EDTA Chelation Therapy to Reduce Cardiovascular Events in Persons with Diabetes.
The Trial to Assess Chelation Therapy (TACT) was a randomized double-blind placebo-controlled trial enrolling patients age ≥50 years with prior myocardial infarction. TACT used a 2 × 2 factorial design to study ethylene diamine tetraacetic acid (EDTA) chelation and high-dose vitamin supplementation. Chelation provided a modest but significant reduction in cardiovascular endpoints. The benefit was stronger and significant among participants with diabetes but absent in those without diabetes. Mechanisms by which chelation might reduce cardiovascular risk in persons with diabetes include the effects of EDTA chelation on transition and toxic metals. Transition metals, particularly copper and iron, play important roles in oxidative stress pathways. Toxic metals, in particular cadmium and lead, are toxic for the cardiovascular system. This review discusses the epidemiologic evidence and animal and human studies supporting the role of these metals in the development of diabetes and ischemic heart disease and potential ways by which EDTA chelation could confer cardiovascular benefit.


The impact of digital interventions on medication adherence in paediatric populations with attention deficit hyperactivity disorder, depression, and/or anxiety: A rapid systematic review and meta-analysis.
The growing prevalence of mental health disorders in children and adolescents coupled with poor medication adherence in the paediatric population is a major problem within healthcare systems affecting patient outcomes. Digital health interventions (DHIs) are primed to optimise medication adherence given the expansion of digital health markets and the increased usage of digital technologies by children and adolescents. This rapid systematic review evaluates the impact of DHIs on optimising medication adherence amongst children and adolescents with mental health disorders compared to treatment as usual (TAU). A rapid systematic search in electronic databases CINAHL Plus, Cochrane Library, MEDLINE, PubMed, and Scopus was conducted. The scope of the rapid systematic search included randomised controlled trials and quasi-experimental studies (non-randomised controlled trials) evaluating DHIs optimising medication adherence in children and adolescents with attention deficit hyperactivity disorder (ADHD), depression and/or anxiety. Meta-analyses were conducted based on estimating pooled odds ratio (OR) and mean difference (MD) with 95% confidence interval using a random-effects model. Thematic analysis identified key avenues DHIs offer to optimise medication adherence. Four studies were found, with 502 participants included in the meta-analysis. An improvement in medication adherence was observed following DHIs for studies measuring dichotomous and continuous outcomes. However, the effect was not significant for the former. DHIs were shown to help bridge the gaps between patients and healthcare professionals, allowing for more frequent monitoring, communication, and assessments. Medication adherence amongst children and adolescents with acute or chronic ADHD, anxiety or depression may be positively impacted by DHIs, but better-powered studies with a lower risk of bias are necessary. The evidence currently remains inconclusive on DHIs improving medication adherence in children and adolescents.


[Blood transfusion incident analysis by ALARM method].
The hospital risk management department is firstly involved in the methodological analysis of grade zero transfusion incidents. The system is based on a subsequent analysis process in compliance with the ongoing requirements of the Haute Autorité de santé (HAS) for a reactive approach to risk, allowing to identify failures and start the appropriate preventive and corrective measures. The use of the association of litigation and risk management method makes easier the grade zero analysis and brings to light the team or institutional, organizational, temporal, individual factors representative of undesirable effects. Two main factors come out again from this analysis, the absence of the identification bracelet coupled with a disrespect of transfusion procedures in force. The whole institution must be concerned by these improvement actions. Health teams should overcome difficulties to be totally involved in such a process. Human factors' recognition, establishment of clear and effective communication between individuals and information sharing should provide optimum quality care services which are safe and free of unnecessary risks.


R WE ready for reimbursement? A round up of developments in real-world evidence relating to health technology assessment: part 12.
In this latest update we highlight the final results from the RCT-DUPLICATE initiative, the publication of guidance from Haute Autorité de Santé (HAS), the joint viewpoint from the Institute for Quality and Efficiency in HealthCare (IQWIG) and the Belgian HealthCare Knowledge Center, and a position from the European Organization for Research and Treatment of Cancer (EORTC). Finally, we discuss how the NICE RWE framework has been implemented to allow consideration of RWE external control arms.


[NEPHROTIC SYNDROME RECURRENCE POST-RENAL TRANSPLANTATION: 10 YEARS' EXPERIENCE AT SCHNEIDER CHILDREN'S MEDICAL CENTER IN ISRAEL].
A total of 30-50% of pediatric patients presenting with steroid resistant nephrotic syndrome (SRNS) will reach end stage renal disease (ESRD). In patients with primary SRNS, the risk of post-transplant recurrence is around 60% with poor graft outcomes. In the past decade new treatment modalities have emerged in an attempt to improve graft outcomes. To describe the clinical experience at the Schneider Children's Medical Center in Israel in treating children with post-transplant recurrent SRNS in the past decade, and compare its results to a similar study conducted at the same center in previous years. A retrospective chart review was conducted. Data regarding demographic characteristics, clinical course and treatment modalities of patients with post-transplant recurrent SRNS were extracted from patients' charts. Eight patients with post-transplant recurrent SRNS were identified. Median age at initial nephrotic syndrome presentation was 4 (range: 0.8-15) years. Median time to reach ESRD was 43 (range: 12-132) months. All patients were treated with plasmapheresis, seven patients were treated with Rituximab. Low-density lipoprotein (LDL) apheresis, Ofatumumab and Abatacept were used in 1-2 patients each. Median follow-up time post-transplant was 47 (range: 15-93) months. Four patients (50%) responded to treatment, two achieved complete and two partial remission. Four patients reached ESRD within a median time of 24 (range: 12-84) months. Lower rates of acute tubular necrosis and immediate graft loss were observed during the last decade compared to previous years (37.5% vs. 64%; 0% vs. 28.6% respectively). Post-transplant recurrence of SRNS continues to pose a significant treatment challenge. Similar to previous reports, only 50% of our patients responded to treatment while 50% were unresponsive to all treatment modalities and reached ESRD. Immediate post-operative management improved over the last decade, however long-term outcome continues to be grim. There is a need to better identify disease mechanisms that will allow us to tailor more effective treatment modalities to improve patients' outcome.


Cognitive development in childhood and drinking behaviour over two decades in adulthood.
Childhood cognition predicts adult morbidity and mortality, potentially working through health behaviours. This study investigates if childhood cognition influences life course (i) non-drinking and (ii) binge drinking and pathways through which this might act-namely, childhood behaviour problems, adult social position and educational qualifications. Prospective cohort of British births in March 1958, with information on cognition at 7, 11 and 16 years and alcohol use at 23, 33 and 42 years. Non-drinkers drank "infrequently/on special occasions" or "never". Binge drinkers consumed >or=10 units/occasion (men) and >or=7 units/occasion (women). Lower cognitive ability increased the odds of non-drinking at each adult survey (for example, for men at 42 years OR 1.52 (95% CI 1.34 to 1.72) per SD decrease in 7-year maths). Associations remained after adjustment for pathway factors (i) behaviour problems, (ii) adult social position and (iii) educational qualifications. Decreased ability rank across childhood (7-16 years) also increased odds of non-drinking at 42 years, but the association operated via pathway factors. Lower 7-year ability elevated the odds of 42-year binge drinking, operating via pathway factors. Declining ability rank across childhood also increased the odds of adult binge drinking; associations operated through behavioural problems, adult social position and qualifications. In women, the decline in risk of binge drinking from an age 23-year peak to 42 years was associated with higher 7-year score. Poorer childhood cognition was associated with non-drinking and binge drinking up to the early 40s. Associations between childhood cognition and drinking status may mediate between childhood cognition and adult health.


Association between ambient air pollutants and lipid profile: A systematic review and meta-analysis.
Studies of the effects of atmospheric pollutants on lipid profiles remain inconsistent and controversial. The study was aimed to investigate the relationship between the exposure to ambient air pollutants and variations in the blood lipid profiles in the population. A comprehensive search of three different databases (PubMed, Web of Science, and the Cochrane Library) until December 17, 2022, yielded 17 origional studies fulfilling the inclusion criteria for a meta-analysis. Aggregate effect measures and 95% confidence intervals (95% CI) for the relevant ambient air pollutants were deduced employing random effects models. The collective meta-analysis indicated that long-term exposure to PM1, PM2.5, PM10 and CO showed a substantial correlation with TC (PM1: β = 2.04, 95%CI = 0.15-3.94; PM2.5: β = 1.11, 95%CI = 0.39-1.84; PM10: β = 1.70, 95%CI = 0.67-2.73; CO: β = 0.08, 95%CI = 0.06-0.10), PM10 exhibited a significant association with TG (β = 0. 537,95% CI = 0.09-0.97), whereas HDL-C demonstrated notable relationships with PM1, PM10, SO2 and CO (PM1: β = -2.38, 95%CI = -4.00 to -2.76; PM10: β = -0.77, 95%CI = -1.33 to -0.21; SO2: β = -0.91, 95%CI = -1.73 to -0.10; CO: β = -0.03, 95%CI = -0.05 to 0.00). PM2.5, PM10 also showed significant associations with LDL-C (PM2.5: β = 1.44 95%CI = 0.48-2.40; PM10: β = 1.62 95%CI = 0.90-2.34). Subgroup analysis revealed significant or stronger correlations predominantly in cohort study designs, with higher male comparisons, and in regions exhibiting elevated contaminant levels. In summary, the analysis substantiates that ambient air pollutants can be recognized as potent contributors to alterations in lipid profiles, particularly particulate pollutants which exert more obvious effects on lipid profiles.


The effect of the presence of valinomycin on the interfacial tension of lecithin membrane.
The effect of the presence of valinomycin in lecithin membrane on its interfacial tension has been studied. The experiments have been carried out at various forming solution compositions and at various potassium ion concentrations in electrolyte solution. Potassium chloride was used as the electrolyte. A complex was formed between the valinomycin molecule and K+ ion. The following parameters describing the complex were determined: K, the stability constant of the valinomycin-K+ complex and B, partition coefficient. These values are equal to 3.52 x 10(5) m3 mol(-1) and 6.0, respectively.


Angiotensin-converting-enzyme insertion/deletion polymorphism, ACE activity, and COVID-19: A rather controversial hypothesis. A case-control study.
Accumulating data has shown a contribution of the renin-angiotensin system in COVID-19 pathogenesis. The role of angiotensin-converting enzyme (ACE) insertion (I)/deletion (D) polymorphism as a risk factor in developing COVID-19 disease comes from epidemiological data and is controversially discussed. We conducted a retrospective case-control study and assessed the impact of ACE I/D genotype in COVID-19 disease prevalence and severity. In 81 COVID-19 patients explicitly characterized and 316 controls, recruited during the first wave of COVID-19 pandemic, ACE I/D genotype, and ACE activity were determined. A generalized linear model was used and Poisson regression analysis estimated the risk ratios (RRs) of alleles and genotypes for disease severity. DD patients had almost 2.0-fold increased risk (RR: 1.886, confidence limit [CL] 95%: 1.266-2.810, p = 0.0018) of developing a more severe disease when contrasted to ID and II individuals, as did D allele carriers compared to I carriers (RR: 1.372; CL 95%: 1.051-1.791; p = 0.0201). ACE activity (expressed as arbitrary units, AU/L) was lower in patients (3.62 ± 0.26) than in controls (4.65 ± 0.13) (p < 0.0001), and this reduction was observed mainly among DD patients compared to DD controls (3.97 ± 0.29 vs. 5.38 ± 0.21; p = 0.0014). Our results demonstrate that ACE DD genotype may predispose to COVID-19 increased disease severity via a mechanism associated, at least in part, with the significant fall in their ACE activity. Our findings suggest a more complex pattern of synergy between this polymorphism and ACE activity in COVID-19 patients compared to healthy individuals and set the grounds for large-scale studies assessing ACE genotype-based optimized therapies with ACE inhibitors and angiotensin receptor blockers.


A numerical reconstruction of the effects of late stimulation on a cardiac ventricular action potential.
Numerical simulations of a propagating cardiac action potential utilizing Beeler-Reuter and Drouhard-Roberge physiological routines for the membrane current have been performed. These action potentials show increases in action potential duration when subjected to strong late stimuli of either positive or negative polarity. The mechanism is the same as that reported in an earlier paper which utilized a different physiological approach: repolarizing stimuli can reset the fast sodium gates locally so that they can be retriggered by diffusive return of charge from surrounding tissue. This results in a large depolarizing transient that lengthens action potential duration.


Effect of the stacking order, annealing temperature and atmosphere on crystal phase and optical properties of Cu2SnS3.
Cu2SnS3 (CTS) is emerging as a promising absorber for the next generation thin film solar cells (TFSC) due to its excellent optical and electronic properties, earth-abundance and eco-friendly elemental composition. In addition, CTS can be used as precursor films for the Cu2ZnSnS4 (CZTS) synthesis. The optical properties of CTS are influenced by stoichiometry, crystalline structure, secondary phases and crystallite size. Routes for obtaining CTS films with optimized properties for TFSC are still being sought. Here, the CTS thin films synthesized by magnetron sputtering on soda lime glass (SLG) using Cu and SnS2 targets in two different stacks, were studied. The SLG\Cu\SnS2 and SLG\SnS2\Cu stacks were annealed in S and Sn + S atmospheres, at various temperatures. Both stacks show a polymorphic structure, and higher annealing temperatures favor the monoclinic CTS phase formation. Morphology is influenced by the stacking order since a SnS2 top layer generates several voids on the surface due to the evaporation of SnS, while a Cu top layer provides uniform and void-free surfaces. The films in the copper-capped stack annealed under Sn + S atmosphere have the best structural, morphological, compositional and optical properties, with tunable band gaps between 1.18 and 1.37 eV. Remarkably, secondary phases are present only in a very low percent (< 3.5%) in samples annealed at higher temperatures. This new synthesis strategy opens the way for obtaining CTS thin films for solar cell applications, that can be used also as intermediary stage for CZTS synthesis.


The Effects of Hydroxyethyl Starch 6% and Crystalloid on Volume Preloading Changes following Spinal Anesthesia.
Hypotension is one of the most common complications after spinal anesthesia for cesarean delivery. Normally, preloading with fluids, especially crystalloids, is used to prevention of hypotension. In the present randomized clinical trial study, 120 parturients presenting for elective cesarean section with the American Society of Anesthesiologists Class I and II received either 15 cc normal saline or 7 cc/kg hydroxyethyl starch 6% (Voluven) fluid. Information regarding to systolic, diastolic, mean arterial pressure, and heart rate, incidence of hypotension, adverse effects, the total dose of atropine, and ephedrine were recorded in before and 3, 6, 9, 15, and 20 min after spinal anesthesia. Furthermore, Apgar score of newborn at the 1st and 5th min after birth was recorded. There was no significant difference in mean arterial pressure at different stages such as: Exactly after spinal and 3, 6, 15, and 20 min after spinal anesthesia between two groups (P > 0.05). Total dose of ephedrine and atropine were similar between groups (P > 0.05), respectively. There was no significant difference in Apgar score at the 1st and 5th min after birth between two groups. There were not any adverse effects of drugs in two groups. The results of this study show that hydroxyethyl starch 6% compared to normal saline are similar to prevent hypotension during spinal anesthesia for cesarean delivery.


Surgical approach, complications, and reoperation rates of combined rectal and pelvic organ prolapse surgery.
Our primary objective was to determine rectal prolapse (RP) and pelvic organ prolapse (POP) reoperation rates and postoperative < 30-day complications after combined RP and POP surgery at a single institution. This was an IRB-approved retrospective cohort study of all female patients who received combined RP and POP surgery at a single tertiary care center from 2008 to 2019. Recurrence was defined as the need for subsequent repeat RP or POP surgery at any point after the index surgery. Surgical complications were separated into Clavien-Dindo classes. Sixty-three patients were identified, and 18.3% (12/63) had < 30-day complications (55% Clavien-Dindo grade 1; 27% Clavien-Dindo grade 2; 18% Clavien-Dindo grade 4). Of patients undergoing combined abdominal RP and POP repair, no postoperative < 30-day complications were noted in the MIS group compared to 37.5% of those patients in the laparotomy group (p < 0.01). Overall, in those patients who underwent combined RP and POP surgery, the need for subsequent RP surgery for recurrent RP was 14% and the need for subsequent POP surgery for recurrent POP was 4.8% (p = 0.25). In this cohort of women undergoing combined RP and POP surgery, a higher proportion required subsequent RP surgery compared to those requiring subsequent POP surgery, although this was not statistically significant. Almost one-fifth of patients undergoing combined RP and POP surgery experienced a < 30-day surgical complication, regardless of whether the approach was perineal or abdominal. For those patients undergoing abdominal repair, < 30-day complications were more likely in those patients who had a laparotomy compared to those who had a minimally invasive surgery.


Mass fragmentographic assay of nanogram amounts of the antidepressant drug mianserin hydrochloride (Org GB 94) in human plasma.
For the assay of the antidepressant compound mianserin hydrochloride (Org GB 94) in human plasma, a mass fragmentographic method, using the deuterated analogue as internal standard and a high-performance liquid chromatographie sample clean-up procedure has been developed. The assay specifications obtained are a lower limit for reliable measurements of 1 ng/ml, and accuracy of ca. 0.01 ng/ml, a precision of 6--7% and a capacity of about 60 samples per day. The applicability of the assay method is illustrated by measurements of single-dose and steady-state plasma levels in clinical experiments, demonstrating the possibility of monitoring plasma levels during at least 24 h after a single dose of 15 mg of Org GB 94. The mean steady-state plasma levels after a daily dose of 3 X 20 mg of Org GB 94 appeared to be remarkably constant with time: 38, 36 and 34 ng/ml after 2, 4, and 6 weeks of treatment of 18 depressed patients.


Ubiquitination as a priming process of PKC alpha and PKC epsilon degradation in the alphaT3-1 gonadotrope cell line.
Protein kinase C (PKC) is a family of isoenzymes playing a key role in the regulation of gonadotrope cell functions. Specific PKC isoforms are activated and downregulated differentially by gonadotropin-releasing hormone (GnRH) and the phorbol ester TPA. In the present study, focusing mainly on PKC epsilon, the mechanisms underlying the proteasome-dependent downregulation of GnRH-activated PKC epsilon and TPA-sensitive PKC alpha and epsilon isoenzymes were investigated in alphaT3-1 gonadotrope cells. In pull-down assays involving the use of glutathione-agarose affinity beads conjugated with a GST-fusion protein containing ubiquitin-associated domains of Rad23 that bind very likely to K48-linked polyubiquitinated proteins, TPA induced rapid (within 15 min) and sustained (up to 4 h) PKC alpha and PKC epsilon polyubiquitination. However, GnRH selectively elicited receptor-dependent polyubiquitination of PKC epsilon, but not that of PKC alpha. The GnRH-evoked PKC epsilon polyubiquitination was a strong, fast process (taking place as early as 10 min) which decreased progressively with time (but was still detectable after 4 h of treatment). In addition, no apparent association between PKC epsilon and the lysosomal compartment was observed upon performing double-labeling immunofluorescence and confocal microscopy, after either 10 min or 1 hour of stimulation by GnRH or the phorbol ester. In alphaT3-1 gonadotrope cells, polyubiquitination is therefore the event triggering GnRH-evoked PKC epsilon desensitization as well as TPA-induced PKC alpha and PKC epsilon downregulations; it precedes the respective isoenzyme's degradation by the proteasome complex.


Coordinated rhythmic bursting in respiratory and locomotor muscle nerves in the spinal rabbit.
In unanaesthetized, curarized spinal rabbits (C2 level) treated with Niamide and DOPA, rhythmic activities were recorded from the phrenic nerves; close coordination was observed between the phrenic bursts and the locomotor bursts which developed in hindlimb muscle nerves. The frequency of phrenic bursts was reduced after a second spinal transection at the Th12 level, while rhythms in the hindlimb remained unchanged. It thus appears that in the spinal preparation and under certain pharmacological conditions, phrenic bursts generated by the cervico-thoracic spinal cord can be driven by the lumbar generators of locomotion; spinal links thus exist between these hindlimb locomotion generators and spinal interneuronal networks involved in phrenic motoneuronal activation, may be via hindlimb forelimb driving.


Uterine Sarcoma: A Clinico-Pathological Study.
To analyse the clinical presentation, histological type, management, and prognosis of cases diagnosed with uterine sarcomas. This was a hospital-based retrospective study conducted at the Institute of Obstetrics and Gynaecology, Chennai, and Meenakshi Medical College and RI, Kancheepuram, from 2009 to 2015. Thirty patients who were diagnosed with uterine sarcoma were analysed for type of sarcoma, clinical details, treatment, and prognosis. Leiomyosarcoma was the commonest type seen in ten cases followed by mixed mullerian tumours in nine cases and endometrial stromal sarcomas in six cases. Leiomyosarcomas and mixed mullerian tumours were seen between the ages of 45 and 65 years. Women with endometrial stromal tumours were younger in the age group between 35 and 45 years. Pelvic mass and pain were the predominant symptom in leiomyosarcoma and mixed mullerian tumours. Endodermal stromal tumours presented predominantly with abnormal uterine bleeding. Forty percentage of cases were diagnosed with stage I disease. Twenty-six patients were managed surgically. Post-operative adjuvant therapy was given in 12 patients. Median duration of follow-up was 52 months. During the above period, 11 were alive, eight were lost to follow-up, and 11 were dead. In those who were alive, two cases presented with local recurrences. The pre-operative diagnosis of sarcoma is difficult and prognosis is poor even in early stage disease because of the aggressive nature of the tumours.


Frailty and outcomes after craniotomy for brain tumor.
Frailty has been associated with increased morbidity and mortality in a variety of surgical disciplines. Few data exist regarding the relationship of frailty with adverse outcomes in craniotomy for brain tumor resection. We assessed the relationship between frailty and the incidence of major post-operative complication, discharge destination other than home, 30-day readmission, and 30-day mortality after elective craniotomy for brain tumor resection. A retrospective cohort study was conducted on 20,333 adult patients undergoing elective craniotomy for tumor resection in the 2012-2018 ACS-NSQIP Participant Use File. Multivariate logistic regression was performed using all covariates deemed eligible through clinical and statistical significance. 6,249 patients (30.7%) were low-frailty and 2,148 patients (10.6%) were medium-to-high frailty. In multivariate logistic regression adjusting for age, gender, BMI, ASA classification, smoking status, dyspnea, significant pre-operative weight loss, chronic steroid use, bleeding disorder, tumor type, and operative time, low frailty was associated with increased adjusted odds ratio of major complication (1.41, 95% CI: 1.23-1.60, p < 0.001), discharge destination other than home (1.32, 95% CI: 1.20-1.46, p < 0.001), 30-day readmission (1.29, 95% CI: 1.15-1.44, p < 0.001), and 30-day mortality (1.87, 95% CI: 1.41-2.47, p < 0.001). Moderate-to-high frailty was also associated with increased adjusted odds of major complication (1.61, 95% CI: 1.35-1.92, p < 0.001), discharge destination other than home (1.80, 95% CI: 1.58-2.05), 30-day readmission (1.39, 95% CI: 1.19-1.62, p < 0.001), and 30-day mortality (2.42, 95% CI: 1.74-3.38, p < 0.001). CONCLUSIONS: Frailty is associated with increased odds of major post-operative complication, discharge to destination other than home, 30-day readmission, and 30-day mortality.


Addressing medication errors--The role of undergraduate nurse education.
Medication errors are a persistent problem in today's National Health Service (NHS). Many factors contribute to drug incidents occurring, from the initial prescription stage through to administration and arise from both individual and system failures. The literature identifies the multi-disciplinary nature of the problem and highlights the important contribution that nurses make with regards to ensuring medication safety. However limited evidence exists in the literature regarding the extent to which the current content of undergraduate pharmacology education prepares nurses for their role in the prevention of errors. The report "Building a safer NHS for patients-improving medication safety" [Department of Health, 2004. Building a Safer NHS for Patients: Improving Medication Safety. The Stationary Office, London] concludes that it is now imperative that undergraduate education should emphasise the issue of medication safety. An educational initiative was therefore introduced to address this problem. A "Medication Safety Day" which focused on the causes of medication errors was implemented to highlight how and why drug incidents may occur. This initiative recognises that nurse education should not only ensure adequate theoretical knowledge of pharmacology but should also equip students with an awareness of how many diverse factors may contribute to the occurrence of medication errors.


Cardiopulmonary resuscitation: attitudes and perceptions of junior doctors.
Many junior doctors feel cardiac arrests are unsatisfactorily managed and experience high levels of stress during the procedure, often feeling they are inadequately trained for the task. Juniors also regard 'do not resuscitate' orders as decisions for teams, not individuals.


The presence of teleost-type angiotensin components in lamprey buccal gland suggests a role in endocrine mimicry.
Previous characterization of a native lamprey angiotensin II (LpAng II) that possesses a different sequence and function than teleost-type angiotensin II (Ang II) has raised a question as to the role of teleost-type angiotensin peptides in lampreys. In this study, teleost-type angiotensin like-peptides were identified in the buccal gland of lampreys by immunoassays and immunohistochemistry. The possible sources of angiotensin like-peptides were investigated in lampreys by manipulating their choice of host and food. Ang II immunoreactivity (irAng II) was detected in the buccal gland and plasma of feeding phase sea lampreys exposed to Atlantic cod, but was mostly absent in fasting lamprey. Qualitatively, the HPLC profiles of irAng II observed in the plasma, when present, were highly similar to those in buccal gland, implying that the buccal gland could be a source of plasma Ang II. Japanese lampreys force-fed with dogfish blood had significantly elevated concentrations of irAng II in their buccal glands when compared to unfed individuals, suggesting that feeding stimuli may have enhanced buccal gland activity. Teleost-type Ang II-containing proteins, other than angiotensinogen, are present in the buccal gland as trypsinization generated Ang II in vitro, and the HPLC profile of these irAng II was highly comparable to those naturally present in the buccal gland. [Asn(1), Val(5), Thr(9)]-Ang I that was identified in the buccal gland of Japanese lampreys has the same amino acid sequence to those previously isolated from the incubation of plasma and kidney extract, providing an alternative explanation for the previous isolation of teleost-type Ang I in lampreys. irAng I and irAng II were localized in the granule-like structures in the apical region of the secretory epithelia, suggesting that these peptides may be active components of lamphredin. The teleost-type angiotensin peptides in the buccal gland secretion suggested that these host-specific peptides could be part of the endocrine mimicry strategy used by lampreys to evade host immune responses and reduce immune-rejection.


Biosorption of metals (Cu(2+), Zn(2+)) and anions (F(-), H(2)PO(4)(-)) by viable and autoclaved cells of the Gram-negative bacterium Shewanella putrefaciens.
Microbial biomass represents a potentially cost-effective sorbent for water treatment applications. High sorption capacities for both cations and anions are demonstrated here for viable and autoclaved cell suspensions of the Gram-negative bacterium Shewanella putrefaciens. FTIR absorption spectra and pH-dependent zeta-potentials are similar for the viable and killed bacterial cells. Potentiometric titrations, however, reveal a two to three times higher OH(-) buffering capacity for the living cells. The Cu(2+) sorption capacity of the viable cells is also about twice that of the autoclaved cells. Sorption of fluoride and phosphate is not pH-dependent, although an initial addition of acid or base was needed to activate the anion binding sites. Uptake of fluoride is comparable for viable and killed cells. For the viable cells, the isotherms of Zn(2+) and Cu(2+) indicate the presence of at least two distinct populations of cell wall binding sites. In competitive sorption experiments, Cu(2+) completely inhibits the binding of Zn(2+) to the cells at aqueous concentrations above 150 mg L(-1). The release of dissolved organic compounds by the viable cells depends on the concentrations of metal cations or fluoride to which the cells are exposed. In particular, the presence of Cu(2+) nearly completely suppresses the release of protein-like substances, possibly reflecting Cu(2+) toxicity.


Source apportionment and health risk assessment for potentially toxic elements in size-fractionated road dust in Busan Metropolitan City, Korea.
Potentially toxic elements' (PTEs; V, Cr, Co, Ni, Cu, Zn, As, Cd, Sb, Pb, and Hg) pollution level was investigated in size-fractionated road dust in Busan Metropolitan City. Health risks to humans (adult and children) were also evaluated in fine particle fraction (< 63 μm) of road dust. PTE concentrations in the fine particles (< 63 μm) were ranked as follows (unit: mg/kg): Zn (2511) > Cu (559) > Cr (531) > Pb (385) > Ni (139) > V (83.8) > Sb (31.6) > Co (21.6) > As (17.2) > Cd (4.1) > Hg (0.38). The PTE concentrations in fine particles (< 63 μm) were significantly higher than those in coarse particles except for V, Co, and As. The mean PTE loadings of fine particle fraction (< 63 μm; 233 mg/m2) in road dust were up to 4.5 times higher than other particle fractions. Igeo values of Sb were higher than 5 except for > 1000-μm fraction, indicating extremely polluted status. PCA results and elemental ratios indicated that most of the PTEs in road dust were derived from non-exhaust traffic-related sources such as brake pads and tires. Cr, Pb, and Sb had higher HI values than other metals for both adults and children. Sampling sites of heavy traffic and industrial areas showed that the carcinogenic risk exceeded the maximum threshold level (10 - 4). Especially in children, the mean carcinogenic risk (ingestion pathway) of As (6.8 × 10 - 4) Cd (2.0 × 10 - 4), and Ni (4.1 × 10 - 4) exceeded the maximum threshold level, indicating that continuous exposure to road dust may pose a high cancer risk to children. Therefore, continuous monitoring and management of these metals are needed to protect human health and the urban environment.


First-line single agent treatment with gefitinib in patients with advanced non-small-cell lung cancer.
Lung cancer is a malignant carcinoma which has the highest morbidity and mortality in Chinese population. Gefitinib, a tyrosine kinase (TK) inhibitor of epidermal growth factor receptor (EGFR), displays anti-tumor activity. The present data regarding first-line treatment with single agent gefitinib against non-small-cell lung cancer (NSCLC) in Chinese population are not sufficient. To assess the efficacy and toxicity of gefitinib in Chinese patients with advanced non-small-cell lung cancer (NSCLC), a study of single agent treatment with gefitinib in Chinese patients was conducted. 45 patients with advanced NSCLC were treated with gefitinib (250 mg daily) until the disease progression or intolerable toxicity. Among the 45 patients, 15 patients achieved partial response (PR), 17 patients experienced stable disease (SD), and 13 patients developed progression disease (PD). None of the patients achieved complete response (CR). The tumor response rate and disease control rate was 33% and 71.1%, respectively. Symptom remission rate was 72.5%, and median remission time was 8 days. Median overall survival and median progression-free survival was 15.3 months and 6.0 months, respectively. The main induced toxicities by gefitinib were skin rash and diarrhea (53.3% and 33.3%, respectively). The minor induced toxicities included dehydration and pruritus of skin (26.7% and 22.2%, respectively). In addition, hepatic toxicity and oral ulceration occurred in few patients (6.7% and 4.4%2, respectively). Single agent treatment with gefitinib is effective and well tolerated in Chinese patients with advanced NSCLC.


Development of a nomogram to predict negative postoperative behavioral changes based on a prospective cohort.
It is believed that negative postoperative behavioral changes (NPOBC) is associated with negative perioperative outcomes in children. The importance of development of a predictive model of NPOBC was noted. This study aims to identify potential risk factors develop a nomogram to predict NPOBC on postoperative day 3 based on a prospective cohort. A prospective observational study was conducted on children(American Society of Anesthesiologists I ~ III) aged 2 ~ 12 years who underwent selective surgery under general anesthesia between September 2022 and February 2023. The patient's clinical data were analyzed. The method of measuring NPOBC is with the The Posthospital Behaviour Questionnaire (PHBQ), and all of children remained hospitalized at the time of assessment. The enrolled patients were categorized into the NPOBC group and the non-NPOBC group according to if children developed NPOBC on postoperative day 3. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors and develop the nomogram to predict NPOBC. Internal validation was performed using the parametric bootstrapping method. One hundred ninety-two patients were enrolled in the study, 44.8% (86/192 patients) of children developed NPOBC on postoperative day 3. Univariate and multivariate logistic regression analysis demonstrated that the Pediatric Anesthesia Behavior (PAB) score (OR: 1.23, 95%CI: 1.14-1.33), cerebral desaturation (OR: 1.16, 95%CI: 1.02-1.32), and postoperative pain score (OR: 1.07, 95%CI: 1.02-1.13) were independent predictors for NPOBC on postoperative day 3 (P < 0.05). They were used to develop the prediction model. The calibration curve demonstrated satisfied discrimination and calibration of the prediction model. The model presented with good discriminative ability (area under the receiver operating characteristic curve: 0.762 [95%CI: 0.691-0.833]). The decision curve analysis also revealed the great clinical utility of the nomogram. Based on our prospective observational study, pre-anesthesia patients with higher PAB scores, presence of cerebral desaturation, and higher postoperative pain score were more likely to develop NPOBC on postoperative day 3. We established and validated a nomogram for predicting NPOBC, which could help assess patients individually, identify high-risk groups of NPOBC and improve patient prognosis. Chinese Clinical Trial Registry, ChiCTR-2,200,059,776. Registered 11 May 2022.


Promoting a culture of sharing the error: A qualitative study in resident physicians' process of coping and learning through self-disclosure after medical error.
Most physicians, including residents, experience significant emotional distress after making medical 11 errors. As high reliability organizations (HROs), hospitals must not only support physicians' emotional recovery but also promote their learning from errors. Self-disclosure is a process of communication in which individuals reveal information about themselves to others. While many previous studies have focused on investigating the effectiveness of self-disclosure, little is known about the process itself. Therefore, this study aims to explore residents' processes of coping with their emotional distress and learning through self-disclosure after making errors. Semi-structured interviews were conducted with 22 residents in their second year from two Japanese hospitals where informal error conferences guided by senior residents are implemented regularly. In the interview, four core questions were posed regarding the nature of the error/incident, their emotions and behavior after the error, ways of self-disclosure, and the results of error-sharing in the conference. Interview data were thematically analyzed, drawing upon disclosure decision model as the theoretical framework. Five phases emerged from the analysis: (1) emotional distress and reactions before self-disclosure; (2) self-disclosure to individuals to achieve social rewards; (3) emotional sublimation after self-disclosure to individuals; (4) sharing errors in groups for learning opportunities; and (5) transforming the perspectives on overcoming and learning from errors. This is the study to demonstrate that various types of self-disclosure were embedded in the processes of residents' recovery and learning from medical errors. The study suggests that a better understanding of the processes of residents' coping with their distress and learning from their errors through self-disclosure is fundamental to the creation of a "culture of sharing errors" in hospitals as HROs.


Laparoscopic renal surgery and the risk of rhabdomyolysis: diagnosis and treatment.
Postoperative rhabdomyolysis is a rare but serious complication of laparoscopic renal urologic surgery. The early recognition and treatment of the condition are imperative to minimize the risk of acute renal failure (ARF) and to limit the associated physical debility. Between 1992 and 2003, > 700 laparoscopic renal procedures were performed at 2 institutions. Rhabdomyolysis occurred in 7 patients. Patient records were retrospectively analyzed for operative, postoperative, and convalescence data. Rhabdomyolysis presented in all patients as excessive, immediate postoperative muscular pain in the "downside" hip/flank. The average procedure time among these patients was 7.5 hours (range, 5.8 to 9.4 hours). In 6 of 7 cases, the kidney rest was elevated throughout the procedure. Two patients required emergency fasciotomy to treat a gluteal compartment syndrome. Four patients (57%) experienced ARF with an average peak creatinine of 533.8 micromol/L [7.0 mg/dL] (range, 160.1 to 739.6 micromol/L [2.1 to 9.7 mg/dL]). These patients had bicarbonate alkalinization and diuretic administration initiated at a mean of 24 hours (range, 4 to 48 hours). Two patients required hemodialysis for 1 month postoperatively but had stable serum creatinine (106.8 and 129.6 micromol/L [1.4 and 1.7 mg/dL]) within 2 months. The mean peak serum creatinine kinase (CK) for all patients was 33,912 U/L (range, 9350 to 99,193 U/L). All patients had extended recovery with difficulties including lower extremity weakness (n = 4), local pressure neuropathy (n = 1), long-term leg pain and numbness (n = 1), and disability requiring long-term wheelchair assistance (n = 1). Excessive, immediate postlaparoscopic gluteal muscular pain should prompt immediate evaluation of serum CK to assess for rhabdomyolysis. Aggressive hydration and diuresis are recommended to minimize renal injury. Minimizing operative times, attention to padding of the operative table, and eliminating or limiting the use of a kidney rest may help prevent this complication.


Acquired coarctation due to calcified thrombus in atherosclerosis of the descending thoracic aorta. Two cases and a review.
An extremely rare manifestation of atherosclerosis is described. Two women, aged 57 and 55, presented with upper extremity hypertension and diminished femoral pulses. Plain radiography and total angiographic visualization of the aorta demonstrated focal highly obstructing intraluminal masses containing heavy flocculent calcification in the upper descending thoracic (case 1) and the thoracoabdominal aorta (case 2) producing a significant pressure gradient. The acquired coarctation due to calcified thrombus was relieved by resection and graft replacement in one and placement of a thoracoabdominal bypass graft in the second patient.


Proteomic assessment of sulfur mustard-induced protein adducts and other protein modifications in human epidermal keratinocytes.
Although some toxicological mechanisms of sulfur mustard (HD) have been uncovered, new knowledge will allow for advanced insight in the pathways that lead towards epidermal-dermal separation in skin. In the present investigation, we aimed to survey events that occur at the protein level in human epidermal keratinocytes (HEK) during 24 h after exposure to HD. By using radiolabeled (14)C-HD, it was found that proteins in cultured HEK are significant targets for alkylation by HD. HD-adducted proteins were visualized by two-dimensional gel electrophoresis and analyzed by mass spectrometry. Several type I and II cytokeratins, actin, stratifin (14-3-3sigma) and galectin-7 were identified. These proteins are involved in the maintenance of the cellular cytoskeleton. Their alkylation may cause changes in the cellular architecture and, in direct line with that, be determinative for the onset of vesication. Furthermore, differential proteomic analysis was applied to search for novel features of the cellular response to HD. Partial breakdown of type I cytokeratins K14, K16 and K17 as well as the emergence of new charge variants of the proteins heat shock protein 27 and ribosomal protein P0 were observed. Studies with caspase inhibitors showed that caspase-6 is probably responsible for the breakdown of type I cytokeratins in HEK. The significance of the results is discussed in terms of toxicological relevance and possible clues for therapeutic intervention.


Antiarrhythmic properties of phenylpiperazine derivatives of phenytoin with α₁-adrenoceptor affinities.
An association between α(1)-adrenoceptor affinities, hERG K(+)-antagonistic properties and antiarrhythmic activities for a series of phenylpiperazine derivatives of hydantoin (2a-21a) was investigated. New compounds were synthesized and tested for their affinity for α(1)-adrenoceptors in radioligand binding assay using [(3)H]-prazosin as a selective radioligand. Antiarrhythmic activities in adrenaline- and barium chloride-induced arrhythmia models, an influence of the phenylpiperazine derivatives on the ECG-components and blood pressure were tested in vivo in normotensive rats. The hERG K(+)-antagonistic properties of the most potent antiarrhythmic agents were investigated in silico by the use of program QikProp. The highest α(1)-adrenoceptor affinity (K(i)=4.7 nM) and the strongest antiarrhythmic activity in adrenaline induced arrhythmia (ED(50)=0.1 mg/kg) was found for 1-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butyl)-3-methyl-5,5-diphenylimidazolidine-2,4-dione hydrochloride (19a). The results indicated a significant correlation between α(1)-AR affinities (pK(i)) and antiarrhythmic activity (ED(50)) in adrenaline model (R(2)=0.92, p <0.005). Influence of the examined phenylpiperazine hydantoin derivatives on hERG K(+) channel, predicted by means of in silico methods, suggested their hERG K(+)-blocking properties.


[Reflections on the clinical reports «minimum data set»].
Royal Decree 1093/2010 (3 September 2010) establishes the minimum data set that the clinical reports of discharges and outpatient visits elaborated in the facilities of the National Health System should contain, among others. Until then, the Ministerial Order 221/1984, that only required the drawing up of a discharge report for patients seen in a hospital-regime health care establishment, was in force. In spite of the importance of these documents, their quality is far from that desired, especially that of the reports on visits, which, among other things, are not performed in a high percentage of the cases. Recently the Sociedad Española de Medicina Interna (SEMI) (Spanish Society of Internal Medicine), in collaboration with other scientific societies, issued some recommendations for the drawing up of the discharge reports. In this present work, a series of thoughts are made on the implications of the new decree, especially in the case of the reports of the outpatient clinics.


Relationship between nutritional status and quality of life in patients with cancer.
Patients with cancer frequently suffer a deteriorated quality of life and this is an important factor in the therapeutic decision. The correlation between quality of life and malnutrition seems obvious and bidirectional. The aim of our study was to describe the global quality of life and its various dimensions in patients with cancer, as a function of the nutritional status. A transversal observational study was performed in wards in hospitals in Clermont-Ferrand and Saint Etienne on 907 patients. The EORTC questionnaire, QLQ-C30, was used to assess the quality of life. The mean global quality of life score was 48.8 for patients who had a weight loss of more than 10% since the beginning of their illness, compared with 62.8 for the other patients (p<0.001). A significant association with weight was observed for the main dimensions of the quality of life: physical, functional, cognitive, social, fatigue, nausea, pain, loss of appetite, constipation and diarrhoea. This strong relation between quality of life and weight loss shows the importance of dietary management in patients with cancer.


Upregulation of MAPKAPK5-AS1, PXN-AS1 and URB1-AS1 lncRNAs in non-functioning pituitary adenoma.
Long non-coding RNAs (lncRNAs) have been shown to be dysregulated in a variety of malignant and non-malignant lesions including non-functioning pituitary adenomas (NFPAs). In the current experimental study, we have selected six lncRNAs, namely MAPKAPK5-AS1, NUTM2B-AS1, ST7-AS1, LIFR-AS1, PXN-AS1 and URB1-AS1 to assess their expression in a cohort of Iranian patients with NFPA. MAPKAPK5-AS1, PXN-AS1 and URB1-AS1 were shown to be over-expressed in NFPA tissues compared with control samples (Expression ratios (95% CI) = 10 (3.94-25.36), 11.22 (4.3-28.8) and 9.33 (4.12-21.12); p values < 0.0001, respectively). The depicted ROC curves showed the AUC values of 0.73, 0.80 and 0.73 for MAPKAPK5-AS1, PXN-AS1 and URB1-AS1, respectively. Relative expression level of PXN-AS1 was associated with tumour subtype (p value = 0.49). Besides, relative expression levels of MAPKAPK5-AS1 and LIFR-AS1 were associated with gender of patients (p values = 0.043 and 0.01, respectively). Cumulatively, the current study indicates the possible role of MAPKAPK5-AS1, PXN-AS1 and URB1-AS1 lncRNAs in the pathogenesis of NFPAs.


L-tryptophan injection fails to alter nutrient selection by rats.
Nutritional studies on rats given a choice between two diets differing in protein content have led to the proposal that brain 5-HT content regulates protein intake [2]. Pharmacologic studies under similar conditions of dietary self-selection suggest that brain 5-HT controls carbohydrate intake [41]. We tested the effect of elevating brain 5-HT via tryptophan injection (100 mg/kg) on short-term food intake and selection by rats choosing between two diets differing in protein and carbohydrate content. Under these conditions neither total food intake nor protein and carbohydrate selection were affected despite increases of 50% in brain concentrations of 5-HT and 5-HIAA. The effect of Trp administration was selective to serotonin metabolism as brain concentrations of NE, DA and DOPAC were not affected. These results suggest that alterations in brain 5-HT content which may occur following meal ingestion may not be of physiological importance in regulating nutrient intake and selection.


Direct and indirect effects on the lateral geniculate nucleus neurons of prenatal exposure to methylazoxymethanol acetate.
In this study the morphology of the lateral geniculate nucleus and occipital cortex in rats with methylazoxymethanol acetate (MAM Ac)-induced micrencephaly was examined. The aim was to examine the relative contributions of (a) the direct cytotoxic action of the drug on precursors of dorsal lateral geniculate nucleus (dLGN) neurons in the fetal brain and, (b) the postnatal degeneration of the dLGN following prenatal destruction of target neurons in the occipital cortex, to the final extent of damage to the dLGN. Exposure to MAM Ac on E13 produced severe necrosis in the fetal thalamus and caused a 77% deficit in neuronal numbers in the mature dLGN. Exposure to MAM Ac on E15 did not cause necrosis in the fetal thalamus but when animals exposed at this time were examined at 5 weeks postnatal age there was an 87% deficit in neuronal numbers in the dLGN. The hypothesis that this deficit was the result of postnatal death of the dLGN neurons following the destruction by MAM Ac of their normal target population in laminae iii and iv of the occipital cortex was supported by the observation of severe postnatal degeneration in the dLGN of animals exposed to MAM Ac on E15. The significance of these direct and indirect effects of the cytotoxic teratogen, MAM Ac, for understanding the mechanisms by which brain abnormalities in human micrencephaly are produced is discussed.


Feedback has a positive effect on cognitive function during total sleep deprivation if there is sufficient time for it to be effectively processed.
This study examined whether the provision of feedback and the interval between successive stimuli interact to affect performance on a serial simple reaction time test during sleep deprivation. Sixteen participants (9 female, 7 male, aged 18-27 yr) completed four versions of the 5-min psychomotor vigilance task for a handheld personal digital assistant (PalmPVT) every 2 h during 28 h of sustained wakefulness. The four versions differed in terms of whether or not they provided feedback immediately after each response, and whether the inter-stimulus intervals (ISIs) were long (2-10 s) or short (1-5 s). Cognitive function was assessed using reciprocal response time and percentage of responses that were lapses (i.e., had a response time ≥ 500 ms). Data were analysed using repeated measures ANOVA with three within-subjects factors: test session, feedback, and ISI. For both measures, the only significant interaction was between feedback and ISI. Cognitive function was enhanced by feedback when the ISIs were long because it provided motivation. Cognitive function was not affected by feedback when the ISIs were short because there was insufficient time to both attend to the feedback and prepare for the subsequent stimulus.


Abnormal interaction of Rlip with mutant APP/Abeta and phosphorylated tau reduces wild-type Rlip levels and disrupt Rlip function in Alzheimer's disease.
Alzheimer's disease (AD) is a neurodegenerative disease that affects a large proportion of the aging population. RalBP1 (Rlip) is a stress-activated protein, that plays an important role in aging and neurodegenerative diseases such as Alzheimer's disease. Mutant APP and mutant Tau interact with the Rlip protein which leads to decreased wild-type Rlip levels and disrupt Rlip function in Alzheimer's disease. Rlip is a promising new target for aging, Alzheimer's disease, and other neurological diseases.


Benchmarked molecular docking integrated molecular dynamics stability analysis for prediction of SARS-CoV-2 papain-like protease inhibition by olive secoiridoids.
We performed a virtual screening of olive secoiridoids of the OliveNetTM library to predict SARS-CoV-2 PLpro inhibition. Benchmarked molecular docking protocol that evaluated the performance of two docking programs was applied to execute virtual screening. Molecular dynamics stability analysis of the top-ranked olive secoiridoid docked to PLpro was also carried out. Benchmarking virtual screening used two freely available docking programs, AutoDock Vina 1.1.2. and AutoDock 4.2.1. for molecular docking of olive secoiridoids to a single PLpro structure. Screening also included benchmark structures of known active and decoy molecules from the DEKOIS 2.0 library. Based on the predicted binding energies, the docking programs ranked the screened molecules. We applied the usual performance evaluation metrices to evaluate the docking programs using the predicted ranks. Molecular dynamics of the top-ranked olive secoiridoid bound to PLpro and computation of MM-GBSA energy using three iterations during the last 50 ps of the analysis of the dynamics in Desmond supported the stability prediction. Predictiveness curves suggested that AutoDock Vina has a better predictive ability than AutoDock, although there was a moderate correlation between the active molecules rankings (Kendall's correlation of rank (τ) = 0.581). Interestingly, two same molecules, Demethyloleuropein aglycone, and Oleuroside enriched the top 1 % ranked olive secoiridoids predicted by both programs. Demethyloleuropein aglycone bound to PLpro obtained by docking in AutoDock Vina when analyzed for stability by molecular dynamics simulation for 50 ns displayed an RMSD, RMSF<2 Å, and MM-GBSA energy of -94.54 ± 6.05 kcal/mol indicating good stability. Molecular dynamics also revealed the interactions of Demethyloleuropein aglycone with binding sites 2 and 3 of PLpro, suggesting a potent inhibition. In addition, for 98 % of the simulation time, two phenolic hydroxy groups of Demethyloleuropein aglycone maintained two hydrogen bonds with Asp302 of PLpro, specifying the significance of the groups in receptor binding. AutoDock Vina retrieved the active molecules accurately and predicted Demethyloleuropein aglycone as the best inhibitor of PLpro. The Arabian diet consisting of olive products rich in secoiridoids benefits from the PLpro inhibition property and reduces the risk of viral infection.


Pelvi-ureteric obstruction due to renal pelvis cyst.
Intramural cysts of the renal pelvis are a separate clinical entity and must not be mistaken for neoplasms. Simple enucleation can result in complete restoration of renal function previously impaired by pelvi-ureteric obstruction.


The effects of a 24-h psychological training program on attitudes, communication skills and occupational stress in oncology: a randomised study.
The usefulness of psychological training programs (P.T.P.) in health care settings devoted to cancer care is beginning to be recognised but their content, form and effectiveness need further investigation. Seventy-two oncology nurses were randomly assigned to a 24-h P.T.P. or to a waiting list period. Attitudes were assessed by a semantic differential questionnaire, occupational stress was assessed by the Nursing Stress Scale and communication skills were assessed by standardised videotaped role-playing exercises. These were used to compare trained (T.S.) and control subjects (C.S.). The results show a significant training effect on attitudes (P = 0.05), especially on those related to self concept (P = 0.004), and on the level of occupational stress related to inadequate preparation (P = 0.02). Limited changes were found regarding post-training communication skills. T.S. were significantly more in control of the interview than C.S. (P = 0.02). The results indicate that 24-h P.T.P. assessed here are effective. The data also demonstrate the need to consolidate the skills acquired by regular post-training sessions.


Splenic artery aneurysm that gradually increased in size over 4 years until threatening rupture.
A 47-year-old man was referred to our hospital due to a splenic artery aneurysm. The course of the disease was monitored by ultrasound every 6 months. At each examination, the tumor was found to have increased in size by several millimeters, but the sonographer decided that the increase was within the range of error. After 4 years, the tumor showed a rapid increase in size. With a diagnosis of threatened rupture, the patient's life was saved by surgical intervention. In this case, the observations were only compared to the findings from the previous examination, and the slight increase in tumor size was considered within the range of error. It is important to compare the findings not only with those from the previous examination but also with earlier results.


Circular DNA is a product of the immunoglobulin class switch rearrangement.
The class of immunoglobulin is defined by the constant region of its heavy chain. When a B lymphocyte switches the class of heavy chain it produces, the constant region of mu-type heavy chain is replaced; this occurs through a DNA rearrangement that brings the gene segment encoding the new constant region close to the VDJ segment encoding the variable region. The pre-B-cell line 18-81, which switches from heavy chain mu to gamma 2b production in culture, occasionally abnormally rearranges the heavy chain locus so that DNA sequences between the switch regions of mu and gamma 2b are inverted. Because looping-out is an intermediate step in generating an inversion, the switch rearrangement could occur by looping-out and deletion. Provided that recombination is reciprocal, this would produce a circle of DNA. Indeed, circular DNA molecules have been isolated as products of rearrangement among gene segments encoding the variable regions of the T-cell receptor and of the immunoglobulin heavy chain and light chain. But whereas the breakpoints for the variable region rearrangement are precisely defined, the breakpoints for any given heavy chain class switch are scattered over a length of greater than 6 kilobases, including both switch regions. We have now isolated circular DNA containing the sequences deleted by class-switching, thereby showing that the immunoglobulin heavy chain class switch occurs through looping-out and deletion.


Improved survival following right trisectionectomy with caudate lobectomy without operative mortality: surgical treatment for hilar cholangiocarcinoma.
We conducted this study to assess the safety of performing right trisectionectomy with caudate lobectomy for hilar cholangiocarcinoma by analyzing postoperative mortality and morbidity, and to evaluate the effect of such procedure on pathological curability and long-term overall survival. A retrospective clinicopathological analysis was performed for 16 hilar cholangiocarcinoma patients who underwent right trisectionectomy with caudate lobectomy from June 1999 to April 2003. The median follow-up period was 36.9 months. The preoperative Bismuth-Corlette type was type II in four patients, type III(A) in 10 patients, and type IV in two patients. The median liver volume after hepatic resection was 21.9% of the total liver volume. Postoperative complications including one chronic liver failure developed in 12 patients, but no in-hospital deaths occurred. A postoperative pathological examination showed a cancer free margin in all of the proximal resection sites, although three cases had carcinoma in situ (CIS) lesions in the distal margin that were confirmed during surgery. The 1-, 3-, and 5-year overall survival rates were 94.1%, 64.2%, and 64.2%, respectively. We obtained excellent survival rates without any in-hospital deaths following right trisectionectomy with caudate lobectomy. This procedure may be an effective surgical procedure that can be executed to achieve low mortality rate and high pathological curability for hilar cholangiocarcinomas, except for Bismuth type III(B).


Clonal integration and its ecological significance in Hedysarum laeve, a rhizomatous shrub in Mu Us Sandland.
Hedysarum laeve, a rhizomatous clonal half-shrub, commonly dominates in inland dunes in semiarid areas of northern China. This species propagates vegetatively by the extension of horizontal rhizomes resulting in programmed reiteration of apical and/or axillary meristems. In this study, (14)C labeling and experimental defoliation were employed to test the photosynthate translocation within the interconnected parent-daughter ramet pairs. A proportion of (14)C-photosynthates was transported from the parent ramet into the daughter ramet, the roots of the daughter ramet, and the rhizome; these three components showed more than 70% sink activity after 24-h translocation. On the other hand, the basipetal translocation (from daughter ramet into parent ramet) was relatively small with sink activity of less than 5%, but sink activity of the rhizome exceeded 10%. Defoliation had an influence on the photosynthate translocation between parent and daughter ramets. The intact parent ramets significantly increased their (14)C-photosynthate translocation into defoliated daughter ramets when compared to intact daughter ramets. The daughter ramets transported significantly more (14)C-photosynthates to the defoliated parent ramets than to the intact parent ramets. A portion of (14)C-photosynthates was transported into the rhizome from both parent and daughter ramets, indicating that the rhizome is supported by both ramets for photosynthates. The clonal integration between ramets of the species through rhizome connection may confer benefit both to the ramets and the genet in adverse environments.


The monomeric state of the proton-coupled folate transporter represents the functional unit in the plasma membrane.
Folic acid is an essential vitamin required for de novo biosynthesis of nucleotides and amino acids. The proton-coupled folate transporter (PCFT; SLC46A1) has been identified as the major contributor for intestinal folate uptake. It is also involved in folate transport across the blood-brain barrier and into solid tumors. PCFT belongs to the major facilitator superfamily. Major facilitator superfamily members can exist in either monomeric or homo-oligomeric form. Here, we utilized blue native polyacrylamide gel electrophoresis (BN/PAGE) and crosslinking with bi-functional chemicals to investigate the quaternary structure of human PCFT after heterologous expression in Xenopus laevis oocytes and CHO cells. PCFT was expressed in the plasma membrane in both expression systems. The functionality of the utilized PCFT construct was confirmed in oocytes by folic acid induced currents at acidic pH. For both the oocyte and CHO expression system [(3)H]folic acid uptake studies indicated that PCFT was functional. To analyze the oligomeric state of PCFT in the plasma membrane, plasma membranes were isolated by polymerization with colloidal silica and polyacrylic acid and subsequent centrifugation. The digitonin-solubilized non-denatured PCFT migrated during BN/PAGE as a monomer, as judged by comparison with a membrane protein (5-HT(3A) receptor) of known pentameric assembly that was used to create a molecular sizing ladder. The chemical crosslinkers glutaraldehyde and dimethyl adipimidate were not able to covalently link potential higher order PCFT structures to form oligomers that were stable following SDS treatment. Together, our results demonstrate that plasma-membrane PCFT functions as a monomeric protein.


Diagnosis of intracranial hemorrhage in utero after a maternal seizure.
Reported is a patient who noted decreased fetal movements after a seizure at 32 weeks' gestation. Sonography revealed fetal death and findings consistent with an intraventricular hemorrhage. The possible explanations for and the significance of an association between a maternal seizure and fetal intraventricular hemorrhage are discussed.


Protein structure prediction and design.
Proteins have a unique native conformation, which can be proven in many instances to be determined by the amino acid sequence alone. The folding problem, that is the understanding of how the amino acid sequence directs folding, is still unsolved, despite more than 30 years of effort. However, many new methods have appeared in the past few years. This chapter describes the different principles underlying them and tries to give an overview of their successes and pitfalls.


Skeletal X-ray findings and bone histology in patients on hemodialysis.
X-ray films of the hand skeleton (mammography technique), serum chemistry, and quantitative bone histology (micromorphometry of undecalcified sections, iliac crest spongiosa) were compared in 25 patients on maintenance hemodialysis. The X-ray findings correlated better with serum PTH levels than with bone histology. Of all radiological signs of renal osteodystrophy, pronounced subperiosteal resorption (radial aspect, second finger, middle phalanx) and periosteal new bone formation (middle phalanx) correlated best with histological indicators of osteitis fibrosa. These signs were never seen in control patients. Acroosteolysis (endphalanx) and intracortical or endosteal resorption (middle phalanx) were less specific (i.e., seen even in the absence of metabolic bone disease) and correlated less with bone histology. Osteosclerosis in iliac cancellous bone was paralleled by abnormal texture of spongy bone in the proximal metaphysis of the middle phalanx (second finger).


Rebleeding and Outcome in Patients with Symptomatic Brain Stem Cavernomas.
We sought to evaluate the long-term functional outcomes and identify the potential risk factors for rebleeding in patients with brain stem cavernous malformations (BCMs) who presented with hemorrhages and were surgically or conservatively treated and prospectively monitored. From January 1990 to July 2015, we included patients with first hemorrhagic episodes secondary to single BCMs. Modified Rankin score (mRS) was used for neurological status assessment. Univariate and multivariate regression statistics were used to identify the risk factors for rebleeding. A total of 99 patients with BCMs hemorrhages were included (59 [59.6%] women, mean age 37± 13 years). As initial treatments, 37 patients (37.4%) underwent surgery and 62 (62.6%) received conservative treatment. The median follow-up was 3.33 years (interquartile range 1.16-7 years; 408.3 patient/years). The rebleeding rate by patient/year was 10% in conservatively treated patients. Deterioration was significantly more frequent in patients with rebleeding (p = 0.0001). At the end of the follow-up, the mRS were favorable in 49 patients (65.3%) without rebleeding, whereas only 8 (33.3%) with rebleeding evolved to favorable outcomes (p = 0.006). Lesion size >18 mm (hazards ratio, HR 3.34, 95% CI 1.54-7.26; p = 0.0001) and ventral location or crossing the brain stem's midpoint (HR 2.5, 95% CI 1.14-5.46; p = 0.022) were associated with a major risk of rebleeding in the univariate analysis, but only a lesion >18 mm remained statistically significant (HR 2.7, 95% CI 1.2-6.21; p = 0.016) in the multivariate analysis. A lesion size >18 mm was the principal factor associated with hemorrhage recurrence. The overall functional outcome was good. However, significant morbidity was attributable to rebleeding.


Three-component, room temperature crotylation catalyzed by solid-supported Brønsted acid: enantioselective synthesis of homoallylic carbamates.
[reaction: see text] A heterogeneous, three-component crotylation of in situ generated N-acyl iminium ions has been developed. This reaction proceeds under ambient temperature in MeCN and is catalyzed by macroporous polystyrene-bound sulfonic acid (MP-TsOH). Workup is accomplished by filtration, upon which the catalyst is recoverable. A range of homoallylic amine equivalents have been prepared from the corresponding aldehydes, carbamates, and chiral (E)-crotylsilanes in a highly stereoselective manner.


A mutant lactose repressor with altered inducer and operator binding parameters.
The lactose repressor protein from the mutant Escherichia coli BG185 contains valine at position 81 instead of alanine. Spectroscopic, chemical and direct binding measurements demonstrate that the BG185 protein exhibits properties similar to the wild-type repressor-inducer complex. Kinetic measurements of inducer binding to BG185 repressor yielded rate constants that were more than two orders of magnitude smaller than those observed for wild-type repressor; these results suggest that the structural transitions required for inducer binding are markedly impaired by the mutation. The fluorescence spectral shift in response to inducer binding was identical for mutant and wild-type proteins. This identity indicates direct effects of inducer binding on the tryptophan(s) near the sugar binding site rather than environmental changes consequent to conformational shifts. Analogy to the bacterial sugar binding proteins suggest that the Ala to Val change at position 81 in BG185 repressor yields a molecule that is fixed in a closed, sugar-binding conformation.


Should balloon-occluded retrograde transvenous obliteration be the first-line interventional radiologic treatment for bleeding duodenal varices? A case report and review of the literature.
We report a 78-year-old woman who presented with repeated tarry stools, and having lower duodenal variceal bleeding caused by portal hypertension. Endoscopic therapy had been attempted, but was impossible because the endoscope could not be inserted into the lower duodenum. Thus, the lower duodenal variceal bleeding was treated with balloon-occluded retrograde transvenous obliteration in combination with embolization using microcoils. Complete hemostasis was achieved without complications, and neither the recurrence of varices nor rebleeding has occurred for the last 3 years. A review of the English-language literature reveals only 11 such cases. The world literature is reviewed.


Comprehension of Nonvalvular Atrial Fibrillation and Anticoagulant Adherence in Elderly Patients in a Subcohort Study of the All Nippon Atrial Fibrillation in the Elderly Registry.
In this subcohort study of the ANAFIE (All Nippon Atrial Fibrillation In the Elderly) Registry enrolling >30,000 Japanese elderly (aged ≥75 years) patients with nonvalvular atrial fibrillation (NVAF), we assessed the association between patient comprehension of NVAF and adherence to anticoagulant therapy with clinical outcomes. Data from 1,968 patients evaluated for NVAF comprehension by a questionnaire consisting of 4 key questions, and 2,362 patients who completed the Morisky Medication Adherence Scale-8 questionnaire were analyzed. Overall, NVAF comprehension was low (81.9% had <3 points), and compared with high comprehension (score ≥3), low comprehension (0 points: 42.1%) was associated with poor prognosis, nonsignificantly higher risk of stroke or systemic embolic event (adjusted hazard ratio [aHR] 2.60 [95% confidence interval 0.97 to 6.94, p = 0.057]), all-cause death (aHR 1.71 [0.96 to 3.04, p = 0.069]), and significantly higher risk of net clinical outcome (composite of stroke/systemic embolic events, major bleeding, and all-cause death) (aHR 1.63 [1.04 to 2.54, p = 0.032]). Adherence to anticoagulant therapy assessed by Morisky Medication Adherence Scale-8 was high (64.9% had high adherence; 29.2%, had medium adherence), but compared with high adherence (score 8), low adherence (score <6: 5.9%) was associated with poor prognosis, significantly higher risk of ischemic stroke (aHR 2.95 [1.08 to 8.04, p = 0.035]), all-cause death (aHR 1.93 [1.16 to 3.21, p = 0.011]), and net clinical outcome (aHR 1.75 [1.12 to 2.75, p = 0.015]). Overall, NVAF comprehension and adherence showed a weak correlation to anticoagulant therapy at baseline (correlation coefficient 0.049). In conclusion, low NVAF comprehension and low anticoagulant adherence were associated with poor clinical outcomes in elderly patients with NVAF.


Lactobacillus johnsonii L531 Ameliorates Escherichia coli-Induced Cell Damage via Inhibiting NLRP3 Inflammasome Activity and Promoting ATG5/ATG16L1-Mediated Autophagy in Porcine Mammary Epithelial Cells.
Escherichia coli (E. coli), a main mastitis-causing pathogen in sows, leads to mammary tissue damage. Here, we explored the effects of Lactobacillus johnsonii L531 on attenuating E. coli-induced inflammatory damage in porcine mammary epithelial cells (PMECs). L. johnsonii L531 pretreatment reduced E. coli adhesion to PMECs by competitive exclusion and the production of inhibitory factors and decreased E. coli-induced destruction of cellular morphology and ultrastructure. E. coli induced activation of NLRP3 inflammasome associated with increased expression of NLRP3, ASC, and cleaved caspase-1, however, L. johnsonii L531 inhibited E. coli-induced activation of NLRP3 inflammasome. Up-regulation of interleukin (Il)-1β, Il-6, Il-8, Il-18, tumor necrosis factor alpha, and chemokine Cxcl2 expression after E. coli infection was attenuated by L. johnsonii L531. E. coli infection inhibited autophagy, whereas L. johnsonii L531 reversed the inhibitory effect of E. coli on autophagy by decreasing the expression of autophagic receptor SQSTM1/p62 and increasing the expression of autophagy-related proteins ATG5, ATG16L1, and light chain 3 protein by Western blotting analysis. Our findings suggest that L. johnsonii L531 pretreatment restricts NLRP3 inflammasome activity and induces autophagy through promoting ATG5/ATG16L1-mediated autophagy, thereby protecting against E. coli-induced inflammation and cell damage in PMECs.


Deriving functional safety (ISO 26262) S-parameters for vulnerable road users from national crash data.
Currently, advanced driver assistance systems (ADAS) and automated vehicles (AV) are designed for use in the existing road infrastructure. These partially and fully automated vehicles will be operated in a shared space not only with other vehicles but also with vulnerable road users (VRU). Even though crashes between ADAS equipped vehicles or AV and VRU seem inevitable in such a scenario, functional safety, i.e., the assessment of the quality and safety level of the automation system, plays a crucial role in minimizing the crash frequency and the injury severity. We develop a data-driven approach to injury severity estimation for functional safety, i.e., ISO 26262 S-parameters, for four types of VRU: pedestrians, bicyclists, scooterists, and motorcycle riders. To estimate the S-parameter, the 90th-percentile of the injury severity distribution in the S-scale, a population-based data set (Germany's national data set DESTATIS) is used. Since the description of the injury severity in DESTATIS is not detailed enough for a direct one-to-one mapping to the S-scale, we enhance the level of detail in the population-based data set by using additional information from the German in-depth accident study (GIDAS), an in-depth, size-limited survey of part of the same population. Thus, we are able to transform the 4-level injury scale (uninjured, slightly injures, severely injured, and fatal) of the police reports found in DESTATIS into the three breakpoints of the injury severity scale (ISS) (ISS ≥{4, 9, 16}) which in turn directly translate to the four levels of the S-scale. Furthermore, the ISS ≥9 breakpoint more or less equates to MAIS 3+, the definition of 'severe injury' in nearly all international road safety goals that look beyond fatalities. The derived injury scale transformation can be utilized to translate the injury severities of the police-reported cases to the politically needed MAIS 3+ distribution. Thus, population-based data can be directly used to estimate the proportion of these 'severely injured.' The crashes are analyzed from the perspective of the VRU as well as from the vehicle type involved. We stratified the opposing vehicles by injury mechanism: wrap projection for bonnet type passenger vehicles (BTV), forward projection for box type vehicles like light trucks (LTV), as well as single-vehicle crashes. We cluster the crash data into traffic domains based on the speed limit: shared zone, residential streets, city roads, arterial thoroughfares, rural roads, and autobahn. For each VRU type, injury mechanism, and traffic domain, the S-parameters, i.e., the 90th-percentile of the injury severity measured in S-scale, are calculated with a one-sided 95% confidence level. Exemplary applications of the results are given in the discussion: an evaluation of an AV hitting a crossing pedestrian, an in-lane swerving ADAS system for VRU avoidance, and the rating of the nominal performance of an inflatable helmet for pedestrians.


Aerobic exercise training enhances the in vivo cholesterol trafficking from macrophages to the liver independently of changes in the expression of genes involved in lipid flux in macrophages and aorta.
Regular exercise prevents and regresses atherosclerosis by improving lipid metabolism and antioxidant defenses. Exercise ameliorates the reverse cholesterol transport (RCT), an antiatherogenic system that drives cholesterol from arterial macrophages to the liver for excretion into bile and feces. In this study we analyzed the role of aerobic exercise on the in vivo RCT and expression of genes and proteins involved in lipid flux and inflammation in peritoneal macrophages, aortic arch and liver from wild type mice. Twelve-week-old male mice were divided into sedentary and trained groups. Exercise training was performed in a treadmill (15 m/min, 30 min/day, 5 days/week). Plasma lipids were determined by enzymatic methods and lipoprotein profile by fast protein liquid chromatography. After intraperitoneal injection of J774-macrophages the RCT was assessed by measuring the recovery of (3)H-cholesterol in plasma, feces and liver. The expression of liver receptors was determined by immunoblot, macrophages and aortic mRNAs by qRT-PCR. (14)C-cholesterol efflux mediated by apo A-I and HDL2 and the uptake of (3)H-cholesteryl oleoyl ether ((3)H-COE)-acetylated-LDL were determined in macrophages isolated from sedentary and trained animals 48 h after the last exercise session. Body weight, plasma lipids, lipoprotein profile, glucose and blood pressure were not modified by exercise training. A greater amount of (3)H-cholesterol was recovered in plasma (24 h and 48 h) and liver (48 h) from trained animals in comparison to sedentary. No difference was found in (3)H-cholesterol excreted in feces between trained and sedentary mice. The hepatic expression of scavenger receptor class B type I (SR-BI) and LDL receptor (B-E) was enhanced by exercise. We observed 2.8 and 1.7 fold rise, respectively, in LXR and Cyp7a mRNA in the liver of trained as compared to sedentary mice. Macrophage and aortic expression of genes involved in lipid efflux was not systematically changed by physical exercise. In agreement, (14)C-cholesterol efflux and uptake of (3)H-COE-acetylated-LDL by macrophages was similar between sedentary and trained animals. Aerobic exercise in vivo accelerates the traffic of cholesterol from macrophages to the liver contributing to prevention and regression of atherosclerosis, independently of changes in macrophage and aorta gene expression.


Are short press-fit stems comparable to standard-length cemented stems in reverse shoulder arthroplasty? A prospective, randomized clinical trial.
The literature comparing humeral implants in reverse shoulder arthroplasty is sparse. With minimal supporting literature, there has been a trend away from standard-length cemented humeral implants to press-fit stems and, recently, to shorter-stem implants. It is known that early implant migration, within the first 2 years postoperatively, is predictive of later implant loosening and possible revision surgery. Therefore, the purpose of this study was to compare clinical outcomes and implant migration between cemented standard-length humeral stems and press-fit short stems using model-based radiostereometric analysis. After a power analysis, 41 shoulders were prospectively randomized to receive either a cemented standard-length or press-fit short humeral stem for primary reverse shoulder arthroplasty between July 2017 and June 2019. Following surgery, participants were imaged with stereo radiographs acquired at 6 weeks (baseline), 3 months, 6 months, 1 year, and 2 years. Migration of the humeral stem at each time point was compared with baseline, with differences in migration between cohorts assessed using a mixed-effects model with the Bonferroni test for multiple comparisons. Patient-reported outcome measures (Subjective Shoulder Value; American Shoulder and Elbow Surgeons shoulder score; Simple Shoulder Test score; Disabilities of the Arm, Shoulder and Hand score; and Constant score) were also compared. At 6 months (P = .025), 1 year (P = .004), and 2 years (P = .001) postoperatively, press-fit short stems migrated significantly more than cemented stems along the superior-inferior translation axis; in addition, they showed greater total translation at 2 years (P = .003). Mean total translation (± standard deviation) at 2 years was 0.4 ± 0.2 mm and 1.0 ± 1.1 mm for the cemented and press-fit cohorts, respectively. Mean migration between the 1- and 2-year time points was minimal for both stem fixation groups along all axes (<0.1 mm and 0.6°). There was no difference in active range of motion, pain, or validated outcome measures between the cohorts at 2 years (P ≥ .170). This randomized clinical trial shows that press-fit short humeral stems subside substantially more than standard-length cemented stems but ultimately achieve stability from 1 year through 2 years. Conversely, no significant differences were observed in clinical outcomes between cohorts.


Effects of various inhibitors on platelet activation induced by TP 82, a CD 9 monoclonal antibody.
TP 82, a monoclonal antibody against CD 9 antigen, induced human platelet activation at concentrations higher than 0.4 microgram/mL in terms of aggregation, release of intracellular granule contents, production of arachidonic acid metabolites, and elevation of the intracellular Ca2+ concentration. The effects of a competitive inhibitor of ADP, acetylsalicylic acid, EGTA, and GRGDSP which blocks fibrinogen binding to IIb/IIIa complex suggested that each of released ADP, thromboxane A2, extracellular Ca2+, and close cell contact acts together to potentiate platelet activation induced by TP 82. While each of these inhibitors severely suppressed platelet activation induced by lower concentrations of the antibody (less than or equal to 0.8 microgram/mL), that induced by higher concentrations (greater than or equal to 3.2 micrograms/mL) was only partially blocked. Intracellular Ca2+ elevation was totally dependent upon the production of thromboxane A2, regardless of the antibody concentrations.


Risk factors for nonclosure of defunctioning stoma and stoma-related complications among low rectal cancer patients after sphincter-preserving surgery.
Defunctioning stoma is widely used to reduce anastomotic complications in rectal cancer surgery. However, the complications of stoma and stoma reversal surgery should not be underestimated. Furthermore, in some patients, stoma reversal failed. Here, we investigated the complications of defunctioning stoma surgery and subsequent reversal surgery and identify risk factors associated with the failure of getting stoma reversed. In total, 154 patients who simultaneously underwent low anterior resection and defunctioning stoma were reviewed. Patients were divided into two groups according to whether their stoma got reversed or not. The reasons that patients received defunctioning stoma and experienced stoma-related complications and the risk factors for failing to get stoma reversed were analysed. The mean follow-up time was 47.54 (range 4.0-164.0) months. During follow-up, 19.5% of the patients suffered stoma-related long-term complications. Only 79 (51.3%) patients had their stomas reversed. The morbidity of complications after reversal surgery was 45.6%, and these mainly consisted of incision-related complications. Multivariate analyses showed that pre-treatment comorbidity (HR = 3.17, 95% CI 1.27-7.96, P = 0.014), postoperative TNM stage (HR = 2.55, 95% CI 1.05-6.18, P = 0.038), neoadjuvant therapy (HR = 2.75, 95% CI 1.07-7.05, P = 0.036), anastomosis-related complications (HR = 4.52, 95% CI 1.81-11.29, P = 0.001), and disease recurrence (HR = 24.83, 95% CI 2.90-213.06, P = 0.003) were significant independent risk factors for a defunctioning stoma to be permanent. Defunctioning stoma is an effective method to reduce symptomatic anastomotic leakage, but the stoma itself and its reversal procedure are associated with high morbidity of complications, and many defunctioning stomas eventually become permanent. Therefore, surgeons should carefully assess preoperatively and perform defunctioning stomas in very high risk patients. In addition, doctors should perform stoma reversal surgery more actively to prevent temporary stomas from becoming permanent.


[Translocated gastroduodenal anastomosis in surgical treatment of penetrating duodenal ulcer].
The method of operative treatment of complicated duodenal ulcer disease consisting gastroduodenostomy, translocated by 3-4 cm medially and lower from the ulcer crater and strengthened by a spur on a small curvature side.


[Phenotypic and genotypic analysis of a pedigree affected with hereditary protein C deficiency due to heterozygous deletional mutation of PROC gene].
To analyze the phenotype and genetic variants of a pedigree affected with hereditary protein C (PC) deficiency. The protein C activity (PC:A) of the proband and her family members (a four-generation pedigree including 11 individuals) were tested by chromogenic substrate method, and the protein C antigen (PC:Ag) was detected with an enzyme-linked immunosorbent assay(ELISA). The 9 exons and flanking sequences of the protein C (PROC) gene were amplified by PCR and directly sequenced. Suspected mutation was validated by clone sequencing and in other members of the family. MutationTaster and ClustalX-2.1-win was used to analyze the pathogenicity and conservation of the mutation site,respectively. Three-dimentional protein model and amino acids interaction were analyzed with Swiss-PdbViewer software. The PC: A and PC: Ag of the proband were decreased to 46% (reference range: 70%-130%) and 50% (referencerange:70%-140%), respectively. Her grandmother,aunt, cousin and younger brother also showed declined PC:A and PC:Ag by approximately 50%. Genetic analysis revealed that the above individuals have all carried a deletional mutation c.1212-1212delG (p.Met364TrpfsX15) in exon 9 of the PROC gene which can cause replacement of Methionine at position 364 by Tryptophan and alteration of 15 downstream amino acids, and produce a premature stop codon at position 378. The score of MutationTaster was 1.000, indicating that the variant is pathogenic. Conservative analysis showed that the 15 altered amino acids are located in a conserved region across nine homologous species. Protein model analysis showed that the mutation has disrupted a catalytic domain of protein C thereby affected its function. The heterozygous c.1212-1212delG deletional mutation in exon 9 of the PROC gene, which was unreported previously,probably accounts for the decrease of PC:A and PC:Ag in this pedigree.


Behavioral responses to riparian and anthropogenic edge effects in mantled howler monkeys (Alouatta palliata) in a disturbed riverine forest.
Fragmented forests contain natural edges, including riparian zones, and anthropogenic edges. Edges generally have lower plant density and fewer large trees than forest interior. Riparian edges, however, contain gap-specialist trees yielding leaves with high protein content, providing primates with important resources. We examined mantled howler monkeys' behavioral responses to riparian and anthropogenic edges at La Suerte Biological Research Station (LSBRS), Costa Rica. We predicted the monkeys would spend more time resting and feeding and less time traveling, and be less spatially cohesive, in both anthropogenic and riparian edges compared to forest interior due to lower resource abundance in edges, and in anthropogenic compared to riparian edge due to higher leaf quality in riparian zones. From 2017 to 2020, we collected data across forest zones on activity and spatial cohesion patterns via focal sampling, recording data every 2 min. Howler monkeys were significantly more likely to rest and significantly less likely to travel in both anthropogenic and riparian edges compared to forest interior; however, there were no differences between these edge types. There were significantly more monkeys within a 5-m radius of focal subjects in both anthropogenic and riparian edges compared to forest interior, but no differences between these edge types. While prior research found no differences across zones when only anthropogenic edge and forest interior were compared, results of this study demonstrate that howler monkeys at LSBRS modify their activity patterns in anthropogenic and riparian edge zones compared to forest interior, highlighting the importance of focusing on both natural and anthropogenic edge zones to fully understand primates' behavioral responses in fragmented landscapes.


Regional Patterns of Elevated Alpha and High-Frequency Electroencephalographic Activity during Nonrapid Eye Movement Sleep in Chronic Insomnia: A Pilot Study.
To examine nonrapid eye movement (NREM) sleep in insomnia using high-density electroencephalography (EEG). All-night sleep recordings with 256 channel high-density EEG were analyzed for 8 insomnia subjects (5 females) and 8 sex and age-matched controls without sleep complaints. Spectral analyses were conducted using unpaired t-tests and topographical differences between groups were assessed using statistical non-parametric mapping. Five minute segments of deep NREM sleep were further analyzed using sLORETA cortical source imaging. The initial topographic analysis of all-night NREM sleep EEG revealed that insomnia subjects had more high-frequency EEG activity (> 16 Hz) compared to good sleeping controls and that the difference between groups was widespread across the scalp. In addition, the analysis also showed that there was a more circumscribed difference in theta (4-8 Hz) and alpha (8-12 Hz) power bands between groups. When deep NREM sleep (N3) was examined separately, the high-frequency difference between groups diminished, whereas the higher regional alpha activity in insomnia subjects persisted. Source imaging analysis demonstrated that sensory and sensorimotor cortical areas consistently exhibited elevated levels of alpha activity during deep NREM sleep in insomnia subjects relative to good sleeping controls. These results suggest that even during the deepest stage of sleep, sensory and sensorimotor areas in insomnia subjects may still be relatively active compared to control subjects and to the rest of the sleeping brain.


Deep learning radiomics model based on breast ultrasound video to predict HER2 expression status.
The detection of human epidermal growth factor receptor 2 (HER2) expression status is essential to determining the chemotherapy regimen for breast cancer patients and to improving their prognosis. We developed a deep learning radiomics (DLR) model combining time-frequency domain features of ultrasound (US) video of breast lesions with clinical parameters for predicting HER2 expression status. Data for this research was obtained from 807 breast cancer patients who visited from February 2019 to July 2020. Ultimately, 445 patients were included in the study. Pre-operative breast ultrasound examination videos were collected and split into a training set and a test set. Building a training set of DLR models combining time-frequency domain features and clinical features of ultrasound video of breast lesions based on the training set data to predict HER2 expression status. Test the performance of the model using test set data. The final models integrated with different classifiers are compared, and the best performing model is finally selected. The best diagnostic performance in predicting HER2 expression status is provided by an Extreme Gradient Boosting (XGBoost)-based time-frequency domain feature classifier combined with a logistic regression (LR)-based clinical parameter classifier of clinical parameters combined DLR, particularly with a high specificity of 0.917. The area under the receiver operating characteristic curve (AUC) for the test cohort was 0.810. Our study provides a non-invasive imaging biomarker to predict HER2 expression status in breast cancer patients.


Progressive leukoencephalopathy with intracranial calcification, congenital deafness, and developmental deterioration.
We report on a 12-year-old male with a unique cerebral white matter disease. His initial symptoms were congenital hearing loss and multiple intracranial calcifications on head CT. He developed severe intellectual disability and epilepsy. MRI showed signal abnormalities in the posterior limbs of the internal capsules, thalami, and cerebral white matter. The abnormalities were progressive over time. The neuropathology revealed diffuse and severe disruption of myelin and axons of the cerebral white matter and cerebrospinal tracts. We performed various metabolic examinations, detailed pathological investigations and genetic analyses, but could not identify the cause. To our knowledge his clinical course has not been described in the literature.


The relation between otoacoustic emissions and the broadening of the auditory filter for higher levels.
The active behaviour of outer hair cells (OHCs) is often used to explain two phenomena, namely otoacoustic emissions (OAEs) and the level dependence of auditory filters. Correlations between these two phenomena may contribute to the evidence of these hypotheses. In this study auditory filters were calculated from probe thresholds in notched-noise maskers over a range of at least 25 dB. Further. transient evoked otoacoustic emissions (TEOAEs) were measured at several stimulation levels. Ten normal-hearing and nine hearing-impaired subjects were tested. A linear increase of the width of the auditory filter with 2.2 dB/Hz was found up to a specific saturation level. The group of selected hearing-impaired subjects with mild hearing loss showed no wider than normal auditory filters. As expected, the increase of the width of the auditory filter correlated positively with the level of TEOAEs for click intensities of about 80 dB peak SPL. However, for subjects with TEOAEs wider auditory filters at a masker level of 65 dB/Hz were found for subjects with larger TEOAEs. This result cannot be explained by a model by which the cochlea shows an active behaviour for lower stimulation levels, influencing both the TEOAE levels and the filter skirts, and a passive behaviour for higher stimulation levels.


[Critical comments on a case history "a death case involving tilidine" (author's transl)].
The author looks critically at the description of a suicide case involving a barbiturate dose that could not be determined exactly and doses of hydroxyzine and tilidine. Drugs with a short and a medium short duration of action obviously had the greatest effect. There was no description of an investigation of the gastric contents. The concentration of barbiturates in the blood alone was sufficient to cause death. The deceased also took hydroxyzine, and then finally 750 mg tilidine in capsule form. Tilidine's action is relatively slow in onset. The author discusses tilidine's possible contribution to the cause of death and comes to a different conclusion from the authors of the case report, especially as regards the key words "Tilidine--Intoxication". The authors of the case report ought to have called it "A Death Case Involving Barbiturates, Hydroxyzine and Tilidine" rather than giving is such a suggestive title as "A Death Case Involving Tildine". This would have been a more accurate representation of the facts and would have assisted the reader to grasp the complex toxicological situation more clearly.


Oxidative bridgehead functionalization of (4 + 3) cycloadducts obtained from oxidopyridinium ions.
Treatment of selected (4 + 3) cycloadducts derived from oxidopyridinium ions with N-iodosuccinimide (NIS) in hexafluoroisopropanol (HFIP) resulted in the formation of bridgehead ethers via a net oxidative C-H activation.