Nicorandil induced penile ulceration.
We report the unusual complication of penile ulceration caused by Nicorandil, a nicotinamide ester used in the treatment of symptomatic angina pectoris.


Stark and field-born resonances of an open square well in a static external electric field.
The resonance positions, widths (inverse lifetimes), and wave functions of a square-potential well in the presence of a static electric field are calculated by using the outgoing boundary conditions. Our study concentrates on the field-born states that, unlike the well-known Stark resonances, are not associated with the field-free bound states. The effect of a lower cutoff of the static field on the field-born resonance phenomena is studied. The feasibility of experiments, where the isolated long-lived and overlapping short-lived field-born resonances can be explored, is discussed.


Rare sex or out of reach equilibrium? The dynamics of F IS in partially clonal organisms.
Partially clonal organisms are very common in nature, yet the influence of partial asexuality on the temporal dynamics of genetic diversity remains poorly understood. Mathematical models accounting for clonality predict deviations only for extremely rare sex and only towards mean inbreeding coefficient [Formula: see text]. Yet in partially clonal species, both F IS < 0 and F IS > 0 are frequently observed also in populations where there is evidence for a significant amount of sexual reproduction. Here, we studied the joint effects of partial clonality, mutation and genetic drift with a state-and-time discrete Markov chain model to describe the dynamics of F IS over time under increasing rates of clonality. Results of the mathematical model and simulations show that partial clonality slows down the asymptotic convergence to F IS = 0. Thus, although clonality alone does not lead to departures from Hardy-Weinberg expectations once reached the final equilibrium state, both negative and positive F IS values can arise transiently even at intermediate rates of clonality. More importantly, such "transient" departures from Hardy Weinberg proportions may last long as clonality tunes up the temporal variation of F IS and reduces its rate of change over time, leading to a hyperbolic increase of the maximal time needed to reach the final mean [Formula: see text] value expected at equilibrium. Our results argue for a dynamical interpretation of F IS in clonal populations. Negative values cannot be interpreted as unequivocal evidence for extremely scarce sex but also as intermediate rates of clonality in finite populations. Complementary observations (e.g. frequency distribution of multiloci genotypes, population history) or time series data may help to discriminate between different possible conclusions on the extent of clonality when mean [Formula: see text] values deviating from zero and/or a large variation of F IS over loci are observed.


Diphtheria immunization rates and the effect of several sociodemographic factors on immunization of children in eastern Turkey.
One of the aims of the World Health Organization is to eliminate diphtheria in all countries. Thus, it is important to achieve a high level of childhood immunization. The present study was performed to determine the level of child immunization against diphtheria and the effect of several sociodemographic factors on immunization of children aged 0-6 years. Using the cluster-sampling method, 767 healthy children were selected at random from three provinces in eastern Turkey. Children were categorized as completely vaccinated, incompletely vaccinated, unvaccinated or vaccination status unknown. If the child had no immunization card, he/she was categorized as vaccination status unknown. Of the 767 children, 72.3% were completely vaccinated, 18.3% were incompletely vaccinated and 5.7% were not vaccinated. Vaccination status was unknown for 3.7% of children. As the age of the children increased, the proportion of completely vaccinated children increased and the proportion of non-vaccinated and incompletely vaccinated children decreased. The vaccination rates increased in parallel with the education level of the parents. While the vaccination rate was significantly correlated with the socioeconomic level of the families, it was inversely correlated with sibling number. The results of the present study show that the immunization status necessary for the elimination of diphtheria has not yet been reached in eastern Turkey. In immunization programs for children in eastern Turkey, priority should be given to increasing primary immunization levels to 90-95% with three or more doses of diphtheria toxoid.


Effect of zolpidem on sleep architecture and its next-morning residual effect in insomniac patients: a randomized crossover comparative study with brotizolam.
This study was conducted to determine the effect of zolpidem (ZOL) 10 mg orally on the sleep architecture and the next-morning residual effect in patients with non-organic insomnia (ICD-10) as compared to the effect of brotizolam (BTM) 0.25 mg orally, a widely used short-acting benzodiazepine (BZD) hypnotic in Japan, in a randomized, crossover comparative study. Fourteen patients with non-organic insomnia (3 males and 11 females; mean age of 54.9+/-S.D. 8.9 years). First three nights with placebo, middle three nights with either ZOL 10 mg or BTM 0.25 mg, and last three nights again with placebo in each session (a total of two sessions). Primary endpoints were polysomnography findings of sleep stages, sleep parameters, and sleep latency (SL) in the morning to examine calculable sleepiness as a residual effect. Secondary endpoint was sleep quality assessed by self-assessment questionnaire. At 150 min after Tmax, both ZOL and BTM significantly increased stage 2 (S2), and ZOL showed significantly longer slow wave sleep (SWS; stage 3+4) as compared to BTM. Stage wake was significantly increased by ZOL at the first withdrawal night and by BTM at the second withdrawal night. ZOL did not affect SL after rising, whereas BTM showed significantly shorter SL. Both drugs reduced the number of nocturnal awakenings and improved subjective sleep quality. The common adverse drug reaction (ADR) was sleepiness (3 patients) in each treatment. All events were mild. No serious adverse events occurred. ZOL is as effective as BTM in improving subjective sleep quality in patients with psychophysiological insomnia (PPI). ZOL has advantages over BTM in having a unique profile of increasing SWS with less next-morning residual effect.


Effect of image registration on longitudinal analysis of retinal nerve fiber layer thickness of non-human primates using Optical Coherence Tomography (OCT).
In this paper we determined the benefits of image registration on estimating longitudinal retinal nerve fiber layer thickness (RNFLT) changes. RNFLT maps around the optic nerve head (ONH) of healthy primate eyes were measured using Optical Coherence Tomography (OCT) weekly for 30 weeks. One automatic algorithm based on mutual information (MI) and the other semi-automatic algorithm based on log-polar transform cross-correlation using manually segmented blood vessels (LPCC_MSBV), were used to register retinal maps longitudinally. We compared the precision and recall between manually segmented image pairs for the two algorithms using a linear mixed effects model. We found that the precision calculated between manually segmented image pairs following registration by LPCC_MSBV algorithm is significantly better than the one following registration by MI algorithm (p < <0.0001). Trend of the all-rings and temporal, superior, nasal and inferior (TSNI) quadrants average of RNFLT over time in healthy primate eyes are not affected by registration. RNFLT of clock hours 1, 2, and 10 showed significant change over 30 weeks (p = 0.0058, 0.0054, and 0.0298 for clock hours 1, 2 and 10 respectively) without registration, but stayed constant over time with registration. The LPCC_MSBV provides better registration of RNFLT maps recorded on different dates than the automatic MI algorithm. Registration of RNFLT maps can improve clinical analysis of glaucoma progression.


Standardization of an indirect PTA-ELISA for detection ofFusarium spp. in infected grains.
Plant pathogenic fungi of the genusFusarium cause agriculturally important diseases of small grain cereals and maize. Especially the contamination of grains with the mycotoxin deoxynivalenol (DON) is harmful for animals and humans. For quantification of the severity ofFusarium head blight (FHB) in resistance evaluation and selection of cereals a fast, economical and reliable method is essential. Immunological methods appear to be particularly suitable for such an assessment. The results demonstrate that a selected antiserum was appropriate for the detection ofFusarium-exoantigens (ExoAg) in cereal grains by an indirect ELISA-format, although a discrimination between variousFusarium-species was not possible. The polyclonal antibody detection system was optimized for different parameters and a standard test protocol was elaborated.


Impact of dry hydrogen peroxide on hospital-acquired infection at a pediatric oncology hospital.
This study aims to describe the effect of Dry Hydrogen Peroxide (DHP), as an adjunct to environmental cleaning and disinfection, on the incidence of hospital-acquired infections (HAIs) at Unidad Nacional de Oncologia Pediatrica (UNOP) in Guatemala City, Guatemala. A retrospective study of all HAI data from the hospital's surveillance system, which follows Centers for Disease Control and Prevention (CDC) protocols, was conducted from January 2019 to November 2020. DHP was installed in all Pediatric Intensive Care Unit (PICU) rooms in January 2020, but nowhere else in the hospital, including the Intermediate Care Unit (IMCU). There were 189 HAI cases during the study period, with 173 occurring in either the PICU or IMCU. A statistically significant decrease in HAI incidence rates occurred in the PICU in 2020 compared to 2019 (P = .028), including Clostridiodes-associated gastroenteritis (P = .048). Logistic multivariate regression yielded a significant association between DHP exposure and reduced odds of developing an HAI during the study (OR = 0.3857, P = .029). The use of DHP as an adjunct technology for environmental cleaning and disinfection contributed to the reduction in HAIs in the PICU. Our study highlights the value of such an approach as an addition to manual cleaning to decrease the risk of infection from environmental contamination.


Further testing of a family nursing instrument (FAFHES).
Cardiac illness in one family member affects the well-being and health of the whole family. When a family member falls ill, life may change for the whole family in many ways. Family members expect nursing staff to provide more support when their family situation changes. To describe further development and testing of a family nursing instrument for assessing the association between social support for the family of an adult cardiac patient and family functioning and perceived family health. The study was conducted in two university hospitals and in two central hospitals in Finland. Questionnaires were given to family members of heart patients. Patients themselves defined who their closest adult relative was. Data were collected from family members of 509 heart patients. Good internal reliability in this further testing of a new instrument was demonstrated. Principal component analysis (PCA) with varimax rotation was performed in each of the three total scales: family functioning, family health and social support. PCA supported the previously proposed theoretical framework. A final scale consisted of 62 items. All the total scales and subscales had acceptable validity and reliability, alpha coefficients ranged from .76 to .98. The Family Functioning, Health and Social Support (FAFHES) provides a reliable and valid instrument when the investigator wishes to measure social support associated with family functioning and the health of families of heart patients.


Bioactive and immunoreactive FSH in serum of normal and oligospermic men.
In men suffering from idiopathic oligospermia and azoospermia the hypothesis was tested that decreased spermatozoa production could be due in part to inadequate hormonal stimulation of spermatogenesis. In 53 healthy male subjects with normal spermatozoa production (n = 10), varying degrees of oligospermia (n = 40), and azoospermia (n = 3), serum immunoreactive LH, testosterone (T), and oestradiol (E2), and immunoreactive and bioactive FSH concentrations were determined. FSH bioactivity was estimated using the rat granulosa cell aromatase bioassay. Mean LH, T, and E2 levels were similar in the control group (spermatozoa concentration greater than 40 x 10(6)/ml) compared with men exhibiting mild (10-20 x 10(6)/ml), moderate (5-10 x 10(6)/ml), or severe oligospermia (1-5 x 10(6)/ml), and in the azoospermia group. An inverse correlation was found between immunoreactive FSH levels and spermatozoa concentration (P less than 0.05), with elevated levels (twofold increase) of FSH in the combined severe oligospermia and azoospermia (P less than 0.01) groups. Moreover, augmented (P less than 0.01) bioactive FSH levels were also observed in this group of patients. The mean bioactive to immunoreactive FSH ratio was also negatively correlated with sperm counts (P less than 0.005). In addition, T/LH ratios were inversely correlated with immunoreactive (P less than 0.05) and bioactive (P less than 0.05) FSH, which may indicate that altered Leydig cell function is involved in the augmented secretion of FSH. The data presented in this study indicate that immunoreactive FSH, as measured in oligospermia and azoospermia, does not exhibit decreased bioactivity.


Effect of different drying techniques on drying kinetics, nutritional components, antioxidant capacity, physical properties and microstructure of edamame.
The present study aimed to investigate the effect of hot air drying (HD), microwave rolling-bed drying (MRD), hot air microwave rolling-bed drying (HMRD), pulse-spouted microwave vacuum drying (PSMVD) and freeze-drying (FD) on the drying characteristics, quality properties and microstructure of edamame. Six models were fitted the drying curves, and quality attributes were analyzed. Results indicated that Page model was the most suited model for edamame drying. Compared with HD, MRD and HMRD improved the quality of edamame and decreased the drying time by 45.59% and 36.03% respectively. The FD and PSMVD possessed higher rehydration ability, nutrient retention and antioxidant capacity compared with other methods. Moreover, PSMVD products showed a crunchy texture, the less color change and the shortest drying time (70 min). Microscopy images demonstrated a distinct porous structure in PSMVD, which facilitated the moisture transfer. Overall, PSMVD is a promising dehydration method for obtaining high value-added edamame products.


Evidence for an internal pool of nucleoside transporters in mammalian reticulocytes.
Comparisons of the site specific binding of nitrobenzylthioinosine (NBMPR) to intact and lysed red cells from various mammalian and avian species suggest the presence of a cytoplasmic pool of nucleoside transporters. In some species the cytoplasmic pool is about 50% of the total (mouse). On the average, the cytoplasmic pool is approx. 20% of the surface pool of NBMPR-binding sites. In sheep reticulocytes, both pools disappear in an energy-dependent manner during the maturation of the reticulocyte in vitro.


[Context analysis of polynucleotide sequences. Methods of detecting non-random repeats. I. Direct repeats in genes of beta-, beta'-, sigma subunits of Escherichia coli RNA-polymerase].
A new method of contextual analysis of polynucleotide sequences in developed. The method finds nonrandom repeats in the sequences of N bases in length with given nucleotide frequencies. The coding regions of genes specifying beta-, beta'-, sigma-subunits of E. coli RNA polymerase were analyzed. The high content of short repeats was found to correspond to the secondary structure of globular proteins coded by the genes. The possible evolutionary role of the nonrandom direct repeats in coding regions of genes is discussed.


Effectiveness and Safety of Subcutaneous Rituximab for Patients With Gastric MALT Lymphoma: A Case-Control Comparison With Intravenous Rituximab.
Rituximab is a standard treatment for gastric mucosa-associated lymphoid tissue (MALT) lymphoma (GML). We sought to compare the effectiveness and safety of subcutaneous and intravenous rituximab in a retrospective case-control study. All consecutive patients with GML treated with subcutaneous rituximab between January 2017 and December 2018 were included and compared to 3 matched control patients (based on Ann Arbor classification, presence of t(11;18) translocation, history of treatment, and type of current treatment) treated with intravenous rituximab between January 2000 and December 2018. Patients with t(11;18) translocation were treated with rituximab in combination with chlorambucil; the other patients were treated with rituximab alone. Effectiveness was assessed at week 52, and safety was assessed through weeks 0 to 52 and compared by the chi-square test. Twenty-five patients were included in the subcutaneous rituximab group and 75 in the intravenous group. There was no difference between the groups in complete remission (78% vs. 76%, P = .99) or overall response rates (91% vs. 89%, P = .99) at week 52. Safety profiles were similar in both groups, with a significant decrease in postinduction grade 2 injection-related reactions and outpatient hospital length of stay in the subcutaneous rituximab group. In a small case-control study, we did not find any difference in the effectiveness or safety profiles between subcutaneously and intravenously delivered rituximab for the treatment of patients with GML. We found a decrease in postinduction grade 2 injection-related reactions and outpatient hospital length of stay in the subcutaneous rituximab group.


New acetylphenol-based acyl thioureas broaden the scope of drug candidates for urease inhibition: synthesis, in vitro screening and in silico analysis.
Helicobacter pylori urease remains a validated drug target for the eradication of pervasive chronic stomach infection that leads to severe human health diseases such as gastritis and stomach cancer. The increased failure of current treatment protocols because of resistance to broadband antibiotics, severe side effects and low compliance underscore the need for a targeted eradication therapy. Therefore, in the present research, we have developed a new series of acetylphenol-based acyl thioureas that can potentially provide a new template for drug candidates to inhibit urease enzyme. Newly synthesized compounds 7a-j were evaluated for urease inhibitory strength using thiourea as a positive control. In vitro inhibitory results revealed that all the tested compounds were significantly potent than the standard drug. The most active lead 7f competitively inhibited the enzyme and displayed an IC50 value of 0.054 ± 0.002 μM, a ~413-fold strong inhibitory potential than thiourea (IC50 = 22.3 ± 0.031 μM). Various insightful structure-activity relationships were developed showing the key structural requirements for potent inhibitory effects. Molecular docking analysis of 7f inside the active pocket of urease suggested several important interactions with amino acid residues such as ILE411, MET637, ARG439, GLN635, ALA636 and ALA440. Finally, pharmacokinetic properties suggested that the tested derivatives are safe to develop as low-molecular-weight drugs to treat ureolytic bacterial infections.


[Ilio-ureteral fistula: a life-threatening complication of an iliac Candida-infected pseudoaneurysm. A case report].
Arterio-ureteral fistula is a rare condition difficult to diagnose. The usual presentation associates acute paroxysmal hematuria with well-identified history and risk factors. We report the case of an 84-year-old man with a life-threatening complication of an ilio-ureteral fistula complicating an anastomotic iliac pseudoaneurysm after prothetic iliofemoral surgery, due to a fungic infection by Candida. After reporting the clinical case and the emergency surgical treatment, we present a review of the literature.


A familial case of MYH9 gene mutation associated with multiple functional and structural platelet abnormalities.
Mutations in the MYH9 gene result in macrothrombocytopenia often associated with hemorrhages. Here, we studied the function and structure of platelets in three family members with a heterozygous mutation R1933X in the MYH9 gene, characteristic of closely related disorders known as the May-Hegglin anomaly and Sebastian syndrome. The examination included complete blood count, blood smear microscopy, platelet flow cytometry (expression of P-selectin and active integrin αIIbβ3 before and after activation), the kinetics of platelet-driven contraction (retraction) of blood clots, as well as scanning/transmission electron microscopy of platelets. Despite severe thrombocytopenia ranging (36-86) × 109/l, none of the patients had hemorrhages at the time of examination, although they had a history of heavy menstruation, spontaneous ecchymosis, and postpartum hemorrhage. Flow cytometry showed background platelet activation, revealed by overexpression of P-selectin and active αIIbβ3 integrin above normal levels. After TRAP-induced stimulation, the fractions of platelets expressing P-selectin in the proband and her sister were below normal response, indicating partial platelet refractoriness. The initiation of clot contraction was delayed. Electron microscopy revealed giant platelets with multiple filopodia and fusion of α-granules with dilated open canalicular system, containing filamentous and vesicular inclusions. The novel concept implies that the R1933X mutation in the MYH9 gene is associated not only with thrombocytopenia, but also with qualitative structural and functional defects in platelets. Platelet dysfunction includes impaired contractility, which can disrupt the compaction of hemostatic clots, making the clots weak and permeable, therefore predisposing patients with MYH9 gene mutations to the hemorrhagic phenotype.


Inactivation of biohazards in healthcare wastewater by E-Beam and Gamma irradiation: a comparative study.
The main objective of this study is to evaluate the effect of irradiation by Gamma rays and Electron Beam (E-Beam) on naturally occurring microorganisms shed in healthcare wastewater issued from multi-specialties hospital. We examined the susceptibility of naturally occurring total indicator bacteriophages towards Gamma rays and E-Beam irradiation to evaluate their appropriateness as viral indicators for healthcare wastewater quality control. Results showed that healthcare wastewater is a rich matrix containing bacteriophages surrogates of pathogenic waterborne viruses (4.5 Log10 PFU/100 mL for SOMCPH and 2.3 Log10 PFU/100 mL for FRNAPH), antibiotic resistant bacteria (Mean concentrations from 2.3 to 5.5 Log10 CFU/100 mL), molds and yeasts (2.7 Log10 CFU/100 mL), and spores of Clostridium perfringens (Mean concentration of 3.3 Log10 CFU/100 mL). After E-Beam irradiation, naturally occurring bacteria in healthcare wastewater showed lower resistance patterns (D10 values ranging between 0.21 ± 0.005 and 0.59 ± 0.005) compared to those obtained after Gamma irradiation (D10 values ranging between 0.25 ± 0.015 and 0.70 ± 0.0001). Spores of Clostridium perfringens were the most resistant assayed microbes either after E-Beam (D10 values of 3.74 ± 0.005) or Gamma irradiation (D10 values of 4.77 ± 0.025) of collected samples. According to inactivation patterns, a dose of 10 kGy was sufficient for a complete inactivation of spores. Bacteriophages isolated from healthcare wastewater showed the same resistance patterns as those previously obtained in urban treated sewage and were inactivated using higher doses than waterborne bacteria (D10 values of SOMCPH 1.46 ± 0.057; D10 values of FRNAPH 1.03 ± 0.057). Their resistance to irradiation treatment in such complex matrix corroborates their use to survey the viral quality of healthcare wastewater before their discharge in the urban sanitation network. D10 value analysis showed that bacteria and bacteriophages inactivation by E-Beam irradiation required lower doses than those required for their inactivation using Gamma rays. According to inactivation patterns, a dose of 7 kGy was sufficient for total inactivation of both pathogenic bacteria and viruses. Thus, E-Beam irradiation seems to be an efficient physical pre-treatment process for healthcare wastewater treatment prior to its discharge in urban sanitation system to ensure compliance with environmental standards and protect public health.


The evaluation of the urban parks in Konya province in terms of quality, sufficiency, maintenance, and growth rate.
Nowadays, the understanding of physically, socially, and visually sufficient and high-standard outdoor arrangements has begun to appear. The most important ones among this kind of spaces are urban parks which contain many recreational opportunities and facilities together. The aim of this study is to identify the current situation of the urban parks in Konya province and the facilities in the parks in terms of quality, sufficiency, growth rate, and maintenance. The second purpose of the study is to obtain information about the park users' evaluations of the park officers within the context of park visits and information sources of the users related to the parks. Within the context of the study, the questionnaires were conducted by face-to-face interviews with 494 park users. The urban parks in Konya province were evaluated by the park users in terms of quality, sufficiency, maintenance, and growth rate criteria. While 44.1% of the users evaluated the parks as "good" in terms of quality, 4.7% of the users stated that the quality of the parks was "bad." Considering the sufficiency of the urban parks, the findings represent that majority of the users identified the parks as sufficient and 27.9% of them identified insufficient. 44.1% of the users stated that the parks were well maintained and 10.1% considered the parks were badly maintained. The growth rate of the urban parks in Konya was described as "fast" by 48.6% of the users and as "normal" by 29.8% of the users.


Irritability rather than depression during interferon treatment is linked to increased tryptophan catabolism.
Treatment with recombinant interferon is associated with high rates of psychiatric comorbidity. We investigated the relation between catabolism of the essential amino acid tryptophan, being rate-limiting of peripheral and cerebral serotonin formation, and psychiatric symptoms in patients undergoing combination treatment with interferon-alpha and ribavirin. Eighteen patients with viral hepatitis C who received interferon were included. A psychiatrist screened patients before and while on interferon-alpha treatment for 2 months, using a structured diagnostic interview. Fasting plasma tryptophan and platelet serotonin levels were measured at each visit. At baseline no evident psychopathology was observed. After 2 months of interferon treatment, 10 patients experienced increased irritability. No other structural psychopathology was observed. Decreased plasma tryptophan level correlated with the presence of irritability (p = .047). Platelet serotonin levels were found to be decreased during treatment (p = .002). Aggressive impulse dysregulation is highly prevalent in patients receiving interferon treatment. This is associated with decreased plasma tryptophan levels which may lead to attenuated peripheral and central serotonergic neurotransmission.


In vivo neurochemical evidence that newly synthesised GABA activates GABA(B), but not GABA(A), receptors on dopaminergic nerve endings in the nucleus accumbens of freely moving rats.
GABA released from accumbal GABAergic interneurons plays an inhibitory role in the regulation of dopamine efflux through GABA(B) and GABA(A) receptors located on accumbal dopaminergic nerve endings. The cytosolic newly synthesised GABA alters vesicular GABA levels and, accordingly, the amount of GABA released from the neuron. Therefore, we hypothesised that glutamic acid decarboxylase (GAD) which generates GABA in accumbal GABAergic neurons, at least partly determines the GABA receptor subtype-mediated GABAergic tonus. To (in)validate this hypothesis, in vivo microdialysis was used to study the effects of an intra-accumbal infusion of the GAD inhibitor l-allylglycine (allylglycine) on the accumbal dopamine efflux of freely moving rats. The intra-accumbal infusion of allylglycine (50.0, 250.0 and 500.0 nmol) dose-dependently increased the accumbal dopamine levels. The co-administration of tetrodotoxin (720 pmol) suppressed the allylglycine (500.0 nmol)-induced dopamine efflux. The intra-accumbal infusion of GABA(B) receptor agonist baclofen (2.5 and 5.0 nmol) inhibited the allylglycine (500.0 nmol)-induced dopamine efflux. The baclofen's effects were counteracted by GABA(B) receptor antagonist saclofen (10.0 nmol). Neither GABA(A) receptor agonist (muscimol: 25.0 and 250.0 pmol) nor antagonist (bicuculline: 50.0 pmol) altered the allylglycine (250.0 and 500.0 nmol)-induced dopamine efflux. The present study provides in vivo neurochemical evidence that newly synthesised GABA that exerts an inhibitory tonus on the accumbal dopaminergic activity, acts at the level of GABA(B) receptors, but not GABA(A) receptors. The present study also shows that there is an allylglycine-insensitive GABA pool that release GABA exerting an inhibitory control of the accumbal dopaminergic activity, at the level of GABA(A) receptors. This article is part of a Special Issue entitled 'Post-Traumatic Stress Disorder'.


Evaluation of a bibliotherapy manual for reducing psychological distress in people with depression: a randomized controlled trial.
This article reports a study to evaluate the efficacy of a self-help manual in reducing psychological distress in individuals with moderate depression. The prevalence of depression in Thailand is increasing markedly (e.g. from 56-197 per 100,000 population between 1997-2007). We conducted a randomized controlled trial with 54 outpatients with depression in Chiang Mai Province in Thailand. Participants were assigned randomly to an intervention or control group. The intervention group participants were given a self-help manual in addition to standard care and treatment while the control group received standard care and treatment. Psychological distress was measured with the Kessler Psychological Distress Scale. Data were collected between October 2007-April 2008. The findings showed statistically significant differences between both groups in their levels of psychological distress (e.g. tiredness, hopelessness, restlessness). At post-test, the distress scores of the intervention group were lower than those in the control group. Between post-test and 1-month follow-up, distress scores continued to decrease steadily in the intervention group but only decreased slightly in the control group. The findings affirm the benefits of bibliotherapy or self-help therapy in book form in helping to reduce psychological distress in people with moderate depression. The approach is easy to use and can be incorporated as an adjunct to standard care and treatment. Bibliotherapy can be used by community mental health nurses and other clinicians to reduce psychological distress and promote recovery in people with moderate depression.


Risk of maternal, fetal and neonatal complications associated with the use of the transcervical balloon catheter in induction of labour: A systematic review.
Induction of labour is one of the most frequently applied obstetrical interventions globally. Many studies have compared the use of balloon catheters with pharmacological agents. Although the safety of the balloon catheter is often mentioned, little has been written about the total spectrum of maternal and fetal morbidity associated with induction of labour using a balloon catheter. We evaluated the safety of labour induction with a transcervical balloon catheter by conducting a literature review with pooled risk assessments of the maternal, fetal and neonatal morbidity. We searched Medline, EMBASE and CINAHL as well as the Cochrane database using the Keywords 'induction of labour', 'cervical ripening', 'transcervical balloon', 'balloon catheter' and 'Foley balloon'. We did not use language or date restrictions. Randomized and quasi-randomized controlled trials as well as observational studies that contained original data on occurrence of maternal, fetal or neonatal morbidity during induction of labour with the balloon catheter were included. Studies were excluded if the balloon catheter was used concurrently with oxytocin and concurrently or consecutively with misoprostol, dinoprostone or extra-amniotic saline infusion. Study selection and quality assessment was performed by two authors independently using a standardized critical appraisal instrument. Outcomes were reported as weighted mean rates. We detected 84 articles reporting on 13,791 women. The overall risk of developing intrapartum maternal infection was 11.3% (912 of 8079 women), 3.3% (151 of 4538 women) for postpartum maternal infection and 4.6% (203 of 4460 women) for neonatal infection. Uterine hypercontractility occurred in 2.7% (148 of 5439) of the women. Uterine rupture after previous caesarean section occurred in 1.9% of women (26 of 1373), while other major maternal complications had an occurrence rate of <1%. The risk for developing minor maternal complications was <2%. The risk of developing a non-reassuring fetal heart rate was 10.8% (793 of 7336 women), 10.1% (507 of 5008 women) for fetal distress and 14.0% (460 of 3295 women) for meconium stained liquor. Neonatal death occurred in 0.29% (6 of 2058) of the deliveries and NICU admission in 7.2% (650 of 9065 deliveries). This review shows that labour induction with a balloon catheter is a safe intervention, with intrapartum maternal infection being the only reasonable risk above 10%.


Focal adhesion kinase, RhoA, and p38 mitogen-activated protein kinase modulates apoptosis mediated by angiotensin II AT2 receptors.
Apoptosis plays an important role in cellular processes such as development, differentiation, and homeostasis. Although the participation of angiotensin II (Ang II) AT2 receptors (AT 2 R) in cellular apoptosis is well accepted, the signaling pathway involved in this process is not well established. We evaluated the participation of signaling proteins focal adhesion kinase (FAK), RhoA, and p38 mitogen-activated protein kinase (p38MAPK) in apoptosis induced by Ang II via AT 2 R overexpressed in HeLa cells. Following a short stimulation time (120 to 240 minutes) with Ang II, HeLa-AT 2 cells showed nuclear condensation, stress fibers disassembly and membrane blebbing. FAK, classically involved in cytoskeleton reorganization, has been postulated as an early marker of cellular apoptosis. Thus, we evaluated FAK cleavage, detected at early stimulation times (15 to 30 minutes). Apoptosis was confirmed by increased caspase-3 cleavage and enzymatic activity of caspase-3/7. Participation of RhoA was evaluated. HeLa-AT 2 cells overexpressing RhoA wild-type (WT) or their mutants, RhoA V14 (constitutively active form) or RhoA N19 (dominant-negative form) were used to explore RhoA participation. HeLa-AT 2 cells expressing the constitutively active variant RhoA V14 showed enhanced apoptotic features at earlier times as compared with cells expressing the WT variant. RhoA N19 expression prevented nuclear condensation/caspase activation. Inhibition of p38MAPK caused an increase in nuclear condensation and caspase-3/7 activation, suggesting a protective role of p38MAPK. Our results clearly demonstrated that stimulation of AT 2 R induce apoptosis with participation of FAK and RhoA while p38MAPK seems to play a prosurvival role.


Decarboxylative Claisen rearrangement reactions: synthesis and reactivity of alkylidene-substituted indolines.
Microwave-assisted decarboxylative Claisen rearrangement (dCr) reactions of substituted acetate derivatives of 3-(hydroxyalkyl)indoles give de-aromatised products. The reactivity of the resultant compounds was evaluated.


Physiology and pathophysiology of oxLDL uptake by vascular wall cells in atherosclerosis.
Atherosclerosis is a progressive disease in which endothelial cell dysfunction, macrophage foam cell formation, and smooth muscle cell migration and proliferation, lead to the loss of vascular homeostasis. Oxidized low-density lipoprotein (oxLDL) may play a pre-eminent function in atherosclerotic lesion formation, even if their role is still debated. Several types of scavenger receptors (SRs) such as SR-AI/II, SRBI, CD36, lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), toll-like receptors (TLRs) and others can promote the internalization of oxLDL. They are expressed on the surface of vascular wall cells (endothelial cells, macrophages and smooth muscle cells) and they mediate the cellular effects of oxLDL. The key influence of both oxLDL and SRs on the atherogenic process has been established in atherosclerosis-prone animals, in which antioxidant treatment and/or silencing of SRs has been shown to reduce atherogenesis. Despite some discrepancies, the indication from cohort studies that there is an association between oxLDL and cardiovascular (CV) events seems to point toward a role for oxLDL in atherosclerotic plaque progress and disruption. Finally, randomized clinical trials using antioxidants have demonstrated benefits only in high-risk patients, suggesting that additional proofs are still needed to better define the involvement of each type of modified LDL in the development of atherosclerosis.


Metabolic modulation by amino acid stimulation of the paraventricular nucleus of the hypothalamus.
The role of the paraventricular nucleus of the hypothalamus (PVN) in the regulation of energy expenditure and energy substrate utilization was investigated after the injection of the excitatory amino acid D,L-homocysteic acid (DLH) or its vehicle. Male Wistar rats with chronic PVN cannulae were tested for 1 h with no food available in an open-circuit calorimeter. Whereas low (0.5 nmol), excitatory doses of DLH increased energy expenditure, the thermogenic effect became smaller and then vanished as the DLH dose was increased to inhibitory levels (7 and 50 nmol). None of these doses affected motor activity, indicating a primary thermogenic effect. The highest dose (100 nmol) increased energy expenditure, but this appeared to be secondary to increased locomotor activity. The increased locomotor activity produced by the highest dose of DLH constitutes the first demonstration of an activity effect induced by stimulating the PVN. However, this effect likely reflects the activation of neighboring areas. Only the 50 nmol dose of DLH increased respiratory quotient, indicating a shift toward the preferential utilization of carbohydrates as an energy substrate. These data complement our findings with neuropeptide Y and insulin in showing that different doses of the same substance injected into the PVN may produce qualitatively different effects. Furthermore, the present study demonstrates that exciting PVN neurons activates catabolic forces, whereas inhibiting them activates anabolic forces.


Non-polio enteroviruses and their association with acute diarrhea in children in India.
A causative agent in approximately 40% of diarrheal cases still remains unidentified. Though many enteroviruses (EVs) are transmitted through fecal-oral route and replicate in the intestinal cells, their association with acute diarrhea has not so far been recognized due to lack of detailed epidemiological investigations. This long-term, detailed molecular epidemiological study aims to conclusively determine the association of non-polio enteroviruses (NPEVs) with acute diarrhea in comparison with rotavirus (RV) in children. Diarrheal stool specimens from 2161 children aged 0-2 years and 169 children between 2 and 9 years, and 1800 normal stool samples from age-matched healthy children between 0 and 9 years were examined during 2008-2012 for enterovirus (oral polio vaccine strains (OPVs) and NPEVs). Enterovirus serotypes were identified by complete VP1 gene sequence analysis. Enterovirus and rotavirus were detected in 19.01% (380/2330) and 13.82% (322/2330) diarrheal stools. During the study period, annual prevalence of EV- and RV-associated diarrhea ranged between 8% and 22%, but with contrasting seasonal prevalence with RV predominating during winter months and NPEV prevailing in other seasons. NPEVs are associated with epidemics-like outbreaks during which they are detected in up to 50% of diarrheic children, and in non-epidemic seasons in 0-10% of the patients. After subtraction of OPV-positive diarrheal cases (1.81%), while NPEVs are associated with about 17% of acute diarrhea, about 6% of healthy children showed asymptomatic NPEV excretion. Of 37 NPEV serotypes detected in diarrheal children, seven echovirus types 1, 7, 11, 13, 14, 30 and 33 are frequently observed, with E11 being more prevalent followed by E30. In conclusion, NPEVs are significantly associated with acute diarrhea, and NPEVs and rotavirus exhibit contrasting seasonal predominance. This study signifies the need for a new direction of research on enteroviruses involving systematic analysis of their contribution to diarrheal burden.


Stereophotogrammetry: an additional method for three-dimensional x-ray examination.
A comparison of stereophotogrammetry and computer tomography is made. Advantages of both methods are shown in some examples from neurosurgical practice.


Low FODMAP diet beyond IBS: Evidence for use in other conditions.
The low FODMAP diet has shifted therapeutic guidelines for symptom management in irritable bowel syndrome. Given FODMAPs are involved in underlying pathological mechanisms of visceral hypersensitivity, research groups are exploring the use of the low-FODMAP diet as a potential management approach in several conditions outside of irritable bowel syndrome. Early data shows promise for functional dyspepsia, improving epigastric symptoms, and although evidence is scant, the diet has been proposed to assist in small intestinal bacterial overgrowth. Characterisation of sucrase-isomaltase deficiency may offer profiling for predicting response to the diet. Although encouraging, carefully controlled broader trials are needed across the conditions discussed to completely understand the effects of the low FODMAP diet on symptoms, safety, and efficacy in clinical practice.


Developmentally-related candidate retinoic acid target genes regulated early during neuronal differentiation of human embryonal carcinoma.
Embryonal carcinoma is a model of embryonic development as well as tumor cell differentiation. In response to all-trans retinoic acid (RA), the human embryonal carcinoma (EC) cell line, NT2/D1, differentiates toward a neuronal lineage with associated loss of cell growth and tumorigenicity. Through the use of cDNA-based microarrays we sought to identify the early downstream targets of RA during differentiation commitment of NT2/D1 cells. A total of 57 genes were induced and 37 genes repressed by RA. RA regulated genes were restricted at 8 h with 27 genes induced and five repressed. The total number of RA-responsive transcripts increased at 24 and 48 h and their pattern of expression was more symmetrical. For a given time point less than 1% of the 9128 cDNAs on the expression array were regulated by RA. Many of these gene products are associated with developmental pathways including those of TGF-beta (Lefty A, NMA, follistatin), homeo domain (HoxD1, Meis2, Meis1, Gbx2), IGF (IGFBP3, IGFBP6, CTGF), Notch (manic fringe, ADAM11), Hedgehog (patched) and Wnt (Frat2, secreted frizzled-related protein 1) signaling. In addition a large cassette of genes induced by RA at 24-48 h are associated with cell adhesion, cytoskeletal and matrix remodeling, growth suppression and intracellular signaling cascades. The majority of repressed genes are associated with protein/RNA processing, turnover or metabolism. The early induced genes identified may play a regulatory role in RA-mediated growth suppression and terminal differentiation and may have physiologic or pharmacologic importance during normal human development and retinoid-based cancer therapy or prevention.


A simple method for coupling aldehydes to solid support.
A new method for attaching aldehydes to solid supports has been developed employing a 2,2-bis(hydroxymethyl)propionic acid (DMPA) functionalized resin. High loading levels are obtained for both aryl and alkyl aldehydes protected as their respective acetals. Treatment of the derivatized resin with 95% TFA then cleanly affords the recovered aldehyde in high yield.


Current Controversies in Metopic Suture Craniosynostosis.
Metopic craniosynostosis is being reported with an increasing incidence and is now the second most common type of isolated suture craniosynostosis. Numerous areas of controversy exist in the work-up and management, including defining the diagnosis in the less severe phenotype, the association with neurodevelopmental delay, the impact of surgical treatment, and the applicability of various techniques and their timing on outcomes.


Metabolic reprogramming of the intestinal microbiome with functional bile acid changes underlie the development of NAFLD.
Bile acids are hepatic metabolites and have many properties considered to be relevant to the pathophysiology of NAFLD. Circulating levels of the intestinal microbiome-modified bile acid deoxycholate are increased in cirrhosis. To further elucidate the role of bile acids and intestinal microbiota linked to bile acids in progressively severe NAFLD, a multiomic study of feces including 16S rRNA sequencing, microbial transcriptomics and metabolomics was performed in a cohort with varying phenotypes of NAFLD. Several bile acids of microbial origin derived from deoxycholic acid (DCA) (glycodeoxycholate, 7-ketodeoxycholic acid, dehydrocholic acid) increased with disease activity and fibrosis stage. These were linked to increased expression of microbial bile salt hydrolase, bile acid operon (BaiCD) and hydroxysteroid dehydrogenases (hdhA) required for DCA and downstream metabolite synthesis providing a mechanistic basis for altered bile acid profiles with disease progression. Bacteroidetes and several genera of Lachnospiraceae family containing DCA generating genes increased with increasing disease severity, whereas several potentially beneficial microbes sensitive to antibacterial effects of DCA e.g., Ruminococcaceae were decreased. The clinical relevance of these data was confirmed in an independent cohort enrolled in a clinical trial for NASH where at entry DCA and its conjugates were associated with advanced fibrosis. In patients treated with placebo, DCA declined in those with fibrosis regression and increased in those with fibrosis progression. DCA rose further in those with compensated cirrhosis when they experienced decompensation. These findings demonstrate a role for bile acids and the bile acid dependent microbiome in the development and progression of NAFLD and set the stage to leverage these findings for NASH biomarker development and for therapeutics.


Comparable outcomes of partially matched related and matched related allogeneic hematopoietic cell transplantation following reduced-intensity conditioning in adult patients with Philadelphia chromosome-negative acute lymphoblastic leukemia.
Reports from multiple centers have shown that reduced-intensity allogeneic hematopoietic cell transplantation (RIC-HCT) is able to benefit some adult patients suffering from Philadelphia chromosome-negative acute lymphoblastic leukemia (ALL). However, the relationship between donor cell source and outcome of RIC-HCT in (Ph-)ALL patients has not been elucidated. In this study, we present the outcome of 57 (Ph-)ALL patients treated with reduced-intensity conditioning (RIC) followed by HCT from HLA-matched related (MRD, n = 34) or HLA partially matched related (PMRD, n = 23) donors from a multicenter cohort. Neutrophil recovery at day 100 occurred in 91.3 % of the PMRD group and 97.1 % of the MRD group (P = 0.84). One hundred days after treatment, the cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 30.4 % (95 % confidence interval [CI], 13.0-53.0 %) in patients who received PMRD grafts, and 27.3 % (95 % CI, 15.0-48.0 %) for those who received MRD grafts (P = 0.76). The cumulative risk of developing chronic GVHD was 59.4 % (95 % CI, 31.0-72.0 %) in the MRD group and 23.4 % (95 % CI, 4.0-43.0 %) in the PMRD group (P = 0.03). The cumulative incidence of relapse in patients who received PMRD grafts was 18.8 % (95 % CI, 3.0-34.0 %), while for those who received MRD grafts it was 37.2 % (95 % CI, 15.0-48.0 %) (P = 0.32). Overall treatment-related mortality was 41.6 % (95 % CI, 20.0-62.0 %) in the PMRD group and 19.9 % (95 % CI, 7.0-35.0 %) in the MRD group (P = 0.08). Relapse was the most common cause of mortality in the MRD group, while infection contributed to the majority of deaths in the PMRD group. The 3-year probability of disease-free survival did not differ significantly between the two groups (55.5 % for the PMRD group vs. 48.4 % for the MRD group; P = 0.81). These data strongly suggest that RIC-HCT performed with PMRD may represent an alternative treatment option for adult patients with (Ph-)ALL.


Routine blood tests as predictors of mortality in hip fracture patients.
The aim of this study was to assess the evidence for the association between different biochemical markers at admission and mortality through a meta-analysis. PubMed-, Embase-, Cochran Library and the Web of Knowledge were searched for cohort studies. Eligible studies were observational studies with a study population larger than 150 subjects, a mean age above 60 years and a study duration below 730 days. Characteristics of studies and outcomes of all-cause mortality were extracted from the retrieved articles. Data were pooled across studies for the individual biomarker using random- or fixed-effect analysis. 15 eligible studies of 5 different markers on mortality were studied. The following markers were found to be of prognostic value on mortality in hip fracture patients: low haemoglobin (odds ratio, 2.78; 95% confidence interval, 2.17-3.55; P<0.00001, 3148 subjects included), low total lymphocyte count, TLC (odds ratio, 2.60; 95% confidence interval, 1.61-4.20; P<0.00001, 1689 subjects included), low albumin (odds ratio, 1.83; 95% confidence interval, 1.31-2.56; P=0.0004, 1680 subjects included), low albumin/low TLC (odds ratio, 3.00; 95% confidence interval, 1.81-4.99; P<0.0001, 704 subjects included), low albumin/high TLC (odds ratio, 3.39; 95% confidence interval, 1.83-6.29; P=0.0001, 704 subjects included), high creatinine (odds ratio, 1.58; 95% confidence interval, 1.25-1.99; P=0.0001, 3761 subjects included), and high PTH (odds ratio, 15.43; 95% confidence interval, 3.60-66.14; P=0.0002, 525 subjects included). Biochemical markers at admission are valid predictors of mortality in hip fracture patients.


Vascular Cognitive Impairment: A Little Bit of Good News for Women or Bad News for Men?
In a recent issue of the Journal of Alzheimer's Disease, Zinman et al. investigated the role of sex in the risk of cognitive impairment in 5,969 patients with a stroke or transient ischemic attacks. Using a short validated clinical screening tool, they noted that men had a 34% higher risk of screening positive for post-stroke cognitive impairment after adjusting for age, education, and stroke severity compared to women. This study highlights that more large, prospective, and multicenter studies are needed to evaluate sex-specific changes after a stroke since sex differences exist in many aspects of stroke presentation and management.


Dose-Dependent Therapeutic Distinction between Active and Passive Targeting Revealed Using Transferrin-Coated PGMA Nanoparticles.
The paradigm of using nanoparticle-based formulations for drug delivery relies on their enhanced passive accumulation in the tumor interstitium. Nanoparticles with active targeting capabilities attempt to further enhance specific delivery of drugs to the tumors via interaction with overexpressed cellular receptors. Consequently, it is widely accepted that drug delivery using actively targeted nanoparticles maximizes the therapeutic benefit and minimizes the off-target effects. However, the process of nanoparticle mediated active targeting initially relies on their passive accumulation in tumors. In this article, it is demonstrated that these two tumor-targeted drug delivery mechanisms are interrelated and dosage dependent. It is reported that at lower doses, actively targeted nanoparticles have distinctly higher efficacy in tumor inhibition than their passively targeted counterparts. However, the enhanced permeability and retention effect of the tumor tissue becomes the dominant factor influencing the efficacy of both passively and actively targeted nanoparticles when they are administered at higher doses. Importantly, it is demonstrated that dosage is a pivotal parameter that needs to be taken into account in the assessment of nanoparticle mediated targeted drug delivery.


In vitro hydroxylation of the synthetic gestagen, norgestrel.
The in vitro metabolism of stereo-isomers (D, L and the racemic mixture DL) of norgestrel by a microsomal fraction from rabbit liver was investigated. The metabolism of the biologically active D-norgestrel was more rapid than that of L-norgestrel which is biologically inactive. This was mainly due to the more ready conversion of D-norgestrel to ring-A reduced metabolites. There was no difference between the two isomers in respect of the amount undergoing hydroxylation; about 40% of each isomer was converted to hydroxylated metabolites after 30 min incubation. However, there were differences between the isomers, D-norgestrel being converted mainly to the 16 beta-hydroxysteroid and L-norgestrel to the 16 alpha-hydroxysteroid. Similar amounts of both isomers were hydroxylated at C-6. The metabolism of the racemic mixture was intermediate between that of the D and L isomers.


Intravenous immunoglobulin therapy enhances suppressive regulatory T cells and decreases innate lymphoid cells in children with immune thrombocytopenia.
This study aimed to investigate the relationship between CD4+ regulatory T cells (Tregs) and innate lymphoid cells (ILCs) in children with primary immune thrombocytopenia (ITP) undergoing high-dose intravenous immunoglobulin (IVIG) therapy. We enrolled a cohort of 30 children with newly diagnosed ITP and 30 healthy controls and collected blood samples for levels of Tregs, ILCs, relevant cytokines, and Treg suppression assay at the diagnosis, two days, four weeks, and one year (only platelet count) after high-dose IVIG treatment. IVIG partial responders was defined by a platelet count less than 100 × 109 /L at 12 months after IVIG treatment. Children with newly diagnosed ITP exhibited elevated levels of ILC1, ILC2, ILC3, Th17, myeloid dendritic cells (DCs), plasmacytoid DCs, and serum IFN-γ and IL-17A levels, accompanied by a decrease in IL-10-producing Tregs. High-dose IVIG therapy reversed these aberrations. Platelet counts positively correlated with Tregs (rho = 0.72) and negatively correlated with both ILC1 (rho = -0.49) and ILC3 (rho = -0.60) (P < 0.05). Significantly lower Tregs and higher ILC1, ILC3, DCs, and serum IL-17A levels were noted in the partial responders (n = 8) versus responders (n = 22; P < 0.05). We found that Tregs suppressed proliferation of ILCs and CD4+ T cells in CD25-depleted peripheral PBMCs and enhanced the apoptosis of CD4+ CD45RO+ T cells in vitro following IVIG therapy. Effective high-dose IVIG therapy for children with newly diagnosed ITP appears to result in the induction of Tregs, which suppresses ILC proliferation in vitro and is associated with platelet response.


Effects of continuous intravenous infusion of diethylstilbestrol into pregnant mice on fetus: testicular morphology at fetal and postnatal period.
Diethylstilbestrol was continuously infused into pregnant mice through the tail vein. In male fetus exposed to diethylstilbestrol (DES) from days 15 to 19 of gestation, Leydig cells of the testis were found to be increased in number when examined at 3-60 days of age. Mitotic rate in the interstitial tissue was elevated in 0- to 3-day-old mice exposed prenatally to DES. The ratio of the intertubular space to testis size was greater at 3 days of age than at 1 day in prenatally DES-exposed mice, while in the controls, the rate was lower at 3 days than at 1 day. Spermatogenic activity was lower in DES-exposed adult mice than in the controls, as shown by the spermatogenic index.


Assessing the sensitivity of diffusion MRI to detect neuronal activity directly.
Functional MRI (fMRI) is widely used to study brain function in the neurosciences. Unfortunately, conventional fMRI only indirectly assesses neuronal activity via hemodynamic coupling. Diffusion fMRI was proposed as a more direct and accurate fMRI method to detect neuronal activity, yet confirmative findings have proven difficult to obtain. Given that the underlying relation between tissue water diffusion changes and neuronal activity remains unclear, the rationale for using diffusion MRI to monitor neuronal activity has yet to be clearly established. Here, we studied the correlation between water diffusion and neuronal activity in vitro by simultaneous calcium fluorescence imaging and diffusion MR acquisition. We used organotypic cortical cultures from rat brains as a biological model system, in which spontaneous neuronal activity robustly emerges free of hemodynamic and other artifacts. Simultaneous fluorescent calcium images of neuronal activity are then directly correlated with diffusion MR signals now free of confounds typically encountered in vivo. Although a simultaneous increase of diffusion-weighted MR signals was observed together with the prolonged depolarization of neurons induced by pharmacological manipulations (in which cell swelling was demonstrated to play an important role), no evidence was found that diffusion MR signals directly correlate with normal spontaneous neuronal activity. These results suggest that, whereas current diffusion MR methods could monitor pathological conditions such as hyperexcitability, e.g., those seen in epilepsy, they do not appear to be sensitive or specific enough to detect or follow normal neuronal activity.


Parental and comorbid epilepsy in persons with bipolar disorder.
Population-based studies have demonstrated an overrepresentation of bipolar disorder (BPD) in individuals with epilepsy. However, few studies have examined the reverse association, i.e. comorbid epilepsy in individuals selected based on BPD diagnosis. No previous population-based study having examined the co-occurrence of BPD and epilepsy has adjusted for parental psychopathology. Such an adjustment is motivated by population-based studies reporting an overrepresentation of various types of parental psychiatric disorders in both BPD and epilepsy. Furthermore, an association between epilepsy in first-degree relatives and BPD has previously only been examined and demonstrated in a small clinical sample. The objective of this study is to examine the associations between parental and comorbid epilepsy and BPD, adjusting for parental psychopathology. This nested case-control study identified 1861 cases with BPD, age up to 25 years, 3643 matched controls, and their parents from Finnish national registers. Conditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) and two-sided significance limits of p<0.05. BPD was associated with comorbid epilepsy (adjusted OR 2.53, 95% CI: 1.73-3.70) but not with parental epilepsy. Epilepsy was found in 3.33% of cases versus 1.29% of controls, 2.69% of cases' parents versus 2.53% of controls' parents. The diagnoses were register-based, not based on standardized procedures with direct ascertainment. An association between BPD and comorbid epilepsy persists even after adjusting for parental psychopathology. Lack of familial clustering of BPD and epilepsy would suggest that the elevated co-occurrence of these disorders is influenced by non-genetic factors.


Invasion by the tufted duck Aythya fuligula into a pond area: implications of diffuse competition.
During the 20th century the Tufted Duck (Aythya fuligula) showed an expansion of its distribution to the west in Europe. We present data for a small fish pond system in northern Bavaria indicating that the Tufted Duck is not fully integrated in the already established communities. The possible mechanism producing this effect seems to be "diffuse competition" by a set of species, which forms a densely packed guild.


Event-related potentials and the semantic matching of faces.
Event-related brain potentials (ERPs) were recorded while subjects determined whether two sequentially presented famous faces depicted individuals belonging to the same or to different occupational categories. During the 1.56 sec interval between the onset of the faces, ERPs recorded from right hemisphere electrodes were more negative-going than those from electrodes over the left hemisphere. The ERPs evoked by the second face on each trial differed as a consequence of whether or not the person depicted belonged to the occupational category specified by the first face. This difference took the form of a bilaterally-distributed negative-going shift in the ERPs evoked by non-matching as opposed to matching faces. This negativity was maximal around 450 msec post-stimulus. The ERP asymmetries during the inter-stimulus interval are interpreted as evidence for the engagement of cognitive processes lateralized to the right hemisphere. The match/non-match differences are considered to reflect the modulation of an "N400" component similar to that evoked by words, and thus suggest that such components can be modulated by associative priming between non-linguistic stimuli.


The potentized homeopathic drug, Lycopodium clavatum (5C and 15C) has anti-cancer effect on hela cells in vitro.
Cancer is a disease that needs a multi-faceted approach from different systems of medicine. The purpose of this study was to evaluate whether homeopathically-potentized ultra-high dilutions of Lycopodium Clavatum (LC-5C and LC-15C, respectively) have any anti-cancer effects on HeLa cells. Cells were exposed to either LC-5C (diluted below Avogadro's limit, i.e., 10(-10)) or LC-15C (diluted beyond Avogadro's limit, i.e., 10(-30)) (drug-treated) or to 30% succussed ethanol ("vehicle" of the drug). The drug-induced modulation in the percent cell viability, the onset of apoptosis, and changes in the expressions of Bax, Bcl2, caspase 3, and Apaf proteins in inter-nucleosomal DNA, in mitochondrial membrane potentials and in the release of cytochrome-c were analyzed by utilizing different experimental protocols. Results revealed that administration of LC-5C and LC-15C had little or no cytotoxic effect in normal peripheral blood mononuclear cells, but caused considerable cell death through apoptosis in cancer (HeLa) cells, which was evident from the induction of DNA fragmentation, the increases in the expressions of protein and mRNA of caspase 3 and Bax, and the decreases in the expressions of Bcl2 and Apaf and in the release of cytochrome-c. Thus, the highly-diluted, dynamized homeopathic remedies LC-5C and LC-15C demonstrated their capabilities to induce apoptosis in cancer cells, signifying their possible use as supportive medicines in cancer therapy.


The effect of antibiotic prophylaxis on the incidence of surgical site infection after laparoscopic appendectomy for chronic appendicitis.
The guidelinesthat specify whether antibiotic prophylaxis should be administered before laparoscopic clean-contaminated wound to prevent postoperative surgical site infection (SSI) need to be improved. Studies have shown that elective laparoscopic cholecystectomy with clean-contaminated wound does not require antibiotic prophylaxis. However, there are no studies on the effect of antibiotic prophylaxis on SSI after laparoscopic appendectomy for chronic appendicitis (LCA), which is a clean-contaminated wound. We conducted a single-center, double-blind, randomized controlled clinical trial. A total of 106 effective patients were randomly divided into the antibiotic group and saline group. Cefuroxime or clindamycin was administered intravenously in the antibiotic group (n = 52). Saline (0.9%) was administered intravenously in the saline group (n = 54). Interventions were administered as a single dose 30 min before surgery. Among the 106 effective patients (median age, 37 years old [IQR, 25-45]; females, 77 [72.6%]), there were 6 cases (5.70%) of SSI: 3 cases (5.56%) in the saline group and 3 cases (5.70%) in the antibiotic group (OR = 1.00, [95% CI (0.20-5.4)], P = 0.96). There were no significant differences in the clinical outcomes of anal exhaust time, postoperative complications, and the symptom of primary abdominal pain between the two groups. For patients with chronic appendicitis undergoing laparoscopic appendectomy, preoperative intravenous antibiotic prophylaxis did not reduce the risk of SSI within 30 days of the surgery compared to the saline group. Registration number of China Clinical Trials Registration Center: ChiCTR2100048336.


Apolipoprotein B gene DNA polymorphisms are associated with macro- and microangiopathy in non-insulin-dependent diabetes mellitus.
The relationship between diabetic macroangiopathy or microangiopathy and apolipoprotein B (apoB) polymorphism was studied in 139 male and 129 female patients with non-insulin-dependent diabetes (NIDDM) mellitus, comprising consecutive patients with poor diabetic control (HBA1 13.2% +/- 2.7 (SD)) referred to our hospital. Plasma cholesterol and triglyceride concentrations were higher in the patients who were homozygous for the X2 allele (presence of XbaI cleavage site). Patients with the X1 allele (absence of XbaI cleavage site) tended to have a higher frequency of macroangiopathy, although the differences were not statistically significant. There was no difference in the prevalence of microangiopathy between the groups. In subjects with only an R1 allele (= R+; homozygous for the presence of EcoRI cleavage site) the prevalence of coronary heart disease (CHD) was observed to be high (61.9%) as compared to the subjects possessing an R2 allele (= R-; homozygous or heterozygous for the absence of the EcoRI cleavage site) (46.7%; p < 0.02). When the polymorphisms XbaI (subjects homozygous for the absence of the cutting site = X+; subjects homozygous or heterozygous for the presence of the cutting site = X-) and EcoRI were combined, the prevalence of macroangiopathy was observed to be high in X+R+ (80.0%) as compared with X+R- (44.2%), X-R+ (56.8%) and X-R- (50.0%) (p < 0.03). The prevalence of macroangiopathy tended to be particularly high in patients with the apoprotein E4 allele (phenotype E4/4 or E4/3), combined with either X+ or R+.(ABSTRACT TRUNCATED AT 250 WORDS)


Association between treatment for retinopathy of prematurity and blood monocyte counts.
To investigate blood monocyte counts as a risk factor for retinopathy of prematurity (ROP) treatment. Retrospective cohort study. Infants who underwent ROP screening at Shiga University of Medical Science Hospital between January, 2011 and July, 2021 were included in this study. Screening criteria were a gestational age (GA) < 32 weeks or birth weight (BW) < 1500 g. The week with the largest difference in monocyte counts between the infants with and without type 1 ROP determined based on the effect size. Multivariate logistic regression analysis was applied to investigate whether the monocyte counts constituted an independent risk factor for type 1 ROP. The objective variable was type 1 ROP, and the explanatory variables were GA, BW, infants' infection, and Apgar score at 1 min and monocyte counts in the week with the largest monocyte-counts difference between the with- and without type 1 ROP groups. In total, 231 infants met the inclusion criteria. The monocyte counts in the fourth week after birth (4w MONO) exhibited the largest difference between infants with and without type 1 ROP. The analysis was performed on 198 infants, excluding 33 infants without 4w MONO data. Thirty-one infants had type 1 ROP, whereas 167 infants did not. BW and 4w MONO were significantly associated with type 1 ROP (odds ratio: 0.52 and 3.9, P < .001 and 0.004, respectively). The 4w MONO was an independent risk factor for type 1 ROP and may be useful in follow-up of infants with ROP.


Infection of human hematopoietic progenitor cells using a retroviral vector with a xenotropic pseudotype.
In an effort to determine if viral envelope type influences the infectivity of human hematopoietic progenitor cells with retroviral vectors, we have pseudotyped the retroviral vector N2, which confers G418-resistance, in either an amphotropic or xenotropic envelope. Vector titres obtained by the pseudotype procedure were nearly two orders of magnitude lower than the titer obtained when N2 was packaged using the amphotropic PA317 packaging cell line. Despite its low titer, xenotropically pseudotyped N2 generated G418-resistant hematopoietic colonies at levels approaching those observed after bone marrow was infected using vector packaged using PA317 cells. These results suggest that manipulations of vector envelope may lead to improvements in the level of infection of human hematopoietic stem cells.


Selective sweeps in SARS-CoV-2 variant competition.
The main mathematical result in this paper is that change of variables in the ordinary differential equation (ODE) for the competition of two infections in a Susceptible-Infected-Removed (SIR) model shows that the fraction of cases due to the new variant satisfies the logistic differential equation, which models selective sweeps. Fitting the logistic to data from the Global Initiative on Sharing All Influenza Data (GISAID) shows that this correctly predicts the rapid turnover from one dominant variant to another. In addition, our fitting gives sensible estimates of the increase in infectivity. These arguments are applicable to any epidemic modeled by SIR equations.


Minimally invasive robotically assisted repair of atrial perforation from a pacemaker lead.
We present the first reported case of robotic-assisted right atrial perforation repair and pacemaker lead extraction. A 75-year-old female with symptomatic sinus node dysfunction underwent atrial single chamber permanent pacemaker insertion via a persistent left superior vena cava approach. At one week follow-up a chest radiograph and a computerized dynamic tomography demonstrated that the right atrial lead had perforated the right atrial free wall. The patient remained asymptomatic without signs of pericardial tamponade, however urgent repair was warranted. Utilizing the da Vinci robotic system (Intuitive Surgical Inc., Sunnyvale, California, USA), the pacer lead perforation was visualized, the lead retracted, and the right atrium repaired. The existing atrial lead was repositioned in the right atrial appendage. The patient's postoperative convalescence was uneventful, and she was discharged home on the third post-operative day. This case demonstrates the increasing clinical utilization of robotic-assisted technology in minimally invasive cardiac surgery.


Bootstrap simulations to estimate relationships between Type I error, power, effect size, and appropriate sample numbers for bioassessments of aquatic ecosystems.
The Extended Bootstrap (EB) assessment approach was developed for the examination of relationships of Type I error, power, sample size (n), and effect size (ES) for statistical tests of ecological data. The EB approach was applied to univariate and multivariate statistical analyses of a large data set collected from an ongoing, multiple stressor bioassessment study of watersheds in the Central Valley, San Francisco, and Central Coast areas of California. Benthic metrics were created that either increased or decreased monotonically with stress (toxicants or metrics indicative of habitat quality). Type I errors were stable for all statistical tests that were evaluated. The relationships between n and ES displayed patterns of "diminishing returns" for all statistical tests: i.e. an increasingly larger n was required to detect decreasingly smaller ES. Nonetheless, the n's collected across the watersheds and within a selected watershed were sufficient to detect even small correlations between representative benthic metrics and potential stressors with high power. The power and robustness of a novel method using EB and previously described statistical techniques designed to address multicollinearity were shown to approach those of simpler univariate regressions. Potential applications of the EB approach for experimental design, data assessment and interpretation, and hypothesis testing are discussed.


The effect of acteoside on histamine release and arachidonic acid release in RBL-2H3 mast cells.
The effect of acteoside, a phenylpropanoid glycoside isolated from Clerodendron trichotomum Thunberg, on histamine and arachidonic acid release was investigated in RBL 2H3 cells. Histamine was dose-dependently released from RBL 2H3 cells by melittin, arachidonic acid and thapsigargin. In extracellular Ca2+-free solution, basal secretion of histamine increased by two fold. The response of histamine release to melittin and thapsigargin in Ca2+-free solution was significantly decreased, whereas the response to arachidonic acid was significantly increased as compared with those in normal solution. Acteoside inhibited histamine release induced by melittin, arachidonic acid and thapsigargin in a dose-dependent manner in the presence or absence of extracellular Ca2+. However, the inhibitory activity of acteoside was more potent in normal solution than that in Ca2+-free solution. These data suggest that inhibitory mechanism of acteoside on histamine release may be related to extracellular Ca2+. On the other hand, acteoside significantly inhibited arachidonic acid release and prostaglandin E2 production induced by 0.5 microM melittin. It is possible that acteoside may be developed as an anti-inflammatory agent.


Two techniques of pyramidalis muscle dissection in Pfannenstiel incision for cesarean section.
The aim of the study was to compare two techniques of pyramidalis muscle dissection during cesarean section. A total of 108 patients undergoing a cesarean section were randomly allocated to group I (N = 57), with the pyramidalis muscle left attached to the rectus muscles, and group II (N = 51), with preservation of the connection between the pyramidalis muscle and the rectus sheath. There were no statistically significant differences between the groups regarding surgery duration, blood loss and postoperative pain. After three months, patients from group II more frequently reported paresthesia in the scar region (47.1 vs. 28.1%; p = 0.041), but their self-assessment of the abdominal appearance and presence of the bulging below the wound were comparable with group I. None of the two techniques of pyramidalis muscle dissection appear to be superior to the other. The technique leaving the pyramidalis muscle attached to the fascia gave more frequent paresthesia during a 3-month follow-up.


Novel 3,4-methylenedioxyde-6-X-benzaldehyde-thiosemicarbazones: Synthesis and antileishmanial effects against Leishmania amazonensis.
A series of eleven 3,4-methylenedioxyde-6-X-benzaldehyde-thiosemicarbazones (16-27) was synthesised as part of a study to search for potential new drugs with a leishmanicidal effect. The thiosemicarbazones, ten of which are new compounds, were prepared in good yields (85-98%) by the reaction of 3,4-methylenedioxyde-6-benzaldehydes (6-X-piperonal), previously synthesised for this work by several methodologies, and thiosemicarbazide in ethanol with a few drops of H2SO4. These compounds were evaluated against Leishmania amazonensis promastigotes, and derivatives where X = I (22) and X = CN (23) moieties showed impressive results, having IC₅₀ = 20.74 μM and 16.40 μM, respectively. The intracellular amastigotes assays showed IC₅₀ = 22.00 μM (22) and 17.00 μM (23), and selectivity index >5.7 and >7.4, respectively, with a lower toxicity compared to pentamidine (positive control, SI = 4.5). The results obtained from the preliminary QSAR study indicated the hydrophobicity (log P) as a fundamental parameter for the 2D-QSAR linear model. A molecular docking study demonstrated that both compounds interact with flavin mononucleotide (FMN), important binding site of NO synthase.


A single-institution 25-year review of true parathyroid cysts.
Parathyroid cysts (PCs) are rare, and their origin is a subject of debate. They have been described as either functional, causing hyperparathyroidism, or non-functional in eucalcaemic patients. We have performed a 25-year departmental review of PCs. Features studied included the clinical presentation and intra-operative findings, and a histological review was performed. Cases of cystic degeneration of parathyroid adenomas and pseudocystic change were excluded. Over 25 years, 22,009 thyroidectomies and 2,505 parathyroidectomies were performed in our department. Amongst these, 38 non-functional PCs were documented in 37 patients. The mode of presentation included incidental findings on routine chest x-ray, compressive symptoms or an asymptomatic palpable neck mass. Aspiration was the initial treatment in 14 patients and was curative in 10 of these. Four out of 14 patients underwent surgical procedures for recurrence of the cyst that occurred 6 to 48 months after aspiration. In 27 patients, surgery was performed and all identified PCs were localized in the inferior parathyroid glands. Histologically, the cyst wall consisted in associations of lymphoid, muscular, thymic, salivary, adipose and mesenchymal tissues. PCs are rare but should be included within the differential diagnosis of a neck lump. True PCs are non-functional. Pathological and immunohistochemical findings are suggestive of a branchial origin. Fine-needle aspiration may be curative and is diagnostic due to the characteristic appearance of the fluid and high PTH levels on assay.


A new method for the isolation of undegraded FMDV-specific RNA from infected BHK cells.
Fractionation of Foot-and-Mouth disease virus infected cells by currently described procedures, leads to the appearance of variable amounts of heterogeneous single-stranded RNA fragments. A new method based upon the fractionation of cultured cells at extremely low temperatures has been developed to minimize the degradation of the viral RNAs by cellular nucleases. It was shown that the viral RNAs obtained by this procedure were almost non-degraded, and similar to those found in other picornavirus infected cells. More than 90 per cent of the polysomal RNAs were found as genome-size molecules, presumably being messenger RNA (mRNA). It was also found that the mRNA analyzed on sucrose gradients sedimented slightly ahead of the 35S genomic RNA. However, no differences were found when the analysis was performed on polyacrylamide gels.


Intrafamilial association of pericentric inversion of chromosome 9, inv (9)(p11-q21), and rapid cycling bipolar disorder.
Association of a chromosome aberration and psychiatric disorder can be useful in highlighting a genomic region that can be profitably explored further using positional cloning. We report the case of a father and daughter both of whom have bipolar disorder II and a pericentric inversion of chromosome 9.


Monitoring of serum proteinase--antiproteinase balance and systemic inflammatory response in prognostic evaluation of acute pancreatitis. Results of a prospective multicenter study.
With the aim of studying the clinical usefulness and applicability of circulating levels of protease inhibitors, complement factors, acute phase reactants, and leukocytic enzymes in the prognostic evaluation of acute pancreatitis (AP), the present prospective multicenter study has been carried out. A total of 182 patients with AP have been included, to whom an exhaustive evolutive protocol has been applied from the time of their hospital admission (2-12 hr from the onset of the disease) until the 15th day of evolution in order to clearly define them. The severe episodes exhibit a greater consumption of alpha 2-macroglobulin, and C3 and C4 complement factors, as well as a greater increase of alpha 1-protease inhibitor, C-reactive protein and polymorphonuclear elastase than mild events, with regards to the underlying pathophysiological condition. The determination of the plasma levels of leukocytic elastase in the first hours of evolution allows a prediction of the severity of the acute pancreatitis event with a high reliability (predictive values that become higher than 90%). The clinical value of the remaining parameters analyzed, in this aspect, is less, being applicable to the monitoring of the disease.


T2-weighted breath-hold MRI of the liver at 1.0 T: comparison of turbo spin-echo and HASTE sequences with and without fat suppression.
To compare the clinical usefulness of T2-weighted breath-hold sequences for imaging the liver, 33 patients with 97 focal hepatic lesions were studied with a 1.0-T scanner by using T2-weighted breath-hold turbo spin-echo (SE) sequences and T2-weighted breath-hold half-Fourier single-shot turbo SE (HASTE) sequences with and without fat suppression. Images were quantitatively analyzed for liver signal-to-noise ratio (SNR) and lesion-to-liver contrast-to-noise ratios (CNR). Qualitative analysis was performed for lesion conspicuity, motion artifacts, and anatomic sharpness of extrahepatic structures. Breath-hold turbo SE imaging with fat suppression showed the highest CNR for cystic lesions and the best lesion conspicuity for cystic and solid lesions among the four sequences. For solid lesions, there was no significant difference of lesion-to-liver CNR between them. HASTE sequence was superior to turbo SE sequences in terms of motion artifacts; however, the usefulness for evaluating focal hepatic lesions was limited compared with turbo SE sequence with fat suppression. Addition of fat suppression was not helpful for HASTE imaging because of decreased lesion conspicuity and extrahepatic details without the advantage of reducing motion artifacts. This study suggests that turbo SE sequence with fat suppression is most useful for breath-hold T2-weighted liver imaging at 1.0 T. Addition of imaging without fat suppression can be considered for evaluating extrahepatic structures. HASTE sequence may have a role for imaging uncooperative patients due to absence of motion artifacts.


Avian and mammalian vitamin D-dependent calcium binding protein in reptilian nephron.
A calcium binding protein (CaBP) with an apparent relative molecular weight of 28,000 was localized in the kidney of Anolis carolinensis with antisera directed against vitamin D-dependent CaBP from either rat kidney (RRCaBP) or chick intestine (CICaBP). When extracts of female saurian kidneys were fractionated by gel filtration on Sephadex G-100, both calcium binding activity, as measured by the chelex resin assay, and CaBP immunoreactivity, as measured by radioimmunoassay for RRCaBP, were observed near the 28,000-Da region similar to RRCaBP and CICaBP. Utilization of the immunoblot technique following SDS-polyacrylamide slab gel electrophoresis resulted in cross-reactivity for CaBP in the Mr 28,000 region for both rat and anolian kidneys. Immunoreactive CaBP was localized in the nephron using the unlabeled antibody peroxidase-antiperoxidase technique. Distal tubules (DT) gave a strong, specific reaction with either antiserum, but not all cells of the DT reacted with equal intensity. Cells in the transition zone between the DT and the terminal tubules, and cells in the collecting tubules, were occasionally positive. Renal corpuscles, proximal tubules, and thin segments gave no specific localization of CaBP. The sexual segment of male kidneys was also negative. The results indicate that a calcium binding protein with an apparent molecular weight of 28K is highly conserved during vertebrate evolution, and thus may have widespread but specific functional significance. The localization of CaBP to the DT suggests that this protein may be involved in the selective reabsorption and/or excretion of calcium.


[Lipoprotein(a) and hemostasis activation markers in angina pectoris].
To analyse whether lipoprotein(a) is a risk factor for myocardial infarction, stroke and acute peripheral arterial occlusion in coronary heart disease and whether this risk can be assessed by clotting activation markers. A partly prospective, partly retrospective study of data on 237 consecutive patients (201 men, 36 women; mean age 55 [24-76] years) who had undergone coronary arteriography because of severe angina. Concentrations were measured for: beta-thromboglobulin, platelet factor 4, fibrinopeptide A, D-dimers, thrombin-antithrombin III factor (TAT), prothrombin fragments 1 + 2, lipoprotein(a), apolipoprotein A-I (apoA-I), cholesterol and triglycerides. Analysis of any relationship between the findings on coronary arteriography (degree of stenosis) and the occurrence of myocardial infarction, stroke and acute peripheral arterial occlusion before and during the 2 years after the arteriography. There was no correlation between lipid parameters and clotting or platelet activation markers. Patients with a history of acute peripheral arterial occlusion had raised values for lipoprotein(a) and TAT. In the prospective part of the study (i.e. during the first 2 years after blood samples had been taken), there was no correlation. In patients with coronary artery disease and angina pectoris no correlation was found between lipoprotein(a) and haemostasis activation markers. None of these parameters--prospectively evaluated--could predict risk of thromboembolism.


Potentiation of etoposide cytotoxicity against a human ovarian cancer cell line by pretreatment with non-toxic concentrations of methotrexate or aphidicolin.
Exposure of human ovarian cancer SW626 cell line to 0.08 mumol/l methotrexate or 25 mumol/l aphidicolin for 24 h caused no cytotoxicity but enhanced etoposide cytotoxicity. Methotrexate or aphidicolin treatment induced a reversible blockade at the beginning of S phase which was reversed upon drug removal with a consequent wave of synchronisation. The enhancement of etoposide cytotoxicity was not due to higher etoposide intracellular uptake in the methotrexate or aphidicolin-pretreated cells. The topoisomerase II content in methotrexate or aphidicolin pretreated SW626 cells was higher than in control cells assessed by western blotting or flow cytometry. The higher etoposide cytotoxicity observed after synchronization with methotrexate or aphidicolin was apparently unrelated to the number of drug-induced DNA-topoisomerase II complexes evaluated as DNA double strand breaks or DNA-protein crosslinks. These data support the view that etoposide-induced DNA-topoisomerase II complexes are more cytotoxic in cells which are in S-phase.


Menarchal age and the stress of war: an example from Bosnia.
The aim of this study was to examine the influence of very low socioeconomic status, physical injury and psychological trauma on the menarchal age of deported girls who lived in besieged Srebrenica, a town that had a highly disrupted environment from the end of 1992 to mid 1995. The Srebrenica girls had a significantly higher mean menarchal age compared with a control group who lived mainly in peaceful communities in the unoccupied territory of Bosnia and Herzegovina. Our results show that psychological trauma, physical injury and low socioeconomic status, which provoked by the events of war, delay the age of menarche.


Poorly Differentiated Lung Cancer with Intracardiac Extension Causing Malignant Stroke in a Peritoneal Dialysis Patient: a Case Report.
Cardiac involvement occurs in an almost one quarter of all the patients with lung cancer. Lymphatogenous spread is a more common route of tumor dissemination than the hematogenous spread. It was a retrospective case report. We hereby report a case of myocardial involvement by non-small cell lung cancer leading to an uncommon presentation of a malignant stroke and death in a peritoneal dialysis patient.


Transmitted-light plethysmography detects changes in human pulpal blood flow elicited by innocuous tooth cooling and foot heating.
The present study aimed firstly, to investigate whether pulpal circulatory changes elicited by innocuous tooth cooling and foot heating can be monitored with transmitted-light plethysmography (TLP), which detects pulpal blood volume changes, and secondly, to assess the effect of autonomic nervous control on TLP values. Thirty sound permanent maxillary incisors in 30 healthy volunteers (age: 25-35 years) were examined. The photodiode and 525-nm light-emitting diode of a prototype TLP system (J. Morita) were fixed onto the palatal and labial side, respectively, of each tooth with a custom-made acrylic cap. The subjects were stimulated for 10 min by cold (0 °C) water application to the experimental tooth or 30 min by foot heating with a footbath (43 °C). TLP and finger plethysmography were simultaneously recorded before (baseline), during and after stimulation. TLP values and autonomic nerve activity were statistically analyzed using a repeated measures one-way ANOVA followed by Tukey post-hoc test and partial correlation analysis. TLP values decreased significantly after both innocuous stimuli (P < 0.05), and returned to their baseline levels shortly after the removal of the stimuli. There was no significant serial correlation between the autonomic nervous activity and TLP values (P > 0.05). TLP was able to monitor the pulpal circulatory changes evoked by innocuous stimuli. Systemic autonomic nervous control mechanisms were not associated with the pulpal circulatory changes, suggesting the involvement of other mechanisms, such as somatosensory-sympathetic nervous control.


Accommodation and chromatic aberration: effect of spatial frequency.
When subjects view an edge in white light, a colour fringe, produced by longitudinal chromatic aberration (LCA) of the eye, is formed at the edge. The colour fringe changes with changes in focus, and serves as a complex colour-coded cue for reflex accommodation. Fincham found that 60% of his subjects failed to accommodate appropriately when the colour fringe was removed with an achromatizing lens or by the use of monochromatic light. Our experiment sought to determine the spatial frequencies at which LCA is most effective. We monitored accommodation in 10 subjects while they viewed sinusoidally moving sine-wave gratings (1-3 D at 0.2 Hz; 1-10.5 c/deg) in a Badal optometer. The targets were 'white' gratings with LCA normal, doubled, neutralized or reversed. Doubling the aberration has minimal effect, removing the aberration reduces gain and increases phase-lag, and reversing the aberration severely disrupts accommodation. Sensitivity to these chromatic cues exists at all spatial frequencies tested, but is most prominent between 3 and 5 c/deg. These results support the view that the system monitors focus by comparing contrast in red-green and perhaps blue-yellow colour-opponent mechanisms.


What do you mean with "direction"? Local and global cues to biological motion perception in pigeons.
Biological motion point-light displays are a rich and versatile instrument to study perceptual organization. Humans are able to retrieve information from biological motion through at least two different channels: The global articulated structure as revealed by the non-rigid, yet highly constrained deformation of the dot pattern, and the characteristics of local motion trajectories of individual dots. Here, we tested eight pigeons on a task in which they had to discriminate a left-facing from a right-facing biological motion point-light figure. Since the two stimuli were mirror-flipped versions of each other, we were not sure if the birds would be able to solve the task at all. However, all birds learned the discrimination quickly and performed at high accuracy. We then challenged them with a number of test trials introduced into the sequence of the normal training trials. Tested on backwards moving walkers, the majority of the birds indicated that they used local motion cues to solve the training task, while the remaining birds obviously used global, configural cues. Testing the pigeons on different versions of scrambled biological motion confirmed that each individual bird had made a clear decision for one of the two potentially available strategies. While we confirm a previously described local precedence in processing visual patterns, the fact that some birds used global features suggests that even the birds who relied on local cues probably dispose of the perceptual abilities to use global structure, but "chose" to not use them.


Fatal fungal peritonitis in an adolescent on continuous ambulatory peritoneal dialysis: association with deferoxamine.
An unusual case of Rhizopus microsporus (mucormycosis) fungal infection in a teenage boy on continuous ambulatory peritoneal dialysis is presented. Premortem cultures were negative and the patient developed a rapidly disseminated fatal infection. The patient was being treated with deferoxamine (DFO) for iron and aluminum overload. An argument is made for a probable association between DFO and this fatal fungal infection in patients with end-stage renal disease.


Climatic factors and the incidence of pyelonephritis during pregnancy.
Numerous published reports have linked various disease states and pregnancy-related conditions with meteorologic factors such as weather, humidity, and temperature. The purpose of this study was to determine if temperature and dew point affect the incidence of pyelonephritis during pregnancy. A retrospective chart review of a 4-year period from 1989 to 1992 was performed. The records of women who were diagnosed with pyelonephritis during pregnancy were abstracted for the dates of admission. The climatic records of the Tampa Bay area of Florida were obtained from the National Weather Service. The average, minimum, or maximum daily temperature or average daily dew point during the month of admission had no significant effect on the rate of pyelonephritis during pregnancy in the Tampa Bay area. The rate of pyelonephritis during pregnancy per number of deliveries in the Tampa Bay area was not affected by the average, minimum, or maximum daily temperature or average daily dew point.


Family violence. Development of a master's level specialty track in family abuse.
Family violence is a societal reality. It will not disappear if society closes its eyes and fails to recognize its existence. When this is done, the abusive cycle is perpetuated. The specialty track described in this article was the nation's first graduate nursing educational program in the area of Family Violence. This program demonstrates nursing's potential contribution to the development of competent professionals with the expertise necessary to intervene in the abusive cycle.


Induction of autoantibodies to glutamate in patients with Alzheimer's disease.
Autoantibodies to glutamate were found in blood plasma from patients with Alzheimer's disease. The content of autoantibodies to glutamate in blood plasma from patients with moderate and severe dementia was 2-fold higher compared to patients with mild dementia.


In-capillary self-assembly and proteolytic cleavage of polyhistidine peptide capped quantum dots.
A new method using fluorescence coupled capillary electrophoresis (CE-FL) for monitoring self-assembly and proteolytic cleavage of hexahistidine peptide capped quantum dots (QDs) inside a capillary has been developed in this report. QDs and the ATTO 590-labeled hexahistidine peptide (H6-ATTO) were injected into a capillary, sequentially. Their self-assembly inside the capillary was driven by a metal-affinity force which yielded a new fluorescence signal due to Förster resonance energy transfer (FRET). The highly efficient separation of fluorescent complexes and the FRET process were analyzed using CE-FL. The self-assembly of QDs and biomolecules was found to effectively take place inside the capillary. The kinetics of the assembly was monitored by CE-FL, and the approach was extended to the study of proteolytic cleavage of surface conjugated peptides. Being the first in-depth analysis of in-capillary nanoparticle-biomolecule assembly, the novel approach reported here provides inspiration to the development of QD-based FRET probes for biomedical applications.


Incidence and Possible Predictive Factors of Facial Nerve Paralysis after Superficial Parotidectomy for Benign Tumours: Our Experience.
Salivary gland tumors represent 3-10% of all head and neck neoplasms. Most of the tumours are benign with parotid gland being most commonly affected. Surgical intervention in the form of parotidectomy forms the mainstay of treatment. Among the various postoperative complications that may occur after parotidectomy, facial nerve weakness is the most dreaded one for both the surgeon as well as the patient. In the literature, the incidence of transient facial weakness after parotid surgery ranges from 10 to 68%, and long-term dysfunction ranges from 0 to 19%. Apart from injury mechanisms such as nerve division, stretch, thermal injuries, ischemia, several other risk factors such as tumour size, disease duration etc. have also been identified for post parotidectomy facial nerve dysfunction which vary considerably from study to study. Thus, facial nerve injury despite being a common and dreaded complication is also a preventable one. We in our institute conducted a retrospective study from January 2018 to December 2021 to evaluate the incidence of facial nerve weakness and possible predictive factors among 60 patients who underwent superficial parotidectomy for benign tumours and found that when it comes to benign tumours surgical technique rather than tumour factors are more important in preventing nerve injury. Undertaking this study was important in order to emphasize the importance of extensive preoperative planning and better surgical practices among budding head and neck surgeons in our country.