Preventive services in occupational health and safety in Europe: developments and trends in the 1990s.
This article outlines the legislative requirements for preventive services in health and safety in 13 European countries and considers the implementation and coverage of such services. The author identifies the predominant models of preventive services operating in the European Union, then assesses the influence of the E.U. Framework Directive 89/391 on the development and integration of preventive services and the role of workers in their organization and accountability. Significant differences exist in the extent and functions of preventive services in European countries, including differences in coverage between southern and northern European countries, different degrees to which employees in small enterprises and large enterprises are covered by preventive services, and overall differences in legislative approach.


Laparoscopic vs open partial nephrectomy in consecutive patients: the Cornell experience.
To compare a contemporary series of laparoscopic partial nephrectomy (LPN) and open partial nephrectomy (OPN) at one institution, to evaluate the size and types of tumour in each group and the early outcome after each procedure, as LPN is replacing open radical nephrectomy as the standard of care for uncomplicated renal tumours but partial nephrectomy remains significantly more difficult laparoscopically, especially if the goal is to duplicate the open surgical technique. We retrospectively analysed the records of all patients who underwent partial nephrectomy at our institution from January 2000 to April 2004, identifying 66 who had LPN and compared them with 59 who had OPN (mean age at LPN and OPN, 62.1 and 64.2 years, respectively; 70% men in each group). Variables analysed included operative time, blood loss, creatinine levels before and after partial nephrectomy, time to resuming clear liquids and regular diet, length of stay, tumour size, tumour pathological type and complications. Groups were compared using Student's t-test, with P < 0.05 taken to indicate significance. Of those having LPN, 59% had right-sided tumours, vs 53% in the OPN group; the respective mean tumour size was 2.2 and 3.4 cm, the mean operative duration 144 and 239 min (both P < 0.001), and the mean estimated blood loss 236 and 363 mL (P = 0.09). Seven patients in the OPN group had obligatory partial nephrectomy for either a solitary kidney (two) or azotaemia (five). No patient in the LPN group required an obligatory partial nephrectomy. Serum creatinine levels were measured before and 1 and 2 days after surgery, and were 88, 88 and 97 micromol/L for the LPN group, and 97, 106 and 106 micromol/L for the OPN group. Clear fluids were started a mean of 41 h after surgery, a regular diet resumed 76 h after and discharge was 129 h after surgery in the OPN group; the respective values for the LPN group were 24 h (P = 0.01), 49 h (P = 0.2) and 82 h (P < 0.001). Complications were similar in both groups but the pathological subtypes differed. LPN offers early functional advantages over OPN in terms of earlier resumption of diet and slightly earlier discharge. However, the two groups of patients were clearly not evenly matched for size nor pathological subtypes, with larger, malignant subtypes more predominant in the OPN group. These results suggest that while LPN is a safe, effective treatment for small renal tumours, obligatory partial nephrectomy or large tumours continue to be performed using open techniques with good results.


Parental control, parental warmth, and psychosocial adjustment in a sample of substance-abusing mothers and their school-aged and adolescent children.
Parenting interventions for substance-abusing adults have been broadly based on two approaches, one emphasizing parental control as a means to managing children's behavior and the second emphasizing parental warmth and sensitivity as means to fostering children's psychological development. In this investigation, we examined associations of parental control and parental warmth, respectively, with children's behavioral and psychological adjustment in a sample of 98 women enrolled in methadone maintenance and their school-aged and adolescent children. Using collateral data collected during the baseline phase of a randomized clinical trial (Luthar, S. S., Suchman, N. E., & Altomare, M. [in press]. Relational Psychotherapy Mothers Group: A randomized clinical trial for substance abusing mothers [in preparation]), we tested predictions that (a) parental control would be more strongly associated with children's behavioral adjustment and (b) parental warmth would be more strongly associated with children's psychological adjustment. Both predictions were generally confirmed, although some crossover among parenting and child dimensions was also evident. Results support the theoretical stance that parental limit setting and autonomy support, as well as nurturance and involvement, are important factors, respectively, in children's behavioral and psychological adjustment.


Extracellular Polysaccharide Extraction from Streptococcus thermophilus in Fermented Milk.
Lactic acid bacteria such as Streptococcus thermophilus are known to produce extracellular polysaccharide (EPS) in fermented foods that enhance the creaminess and mouthfeel of the product, such as yogurt. Strains producing larger amounts of EPS are highly sought-after, and therefore, robust and accurate quantification methodologies are important. This study found that two commonly used methodologies significantly underestimated the amount of EPS produced as measured using a milk matrix. To this end, a proteolytic step was implemented prior to EPS extraction (Method C). An initial proteolytic step using xanthan gum-spiked milk significantly increased recovery yield to 64%, compared to 27.8% for Method A and 34.3% for Method B. Method C showed no improvement when assessed using a chemically defined medium. Method C was further validated using three strains of S. thermophilus with varying EPS-production capabilities (STLOW, STMID, STHIGH). Overall, Method C demonstrated significant improvements in the EPS extraction yield for all three S. thermophilus strains in fermented milk. On average, Method C improved isolation yield by ∼3- to 6-fold compared with Method A and by ∼2- to 3-fold compared with method B. There were no significant differences between samples when they were grown in a chemically defined medium, highlighting the importance of a proteolytic step specifically for fermented milk samples. In commercial applications, accurate quantification of EPS-production is an important aspect when finding new strains. IMPORTANCE Extracellular polysaccharide (EPS) production by milk-fermenting microorganisms is a highly sought-after trait in improving the perceived thickness, creaminess, and mouthfeel of yogurt. Streptococcus thermophilus are commonly isolated and their EPS production is quantified in the search for higher-producing strains. In this study, we demonstrated that two commonly used methods for isolating EPS from milk samples significantly underestimated the true amount of EPS present. We demonstrated that the addition of a proteolytic step prior to EPS extraction isolated over 2-fold more EPS than identical samples processed using the traditional protocols. We further validated this method in fermented milk samples from three strains of S. thermophilus that included a low-, mid-, and high-EPS producing strain. Again, we showed significant improvements in EPS isolation using a proteolytic step. In the search for new S. thermophilus strains with enhanced EPS production, accurate quantification in an optimal medium is essential.


The economy of the enterohepatic circulation of bile acids in the baboon. 1. Studies of controlled enterohepatic circulation of bile acids.
A primate model with controlled enterohepatic circulation has been developed which allowed short-term evaluation of bile salt pool size, cycling frequency, and fecal losses. We found that when bile salt secretion into the small bowel was increased above 700 mumol/hr bile acid pool cycling frequency was also increased. The latter allowed short-term regulation of bile salt pool size by affecting increased fecal losses. These compensatory mechanisms were associated with a return of bile acid secretion and cycling frequency to normal usually within 12-24 hours. Conversely, during decreased bile salt secretion, regulation of bile salt pool size was accomplished by decreased pool cycling, which decreased fecal losses. Bile acid secretion into the intestine was therefore a major determinant of bile salt cycling frequency. The latter affected bile salt fecal loss to provide short-term regulation of bile salt pool when feedback regulation of bile salt synthesis was nonoperative.


Zinc chromate induces chromosome instability and DNA double strand breaks in human lung cells.
Hexavalent chromium Cr(VI) is a respiratory toxicant and carcinogen, with solubility playing an important role in its carcinogenic potential. Zinc chromate, a water insoluble or 'particulate' Cr(VI) compound, has been shown to be carcinogenic in epidemiology studies and to induce tumors in experimental animals, but its genotoxicity is poorly understood. Our study shows that zinc chromate induced concentration-dependent increases in cytotoxicity, chromosome damage and DNA double strand breaks in human lung cells. In response to zinc chromate-induced breaks, MRE11 expression was increased and ATM and ATR were phosphorylated, indicating that the DNA double strand break repair system was initiated in the cells. In addition, our data show that zinc chromate-induced double strand breaks were only observed in the G2/M phase population, with no significant amount of double strand breaks observed in G1 and S phase cells. These data will aid in understanding the mechanisms of zinc chromate toxicity and carcinogenesis.


Premenstrual Syndrome and Premenstrual Dysphoric Disorder.
Premenstrual disorders affect up to 12% of women. The subspecialties of psychiatry and gynecology have developed overlapping but distinct diagnoses that qualify as a premenstrual disorder; these include premenstrual syndrome and premenstrual dysphoric disorder. These conditions encompass psychological and physical symptoms that cause significant impairment during the luteal phase of the menstrual cycle, but resolve shortly after menstruation. Patientdirected prospective recording of symptoms is helpful to establish the cyclical nature of symptoms that differentiate premenstrual syndrome and premenstrual dysphoric disorder from other psychiatric and physical disorders. Physicians should tailor therapy to achieve the greatest functional improvement possible for their patients. Select serotonergic antidepressants are first-line treatments. They can be used continuously or only during the luteal phase. Oral contraceptives and calcium supplements may also be used. There is insufficient evidence to recommend treatment with vitamin D, herbal remedies, or acupuncture, but there are data to suggest benefit from cognitive behavior therapy.


The interaction of language and thought in children's language acquisition: a crosslinguistic study.
The purpose of this research was to investigate the potential interaction of conceptual representations and linguistic systems in the process of language acquisition. Language-thought interactions were studied in 80 American, 48 Finnish and 48 Polish preschool children. The research focused on the conceptual and linguistic development of space and time. The spatial and temporal conceptual tasks were designed to measure the transition from experimental to inferential knowledge of space/time representations. In the linguistic domain, comprehension and production tests were used to evaluate the children's capacity to understand mono- and bi-referential location in space and time, where mono-referential location involves a single referent object/event with intrinsic properties (e.g. in/on or past/non-past), and bi-referential location requires two or more referent objects/events and relative perspective (e.g. deictic front/back or before/after). The conceptual and linguistic tests revealed significant changes during the period from two to five years of age, and measures of conceptual development were correlated with measures of linguistic development. As spatial and temporal representations became more structured, children were able to move from mono- to bi-referential location. In a comprehension test, we discovered an interaction of language by dimension. Finnish children found spatial distinctions relatively easy and Polish children found temporal distinctions relatively easy. This interaction was expected on the basis of the relative complexity of the morpho-syntactic coding in the spatial and temporal systems of the two languages. However, the argument relating the timing of acquisition to the transparency versus opacity of the linguistic systems was not supported by the English language comparison. Finally, the Finnish children were relatively better able to accomplish the spatial conceptual tasks as compared to the Polish children. This finding is consistent with a developmental concept of linguistic relativity. In general, the research indicates that spatial and temporal linguistic systems and representational knowledge interact during development with the influence occurring in both directions.


Decreased NOTCH1 signaling activated autophagy in the mid-secretory endometrium of patients with recurrent implantation failure†.
Recurrent implantation failure severely impairs fertility in females of childbearing age, which poses a great challenge to assisted reproductive technology, and its etiology is still unclear. Several studies have demonstrated that endometrial autophagy takes an important part in human endometrial receptivity, but its role in recurrent implantation failure remains largely unknown. Here, we collected mid-secretory endometrial tissue from recurrent implantation failure patients and fertile controls during menstruation and early pregnancy. Immunohistochemistry, western blotting, and quantitative real-time PCR were performed to compare the expression of microtubule-associated protein 1 light chain 3B, sequestosome 1, NOTCH1 signaling pathway members, and endometrial receptivity markers between recurrent implantation failure and control groups. In addition, to assess endometrial autophagy, transmission electron microscopy was used to observe autophagosomes. By RNA interference, we further investigated the effects of NOTCH1 on autophagy in Ishikawa cells. We found that endometrial autophagy was upregulated in the mid-secretory and decidual phases than in the early-proliferative phase. Compared to the control group, more autophagosomes were observed in the mid-secretory endometrium of recurrent implantation failure patients, which was accompanied by the downregulation of NOTCH1 signaling pathway members and endometrial receptivity markers. Moreover, knockdown of NOTCH1 impaired the receptivity of Ishikawa cells via protein kinase B/mammalian target of rapamycin pathway-mediated autophagy activation. Our data suggested that abnormally elevated autophagy and decreased NOTCH1 signaling pathway activity were observed in the mid-secretory endometrium of patients with recurrent implantation failure, perhaps due to decreased NOTCH1 pathway-mediated autophagy activation in endometrial cells impairing receptivity.


9q34 rearrangements in BCR/ABL fusion-negative acute lymphoblastic leukemia.
The t(9;22)(q11.2;q34) translocation is found in a subset of acute lymphoblastic leukemia (ALL). The presence of this translocation involving the fusion of BCR/ABL genes represents a poor prognostic group. Because of the importance in detecting t(9;22) in ALL patients and because occasionally a cytogenetically cryptic BCR/ABL fusion is detected with fluorescence in situ hybridization (FISH), our laboratory routinely performs BCR/ABL FISH tests on all newly diagnosed ALL patients. In the past year, 25 consecutive, newly diagnosed, untreated ALL cases were analyzed. We report the cytogenetics and FISH findings of three cases containing a rearranged 9q34 region with an intact BCR (22q11.2) region and an absence of the BCR/ABL fusion. A split ABL signal representing a translocation of the 9q34 region with chromosome segments other than 22q11.2 (BCR) was observed in 3 cases. Two of these patients were 3 years old; one was 21 at the time of diagnosis. A split ABL FISH signal without the involvement of BCR does not represent a t(9;22) translocation, and prognostic implications of this apparent subgroup of ALL cases have not been determined. Cytogenetic, pathologic, and clinical aspects of these three cases are presented.


A Longitudinal Study of the Bidirectional Relations Between Anxiety Symptoms and Peer Victimization in Urban Adolescents.
The current study examined bidirectional relations between anxious symptoms and two forms of peer victimization (i.e., overt and relational) within an underrepresented sample of urban adolescents during key transition periods (i.e., elementary to middle school; middle school to high school) and the following 2 years. A predominantly African American sample (91%) of 358 adolescents (56% female, mean age = 12.10 years) living in low-income urban areas were assessed annually across 4 years. Using self-report measures, adolescents reported on their past year experiences of anxiety and peer victimization. Longitudinal path analyses tested progressively complex models for each type of victimization. Anxious symptoms predicted both overt and relational victimization at the time of transition (Wave 1 to Wave 2) and the following year (Wave 2 to Wave 3). Furthermore, whereas previous levels of victimization and future anxious symptoms were positively correlated over time, only relational victimization at Wave 1 predicted anxious symptoms at Wave 2. Prior levels of each construct were the strongest predictor of future outcomes (e.g., anxious symptoms at Wave 1 predicting anxious symptoms at Wave 2). Overall, there was little support for bidirectional relations between anxiety symptoms and peer victimization. Intervention and prevention programs seeking to reduce peer victimization or anxiety should start by targeting the symptom/behavior of interest. Interventions that target anxious thoughts and feelings during these key transition times in adolescence should be assessed as areas of priority.


Mechanisms for quick and variable responses.
Dominant and subordinate males produce neuroendocrine stress responses during aggressive social interaction. In addition, stress responsiveness has both acute and chronic temporal components. A neurochemical marker that distinguishes social status and aggression by temporal and regional differentiation is the activity of serotonergic nuclei and terminals. A unique model for distinguishing the relationships among the neuroendocrine machinery of stress, social status and behavior is the lizard Anolis carolinensis. Dominant males exhibit more aggression and have temporally advanced serotonergic responses. Chronic serotonergic activity is associated with subordinate social status and reduced aggression. Acute and chronic serotonergic responses occur in both dominant and subordinate males, and are distinguished temporally. This provides a fundamental question that may elucidate basic differences in behavior: What causes temporally advanced serotonergic activity in response to stress in dominant males? Secondarily, what is the neural basis for the acute and chronic responses? The neural mechanisms for transduction of the relevant behavioral signals are very plastic. Behavioral experience and visual stimuli can produce very rapid responses. Faster and greater responsiveness may be stimulated by restraint stress, social stress and the absence of social sign stimuli (e.g. eyespots of the lizard Anolis carolinensis). Stress response machinery provides regulatory factors necessary to modify social behavior, and to adapt it for specific contexts. Serotonergic activity is rapidly modified by glucocorticoids and GABA, and also by CRF under conditions of previous stress or in combination with AVP. Advancing acute elevation of serotonergic activity may be a distinguishing characteristic of dominant males. Social events add contextual conditioning to brain transmitter activity, with social information processed in a distributed fashion. Medial amygdala manifests delayed serotonergic response compared to hippocampus and nucleus accumbens, and is therefore a good candidate to mediate chronic stress responsiveness. Limiting or delaying acute effects, in addition to chronic serotonergic activity, may be the distinguishing characteristics of subordinate males. Monoamines, glucocorticoids, testosterone, CRF, AVP, AVT, play neuromodulatory roles producing context appropriate behavior.


Secukinumab-induced systemic lupus erythematosus in psoriatic arthritis.
A 68-year-old male treated with secukinumab for psoriatic arthritis suspended treatment for three months due to COVID pandemic. Upon secukinumab reintroduction, anorexia and weight loss ensued and four months later he had an abrupt onset of low-grade fever, fatigue, flu-like symptoms, dyspnoea and widespread inflammatory arthralgias. Laboratory investigations showed de novo anaemia, leukopenia, lymphopenia, cytocholestasis, elevated acute phase reactants, C3 complement consumption, proteinuria (1630mg/24h), active urine sediment, positive antinuclear (1:1280) and anti-double-stranded DNA (212.3 IU/mL) antibodies. Chest imaging showed peripheral pulmonary embolism, lobar pneumonia, and a small bilateral pleural effusion. Drug-induced lupus erythematosus (DILE) was suspected, and the patient was hospitalised. Secukinumab was discontinued and treatment with enoxaparin, antibiotics, enalapril, hydroxychloroquine and prednisolone 0.5mg/kg qd was started. Clinical and laboratorial remission ensued after one month except for proteinuria (decreased to 653mg/24h). Proliferative lupus nephritis was assumed and mycophenolate mofetil was introduced, with sustained complete remission over a 33-month follow-up. This is the second reported case of systemic secukinumab-associated DILE, and the first with renal involvement. Clinical and laboratory features of DILE are reviewed and compared with previously described cases.


Fate of anilide and aniline herbicides in plant-materials-amended soils.
The fate of herbicides trifluralin, pendimethalin, alachlor and metolachlor in paddy field soils amended with plant materials was investigated. The plant materials were purple sesbania, vegetable soybean and rice straw. The investigation was performed at two temperatures (25 and 40 degrees C) and two soil water moistures (60 and 90% water-holding capacity). The results showed linear and Freudlich equations described the adsorption of amide compound to soil. Adsorption coefficient (K(d)) fit to linear equation were in general greater in plant material-amended soils than in non-amended soil, especially in soil amending with rice straw. Increasing temperature and soil water moisture content shortened the half-lives of compounds in various treated soils. The movement of compounds in the soil columns showed the maximum distribution of aniline type compound, trifluralin and pendimethalin, appeared at the upper top of 0 to 5 and 0 to 10 cm of soil column, respectively, and of anilide type, alachlor and metolachlor, were distributed at 0 to 25 cm of the soil column. The mobility of chemicals in the different treated soils was simulated by the behavior assessment model (BAM). There was no significant difference among different plant material incubated soils on dissipation and mobility of compounds in soils.


Clinical features of multiple primary carcinomas of the oral cavity.
The present study aimed to elucidate the clinical characteristics of multiple primary carcinomas of the oral cavity. The clinical records of 1,024 patients who were treated during follow-up for oral cancer at the Department of Stomatology, Henan Provincial People's Hospital, between March 2013 and December 2014 were retrospectively reviewed. The clinical characteristics of 961 patients who developed single primary oral squamous cell carcinoma (SCC) during follow-up and 54 patients who subsequently developed multiple primary carcinomas in the oral cavity were compared. Multiple primary carcinomas exhibited a female predilection, were most prevalent in the gingiva, and tended to show earlier tumor and nodal stages, as compared with single primary carcinomas. The local recurrence rate was higher for multiple primary carcinomas, as compared with single primary carcinomas, and was demonstrated to increase with the number of multiple primary occurrences. The cumulative incidence rates for metachronous second primary carcinomas following the onset of the first carcinoma at 10 years was 8.0%. Recurrence of multiple primary carcinomas did not decrease the survival rates of the patients assessed in the present study. Furthermore, differences were detected in the clinical characteristics between patients with single oral SCC and those with multiple primary oral carcinomas. The results of the present study indicated that early diagnosis and treatment and close long-term follow-up are required for patients with multiple primary oral carcinomas.


The management of atrial fibrillation: current perspectives.
The management of atrial fibrillation is evolving in response to recently published data. Low-risk patients with new-onset atrial fibrillation may not need to be hospitalized. Beta blockers may be the most effective drugs for controlling the heart rate. When a patient does not respond to drug therapy, it is still appropriate to search for the cause of the arrhythmia and to use direct-current cardioversion. Clear evidence now exists that patients with chronic atrial fibrillation should be given anticoagulant drugs to reduce the risk of stroke. Antiarrhythmic drugs should be used cautiously, because they may cause life-threatening arrhythmias.


The effects in the excess administration of prostaglandin E1 on the indicator enzymes of organella membrane in gastric mucosa.
Administration of excess vitamin A to rats causes gastric ulceration. In this study the effects on the gastric mucosa of excess vitamin A and excess prostaglandin E1, alone and in combination, were studied. Prostaglandin E1 protected against ulceration by vitamin A. Vitamin A labilized marker enzymes from four different membrane systems, namely those of the lysosomes, mitochondria, endoplasmic reticulum and plasma membrane, whereas only the effect on lysosomes was prevented by prostaglandin E1. Indeed, the prostaglandin alone labilized the enzymes from plasma membrane and endoplasmic reticulum and also damaged mitochondrial membranes. Both vitamin A and prostaglandin E1 caused a reduction in the total number and an increase in irregularly-shaped mitochondria in the parietal cells and produced dilation of the endoplasmic reticulum in both parietal and chief cells. It is noteworthy that prostaglandin E1 effectively prevents ulceration by vitamin A despite the extent to which it damages these membrane systems. These findings lend support to the hypothesis that vitamin A ulceration of the gastric mucosa is mediated via release of lysosomal enzymes, following damage to the lysosomal membranes.


Technological Maturity and Systematic Review of Medicinal Plants with Pharmacological Activity in the Central Nervous System.
Medicinal plants present activities against neurodegenerative diseases with potential for the pharmaceutical industries. Therefore, the objective of this study was to investigate the current panorama of patents and articles of Brazilian medicinal plants with pharmacological activities in the Central Nervous System (CNS), regarding such aspects as the number of patents by countries, areas of knowledge, and technological maturity. We carry out a technological exploration on the Questel Orbit® platform with the descriptors: Agave sisalana P., Amburana cearenses A., Dimorphandra mollis B., Jatropha curcas L., Poincianella pyramidalis T. and Prosopis juliflora (Sw.) DC. with pharmacological activity and scientific exploration in PubMed and Science Direct associated with the CNS in the title, abstract, and methodology. A total of 642 patents were identified between the years 1999-2019. India, China, and Brazil are highlighted, 6th place, out of a total of 48 countries. Of these, 30 patents were not in the National Institute of Industrial Property, and 10% are Brazilian in biotechnology and pharmaceutical products. Eleven articles were used in PubMed and Science Direct with scientific domains (anticancer, neuroprotection and anti-inflammatory). The Federal University of Bahia is highlighted, showing Technology Readiness Levels (TRL4), basic skills of pre-clinical research. Brazilian public universities have a significant role in the scientific, technological and innovative development of therapeutic assets for CNS.


The effect of fluoridated milk on human dental enamel in an in vitro demineralization model.
Fifty-seven sound human permanent premolars were demineralized for 14 days and then exposed to six different treatments: group 1, 1 mg/1 fluoride in milk for 7 days; group 2, 1 mg/l fluoride in milk for 14 days; group 3, 10 mg/l fluoride in milk for 7 days; group 4, 10 mg/l fluoride in milk for 14 days; group 5, control non-fluoridated milk for 14 days, and group 6, control tap water for 14 days. Enamel etch samples were taken and analysed for fluoride and for phosphorus. An increase in the enamel surface fluoride content was observed in groups 1-3. A statistically significant elevation (p < 0.01) of fluoride content and a significant decrease (p > 0.001) of acid solubility were found only in group 4.


Modeling the C9ORF72 repeat expansion mutation using human induced pluripotent stem cells.
C9ORF72 repeat expansion is the most frequent causal genetic mutation giving rise to amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia (FTD). The relatively recent discovery of the C9ORF72 repeat expansion in 2011 and the complexity of the mutation have meant that animal models that successfully recapitulate human C9ORF72 repeat expansion-mediated disease are only now emerging. Concurrent advances in the use of patient-derived induced pluripotent stem cells (iPSCs) to model aspects of neurological disease offers an additional approach for the study of C9ORF72 mutation. This review focuses on the opportunities of human C9ORF72 iPSC platforms to model pathological aspects of disease and how findings compare with other existing models of disease and post mortem data.


Tumor necrosis factor-alpha promoter polymorphism is associated with the risk of Parkinson's disease.
Inflammatory events may contribute to the pathogenesis of Parkinson's disease (PD). We conducted a case-control study in a cohort of 369 PD cases and another cohort of 326 ethnically matched controls to investigate the association of tumor necrosis factor-alpha (TNF-alpha) promoter single nucleotide polymorphisms (SNPs) with the risk of PD. The overall genotype distribution at T-1031C and C-857T sites showed significant difference between PD cases and controls (P = 0.0062 and 0.0035, respectively). However, only the more frequent -1031 CC genotype was evidently associated with PD (P = 0.0085, odds ratio: 2.96; 95% CI: 1.38-7.09). Pairwise SNP linkage disequilibrium showed -1031 and -863 sites are in strong linkage disequilibrium (D' = 0.93, Delta(2) = 0.80). Pairwise haplotype analysis among the four sites showed that -1031C-863A may act as a risk haplotype among PD cases (P = 0.0028, odds ratio: 2.18; 95% CI: 1.33-3.69).


The solubility and stability of amino acids in biocompatible ionic liquids.
In recent years, ionic liquids (ILs) represent a new class of biocompatible co-solvents for biomolecules. In this work, we report the apparent transfer free energies (ΔG'tr) for six amino acids (AA) from water to aqueous solutions of six ammonium based ILs (diethylammonium acetate (DEAA), diethylammonium sulfate (DEAS), triethyl ammonium acetate (TEAA), triethylammonium sulfate (TEAS), triethylammonium dihydrogen phosphate (TEAP), and trimethylammonium acetate (TMAA)) through solubility measurements, as a function of IL concentration at 298.15 K under atmospheric pressure. Salting-out effect was found for AA in aqueous IL solutions with increasing IL concentrations. In addition, we observed positive values of ΔG'tr for AA from water to ILs, indicating that the interactions between ILs and AA are unfavorable. From the obtained results, we found that the selected ammonium based ILs act as stabilizers for the structure of AA.


Serum phospholipase A2 in patients with multiple injuries.
Catalytic phospholipase A2 activity (CA-PLA2) and the concentration of immunoreactive pancreatic PLA2 (IR-PLA2) were measured in serum samples from 12 patients with multiple injuries (median Injury Severity Score: 41). CA-PLA2 was increased in all patients and positive correlations were found between the extent of the increase of CA-PLA2, mortality, and impairment of pulmonary function. IR-PLA2 values were slightly increased in the serum of nine patients with multiple injuries. Of these nine patients, eight had an additional blunt abdominal trauma. On the other hand, no relationship was found between IR-PLA2 and CA-PLA2 values. This finding was confirmed by immunoadsorption experiments with an antiserum to human pancreatic PLA2, which demonstrated that the increased serum levels of IR-PLA2 were not responsible for the increased CA-PLA2 values. The results suggest the existence of at least two immunologically different phospholipase A2 enzymes in sera of patients with multiple injuries.


Macrophage polarization alters the expression and sulfation pattern of glycosaminoglycans.
Macrophages are major cells of inflammatory process and take part in a large number of physiological and pathological processes. According to tissue environment, they can polarize into pro-inflammatory (M1) or alternative (M2) cells. Although many evidences have hinted to a potential role of cell-surface glycosaminoglycans (GAGs) in the functions of macrophages, the effect of M1 or M2 polarization on the biosynthesis of these polysaccharides has not been investigated so far. GAGs are composed of repeat sulfated disaccharide units. Heparan (HS) and chondroitin/dermatan sulfates (CS/DS) are the major GAGs expressed at the cell membrane. They are involved in numerous biological processes, which rely on their ability to selectively interact with a large panel of proteins. More than 20 genes encoding sulfotransferases have been implicated in HS and CS/DS biosynthesis, and the functional repertoire of HS and CS/DS has been related to the expression of these isoenzymes. In this study, we analyzed the expression of sulfotransferases as a response to macrophage polarization. We found that M1 and M2 activation drastically modified the profiles of expression of numerous HS and CS/DS sulfotransferases. This was accompanied by the expression of GAGs with distinct structural features. We then demonstrated that GAGs of M2 macrophages were efficient to present fibroblast growth factor-2 in an assay of tumor cell proliferation, thus indicating that changes in GAG structure may contribute to the functions of polarized macrophages. Altogether, our findings suggest a regulatory mechanism in which fine modifications in GAG biosynthesis may participate to the plasticity of macrophage functions.


A Sex-Stratified Prognostic Nomogram Incorporating Body Compositions for Long-Term Mortality in Cirrhosis.
Alterations in body compositions are related to poor outcomes and the presence of complications in cirrhosis. However, no predictive tools combining all these anthropometric parameters are applicable in the clinical setting. We aimed to clarify the potential utility of body compositions and develop a nomogram incorporating any independent factor for prognosticating long-term mortality in cirrhosis. A total of 414 patients were randomized into primary (n = 274) and validation (n = 140) cohorts. X-tile was performed to identify optimal cut points for stratifying participants. Multivariate Cox regression was performed, and nomogram incorporating body compositions were generated. The utility of developed models was evaluated by Harrell concordance index (C-index), calibration curve, and decision curve analysis (DCA). Stratifying by X-tilederived cut points, low skeletal muscle index (myopenia), high intramuscular adipose tissue content (myosteatosis), and the ratio of high visceral to subcutaneous adipose tissue area (adiposity) was independently associated with 3-year mortality. A sex-stratified nomogram incorporating anthropometric indices and clinical factors resulted in moderate discriminative accuracy, with a C-index of 0.787 (95% CI, 0.736-0.838) and 0.789 (95% CI, 0.727-0.851) in males and females, respectively. The calibration curve showed predictive survival corresponding optimally with the actual outcomes. Our models were feasible in the clinical settings based on DCA. Similar results were observed in the validation cohort. Additionally, participants could be classified into 3 distinct risk groups by the nomogram. Our proposed nomogram embedding body compositions rendered an individualized predictive tool for long-term mortality in cirrhosis.


Study of the morphology of the three-phase contact line and its evolution by morphological examination after droplet evaporation of aqueous polymer solutions.
The local morphology and its evolution of an air-liquid-solid three-phase contact line was studied on the homogeneous surfaces of homopolymer of polystyrene (PS) and poly(methyl methacrylate) (PMMA) and the nanostructured surface of diblock copolymer of PS- b-PMMA by the approach of the morphological study of the residual solid after droplet evaporation of water-soluble polymers such as poly(vinylpyrrolidone) (PVP) and poly(acrylic acid). The observation by atomic force microscopy discovered the stripelike "button-and-ribbon" structure of the precipitated polymer solute along the moving direction of the contact line. On the surface of PS- b-PMMA, the morphology of PVP has a close correlation with the nanostructure of PS- b-PMMA. The results exhibit the local morphology of the contact line and its evolution, revealing its pinning and depinning processes on the nanometer scale.


Laparoscopic management of cholecystoenteric fistulas.
Cholecystoenteric fistulas are a rare complication of gallstone disease and affect 3-5% of patients with cholelithiasis. Most fistulas are diagnosed intraoperatively. Between January 1997 and June 2003, 12428 patients underwent laparoscopic cholecystectomy at our department. Cholecystoenteric fistula was diagnosed intraoperatively and treated in 63 patients: 45 patients (71.4%) had cholecystoduodenal fistulas, while cholecystogastric and cholecystocolic fistulas were found in 9 patients (14.3%) and 4 patients (6.3%), respectively; and 5 patients (7.9%) were found to have Mirizzi syndrome type I along with a cholecytoenteric fistula. The operation could be completed laparoscopically in 59 patients. An endostapler was used in 47 patients to transect the fistula and in 12 patients the defect in the bowel was repaired with intracorporeal sutures. Major morbidity occurred in 3 patients (4.76%). One patient developed a loculated subdiaphragmatic collection which was treated by ultrasound guided aspiration and antibiotic therapy. Prolonged biliary drainage occurred in 2 patients. In addition, 7 patients (11.11%) had minor postoperative complications. The mean postoperative hospital stay was 5.2 days. All the patients are asymptomatic at a mean follow-up of 2.4 years. Cholecystoenteric fistula is a difficult problem usually diagnosed intraoperatively. A high degree of suspicion at operation is mandatory. A stapled cholecystofistulectomy may be the procedure of choice since it avoids contamination of the peritoneal cavity. Complete laparoscopic management of cholecystoenteric fistulas is possible in well-equipped high-volume centers.


Measurements of the wavelength dependent extinction of aerosols by cavity ring down spectroscopy.
Cavity ring down measurements are performed on accumulation mode aerosol, 240 nm to 700 nm in diameter, over a range in wavelength, extending from 540 to 570 nm. We demonstrate that the measured variation in extinction efficiency with wavelength can be used to retrieve the dispersion in the real part of the refractive index. These measurements are contrasted with previous aerosol cavity ring down studies which have focussed on investigating the variation in optical extinction with particle size parameter through a variation in the sampled particle size distribution. In the measurements reported here, the gradient in the optical extinction can be recorded with fine resolution in size parameter (approximately 0.02) through variation in laser wavelength. Such an approach, as well as allowing a determination of the dispersion in refractive index, could be used to constrain the retrieval of refractive index at a single wavelength.


Detection and F0 discrimination of harmonic complex tones in the presence of competing tones or noise.
Normal-hearing listeners' ability to "hear out" the pitch of a target harmonic complex tone (HCT) was tested with simultaneous HCT or noise maskers, all bandpass-filtered into the same spectral region (1200-3600 Hz). Target-to-masker ratios (TMRs) necessary to discriminate fixed fundamental-frequency (F0) differences were measured for target F0s between 100 and 400 Hz. At high F0s (400 Hz), asynchronous gating of masker and signal, presenting the masker in a different F0 range, and reducing the F0 rove of the masker, all resulted in improved performance. At the low F0s (100 Hz), none of these manipulations improved performance significantly. The findings are generally consistent with the idea that the ability to segregate sounds based on cues such as F0 differences and onset/offset asynchronies can be strongly limited by peripheral harmonic resolvability. However, some cases were observed where perceptual segregation appeared possible, even when no peripherally resolved harmonics were present in the mixture of target and masker. A final experiment, comparing TMRs necessary for detection and F0 discrimination, showed that F0 discrimination of the target was possible with noise maskers at only a few decibels above detection threshold, whereas similar performance with HCT maskers was only possible 15-25 dB above detection threshold.


The biodegradation of mixtures of organic solvents by mixed and monocultures of bacteria.
Much more information concerning the biodegradation kinetics of mixtures of common industrial chemicals, such as organic solvents, needs to be gathered before wastewater biotreatment process performance can become a matter of design. Here, the biooxidation of a solvent mixture comprizing methanol, acetone, isopropanol, and methylene chloride is examined. The fact that the enrichment culture obtained comprized only two solvent-utilizing strains, together with only minor percentages of nonsolvent utilizing satellite strains, was contrary to the theory of microbial competition. In addition, the complex relationship between the two solvent-utilizing strains indicates that further work is necessary on the pathways involved in isopropanol and acetone biooxidation and on the effects of operating conditions on the fluxes along such pathways.


Direct experimental observation of stacking fault scattering in highly oriented pyrolytic graphite meso-structures.
Stacking fault defects are thought to be the root cause for many of the anomalous transport phenomena seen in high-quality graphite samples. In stark contrast to their importance, direct observation of stacking faults by diffractive techniques has remained elusive due to fundamental experimental difficulties. Here we show that the stacking fault density and resistance can be measured by analyzing the non-Gaussian scatter observed in the c-axis resistivity of mesoscopic graphite structures. We also show that the deviation from Ohmic conduction seen at high electrical field strength can be fit to a thermally activated transport model, which accurately reproduces the stacking fault density inferred from the statistical analysis. From our measurements, we conclude that the c-axis resistivity is entirely determined by the stacking fault resistance, which is orders of magnitude larger than the inter-layer resistance expected from a Drude model.


Chronic thromboembolic pulmonary hypertension as the first manifestation of nephrotic syndrome in a 12-year-old child.
Chronic thromboembolic pulmonary hypertension (CTEPH) is rare in children and determining the underlying etiologies is essential for treatment. Venous thromboembolism, a well-known complication in nephrotic syndrome (NS), always occurrs during the treatment in course of the disease. However, CTEPH as the first manifestation of NS has not been reported till now. A 12-year-old boy initially complained of hemoptysis, cough and shortness of breath with exertion, any symptoms regarding NS such as edema were not presented. Due to the identification of P2 enhancement, liver enlargement (2 cm below the rib) and jugular vein distension, pulmonary hypertension (PH) was firstly suspected and ultimately confirmed by detection of enlargement of right atrium (RA) and right ventricle (RV) enlargement (RA = 45mm, RV = 30mm), mild tricuspid valve regurgitation (TR) and elevation of pulmonary arterial pressure (63 mmHg) on echocardiogram. In order to search the underlying causes of PH, series of targeted laboratory evaluation and imaging were conducted, and pulmonary arterial embolism (PE) in inferior lobes of double lungs was found on chest contrast-enhanced computed tomography. NS was unexpectedly discovered by detection of lower serum albumin level (24.4 g/L), severe proteinuria (+++, 4.62 g/24 h) when we were searching for the predisposing factors causing thromboembolism. After treatment of NS, the symptom regarding shortness of breath with exertion gradually became less apparent and was relieved one month later. Proteinuria and microscopic hematuria also disappeared. Encouragingly, RA and RV dilation, and the pulmonary arterial pressure almost returned to a normal range half a year later, with alleviation of MR. CTEPH can occur rarely in children and NS is an important predisposing factor. PE could be the first manifestation of NS. When pediatricians encounter children with PE or CTEPH, NS as the underlying etiology should be considered. Except for renal venous thrombosis, the possibility of PE needs to be paid more attention in children with NS.


Systemic vasculitis: a dual diagnosis?
The authors describe a 25-year-old male with systemic vasculitis fulfilling the American College of Rheumatology classification criteria for both granulomatosis with polyangiitis (Wegener's granulomatosis) and polyarteritis nodosa. The patient was diagnosed with granulomatosis with polyangiitis following a mediastinal biopsy which revealed necrotising granulomas of the large airways, a positive cytoplasmic antineutrophil cytoplasmic antibodies and high antiproteinase 3 antibody titre. He then developed acute right-sided abdominal and testicular pain as well as areas of hyperaesthesia and parasthesiae on both lower limbs. He was found to have focal crescentic glomerulonephritis and mononeuritis multiplex, in keeping with his diagnosis of granulomatosis with polyangiitis, as well as two areas of infarction in his right testicle and multiple aneurysms of his hepatic and right renal arteries, more typical of polyarteritis nodosa. His symptoms developed 6 weeks after hepatitis B vaccination, which may have played an aetiological role.


Multiparametric MR Imaging of the Prostate after Treatment of Prostate Cancer.
The use of multiparametric magnetic resonance (MR) imaging in prostate cancer therapy is increasing, as newer treatment methods and management approaches emerge. The mainstays of therapy-radiation and surgery-are being supplemented (and even replaced) by novel focal therapy methods. Laser and ultrasonographic ablation, photodynamic therapy, electroporation, and cryoablation are the most common focal therapies, each with its own imaging findings. Typical ablation zones have a central focus of enhancement with peripheral rim enhancement; thus, dynamic contrast material-enhanced (DCE) MR imaging is the most important sequence for evaluation of treatment in the immediate posttherapeutic setting. Detection of recurrence can initiate salvage therapy, but recurrence can be difficult to detect on T2-weighted images, again necessitating DCE MR imaging and also diffusion-weighted imaging. Furthermore, the location of recurrence can vary depending on the therapy. With radiation therapy, the most common site of recurrence is the prior tumor site, whereas after prostatectomy, the recurrence usually occurs around the vesicoureteral anastomosis. Regarding management, there is an increased emphasis on watchful waiting and active surveillance, for which MR imaging has a critical role in both selection and follow-up of patients who undergo active surveillance. As MR imaging is being increasingly used for imaging suspected recurrence, it is important for radiologists to be familiar with the normal posttreatment findings and patterns and MR imaging findings of recurrence. ©RSNA, 2018.


Symptom Prevalence of Patients with Cancer in a Tertiary Cancer Center in Jordan.
Prevalence of symptoms experienced by patients with cancer was studied in different parts of the world. In Jordan, to the best of our knowledge, there is no published data on the prevalence of symptoms among patients with cancer. The aim of this study is to estimate the prevalence of symptoms among patients with cancer in Jordan. This was a secondary analysis of crosssectional survey that evaluate the psychometric properties of the Arabic version of the European Organization for Research and Treatment of Cancer Quality of Life 15 items Questionnaire for Palliative Care (EORTC QLQ-C15-PAL) among patients admitted to a tertiary cancer center in Jordan. A total of 175 patients with cancer participated in the study; 51.4% were males, 48.6 % were females, mean age of patients was 50 years. Median number of symptoms per patient was 6, interquartile range was 5-7. The majority of patients (143; 81%) had more than 3 non-pain symptoms each. The most frequently reported symptom was tiredness (82%), whereas the least prevalent symptom was depression (55%). Pain was prevalent in 71% of patients, median severity score was 50%. Patients with cancer suffer from a large constellation of symptoms, frequent assessment with a designated tool can help early identification of these symptoms and subsequent management. This highlights the need for integrated palliative services along with other health care provision.


[Phase II clinical study of RP56976 (docetaxel) in patients with carcinoma ovarii or carcinoma colli uteri].
An early phase II clinical study of RP56976 (docetaxel), a new semisynthetic agent, in patients with carcinoma ovarii or carcinoma colli uteri was undertaken by a cooperative study group of 23 institutes. Docetaxel was administered at an initial intravenous dose of 60 mg/m2 with dose-free intervals of 3-4 weeks, and its efficacy and safety were evaluated. Of the 47 patients with carcinoma ovarii enrolled, 44 patients were eligible and 36 patients completed the scheduled course of treatment. Of the 23 patients with carcinoma colli uteri enrolled, 20 patients were eligible and 15 patients completed the scheduled course of treatment. For antitumor efficacy in patients with carcinoma ovarii, 1 patient showed partial response (PR), 10 showed no changes (NC) (2 showed minor response (MR)), and 25 had progressive disease (PD). The overall response rate was 2.8% (1/36). Of patients with carcinoma colli uteri, 7 patients showed no changes (NC) (1 patient showed minor response (MR)), 8 patients had progressive disease (PD). Major adverse reactions included 64/65 (98.5%) leukopenia, 56/59 (94.9%) neutropenia, 40/60 (61.5%) decrease of hemoglobin, 12/64 (18.8%) thrombocytopenia, 30/65 (46.2%) anorexia, 23/65 (35.4%) nausea/vomiting, 37/65 (56.9%) alopecia, and 26/65 (40.0%) fatigue, all of which were mild.


Simultaneous measurement of magnetization and magnetostriction in 50 T pulsed high magnetic fields.
To simultaneously perform magnetization and magnetostriction measurements in high magnetic fields, a miniaturized device was developed that combines an inductive magnetometer with a capacitive dilatometer and, therefore, it is called "dilamagmeter." This combination of magnetic and magnetoelastic investigations is a new step to a complex understanding of solid state properties. The whole system can be mounted in a 12 mm clear bore of any cryostat usually used in nondestructive pulsed high field magnets. The sensitivity of both methods is about 10(-5) A m(2) for magnetization and 10(-5) relative changes in length for striction measurements. Measurements on a GdSi single crystal, which are corrected by the background signal of the experimental setup, agree well with the results of steady field experiments. All test measurements, which are up until now performed in the temperature range of 4-100 K, confirm the perfect usability and high stability in pulsed fields up to 50 T with a pulse duration of 10 ms.


A direct method for air kerma-length product measurement in CT for verification of dose display calibrations.
The dose display values of computed tomography (CT) devices are used for patient dose estimation and as a tool for optimisation. Therefore, the dose display value accuracy should be verified. In practice, this means doing measurements in the standard phantoms and comparing results with the dose display values. The traditional method for measuring CT dose enables measurements only for one axial rotation, and there has not been a method for measuring the dose of a complete helical scan sequence. In this work, a new method for a direct measurement of the dose of a complete helical sequence is developed and tested. Results show that this method is practical and that the accuracy of the modern CT devices seems to be at the sufficient level, so that the dose display values can be used for patient dose estimation.


MRI texture features as biomarkers to predict MGMT methylation status in glioblastomas.
Imaging biomarker research focuses on discovering relationships between radiological features and histological findings. In glioblastoma patients, methylation of the O(6)-methylguanine methyltransferase (MGMT) gene promoter is positively correlated with an increased effectiveness of current standard of care. In this paper, the authors investigate texture features as potential imaging biomarkers for capturing the MGMT methylation status of glioblastoma multiforme (GBM) tumors when combined with supervised classification schemes. A retrospective study of 155 GBM patients with known MGMT methylation status was conducted. Co-occurrence and run length texture features were calculated, and both support vector machines (SVMs) and random forest classifiers were used to predict MGMT methylation status. The best classification system (an SVM-based classifier) had a maximum area under the receiver-operating characteristic (ROC) curve of 0.85 (95% CI: 0.78-0.91) using four texture features (correlation, energy, entropy, and local intensity) originating from the T2-weighted images, yielding at the optimal threshold of the ROC curve, a sensitivity of 0.803 and a specificity of 0.813. Results show that supervised machine learning of MRI texture features can predict MGMT methylation status in preoperative GBM tumors, thus providing a new noninvasive imaging biomarker.


The use of tetracycline-containing controlled-release fibers in the treatment of refractory periodontitis.
The purpose of this study was to evaluate the safety and clinical efficacy of controlled-release tetracycline-containing fibers in patients with refractory periodontitis versus the preceding classical treatment. One hundred twenty-one sites in 20 patients were followed from baseline to 6 months after fiber insertion. Each selected site was > or = 5 mm deep and bled on probing. All 20 patients had at least one site > or = 7 mm which bled on probing. Those pockets remained after intense and repeated conventional therapy (scaling and root planing and often surgery), often including the use of systemic antibiotics. This treatment period, the so-called control period, preceded the experimental period by at least 3 years, when the fibers were placed. Both treatments (in control and test period) were performed in the Department of Periodontology at the University Hospital in Leuven. At the start of the experimental period, all pockets > or = 5 mm were treated by the placement of fibers impregnated with 25% tetracycline. The fibers were removed after 10 days. Probing depth, clinical attachment level, gingival recession, and bleeding on probing were recorded at baseline, and at 1, 3, and 6 months following treatment. Analysis of data from all sites indicated that a significant decrease in probing depth and gain in attachment were present at all follow-up visits. The mean probing depth reduction for sites > or = 7 mm was 3.2 mm at month 6, with a gain in attachment of 2.7 mm, while this was -1.0 mm and -1.9 mm, respectively, during the preceding control period. The fraction of bleeding pockets was reduced from 77% to 27% and from 80% to 77% during the experimental and control periods, respectively. No significant adverse side-effects were observed, except for a transient redness at fiber removal in 2 sites. Fiber insertion appeared to be time-consuming even when the operator was familiarized with the procedure. The results of this study prove that tetracycline-impregnated fibers can reduce probing depth significantly for a period of 6 months in patients not responding to thorough and repeated classical periodontal treatment.


Different profiles of wheat antigens are recognised by patients suffering from coeliac disease and IgE-mediated food allergy.
Dietary intake of wheat can cause two distinct immunologically mediated diseases with severe gastrointestinal manifestations, coeliac disease (CD) and IgE-mediated food allergy. The pathomechanisms underlying these diseases are different, but the profile of the target antigens in wheat has not been compared for the two diseases. We compared IgA- and IgE-reactive antigens in wheat using sera from patients with coeliac disease (n = 35) and food allergy to wheat (n = 16) by one- and two-dimensional immunoblotting. Furthermore, the IgG subclass (IgG1-IgG4) reactivity to wheat antigens was studied by enzyme-linked immunosorbent assay. IgA antibodies from CD patients and IgE antibodies from allergic patients recognised distinct profiles of wheat antigens. Furthermore, the IgG subclass responses to wheat antigens were different in CD and wheat-allergic patients. This study thus demonstrates that wheat contains antigens/epitopes which are preferentially recognised by CD patients, whereas others elicit IgE-mediated food allergy. This finding suggests that the nature of a food antigen may influence the quality of the pathological immune response in the gut and has implications for the diagnosis and therapy of hypersensitivity to wheat.


Molecular investigation of evaporation of biodroplets containing single-strand DNA on graphene surface.
In this study, the water droplet behaviour of four different types of single-strand DNA with homogeneous base sequence on a graphene substrate during evaporation of the droplet was investigated using molecular dynamics (MD) simulation. The simulation results indicated that the evaporation depended on the DNA sequence. The observed changes can be divided into four parts: (i) vaporization mode, (ii) evaporation flux, (iii) mechanism of single-strand placement on the surface, and (iv) consideration of remaining single strands after evaporation. Our simulation observations indicated different evaporation modes for thymine biodroplets as compared to those for other biodroplets. The evaporation of the thymine biodroplets occurred with an increase in the contact angle, while that of the other biodroplets occur in a constant contact angle mode. Moreover, thymine biodroplets generate the lowest contact line compared to other single strands, and it is always placed far away from the centre of the droplets during evaporation. Investigating variations in the evaporation flux shows that thymine has the highest evaporation flux and guanine has the lowest. Moreover, during initial evaporation, the flux of evaporation increases at the triple point of the biodroplets containing thymine single strands, while it decreases in the other biodroplets. The following observation was obtained from the study of the placement of single strands on the substrate: guanine and thymine interacted slower than other single strands during evaporation with graphene, adenine single strand had a higher folding during evaporation, and guanine single strand showed the lowest end-to-end distance. The investigation of single-strand DNA after evaporation shows that adenine produces the most stable structure at the end of evaporation. In addition, cytosine is the most stretched single-strand DNA due to its lack of internal π-π stacking and hydrogen bonding. Therefore, cytosine single strand is more accessible for use in microarrays to detect target single strands.


Comparison of MRI Sequences to Predict ATRX Status Using Radiomics-Based Machine Learning.
ATRX is an important molecular marker according to the 2021 WHO classification of adult-type diffuse glioma. We aim to predict the ATRX mutation status non-invasively using radiomics-based machine learning models on MRI and to determine which MRI sequence is best suited for this purpose. In this retrospective study, we used MRI images of patients with histologically confirmed glioma, including the sequences T1w without and with the administration of contrast agent, T2w, and the FLAIR. Radiomics features were extracted from the corresponding MRI images by hand-delineated regions of interest. Data partitioning into training data and independent test data was repeated 100 times to avoid random effects. Feature preselection and subsequent model development were performed using Lasso regression. The T2w sequence was found to be the most suitable and the FLAIR sequence the least suitable for predicting ATRX mutations using radiomics-based machine learning models. For the T2w sequence, our seven-feature model developed with Lasso regression achieved a mean AUC of 0.831, a mean accuracy of 0.746, a mean sensitivity of 0.772, and a mean specificity of 0.697. In conclusion, for the prediction of ATRX mutation using radiomics-based machine learning models, the T2w sequence is the most suitable among the commonly used MRI sequences.


Fractional diffusion model for force distribution in static granular media.
We present the results of a numerical and an experimental investigation of the probability distribution of normal contact forces in static packs of particles with two different hardnesses. Force distributions are computed and compared with existing models and experimental data. It is found that the probability distribution function of normal contact forces P(f) is well described by a semiempirical model derived from a fractional diffusion equation. This model reproduces most of the features common to force distributions observed in experimental and numerical studies including the finite value for P(f) as the forces tend to zero. The results indicate that the fractional model fits well both the numerical and experimental data over a wide range of particle deformations in contrast to the existing models. These results provide an insight into the physics of granular media and complement previous findings.


Mature artificial intelligence- and machine learning-enabled medical tools impacting vascular surgical care: A scoping review of late-stage, US Food and Drug Administration-approved or cleared technologies relevant to vascular surgeons.
Artificial intelligence and machine learning (AI/ML)-enabled tools are shifting from theoretical or research-only applications to mature, clinically useful tools. The goal of this article was to provide a scoping review of the most mature AI/ML-enabled technologies reviewed and cleared by the US Food and Drug Administration relevant to the field of vascular surgery. Despite decades of slow progress, this landscape is now evolving rapidly, with more than 100 AI/ML-powered tools being approved by the US Food and Drug Administration each year. Within the field of vascular surgery specifically, this review identified 17 companies with mature technologies that have at least one US Food and Drug Administration clearance, all occurring between 2016 and 2022. The maturation of these technologies appears to be accelerating, with improving regulatory clarity and clinical uptake. The early AI/ML-powered devices extend or amplify clinically entrenched platform technologies and tend to be focused on the diagnosis or evaluation of time-sensitive, clinically important pathologies (eg, reading Digital Imaging and Communications in Medicine-compliant computed tomography images to identify pulmonary embolism), or when physician efficiency or time savings is improved (eg, preoperative planning and intraoperative guidance). The majority (>75%) of these technologies are at the intersection of radiology and vascular surgery. It is becoming increasingly important that the contemporary vascular surgeon understands this shifting paradigm, as these once-nascent technologies are finally maturing and will be encountered with increasingly regularity in daily clinical practice.


Favorable response to pemetrexed, cisplatin and bevacizumab in invasive mucinous adenocarcinoma: A case report and literature review.
Invasive mucinous adenocarcinoma (IMA) was formerly referred to as mucinous bronchioloalveolar carcinoma. The lack of effective chemotherapy and comprehensive treatment for this type of tumor poses a great challenge in clinical practice. We herein report the case of a male patient with IMA who was treated with a combination of pemetrexed (500 mg/m2), cisplatin (75 mg/m2) and bevacizumab (15 mg/kg) as first-line chemotherapy. The patient achieved significant radiological improvement with 6 courses of this regimen. After the tumor progressed, the patient again achieved marked improvement with an additional 4 courses of the same regimen. The patient survived for a total of 30 months after the first chemotherapy. Therefore, bevacizumab in combination with pemetrexed/cisplatin may be an effective strategy for the treatment of IMA. The available literature on this chemotherapy regimen was also reviewed and discussed in the present study.


[Progress in research of family-based cohort study on common chronic non-communicable diseases in rural population in northern China].
Family-based cohort study is a special type of study design, in which biological samples and environmental exposure information of the member in a family are collected and related follow up is conducted. Family-based cohort study can be applied to explore the effect of genetic factors, environmental factors, gene-gene interaction, and gene-environment interaction in the etiology of complex diseases. This paper summarizes the objectives, methods and results, as well as the opportunities and challenges of the family-based cohort study on common chronic non-communicable diseases in rural population in northern China.


Uncoupling Amphipathicity and Hydrophobicity: Role of Charge Clustering in Membrane Interactions of Cationic Antimicrobial Peptides.
Peptides with a combination of high positive charge and high hydrophobicity have high antimicrobial activity, as epitomized by peptide venoms, which are designed by nature as disruptors of host membranes yet also display significant efficacy against pathogens. To investigate this phenomenon systematically, here we focus on ponericin W1, a peptide venom isolated from Pachycondyla goeldii ants (WLGSALKIGAKLLPSVVGLFKKKKQ) to examine whether Lys positioning can be broadly applied to optimize the functional range of existing natural sequences. We prepared sets of ponericin W1 analogues, where Lys residues were either distributed in an amphipathic manner throughout the sequence (PonAmp), clustered at the N-terminus (PonN), or clustered at the C-terminus (PonC), along with their counterparts of reduced hydrophobicity through 2-4 Leu-to-Ala replacements. We found that wild-type ponericin W1 and all three variants displayed toxicity against human erythrocytes, but hemolysis was eliminated by the replacement of two or more Leu residues by Ala residues. As well, peptides containing up to 3 Leu-to-Ala replacements retained antimicrobial activity against E. coli bacteria. Biophysical analyses of peptide-membrane interaction patterns by circular dichroism spectroscopy revealed a novel mode of cluster-dependent peptide positioning vis-à-vis the water-membrane interface, where PonAmp and PonC peptides displayed full or partial helical structures, while PonN peptides were unstructured, likely due, in part, to dynamic interchange between aqueous and membrane surface environments. The overall findings suggest that the lower membrane penetration of N-terminal charge-clustered constructs coupled with moderate sequence hydrophobicity may be advantageous for conferring enhanced target selectivity for bacterial versus mammalian membranes.


Tuberculosis After Kidney Transplant in the Samara Region of Russia: Possible Solutions to Diagnosis and Treatment.
Infections are the most important of all fatal complications in the first year after kidney transplant. They often differ in the severity of their course and can manifest in atypical symptoms. Further, their complex presentation significantly impedes diagnosis and treatment selection. Tuberculosis is unique among infections that affect patients posttransplant because it is accompanied by significant difficulties in detection, treatment, and prevention. The clinical application of a decision support system that can predict the likelihood (percentage) of patients developing posttransplant tuberculosis appears promising.


Protein kinase C-alpha mediates TNF release process in RBL-2H3 mast cells.
1 To clarify the mechanism of mast cell TNF secretion, especially its release process after being produced, we utilized an antiallergic drug, azelastine (4-(p-chlorobenzyl)-2-(hexahydro-1-methyl-1H-azepin-4-yl)-1-(2H)- phthalazinone), which has been reported to inhibit TNF release without affecting its production in ionomycin-stimulated RBL-2H3 cells. 2 Such inhibition was associated with the suppression of an ionomycin-induced increase in membrane-associated PKC activity rather than the suppression of Ca2+ influx, suggesting that PKC might be involved in TNF release process. 3 To see whether conventional PKC family (cPKCs) are involved, we investigated the effects of a selective cPKC inhibitor (Gö6976) and an activator (thymeleatoxin) on TNF release by adding them 1 h after cell stimulation. By this time, TNF mRNA expression had reached its maximum. Gö6976 markedly inhibited TNF release, whereas thymeleatoxin enhanced it, showing a key role of cPKC in TNF post-transcriptional process, possibly its releasing step. 4 To determine which subtype of cPKCs could be affected by azelastine, Western blotting and live imaging by confocal microscopy were conducted to detect the translocation of endogenous cPKC (alpha, betaI and betaII) and transfected GFP-tagged cPKC, respectively. Both methods clearly demonstrated that 1 microM azelastine selectively inhibits ionomycin-triggered translocation of (alpha)PKC without acting on betaI or betaIIPKC. 5 In antigen-stimulated cells, such a low concentration of azelastine did not affect either (alpha)PKC translocation or TNF release, suggesting a functional link between (alpha)PKC and the TNF-releasing step. 6 These results suggest that (alpha)PKC mediates the TNF release process and azelastine inhibits TNF release by selectively interfering with the recruitment of (alpha)PKC in the pathway activated by ionomycin in RBL-2H3 cells.


Oncologic specimen from laparoscopic assisted gastrectomy for gastric adenocarcinoma is comparable to D1-open surgery: the experience of a Canadian centre.
The Eastern experience has reported the safety of laparoscopic assisted gastrectomy (LAG) for gastric cancer. Its use in Western countries is still debated owing to concerns about its oncologic equivalence to open gastrectomy (OG). We sought to review and compare their operative outcomes and oncologic specimen quality (number of harvested lymph nodes and surgical margins) for gastric adenocarcinoma (GA). We reviewed the charts of all patients undergoing LAG (2007-2010) and OG (2000-2010) for GA in a single institution. Several surgeons performed the OGs, whereas 1 fellowship-trained laparoscopic surgeon performed LAGs. The primary outcome was quality of the surgical specimen, assessed by the number of harvested lymph nodes (LNs) and margin status. Secondary outcomes were perioperative events. Data were analyzed as intention to treat. We retrieved 60 cases (47 OGs, 13 LAGs). The conversion rate was 23%. Mean operative time was 115 minutes longer and blood loss was 425 mL less (both p < 0.001) for LAGs. A mean of 14.4 (standard deviation [SD] 9.8) and 11.2 (SD 8.2) LNs were harvested for OGs and LAGs, respectively (p = 0.29). Negative margins were achieved for all patients. Mean length of stay was similar (LAG: 19 d v. OG: 18.9 d; p = 0.91). The groups did not differ on major postoperative complications (12.7% v. 23.1%; p = 0.39) or operative mortality (2.1% v. 7.7%; p = 0.32). Laparoscopic assisted gastrectomy is a challenging but safe and feasible procedure in experienced hands. It offers the same radical resection as OG regarding negative margins and LN retrieval. Long-term follow-up is warranted.


Effect of sintering temperature on the thermal properties of diopside-based glass-ceramics of varying CaO/MgO ratio.
The thermal properties of diopside (CaMgSi2O6)-based glass-ceramics of varying CaO/MgO ratio were investigated as a function of sintering temperature. The crystallization behavior of the glass was studied by a non-isothermal method using a differential thermal analysis (DTA) with various heating rates. Diopside, as a main crystalline phase, and cordierite, as a minor phase, were formed in the glass-ceramics with an - 0.67-2.23 CaO/MgO ratio. The X-ray diffraction peak for diopside in the glass-ceramic becomes higher with an increase of the CaO/MgO ratio. The crystallization volume fraction with sintering temperature was calculated showing that both the initiation temperature for crystallization and a temperature range of crystallization increased with an increased heating rate. The microstructure of all glass-ceramics had a lump area composed of several tens-of-nanometer particles and a matrix composed of rows of particles, and the matrix area decreased with a decreasing CaO/MgO ratio. The thermal conductivity of glass-ceramics of CaO/MgO = 2.23 was 44% higher than that of CaO/MgO = 0.67 owing to the higher crystallinity and less voids in a microstructure. All glass-ceramics fabricated in this study were sintered at below 955 degrees C, which makes them applicable to the LTCC process for light-emitting diode packaging.


Doping dependence of the pressure response of Tc in the SmO(1-x)F(x)FeAs superconductors.
The superconducting transition temperature of the high-Tc SmO1-xFxFeAs superconductors increases monotonically as the F-doping level x increases to 0.20. High-pressure magnetization experiments reveal a strong sensitivity of Tc to interatomic distances in the underdoped regime (x </= 0.12) with the pressure coefficient of Tc, d(ln Tc)/dP being strongly positive. However, as the doping level increases further to x = 0.15, we find that this sensitivity is strongly suppressed and at the same time, d(ln Tc)/dP sharply switches over to assume negative values with Tc decreasing with increasing applied pressure. The abrupt change in the pressure response of the superconducting properties of the SmO1-xFxFeAs phases coincides with the putative existence of a quantum critical point (QCP) near x approximately 0.14, as proposed by resistivity and Hall effect measurements.


Antiepileptic drug withdrawal--a good idea?
Patients who are seizure free for 2 years or more are candidates for antiepileptic drug (AED) withdrawal. A MEDLINE search of the English language literature from 1980-1996 was performed to identify articles dealing with AED withdrawal in both adults and children. Factors examined included advantages and disadvantages of withdrawal, risks of relapse, prognostic factors of outcome, and methods of withdrawal. Advantages include psychosocial benefits, cost savings (direct drug costs, indirect monitoring costs), and avoidance of adverse effects and toxicity. The benefits must be balanced against the risks and impact of seizure relapse, which are different for each individual patient. A review of the prognostic factors that influence the risk of relapse will aid clinicians in determining appropriate candidates for AED withdrawal.


Quantitative assessment of lung cancer perfusion using MDCT: does measurement reproducibility improve with greater tumor volume coverage?
To date, quantitative assessment of tumor vascularity using perfusion CT has been limited to a single tumor level, with the potential for measurement error in heterogeneous tumors. We aimed to determine if greater z-axis tumor coverage improves the reproducibility of perfusion CT measurements in lung cancer. Paired perfusion studies were performed on 10 patients who had histologically confirmed advanced non-small cell lung cancer. Using 16-MDCT, multiple sequential volumetric acquisitions encompassing the entire tumor were acquired after infusion of i.v. contrast material. Using Patlak analysis, median values of tumor permeability (mL/100 mL/min) and blood volume (mL/100 mL) were measured for 10-mm z-axis coverage, and for 40-mm z-axis coverage in each of the paired perfusion studies. Measurement reproducibility was evaluated using Bland-Altman statistics. Mean difference (95% limits of agreement) for tumor permeability was 1.4 (-4.0 to 6.8) for 10-mm coverage and 0.8 (-3.6 to 5.2) for 40-mm coverage. Mean difference (95% limits of agreement) for blood volume was 1.9 (-5.1 to 8.9) for 10-mm coverage and 1.4 (-3.7 to 6.6) for 40-mm coverage. The coefficient of variation for permeability was 18.7% for 10-mm coverage, improving to 11.9% for 40-mm coverage. The coefficient of variation for blood volume was 41.7% for 10-mm coverage, improving to 32.6% for 40-mm coverage. Our results show that an improvement in tumor perfusion measurement reproducibility may be achieved with greater z-axis coverage.


Effects of ethinyl estradiol on hepatic microsomal proteins and the turnover of cytochrome P-450.
The effect of ethinyl estradiol, a steroid commonly used in birth control pills and possibly associated with impaired drug metabolism in humans, on the activity of and turnover of components of the hepatic microsomal mixed-function oxidase system was studied in male rats. After 5 days of ethinyl estradiol, 5 mg/kg/day, there was a significant decrease in the activity of ethylmorphine-N-demethylase and in cytochrome P-450, cytochrome b2, and NADPH cytochrome c reductase. Cytochrome P-450 apoproteins were identified within an SDS-polyacrylamide gel system, and the rate of turnover of cytochrome P-450 apoproteins was studied by double-isotope labeling techniques. After 5 days of ethinyl estradiol administration, the rate of degradation of cytochrome P-450 apoprotein was reduced (half-life of 50 hr compared to 24 hr in control), and their relative rate of synthesis was likewise reduced, indicating that a new steady state of protein turnover associated with reduced synthesis rate had been reached. This was confirmed by studies of the effect of ethinyl estradiol on the level of microsomal cytochrome P-450 over a 10-day period.


[Dehiscence of the anterior semicircular canal and otosclerosis: a case report].
The dehiscence of the anterior semicircular canal is a new clinical entity, it is necessary to consider this when a gusher occurs during stapedial surgery. We report a rare case of dehiscence of the anterior canal associated with otosclerosis. This was revealed by a gusher during the initial stapedectomy. At 3 months, an obliteration of the dehiscence was necessary by middle cranial fossa approach (persistant vestibular symptoms), seven months later. Revision stapedial surgery resulted in complete closure of the air-bone-gap. High resolution CT scans of the temporal bone are the key to diagnosis. It is necessary to appreciate this pathology with advances in canal and vestibular surgery.


Profile of epilepsy in a regional hospital in Al qassim, saudi arabia.
Epilepsy is a diverse set of chronic neurological disorders characterized by seizures. It is one of the most common of the serious neurological disorders. About 3% of people will be diagnosed with epilepsy at some time in their lives. We aimed to address the commonest types of seizures, their aetiologies, EEG and neuroimaging results and prognosis of patients presented to neurology services of the King Fahad Specialist Hospital- AlQassim (KFSH). In this retrospective epidemiological study we investigated the medical records of patients with epilepsy, who attended the neurology services of KFSH, during the study period (26/10/2011-26/4/2012). The study included 341 patients; 189 (55.4%) males and 152 (44.6%) females. Their ages ranged between 12 and 85 years (mean ± SD = 31±16.9). The majority of patients had Generalised Tonic Clonic Seizures (76.2%), followed by Complex Partial Seizures (7.6%). 73% of our patients had idiopathic epilepsy. The commonest causes for symptomatic epilepsy were Cerebro Vascular Accidents and Head trauma. Hemiplegia, mental retardation and psychiatric illness were the commonest comorbidity. 69.3% of patients had controlled seizures. Patients with idiopathic epilepsy were significantly controlled than patients with symptomatic epilepsy (P=0.01), and those using one Anti Epileptic Drug were significantly controlled compared to patients using polytherapy (P=0.0001) there was no significant relation between controlled seizure and duration of illness or hospitalization or EEG changes. Seizure types, aetiology, drug therapy, Comorbidities and outcome in a tertiary care hospital in Saudi Arabia are similar to previous local and international studies. 35.3% of patients were hospitalized, higher rates than previous studies. Seizure control was better in generalized seizures and idiopathic epilepsy compared to complex partial seizures or partial seizures with secondary generalization and symptomatic epilepsy.


Regulatory effect of amino acids on the pasting behavior of potato starch is attributable to its binding to the starch chain.
The binding of an amino acid, glycine (Gly), alanine (Ala), epsilon-aminocaproic acid (-AC), monosodium glutamate (GluNa), or lysine (Lys), to starch was examined by a biomolecular interaction analyzer (IAsys). A starch sample (ATS) hydrolyzed to an extent of 1% hydrolysis rate with 15% sulfuric acid was used as a model starch for the binding examination. The reducing end of ATS was oxidized by the Somogyi reagent, and the conversion of the reducing end to the carboxyl group of ATS was confirmed by a carboxylic acid fluorescence labeling reagent. The oxidized ATS was immobilized to the amino group of a sensor cuvette by using water-soluble carbodiimide and N-hydroxysuccinimide through an amide bond. The IAsys examination showed that Gly, Ala, and epsilon-AC scarcely bound to the immobilized starch chains but that GluNa and Lys favorably bound with their increasing concentrations. The relative binding index (RBI) of each amino acid was defined by the ratio of the slope of the linear regression equation between the binding response and the concentration for each amino acid to that for Gly. Because the relationships between the RBI and the pasting characteristics (pasting temperature, peak viscosity, breakdown, and swelling index) could each be expressed by a linear regression equation with a high correlation coefficient, it is concluded that the regulation of the pasting behavior of starch with an amino acid is caused by binding of the amino acid to the starch chains.


A quantitative framework for whole-body coordination reveals specific deficits in freely walking ataxic mice.
The coordination of movement across the body is a fundamental, yet poorly understood aspect of motor control. Mutant mice with cerebellar circuit defects exhibit characteristic impairments in locomotor coordination; however, the fundamental features of this gait ataxia have not been effectively isolated. Here we describe a novel system (LocoMouse) for analyzing limb, head, and tail kinematics of freely walking mice. Analysis of visibly ataxic Purkinje cell degeneration (pcd) mice reveals that while differences in the forward motion of individual paws are fully accounted for by changes in walking speed and body size, more complex 3D trajectories and, especially, inter-limb and whole-body coordination are specifically impaired. Moreover, the coordination deficits in pcd are consistent with a failure to predict and compensate for the consequences of movement across the body. These results isolate specific impairments in whole-body coordination in mice and provide a quantitative framework for understanding cerebellar contributions to coordinated locomotion.


Detection of active left ventricular thrombosis during acute myocardial infarction using indium-111 platelet scintigraphy.
Platelet scintigraphy with radioactive indium-111 may be used both to identify and to reflect the activity of thrombin in vivo in man. Forty-one patients with acute myocardial infarction were studied for active left ventricular thrombosis by platelet scintigraphy and followed until in-hospital death, discharge, or same-admission cardiac surgery for evidence of systemic embolization. A total of 4.7 +/- 2.4 X 10(9) platelets (mean +/- 1 SD) labelled with 381 mu Ci +/- 51 mu Ci of indium-111 was injected intravenously at 91 +/- 88 hours following the onset of chest pain. Patients were imaged in multiple views on the day of and three to four days after injection of the platelet suspension. Group 1 (n = 29) had transmural myocardial infarctions, of which 21 were anterior (peak total level of creatine phosphokinase [CPK], 2,272 +/- 2,026 IU; mean +/- 1 SD) and eight were inferior (CPK level, 1,673 +/- 589 IU). Group 2 (n = 12) had subendocardial myocardial infarctions (CPK level 799 +/- 751 IU). Those with subendocardial and transmural inferior myocardial infarctions had neither left ventricular thrombosis nor emboli. Ten (48 percent) of 21 with anterior transmural myocardial infarctions had left ventricular thrombosis by platelet scintigraphy. Three with and one without such thrombosis by scintigraphy had acute neurologic episodes. In the group with anterior myocardial infarctions, seven of ten patients with and four of 11 without left ventricular thrombosis received heparin subcutaneously (chi 2 = 1.22 [Yates correction]; p greater than 0.30). We conclude that platelet scintigraphy may be used to monitor antiplatelet and anticoagulant therapy in patients with anterior transmural myocardial infarctions who are at risk for left ventricular thrombosis and systemic embolization.


The relationship between difficulties in psychological adjustment in young adulthood and exposure to bullying behaviour in childhood and adolescence.
This study investigates the relationship between involvement in bullying in childhood and adolescence and psychological difficulties in young adulthood. A total of 249 college students completed the Retrospective Bullying Questionnaire and Trauma Symptom Checklist. The results showed significant differences in psychological adjustment among respondents who were exposed to bullying compared to respondents who were not exposed to bullying. Those exposed to bullying had significantly higher levels of anxiety, depression, sleeping problems, and dissociative and traumatic symptoms compared to those who were not exposed to bullying. Respondents who were exposed to bullying in all three examined periods (the period from the first to fourth grade, the period from the fifth to eighth grade and the high school period) had higher scores on the subscale of dissociative symptoms and sexual trauma symptoms compared to respondents who were exposed through one or two periods. Victims abused in all three periods have more symptoms of anxiety and sleeping problems compared to the subjects exposed to bullying during one examination period. There were no differences in the level of depressive symptoms and sexual problems regarding the duration of bullying. Also, there were no differences in psychological adjustment between respondents who were bullied during one specific period. Bullying experiences in childhood and adolescence are connected with difficulties in psychological adjustment in young adulthood.


In vitro inactivation of two Egyptian A/H5N1 viruses by four commercial chemical disinfectants.
The highly pathogenic H5N1 avian influenza virus (A/H5N1) devastated the poultry industry and posed a serious health threat. Cleaning and disinfection are essential parts of preventative and postoutbreak management of A/H5N1 infections in poultry. In this preliminary study, we used suspension and carrier tests to evaluate the impact of concentration, time of exposure, surface porosity, and organic matter on the ability of four commercial chemical disinfectants to inactivate two A/H5N1 viruses of clade 2.2.1 isolated in 2006 and 2010 from broiler flocks in Egypt. Viruses were incubated with 0.5%, 1%, and 2% of formalin, glutaraldehyde, TH4, and Virkon S for 15, 30, 60, and 120 min at room temperature (22 +/- 2 C). In suspension tests, in the absence of organic matter, all disinfectants, at each concentration, except Virkon S 0.5%, effectively inactivated virus suspensions after a 15-min exposure time. In the presence of organic matter, the use of low concentrations of formalin (0.5%), glutaraldehyde (0.5%), or Virkon S (0.5%) was not sufficient to inactivate the viruses after 15 min. In gauze carrier tests, only formalin at any concentration for 15 min was sufficient to inactivate the viruses, whereas different concentrations or exposure times were required for glutaraldehyde (0.5% for 60 min), TH4 (0.5% for 30 min), and Virkon S (0.5% for 60 min or 1% for 30 min). In wood carrier tests, total inactivation of the virus was obtained at concentrations of 0.5% for 30 min (formalin and TH4) or 60 min (glutaraldehyde and Virkon S). This study emphasizes the need to use high concentrations of and/or extended time of exposure to disinfectants for efficient inactivation of A/H5N1, particularly in the presence of organic matter or different surfaces, which are common in poultry operations. In addition, it seemed that the virus isolated in 2010 was more resistant to disinfectants than the isolate from 2006 when wood was used as a carrier.


Prognostic value of Notch receptors in postsurgical patients with hepatitis B virus-related hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies and a major cause of cancer involved death worldwide. Prognosis remains poor because of high recurrence rates and lack of effective relapse prevention strategies. Notch pathway plays an important role in tumor progression and metastasis, and it is associated with the prognosis of cancer. A total of 465 hepatitis B virus (HBV)-related HCC patients who underwent surgery were enrolled. Single nucleotide polymorphisms (SNP) of Notch pathway receptors were genotyped using Sanger DNA sequencing. Kaplan-Meier curves and the Cox proportional hazards regression model were adopted to analyze the association of polymorphisms and mRNA expression with clinical and pathological features, respectively. Four SNPs (rs1043996 in Notch3 and rs422951, rs520692, rs3830041 in Notch4) were significantly associated with overall survival (OS) (P = 0.023, P = 0.042, P = 0.028, and P = 0.001 respectively). Patients carrying the AA genotype in rs1043996 and TT/TC genotypes in rs422951 and rs520692 significantly decreased risks of death, compared to those carrying the AG/GG genotype in rs1043996 and CC genotype in rs422951 and rs520692, respectively. Patients carrying the TT genotype in rs3830041 showed poorer OS, compared with those carrying the TC/CC genotype. A haplotype block (rs422951 was in strong LD with rs520692, r2 = 0.843) was identified in Notch4. Notch3 mRNA expression significantly increased in tumor tissue, compared with nontumor normal tissue (P < 0.0001). Moreover, higher expression of Notch3 was associated with poorer OS (HR = 2.11, 95% CI = 1.32-3.37, P = 0.002) and shorter recurrence time of HBV-related HCC (HR = 1.96, 95% CI = 1.31-2.93, P = 0.001). Our findings collectively indicate that Notch receptors variants (rs1043996 in Notch3 and rs422951, rs520692, rs3830041 in Notch4) are independent predictive targets for OS in HBV-related HCC patients. Notch3 expression is a potential prognostic biomarker of OS and recurrence-free survival (RFS) prediction in HBV-related HCC patients following surgical treatment.


B-cell lymphoma developing de novo hepatitis B after salvage therapies including rituximab through seroconversion of surface antibody.
The patient was a 73-year-old woman. At 63 years of age, she had developed follicular lymphoma that showed a complete response to R-CHOP therapy. Over the subsequent 8 years, she experienced 4 relapses and was administered rituximab monotherapy once, combined rituximab-fludarabine therapy twice, and CHASE-R therapy once, achieving a complete response each time. Before her first therapy, hepatitis B virus (HBV) surface antigen was negative, while hepatitis B surface antibody (anti-HBs) and hepatitis B core antibody were not measured. Later, before her second salvage therapy, anti-HBs was negative, but then changed to positive before her third salvage therapy. HBV-DNA was negative before CHASE-R therapy. At 16 months after completing the CHASE-R therapy, she developed hepatitis and HBV-DNA had changed to positive. Hepatitis did not become fulminant and entecavir administration was effective. It was surmised that HBV had resolved, but she became negative for anti-HBs following the rituximab-containing chemotherapy. Therefore, this is a rare case in which de novo hepatitis developed after the final chemotherapy. The prognosis of patients with de novo hepatitis accompanying treatment of B-cell lymphoma is poor. In those who undergo lymphoma salvage therapy, the risk for and clinical course of HBV reactivation might differ from those of treatment-naïve patients.


Characteristics and outcomes among a hospitalized patient cohort with Streptococcus pneumoniae infection.
Infection due to Streptococcus pneumoniae (SP) requiring hospitalization is common. However, recent clinical studies describing patient characteristics and outcomes for SP infection in adults requiring hospitalization are lacking. Our goal was to evaluate patient characteristics, contemporary antibiotic resistance, and clinical outcomes among hospitalized adults with SP infections.A retrospective cohort study was conducted at Barnes-Jewish Hospital (1350 beds) in St. Louis, Missouri, USA for years 2012 through 2016. During the study period, 358 hospitalized adults, excluding those with meningitis, were identified with SP infection. Forty-four patients (12.3%) died within 30 days of the identification of their infection. Among these infections, 99 (27.7%) were assessed to be hospital-acquired and 259 (72.3%) were community-onset infections. The majority of infections involved the respiratory tract (88.5%). Azithromycin resistance was the most common antibiotic resistance at 51.4%, followed by enteral penicillin resistance (45.3%), trimethoprim-sulfamethoxazole (34.1%), second-generation cephalosporin (cefuroxime) (30.7%), and meropenem (22.6%). There were 70 isolates (19.6%) classified as multidrug resistant. Independent predictors of hospital mortality included increasing weight in 1-kilogram increments (adjusted odds ratio [AOR], 1.02; 95% CI, 1.01 - 1.02; P = .048), increasing Charlson Comorbidity Index scores (AOR, 1.31; 95% CI, 1.21 - 1.42; P = .001), and the presence of septic shock (AOR, 3.89; 95% CI, 2.31 - 6.57; P = .009). The median [interquartile range] hospital length of stay was 8.1 days [4.5 days, 16.8 days].Hospitalized patients with infection attributed to SP have significant 30-day mortality and use of hospital resources. Antibiotic resistance is common among isolates associated with infection. Determinants of mortality are primarily severity of illness, underlying comorbidities and increasing patient weight. Efforts to improve the treatment and prevention of SP infections are needed.