic disease, although its exact etiology remains poorly understood. The objective of this study was to identify key biomarkers and potential molecular mechanisms in the development of T2D. Human RNA-Seq datasets across different tissues (GSE18732, GSE41762, and GSE78721) were collected from the Gene Expression Omnibus (GEO) database and differentially expressed genes (DEGs) between T2D and controls were identified using differential analysis. A total of 90 overlapping DEGs were identified, among which YTHDF2, DDX21, and MDM2 were considered as key genes due to their central positions in the PPI network and the same regulatory pattern in T2D. Logistic regression analysis showed that low expression of the key genes increased the risk of T2D. Enrichment analysis revealed that the key genes are involved in various important biological functions and signaling pathways including Notch, Fork head box O (FOXO), and phosphoinositide 3-kinase (PI3K)-Akt. RT-qPCR and Western blot analysis showed that all three key genes were down-regulated in pancreatic islets of both prediabetic and diabetic mouse models. Finally, the insulin-sensitizer, pioglitazone was used to treat db/db mice and immunofluorescence analysis showed that the expression of all three key genes was significantly down-regulated in db/db islets, an effect that was overcome by pioglitazone treatment. Together, these results suggest that the identified key genes could be involved in the development of T2D and serve as potential biomarkers and therapeutic targets for this disease.


Identification of a novel LAMA2 c.2217G > A, p.(Trp739*) mutation in a Moroccan patient with congenital muscular dystrophy: a case report.
Merosin-deficient congenital muscular dystrophy type 1A (MDC1A) is a rare autosomal recessive genetic condition caused by deleterious mutations in the LAMA2 gene encoding the laminin-α2 chain. It is the most frequent subtype of congenital muscular dystrophies (CMDs) characterized by total laminin-α2 deficiency with muscle weakness at birth or in the first six months of life. To the best of our knowledge, this study reports the first molecular diagnosis and genetic defect of this heterogeneous form of CMD performed in a Moroccan medical genetic center using next-generation sequencing (NGS). It allows us to expand the mutational spectrum of the LAMA2 gene. We report the case of a female Moroccan child with clinical and paraclinical features in favor of a CMD. She has global congenital hypotonia with generalized muscle weakness, psychomotor retardation, increased serum creatine kinase, and normal brain scan at the age of six months. Targeted NGS leads to the identification of a novel homozygous nonsense mutation c.2217G > A, p.(Trp739*) in the exon 16 of LAMA2. Sanger sequencing confirmed this mutation in the affected patient and showed that her parents are heterozygous carriers. A modern genetic analysis by NGS improves the genetic diagnosis pathway for adequate genetic counseling of affected families more precisely. An accession number from the National Center for Biotechnology Information (NCBI) ClinVar database was retrieved for this novel LAMA2 mutation.


A protective effect of lithium on rat behaviour altered by ibotenic acid lesions of the basal forebrain cholinergic system.
Lithium was tested on an animal model of a brain cholinergic excitotoxic lesion. Male Wistar rats received unilaterally 50 nmol ibotenic acid in the nucleus basalis magnocellularis. Some were treated intraperitoneally with LiCl from two days before to six days after lesioning. Such treated rats showed less deficits than untreated lesioned animals on passive avoidance, ambulatory behaviour and choline acetyltransferase activity in the lesioned cortex. Lithium protection against excitatory amino acid neurotoxicity is suggested.


The genetic basis of dental anomalies and its relation to orthodontics.
The interruption of odontogenesis by any etiological factor may result in dental anomalies. Apart from the environmental factors, the impact of genetics in dental anomalies was found to be a factor in different levels. Many authors had questioned a common genetic defect resulting in different phenotypic conditions such as absent, malformed, malposed or ectopic teeth. Because the multidisciplinary treatment of these dental anomalies such as hypodontia, impaction etc., involves orthodontic intervention, orthodontists must be aware of the etiology and possible correlative conditions with dental anomalies.


Effect of skeleton size on the performance of octadecylsilylated continuous porous silica columns in reversed-phase liquid chromatography.
We prepared continuous porous silica rods that had silica skeletons with sizes of 1.0-1.7 microns and through-pores of 1.5-1.8 microns, and evaluated their performance as a column in reversed-phase liquid chromatography. The mesoporous silica monoliths (mesopore size: 14 or 24 nm) were derivatized to C18 phase by on-column reaction with octadecyldimethyl-N,N-diethylaminosilane. The C18 silica rods gave minimum plate heights of 10-15 microns for aromatic hydrocarbons in 80% methanol and of 20-30 microns for insulin in acetonitrile-water mixtures in the presence of trifluoroacetic acid. The performance of the silica rods at a high flow-rate was much better than that of conventional columns packed with 5 microns C18 silica particles with pores of 12 or 30 nm, especially for high-molecular-mass species. Silica rods with the smaller sized silica skeletons resulted in Van Deemter plots showing a minimum plate height linear velocity of the mobile phase and a smaller dependence of plate height on the linear velocity. Separation impedance of less than 1000 was achieved with the continuous silica columns. The higher performance and lower pressure drop of silica rods at high flow-rates compared with particle-packed columns is provided by the small silica skeletons and large through-pores.


Marginal adaptation of glass-ionomer cements.
The effect of thermocycling on the marginal adaptation of two glass-ionomer cements was determined by means of scanning electron microscopy. Small gaps in the cement as well as at the enamel-cement interface were observed after curing, but these phenomena were not enhanced by thermocycling. Localized areas of surface deterioration were observed for both cements after thermocycling.


Perineal Cyst in Transgender Men: A Rare Complication Following Gender Affirming Surgery - A Case Series and Literature Overview.
Genital gender affirming surgery (gGAS) is usually the final stage in the medical transition for transgender men and consists of creating a neophallus and neo-scrotum, with or without urethral lengthening(UL). To reduce the complication risks of UL, a mandatory colpectomy is performed prior to UL. Colpectomy is considered a complex surgery, which may lead to various perioperative complications. There are few long-term complications reported. To describe the clinical presentation and management of 3 consecutive transgender men presenting with a perineal cyst following gGAS. After obtaining informed consent all clinical data was collected, including medical history, current symptoms, imaging, as well as surgery and histological outcomes. Furthermore, a literature search was performed. To hypothesize the aetiology of the perineal cyst based on current published literature. Three otherwise healthy transgender men, ages 26-46 with a similar medical history, presented with a perineal cyst several months or years following colpectomy and gGAS with UL. All patients underwent surgery to remove the cyst. Several theories regarding aetiology of this perineal cyst are discussed in this report. There remain several gaps in our knowledge regarding the aetiology and management of this perineal cyst. Therefore, further research is necessary. Asseler JD, Ronkes BL, Groenman FA, et al. Perineal Cyst in Transgender Men: A Rare Complication Following Gender Affirming Surgery - A Case Series and Literature Overview. J Sex Med 2021;9:100415.


[The comparison of 4th, 5th and 6th year medical students knowledge of rules and practical skills in the interpretation of electrocardiograms at Jagiellonian University].
The electrocardiogram (ECG) examination is one of the most frequent administered diagnostic tests. It is commonly ordered by General Practitioners, and it has became a routinely administered examination during admission to the hospital. During their studies, medical students has numerous opportunities to review and interpret the results of these tests. The aim of our research was to statistically compare and contrast the knowledge of the rules and practical skills in the interpretation of ECGs in 4th, 5th and 6th year medical students at Jagiellonian University. We wanted to better define in which year the students acquire the most of their clinical skills and determine if 6th year students have sufficient knowledge and skills to adequately perform in their future career. We additionally wanted to understand from which source students draw their knowledge of the ECG. The population of 249- 4th, 5th and 6th year medical students of Jagiellonian University were asked to reply to an anonymous questionnaire. The questionnaire was comprised of three parts. The fist part contains four simple ECGs (STEMI, RBBB, PVC, normogram--sinus rhythm). The second part contained six questions regarding their theoretical knowledge. The third part contained seven questions which evaluated the students' background and approach to the problem. Students filled the questionnaire without prior preparation to avoid the short-term "examination knowledge". The question that was most frequent answered correctly was question regarding the proper time (in milliseconds) of QRS complex (24.1%). Differences in the percentage of correct answers to questionnaire amongst 4th and 5th year students were statistically uncharacteristic. The percentage of correct answers of 6th year students increased by about 16% (p < 0.0001). The comparison of answers between 6th year students - who in prior semester completed a cardiology course (group A 6th year) and 6th year students who did not yet complete cardiology course (group B 6th year) showed significant improvement in group A in the percentage of correct answers for all questions about ECG. The percentage of correct answers in group A was an average 62% and in group B 45.5% (p < 0.00025). In case of 4th and 5th year students, the picture was uncharacteristic. Self study of ECG had a significant, positive influence in the percentage of correct answers amongst respondents, especially in the 6th year student population. Improvement was also seen in 4th and 5th students, but to a lesser degree. Among the 6th year students who benefited from self study, their percentage of correct answers was nearly two times then that of their fellow of 6th year students who did not self study (p < 0.0001). Only 3 of questioned students stated that they felt that their present knowledge of ECG is sufficient. 4th and 5th year students have comparable knowledge of ECG. 6th year students showed a significantly improved ability to interpret the ECG, especially those who had already completed cardiology course in present term. The increase in skills of interpretation of ECG is gained primarily by self study.


Second to fourth (2D:4D) digit ratio and their relationships among a mother and child population in Ghana.
The study aimed to determine the relationship between digit ratios among a mother-child population in Ghana. This was a cross-sectional study from December 2020 to April 2021 involving 272 mothers, their daughters (n = 132) and their sons (n = 140). The right (2D:4DR) and the left (2D:4DL) digit ratios were measured using computer-assisted analysis. The data were analysed in SPSS (v23) and GraphPad Prism (v8) at an alpha value of 0.05. The mean ± SD age of the mothers was 23.9 ± 3.67 years while the median (IQR) age of daughters was 116(54-240) days and sons, 134(54-240) days. The mean ± SD 2D:4DR were 0.94 ± 0.04, 0.91 ± 0.04 and 0.90 ± 0.04 respectively for mothers, daughters and sons. The mean ± SD 2D:4DL was 0.93 ± 0.04, for mothers, 0.92 ± 0.05 for daughters and 0.92 ± 0.05 for sons. The daughters and sons showed leftward asymmetry while the mothers showed rightward asymmetry in digit ratios. The 2D:4DR of sons was significantly lower than daughters (P = 0.031). There were negative correlations between the 2D:4DL and age of daughters (r = -0.182, P = 0.043) and sons (r = -0.221, P = 0.012). The 2D:4DR of mothers was positively correlated with that of daughters (r = 0.332, P = 0.000) and that of sons (r = 0.233, P = 0.008). There are significant relationships between digit ratios in a mother-child population.


Physiological Traits and Adherence to Sleep Apnea Therapy in Individuals with Coronary Artery Disease.
Rationale: Untreated obstructive sleep apnea (OSA) is associated with adverse outcomes in patients with coronary artery disease (CAD). Continuous positive airway pressure (CPAP) is the most common treatment, but despite interventions addressing established adherence determinants, CPAP use remains poor. Objectives: To determine whether physiological traits that cause OSA are associated with long-term CPAP adherence in patients with CAD. Methods: Participants in the RICCADSA (Randomized Intervention with CPAP in CAD and OSA) trial with objective CPAP adherence (h/night) over 2 years and analyzable raw polysomnography data were included (N = 249). The physiological traits-loop gain, arousal threshold (ArTH), pharyngeal collapsibility (Vpassive), and pharyngeal muscle compensation (Vcomp)-were measured by using polysomnography. Linear mixed models were used to assess the relationship between the traits and adherence. We also compared actual CPAP adherence between those with physiologically predicted "poor" adherence (lowest quartile of predicted adherence) and those with physiologically predicted "good" adherence (all others). Measurements and Main Results: The median (interquartile range) CPAP use declined from 3.2 (1.0-5.8) h/night to 3.0 (0.0-5.6) h/night over 24 months (P < 0.001). In analyses adjusted for demographics, anthropometrics, OSA characteristics, and clinical comorbidities, a lower ArTH was associated with worse CPAP adherence (0.7 h/SD of the ArTH; P = 0.021). Both high and low Vcomp were associated with lower adherence (P = 0.008). Those with predicted poor adherence exhibited markedly lower CPAP use than those with predicted good adherence for up to 2 years of follow-up (group differences of 2.0-3.2 h/night; P < 0.003 for all). Conclusions: A low ArTH, as well as a very low and high Vcomp, are associated with worse long-term CPAP adherence in patients with CAD and OSA. Physiological traits-alongside established determinants-may help predict and improve CPAP adherence. Clinical trial registered with www.clinicaltrials.gov (NCT00519597).


Prospective screening for myocarditis in cancer patients treated with immune checkpoint inhibitors.
Immune checkpoint inhibitors (ICIs) improve clinical outcomes in various cancers, but sometimes induce autoimmune adverse effects, including myocarditis, which is the most serious complication. There are many reports on ICI-induced myocarditis; however, only a few prospective surveillance reports exist. Therefore, we developed a prospective screening protocol and performed monitoring clinically suspected myocarditis in every patient treated with ICIs. We prospectively enrolled 126 consecutive patients treated with ICIs in this cohort. Outcomes of patients were determined and analyzed between April 2017 and May 2020. We evaluated vital signs, biomarkers, electrocardiograms, chest radiographs, and echocardiographs before and at 7 ± 3, 14 ± 3, 21 ± 3, and 60 ± 7 days after ICI initiation. Eighteen (14.3 %) presented troponin I elevation and 13 of them presented signs of clinically suspected myocarditis (10.3 %). Among the 13 patients, ICI was discontinued in four cases (3.2 %) without fatal events. Myocarditis appeared at an early stage of ICI treatment, regardless of severity (median, 44 days). We observed the frequency of patients with myocarditis or myocardial damage through a prospective screening program in the real world. Although the frequency was higher than expected, most cases were mild and ICI treatment could be continued under careful observation.


Factors related to severe uveitis at diagnosis in children with juvenile idiopathic arthritis in a screening program.
To identify factors associated with severe uveitis at diagnosis of eye disease in children with juvenile idiopathic arthritis (JIA) who were observed in a screening program, and to identify temporal changes in findings associated with screening during the period 1986 to 2000. Case control study. Uveitis was defined as being severe at diagnosis if there were associated synechiae, cataracts, or retinal edema. Clinical factors for all patients undergoing screening for JIA-associated uveitis from 1986 to 2000 at one institution were studied retrospectively. Children with severe uveitis at diagnosis (cases) were compared with those with mild uveitis at diagnosis and those who never developed uveitis during follow-up in the screening program (controls). Severe uveitis was present at diagnosis in 22 (5.4%) of 409 patients. Male patients were more likely to have severe uveitis at diagnosis (odds ratio [OR] 3.7 [95% confidence interval 1.3 to 10.7], P =.014). A longer interval from the onset of arthritis symptoms to the diagnosis of uveitis was associated with a reduced risk of severe uveitis at diagnosis (OR 0.95 [0.91 to 1.0], P =.044). There was no difference in the frequency of severe uveitis at diagnosis between two screening periods: 1986 to 1993 (before American screening guidelines were published) and 1994 to 2000. Male children are more likely than female children to have severe uveitis at diagnosis. The proportion of children with severe uveitis at diagnosis has not changed since current screening guidelines have been widely publicized, suggesting the need for refinements in screening procedures to target high-risk children with increased surveillance.


Evaluating pain behaviours: Widely used mechanical and thermal methods in rodents.
Globally, over 300 million surgical procedures are performed annually, with pain being one of the most common post-operative side effects. During the onset of injury, acute pain plays a protective role in alerting the individual to remove noxious stimuli, while long-lasting chronic pain without any physiological reason is detrimental to the recovery process. Hence, it created an urgent need to better understand the pain mechanism and explore therapeutic targets. Despite the hardship in performing human pain studies due to ethical considerations, clinically relevant rodent pain models provide an excellent opportunity to perform pain studies. Several neurobehavioural tests are used to assess the drug efficacy in rodents to determine avoidance behaviour latency and threshold. This review article provides a methodological overview of mechanical (i.e. von Frey, Mechanical Conflict System) and thermal (i.e. Hargreaves Assay, Hot and Cold Plate, Temperature Place Preference) tests to assess pain in clinically relevant pain rodent models. We further discussed the current modifications of those tests along with their use in literature, the impact of confounding variables, advantages and disadvantages.


The MHC-II antigen presentation machinery and B7 checkpoint ligands display distinctive patterns correlated with acute myeloid leukaemias blast cells HLA-DR expression.
Acute Myeloid Leukaemia (AML) is a neoplasia characterised by rapid proliferation and an increased rate of relapses. The AML blasts display features of antigen-presenting cells (APC), and thus can directly modulate the anti-tumour T cell responses. The bone marrow of a group consisting of 30 newly diagnosed patients and four healthy donors (HD) was investigated for the expression of HLA-DR, several molecules involved in MHC-II antigen-presentation and MHC-II groove editing, like HLA-DM, CD74 and CLIP, as well as a set of immune checkpoint ligands, like ICOS-L, B7.2, PD-L2 and B7-H3. The patients were further characterised for their genetic anomalies and distributed to favourable, intermediate and adverse ELN risk categories. We were able to show that while 23% of our patients displayed a low level of HLA-DR surface expression, all patients displayed higher HLA-DM and CD74 expression compared to HD. However, a higher CLIP expression was noticed only in the HLA-DR low patients. The co-inhibitory PD-L2 and B7-H3 molecules were increased in the cases with normal HLA-DR expression; oppositely, the co-stimulatory ICOS-L and the dual function B7.2 were significantly increased in the cases with HLA-DR low expression. Furthermore, no favourable ELN risk cases were found within the HLA-DR low group. All in all, these data show that the AML with low versus normal HLA-DR expression display different profiles of MHC class II machinery molecules and B7 ligands, which are correlated with distinct ELN stratification. Furthermore, as our study included healthy individuals, it offers valuable information about the expression levels that should be considered as normal for these markers known to cause differences in peptide repertoires, reflected further in distinct T-cells polarisation pathways.


Potential of multisyringe chromatography for the on-line monitoring of the photocatalytic degradation of antituberculosis drugs in aqueous solution.
In this study, a multisyringe chromatography system (MSC) using a C18 monolithic column was proposed for the on-line monitoring of the photocatalytic degradation of isoniazid (INH, 10 mg L(-1)) and pyrazinamide (PYRA, 5mgL(-1)) mixtures in aqueous solution using a small sample volume (200 μL) with an on-line filtration device in a fully automated approach. During the photocatalytic oxidation using TiO2 or ZnO semiconductor materials, total organic carbon (TOC) and the formed intermediates were analyzed off-line using ion chromatography, ion exclusion HPLC, and ESI-MS/MS. The results showed that TiO2 exhibits a better photocatalytic activity than ZnO under UV irradiation (365 nm) for the degradation of INH and PYRA mixtures, generating 97% and 92% degradation, respectively. The optimal oxidation conditions were identified as pH 7 and 1.0 g L(-1) of TiO2 as catalyst. The mineralization of the initial organic compounds was confirmed by the regular decrease in TOC, which indicated 63% mineralization, and the quantitative release of nitrate and nitrite ions, which represent 33% of the nitrogen in these compounds. The major intermediates of INH degradation included isonicotinamide, isonicotinic acid, and pyridine, while the ESI-MS/MS analysis of PYRA aqueous solution after photocatalytic treatment showed the formation of pyrazin-2-ylmethanol, pyrazin-2-ol, and pyrazine. Three low-molecular weight compounds, acetamide, acetic acid and formic acid, were detected during INH and PYRA decomposition. PYRA was more resistant to photocatalytic degradation due to the presence of the pyrazine ring, which provides greater stability against OH attack.


Improved Re-estimation of Perioperative Cardiac Risk Using the Surgical Apgar Score: A Retrospective Cohort Study.
To assess whether the Surgical Apgar Score (SAS) improves re-estimation of perioperative cardiac risk. The SAS is a novel risk index that integrates three relevant and easily measurable intraoperative parameters (blood loss, heart rate, mean arterial pressure) to predict outcomes. The incremental prognostic value of the SAS when used in combination with standard preoperative risk indices is unclear. We conducted a retrospective cohort study of adults (18 years and older) who underwent elective noncardiac surgery at a quaternary care hospital in Canada (2009-2014). The primary outcome was postoperative acute myocardial injury. The SAS (range 0-10) was calculated based on intraoperative estimated blood loss, lowest mean arterial pressure, and lowest heart rate documented in electronic medical records. Incremental prognostic value of the SAS when combined with the Revised Cardiac Risk Index was assessed based on discrimination (c-statistic), reclassification (integrated discrimination improvement, net reclassification index), and clinical utility (decision curve analysis). The cohort included 16,835 patients, of whom 607 (3.6%) patients had acute postoperative myocardial injury. Addition of the SAS to the Revised Cardiac Risk Index improved risk estimation based on the integrated discrimination improvement [2.0%; 95% confidence interval (CI): 1.5%-2.4%], continuous net reclassification index (54%; 95% CI: 46%-62%), and c-index, which increased from 0.68 (95% CI: 0.65-0.70) to 0.75 (95% CI: 0.73-0.77). On decision curve analysis, addition of the SAS to the Revised Cardiac Risk Index resulted in a higher net benefit at all decision thresholds. When combined with a validated preoperative risk index, the SAS improved the accuracy of cardiac risk assessment for noncardiac surgery. Further research is needed to delineate how intraoperative data can better guide postoperative decision-making.


The Impact of an Integrated Care Management Program on Acute Care Use and Outpatient Appointment Attendance Among High-Risk Patients With Lupus.
Patients with systemic lupus erythematosus (SLE) often struggle with high acute care use (emergency department [ED] visits and hospitalizations) and missed appointments. A nurse-led integrated care management program (iCMP) at our multihospital system coordinates care for patients at high risk for frequent acute care use due to comorbidities, demographics, and prior use patterns. We studied whether iCMP enrollment was associated with decreased acute care use and missed appointment rates among patients with SLE. We used a validated electronic health record (EHR) machine learning algorithm to identify adults with SLE and then determined which patients were enrolled in the iCMP from January 2012 to February 2019. We then used EHR data linked to insurance claims to compare the incidence rates of ED visits, hospitalizations, potentially avoidable ED visits and hospitalizations, and missed appointments during iCMP enrollment versus the 12 months prior to iCMP enrollment. We used Poisson regression to compare incidence rate ratios (IRRs) during the iCMP versus pre-iCMP for each use measure, adjusted for age, sex, race and ethnicity, number of comorbidities, and calendar year, accounting for within-patient clustering. We identified 67 iCMP enrollees with SLE and linked EHR claims data. In adjusted analyses, iCMP enrollment was associated with reduced rates of ED visits (IRR 0.63, 95% confidence interval [CI] 0.47-0.85), avoidable ED visits (IRR 0.50, 95% CI 0.28-0.88), and avoidable hospitalizations (IRR 0.37, 95% CI 0.21-0.65). A nurse-led iCMP was effective at decreasing the rate of all ED visits and potentially avoidable ED visits and hospitalizations among high-risk patients with SLE. Further studies are needed to confirm these findings in other patient populations.


The LexA protein does not bind specifically to the two SOS box-like sequences immediately 5' to the phr gene.
There are two SOS box-like sequences located at the regions -161 to -142 and -69 to -50 with regard to the initiation codon of phr. Ihara et al. (1987) constructed a phr'-'lacZ fusion plasmid in which these sequences and the amino terminal end of the phr gene was fused to lacZ and therefore lacZ was under the regulatory control of phr promoter-operator. The authors found that in cells carrying this plasmid beta-galactosidase was inducible by UV and UV-mimetic agents and concluded that phr was controlled by the LexA repressor. We wished to confirm these results by theoretical analysis of the SOS-like sequences by the method developed by Berg (1987) as well as by measuring the binding of LexA protein to the putative SOS boxes by a novel gel retardation assay. Both theoretical analysis and experimental results indicate that the putative SOS boxes immediately 5' to phr have no specific affinity for LexA protein.


Anion-selective electrodes based on ionic liquid membranes: effect of ionic liquid anion on observed response.
A systematic study of the behavior of ion-exchanger anion-selective electrodes prepared from seven different trihexyltetradecylphosphonium ionic liquids (ILs) was performed. The effective ion-exchange capacity of prepared ion-selective electrodes (ISEs) increased with decreasing IL anion lipophilicity, and analyte anion response slopes became more Nernstian concomitantly. With ILs having the most lipophilic constituent anions, incorporation of tridodecylmethylammonium chloride into membranes significantly enhanced responses toward all ions. However, ILs based on bis(trifluoromethylsulfonyl)imide and dodecylsulfate maintained sub-Nernstian responses upon such addition apparently due to their ability to coordinate cations. Electrodes prepared with high IL content displayed regions of super-Nernstian response, which could be eliminated by reducing percent of IL in the membrane; percentages at which optimal linear range was achieved also followed a trend with decreasing constituent IL anion lipophilicity. While selectivities of all electrodes followed the Hofmeister pattern, selectivity coefficient ranges generally were narrower than observed with traditionally plasticized ISEs, and selectivities for more hydrophilic analytes were improved slightly in ILs containing the most hydrophilic constituent anions.


Severe colitis induced by soap enemas.
A patient had severe colitis after soap enemas for five days. Elimination of the soap enemas resulted in resolution of the colitis. We suggest that soap enemas be avoided.


Restriction of primary responses to the IgG class and dependency of IgM responses on secondary immunization for the copolymers of L-glutamic acid, L-tyrosine, and L-alanine.
Primary responses to the linear polymers of L-glutamic acid, L-tyrosine, and L-alanine are restricted to the IgG class of antibodies. The appearance of specific IgM antibodies against these antigens is dependent upon secondary immunization, in contrast to many classical antigenic systems. The presence of an IgM response was verified by a direct plaque-forming cell assay, the inhibition of direct plaques by an antiserum specific for mouse micron-chain, and the physical separation of IgM and IgG GAT-specific antibodies by gel filtration. Preimmunization of the appropriate nonresponder strain with GAT or GT inhibits both the secondary IgM and IgG responses to GAT-MBSA and GT-MBSA, respectively. The tolerance observed is due to the induction of suppressor cells as demonstrated by cell transfer experiments.


Chemotactic activity for polymorphonuclear and mononuclear leukocytes in rheumatoid synovial fluids.
In order to why polymorphonuclear leukocytes (PMNs) are predominant and mononuclear leukocytes (MNLs) are few in rheumatoid synovial fluids, chemotactic factor(s) for PMNs and MNLs were studied in the synovial fluids of rheumatoid arthritis (RA-SF) and osteoarthritis (OA-SF) using both Boyden's and agarose methods. The RA-SF showed strong chemotactic activity for human peripheral blood PMNs compared with non-rheumatoid OA-SF. The chemotactic activity for PMNs was well correlated with the number of PMNs in RA-SF, suggesting that it was a natural mediator for PMN emigration into rheumatoid joint cavity. The major chemotactic factor for PMN in RA-SF was of apparent molecular weight of 14,000 and its activity was suppressed to less than 10 percent by anti-C5a antibody, but it failed to show any anaphylatoxin activity which was an attribute of C5a. It was, therefore, suggested to be C5a-like molecule but not C5a itself. The possibility that the factor may be a C5a des-Arg was discussed. On the contrary, the chemotactic activity for MNLs was not found neither in RA-SF nor OA-SF. These findings may explain the fact that PMNs are predominant in rheumatoid synovial fluids.


An unusual case of primary effusion lymphoma in a HIV-negative patient not pathogenetically associated with HHV8.
The development of an unusual case of primary pleural effusion in a 90-year-old human immunodeficiency virus (HIV)-negative Japanese woman with no identifiable tumor mass has been described. Pleural effusion specimens contained large diffuse lymphoma cells, with the phenotype and genotype of a B-cell lineage (positive for CD20, CD79a and clonal rearrangement of Ig heavy chain) and the c-myc gene rearrangement, but were negative for T-cell markers (CD45RO and CD3). The patient was negative for human herpes virus 8 (HHV8), Epstein-Barr virus (EBV) and hepatitis C virus (HCV), as well as human T-cell lymphotropic virus type-1 (HTLV-1). The patient died of respiratory failure 5 months after the diagnosis of primary effusion lymphoma (PEL), and an autopsy was performed. Autopsy findings revealed no evidence of tumor mass or bone marrow involvement of lymphoma cells. This case has been considered as a PEL in a HIV-, HHV8-, EBV- and HCV-negative patient. Although cytomorphology of lymphoma cells was classified as large-cell lymphoma in this case, it is interesting that the present case may represent an unusual subset of Burkitt-like disease because of clear B-cell phenotype and c-myc gene rearrangement.


Immunomodulation of MiRNA-223-based nanoplatform for targeted therapy in retinopathy of prematurity.
Retinopathy of prematurity (ROP) is characterized by pathological angiogenesis and associated inflammation in the retina and is the leading cause of childhood blindness. MiRNA-223 (miR-223) drives microglial polarization toward the anti-inflammatory phenotype and offers a therapeutic approach to suppress inflammation and consequently pathological neovascularization. However, miRNA-based therapy is hindered by the low stability and non-specific cell-targeting ability of delivery systems. In the present study, we developed folic acid-chitosan (FA-CS)-modified mesoporous silica nanoparticles (PMSN) loaded with miR-223 to regulate retinal microglial polarization. The FA-CS/PMSN/miR-223 nanoparticles exhibited high stability and loading efficiency, achieved targeted delivery, and successfully escaped from lysosomes. In cultured microglial cells, treatment with FA-CS/PMSN/miR-223 nanoparticles upregulated the anti-inflammatory gene YM1/2 and IL-4RA, and downregulated the proinflammatory genes iNOS, IL-1β, and IL-6. Notably, in a mouse oxygen-induced retinopathy model of ROP, intravitreally injected FA-CS/PMSN/miR-223 nanoparticles (1 μg) decreased the retinal neovascular area by 52.6%. This protective effect was associated with the reduced and increased levels of pro-inflammatory (M1) and anti-inflammatory (M2) cytokines, respectively. Collectively, these findings demonstrate that FA-CS/PMSN/miR-223 nanoparticles provide an effective therapeutic strategy for the treatment of ROP by modulating the miR-223-mediated microglial polarization to the M2 phenotype.


Trends of self-reported sleep duration in Korean Adults: results from the Korea National Health and Nutrition Examination Survey 2007-2015.
Sleep plays a vital role in maintaining homeostasis and promoting individual health. This study aimed to investigate the trends of sleep duration in Korean adults. We collected data from individuals who were adults (≥18 years) and participated in three cycles (2007-2009, 2010-2012, and 2013-2015) of the Korea National Health and Nutrition Examination Survey (KNHANES) for the analysis of self-reported sleep duration pattern. A total of 51,545 adults (21,937 men and 29,608 women) were included. Sleep duration decreased among both men and women from 2007 to 2009 KNHANES to 2013-2015 KNHANES. Sleep duration differed by age group and sex. Moreover, sleep duration declined among middle-aged (30-49 years old) and older (50-64 years old) men and young (18-29 years old) and middle-aged (30-49 years old) women, although not among older and elderly women. The young and middle-aged adult groups (18-49 years old) showed a significant decline in sleep duration in the KNHANES 2007-2015.


Z-ligustilide isolated from Radix Angelicae sinensis ameliorates the memory impairment induced by scopolamine in mice.
We investigated the effect of Z-ligustilide (LIG) on scopolamine-induced memory impairment in ICR mice. LIG (2.5-40 mg/kg) or tacrine (10 mg/kg) was orally administrated for 26 days. Behavior was examined in the Morris water maze and Y-maze after scopolamine administration (2 mg/kg, i.p.). The central acetylcholinesterase (AChE) and choline acetyltransferase (ChAT) activities were assessed spectrophotometrically. LIG significantly improved spatial long-term memory and short-term memory impairment, inhibited AChE activity and increased ChAT activity. Moreover, LIG and tacrine showed the comparable efficacy in both neurobehavioral and cholinergic evaluation. These data suggest that LIG may alleviate memory deficits probably via enhancing cholinergic function.


A new, precise definition of acute myocardial infarction.
Several international cardiovascular societies have revised their diagnostic criteria for acute myocardial infarction (MI) (J Am Coll Cardiol 2007; 50:2173-2188). The cornerstone of diagnosis remains a high level of clinical suspicion, serial electrocardiograms, and troponin levels. This article reviews the new definition and the appropriate clinical tools necessary to diagnose acute MI accurately.


Analytical methodology for the profiling and characterization of androgen receptor active compounds in human placenta.
The exposure to endocrine disrupting chemicals during foetal development has been proposed to cause reproductive dysfunctions in the neonate or later life. In order to support such studies, an analytical method was developed to profile the receptor mediated (anti)androgenic activities present in extracts of placenta samples. Placenta samples from women giving birth to healthy male neonates were extracted and fractionated by HPLC. Fractions containing androgen receptor (AR) activity were detected using an in vitro yeast-based human androgen receptor transcription screen. GC-MS analyses of receptor active fractions resulted in detection of chemical contaminants including antimicrobial and cosmetic compounds which exhibited AR antagonist activity in the yeast screen, and endogenously derived steroids which contributed to both the agonist and antagonistic activity in the samples. The bioassay-directed fractionation methodology developed in this study revealed the potential to identify mixtures of chemical contaminants that should be investigated for potential effects on the reproductive system.


Synthesis, characterization and photoluminescence properties of CaSiO3:Eu3+ red phosphor.
CaSiO3:Eu3+ (1-5 mol%) red emitting phosphors have been synthesized by a low-temperature solution combustion method. The phosphors have been well characterized by powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) and optical spectroscopy. PXRD patterns reveal monoclinic CaSiO3 phase can be obtained at 900°C. The SEM micrographs show the crystallites with irregular shape, mostly angular. Upon 254 nm excitation, the phosphor show characteristic fluorescence 5D0→7FJ (J=0, 1, 2, 3, 4) of the Eu3+ ions. The electronic transition located at 614 nm corresponding to 5D0→7F2 of Eu3+ ions, which is stronger than the magnetic dipole transition located at 593 nm corresponding to 5D0→7F1 of Eu3+ ions. Different pathways involved in emission process have been studied. Concentration quenching has been observed for Eu3+ concentration>4 mol%. UV-visible absorption shows an intense band at 240 nm in undoped and 270 nm in Eu3+ doped CaSiO3 which is attributed to oxygen to silicon (O-Si) ligand-to-metal charge-transfer (LMCT) band in the SiO3(2-) group. The optical energy band gap is widened with increase of Eu3+ ion dopant.


Protein-carbohydrate regulation and nutritionally mediated responses to Bt are affected by caterpillar population history.
The widespread adoption of genetically modified crops, including Bacillius thuringensis (Bt) crops that target chewing insects, has transformed agricultural pest management. This increased use of Bt has raised concerns about the onset of resistance amongst target pests. Recent studies have shown that for some caterpillars, nutritional foraging (e.g. the ratio of proteins and carbohydrates consumed) can affect the insect susceptibility to the Bt toxin Cry1Ac. However, studies on both nutritional foraging and Bt susceptibility tend to rely on laboratory colonies without specifically addressing physiological differences that may occur between populations of the same species. Here, we used choice assays, no choice assays and dose response assays to address two overarching questions: Do populations of Spodoptera frugiperda (J.E. Smith) vary in their protein-carbohydrate foraging behavior? and Does protein-carbohydrate intake impact S. frugiperda's susceptibility to the Bt toxin Cry1F? All three of our S. frugiperda populations actively regulated their protein-carbohydrate intake, but we observed significant differences between populations with respect to their self-selected protein-carbohydrate intake. We also found that feeding at the protein-carbohydrate intake target slightly increased Cry1F susceptibility for one S. frugiperda population, but had no effect on the other two populations. Our findings indicate that inherent differences exist in the nutritional physiology of three S. frugiperda populations, possibly related to the time spent in culture. This suggests that population-level differences are an important consideration when drawing parallels between field-collected and laboratory-reared insects.


Is intraspecific variability of growth and mycotoxin production dependent on environmental conditions? A study with Aspergillus carbonarius isolates.
The aim of this study was to assess the impact of suboptimal environmental conditions on the intraspecific variability of A. carbonarius growth and OTA production using thirty isolates of A. carbonarius. Three a(w)/temperature conditions were tested, one optimal (0.98a(w)/25°C) and two suboptimal: 0.90a(w)/25°C and 0.98a(w)/37°C as suboptimal water activity and temperature, respectively, which might take place through over ripening and dehydration of grapes. For each condition, 12 Petri dishes were inoculated, and colony growth and OTA production were measured over time. ANOVA revealed significant differences among μ and λ within the 30 assayed isolates. Coefficients of variation (CV%) revealed a wider dispersion of growth rates at 0.90a(w)/25°C compared to 0.98a(w)/25°C, and a more than 4-fold higher CV at 0.98a(w)/37°C compared to 0.98a(w)/25°C. However, dispersion of lag phases was similar at 0.98a(w)/25°C and 0.90a(w)/25°C and wider at 0.98a(w)/37°C. There were significant differences (p<0.05) among OTA levels (ng/mm(2)) for the different conditions, values being lower under marginal conditions, and particularly at 0.98a(w)/37°C. Coefficients of variation (CV%) revealed a wider dispersion of OTA production at 0.90a(w)/25°C compared to 0.98a(w)/25°C, while CV at 0.98a(w)/37°C was similar to that at 0.98a(w)/25°C. In order to address the strain variability in growth initiation and prove the well-established notion of reducing OTA in foods by preventing fungal growth, a greater number of strains should be included when developing models for conditions that are suboptimal both for a(w) for OTA production and temperature levels for growth.


Depression, anxiety and stress among pregnant migraineurs in a pacific-northwest cohort.
The co-occurrence of migraine and unipolar psychiatric disorders has been well documented in non-pregnant populations, however little is known in pregnant populations. A cohort of 1321 women was interviewed during the first trimester of pregnancy. At the time of interview lifetime migraine status was ascertained using International Classification of Headache Disorders diagnostic criteria (ICHD-II). Information regarding unipolar depression, anxiety and stress during pregnancy was collected using the Patient Health Questionnaire Depression Module-9 (PHQ-9), and the Depression Anxiety Stress Scales 21-item Short Form (DASS-21). Multivariable logistic regression procedures were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association of migraine and mood disorders during pregnancy. Approximately 28.2% (N=372) were classified as having a lifetime history of migraine; among migraineurs 122 were classified as migraineurs with aura and 250 as migraineurs without aura. Compared with non-migraineurs, migraineurs were associated with 1.60-fold increased odds of depression as measured by a PHQ-9 score ≥10 (AOR=1.60; 95% CI: 1.12-2.31). Overall, migraine with aura was more strongly associated with depression than was migraine without aura. Migraineurs, as compared with non-migraineurs, also had higher odds of mood disorders as measured by the DASS-21. The comorbidity of mood and migraine disorders in pregnant populations supports the need for integrated mental and physical clinical evaluation, increased vigilance, and treatment of patients with such disorders.


Differing Time Courses of Reward-Related Attentional Processing: An EEG Source-Space Analysis.
Since our environment typically contains more information than can be processed at any one time due to the limited capacity of our visual system, we are bound to differentiate between relevant and irrelevant information. This process, termed attentional selection, is usually categorized into bottom-up and top-down processes. However, recent research suggests reward might also be an important factor in guiding attention. Monetary reward can bias attentional selection in favor of task-relevant targets and reduce the efficiency of visual search when a reward-associated, but task-irrelevant distractor is present. This study is the first to investigate reward-related target and distractor processing in an additional singleton task using neurophysiological measures and source space analysis. Based on previous studies, we hypothesized that source space analysis would find enhanced neural activity in regions of the value-based attention network, such as the visual cortex and the anterior cingulate. Additionally, we went further and explored the time courses of the underlying attentional mechanisms. Our neurophysiological results showed that rewarding distractors led to a stronger attentional capture. In line with this, we found that reward-associated distractors (compared with reward-associated targets) enhanced activation in frontal regions, indicating the involvement of top-down control processes. As hypothesized, source space analysis demonstrated that reward-related targets and reward-related distractors elicited activation in regions of the value-based attention network. However, these activations showed time-dependent differences, indicating that the neural mechanisms underlying reward biasing might be different for task-relevant and task-irrelevant stimuli.


Involvement of neural substrates in reward and aversion to methamphetamine addiction: Testing the reward comparison hypothesis and the paradoxical effect hypothesis of abused drugs.
Clinical studies of drug addiction focus on the reward impact of abused drugs that produces compulsive drug-seeking behavior and drug dependence. However, a small amount of research has examined the opposite effect of aversion to abused drugs to balance the reward effect for drug taking. An aversive behavioral model of abused drugs in terms of conditioned taste aversion (CTA) was challenged by the reward comparison hypothesis (Grigson, 1997). To test the reward comparison hypothesis, the present study examined the rewarding or aversive neural substrates involved in methamphetamine-induced conditioned suppression. The behavioral data showed that methamphetamine induced conditioned suppression on conditioning and reacquisition but extinguished it on extinction. A higher level of stressful aversive corticosterone occurred on conditioning and reacquisition but not extinction. The c-Fos or p-ERK immunohistochemical activity showed that the cingulated cortex area 1 (Cg1), infralimbic cortex (IL), prelimbic cortex (PrL), basolateral amygdala (BLA), nucleus accumbens (NAc), and dentate gyrus (DG) of the hippocampus were overexpressed in aversive CTA induced by methamphetamine. These data may indicate that the Cg1, IL, PrL, BLA, NAc, and DG probably mediated the paradoxical effect-reward and aversion. Altogether, our data conflicted with the reward comparison hypothesis, and methamphetamine may simultaneously induce the paradoxical effect of reward and aversion in the brain to support the paradoxical effect hypothesis of abused drugs. The present data implicate some insights for drug addiction in clinical aspects.


Nomograms to predict 2-year overall survival and advanced schistosomiasis-specific survival after discharge: a competing risk analysis.
The prognosis of patients with advanced schistosomiasis is poor. Pre-existing prognosis studies did not differentiate the causes of the deaths. The objectives were to evaluate the 2-year overall survival (OS) and advanced schistosomiasis-specific survival (ASS) in patients with advanced schistosomiasis after discharge through competing risk analysis and to build predictive nomograms. Data was extracted from a previously constructed database from Hubei province. Patients were enrolled from September 2014 to January 2015, with follow up to January 2017. OS and ASS were primary outcome measures. Nomograms for estimating 2-year OS and ASS rates after discharge were established based on univariate and multivariate Cox regression model and Fine and Gray's model. Their predictive performances were evaluated using C-index and validated in both internal and external validation cohorts. The training cohort included 1487 patients with advanced schistosomiasis. Two-year mortality rate of the training cohort was 8.27% (123/1487). Competing events accounted for 26.83% (33/123). Older age, splemomegaly clinical classification, abnormal serum DBil, AST, ALP and positive HBsAg were significantly associated with 2-year OS. Older age, splemomegaly clinical classification, abnormal serum AST, ALP and positive HBsAg were significantly associated with 2-year ASS. The established nomograms were well calibrated, and had good discriminative ability, with a C-index of 0.813 (95% CI 0.803-0.823) for 2-year OS prediction and 0.834 (95% CI 0.824-0.844) for 2-year ASS prediction. Their predictive performances were well validated in both internal and external validation cohorts. The effective predictors of 2-year OS and ASS were discovered through competing risk analysis. The nomograms could be used as convenient predictive tools in clinical practice to guide follow-up and aid accurate prognostic assessment.


Differential alcohol drinking behaviour and dependence in the Naples low- and high-excitability rat lines.
Alcoholism is composed of a series of phenomena, which can be approached in model systems. Our aim was to investigate psychogenetics of alcohol drinking behaviour and dependence in the Naples rat lines. Thus, adult male rats of the Naples low- (NLE), high-excitability (NHE) and random-bred control (NRB) lines had 24-h access to a four-bottle system with tap water and 5, 10 and 20% alcohol solutions. Total voluntary alcohol intake and preference were measured during a 6-week period. In order to analyze behavioural dependence, two abstinence periods were introduced, followed by re-exposure to the bottles. The first was a pure re-test and the second was a quinine test (adding 0.02% quinine alcohol solution). Finally, to verify the role of opioids on alcohol drinking behaviour, rats received naltrexone (5 mg/kg i.p.). Thirty minutes later, they had access for 2 h to a three-bottle system with water, 5 and 20% alcohol solution, respectively. Results indicate that (i) total alcohol intake on day 1 was higher in both NLE/NHE, becoming higher in NLE rats during the 6-week period, (ii) different alcohol preference patterns in the Naples lines were observed over time of testing, (iii) during re-test, NLE rats showed neither reversibility nor alcohol deprivation effect, (iv) during quinine test, only NLE rats reduced alcohol intake to a lower extent and (v) naltrexone reduced by 50% the intake of the preferred solution. Therefore, the NLE rats appear as a new model for studying the neural substrates of the dependence behaviour.


Failure of naloxone to reverse the nitrous oxide-induced depression of a brain stem reflex: an electrophysiologic and double-blind study in humans.
The effects of 33% nitrous oxide on the two components of the blink reflex were studied on seven healthy volunteers. The blink responses were elicited by a supraorbital nerve stimulation and recorded from the ipsilateral orbicularis oculi muscle. The intensity of stimulation was chosen at two to three times the reflex threshold in order to obtain stable suprathreshold reflex responses as well as a tolerable pain sensation reported by the volunteers. Nitrous oxide administration resulted in a potent depression of the two components of the blink reflex. This depressive effect was more marked upon the late (R2) nociceptive component (83%) than upon the early (R1) component (41%). Simultaneously, subjects reported either a decrease in pain sensation or an indifference toward the painful stimulus. None of these effects were reversed by a double-blind intravenous naloxone (1.4 mg) injection. The analgesic effect of nitrous oxide is a nonspecific depressant action on the transmission of the nociceptive messages in central nervous structures, independent of pain-suppressive endogenous morphine-like systems.


Centrally administered butyrate improves gut barrier function, visceral sensation and septic lethality in rats.
Short chain fatty acids readily crosses the gut-blood and blood-brain barrier and acts centrally to influence neuronal signaling. We hypothesized that butyrate, a short-chain fatty acid produced by bacterial fermentation, in the central nervous system may play a role in the regulation of intestinal functions. Colonic permeability and visceral sensation was evaluated in rats. Septic lethality was evaluated in a sepsis model induced by subcutaneous administration of both lipopolysaccharide and colchicine. Intracisternal butyrate dose-dependently improved colonic hyperpermeability and visceral nociception. In contrast, subcutaneous injection of butyrate failed to change it. Intracisternal orexin 1 receptor antagonist or surgical vagotomy blocked the central butyrate-induced improvement of colonic hyperpermeability. The improvement of intestinal hyperpermeability by central butyrate or intracisternal orexin-A was blocked by cannabinoid 1 or 2 receptor antagonist. Intracisternal butyrate significantly improved survival period in septic rats. These results suggest that butyrate acts in the central nervous system to improve gut permeability and visceral nociception through cannabinoid signaling. Endogenous orexin in the brain may mediate the reduction of intestinal hyperpermeability by central butyrate through the vagus nerve. We would suggest that improvement of leaky gut by central butyrate may induce visceral antinociception and protection from septic lethality.


Neutron flux evaluation model provided in the accelerator-based boron neutron capture therapy system employing a solid-state lithium target.
An accelerator-based boron neutron capture therapy (BNCT) system employing a solid-state Li target can achieve sufficient neutron flux for treatment although the neutron flux is reduced over the lifetime of its target. In this study, the reduction was examined in the five targets, and a model was then established to represent the neutron flux. In each target, a reduction in neutron flux was observed based on the integrated proton charge on the target, and its reduction reached 28% after the integrated proton charge of 2.52 × 106 mC was delivered to the target in the system. The calculated neutron flux acquired by the model was compared to the measured neutron flux based on an integrated proton charge, and the mean discrepancies were less than 0.1% in all the targets investigated. These discrepancies were comparable among the five targets examined. Thus, the reduction of the neutron flux can be represented by the model. Additionally, by adequately revising the model, it may be applicable to other BNCT systems employing a Li target, thus furthering research in this direction. Therefore, the established model will play an important role in the accelerator-based BNCT system with a solid-state Li target in controlling neutron delivery and understanding the neutron output characteristics.


Analytical model of I-bar clasps for removable partial dentures.
Clasps of removable partial dentures (RPDs) often suffer from fatigue stress that leads to plastic deformation, loss of retention, and RPD failure. Recently, computer-based technologies were proposed to optimize clasp geometry design. The objective of this study was to create an analytic model of I-bar clasps for computer-aided design (CAD)-RPD. The analytical model based on mechanical laws was established to simulate I-bar clasp retention, and optimize its design. The model considered the lengths of the vertical (L1) and horizontal (L2) arms of the I-bar as well as the radius (r) of its half-round cross-section. The analytical model was validated with mechanical experiments evaluating the retention of cobalt-chromium (Co-Cr) clasps in vitro and compared with finite element analysis (FEA). The analytical model was in good agreement with the mechanical experiments and FEA, and showed that I-bar clasp design could provide optimal mechanical performance as long as the length of arms (L1 and L2) do not exceed 6 mm. Clasps with L1 > 8 mm and L2 > 9 mm presented stress values exceeding the fatigue limit of Co-Cr. The proposed solution was to increase the radius of I-bar to conserve the initial mechanical performance of Co-Cr. Co-Cr I-bar clasps perform best on teeth with reduced mesiodistal dimensions (canine and premolar), and their designs could be optimized to prevent stress from reaching the yield strength and the fatigue failure limit.


Weight, length and head circumference standards based on a population of Danish newborn boys and girls in gestational weeks 25 to 43.
Growth standards of birth weight, birth length and birth head circumference were constructed based on a population of Danish newborn boys and girls in gestational weeks twenty-five to forty-three. Study populations were residents of the municipality of Odense for later gestational ages and residents of the county of Funen for early gestational ages. Strict selection criteria were employed.


Status epilepticus following intentional overdose of fluvoxamine: a case report with serum fluvoxamine concentration.
Fluvoxamine is a selective serotonin reuptake inhibitor (SSRI) that is used in the management of depression and obsessive compulsive disorders. We report a patient with status epilepticus requiring quadruple anti-convulsant treatment following a fluvoxamine overdose. A 25-year-old female presented with drowsiness at 12 hours following deliberate ingestion of 9.6 grams of fluvoxamine. Sixteen hours after ingestion, she developed status epilepticus that required treatment with benzodiazepines (lorazepam and midazolam), thiopentone, phenytoin and phenobarbitone. Her serum fluvoxamine concentration on presentation was 1970 microg/L (therapeutic 160-220 microg/L) and routine toxicological screening was negative for other drugs. She was discharged home after 72 hours with no further episodes of seizures. Most patients with fluvoxamine poisoning are either asymptomatic or may develop mild signs of serotonergic toxicity. Although serotonin syndrome and isolated seizures are reported in fluvoxamine poisoning, we report the first patient with confirmed isolated fluvoxamine toxicity who developed status epilepticus.


Optimizing HIV Prevention Efforts to Achieve EHE Incidence Targets.
A goal of the US Department of Health and Human Services' Ending the HIV Epidemic (EHE) in the United States initiative is to reduce the annual number of incident HIV infections in the United States by 75% within 5 years and by 90% within 10 years. We developed a resource allocation analysis to understand how these goals might be met. We estimated the current annual societal funding [$2.8 billion (B)/yr] for 14 interventions to prevent HIV and facilitate treatment of infected persons. These interventions included HIV testing for different transmission groups, HIV care continuum interventions, pre-exposure prophylaxis, and syringe services programs. We developed scenarios optimizing or reallocating this funding to minimize new infections, and we analyzed the impact of additional EHE funding over the period 2021-2030. With constant current annual societal funding of $2.8 B/yr for 10 years starting in 2021, we estimated the annual incidence of 36,000 new cases in 2030. When we added annual EHE funding of $500 million (M)/yr for 2021-2022, $1.5 B/yr for 2023-2025, and $2.5 B/yr for 2026-2030, the annual incidence of infections decreased to 7600 cases (no optimization), 2900 cases (optimization beginning in 2026), and 2200 cases (optimization beginning in 2023) in 2030. Even without optimization, significant increases in resources could lead to an 80% decrease in the annual HIV incidence in 10 years. However, to reach both EHE targets, optimization of prevention funding early in the EHE period is necessary. Implementing these efficient allocations would require flexibility of funding across agencies, which might be difficult to achieve.


Habitat heterogeneity helps to mitigate pollinator nectar sugar deficit and discontinuity in an agricultural landscape.
The scarcity of floral resources and their seasonal discontinuity are considered as major factors for pollinator decline in intensified agricultural landscapes worldwide. The consequences are detrimental for the stability of the environment and ecosystems. Here, we quantified the production of nectar sugars in plant species occurring in man-made, non-cropped areas (non-forest woody vegetation, road verges, railway embankments, field margins, fallow areas) of an agricultural landscape in SE Poland. We also assessed changes in the availability of sugar resources both in space (habitat and landscape scales) and in time (throughout the flowering season), and checked to what extent the sugar demands of honeybees and bumblebees are met at the landscape scale. At landscape-level, 37.6% of the available sugar resources are produced in man-made, non-cropped habitats, while 32.6% and 15.0% of sugars derive from winter rape crops and forest vegetation, respectively. Nectar sugar supplies vary greatly between man-made, non-cropped habitat types/sub-types. These areas are characterized by a high richness of nectar-producing species. However, a predominant role in total sugar resources is ascribable to a few species. Strong fluctuations in nectar resources are recorded throughout the flowering season. March and June are periods with food shortages. Abundant nectar sugars are generally found in April-May, mainly due to the mass flowering of nectar-yielding species in the forests, meadows/pastures and orchards/rapeseed crops. Heterogeneity of man-made, non-cropped habitats is essential to support the supply of July-October nectar sugars for honeybees and bumblebees. Reduced flowering in man-made non-cropped habitats can generate serious food deficiencies, as from summer towards the end of the flowering season >90% of sugars are provided by the flora of these areas. Therefore, highly nectar-yielding plant species that flower during periods of expected food shortages should be a priority for conservation and restoration programs.


On the mechanism of the Menière attack.
Three theories are discussed dealing with the origin of the Menière attack: 1) The hypothesis of pressure induced changes is disproved. 2. The stimulation of the crista epithelium by a mechanical cupula deviation has been investigated. The results showed that the changes in action potential frequency of the ampullary nerve induced by maintained bending of the cupula, always declined and returned to resting potential frequency within a very short period of time usually within 1 min. Preventing the "elastic return" of the cupula did not change the time constant of this response decline. This proves that a Menière nystagmus lasting for hours, can not be elicited by a mechanical deformation of the cupula. 3) The paralyzing influence on vestibular nerve fibres by K+ ions in endolymph, leaking into perilymph spaces has earlier been demonstrated by the author. When the distended membranous labyrinth ruptures at predestined weak spots, leaking endolymph may reach and paralyze different nerve branches. This can explain all the main symptoms of a Menière attack.


Determination of raloxifene and its glucuronides in human urine by liquid chromatography-tandem mass spectrometry assay.
A selective, sensitive, accurate and precise liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determination of raloxifene and its three glucuronides: raloxifene-6-β-glucuronide (M1), raloxifene-4'-β-glucuronide (M2), raloxifene-6,4'-diglucuronide (M3) in urine samples is presented in this paper. To our knowledge the developed analytical method is the first fully validated method capable of simultaneous determination of raloxifene and its glucuronides in real urine samples. Moreover, for the first time a method for determination of raloxifene diglucuronide in relevant biological samples was introduced. Metabolites were obtained by a bioconversion process of raloxifene to its glucuronides using the microorganism Streptomyces sp. and were used as standards for validation. Urine samples were introduced to a simple solid phase extraction prior to the analysis by LC-MS/MS. The method was linear in a wide range with high determination coefficient (r(2) > 0.997). The limits of quantification achieved were 1.01, 1.95, 2.83 and 4.69 nM for raloxifene, M1, M2 and M3, respectively. The recoveries were higher than 92.5%, the accuracy was within 100 ± 8.8% and the precision was better than 12% for all compounds. The developed method was successfully applied to the real urine samples and showed to be appropriate for use in further research of still not completely discovered raloxifene pharmacokinetics. Furthermore, the presented method could also serve for a potential application in anti-doping analysis.


Phylogenetic insights and antimicrobial biosynthetic potential of Serratia sp. XAFb12 and Pseudomonas sp. XAFb13 from Xylopia aethiopica.
The extensive distribution of Xylopia aethiopica across the continent of Africa has firmly established its medicinal value in diverse disease management. While its phytochemistry is well established, the diversity, molecular, biochemical, and antimicrobial-biosynthetic characterizations of culturable bacterial endophytes residing in fruits of X. aethiopica have not been studied previously. Additionally, danger continues to loom the global health care and management due to antibiotic resistance; hence, the discovery of microbial natural products especially from endophytes could offer a lasting solution to the quest for novel antimicrobial compounds. In this study, we isolated two bacterial endophytes Serratia sp. XAFb12 and Pseudomonas sp. XAFb13 from fresh X. aethiopica fruit. The 16S rRNA gene sequencing, Vitex biochemical test, Gram staining, and 16S rRNA gene analysis were used to confirm their phenotypic and genotypic profiles. Phylogenetic tree analysis reveals their divergence in a separate branch, indicating their uniqueness. The crude extract of both strains showed inhibition against all tested bacterial and fungal pathogens. The minimum inhibition concentration (MIC) ranged from 2.5 to 10%. Chemical analysis of the crude extracts using gas chromatography-mass spectroscopy (GC-MS) revealed the most abundant compounds to be hydrocinnamic acid, 2-piperidinone, 5-isopropylidene-3,3-dimethyl-dihydrofuran-2-one, and diethyl trisulfide. The bacterial endophytes linked to X. aethiopica were described in this study for the first time in relation to clinically significant pathogens. Our findings imply that crude extracts of the endophytic bacteria from X. aethiopica could be potentially employed as antibiotics. Hence, it is crucial to characterize the active ingredient in further detail for future pharmaceutical applications.


Crosstalk of cell polarity signaling pathways.
Cell polarity, the asymmetric organization of cellular components along one or multiple axes, is present in most cells. From budding yeast cell polarization induced by pheromone signaling, oocyte polarization at fertilization to polarized epithelia and neuronal cells in multicellular organisms, similar mechanisms are used to determine cell polarity. Crucial role in this process is played by signaling lipid molecules, small Rho family GTPases and Par proteins. All these signaling circuits finally govern the cytoskeleton, which is responsible for oriented cell migration, cell shape changes, and polarized membrane and organelle trafficking. Thus, typically in the process of cell polarization, most cellular constituents become polarized, including plasma membrane lipid composition, ion concentrations, membrane receptors, and proteins in general, mRNA, vesicle trafficking, or intracellular organelles. This review gives a brief overview how these systems talk to each other both during initial symmetry breaking and within the signaling feedback loop mechanisms used to preserve the polarized state.


Genetic screening of Filipinos suspected with familial Parkinson's disease: A pilot study.
Although genetic factors are known to play a role in the pathogenesis of Parkinson's disease (PD), true prevalence of familial PD is unknown. We conducted this pilot study to identify genes implicated in familial Parkinson's disease among Filipinos. Eighteen Filipino patients belonging to 11 families with personal and family history of PD underwent thorough evaluation by movement disorders specialists. Samples were analyzed in Juntendo University, Tokyo, Japan. Sanger sequencing of polymerase chain reaction products was performed. Each sample was screened for 23 genes (SNCA, PARK 2, UCHL1, PINK 1, DJ-1, LRRK2, ATP13A2, GIGYF2, HTRA2, PLA266, FBX07, VPS35, EIF461, DNAJC13, CHCHD2, GCH1, MAPT, NR4A2, VPS13c, PSEN1, and GRN). Out of 18 patients, six harbored Parkinson-related gene mutations. Five individuals from three families were positive for PINK1 c.10140T > C(p.L347P) mutation while one had heterozygous variant PRKN c.136G>T(p.A465) gene mutation. Three families displayed autosomal recessive pattern while one family with PINK1 mutation showed autosomal dominant mode of inheritance. Bradykinesia and tremor were predominant symptoms. Mean age at onset of symptoms was 40.4 years among those with PINK1 mutations. In this study, we presented the clinical profiles and identified two genetic mutations among a small group of Filipino patients with familial PD. They were congruent with most studies showing these mutations as the most common causes of autosomal recessive early-onset PD. Preliminary data from this pilot study will guide planning for larger scale studies, such as collaborative projects including The Global Parkinson's Genetics Program (GP2).


Outcomes of a Quality Improvement Project Examining Early Childhood Caries and Improving Identification of At Risk Patients in a Pediatric Medical Home Setting.
Early childhood caries (ECC) is a widespread childhood disease that disproportionately affects children with disabilities, those in lower-income households and minority children. The American Academy of Pediatrics (AAP) recommends that all children be screened for ECC and referred to a dentist by the age of one. This quality improvement project took place at a hospital-affiliated pediatric clinic. A caries risk screening tool was implemented at 9-, 12-, and 18-month well child check-ups for 3 months. A retrospective chart review was performed for comparison purposes. The quality improvement project indicated improvement in identification of children at high-risk for ECC.


Volunteer human subjects' understandings of their participation in a biomedical research experiment.
The paper focuses on how volunteer human subjects in research understand their own participation in experimentation. We ask how they view their own role, the experimental setting, and how they articulate their understanding of the researcher-subject relationship. The empirical basis of the study is participant-observation and qualitative semi-structures interviews with volunteers in an experimental setting far removed from the more commonly studied randomised control trial (RCT), namely, the early stage testing of a prototype instrument for breast imaging. Analysis of this empirical data leads us to conclude that research subjects do not conform solely to one or other of the models of the researcher-subject relationship suggested in the literature. Rather, the interaction needs to be considered as a social situation which volunteer subjects actively negotiate in real time. They move through multiple roles and identities as part of the navigation through unfamiliar social territory, in order to establish a relationship in which they can feel socially comfortable and appropriately valued.


Soft tissue trauma and scar revision.
Numerous techniques and treatments have been described for scar revision, with most studies focusing on the adult population. A comprehensive review of the literature reveals a paucity of references related specifically to scar revision in children. This review describes the available modalities in pediatric facial scar revision. The authors have integrated current practices in soft tissue trauma and scar revision, including closure techniques and materials, topical therapy, steroid injection, cutaneous laser therapy, and tissue expanders.


Getting personal: understanding how genetic variation affects clinical outcomes in patients with tetralogy of Fallot.
The work by Jeewa et al. is an important step toward "personalizing" or individualizing our approach to care of patients with tetralogy of Fallot. Although future studies will need to confirm the potential role of HIF1A-mediated signaling in right ventricular remodeling, it raises the possibility that modulation of the HIF1A signaling pathway or its downstream effectors such as TGF-β may allow better preservation of ventricular function in patients with TOF. Furthermore, directed genotyping for HIF1A and other genetic variants may help identify patients at risk for adverse outcomes. This study demonstrates the potential for genetics-of- outcomes studies to evaluate novel therapeutic targets and to identify at-risk populations that may require specific therapeutic considerations.


Continuous pressurized extraction versus electric fields-assisted extraction of cyanobacterial pigments.
Cyanobacteria pigments, in special carotenoids and phycobiliproteins, are usually used in industry as raw extracts, although there is still no standard methodology for their extraction. For the co-extraction of carotenoids and phycobiliproteins from the marine cyanobacterium Cyanobium sp., a continuous pressurized solvent extraction (CPSE) system and an electric fields-assisted extraction system based in ohmic heating were optimized using Central Composite Designs, with three factors each: time (t), temperature (T) and, flow (f) for CPSE; and time, temperature and frequency (F) for ohmic heating. The content of pigments and the antioxidant capacity of extracts were evaluated. All tested factors seem to influence the extraction of pigments in different ways: a high temperature (70 °C) had a positive impact on the extraction rate in both methods, while the influence of time depended on the extraction principle. Flow and frequency affected directly the extraction efficiency and these methods are indeed suitable for cyanobacterial pigments extraction, achieving good extraction results. Optimal conditions for co-extraction of carotenoids and phycobiliproteins in CPSE were T = 70 °C, t = 20 min and f = 1.5 mL min-1, and for ohmic heating they were T = 70 °C, t = 5 min and F = 20 kHz. Both, CPSE and ohmic heating systems allowed obtaining better extraction yields when compared with a previously optimized extraction method (homogenization), used here as a reference. However, ohmic heating was the best methodology for pigments co-extraction from Cyanobium sp.


Beating-heart surgery for hypoplastic left heart syndrome with coronary artery fistulas.
The presence of ventriculocoronary connections in patients with hypoplastic left heart syndrome and mitral stenosis-aortic atresia is a suggested risk factor for myocardial ischemia after surgical palliation. We describe a neonate with this anatomic variant of hypoplastic left heart syndrome who underwent a successful beating-heart Norwood operation, with continuous coronary perfusion. The ventricular condition could be visually confirmed during the procedure, and a postoperative echocardiogram showed preserved ventricular function. This technique is considered an effective option for minimizing myocardial damage in this patient subtype.


Epidemiological and clinical presentations of hospitalized COVID-19 patients in Libya: An initial report from Africa.
The first case of the novel coronavirus disease 2019 (COVID-19) in Libya was diagnosed in March 2020. We aimed to determine the epidemiological, clinical, and laboratory characteristics of COVID-19 in Libya. In this retrospective descriptive study, we analyzed the demographics, initial clinical presentation, history, comorbidities, laboratory findings, complications, and outcomes of hospitalized patients with COVID-19 at several centers in the Western part of Libya between March 24, 2020, and December 3, 2020. The study included 811 (67.2%) men and 396 (32.8%) women. The median (interquartile range [IQR]) age was 56 (40-64). A total of 173 (14.3%) patients developed respiratory distress syndrome, while 70 (5.8%) developed circulatory shock and hypotension; 190 (15.7%) were admitted to the intensive care unit. Acute cardiac injury occurred in 27 (2.2%) patients, and 45 (3.7%) developed arrhythmia. Acute kidney injury occurred in 44 (3.6%) patients. Of the patients admitted during the study period, 149 (12.3%) died. The predominant comorbidities ordered in a descending manner were as follows; diabetes mellitus, presented 490 (40.6%), hypertension in 414 (34.3%), chronic kidney disease in 114 (9.4%), and lung diseases in 103 (8.5%). The total white blood cell, neutrophil; monocyte; D-dimer; creatinine kinase; creatine kinase-MB; creatinine; total bilirubin; alanine and aspartate aminotransferase; and hypersensitive troponin were increased among non-survivors, whereas lymphocyte and platelet counts were decreased among non-survivors. This is the first report of the clinical presentations and laboratory findings in patients hospitalized with COVID-19 in Libya. Libyan authorities must implement several restrictions to control the pandemic. However, incoming international travelers pose a challenge to the local authorities, especially with the recent discovery of new variants.


[Aglossia-adactilia syndrome].
A 7 month-old girl was studied and found to have aglossia--adactylia syndrome. The etiopathogenic aspects of this disorder are discussed.


Calcific uremic arteriolopathy treated with cinacalcet, paricalcitol, and autologous growth factors.
Calcific uremic arteriolopathy is an uncommon cutaneous ischemic necrotizing disease, most commonly associated with renal disease and hyperparathyroidism, bearing a high mortality rate. A case of a 57-year-old female renal patient with hyperparathyroidism who was successfully treated with combined paricalcitol and cinacalcet systemically, while autologous growth factors were locally applied, is herein presented. The combination of cinacalcet and paricalcitol is a reliable alternative to parathyroidectomy in patients with calcific uremic arteriolopathy and hyperparathyroidism. Meticulous débridement of necrotic tissues is essential and application of autologous growth factors promotes healing.


Is it possible to evaluate addiction from clinical records? Testing a retrospective addiction severity evaluation measure.
To compare an addiction severity score estimated from clinical records to addiction severity index (ASI) scores. During April-May 2004, 31 patients treated in a therapeutic community in the Piedmont region (Italy) were interviewed using the ASI questionnaire and their clinical records were used to obtain severity scores in seven areas: physical health, occupational functioning, alcohol use, drug use, legal problems, family/social relationships, psychological health. Correlation, agreement, and discriminatory capacity of the clinical records score in correctly classifying persons with low or high severity were investigated using Spearman, Kappa coefficient, and receiver operating characteristics curves. Clinical records score showed good correlation, agreement, and discriminatory accuracy with respect to ASI scores, especially in the drug use and legal problems areas. Further research is suggested to study the use of the score in other settings.


Temporal-spatial variations, source apportionment, and ecological risk of trace elements in sediments of water-level-fluctuation zone in the Three Gorges Reservoir, China.
The Three Gorges Reservoir (TGR) plays a crucial role in providing electricity for mega-cities across China. However, since the impoundment was completed in 2006, attention to environmental concerns has also been intensive. In order to determine the distribution, sources, and pollution status of trace elements in the water fluctuation zone of the TGR following ten years of repeated "submergence" and "exposure", we systematically collected 16 paired surface sediment samples (n = 32) covering the entire main body of the TGR in March 2018 (following 6 months of submergence) and September 2018 (after 6 months of exposure), and quantitatively analyzed 13 elements (e.g., Mn, Fe, V, Cr, Ni, Cu, Zn, As, Sr, Y, Zr, Ba, and Pb) using X-ray fluorescence spectrophotometry (XRF). The results showed that, except for Sr, concentrations of trace metals following submergence were generally higher than those after exposure due to the less settling of suspended solids at the faster flow velocity during the drawdown period. Assessment using enrichment factors (EFs) and a geo-accumulation index (Igeo) both characterized a relatively serious anthropogenic pollution status of metals in the upper reaches of the TGR with respect to the middle-lower reaches. Source apportionment by positive matrix factorization (PMF) analysis indicated that agricultural activities (24.8 and 24.3%, respectively) and industrial emissions (24.5 and 22.9%, respectively) were the two major sources in these two periods, followed by natural sources, domestic sewage, and ore mining. Ecological risk assessment showed that metalloid arsenic (As) could be the main potential issue of risk to aquatic organisms and human health. A new source-specific risk assessment method (pRI) combined with PMF revealed that agricultural activities could be the major source of potential ecological risk and should be prioritized as the focus of metal/metalloid risk management in the TGR.


Actin' as a death signal.
Cell death needs to be detected by immune cells. In this issue of Immunity, Ahrens et al. (2012) and Zhang et al. (2012) show that actin filaments become exposed on necrotic cells and act as ligands for the C-type lectin receptor Clec9a.


Harms of third party criminalisation under end-demand legislation: undermining sex workers' safety and rights.
After Canada's laws criminalising sex work were struck down by the Supreme Court for violating sex workers' rights and new end-demand legislation was passed in 2014. These new laws however continue to criminalise sex work third parties (i.e. venue owners/managers) who gain material benefits, despite evidence that managed in-call venues can provide important protections for sex workers. As part of a longstanding community-based study in Vancouver, this analysis drew on 25 in-depth interviews with third parties who provide services for indoor sex workers. We explored how end-demand third party criminalisation shapes indoor sex workers' working conditions, health and safety. We found that most third parties were women and current/former sex workers, problematising assumptions of third parties as exploitative male "pimps". Third parties provided client screening, security and sexual health resources for sex workers, yet end-demand laws restricted condom availability and access to police protections in case of violence, thereby undermining sex workers' health and safety. Our findings highlight that third party criminalisation under end-demand legislation reproduces the unsafe working conditions under the previous laws deemed unconstitutional by Canada's highest court. Legislative reforms to decriminalise all aspects of the sex industry, including sex workers' right to work with third parties, are urgently needed.


An unusual glycoform of human salivary mucin MG2.
Since in a previous study we encountered a subject with an unusual split MG2 banding pattern, the aim of this study was to investigate the molecular basis of this observation. Submandibular/sublingual secretion was collected under resting and stimulated conditions and examined on Western blots probed with anti-MG2 antibodies or on gels stained with periodic acid-Schiff reagent. Genomic DNA was isolated and the N-, tandem repeat (TR), and C-terminal regions of MUC7 were amplified by PCR since MG2 is known to display a genetic polymorphism. Although the typical appearance of MG2 on blots and gels is a single 180 kDa band, salivary secretions from the subject exhibited doublet immunoreactive bands of approximately 180 and 125 kDa. Additionally, under resting conditions the 180 kDa band was predominant whereas upon stimulation the 125 kDa band became predominant. Genomic DNA analysis showed that MUC7 in the individual with split MG2 bands was not truncated and that the MUC7 genotype in this individual was (6/6) where both alleles encoded six TRs. The MG2 split banding pattern observed in this subject was not derived from proteolytic degradation of this salivary mucin in whole saliva or from genetic polymorphism. The expression of two isoforms of MG2 could in principle improve or reduce the activity of this key component of the oral host defense system.


Machine Learning and Deep Learning in Medical Imaging: Intelligent Imaging.
Artificial intelligence (AI) in medical imaging is a potentially disruptive technology. An understanding of the principles and application of radiomics, artificial neural networks, machine learning, and deep learning is an essential foundation to weave design solutions that accommodate ethical and regulatory requirements, and to craft AI-based algorithms that enhance outcomes, quality, and efficiency. Moreover, a more holistic perspective of applications, opportunities, and challenges from a programmatic perspective contributes to ethical and sustainable implementation of AI solutions.


RhoB as a tumor suppressor: It's all about localization.
The small GTPase RhoB is distinguished from other Rho proteins by its unique subcellular localization in endosomes, multivesicular bodies, and nucleus. Despite high sequence homology with RhoA and RhoC, RhoB is mainly associated with tumor suppressive function, while RhoA and RhoC support oncogenic transformation in most malignancies. RhoB regulates the endocytic trafficking of signaling molecules and cytoskeleton remodeling, thereby controlling growth, apoptosis, stress response, immune function, and cell motility in various contexts. Some of these functions may be ascribed to RhoB's unique subcellular localization to endocytic compartments. Here we describe the pleiotropic roles of RhoB in cancer suppression in the context of its subcellular localization, and we discuss possible therapeutic avenues to pursue and highlight priorities for future research.


Hospital trainees' worries, perceived sufficiency of information and reported psychological health during the COVID-19 pandemic.
The COVID-19 pandemic has been unsurpassed in clinical severity or infectivity since the 1918 Spanish influenza pandemic and continues to impact the world. During the A/H1N1 pandemic, healthcare workers presented concerns regarding their own and their families' health, as well as high levels of psychological distress. We aim to assess hospital trainees' concerns, perceived sufficiency of information, behaviour and reported psychological health during the COVID-19 pandemic. Single 39-point questionnaire. A large NHS foundation trust in London. 204 hospital trainee doctors. 204 trainees participated, of whom 91.7% (n=187) looked after COVID-19 patients. 91.6% (n=164) were worried about COVID-19; the most frequent concern was that of family and friends dying from COVID-19 (74.6%, n=126). 22.2% (n=36) reported being infected with COVID-19. 6.8% (n=11) of trainees considered avoiding going to work. Perceived sufficiency of information about COVID-19 was moderately high. 25.9% (n=42) reported social distancing at work compared with 94.4% (n=152) outside work. 98.2% (n=159) reported using PPE and 24.7% (n=40) were confident the provided PPE protected them. 41.9% (n=67) reported their psychological health had been adversely affected. 95.6% (n=153) supported provision of psychological support services and 62.5% (n=100) stated they would consider using them. A significant proportion of hospital trainees expressed worries about COVID-19, above all with regards to the wellbeing of their loved ones over their own. Confidence in sufficiency of provided information was high and in utilised infection control measures low. A larger proportion of trainees reported psychological as compared with physical health concerns, with a smaller proportion confirming having been infected with COVID-19 although most perceived their risk of infection as high. Seeking solutions to support hospital trainees in their duties and their wellbeing with their input would help to empower them and improve their health and morale while working during pandemics.