Metabolic epidemiology of large bowel cancer: fecal bulk and constituents of high-risk North American and low-risk Finnish population.
The dietary pattern and fecal constituents of two populations with distinct risk for the development of colon cancer, a high-risk population in New York Metropolitan area and a low-risk population in rural Kuopio, were studied. The average daily intake of dietary fat and protein was the same in the two groups, but the sources of fat were different, a greater portion coming from dairy products in rural Kuopio and from meat in the New York Metropolitan area. Not only the frequency of bowel movements was higher, but also the daily total stool output as well as the fecal fiber excretion were greater in Kuopio compared with New York due to high dietary intake in rural Kuopio of cereal products rich in fiber. The concentration of fecal secondary bile acids and bacterial beta-glucuronidase activity was lower in rural Kuopio, but the total daily excretion of these constituents was the same in two populations. The daily fecal excretion of bacterial nuclear dehydrogenase activity and of neutral sterols was higher in rural Kuopio, and the concentration of these constituents was the same in the two groups. The high daily excretion of cholesterol metabolites in Kuopio might be due to high dietary intake of dairy products. The data suggest that one of the factors contributing to the low-risk of large bowel cancer in Finland, in spite of high dietary intake of fat, appears to be the fact that a high dietary fiber leads to an increase in stool bulk, thus diluting bile acids, which have promoting activity.


Intracellular transport and peptide loading of MHC class II molecules: regulation by chaperones and motors.
MHC class II molecules are important in the onset and modulation of cellular immune responses. Studies on the intracellular transport of these molecules has provided insight into the way pathogens are processed and presented at the cell surface and may result in future immunological intervention strategies. Recent reviews have extensively described structural properties and early events in the biosynthesis of MHC class II (1-3). In this review, the focus will be on the function of the dedicated chaperone proteins Ii, DM and DO in the class II assembly, transport and peptide loading as well on proteins involved in transport steps late in the intracellular transport of MHC class II.


A perspective on molecular signalling dysfunction, its clinical relevance and therapeutics in autism spectrum disorder.
Intellectual disability (ID) and autism spectrum disorder (ASD) are neurodevelopmental disorders that have become a primary clinical and social concern, with a prevalence of 2-3% in the population. Neuronal function and behaviour undergo significant malleability during the critical period of development that is found to be impaired in ID/ASD. Human genome sequencing studies have revealed many genetic variations associated with ASD/ID that are further verified by many approaches, including many mouse and other models. These models have facilitated the identification of fundamental mechanisms underlying the pathogenesis of ASD/ID, and several studies have proposed converging molecular pathways in ASD/ID. However, linking the mechanisms of the pathogenic genes and their molecular characteristics that lead to ID/ASD has progressed slowly, hampering the development of potential therapeutic strategies. This review discusses the possibility of recognising the common molecular causes for most ASD/ID based on studies from the available models that may enable a better therapeutic strategy to treat ID/ASD. We also reviewed the potential biomarkers to detect ASD/ID at early stages that may aid in diagnosis and initiating medical treatment, the concerns with drug failure in clinical trials, and developing therapeutic strategies that can be applied beyond a particular mutation associated with ASD/ID.


Prehospital Simple Thoracostomy Does Not Improve Patient Outcomes Compared to Needle Thoracostomy in Severely Injured Trauma Patients.
ATLS suggests simple thoracostomy (ST) after failure of needle thoracostomy (NT) in thoracic trauma. Some EMS agencies have adopted ST into their practice. We sought to describe our experience implementing ST in the prehospital setting, hypothesizing that prehospital ST would reduce failure rates and improve outcomes compared to NT. This was a retrospective review of adult trauma patients who received prehospital ST or NT from 2017 to 2020. There were 48 patients with 64 procedures included. 83.7% were male and 65.8% injured by penetrating mechanism and of median (IQR) age of 31 (25-46) years. 28 (43.8%) procedures were NT and 36 (56.3%) were ST. Rates of improved patient response (P = .15), noted return of blood/air (P = .19), and return of spontaneous circulation (P = .62) did not differ. On-scene times were higher for ST (16.8 vs 11.5 minutes; P < .02). Overall mortality did not differ between ST and NT (68.2% vs 46.4%, respectively; P = .125). For patients that survived beyond the ED, procedure-related complication rates were 2 of 21 patients (9.5%) in ST and 1 of 12 (8.3%) in NT. In penetrating trauma, simple thoracostomy had longer on-scene time and total prehospital time. ST did not improve success rates of ROSC and was associated with prolonged prehospital times, especially in penetrating trauma patients. Given the benefit of "scoop and run" in urban penetrating trauma, consideration should be given to direct transport in lieu of ST. Use of ST in blunt trauma should be evaluated prospectively.


Ly49Q, a member of the Ly49 family that is selectively expressed on myeloid lineage cells and involved in regulation of cytoskeletal architecture.
Here, we identified and characterized a Ly49 family member, designated as Ly49Q. The Ly49q gene encodes a 273-aa protein with an immunoreceptor tyrosine-based inhibitory motif (ITIM) at the N terminus of its cytoplasmic domain. We show that the ITIM of Ly49Q can recruit SHP-2 and SHP-1 in a tyrosine phosphorylation-dependent manner. In contrast to other known members of the Ly49 family, Ly49Q was found not to be expressed on NK1.1(+) cells, but instead was detectable on virtually all Gr-1(+) cells, such as myeloid precursors in bone marrow. Monocytes/macrophages also expressed low levels of Ly49Q, and the expression was enhanced by the treatment of cells with IFN-gamma. Treatment of activated macrophages with anti-Ly49Q mAb induced rapid formation of polarized actin structures, showing filopodia-like structure on one side and lamellipodial-like structure on the other side. A panel of proteins became tyrosine-phosphorylated in myeloid cells when treated with the mAb. Induction of the phosphorylation depends on the ITIM of Ly49Q. Thus, Ly49Q has unique features different from other known Ly49 family members and appears to be involved in regulation of cytoskeletal architecture of macrophages through ITIM-mediated signaling.


Multimorbidity Among Adult Outpatients With Type 1 Diabetes in Germany.
The aim of this cross-sectional retrospective study was to estimate the prevalence of different physical and psychiatric disorders as well as multimorbidity in outpatients with type 1 diabetes (T1D) in Germany. A total of 6967 adult patients with T1D from 958 general or diabetologist practices in Germany between January 2015 and December 2019 from the Disease Analyzer database (IQVIA) were included. The main outcome of the study was the prevalence of different diabetes-related and nondiabetes-related disorders within 12 months prior to the last outpatient visit. Multivariate logistic regression models were fitted with multimorbidity differently defined as >2, >3, >4, and >5 different disorders as a dependent variable and age, sex, glycated hemoglobin (HbA1c) values, and insulin pump therapy as impact variables. Mean age (standard deviation [SD]) was 45.3 (16.7) years; 42.9% were women, the mean HbA1c was 7.9% (SD: 1.4%). The most frequent disorder was arterial hypertension (31.2%), followed by dyslipidemia (26.4%), dorsalgia (20.4%), diabetic neuropathy (17.3%), and depression (14.6%). The proportion of thyroid gland disorders, retinopathy, urethritis, iron deficiency anemia, and psychiatric disorders was higher in women than in men. Hypertension and mental and behavioral disorders due to the use of tobacco were higher in men. On average, each patient was diagnosed with 3.1 different disorders. Age had the strongest association with multimorbidity, followed by HbA1c value and female sex. In summary, patients with T1D are often multimorbid, and the multimorbidity is associated with higher gender, female sex, and high HbA1c values. Understanding all of these factors can help practitioners create a risk profile for every patient.


Report of the 10(th) Asia-Pacific Federation of Societies for Surgery of the Hand Congress (Organising Chair and Scientific Chair).
A report on the 10(th) Asia-Pacific Federation of Societies for the Surgery of the Hand and 6(th) Asia-Pacific Federation of Societies for Hand Therapists is submitted detailing the numbers of attendees participating, papers presented and support received as well the some of the challenges faced and how best to overcome them from the local conference chair and scientific chair point of view.


Selection of a pentameric host in the host-guest complexes [[[[P(mu-NtBu)]2(mu-NH)]5].I]-[Li(thf)4]+ and [[[P(mu-NtBu)]2(mu-NH)]5].HBr.THF.
The structures of the host-guest complexes [[[[P(mu-NtBu)]2(mu-NH)]5]I]-.[Li(thf)4]+ [2.I[Li(thf)4]] and [[[P(mu-NtBu)]2(mu-NH)]5].HBr.THF (2.HBr.THF) show that increased distortion of the framework of the pentameric macrocycle [[[P(mu-NtBu)]2(mu-NH)]5] (2) occurs with the larger halide ions. Theoretical studies show that the thermodynamic stabilities of the model host-guest anions [2.X]- (X=Cl, Br, I) are in the order Cl- approximately Br->I-, that is, the reverse of the templating trend observed experimentally. These studies support the view that the selection of the pentamer 2 over the tetramer [[[P(mu-NtBu)]2(mu-NH)]4] (1) is kinetically controlled, a conclusion which is also consistent with the previous observation that the frameworks of 1 and 2 are not in dynamic equilibrium with each other.


Movement of Indole-3-acetic Acid and Tryptophan-derived Indole-3-acetic Acid from the Endosperm to the Shoot of Zea mays L.
The structures and the concentrations of all of the indolylic compounds that occur in the endosperm of the seeds of corn (Zea mays L.) are known. Thus, it should be possible to determine which, if any, of the indolylic compounds of the endosperm can be transported to the seedling in significant amounts and thus help identify the seed-auxin precursor of Cholodny (1935. Planta 23:289-312) and Skoog (1937. J. Gen. Physiol. 20:311-334). Of interest is the transport of tryptophan, indole-3-acetic acid (IAA), and the esters of IAA, which comprise 95% of the IAA compounds of the seed. We have shown that: (a) IAA can move from the endosperm to the shoot; (b) the rate of movement of IAA from endosperm to shoot is that of simple diffusion; (c) 98% of the transported IAA is converted into compounds other than IAA, or IAA esters, en route; (d) some of the IAA that has moved into the shoot has been esterified; (e) labeled tryptophan applied to the endosperm can be found as labeled IAA in the shoot; and (f) with certain assumptions concerning IAA turnover, the rate of movement of IAA and tryptophan-derived IAA from the endosperm to shoot is inadequate for shoot growth or to maintain IAA levels in the shoot.


The aim of the study was to evaluate the association between the angiotensin-converting enzyme ACE I/D (rs4340) polymorphism and DNA damage in pati-ents with essential hypertension (EH). The I/D polymorphism of ACE was determined by polymerase chain reaction in 170 male hypertensive patients and 64 normotensive blood donors. We used flow cytometry to determine the levels of cell death, micronuclei and accumulation of peripheral blood leukocytes in G1/G0, S, G2/M phases of the cell cycle. Additionally, the whole blood samples were incubated in vitro at 4 ºC for 24 h to investigate the genotype effects on the susceptibility of cells to DNA damage. We found lower frequency of cells in DNA synthesis S phase and higher levels of micronuclei in the hypertensive compared to normotensive group (p<0.05); increased formation of micronuclei was seen due to elevated micronuclei fre-quencies in patients with the ACE II genotype (p < 0.05), but not in ID or DD genotype carriers. Incubation of whole blood samples of normotensive individuals lead to the most active cell death (p < 0.05) and micronuclei formation (p > 0.05) in the II genotype carriers too. However, hypertensive patients displayed different cellular response to incubation-induced DNA damages in the ACE I/D genotype groups; after incubation, the frequencies of micronuclei were significantly higher in the DD genotype carriers (p < 0.05). To conclude, the study suggests that the ACE I/D polymorphism may contribute to mechanisms and intensity of DNA damages in hypertensive and normotensive individuals.


Influenza vaccination: opinions of health care professionals working in pediatric emergency departments.
Vaccine coverage of health care professionals against influenza is still low in Italy, as well as in other European countries. Between March and May 2018, this study was performed to collect the opinions of Pediatric health care professionals, working in emergency departments, regarding the efficacy and safety of the influenza vaccine. An anonymous online survey was employed to evaluate socio-demographic and professional characteristics, knowledges, beliefs and attitudes. Five hundred four health care professionals completed the survey: 331 physicians, 140 nurses and 33 other health are professionals. During the 2017-18 season, 55.8% of physicians, 19.3% of nurses and 12.1% of other health care professionals had vaccinated against the influenza virus. Not vaccinated physicians and nurses with less than 40 years of age were fewer than not vaccinated physicians and nurses with more than 40 years of age. Nurses and other health care professionals were less trustworthy of the influenza vaccination, less aware of the possibility of contracting and transmitting influenza and other vaccine-preventable diseases. Insufficient adherence to the influenza vaccination in physicians, nurses and other health care professionals is a concern for those assisting high-risk patients, especially in emergency departments. Therefore, it is vital to promote education of health care professionals and students regarding vaccinations. High vaccine coverage should be embedded in the safe hospital paradigm and should become a goal for the hospital's directors.


Antiferromagnetic Domain Wall Motion Driven by Spin-Orbit Torques.
We theoretically investigate the dynamics of antiferromagnetic domain walls driven by spin-orbit torques in antiferromagnet-heavy-metal bilayers. We show that spin-orbit torques drive antiferromagnetic domain walls much faster than ferromagnetic domain walls. As the domain wall velocity approaches the maximum spin-wave group velocity, the domain wall undergoes Lorentz contraction and emits spin waves in the terahertz frequency range. The interplay between spin-orbit torques and the relativistic dynamics of antiferromagnetic domain walls leads to the efficient manipulation of antiferromagnetic spin textures and paves the way for the generation of high frequency signals from antiferromagnets.


[Progress of Researches on Protective Effect of Acupuncture and Moxibustion in Relieving Intracellular Calcium Overload of Cradiomyocytes].
Myocardial contraction and relaxation are regulated by increases and decreases of the intracellular cytoplasmic calcium (Ca2+) concentration. Intracellular calcium ion is also a ubiquitous second messenger, and its related signal transduction pathways involve a variety of physiological activities and pathological changes. It has been well documented that intracellular calcium overload is involved in myocardial cellular injury. In the present paper, the authors make a review about experimental researches on the underlying mechanisms of acupuncture and moxibustion in the prevention and treatment of ischemic myocardial injury from reducing calcium overload in recent 10 years. Results of recent studies indicate that acupuncture and moxibustion interventions have a cardioprotective effect by raising Ca2+-ATPase activity and nitric oxide content, lowering L-type voltage depen-dent calcium channel activity, and ameliorating calcium overload in ischemic cardiomyocytes mainly through cytomembrane, sarcoplasmic reticulum membrane and mitochondrial membrane pathways. However, the current studies on the mechanisms of acupuncture in the improvement of the ischemic myocardial injury are far unclear up to now and do not closely combine the clinical application.


Evaluation of a psychosocial intervention on social support, perceived control, coping strategies, emotional distress, and quality of life of breast cancer patients.
The purpose of this research was to demonstrate that a specific psychosocial intervention changes reactions to cancer and quality of life. This study was carried out on 66 patients with a first breast cancer. Patients were randomly divided into two groups: a specific intervention group (G1, 8 sessions) or a support group (G2, 8 sessions). A control group (G3) was composed of patients who refused to participate in psychological intervention. Social support, perceived control, repression of emotions, coping strategies, emotional distress, and quality of life were assessed one week before (T1) and at the end (T2) of the psychological intervention. Results showed that G1 did not have significantly modified quality of life or psychological scores. Patients of G2 had poorer emotional quality of life, use of internal causal attributions, and minimized their illness at T1 as compared to patients of G3. At Time 2 these differences were not observed.


Thermal-Insulation Effect and Evaluation Indices of Asphalt Mixture Mixed with Phase-Change Materials.
Under strong winds and at low temperatures, heat loss of hot-mix asphalt mixtures is likely to occur, which leads to temperature segregation. Temperature segregation affects the forming quality and the performance of asphalt pavements. In this study, a phase-change thermal-insulation agent (PCTIA) was prepared for reducing the temperature dissipation. A cooling simulation experiment was performed to test the temperature-dissipation process for an ordinary asphalt mixture and the asphalt mixture mixed with PCTIA (AM-PCTIA). The thermal-insulation effect was analyzed according to the temperature difference and the thermal-insulation extension time. Moreover, two indices-the thermal-insulation accumulated time difference value (IATDV) and thermal-insulation accumulated time difference index (IATDI)-were proposed for evaluating the thermal-insulation ability and efficiency. The results indicated that the temperature at the center of the AM-PATIA was 4 °C higher than that for the ordinary asphalt mixture. The insulation time was prolonged by 29.8 min at the ambient temperature of 15 °C. As the ambient temperature increased, the thermal-insulation effect of the PCTIA improved.


Drinking Cultures and the Position of Women in Nine European Countries.
Nine European countries involved in the Biomed Project "Alcohol Consumption and Alcohol Problems Among Women in European Countries" are described in relation to sociodemographic characteristics and drinking patterns. The populations of the nine countries, especially women, have become much older during the period 1950-1995. Also, women tend to have fewer children, and at an older age, so that the percentage of the younger age groups is decreasing. If we connect this to the fact that women now are more a part of the labor force than before, we might infer that the observed decrease in gender difference in alcohol use is to be explained in relation to economic factors. In terms of drinking patterns, a broad division can be made between two wide regions: (a) the northern dry area, where beer is the leading beverage, consumed on weekends and outside mealtimes; and (b) the southern, or Mediterranean, wet area, where wine is the main beverage, usually drunk at meals. However, the dispersion in alcohol consumption found among the study countries in 1961 declined considerably by 1997. In this respect, European countries are getting more similar, so that we may consider this phenomenon a "convergence" of alcohol drinking in Europe. More generally, changes from a more traditional drinking pattern to a novel one from another country may be due to several factors, one of which is the increasing relevance of women in the drinking context. On the treatment side, such a relevance is nowadays visible through the better availability of both health services and nonstatutory organizations to take care of women affected with alcohol-related problems.


Atypical Unilateral Sacroiliitis Secondary to Mechanical Stress Injury.
We report for the first time a case of atypical unilateral sacroiliitis secondary to mechanical stress injury. Unilateral sacroiliitis can be caused by a variety of etiologies. The first diagnosis to rule out is infection since it requires urgent treatment to avoid its serious consequences. Spondyloarthritis can be manifested by unilateral sacroiliitis in its early stage. Sacral fractures should always be looked for on the imaging modalities performed. In our case, no signs of infection or systemic disease were found. No fracture was seen on the imaging examinations and we had negative cultures on the computed tomography-guided biopsy realized. A history of mechanical stress was the only clue found suggesting the diagnosis of a probable stress related sacroiliitis. A thorough review of the literature will be provided stating the different causes of sacroiliitis described till now, with discussion of this new reported entity.


Volumetric MRI study of orbito-frontal cortex and thalamus in obsessive-compulsive personality disorder.
Obsessive compulsive personality disorder (OCPD) is currently thought to bear a close relationship with obsessive-compulsive disorder (OCD), and other compulsive disorders such as eating disorder and autistic spectrum disorder, as well as with the personality disorders, focusing on some important dimensions like phenomenology, heritability, environmental risk factors, comorbidity, course of illness, neurocognitive endophenotypes, and treatment response. In the present study, when we have taken into consideration the knowledge aforementioned, we aimed to examine OFC and thalamus volumes in patients with OCPD. We comparatively measured orbito-frontal cortex (OFC) and thalamus volumes of patients with OCPD and healthy control subjects. Patients with OCPD had considerably smaller left and right OFC volumes compared to those of healthy control subjects. We also found that thalamus volumes of patients were statistically significantly greater than those of healthy comparisons for both sides of region of interest. We consider that volumetric alterations determined in the present study may be involved in the pathophysiology of the OCPD, considering that OCPD might be related to OCD spectrum disorders neuroanatomically.


Quality indicators for pharmaceutical care: a comprehensive set with national scores for Dutch community pharmacies.
Background The quality of pharmaceutical care in community pharmacies in the Netherlands has been assessed annually since 2008. The initial set has been further developed with pharmacists and patient organizations, the healthcare inspectorate, the government and health insurance companies. The set over 2012 was the first set of quality indicators for community pharmacies which was validated and supported by all major stakeholders. The aims of this study were to describe the validated set of quality indicators for community pharmacies and to report their scores over 2012. In subanalyses the score development over 5 years was described for those indicators, that have been surveyed before and remained unchanged. Methods Community pharmacists in the Netherlands were invited in 2013 to provide information for the set of 2012. Quality indicators were mapped by categories relevant for pharmaceutical care and defined for structures, processes and dispensing outcomes. Scores for categorically-measured quality indicators were presented as the percentage of pharmacies reporting the presence of a quality aspect. For numerical quality indicators, the mean of all reported scores was expressed. In subanalyses for those indicators that had been questioned previously, scores were collected from earlier measurements for pharmacies providing their scores in 2012. Multilevel analysis was used to assess the consistency of scores within one pharmacy over time by the intra-class correlation coefficient (ICC). Results For the set in 2012, 1739 Dutch community pharmacies (88 % of the total) provided information for 66 quality indicators in 10 categories. Indicator scores on the presence of quality structures showed relatively high quality levels. Scores for processes and dispensing outcomes were lower. Subanalyses showed that overall indicators scores improved within pharmacies, but this development differed between pharmacies. Conclusions A set of validated quality indicators provided insight into the quality of pharmaceutical care in the Netherlands. The quality of pharmaceutical care improved over time. As of 2012 quality structures were present in at least 80 % of the community pharmacies. Variation in scores on care processes and outcomes between individual pharmacies and over time can initiate future research to better understand and facilitate quality improvement in community pharmacies.


Partial molar appearance of the placenta in trisomy 13.
Although molecular studies have shown that more than 90% of partial moles are secondary to diandric triploidy, there are some rare cases with tetraploidy or unspecified aneuploidies. We diagnosed 3 cases of partial mole presentation during the 2nd trimester of pregnancy with multiple fetal abnormalities. In all 3 cases, cytogenetic studies showed trisomy 13. We present the cases and discuss the clinical and pathological aspects of the conditions presented as partial moles.


Targeted disruption of the murine zyxin gene.
Zyxin is an evolutionarily conserved protein that is concentrated at sites of cell adhesion, where it associates with members of the Enabled (Ena)/vasodilator-stimulated phosphoprotein (VASP) family of cytoskeletal regulators and is postulated to play a role in cytoskeletal dynamics and signaling. Zyxin transcripts are detected throughout murine embryonic development, and the protein is widely expressed in adults. Here we used a reverse genetic approach to examine the consequences of loss of zyxin function in the mouse. Mice that lack zyxin function are viable and fertile and display no obvious histological abnormalities in any of the organs examined. Because zyxin contributes to the localization of Ena/VASP family members at certain subcellular locations, we carefully examined the zyxin(-/-) mice for evidence of defects that have been observed when Ena/VASP proteins are compromised in the mouse. Specifically, we evaluated blood platelet function, nervous system development, and skin architecture but did not detect any defects in these systems. Zyxin is the founding member of a family of proteins that also includes the lipoma preferred partner (LPP) and thyroid receptor-interacting protein 6 (TRIP6). These zyxin family members display patterns of expression that significantly overlap that of zyxin. Western blot analysis indicates that there is no detectable upregulation of either LPP or TRIP6 expression in tissues derived from zyxin-null mice. Because zyxin family members may have overlapping functions, a comprehensive understanding of the role of these proteins in the mouse will require the generation of compound mutations in which multiple zyxin family members are simultaneously compromised.


[Effect and mechanism of total flavonoids of orange peel on rat adjuvant arthritis].
To investigate the effect of the total flavonoids of orange peel (TFO) against adjuvant arthritis (AA) and the underlying mechanism. AA model was induced in male Wistar (correction of SD) rats by immunization with Freund's complete adjuvant Pad thickness was assayed by caliper. Pathological impairment of ankle joint was analysised by hematoxylin and eosin (H&E) staining. Levels of tumor necrosis factor (TNF)-alpha, Interleukin (IL)-1beta and prostaglandin (PG) E2 in serum was detected by radioimmunoassay method. Cyclooxygenase (COX)-2 expression in synovium tissues was measured by Western blot assay. The 75 mg x kg(-1) and 150 mg x kg(-1) TFO treatment obviously decreased the pad thickness and improve the pathological impairment of ankle joint of AA rats. In addition, abnormal elevation of TNF-alpha, IL-1beta and PGE2 in serum and COX-2 expression in synovium tissues of AA rats were markedly repressed by TFO treatment. TFO can inhibit the development of AA in rats, and the mechanism were likely due to depressing inflammatory mediators production.


Contrast-enhanced ultrasound (CEUS) and perfusion imaging using VueBox®.
The external perfusion software (VueBox™) for contrast-enhanced ultrasound (CEUS), enables the quantitative analysis of micro-vascularization within non-cystic lesions in terms of characterization and detection. This review summarizes our work about parathyroid gland, thyroid gland, liver, prostate and other tissues as well as original studies in the use of parametric perfusion imaging. Useful perfusion parameters are introduced.


Online University Counselling Services and Psychological Problems among Italian Students in Lockdown Due to Covid-19.
Introduction: With the advent of Covid-19, Italian university students were overwhelmed by fear of the pandemic and the social restrictions of the lockdown phase, with all didactic activity provided online. These stress factors caused people to experience psychological problems and/or the aggravation of pre-existing mental symptomatology. Psychological support is, therefore, important for the university-student population. Aims: (1) Analyzing the psychological difficulties and mental problems relative to lockdown from Covid-19 of students who asked for help from the Center of Psychological Counseling of the University of Salerno. (2) Describing the online services of the university's psychological counseling treatment. Participants: 266 university students, but only 49 were undergoing psychological treatment during the Covid-19 lockdown at the center. Methods: (1) Semistructured interview; (2) Questionnaire consisting of sociodemographic information and ad hoc questions; and (3) Scl-90-r test. Results and Conclusions: Aim 1: The main results highlight high levels of anxiety and stress, concentration disorders, and psychosomatization. In several cases, there was a reactivation of previous traumas and sleep was found qualitatively compromised. Aim 2: Counseling services included telephone listening activities, online psychological interviews, psychoeducational groups for interventions of anxiety management, and workshops on study methods conducted in small groups. The online counseling intervention, in times of emergency, increased the resilience and identified any psychological problems in order to implement timely management.


Seroepidemiology of Toxoplasma gondii infection in women from the North of Portugal in their childbearing years.
Seroprevalence of Toxoplasma gondii infection and associated risk factors were investigated in 401 women of childbearing age from the North of Portugal. Of the 98 (24·4%) seropositive women, 92 (93·9%) only had immunoglobulin (Ig)G, two (2·0%) only had IgM, and four (4·1%) others had both IgG and IgM. Risk factors for T. gondii infection in women were: engaging in soil-related activities without gloves [odds ratio (OR) 8·4], consumption of unwashed raw vegetables or fruit (OR 7·6), and consumption of smoked or cured (non-cooked) processed pork products (OR 2·5). Most women of childbearing age from the North Portugal are susceptible to primary infection with T. gondii and, therefore, the risk of congenital toxoplasmosis remains high.


Temporal change in the reproducibility of a self-administered food frequency questionnaire.
The authors studied temporal change in the reproducibility of a self-administered food frequency questionnaire. During 1988-1994, 492 residents of a rural Japanese town completed five questionnaires including 27 food items, with intervals ranging from 2 weeks through 5.5 years. The reproducibility decreased steadily over time for pairs of the questionnaires administered in the same season (median Spearman's r at 2 weeks and 5 years = 0.62 and 0.28, respectively). The reduction was less marked for those surveyed in different seasons (median r at 5 months and 5.5 years = 0.35 and 0.28, respectively). The short-term, different season correlation at 5 months was lower than the short-term, same season correlation at 1 year. For individual food items, a lower initial reproducibility, infrequent consumption, and a larger difference in seasonal intake were associated with a greater reduction in reproducibility over time. The results indicate that reproducibility studies should deliberately choose the intervals and the seasons for surveys.


[The treatment of thymoma with myasthenia gravis: report of 20 cases].
Sixty-eight patients with myasthenia gravis underwent thymic surgery in our department. Among of 68 cases, twenty patients with thymoma were followed and their prognosis were investigated. Sixteen cases received a extended thymectomy with thymomectomy, six cases received local irradiation, and 16 cases received a chemotherapy. Among of 16 cases, 13 cases received corticosteroid only, and 3 cases received CHOP (CPA+ADM+VCR+PSL). Survival rates for thymoma of 20 cases were 94.7%, 88.9%, 78.6%, and 54.5% at 1, 3, 5 and 7 years, respectively. Survival rates for thymoma at 5 years were 83.3%, 50.0%, 100%, and 100% in stage I (complete encapsulation of 8), II (invasion into pericapsular fatty tissue of 7), III (invasion into surrounding organ of 3), and IV a (pleural dissemination of 2), respectively. Survival rate for extended thymectomy with thymomectomy of 16 cases was 81.8% at 5 years. Among of 18 total resection cases of thymoma, a recurrence occurred (5.6%). Causes of 6 death after surgery were crises of myasthenia gravis (3), other diseases (2), and recurrence of thymoma (1).


Association of p53 with Bid induces cell death in response to etoposide treatment in hepatocellular carcinoma.
Appropriate subcellular localization of proteins is crucial for regulating their functions. Both p53 and the BH3-only Bid play roles in the development and the treatment of hepatocellular carcinoma (HCC). They both participate in the cross talk of cell cycle arrest and apoptosis in response to DNA damage. However, some important issues related to their pathways are not yet resolved. Bid genomic loci contain p53-binding DNA response elements and Bid can mediate p53-dependent transactivation. Here, we showed that etoposide-induced DNA damage could significantly induce p53 and Bid nuclear export. When cells were stimulated by etoposide, p53 could, through the association with Bid, cause translocation of Bid from the nucleus to the cytoplasm and on to its ultimate location in the mitochondria. p53 was physically associated with Bid, and both p53 and Bid cooperatively promoted cell death induced by etoposide. Knockdown of Bid expression notably attenuated cell death induced by etoposide and also released p53 from the mitochondria. These findings reveal a novel mechanism by which p53 is associated with Bid in the nucleus to facilitate exportation of Bid to the mitochondria and induce apoptosis in response to etoposide-induced DNA damage in HCC.


[Cytopathological effect of Bacillus thuringiensis israelensis endotoxins on the intestines of Aedes aegypti mosquito larvae].
The dynamics of pathological changes in the intestine of Aedes aegypti larvae under the influence of toxins Cry11A and Cry4B produced by Bacillus thuringiensis israelensis was studied by means of electron microscope. Most significant ultrastructure changes in the intestine of the second instar larvae were observed in the midgut. The cytoplasm of cells disintegrated, and elongated lacunae appeared. The number of microvilli decreased, or they disappeared in the result of destruction. The peritrophic membrane displaced to the lumen of midgut. Any changes in epithelial cells and cuticle in time of foregut and hindgut were not observed in a comparison to control. The toxin Cry4B caused the most effective destruction of the midgut epithelium.


Professional and normative standards in midwifery in six Southeast European countries: A policy case study.
The aim of this study is to consider possibilities of defining common professional and normative standards of the midwifery profession in six neighbouring Southeast European countries, and to create preconditions for the internationalisation of midwifery studies and form of continuous midwifery education, based on a common core curriculum. This article consists of three parts. First, the basic guidelines on the professional standards of the midwifery profession are introduced and analysed. Special emphasis is placed on quantitative and qualitative analyses of the teaching programmes according to which midwives are educated in Croatia and neighbouring countries. The emphasis is on: a) acquisition of knowledge aimed at professional obligations and responsibilities, b) application of knowledge, skills and competences to midwifery practice, and c) improvement of the quality of midwifery care in the best interest of patients/clients, newborns, and members of their families. Second, the normative standards of midwifery profession are presented. The framework of the normative standards consists of legal and ethical norms that oblige midwives to provide quality midwifery care and to act in a professionally responsible manner. The laws and ethical codes of the neighbouring countries are analysed, with which application midwives can assess their everyday practices and activities in relation to how much these activities are ethical and allowed by legal norms. Third, the activities of the professional associations of midwives are presented; their organizational, contextual and methodological perspectives, particularly the scope of their participation in the development of the standards of midwifery profession are given; and whether, and in what measure, the external evaluation of the accomplished learning outcomes is conducted, based on the level of midwifery education. Recommendations are outlined in the conclusions.


Recent Advances in the Chemistry of Conjugated Nitrosoalkenes and Azoalkenes.
This review aims to present the most recent contributions in the chemistry of nitrosoalkenes and azoalkenes, highlighting the chemical behavior that makes them important and versatile building blocks in organic synthesis. These are heterodienes used in the assembly of a variety of heterocyclic systems, spanning from five- to seven-membered heterocycles, as well as for the functionalization of heterocycles.


Effect of denervation on burn wound healing.
The skin is a natural barrier between the interior milieu of the organism and its environment. This barrier has multiple physiological functions and may be affected by an array of pathologies including wounds and burns. The present study aims to determine the effect of the nervous system on wound healing. Specifically, this study tested the effect of denervation by chemical ablation on the burn wound healing process using guanethidine for denervation of the sympathetic postganglionic neurons and resiniferatoxin for denervation of the sensory capsaicin-sensitive fibres. Animals were divided into 8 different groups: (1) control group, (2) sensory denervated and burned, (3) sensory denervated non-burned, (4) sympathetic denervated and burned, (5) sympathetic denervated non-burned, (6) vehicle sensory burned, (7) vehicle sympathetic burned, (8) non-denervated burned. We measured different morphologic and biochemical parameters such as wound surface area, histological alterations and mast cells. In addition, NGF, IL-1β, IL-6 and IL-8 levels were determined using the ELISA technique. The gross observations, the histological data including mast cell modulation, as well as the molecular data, speak in favour of a significant delay in burn wound healing caused by sensory denervation. On the other hand, results support the positive role of sympathetic denervation in speeding up the healing process. The dual effect of the nervous system on burn wound healing is being documented in an animal model for the first time.


SOD1 Is Essential for the Viability of DT40 Cells and Nuclear SOD1 Functions as a Guardian of Genomic DNA.
Reactive oxygen species (ROSs) are produced during normal cellular metabolism, particularly by respiration in mitochondria, and these ROSs are considered to cause oxidative damage to macromolecules, including DNA. In our previous paper, we found no indication that depletion of mitochondrial superoxide dismutase, SOD2, resulted in an increase in DNA damage. In this paper, we examined SOD1, which is distributed in the cytoplasm, nucleus, and mitochondrial intermembrane space. We generated conditional SOD1 knockout cells from chicken DT40 cells and analyzed their phenotypes. The results revealed that SOD1 was essential for viability and that depletion of SOD1, especially nuclear SOD1, increased sister chromatid exchange (SCE) frequency, suggesting that superoxide is generated in or near the nucleus and that nuclear SOD1 functions as a guardian of the genome. Furthermore, we found that ascorbic acid could offset the defects caused by SOD1 depletion, including cell lethality and increases in SCE frequency and apurinic/apyrimidinic sites.


Adherence to rivaroxaban for the treatment of venous thromboembolism-Results from the FIRST registry.
Medication nonadherence can result in poor clinical outcomes and significant costs to health care providers. When treating venous thromboembolism (VTE), subtherapeutic anticoagulation may contribute to complications such as recurrent VTE or postthrombotic syndrome. To describe the extent, reasons for, and predictors of nonadherence to rivaroxaban for the treatment of VTE in clinical practice in the United Kingdom reported by participants of the FIRST registry. The FIRST registry was an observational, multicenter registry reporting on the use of rivaroxaban in routine clinical practice. FIRST registry participants completed an adherence screening questionnaire during their treatment and follow-up. In total, 1028 participants completed 1660 questionnaires over 2 years. One hundred thirteen of 1028 (11%) reported nonadherence at 28 days (interquartile range, 21-45). Reasons given for nonadherence at 1 month were forgetfulness (8.6% vs 74.7%; P < .001), carelessness (2.7% vs 27.3%; P < .001) or a change in routine (7.4% vs 25.5%; P < .001) reported by adherent and nonadherent participants, respectively. Older age (10-year increments) was the strongest predictor of good adherence (adjusted odds ratio, 1.21; 95% confidence interval, 1.06-1.39; 1 = adherent). Overall adherence to rivaroxaban was high, and most nonadherence was unintentional. Identification of those at risk of nonadherence may reduce the risk of VTE recurrence and long-term complications.


Mucosal immune responses associated with polynucleotide vaccination.
A variety of gene delivery technologies can be used to express antigens within somatic tissues, resulting in systemic humoral and cellular immune responses. This observation has led to the development of polynucleotide vaccine preparations for stimulation of systemic immunity. Mucosal immune responses are functionally distinct from systemic immune responses, and are stimulated by antigen presentation within specialised mucosal-associated inductor tissues. We hypothesize that mucosal genetic vaccine will require gene transfer methods which target mucosal-associated inductor tissues such as the oropharyngeal Waldeyer's ring or intestinal Peyer's patches. We have tested this hypothesis by expressing a test antigen using a replication-defective recombinant Semliki Forest Virus (SFV) preparation. Mice treated with recombinant SFV via an intravascular or intratracheal route generated systemic immune responses against the test antigen. In contrast, intranasal inoculation resulted in the production of IgA within pulmonary fluids, one hallmark of a mucosal immune response. These results indicate that transfection of mucosal effector tissues may not be sufficient for the generation of a universal mucosal immune response. Furthermore, the results predict that techniques which target transfection or transduction to mucosal inductor tissues will enable the development of a new class of polynucleotide vaccines which exploit current concepts in mucosal immunology.


Registered nurses integrate traditional Chinese medicine into the triage process.
People in the United States often consult registered nurses (nurses) for advice when they want to explore alternatives to Western medicine, such as traditional Chinese medicine (TCM). Nurses find themselves confronting dilemmas when they are caught between these radically different worlds of medical cultures and thinking. Twenty Minnesota nurses were interviewed to learn how they integrate TCM into their triage process. Symbolic interactionism was the research framework used, and mixed coding methods facilitated data analysis. Several sociological theories explain the findings. The major finding is that nurses use a four-step triage process that begins from the Western medical perspective and includes consideration of TCM use. Nurses' recommendations are influenced by their situational roles and relationships, and by the cues they read from the person who is asking their advice. The results point to nurses being natural disseminators of TCM information and education in their resource role for others making health care decisions.


Medicinal Effect, In Silico Bioactivity Prediction, and Pharmaceutical Formulation of Ageratum conyzoides L.: A Review.
Goat weed (Ageratum conyzoides L.), or bandotan in Indonesia, is an herbaceous plant that broadly grows up in both subtropical as well as tropical areas. This herb contains many phytoconstituents which have many benefits in different aspects. The essential oil contains phytochemicals such as phenol, phenolic ester, and coumarin, whereas many compounds can been identified in the whole part such as terpenoid, steroid, chromene, pyrrolizidine alkaloid, and flavonoid. Empirically, this herb has been used as an antihemorrhagic, antiseptic, antileprosy, and wound-healing agent. This article reviews the potency of the herb in medication according to the chemical substances being deposited, which are collected from numerous studies, followed by its in silico bioactivity prediction as well as its pharmaceutical dosage form formulation.


[Evaluation of cyclin E expression in endometrial hyperplasia and cancer in postmenopausal women].
The aim of present study was to determine expression of cyclin E in endometrial hyperplasia without atypia, atypical endometrial hyperplasia and endometrial cancers in comparison with expression of cyclin E in atrophic endometrium of postmenopausal women. We have also estimated relationship between cyclin E expression and prognostic factors for endometrial cancer such as: histological type, cancer stage and histological grade. 154 women were enrolled into study Women were divided into 4 groups. The first group consist of 38 women with endometrial hyperplasia without atypia, the second group consist of 18 women with atypical endometrial hyperplasia. The third group comprise 62 women with endometrial cancer and the forth 36 women with atrophic endometrium. Cyclin E expression was estimated in formalin-fixed, paraffin-embedded tissues obtained from enrolled women with the use of immunohistochemical techniques. We estimated labelling index (LI) - the number of cells that stained for cyclin E in relation to all cells at the certain field of view. Medians of labelling indices of cyclin E in atrophic endometrium, endometrial hyperplasia with atypia, atypical endometrial hyperplasia end endometrial cancer were 13.7%, 34.7%, 62%, 72.2% respectively These differences were statistically significant. In our study we haven't found relationship between cyclin E expression and histological type of tumour (p = 0.186), cancer stage (p = 0.186) and histological grade (p = 0.539) CONCLUSIONS: In the carcinogenesis of endometrial tumours in postmenopausal women there is a progressive disorder in mechanisms regulating cell cycle. It seems impossible to use cyclin E as prognostic factor for endometrial cancer.


Genochondromatosis type I: A clinicoradiological study of four family members.
Genochondromatosis is an extremely rare autosomal dominant disorder, which manifests during childhood and tends to regress in adult life. The bony lesions are symmetrically distributed with characteristic localization at the metaphysis of proximal humerus and distal femur. Two types have been described based on the involvement of clavicle. Usually asymptomatic, sometimes patients may present with pathological fractures. In this communication, we describe four members of a family with Genochondromatosis type I, with some additional clinical and radiological findings not reported previously.


Parameters of sagittal balance in view of studies on patients suffering from rheumatoid arthritis with cervical spine instability.
Rheumatoid arthritis (RA) is a systemic inflammation, with cervical spine instability being one of the consequences. The instability may lead to myelopathy and even death of the patient due to compression on the spinal vessels and nerve structures of the cervical section. Sagittal balance is one of the issues that has recently contributed to deepening the understanding of spine pathology. As regards RA, sagittal balance is of particular importance due to the nature of the disease, which naturally leads to damage in the physiological joints stabilisers. Joints damaged in the course of the disease become particularly vulnerable to biomechanical balance disorders. Managing patients suffering from RA with cervical spine instability is a serious issue. The literature pays little attention to the sagittal balance in patients suffering from RA. The goal of this paper is to draw attention to the selected parameters of sagittal balance and their mutual relations, as regards cervical spine.


Changing state structures: outside in.
In explaining the development of institutional structures within states, social science analysis has focused on autochthonous factors and paid less attention to the way in which external factors, especially purposive agent-directed as opposed to more general environmental factors, can influence domestic authority structures. For international relations scholarship, this lacunae is particularly troubling or perhaps, just weird. If the international system is anarchical, then political leaders can pursue any policy option. In some cases, the most attractive option would be conventional state to state interactions, diplomacy, or war. In other instances, however, changing the domestic authority structures of other states might be more appealing. In some cases, domestic authority structures have been influenced through bargaining, and in others through power. Power may reflect either explicit agent-oriented decisions or social processes that reflect the practices, values, and norms of more powerful entities.


Tegumental changes of Alaria marcianae (Trematoda) during migration in the domestic cat.
Mesocercariae of Alaria marcianae were removed from snake paratenic hosts and fed to domestic cats. The cats were necropsied at specified intervals, the parasites recovered, and studied by SEM. During the prepulmonary phase of migration in cats, mesocercariae recovered from the stomach wall, abdominal cavity, diaphragm, liver, and heart underwent no tegumental modification compared to those fixed immediately after removal from the paratenic host. The mesocercaria resembled the body of an enlarged cercaria. The oral sucker was encircled by 14 or 15 rows of simple, posteriorly directed spines. Similar spines were also located along the margins of the venter and equatorially at the level of the acetabulum. This spinal pattern left two regions, one anterior and one posterior to the acetabulum, devoid of spines. Uniciliate papillae were found in a distinct pattern associated with the spined areas. In the pulmonary phase, the mesocercariae transformed into diplostomula. Earlike lappets on either side of the oral sucker developed with subsequent differentiation of microvilliform processes on their ventral sides. Body spines divided to give rise to three-pronged serrations. A depression on the venter between the acetabulum and posterior end of the body gave rise to the tribocytic organ. Stout, densely-clustered spines arose de novo on this organ. A rudimentary cylindrical hindbody gave the diplostomulum a distinct scoop-shaped appearance. Worms coughed up from the lungs and swallowed were later found in the duodenum. This postpulmonary phase of migration was a quick event and young worms in the duodenum were indistinguishable from those in the lungs. Within 4 days, the diplostomula in the duodenum matured to adulthood.(ABSTRACT TRUNCATED AT 250 WORDS)


[Investigator-Initiated Clinical Trial of 211At-NaAt against Refractory Thyroid Cancer].
Radioactive iodine has long been used clinically for patients with differentiated thyroid cancer. Radioiodine(131I) is used for the ablation of thyroid remnants or treatment of metastatic thyroid cancer. However, some patients with multiple metastases are refractory to repetitive 131I treatment, despite the targeted regions showing sufficient iodine uptake. In such patients, β- particle therapy using 131I is inadequate and another strategy is needed using more effective radionuclide targeting the sodium/iodide symporter(NIS). Astatine(211At)is receiving increasing attention as an α-emitter for targeted radionuclide therapy. 211At is a halogen element with similar chemical properties to iodine. α particles emitted from 211At has higher linear energy transfer as compared to β particles from 131I and exert a better therapeutic effect by inducing DNA double strand breaks and free radical formation. We showed that increase of the radiochemical purity of astatide of 211At solution by addition of ascorbic acid was associated with significantly enhanced uptake of 211At by both normal thyroid tissue and differentiated thyroid cancer cells. The treatment effect of 211At solution in the K1-NIS xenograft model was dose-dependent and was associated with prolonged survival, suggesting the potential applicability of targeted α therapy for the treatment of advanced differentiated thyroid cancer. Thus, targeted α therapy using 211At is highly promising for the treatment of advanced differentiated thyroid cancer. We have already started the clinical trial of 211At-NaAt in Osaka University Hospital since November 2021 after getting the approval by IRB and PMDA investigation. We would like to get the proof of concept that astatine can be used safely and effectively in patients, aiming at the drug approval as a targeted α therapeutic from Japan.


Two Faces Under a Hood: Unravelling the Energy Harnessing and Storage Properties of 1T-MoS2 Quantum Sheets for Next-Generation Stand-Alone Energy Systems.
The two-dimensional 1T-MoS2 quantum sheets (QSs) continuously seek attention due to their extraordinary energy harnessing and storage properties towards designing an all-in-one self-charging power system (SCPS). Herein, we have utilized the superior dual-functional nature of exfoliated MoS2 QSs for SCPS via fabricating all-solid-state microsupercapacitors (MSC) as an energy storage device and triboelectric nanogenerator (TENG) with MoS2 QSs based charge-trapping interfacial layer as the energy harvester. The electrochemical analysis of MoS2 QSs MSC indicated their superior capacitive properties with a high areal capacitance (4.3 mF cm-2), energy density (0.38 μWh cm-2), and long cycle life. Furthermore, we emphasize the fabrication of MSC with shape diversity and performance uniformity via construction in several designable shapes, which exhibit superior electrochemical performances. The MoS2 QSs based charge-trapping layer enhances the output performance of TENG dramatically with a peak power density as large as 10 μW cm-2, which is 13-fold greater than that of the pristine TENG. As proof of the concept, we fabricated an all MoS2 based SCPS which showed their ability to self-charge up to a maximum of 1050 mV, outperforming many SCPS reported previously. Overall, this work creates a way to utilize the bifunctional properties of MoS2 QSs for the development of next-generation SCPS.


Analytic description of adaptive network topologies in a steady state.
In many complex systems, states and interaction structure coevolve towards a dynamic equilibrium. For the adaptive contact process, we obtain approximate expressions for the degree distributions that characterize the interaction network in such active steady states. These distributions are shown to agree quantitatively with simulations except when rewiring is much faster than state update and used to predict and to explain general properties of steady-state topologies. The method generalizes easily to other coevolutionary dynamics.


Home blood pressure monitor use in patients with chronic kidney disease.
Home blood pressure monitoring (HBPM) is recommended in patients with chronic kidney disease (CKD) and hypertension (HTN). However, little is known about the use and pattern of HBPM in CKD patients. A cross-sectional study was conducted in an out-patient nephrology clinic. A total of 285 patients participated in the study. Of all patients, 66% reported using HBPM. Self-reported compliance with BP medications (93.9% vs. 85.1%, p 0.03), exercise >3 days/week (45.9 vs. 26.3%, p <0.001) and dietary sodium restriction (85.6% vs. 71.6%, p < 0.001) were more common in HBPM users vs. non-HBPM users. Most patients with HBPM used upper arm cuff (82.3%), reported receiving education on correct use of HBPM (82.5%), had perception that home BP was controlled (75.4%) and believed that HBPM is helpful in managing hypertension (85.4%). Most common reason for not using HBPM was lack of advice by a physician (43.4%). HBPM use is common in patients with CKD and HTN. HBPM users are more likely to follow life-style and dietary modifications for blood pressure control.


Using data mining tools to discover novel clinical laboratory test batteries.
Using statistical analysis and data mining tools, we examined possible associations among clinical laboratory orders placed at the Ohio State University Medical Center between January and October of 2006. Upon applying the Frequent Itemset data mining technique to this data set, the results indicated that, while the most frequently ordered battery of tests was not associated with others, some highly associated orders may be good candidates to comprise new test batteries.


Transforming CO2 into Methanol with N-Heterocyclic Carbene-Stabilized Coinage Metal Hydrides Immobilized in a Metal-Organic Framework UiO-68.
By synergizing the advantages of homogeneous and heterogeneous catalysis, single-site heterogeneous catalysis represents a highly promising opportunity for many catalytic processes. Particularly, the unprecedented designability and versatility of metal-organic frameworks (MOFs) promote them as salient platforms for designing single-site catalytic materials by introducing isolated, well-defined active sites into the frameworks. Herein, we design new MOF-supported single-site catalysts for CO2 hydrogenation to methanol (CH3OH), a reaction of great significance in CO2 valorization. Specifically, N-heterocyclic carbene (NHC), a class of excellent modifiers and anchors, is used to anchor coinage metal hydrides M(I)-H (M = Cu, Ag, and Au) onto the organic linker of UiO-68. The strong metal-ligand interactions between NHC and M(I)-H verify the robustness and feasibility of our design strategy. On the tailor-made catalysts, a three-stage sequential transformation is proposed for CH3OH synthesis with HCOOH and HCHO as the transit intermediates. A density functional theory-based comparative study suggests that UiO-68 decorated with NHC-Cu(I)-H performs best for CO2 hydrogenation to HCOOH. This is further rationalized by three linear relationships for the Gibbs energy barrier of CO2 hydrogenation to HCOO intermediate, the first with the NBO charge of the hydride in NHC-M(I)-H, the second with the electronegativity of M, and the third with the gap between the lowest unoccupied molecular orbital of CO2 and the highest occupied molecular orbital of the catalyst. It is confirmed that the high efficiency of MOF-supported NHC-Cu(I)-H for CO2 transformation to CH3OH is via the proposed three-stage mechanism, and in each stage, the step involving heterolytic dissociation of H2 together with product generation is the most energy-intensive. The rate-limiting step in the entire mechanism is identified to be H2 dissociation accompanying with simultaneous HCHO and H2O formation. Altogether, the tailor-made UiO-68 decorated with NHC-Cu(I)-H features well-defined active sites, enables precise manipulation of reaction paths, and demonstrates excellent reactivity for CO2 hydrogenation to CH3OH. It is also predicted to surpass a recently reported MOF-808 catalyst consisting of neighboring Zn2+-O-Zr4+ sites. The designed MOFs as well as the proposed strategy here establish a new paradigm and can be extended to other hydrogenation reactions.


[Effect of intraperitoneal chemotherapy on experimental peritoneal dissemination of gastric cancer].
In vitro chemosensitivity test using a collagen-gel method was done on 165 primary gastric cancers. All of 5-FU, CBDCA, CDDP and docetaxel showed a high sensitivity. The effects of per oral (po) administration of TS-1, a combination of po TS-1 and intraperitoneal (ip) administration of CDDP, ip 5-FU and ip docetaxel, were evaluated in athymic mice bearing peritoneal dissemination of a gastric cancer cell line (MKN-45-P that shows a high rate of metastasis to the peritoneal cavity of nude mice). Nude mice were inoculated by ip with 10(7) MKN-45-P cells. No survival benefit was obtained after po administration of TS-1 (12 mg/kg) alone or ip CDDP alone. However, a combination of po TS-1 (8 mg/kg x 10 days, from day 3) and ip CDDP (3.5 mg/kg, day 6 and 13) showed a significant survival improvement than that of po TS-1 or ip CDDP treatment alone. ip administration of 30 mg/kg (3 times/week x 3 weeks) or 15 mg/kg (6 times/week x 3 weeks) of 5-FU significantly improved the survival of mice bearing MKN-45-P. 5-FU concentration of ascites after ip administration of 30 mg/kg of 5-FU was 600-fold higher than po administration of 12 mg/kg of TS-1 at peak level. ip injections of docetaxel of 8 mg/kg, and 2 mg/kg improved the survival of 4 and 1 mice, respectively, and they were tumor-free on day 90. Survival of mice treated with ip injection of CBDCA (100 mg/kg, on day 3, or 50 mg/ kg on day 3 and 10) was significantly better than the control group. These results suggest the potential of po TS-1 + ip CDDP, ip 5-FU, ip docetaxel and ip CBDCA administration for the treatment of peritoneal dissemination of gastric cancer.


Long-term restoration of corneal sensitivity in neurotrophic keratopathy after rhNGF treatment.
To report the long-term effects of the new rhNGF treatment on corneal sensitivity in patients with. We present three cases of corneal ulcers due to NK that were treated with rhNGF. In each patient wound healing evolution was documented by clinical pictures and corneal sensitivity measured by Cochet-Bonnet aesthesiometry. Best corrected visual acuity and Type I Schirmer test were also assessed neurotrophic keratopathy.All patients healed within 8 weeks and NK showed no recurrences in the mean follow-up period of 35 weeks. Each subject showed a significant increase of corneal sensitivity and tear secretion, with concomitant improvement in visual acuity. Corneal sensitivity, measured by Cochet-Bonnet aesthesiometer, markedly increased in all eyes. Further studies are warranted to demonstrate a possible mechanism of nerve restoration with rhNGF treatment.


Are there any differences in three-dimensional placental vascular indices obtained using conventional power Doppler and high-definition flow imaging?
The purpose of this study was to determine whether there are differences in values and reproducibility of three-dimensional (3D) vascular indices obtained on placental volumes using power Doppler (PD) or high-definition flow imaging (HDFI) techniques. A prospective study was performed on 121 uncomplicated singleton pregnancies at 11 + 0 to 13 + 6 weeks of gestation. Two placental volumes were acquired from each pregnancy. Vascularization index (VI), flow index (FI) and vascularization flow index (VFI) were then analyzed and compared. In order to assess the reproducibility of the measurements, two additional placental volumes obtained with both PD and HDFI were acquired in 31 pregnancies and the agreement assessed by intraclass correlation coefficients. Inter-observer variability was assessed by analyzing all the volumes by two observers blinded to each other's. A significant relationship was observed between the vascular indices values obtained with the two techniques (VI Pearson's r=0.891 p<0.001; FI r=0.769 p<0.001; VFI r=0.847 p<0.001). The median values of VI, FI and VFI were significantly higher when obtained with HDFI imaging. In serial recordings, the ICCs resulted higher when volumes were acquired with HDFI rather than with PD techniques. Similarly, HDFI demonstrated a higher inter-observer reproducibility. 3D vascular indices calculated using HDFI are higher than those calculated using conventional PD. Although the relationship between the two methods is high, HDFI shows a better reproducibility suggesting its potential clinical application.


[A resected case under thoracoscopic surgery of bilateral pulmonary metastases of renal cell carcinoma ten years after radical nephrectomy].
A 68-year-old male had received a left nephrectomy for renal cell carcinoma of the clear cell type in October, 1987. He had been given Interferon alpha (IFN alpha) for one year since then. He was referred to our hospital for bilateral abnormal shadows on the chest roentgenogram in December, 1997. He underwent a video-assisted thoracoscopic biopsy of bilateral lung in January, 1998, 11 years after his nephrectomy. The resected specimens contained a coin lesions measuring approximately 2 cm in diameter, and the lesions were microscopically diagnosed as a renal cell carcinoma of the clear cell type metastatic to the lung. The patient is doing well with no signs of re-recurrence five months after the resection of the metastatic lesion.


Effect of isoflurane on proliferation and Na+,K+-ATPase activity of alveolar type II cells injured by hydrogen peroxide.
The influence of isoflurane (Iso) on proliferation and Na+,K+-ATPase activity of alveolar type II cells (ATII cells) injured by hydrogen peroxide (H2O2) was investigated. ATII cells isolated and purified from adult Sprague-Dawley rats were randomly divided into six groups: control group, 0.28 mM Iso group, 2.8 mM Iso group, 75 microM H2O2 group, 75 microM H2O2 + 0.28 mM Iso group, and 75 microM H2O2 + 2.8 mM Iso group. After primary culture for 32 hours, the proliferation of ATII cells was detected by MTT assay, and after culture for 24 hours the activity of Na+,K+-ATPase and lactate dehydrogenase (LDH) in the cells, and malonaldehyde (MDA) content of the culture medium, were measured by colorimetry. It was found that 0.28 mM and 2.8 mM Iso had no effect on the proliferation of ATII cells (p > 0.05), but 75 microM H2O2 inhibited their proliferation (p < 0.05) compared with untreated controls; 0.28 mM and 2.8 mM Iso significantly decreased Na+,K+-ATPase activity of ATII cells compared with untreated control cells (p < 0.05), and 75 microM H2O2 markedly decreased Na+,K+-ATPase activity of ATII cells (p < 0.01) with untreated control cells. 0.28 mM and 2.8 mM Iso aggravated the decrease of Na+,K+-ATPase activity induced by H2O2. Iso had no effect on LDH activity and MDA content of the culture medium of normal ATII cells, but significantly increased LDH activity and MDA content of the culture medium of ATII cells injured by H2O2. These findings suggest that Iso itself may decrease the activity of Na+,K+-ATPase of ATII cells in vitro and further damage the cells' function under peroxidation conditions, but has no effect on the proliferation of ATII cells.


Incidence, clinical course and risk factor for recurrent PCR positivity in discharged COVID-19 patients in Guangzhou, China: A prospective cohort study.
The phenomenon of COVID-19 patients tested positive for SARS-CoV-2 after discharge (redetectable as positive, RP) emerged globally. The data of incidence rate and risk factors for RP event and the clinical features of RP patients may provide recommendations for virus containment and cases management for COVID-19. We prospectively collected and analyzed the epidemiological, clinical and virological data from 285 adult patients with COVID-19 and acquired their definite clinical outcome (getting PCR positive or not during post-discharge surveillance). By March 10, 27 (9.5%) discharged patients had tested positive for SARS-CoV-2 in their nasopharyngeal swab after a median duration of 7·0 days (IQR 5·0-8·0). Compared to first admission, RP patients generally had milder clinical symptoms, lower viral load, shorter length of stay and improved pulmonary conditions at readmission (p<0.05). Elder RP patients (≥ 60 years old) were more likely to be symptomatic compared to younger patients (7/8, 87.5% vs. 3/19, 18.8%, p = 0.001) at readmission. Age, sex, epidemiological history, clinical symptoms and underlying diseases were similar between RP and non-RP patients (p>0.05). A prolonged duration of viral shedding (>10 days) during the first hospitalization [adjusted odds ratio [aOR]: 5.82, 95% confidence interval [CI]: 2.50-13.57 for N gene; aOR: 9.64, 95% CI: 3.91-23.73 for ORF gene] and higher Ct value (ORF) in the third week of the first hospitalization (aOR: 0.69; 95% CI: 0.50-0.95) were associated with RP events. In conclusion, RP events occurred in nearly 10% of COVID-19 patients shortly after the negative tests, were not associated with worsening symptoms and unlikely reflect reinfection. Patients' lack of efficiency in virus clearance was a risk factor for RP result. It is noteworthy that elder RP patients (≥ 60 years old) were more susceptible to clinical symptoms at readmission.


Oteseconazole for the Treatment of Recurrent Vulvovaginal Candidiasis: A Drug Review.
The objective of the study is to describe and analyze the pharmacodynamics and pharmacokinetics of oteseconazole as well as the clinical evidence supporting the efficacy of oteseconazole in treating recurrent vulvovaginal candidiasis (RVVC). A literature search was conducted using MEDLINE and EMBASE databases (2015-June 2023). Search terms included "oteseconazole" OR "VT-1161" or "VIVJOA" AND "RVVC" or "recurrent vulvovaginal candidiasis" or "vulvovaginal candidiasis." Conference abstracts, bibliographies, clinical trials, and drug monographs were included for review. Relevant studies in English and clinical trials conducted in humans were reviewed. Oteseconazole is approved for the treatment of RVVC. In 2 identical phase III studies, oteseconazole was superior to placebo through 48 weeks for preventing recurrence of RVVC (6.7% vs 42.8%, P < 0.001 and 3.9% vs 39.4%, P < 0.001). In the only phase III trial comparing oteseconazole against active drug, oteseconazole was well tolerated and exhibited noninferiority to fluconazole in acute treatment and superiority to placebo for prevention maintenance through 50 weeks (5.1% vs 42.2%, P < 0.001). This review describes the use of oteseconazole for the treatment of RVVC as compared with fluconazole. Oteseconazole is an effective treatment option for common pathogens causing vulvovaginal candidiasis, including Candida and fluconazole-resistant Candida. Oteseconazole is an effective and safe treatment option for the management of RVVC though current research lacks comparison with established maintenance regimens. Additional research is needed to ascertain the placement of oteseconazole in the treatment of RVVC.


Polylysine-mediated translocation of the diphtheria toxin catalytic domain through the anthrax protective antigen pore.
The protective antigen (PA) moiety of anthrax toxin forms oligomeric pores in the endosomal membrane, which translocate the effector proteins of the toxin to the cytosol. Effector proteins bind to oligomeric PA via their respective N-terminal domains and undergo N- to C-terminal translocation through the pore. Earlier we reported that a tract of basic amino acids fused to the N-terminus of an unrelated effector protein (the catalytic domain diphtheria toxin, DTA) potentiated that protein to undergo weak PA-dependent translocation. In this study, we varied the location of the tract (N-terminal or C-terminal) and the length of a poly-Lys tract fused to DTA and examined the effects of these variations on PA-dependent translocation into cells and across planar bilayers in vitro. Entry into cells was most efficient with ∼12 Lys residues (K12) fused to the N-terminus but also occurred, albeit 10-100-fold less efficiently, with a C-terminal tract of the same length. Similarly, K12 tracts at either terminus occluded PA pores in planar bilayers, and occlusion was more efficient with the N-terminal tag. We used biotin-labeled K12 constructs in conjunction with streptavidin to show that a biotinyl-K12 tag at either terminus is transiently exposed to the trans compartment of planar bilayers at 20 mV; this partial translocation in vitro was more efficient with an N-terminal tag than a C-terminal tag. Significantly, our studies with polycationic tracts fused to the N- and C-termini of DTA suggest that PA-mediated translocation can occur not only in the N to C direction but also in the C to N direction.


Targeting MET in cancer: rationale and progress.
Uncontrolled cell survival, growth, angiogenesis and metastasis are essential hallmarks of cancer. Genetic and biochemical data have demonstrated that the growth and motility factor hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, the tyrosine kinase MET, have a causal role in all of these processes, thus providing a strong rationale for targeting these molecules in cancer. Parallel progress in understanding the structure and function of HGF/SF, MET and associated signalling components has led to the successful development of blocking antibodies and a large number of small-molecule MET kinase inhibitors. In this Review, we discuss these advances, as well as results from recent clinical studies that demonstrate that inhibiting MET signalling in several types of solid human tumours has major therapeutic value.


RNA-seq analysis of early enteromyxosis in turbot (Scophthalmus maximus): new insights into parasite invasion and immune evasion strategies.
Enteromyxum scophthalmi, an intestinal myxozoan parasite, is the causative agent of a threatening disease for turbot (Scophthalmus maximus, L.) aquaculture. The colonisation of the digestive tract by this parasite leads to a cachectic syndrome associated with high morbidity and mortality rates. This myxosporidiosis has a long pre-patent period and the first detectable clinical and histopathological changes are subtle. The pathogenic mechanisms acting in the early stages of infection are still far from being fully understood. Further information on the host-parasite interaction is needed to assist in finding efficient preventive and therapeutic measures. Here, a RNA-seq-based transcriptome analysis of head kidney, spleen and pyloric caeca from experimentally-infected and control turbot was performed. Only infected fish with early signs of infection, determined by histopathology and immunohistochemical detection of E. scophthalmi, were selected. The RNA-seq analysis revealed, as expected, less intense transcriptomic changes than those previously found during later stages of the disease. Several genes involved in IFN-related pathways were up-regulated in the three organs, suggesting that the IFN-mediated immune response plays a main role in this phase of the disease. Interestingly, an opposite expression pattern had been found in a previous study on severely infected turbot. In addition, possible strategies for immune system evasion were suggested by the down-regulation of different genes encoding complement components and acute phase proteins. At the site of infection (pyloric caeca), modulation of genes related to different structural proteins was detected and the expression profile indicated the inhibition of cell proliferation and differentiation. These transcriptomic changes provide indications regarding the mechanisms of parasite attachment to and invasion of the host. The current results contribute to a better knowledge of the events that characterise the early stages of turbot enteromyxosis and provide valuable information to identify molecular markers for early detection and control of this important parasitosis.


Clinical implication of immunohistochemical markers.
The role of the pathologist is to establish accurate diagnosis more and more with the help of complementary techniques. At present immunohistochemical expression of some diagnostic and prognostic factors may possibly predict the response to specific therapies. We focus here on the expression of three of these markers: epidermal growth factor receptor which overexpression is correlated with aggressive tumoral behaviour and with the possibility of a targeted therapy, cytokeratins 7 and 20 with their diagnostic implication in carcinomatous differentiation, and we close this review with the identification of markers related to hereditary non-polyposis colorectal cancer involving microsatellite instability.


Comparison of bursting pressure on sleeve gastrectomy staple lines between stapling, buttressing, and oversewing.
Backgrounds. One of the major complications after laparoscopic sleeve gastrectomy (LSG) is represented by leaks along the staple line. Several reinforcement techniques have been proposed, but scarce data about the real strengthening offered are present. Thus, we aimed to evaluate if different reinforcements produced different bursting pressures after LSG, and then to verify if the clinical application of the stronger reinforcement produced a reduction in leakage rate. Methods. We prospectively enrolled all consecutive obese patients that underwent LSG. We tested 3 different types of staple lines, as follows: group 1, no reinforcement; group 2, bioabsorbable buttress reinforcement; group 3, invaginating overrunning barbed suture. A burst pressure test was applied to the gastric specimen by means of high-resolution manometric catheter. After burst pressure tests, a subsequent consecutive series of patients were treated with the most effective reinforcement, and rate of leaks was recorded. Results. We enrolled in total 110 obese patients; 20 patients for each group of staple line reinforcement and then other 50 consecutive patients underwent LSG with the higher burst pressure staple line reinforcement. Median burst pressures were similar in group 1 and group 2; group 3 showed a statistically significant pressure increase (P < .0001) than group 1 and group 2, with a 5.2-fold value. Other consecutive 50 obese patients underwent LSG with overrunning reinforcement. In none of them a leak was detected. Conclusions. Reinforcement of the SG staple line, with overrunning suture, seems to drastically increase bursting pressures in an ex vivo model and it is promising when reproduced in vivo.


Pre-expanded occipito-dorsal flap reconstruction for neck burns: A novel approach.
Reconstruction of the neck following a burn injury poses a significant challenge to reconstructive burn surgeons. Here, we report a case of successful application of pre-expanded occipito-dorsal flaps in the reconstruction of postburn scars and contractures in the neck. The patient was a 10-year-old boy who sustained scars and contractures secondary to a burn injury 4 years ago. "Super-thin" flaps were obtained through pre-expansion in the occipito-dorsal area and then transferred to the recipient site. This approach resulted in an esthetic satisfaction and a significant functional improvement, thereby having significant clinical implications in the reconstruction of soft tissue damage secondary to burn injuries in the neck.


Activity of Mesothelin-Specific Chimeric Antigen Receptor T Cells Against Pancreatic Carcinoma Metastases in a Phase 1 Trial.
Pancreatic ductal adenocarcinoma (PDAC) is resistant to T-cell-mediated immunotherapy. We engineered T cells to transiently express a messenger RNA encoding a chimeric antigen receptor (CAR) specific for mesothelin, a protein that is overexpressed by PDAC cells. We performed a phase I study to evaluate the safety and efficacy of adoptive cell therapy with autologous mesothelin-specific CAR T cells (CARTmeso cells) in 6 patients with chemotherapy-refractory metastatic PDAC. Patients were given intravenous CARTmeso cells 3 times weekly for 3 weeks. None of the patients developed cytokine release syndrome or neurologic symptoms and there were no dose-limiting toxicities. Disease stabilized in 2 patients, with progression-free survival times of 3.8 and 5.4 months. We used 18F-2-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography/computed tomography imaging to monitor the metabolic active volume (MAV) of individual tumor lesions. The total MAV remained stable in 3 patients and decreased by 69.2% in 1 patient with biopsy-proven mesothelin expression; in this patient, all liver lesions had a complete reduction in FDG uptake at 1 month compared with baseline, although there was no effect on the primary PDAC. Transient CAR expression was detected in patients' blood after infusion and led to expansion of new immunoglobulin G proteins. Our results provide evidence for the potential antitumor activity of messenger RNA CARTmeso cells, as well as PDAC resistance to the immune response.


[Development-dependent diagnosis in two children with a rare "combined disorder of school readiness" in accordance with ICD-10, F81.3].
The new category (ICD-10) of mixed disorder of scholastic skills (F81.3) includes the combination of specific reading and spelling disorders with specific disorder of arithmetical skills and the combination of specific spelling disorder with specific disorder of arithmetical skills. We could demonstrate such combinations of specific developmental disorders in two children. In addition to diagnostic approaches with standardized testing procedures we used a model that is based on the steps in the development of specific skills. This method can be helpful in determining what kinds of intervention would be most appropriate. Both children with mixed disorders of scholastic skills also had psychiatric disorders.


Application of competitive Hopfield neural network to brain-computer interface systems.
We propose an unsupervised recognition system for single-trial classification of motor imagery (MI) electroencephalogram (EEG) data in this study. Competitive Hopfield neural network (CHNN) clustering is used for the discrimination of left and right MI EEG data posterior to selecting active segment and extracting fractal features in multi-scale. First, we use continuous wavelet transform (CWT) and Student's two-sample t-statistics to select the active segment in the time-frequency domain. The multiresolution fractal features are then extracted from wavelet data by means of modified fractal dimension. At last, CHNN clustering is adopted to recognize extracted features. Due to the characteristic of non-supervision, it is proper for CHNN to classify non-stationary EEG signals. The results indicate that CHNN achieves 81.9% in average classification accuracy in comparison with self-organizing map (SOM) and several popular supervised classifiers on six subjects from two data sets.


Checklist of the tick (Acari: Argasidae, Ixodidae) species of Pakistan.
In developed and underdeveloped countries, ticks are important vectors transmitting various pathogens that cause diseases of veterinary and public health importance, like babesiosis, theileriosis, Crimean‑Congo haemorrhagic fever (CCHF) and many more. Many species of ticks have been reported in scientific literature from Pakistan, which need to be listed for ready reference. For this purpose, a checklist of tick species recorded in Pakistan is presented here after comprehensive review of the available literature on the subject. Overall, nine genera and 53 species of ticks infesting animals in Pakistan are presented in this checklist.


Carotenoids can act as antioxidants by oxidizing the superoxide radical anion.
The electron transfer (ET) reaction between carotenoids and the superoxide radical anion is found to be not only a viable process but also a very unique one. The nature of the O(2) (-) inverts the direction of the transfer, with respect to ET involving other ROS: the O(2) (-) becomes the electron donor and carotenoids (CAR) the electron acceptor. Therefore the "antioxidant" activity of CAR when reacting with O(2) (-) lies in their capacity to prevent the formation of oxidant ROS. This peculiar charge transfer is energetically feasible in non-polar environments but not in polar media. In addition the relative reactivity of CAR towards O(2) (-) is drastically different from their reactivity to other ROS. Asthaxanthin (ASTA) is predicted to be a better O(2) (-) quencher than LYC and the other CAR. The CAR + O(2) (-) reactions were found to be diffusion controlled. The agreement with available experimental data supports the density functional theory results from the present work.


Examining the evidence for best practice guidelines in supportive supervision of lay health care providers in humanitarian emergencies: A systematic scoping review.
Supervision is widely recognised as an important form of support for lay health service providers. However, guidance in appropriate supervision practices for task-shifting health interventions within the unique context of humanitarian emergencies is lacking. This review set out to identify empirically supported features of supervisory practices for lay health care providers in humanitarian emergencies, towards a stronger evidential basis for best practice in supportive supervision. In January 2021, six databases and five non-governmental organizations' websites were searched for articles examining the effectiveness of supervision for health care interventions delivered by lay providers in humanitarian settings. The inclusion criteria for study selection were qualitative or quantitative primary studies, articles published in peer reviewed journals or technical reports and the availability of the studies in English. The outcomes of interest were client clinical outcomes, health service efficiency and sustainability, and lay health care providers well-being. All articles were independently reviewed by the first and last authors. A total of 3371 articles were initially identified, with a total of 11 articles retained following the systematic screening process (two quantitative, four mixed methods and five qualitative studies). All studies generally reported positive impacts of supportive supervision on client outcomes, service sustainability, staff well-being and staff performance. Only four studies offered emotional support as part of supportive supervision. No studies evaluated the effect of supportive supervision on service efficiency. The narrative synthesis suggests significant challenges with providing supportive supervision, including excessive workloads, difficult supervisory relationships, geographic dispersion of lay providers, safety concerns, poorly trained supervisors, and lack of supervisory guidelines. More efforts are needed to prioritize supportive supervision in task-shifting frameworks and to ensure that supervision is regular, consistent and of high-quality, with well-trained and well-supported supervisors.


Insular Cortical Thickness in Patients With Somatoform Pain Disorder: Are There Associations With Symptom Severity and Childhood Trauma?
Studies show significant alterations in insular cortical thickness in patients with somatoform pain disorder (SPD). Additionally, associations between childhood maltreatment and morphometric alterations in insular cortex have been observed. Since patients with SPD often report about adverse childhood experiences, we were interested in the interrelationship of exposure to childhood maltreatment and insular cortical thickness in patients with SPD. Fifteen adult patients with SPD (ICD-10 F 45.40/41, DSM-Code 307.80) and thirteen healthy adult controls underwent T1-weighted MR brain imaging. In the voxel-based morphometry (VBM) analysis we compared whole brain cortical thickness between patients and controls using a Student's two-sampled t-test (p < .05). Then we performed a secondary analysis to detect differences in cortical thickness levels in the insular cortex between both groups. For further analysis of differences in insular cortical thickness we used gender, age, depressive symptoms [Patient Health Questionnaire (PHQ)-9], and whole brain cortical thickness as nuisance covariates. Subsequently we explored associations between insular cortical thickness, symptom severity (PHQ-15) and past experiences of childhood maltreatment (CTQ) in both groups. Patients showed reduced insular cortical thickness in a subregion of right Brodmann area (BA) 13 (anterior part of the insular cortex), whereas whole brain cortical thickness did not differ between groups. The between-group difference in the identified insular subregion of right BA 13 was not diminished by any of the covariates. This implies that the reduction in cortical thickness in the identified insular subregion might be due to a specific group effect. The effect sizes indicate that the group of patients experienced more childhood maltreatment than the control group. Nonetheless, significant correlations of insular cortical thickness with symptom severity and childhood maltreatment in the total collective could not be demonstrated for the group of patients. Our data suggest that alterations in the identified insular subregion of right BA 13 are associated with somatoform pain, independent of gender, age, or coincident depression levels. To identify significant associations of insular cortical thickness and experiences of childhood maltreatment in patients with SPD investigations within larger samples are highly recommended.


The application of electropalatography (EPG) to the remediation of speech disorders in school-aged children and young adults.
Electropalatography (EPG) is one of a number of computer-based biofeedback techniques being applied increasingly and apparently successfully to the treatment of speech pathologies. This paper briefly examines the function of such biofeedback systems within the remediation process and looks in particular at the features of the EPG system which render it a useful therapeutic tool. Details are summarised of a project initiated to evaluate the use of EPG in the management of a large group of speech-disordered children and young adults. Successful applications of the technique are presented by examining the different types of motor speech skill which subjects acquired during intervention. These are summarised as the establishment of completely new articulatory patterns, the inhibition of abnormal lingual patterns, and the modification of temporal or spatial aspects of one or several existing patterns. Possible reasons for the success of EPG as a therapeutic technique, and issues concerning subject selection, are discussed.


Unravelling phenotypic plasticity -- why should we bother?
The ability of a genotype to change its phenotype was once considered rather a nuisance -- making it difficult to define a genotype. This led to the idea that there was a problem called 'instability'. But quite early it was recognized that stability was under genetic control, and was a character like other attributes of an individual. From this realization came the idea that there were two sides to the character of 'instability', and that the ability to change could be important. This ability was thus given the title of 'plasticity'. Once recognized, it became clear from surveys of different species and populations that plasticity can (i) be a complex character, and (ii) be selected to fit species to the particular demands of different environments. For plants, which cannot meet variations in environment like animals by behavioural responses, phenotypic plasticity can be very important. Plants should therefore be valuable tools for unravelling the mechanisms of plasticity whilst also demonstrating its contribution to fitness experimentally. We ought also to be able to demonstrate that appropriate genetic variability is available through which complex responses can be built up by selection. Genes must exist not only to determine character means, but also to determine character response, which adds interesting complexity to our ideas about evolution.


Redistribution of the nuclear protein IFI16 into the cytoplasm of ultraviolet B-exposed keratinocytes as a mechanism of autoantigen processing.
The skin has long been recognized as a prominent target tissue in systemic lupus erythematosus (SLE) which plays a crucial role in the initiation and perpetuation of the autoimmune reaction cascade as a consequence of ultraviolet (UV)-induced keratinocyte apoptosis. Antibodies against IFI16 (interferon-inducible protein 16) have been detected in the sera of patients with SLE. To verify whether the induction of autoimmunity against IFI16 involves redistribution of this nuclear protein in keratinocytes during UVB-induced cell death. An in vitro epidermal model was developed to investigate the fate of the IFI16 protein in keratinocytes after irradiation with UVB; both keratinocyte monolayers and human skin explants were used. IFI16 expression and localization were also analysed in diseased skin sections of patients with SLE. We demonstrated that IFI16, normally restricted to the nucleus, can be induced to appear in the cytoplasm under conditions of UVB-induced cell injury. This nucleus to cytoplasm translocation was also observed in skin explants exposed to UVB and in the diseased skin sections from patients with SLE. In addition, IFI16 was found in the supernatants of UVB-exposed keratinocytes. The finding that IFI16 is present in the cytoplasm of diseased skin cells from patients with SLE and the demonstration of IFI16 in the supernatants of UVB-exposed keratinocytes, suggest that UVB irradiation or other stimuli may favour an abnormal IFI16 presentation to the afferent limb of the immune system and potentially an autoimmune response against the protein itself.


Angiographic characteristics of femoropopliteal in-stent restenosis: association with long-term outcomes after endovascular intervention.
The purpose of this study was to identify the relationship between angiographic patterns of restenosis and outcomes after endovascular treatment of femoro-popliteal in-stent restenosis (FP-ISR). ISR is a frequent clinical problem after femoro-popliteal stenting. This was a single center study of all endovascular interventions for FP-ISR from 2006 to 2012. Class I ISR was defined as focal lesions ≤50 mm; Class II ISR as lesions > 50 mm; and Class III ISR as stent chronic total occlusion. Recurrent ISR was defined as peak systolic velocity ratio > 2.4 by duplex ultrasound. Among 75 cases of FP-ISR, 28 (37%) were Class I, 22 (29%) were Class II, and 25 (33%) were Class III. The mean lesion length was 26 mm for Class I, 135 mm for Class II, and 178 mm for Class III ISR. Patients with Class III ISR more frequently had ISR extending into both the superficial femoral and popliteal artery (48% vs. 18%, P = 0.005). Balloon angioplasty was used most frequently to treat Class I ISR, while adjunctive atherectomy and/or stenting was used for almost all cases of Class III ISR. During 2-year follow-up, rates of repeat restenosis were 39% for Class I, 67% for Class II, and 72% for Class III ISR (P = 0.04). Rates of stent occlusion were 8% for Class I, 11% for Class II, and 52% for Class III ISR (P = 0.009). Class III ISR was associated with significantly increased risk of recurrent ISR (HR 2.4, 95% CI 1.1-5.6) and recurrent occlusion (HR 5.8, 95% CI 1.8-19.0) compared to other types of ISR. Angiographic patterns of FP-ISR are important determinants of subsequent outcomes. Repeat restenosis and occlusion remain common despite currently available technologies.


Cytochrome P450-dependent toxicity of dapsone in human erythrocytes.
The most prominent adverse effects seen during treatment with dapsone, an antibacterial and antiprotozoal agent, are hemolysis and methemoglobinemia. An in vitro microsomal/cytochrome P(450) (CYP)-linked assay, which allows reactive metabolites generated in situ to react with the co-incubated human erythrocytes, was employed to profile CYP isoforms responsible for hemotoxicity of dapsone. Dapsone caused a robust generation of methemoglobin in human erythrocytes in the presence of human/mouse liver microsomes, which indicates contribution of CYP-mediated metabolism for hemotoxicity. The highest methemoglobin formation with dapsone was observed with CYP2C19, with minor contributions from CYP2B6, CYP2D6 and CYP3A4. Cimetidine and chloramphenicol completely abrogated methemoglobin generation by dapsone, thus confirming a predominant contribution of CYP2C19. The results provide useful insights into CYP-dependent hemotoxicity of dapsone in human erythrocytes.