[The effects of bromazepam on contingent negative variation and reaction time in a visuomotor task].
Bromazepam is the second most commonly used benzodiazepine in Brazil. Psychophysiological research on this substance is still in its early stages. To determine the neurotoxicity of bromazepam by examining reaction times (RT) and contingent negative variations (CNV). Using a videogame produced in our laboratory for psychophysiological research purposes (Car Acquisition), 14 healthy volunteers (9 males) aged between 23 and 42 drove a vehicle along a road full of curves (i.e. distractors) while they had to respond to imperative stimuli (i.e. orders to press the button on the joystick) that were preceded by warnings (S1-S2-RM paradigm with distractor). We compared RT, amplitudes and latencies of the CNV at each of the three electrodes on the median line (Fz, Cz and Pz) one hour after random, double-blind and crossed administration of placebo (P), 3 mg of bromazepam (B3) or 6 mg of bromazepam (B6) on different days. one-way ANOVA and Post Hoc Scheffé. No significant differences were observed in the RT. At Pz, the CNV amplitudes displayed significant differences for P, B3 and B6 (p = 0.006), and also for B3 and B6 (p = 0.018), with B6 > B3 = P. At Fz, a non-significant tendency (p = 0.074) suggested a difference between the latencies, shorter in B6 than in B3 (p = 0.098), both equivalent to placebo. The mean amplitudes ranged between 2.4 and 5.9 microV. Behavioural and neurophysiological neurotoxicity was insignificant one hour after administration of a single 3 or 6 mg dose of bromazepam in healthy young adults. Low mean amplitudes were compatible with the interference from distractors and did not result in floor effect.


Failure of ablation of a mediastinal parathyroid adenoma by repeated contrast staining.
In a patient with primary hyperparathyroidism an attempt was made to ablate a middle mediastinal parathyroid gland by forceful staining with radiographic contrast material. The gland was stained on two separate occasions, two weeks apart. Both times the serum calcium level temporarily fell to the normal range but reverted to abnormal levels. The patient ultimately required surgery for correction of hypercalcemia. The mechanism of staining and possible reasons for failure as well as potential complications are discussed.


Metacognitive interpersonal therapy-eating disorders versus cognitive behavioral therapy for eating disorders for non-underweight adults with eating disorders: study protocol for a pilot pre-registered randomized controlled trial.
Eating disorders (ED) are serious disorders characterized by an alteration of eating habits and excessive concern about weight and body shapes (Fairburn, 2002), accompanied by significant impairment inequality of life, high mortality rates and serious organic consequences (Jenkins et al., 2011; Treasure et al., 2015; 2020). Although evidence-based psychological therapies for nonunderweight ED presentations such as cognitive behavioral therapy for eating disorders (CBT-ED) are widely available, there is substantial scope for improvements, particularly in terms of efficacy and adherence. One option is to develop interventions to address elements of pathology not fully addressed by existing empirical supported treatments, such as incorporating techniques aimed at addressing interpersonal problems and personality disorder features into existing treatment delivery. We adapted Metacognitive Interpersonal Therapy, a psychological intervention supported by evidence for treating personality disorders and integrated it with existing CBT techniques for eating disorders (MIT-ED). MIT-ED targets aspects of ED that are not included in the transdiagnostic CBT-E model such as poor metacognition, or maladaptive interpersonal schemas. This is a pre-registered (Protocol number: 0000781) pilot randomized clinical trial aimed at assessing acceptability and feasibility of MIT-ED and establishing preliminary evidence of effectiveness for future larger studies. Twenty patients (10 in each arm) will be randomized to 20 sessions of individual psychotherapy, either MIT-ED or CBTE. Repeated follow-ups will be collected up to 24 months. Participants are recruited at a private outpatient clinic for ED treatment. Acceptability will be assessed via session attendance, completion rates and preliminary outcomes. The primary outcome is ED pathology assessed with the Eating Disorder Examination Questionnaire-6. Other ED outcomes assessed will be eating disorder attitudes, clinical impairment and binge eating pathology. Secondary treatment outcomes are anxiety, depression, and global symptomatology. We will also assess emotional awareness, emotion regulation and therapeutic alliance. Based on previous studies of MIT for personality disorders we hypothesize that MIT-ED will be acceptable to patients, evidenced by high treatment adherence and retention. We hypothesize that MIT-ED will be associated with reductions in eating disorder pathology, at least equivalent to CBT-E. Results will be used to inform the study design, sampling, likely effect sizes and choice of outcome measures for future larger trials of MIT-ED in ED samples.


Multiscroll attractors by switching systems.
In this paper, we present a class of three-dimensional dynamical systems having multiscrolls which we call unstable dissipative systems (UDSs). The UDSs are dissipative in one of its components but unstable in the other two. This class of systems is constructed with a switching law to display various multiscroll strange attractors. The multiscroll strange attractors result from the combination of several unstable "one-spiral" trajectories by means of switching. Each of these trajectories lies around a saddle hyperbolic stationary point. Thus, we describe how a piecewise-linear switching system yields multiscroll attractors, symmetric or asymmetric, with chaotic behavior.


The effect of centrifugation at various g force levels on rheological properties of rat, dog, pig and human red blood cells.
Laboratory investigations often require centrifugation of blood samples for various erythrocyte tests. Although there is a lack of data about the effect of centrifugation at various g force levels on erythrocyte rheological properties. We aimed to investigate the effect of a 10-minute centrifugation at 500, 1000 or 1500 g at 15°C of rat, dog, pig and human venous (K3-EDTA, 1.5 mg/ml) blood samples. Hematological parameters, erythrocyte deformability, cell membrane stability, osmotic gradient ektacytometry (osmoscan) and erythrocyte aggregation were determined. Hematological and erythrocyte deformability parameters showed interspecies differences, centrifugation caused no significant alterations. Cell membrane stability for human erythrocytes centrifuged at higher g level showed less decrease in deformability. Osmoscan O min parameter showed slight elevation in dog centrifuged aliquots. Erythrocyte aggregation parameters changed unexpectedly. Rat and dog erythrocyte aggregation indices significantly dropped in centrifuged aliquots. Pig erythrocyte aggregation indices increased significantly after centrifugation. Human erythrocyte aggregation was the most stable one among the investigated species. The used centrifugation protocols caused the largest alterations in erythrocyte aggregation in a controversial way among the investigated species. On the other hand, erythrocyte deformability parameters were stable, cell membrane stability and osmoscan data show minor shifts.


Is juvenile obsessive-compulsive disorder a developmental subtype of the disorder? A review of the pediatric literature.
To examine the clinical correlates of obsessive-compulsive disorder (OCD) in children and adolescents. A systematic review of the extant literature on juvenile OCD was conducted examining age at onset, gender distribution, symptom phenomenology, psychiatric comorbidity, neurological and perinatal history, family psychiatric history, cognitive and neuropsychological profiles, and treatment and outcome in juvenile OCD subjects. Juvenile OCD was associated with a unique peak of age at onset indicating a bimodal incidence of the disorder, male preponderance, a distinct pattern of comorbidity with attention-deficit/hyperactivity disorder and other developmental disorders as well as frequent associated neuropsychological deficits, an increased familial loading for OCD, and frequent absence of insight. These findings show that juvenile OCD is associated with a unique set of correlates that appear to differ from findings reported in studies of adult OCD subjects. Although in need of confirmation, these findings suggest that juvenile OCD may be a developmental subtype of the disorder. Since juvenile OCD is likely to continue into adulthood, these findings stress the importance of considering age at onset in clinical and research studies of adults with OCD.


Spirometric correlates of dyspnea improvement among emergency department patients with chronic obstructive pulmonary disease exacerbation.
To examine whether change in slow vital capacity (SVC) correlates to dyspnea improvement during emergency department (ED) treatment of chronic obstructive pulmonary disease (COPD) exacerbation. We performed a prospective cohort study and enrolled consecutive patients during a 3-week period. ED patients > or = 55 years old with COPD exacerbation were asked to perform bedside spirometry shortly after ED arrival and again at discharge. SVC was measured first, then forced expiratory volume in the first second (FEV1), peak expiratory flow (PEF), and forced vital capacity (FVC). Concurrent with spirometry, patients rated their dyspnea on a 10-cm visual analogue scale. Thirty-six patients were enrolled. The median ED stay was 271 min (interquartile range 219-370 min). Seventy-one percent of the patients reported dyspnea improvement during their ED stay. Change in SVC was significantly higher among the patients whose dyspnea improved than among those whose did not (median increase of 0.15 L vs median decrease of 0.25 L, respectively, p < 0.01). By contrast, the change in spirometry values were similar for FEV1, PEF, and FVC (all p > 0.30). Spearman correlation supported these findings: SVC r = 0.45 (p = 0.02) versus nonsignificant correlation with FEV(1) (r = 0.33), PEF (r = -0.22), and FVC (r = 0.35). Increase in SVC significantly correlated with dyspnea improvement among ED patients with moderate-to-severe COPD exacerbation. Change in SVC merits consideration when evaluating therapeutic response during COPD exacerbation.


Evaluation of three commercial tick removal tools.
To evaluate three commercially available tick removal tools against medium-tipped nontissue tweezers. We evaluated three commercially available tick removal tools against medium-tipped tweezers. Three inexperienced users randomly removed attached American dog ticks (Dermacentor variabilis Say) and lone star ticks (Amblyomma americanum L.) from laboratory rabbits in a university animal facility using all tools during one removal session. Tick damage occurring from removal and quantity of attachment cement were compared. No tool removed nymphs without damage and all tools removed adults of both species successfully. American dog ticks proved easier to remove than lone star ticks, whose mouthparts often remained in the skin. Nymphal ticks were consistently removed more successfully with commercial tools when compared with tweezers but with more difficulty than adults were removed. The commercial tick removal tools tested are functional for removal of nymphs and adults and should be considered as viable alternatives to medium-tipped tweezers.


Impact of Check It: A Novel Community-Based Chlamydia Screening and Expedited Treatment Program for Young Black Men.
This study aimed to estimate the impact of the Check It program, a novel community-based chlamydia seek, test, and treat program for young Black men who have sex with women, on test positivity rates for chlamydia in young Black women. We used a synthetic control model to compare chlamydia test positivity rates in Orleans Parish (intervention site) with other similar parishes (control sites) in Louisiana. We estimated a model that used all other parishes as potential contributors to a synthetic control for Louisiana as well as a sample limited to the 40 parishes in Louisiana with the largest Black populations. The Check It program was associated with a 1.69-percentage-point decline in chlamydia positivity in the first full year of operation and a 2.44-percentage-point decline in chlamydia positivity in the second full year of operation compared with control sites with the largest Black populations (P = 0.05). Results were similar when the treatment site was compared with all other sites in Louisiana. The Check It program was associated with a significant decline in chlamydia testing positivity rates among women in Orleans Parish compared with control sites. Screening of young Black men who have sex with women can decrease rates in women living in the same community. Future recommendations for chlamydia screening of young men should be considered.


Iron deficiency: lessons from anemic mice.
Iron is an essential nutrient, and disorders of iron metabolism are common. Nonetheless, intestinal iron absorption and cellular iron transport are poorly understood. Biochemical approaches to elucidating these processes have yielded little in the past decade. As an alternative approach, we have begun to study spontaneous mouse mutants, that have inherited defects in key steps in iron transport. We have undertaken positional cloning of the gene responsible for microcytic anemia (gene symbol mk). This report describes the important characteristics of these mice, and our progress in studying them.


Effect of neoadjuvant chemotherapy in patients with gastric cancer: a PRISMA-compliant systematic review and meta-analysis.
Neoadjuvant chemotherapy (NAC) is extensively used in the treatment of patients with gastric cancer (GC), particularly in high risk, advanced gastric cancer. Previous trials testing the efficacy of NAC have reported inconsistent results. This study compares the combined use of NAC and surgery with surgery alone for GC by using a meta-analytic approach. We performed an electronic search of PubMed, EmBase, and the Cochrane Library to identify randomized controlled trials (RCTs) on NAC published before Oct 2015. The primary outcome of the studies was data on survival rates for patients with GC. The summary results were pooled using the random-effects model. We included 12 prospective RCTs reporting data on 1538 GC patients. Patients who received NAC were associated with significant improvement of OS (P = 0.001) and PFS (P < 0.001). Furthermore, NAC therapy significantly increased the incidence of 1-year survival rate (SR) (P = 0.020), 3-year SR (P = 0.011), and 4-year SR (P = 0.001). Similarly, NAC therapy was associated with a lower incidence of 1-year (P < 0.001), 2-year (P < 0.001), 3-year (P < 0.001), 4-year (P = 0.001), and 5-year recurrence rate (P = 0.002). Conversely, patients who received NAC also experienced a significantly increased risk of lymphocytopenia (P = 0.003), and hemoglobinopathy (P = 0.021). The findings of this study suggested that NAC is associated with significant improvement in the outcomes of survival and disease progression for GC patients while also increasing some toxicity.


Polarized MT1-MMP-CD44 interaction and CD44 cleavage during cell retraction reveal an essential role for MT1-MMP in CD44-mediated invasion.
The adhesion molecule CD44 and the membrane-type matrix metalloproteinase MT1-MMP act coordinately in tumor cells to promote cell invasion through a yet unclear mechanism. We are interested in studying the interplay between CD44 and MT1-MMP in carcinoma cells embedded in HA containing three-dimensional collagen I matrices (3D HA-Col I) by time-lapse confocal microscopy imaging. Here we report the in vivo interaction between CD44 and MT1-MMP, revealed by fluorescence resonance energy transfer (FRET) microscopy. MT1-MMP interacts with CD44 preferentially at the trailing edge of the invading tumor cells during rear retraction and on membrane fragments released during the invasion process. A fluorescent biosensor designed to monitor the proteolytic processing of CD44 by live cell imaging demonstrates that cleavage of the CD44 extracellular domain is enriched in the retracting rear ends of invasive tumor cells. Invasion assays showed that MT1-MMP mediates CD44-dependent tumor-cell invasion, whereas CD44 is not essential for MT1-MMP-mediated invasion of 3D HA-Col I matrices. Together, our results support a role for MT1-MMP in cell retraction during CD44-mediated cell invasion.


Disorders of sex development in cats with different complements of sex chromosomes.
The genetic background of disorders of sex development (DSDs) in cats is poorly understood, due to a relatively low number of such studies in this species. Here we present three new DSD cases with different complements of sex chromosomes. The first, an Oriental Shorthair cat with a rudimentary penis, abdominal atrophic testicles and lack of uterus appeared to be a freemartin, since leucocyte chimerism XX/XY and a lack of Y-linked genes (SRY and ZFY) were observed in DNA isolated from hair follicles. XXY trisomy was identified in the second case, a tortoiseshell Devon Rex male cat with atrophic scrotal testicles and a normal penis. Finally, a European Shorthair cat with atrophic testicles in a bifid scrotum, rudimentary penis and a lack of uterus had XY complement, including Y chromosome of normal size and morphology. Also presence of eight Y-linked genes, detected by PCR, was confirmed. Due to the low testosterone level in this last patient, we searched for a causative mutation in two candidate genes (HSD3B2 and HSD17B3) involved in the metabolism of this steroid hormone. Altogether, five polymorphic sites in HSD3B2 and two in HSD17B3 were found, but none of them showed associations with DSD phenotype. We thus excluded a possibility that the causative mutation is present in these genes. In conclusion, we confirmed that analysis of the sex chromosome complement is a crucial step in diagnosis of DSDs. However, extensive molecular studies of the genes involved in sex development are needed to elucidate the causes of DSDs in cats with normal complements of sex chromosomes.


Bond strength to crown and root dentin.
To investigate (1) the tensile bond strengths of four commercial dentin bonding systems to bovine crown and root dentin and (2) the structure of the hybrid layers for each system bonded to the two dentin substrates. Superficial surfaces were exposed in bovine crown and root dentin. The teeth were embedded in plaster and a 3 mm diameter bonding area was demarcated. The four bonding systems used were All-Bond 2, Super-Bond D-Liner Plus, Clearfil Liner Bond II, and ProBond. Bonding procedures followed the manufacturers' instructions with the exception of Super-Bond D-Liner Plus where the primer was left in situ for 60 seconds. Tensile bond strengths were tested after 24-hour storage in 37 degrees C deionized water. Specimens were also prepared for SEM observation of the hybrid layer, after treatment with 10% phosphoric acid, and 10% phosphoric acid and 5% sodium hypochlorite. Statistically lower bond strengths to crown dentin when compared with root dentin were observed for All-Bond 2, whereas Liner Bond II showed the opposite (P < 0.01). Both ProBond and Super-Bond D-Liner Plus showed no statistical differences between crown and root dentin (P > 0.05). Hybrid layers could be observed for All-Bond 2, Liner Bond II and Super-Bond D-Liner Plus, with no apparent differences between the hybrid layers of crown and root dentin. In the case of ProBond, where the smear layer was not removed during the priming stage, it appeared that the primer had infiltrated and caused hybridization of the smear layer. The differences in bond strength were thought to be related to the different bonding mechanisms of each material, as well as possible variations in the crown and root dentin substrates.


[Effect of alfa-2b interferon on prognostic parameters and clinical events in HIV positive patients in the LAS/ARC stage].
A number of in vivo and in vitro results suggest that interferons have an antiretroviral effect on HIV. To check this, 15 HIV-positive patients who had no full-blown AIDS, were treated with recombinant interferon alpha 2b (5 mill. IU s. c. three times a week) over a period of six months. Twelve to 16 weeks after the initiation of treatment, an increase in CD 4 lymphocytes (+16%), NK cells (+16%), lymphocytes stimulation by con A (+ 176%), neopterin (+66%), and beta-2-microglobulin (+19%) was observed. By the end of the study, all these parameters had slightly decreased again. In all patients with CD4 lymphocytes greater than 0.2 c/nl, we observed a decrease in p24 antigen levels, but in patients with CD4 lymphocytes less than 0.2 c/nl, an increase. It would thus seem that any antiretroviral effect of IFN (as shown by the p24 antigen parameter) is more pronounced in patients with superior immune parameters.


[The quantitative evaluation of early radiation-induced changes in the salivary glands using MRI].
Objective: To quantitatively evaluate the early radiation injury of salivary glands in patients with nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT). Methods: Twenty patients with NPC between 2014 and 2015 from the Second Affiliated Hospital of Soochow University were retrospectively analyzed.All patients underwent an MRI scan before and after IMRT.The volumes, T(1)WI, T(2)WI signal intensity(SIs) and apparent diffusion coefficient (ADCs) of the parotid and submandibular glands were measured.The relative signal intensity (RSIs) of each salivary gland was calculated with cerebrospinal fluid as control.The quantitative parameters of salivary glands were compared before and after radiotherapy. Results: The volumes (cm(3)) and T(1)WI RSIs of the parotid and submandibular glands (14.88±6.00, 5.21±1.76, 2.98±1.05, 1.88±0.42, respectively) were significantly lower than those before radiotherapy (22.26±8.26, 7.76±2.45, 3.58±1.02, 2.27±0.50, respectively) (t=9.921, 4.013, 10.126, 4.202, respectively, P=0.000 for all). The T(2)WI RSIs and ADCs (×10(-3) mm(2)/s) of the parotid and submandibular glands (0.50 ± 0.08, 0.41±0.04, 1.31±0.19, 1.50±0.13, respectively) were significantly higher than those before radiotherapy (0.45±0.07, 0.33±0.05, 1.02±0.21, 1.23±0.13, respectively) (t=-4.846, -9.276, -9.957, -10.679, respectively, P=0.000 for all). The volumes of parotid and submandibular glands were correlated with ADCs (r=-0.512, P=0.000; r=-0.358, P=0.001; respectively). The volumes and ADCs of submandibular glands were correlated with T(1)WI RSIs and T(2)WI RSIs(P<0.05). Conclusion: MRI can quantitatively evaluate the early changes of salivary glands after radiotherapy of nasopharyngeal carcinoma as a noninvasive method, and has high clinical application potential.


The Community Engagement and Translational Research Speaker Series: An Innovative Model of Health Education.
New models of health education are needed as research is becoming increasingly translational and as health care models are being applied to both medical and community settings. The Community Engagement and Translational Research Speaker Series is an innovative model for community health education that engages academic and community participants in shared learning. Over the previous four years, eight Speaker Series events each consisting of three, distinct educational activities have been developed and implemented. Attendees provided ratings on each series event and a subset of them completed a knowledge and process evaluation. The Speaker Series has been well attended by both academic and community representatives (N = 1,573). Evaluation data indicate that participants were highly satisfied across the three events (95%). Data also indicate that the Speaker Series met its intended goals of incorporating community feedback (91%) and increasing knowledge of community resources (98%), identifying health priorities (85%), and developing academic-community partnerships (95%). The Speaker Series has been evaluated positively by both academic and community representatives. This health education model is comprehensive and could be replicated by medical schools and universities striving to enhance community health education programs and curricula.


Exopolysaccharides from probiotic bacteria and their health potential.
Exopolysaccharides (EPS) are extracellular macromolecules excreted as tightly bound capsule or loosely attached slime layer in microorganisms. They play most prominent role against desiccation, phagocytosis, cell recognition, phage attack, antibiotics or toxic compounds and osmotic stress. In the last few decades, natural polymers have gained much attention among scientific communities owing to their therapeutic potential. In particular the EPS retrieved from probiotic bacteria with varied carbohydrate compositions possess a plenty of beneficial properties. Different probiotic microbes have unique behavior in expressing their capability to display significant health promoting characteristics in the form of polysaccharides. In this new era of alternative medicines, these polysaccharides are considered as substitutes for synthetic drugs. The EPS finds applications in various fields like textiles, cosmetics, bioremediation, food and therapeutics. The present review is focused on sources, chemical composition, biosynthetic pathways of EPS and their biological potential. More attention has been given to the scientific investigations on antimicrobial, antitumor, anti-biofilm, antiviral, anti-inflammatory and immunomodulatory activities.


Atypical pharmacokinetics and metabolism of mycophenolic acid in a young kidney transplant recipient with impaired renal function.
A juvenile, female renal transplant recipient suffered two acute rejection episodes: the first on posttransplant day 31 while taking cyclosporine, prednisone, and mycophenolate mofetil (MMF); and the second on posttransplant day 67, when she was taking tacrolimus, prednisone, and MMF. Dosage of MMF was initially started at 2 g/d (corresponding to 600 mg MMF/m(2) twice daily.), but was reduced to 250 mg/d to 500 mg/d after severe diarrhea and a paralytic ileus on posttransplant day 16. During therapy with tacrolimus, prednisone, and MMF, predose plasma mycophenolic acid (MPA) concentrations varied from 1.1 mg/L to 8.2 mg/L (median 3.0 mg/L). On posttransplant day 91, a 12-hour pharmacokinetic profile was obtained. The concentrations of MPA and its metabolites were determined with a validated high-performance liquid chromatography (HPLC) procedure. After oral MMF (250 mg) administration, the MPA concentration showed an atypical decline from a predose concentration of 6.0 mg/L to a value of 3.8 mg/L at 75 minutes postdose, and 3.4 mg/L at 6 hours postdose, before returning to 6.0 mg/L after 12 hours. The 12-hour area under the concentration-time curve (AUC) values for MPA and its major metabolite the phenolic glucuronide MPAG were 55.1 mg.h/L and 800 mg.h/L, respectively. An unusually high concentration (12-h AUC, 165 mg.h/L) of the phenolic glucose conjugate of MPA was found. The apparent renal clearance of MPAG was only 2.2 mL/min. Her creatinine clearance was 30 mL/min. MPAG clearances have been reported to range from approximately. 5.5 mL/min to 35 mL/min at a creatinine clearance of approximately 30 mL/min in renal transplant recipients. The authors' findings suggest that conjugation and clearance of MPA through the kidney is strongly impaired in this patient. The relatively high predose MPA concentrations could result from an enhanced enterohepatic circulation of MPA and its metabolites.


Electromagnetically induced phase grating.
I propose an electromagnetically induced phase grating based on the giant Kerr nonlinearity of an atomic medium under electromagnetically induced transparency. The atomic phase grating behaves similarly to an ideal sinusoidal phase grating, and it is capable of producing a pi phase excursion across a weak probe beam along with high transmissivity. The grating is created with arbitrarily weak fields, and diffraction efficiencies as high as 30% are predicted.


Intra-Golgi protein transport depends on a cholesterol balance in the lipid membrane.
Transport of proteins between intracellular membrane compartments is mediated by a protein machinery that regulates the budding and fusion processes of individual transport steps. Although the core proteins of both processes are defined at great detail, much less is known about the involvement of lipids. Here we report that changing the cellular balance of cholesterol resulted in changes of the morphology of the Golgi apparatus, accompanied by an inhibition of protein transport. By using a well characterized cell-free intra-Golgi transport assay, these observations were further investigated, and it was found that the transport reaction is sensitive to small changes in the cholesterol content of Golgi membranes. Addition as well as removal of cholesterol (10 +/- 6%) to Golgi membranes by use of methyl-beta-cyclodextrin specifically inhibited the intra-Golgi transport assay. Transport inhibition occurred at the fusion step. Modulation of the cholesterol content changed the lipid raft partitioning of phosphatidylcholine and heterotrimeric G proteins, but not of other (non) lipid raft proteins and lipids. We suggest that the cholesterol balance in Golgi membranes plays an essential role in intra-Golgi protein transport and needs to be carefully regulated to maintain the structural and functional organization of the Golgi apparatus.


Distinguishing Epidermolysis Bullosa Acquisita From Bullous Pemphigoid Without Direct Immunofluorescence.
It has been postulated that periodic acid-Schiff staining of basement membrane can predict direct immunofluorescence patterns seen in epidermolysis bullosa acquisita and bullous pemphigoid. It has also been suggested that the type of inflammatory infiltrate or presence of fraying of basal keratinocytes may differentiate these two conditions. In this study, we aimed to confirm these observations. We reviewed 13 cases of direct immunofluorescence-confirmed epidermolysis bullosa acquisita and 19 cases of direct immunofluorescence-confirmed bullous pemphigoid, all with a subepidermal blister in the routinely processed specimen. The gold standard for diagnosis of epidermolysis bullosa acquisita vs bullous pemphigoid was taken to be identification of immune deposits on the dermal side ('floor' for epidermolysis bullosa acquisita) or the epidermal side ('roof' for bullous pemphigoid) of the salt-split direct immunofluorescence specimen. Our tests to distinguish epidermolysis bullosa acquisita from bullous pemphigoid on the routinely processed biopsy included periodic acid-Schiff basement membrane on the blister roof, neutrophilic infiltrate, lack of eosinophilic infiltrate, and absence of keratinocyte fraying. Sensitivity and specificity for each test were as follows: periodic acid-Schiff staining of roof (sensitivity 25%, specificity 95%), neutrophilic infiltrate (sensitivity 54%, specificity 74%), lack of eosinophilic infiltrate (sensitivity 92%, specificity 68%), and absence of keratinocyte fraying (sensitivity 62%, specificity 58%). Features in the routinely processed biopsy were unable to reliably distinguish between epidermolysis bullosa acquisita and bullous pemphigoid. Direct immunofluorescence on salt-split skin remains the standard for differentiation.


Persistent infection of mouse tumor cells with mumps virus.
A mouse tumor cell line (MCT) persistently infected with mumps virus (strain Urabe) was obtained. No antibody or chemicals were required for establishment or maintenance of the infected cell line (M-MCT). No difference was observed by light microscopy between MCT and M-MCT cells, except for cytoplasmic inclusion bodies in 10--20% of the M-MCT cells. Hemadsorption of chicken erythrocytes, which did not necessarily coincide with inclusion positive cells was shown by 10--20% of the M-MCT cells. Immunofluorescence staining revealed that almost all M-MCT cells contained mumps virus antigens, which were seen mainly in the cytoplasm as fine granules, dots, or large clumps. Infectious mumps virus was consistently detected in the culture fluid and the released virus showed some temperature sensitivity when assayed at 34 degrees C and 40 degrees C. M-MCT was resistant to superinfection with homologous virus and showed some resistance to heterologous viruses. Thirty one clones of M-MCT were isolated by the soft agar method. Some, but not all, clones had viral antigen and all those with antigen released virus into the culture medium. The growth rates of MCT and M-MCT cells as monolayer cultures in vitro were similar, but the transplantability of M-MCT cells in syngeneic C57BL/6 mice was lower than that of MCT cells.


Antinociceptive and antiinflammatory effects of Niga-ichigoside F1 and 23-hydroxytormentic acid obtained from Rubus coreanus.
As an attempt to search for bioactive natural constituents exerting antinociceptive and antiinflammatory activities, we examined the potency of the extract of Rubus coreanus fruits by the activity-guided fractionation. The EtOAc- and BuOH fraction and those alkaline hydrolysates showed significant antinociceptive effects as assessed by writhing-, hot plate- and tail flicks tests in mice and rats as well as antiinflammatory effect in rats with carrageenan-induced edema. BuOH extract was subjected to column chromatography to obtain a large amount of niga-ichigoside F(1) (1,23-hydroxytormentic acid 28-O-glc), which was again hydrolyzed in NaOH solution to yield an aglycone 23-hydroxytormentic acid (1a). The aglycone, 23-hydroxytormentic acid, was much more potent in both antinociceptive and antiinflammatory tests than the glycoside, niga-ichigoside F(1). The antiinflammatory effects of these compounds were further supported by the reduction of carrageenan-induced lipid peroxidation and hydroxyl radical in serum. These results suggested that 23-hydroxytormentic acid might be an active moiety of niga-ichigoside F(1) present in R. coreanus.


Identity determinants of human tRNA(Ser): sequence elements necessary for serylation and maturation of a tRNA with a long extra arm.
Recently, there has been much progress in understanding tRNA identity, i.e. in elucidating the sets of nucleotides that are responsible for the specific aminoacylation of a tRNA with its cognate amino acid. Interest focused, however, on tRNAs from Escherichia coli and yeast. Here we have identified the major and minor determinants of human tRNA(Ser) which were revealed by an identity switch from human tRNA(Val) to tRNA(Ser). We used in vitro transcripts and subsequent aminoacylation by HeLa S100 extract to determine the kinetic parameter Vmax/Km. The two major identity elements which are absolutely required for aminoacylation by human seryl-tRNA synthetase are the discriminator base and the long extra arm. This is in contrast to E. coli tRNA(Ser) where the discriminator base is unimportant, whereas identity determinants in the acceptor stem are required. Other sequence elements have an influence not only on serylation, but also on tRNA maturation in vitro, i.e. on pre-tRNA processing and base modification. These nucleotides are located in the DHU and the T phi C arm and are probably necessary for the proper folding of tRNAs containing a long extra arm. A34 to inosine modification depends highly on the correct three-dimensional structure of the tRNA, whereas A58 to m1A methylation does not rely on the three-dimensional folding of the substrate. This is the first tRNA identity switch involving the exchange of a short versus a long extra arm.


Vasoactive intestinal peptide in the hypothalamohypophysial system of the Mongolian gerbil.
By use of the indirect peroxidase-antiperoxidase immunohistochemical technique the location of perikarya and fibers exhibiting vasoactive intestinal peptide (VIP)-like immunoreactivity was investigated in the hypothalamus and the posterior pituitary of the Mongolian gerbil (Meriones unguiculatus), because of the involvement of VIP in several neuroendocrine functions. In the hypothalamus, a large number of VIP-immunoreactive perikarya were seen in the ventromedial part of the suprachiasmatic nucleus. Few VIP-positive perikarya were present in the periventricular, paraventricular, and supraoptic nuclei and in the medial preoptic area close to the third ventricle. The perikarya in the paraventricular nucleus projected fibers in the direction of the median eminence. In the median eminence VIP-immunoreactive fibers were present especially in the external layer, concentrated in the perivascular spaces surrounding the portal vessels. Scattered VIP-immunoreactive fibers were also located in the internal layer of the median eminence as well as in the posterior pituitary lobe. In the latter, large VIP-positive Herring-like bodies were observed. With receptor autoradiography a large number of grains were demonstrated in the anterior pituitary lobe in contrast to the neural lobe. Many VIP-positive fibers and some perikarya were observed within the ependyma covering the rostroventral part of the third ventricle. Finally, fibers exhibiting VIP immunoreactivity were also seen in the organum vasculosum laminae terminalis (OVLT). These results support the concept that VIP is released into the portal vascular system and plays a role in the regulation of the activity of the anterior pituitary. In addition, VIP might be secreted into the cerebrospinal fluid of the third ventricle.


IL13RA2 targeted alpha particle therapy against glioblastomas.
Glioblastoma (GBM) is the most aggressive primary malignant brain cancer that invariably results in a dismal prognosis. Chemotherapy and radiotherapy have not been completely effective as standard treatment options for patients due to recurrent disease. We and others have therefore developed molecular strategies to specifically target interleukin 13 receptor alpha 2 (IL13RA2), a GBM restricted receptor expressed abundantly on over 75% of GBM patients. In this work, we evaluated the potential of Pep-1L, a novel IL13RA2 targeted peptide, as a platform to deliver targeted lethal therapies to GBM. To demonstrate GBM-specificity, we radiolabeled Pep-1L with Copper-64 and performed in vitro cell binding studies, which demonstrated specific binding that was blocked by unlabeled Pep-1L. Furthermore, we demonstrated real-time GBM localization of [64Cu]Pep-1L to orthotopic GBMs using small animal PET imaging. Based on these targeting data, we performed an initial in vivo safety and therapeutic study using Pep-1L conjugated to Actinium-225, an alpha particle emitter that has been shown to potently and irreversibly kill targeted cells. We infused [225Ac]Pep-1L into orthotopic GBMs using convection-enhanced delivery and found no significant adverse events at injected doses. Furthermore, our initial data also demonstrated significantly greater overall, median and mean survival in treated mice when compared to those in control groups (p < 0.05). GBM tissue extracted from mice treated with [225Ac]Pep-1L showed double stranded DNA breaks, lower Ki67 expression and greater propidium iodide internalization, indicating anti-GBM therapeutic effects of [225Ac]Pep-1L. Based on our results, Pep-1L warrants further investigation as a potential targeted platform to deliver anti-cancer agents.


Milk inhibits the regression of 7,12-dimethylbenz(a)anthracene-induced mammary tumors in ovariectomized rats.
Epidemiological studies have yielded inconsistent results regarding the relation between the milk consumption and breast cancer risk. In this study, rats were induced mammary tumors by 7,12-dimethylbenz(a)anthracene. When tumors developed to acceptable levels, rats were placed into 1 of 3 treatment groups. Those in the negative control group and the milk group were ovariectomized, whereas those in the positive control group were sham operated. After grouping, tumor incidence remained 100%, and tumor number and volume increased in the positive control group. However, tumors in the 2 ovariectomized groups regressed. Compared with the negative control group, tumor incidence and tumor number and volume per rat in the milk group became significantly higher from Week 6 and Week 4, respectively. Insulin-like growth factor-I levels were borderline significantly higher in the milk group than in the negative control group at autopsy. Although plasma 17beta-estradiol levels did not differ significantly, estrogenicity was found in the milk group because uterine weight was significantly heavier in the milk group than in the negative control group. In conclusion, commercial milk inhibited the regression of carcinogen-induced mammary tumors in ovariectomized rats.


The Senior Companion Program Plus: An Innovative Training Approach for Alzheimer's Disease and Related Dementia.
African Americans adults are disproportionately affected by Alzheimer's disease and related dementias (ADRD) and are underrepresented in research about ADRD. Reducing gaps in the knowledge about ADRD in the African American community is important for addressing dementia care disparities. The existing psychoeducation interventions are often limited by cost and scalability; for these reasons, lay provider (i.e., volunteer) interventions are of increasing interest in ADRD research. The purpose of this study was to evaluate a training of African American Senior Companion (SC) volunteers (n = 11) with dementia-specific knowledge (i.e., Senior Companion Program/SCP Plus), as part of a culturally informed, in-home, psychoeducational intervention for African American ADRD family caregivers. Learning outcomes were measured pre- and post-training, using the Knowledge of Alzheimer's Disease/dementia scale (KAD), the Sense of Competence Questionnaire, and the Preparedness for Caregiving Scale. The results showed significant improvements in knowledge of Alzheimer's disease/dementia, one competence item, "It is clear to me how much care my care recipient needs", and preparedness for caregiving. Overall, the study findings suggest the SCP Plus is a promising, culturally relevant, and potentially scalable lay provider training for ADRD with potential benefits that augment the existing Senior Companion Program.


[Clinical significance of serum intestinal fatty acid-binding protein in full-term infants with necrotizing enterocolitis].
To evaluate the clinical value of intestinal fatty acid-binding protein (I-FABP) in full-term newborn infants with necrotizing enterocolitis (NEC). Forty-one full-term infants with a confirmed diagnosis of NEC from February 2012 to January 2014 were recruited as case group (stage I: 24 cases; stage II-III: 17 cases). Sixty-two children diagnosed with non-digestive diseases in the same period were recruited as the control group. Serum levels of I-FABP and C-reactive protein (CRP) were determined by enzyme-linked immunosorbent assay. The diagnostic value of I-FABP for NEC was assessed using the receiver operating characteristic (ROC) curve. Stage I and stage II-III cases in the case group had significantly higher serum I-FABP levels than the control group (P<0.05), and stage II-III cases had significantly higher serum I-FABP levels than stage I cases (P<0.05). The area under the ROC curve for serum I-FABP was 0.85 (95% CI: 0.78-0.92), with the optimal cut-off point of 2.25 ng/mL. Under this cut-off point, the sensitivity and specificity were 80.49% and 70.19%, respectively. There was no significant difference in serum CRP level between the case and control groups (P>0.05). In newborn infants with NEC, serum I-FABP level increases significantly in stage I , and it is correlated with the disease severity. Therefore, serum I-FABP can be used as a biomarker for the diagnosis of NEC.


Characterization of the DNA molecular sequence of complete plastid genome of Paeonia rockii subsp. taibaishanica, an endemic species in China.
Paeonia rockii subsp. taibaishanica (Paeoniaceae), one of the tree peony species, is endemic to the Qinling Mountains in central China. In this study, we characterized its whole plastid genome sequence using the Illumina sequencing platform. The complete plastid genome size of P. rockii subsp. taibaishanica is 153,368 bp in length, including a large single copy (LSC) region of 85,030 bp, a small single copy (SSC) region of 17,042 bp, and a pair of inverted repeats (IRs) of 25,648 bp. The genome contains 131 genes, including 83 protein-coding genes, 37 tRNA genes, and 8 rRNA genes. The GC contents in chloroplast genome, LSC region, SSC region, and IR region were 38.3%, 36.6%, 32.6%, and 43.1%, respectively. A total of 16 species are used to construct the phylogenetic tree of Paeoniaceae, the results showed that P. rockii subsp. taibaishanica is more closely related with congeneric Paeonia suffruticosa and Paeonia ostii, these species were clustered into a clade with high bootstrap support.


Pathological Changes in the Lymphatic System of Patients with Secondary Lower Limb Lymphedema Based on Single Photon-Emission Computed Tomography/Computed Tomography/Lymphoscintigraphy Images.
Background: In patients with secondary upper limb lymphedema, positive correlations have been observed between the dermal back flow (DBF) type and visualization of lymph nodes around the clavicle, between the former and the lymph flow pathway type, and between the latter and the visualization of lymph nodes around the clavicle when using single photon-emission computed tomography/computed tomography/lymphoscintigraphy (SPECT-CT LSG). Methods and Results: We analyzed the associations between the visualization of inguinal lymph nodes, the lymph flow pathway type, and the DBF type using SPECT-CT LSG in 81 patients with unilateral secondary lower limb lymphedema by statistical analysis using Fisher's exact test. We revealed that the lymph flow pathways in the lower limb can be classified into nine types because the type in the lower leg is not always equal to the type in the thigh. Associations were observed between the visualization of inguinal lymph nodes and types of DBF (p < 0.01), between the types of lymph flow pathway in the thighs and visualization of the inguinal lymph nodes (p = 0.02), and between the lymph flow pathway types in the thighs and lower legs (p < 0.01). Conclusion: Detriment to the superficial lymph flow pathways in the lower limb appears to usually start from the proximal side, and deep pathways are considered to become dominant from a compensatory perspective as lymphedema severity increases.


[Clinical features and therapeutic responses of perianal lesions in Crohn's disease].
The aim of this study was to assess the clinical features and therapeutic responses of perianal lesions in Crohn's disease. We retrospectively reviewed medical records of 94 cases with perianal lesions among 231 cases registered as Crohn's disease in Seoul National University Hospital between January 1975 and June 2001. The cases were investigated after dividing into two different groups. One group included the cases registered between January 1975 and December 1996 and the other group between January 1997 and June 2001. The perianal lesions were observed in 41% of the cases. Perianal lesions were more frequent in colonic Crohn's disease after 1997, but not before 1996. Fistula was significantly prevalent, followed by abscess, fissure, and stricture. Perianal lesions preceded intestinal symptoms such as abdominal pain and diarrhea in 25% of the cases. The remission rate with non-specific conservative treatment (10%) was lower than that before 1996. The remission rate after specific treatment (77%) was higher than that after surgery (53%). In cases of specific treatment, cumulative relapse rates were 7% in 1 year and 39% in 5 years. Crohn's disease should be considered in young male patients who have the refractory perianal lesions. Perianal lesions should be managed initially with medical treatment.


A therapeutic milieu for establishing and expanding communicative behaviors in psychotic children.
This study describes a clinical intervention program that was used to facilitate development of receptive and expressive language skills in a group of four psychotic children. A group format utilizing an interactive language development teaching procedure combined with a therapeutic milieu was shown to be effective in establishing and expanding communicative behaviors in psychotic children. Nine diagnostic measures were utilized to assess children's performance prior to therapy and at the end of three-month and six-month intervals. Results indicated substantial reduction of delayed and immediate echolalia, jargon, inappropriate stress, pitch, and intonation. Substantial improvement was noted in expressive syntactic and morphological functioning and in the children's ability to generate novel utterances about day-to-day experiences, family, and toys. Increases in children's concept of body image and ego functioning paralleled their improvement in receptive and expressive language development.


Predictors of Remission of Early-Onset Poststroke Depression and the Interaction Between Depression and Cognition During Follow-Up.
Objectives: This study aimed to examine the rate of remission in individuals experiencing early-onset poststroke depression (PSD) in China and to identify predictors of remission during a 3-month follow-up. This study also explored the interaction between cognitive impairment and depression. Methods: A total of 820 patients with PSD from a massive multicenter prospective cohort project in China (PRIOD) were included in the present study. Depressive symptoms were measured with the Hamilton Depression Rating Scale (17 Items, HDRS-17) at 2 weeks and the endpoint of the 3-month follow-up. The cut-off score of HDRS-17 (< 8) was used to define remission of depression at the endpoint. The Mini-Mental State Exam (MMSE) was used to evaluate the cognitive impairment of the patients (at the 2-week follow-up and 3-month endpoint). The National Institutes of Health Stroke Scale (NIHSS) was used to measure the severity of stroke. Results: (1) Six hundred and forty-two patients completed the 3-month follow-up, and 332 (51.7%) patients remitted by the end of the study. Univariate analyses indicated that there was a higher proportion of patients who had hypertension, frontal lobe lesion, basal ganglia lesion, poor outcome at 2 weeks, high scores on the NIHSS at 2 weeks, major life events within 3 months, and major medical diseases within 3 months in the nonremission group. In stepwise multiple logistic regression analyses, remission was significantly predicted by lower NIHSS scores at 2 weeks (p = 0.001, OR = 1.086, 95% CI 1.035-1.139), fewer major life events (p = 0.036, OR = 5.195, 95% CI 1.111-27.283), fewer major medical comorbidities (p = 0.015, OR = 2.434, 95% CI 1.190-4.979), and fewer frontal lobe lesions (p = 0.042, OR = 1.717, 95% CI 1.019-2.891). (2) After controlling for confounding variables, repeated measures analysis of variance revealed a significant interaction between time (2 weeks vs. 3 months) and group (remitters vs. nonremitters) on MMSE scores [F (1, 532) = 20.2, p < 0.001]. Conclusions: Early-onset PSD patients with milder neurological impairment, fewer major life events, fewer major medical comorbidities and no frontal lobe lesion at baseline were more likely to achieve remission 3 months after stroke. Only remitters of PSD improved significantly in cognitive impairment after stroke. The PRIOD trial is registered at http://www.isrctn.com/, number ISRCTN62169508.


Preliminary observations on the activity of progabide, administered as monotherapy in complex partial seizures.
Progabide (PGB), a gamma-amino-butyric acid receptor agonist, was administered, according to an open-label long-term design, to 40 adult patients suffering from complex partial seizures, with or without secondary generalization, whose response to carbamazepine (CBZ) monotherapy was unsatisfactory. A reference-baseline period of two months with carbamazepine monotherapy was followed by a two-month "add-on" period where increasing doses of progabide were added without modifying the CBZ regimen; then CBZ was withdrawn over 15-60 days and patients were followed up to 12 months' progabide treatment. Twenty-seven patients completed the trial but 12 of them had to be returned to CBZ + PGB bitherapy due to an increase of seizures following CBZ withdrawal. A definite therapeutic effect could be observed in nine patients on PGB monotherapy and in six patients on CBZ + PGB bitherapy. Side-effects of clinical relevance occurred in three cases and were represented by remarkable anxiety in two patients and a rise in serum glutamic oxalo-acetic acid and pyruvic transaminases with clinical symptoms of liver dysfunction in one, with rapid recovery following progabide discontinuation. In conclusion, progabide was effective against complex partial seizures in about 40% of patients not responding satisfactorily to available antiepileptic drugs. Although the withdrawal of previous antiepileptic drugs was not possible in all patients, progabide monotherapy was sometimes more effective than CBZ monotherapy, and several patients in whom bitherapy had to be restored benefited from the association of progabide.


[Diagnostic aspects of familial juvenile hyperuriceamic nephropathy].
BACKGROUND; Familial juvenile hyperuricemic nephropathy (FJHN) is a genetic disorder with the autosomal dominant mode of hereditability; characterized with hyperuricemia, gout and progressive renal disease. Characterization of the disease together with clinical and biochemical findings in patients of Czech population is described. The bloodlines of three Czech families with FJHN were set up on the basis of their family history. The specimens of blood and urine were taken from 57 family members for biochemical investigations and isolations of genomic DNA. Blood and urinary concentrations of the uric acid and creatinine together with values of excretion fraction of uric acid and Kaufman's index were determined. Based on these results diagnosis of FJHN was established or confirmed in 19 patients. One additional patient was diagnosed on the results of linkage analysis. FJHN is a disorder sharing non-specific clinical and biochemical signs with the group of familial renal disorders. The effective diagnosis is difficult due to the heterogeneity of the disorder and limited availability of molecular genetic analysis. Detailed purine metabolic investigation together with precise family history is thus necessary and very important in family members with hyperuricemia and/or gout (particularly in childhood or young women) as well as in patients with familial renal disease.


A new neuropeptide insect parathyroid hormone iPTH in the red flour beetle Tribolium castaneum.
In the postgenomics era, comparative genomics have advanced the understanding of evolutionary processes of neuropeptidergic signaling systems. The evolutionary origin of many neuropeptidergic signaling systems can be traced date back to early metazoan evolution based on the conserved sequences. Insect parathyroid hormone receptor (iPTHR) was previously described as an ortholog of vertebrate PTHR that has a well-known function in controlling bone remodeling. However, there was no sequence homologous to PTH sequence in insect genomes, leaving the iPTHR as an orphan receptor. Here, we identified the authentic ligand insect PTH (iPTH) for the iPTHR. The taxonomic distribution of iPTHR, which is lacking in Diptera and Lepidoptera, provided a lead for identifying the authentic ligand. We found that a previously described orphan ligand known as PXXXamide (where X is any amino acid) described in the cuttlefish Sepia officinalis has a similar taxonomic distribution pattern as iPTHR. Tests of this peptide, iPTH, in functional reporter assays confirmed the interaction of the ligand-receptor pair. Study of a model beetle, Tribolium castaneum, was used to investigate the function of the iPTH signaling system by RNA interference followed by RNA sequencing and phenotyping. The results suggested that the iPTH system is likely involved in the regulation of cuticle formation that culminates with a phenotype of defects in wing exoskeleton maturation at the time of adult eclosion. Moreover, RNAi of iPTHRs also led to significant reductions in egg numbers and hatching rates after parental RNAi.


[A new system of prolonged genetic instability induced by N-ethyl-N-nitrosourea in Drosophila melanogaster].
A novel system of prolonged genetic instability induced by N-ethyl-N-nitrosourea in D. melanogaster was obtained. The instability was associated with the appearance of new mutations in loci yellow, scute, white, cut, singed, miniature, vermilion and extended for 40 generations. Some mutants of locus cut were obtained by the method of Southern blot-hybridisation. The reversion ct+ appeared as a result of excision of gypsy element. The mutation ctpN34 was localized in the second complementation group of cut locus and was the consequent of deletions of gypsy element and small DNA fragment and an insertion of a DNA sequence 7.8 kb in size.


Expression of osteopontin in patients with thyroid dysfunction.
Thyroid dysfunctions are common endocrine problems. They are often misdiagnosed, misunderstood, and frequently overlooked. These disorders affect almost every aspect of health. Most of them remain undetected because the clinical assessment alone lacks both sensitivity and specificity. As it is not sufficient enough we require the biochemical tests to confirm the diagnosis. As a consequence there is still great interest in new biomarkers that complement existing diagnostic tools. Osteopontin, a glycoprotein that can be detected in plasma, was found to be upregulated in several patients with hyperthyroidism and downregulated in hypothyroid patients so it may represent a new biomarker. 100 patients with thyroid dysfunctions (50 hyperthyroid, 50 hypothyroid) and 100 normal subjects were included in the study. Osteopontin and other clinical parameters for diagnosis of thyroid disorders were measured. Osteopontin is positively correlated with T3 and T4 (r = 0.62 and r = 0.75 respectively) while it is negatively correlated with thyroid stimulating hormone (r = -0.52) showing a significant correlation (p-value <0.001). Our findings suggest that osteopontin might be useful as a novel prognostic biomarker in patients with impaired thyroid function.


The current landscape of genetic test stewardship: A multi-center prospective study.
Genetic counselors (GCs) play a pivotal role in selecting clinically appropriate and cost-effective genetic testing. Several single-institution reports over the past decade provide evidence of the value GCs bring to this stewardship role across diverse settings in healthcare, including hospital laboratories, commercial laboratories, and insurance companies. This multi-center, prospective, and quantitative study describes the outcomes of GC review of genetic test requests over a four-week period at six hospital laboratories and three commercial laboratories, thus expanding our understanding of this emerging specialty in the genetic counseling field. This study also highlights the added value of utilizing GC expertise in stewardship efforts, namely selecting the most appropriate genetic testing and realizing significant cost savings. GC review of genetic test requests led to an average order modification rate of 22%-25%. It also resulted in significant cost savings to institutions. The projected average annual savings after GC review of genetic test requests approximated $665,600 for hospital laboratories and $1,651,000 for commercial laboratories. These study findings demonstrate the significant value of GC-led genetic test stewardship programs, allow for comparisons across institutions currently performing genetic test stewardship, and support the implementation of a GC-led stewardship program at institutions who currently do not have one.


Empirical Analysis of Preferences of Older Adults for Care Facilities in Japan: Focusing on Household Structure and Economic Status.
Japan is advancing into a super-aged society at an unprecedented speed, and the proportion of the elderly population will continue to rise. The number of older adults needing nursing care will also increase with the aging population. We used a cross-sectional dataset of older Japanese adults to examine their future preferences for care facilities and their relationship with individual characteristics, household structure, and economic status. We further focused on a subgroup of those who lived alone and were experiencing poverty and examined their care needs through their choice of care facilities. We found the following results from multinomial logit and probit regressions. First, compared with living alone, older adults who live with their spouses or other members prefer to live in their own houses. Second, older adults experiencing poverty preferred to choose facilities geared towards low-income groups, while wealthy older adults preferred to choose fee-based nursing homes/nursing homes with diverse services and high costs. Third, single older adults in poverty were less likely to choose to live in facilities. Covariates such as sex, age, and health status also mattered in their choices. Therefore, tailoring the formal care services to the preferences and actual needs of older adults is imperative.


PKC signaling is involved in the regulation of progranulin (acrogranin/PC-cell-derived growth factor/granulin-epithelin precursor) protein expression in human ovarian cancer cell lines.
Overexpression of progranulin (also named acrogranin, PC-cell-derived growth factor, or granulin-epithelin precursor) is associated with ovarian cancer, specifically with cell proliferation, malignancy, chemoresistance, and shortened overall survival. The objective of the current study is to identify the signaling pathways involved in the regulation of progranulin expression in ovarian cancer cell lines. We studied the relation of protein kinase C (PKC), phosphatidylinositol 3-kinase, protein kinase A, P38, extracellular signal-regulated kinase, and Akt pathways on the modulation of progranulin expression levels in NIH-OVCAR-3 and SK-OV-3 ovarian cancer cell lines. The different pathways were examined using pharmacological inhibitors (calphostin C, LY294002, H89, SB203580, PD98059, and Akt Inhibitor), and mRNA and protein progranulin expression were analyzed by reverse transcriptase polymerase chain reaction and Western blot techniques, respectively. Inhibition of PKC signal transduction pathway by calphostin C decreased in a dose-dependent manner protein but not mRNA levels of progranulin in both ovarian cancer cell lines. LY294002 but not wortmannin, which are phosphatidylinositol 3-kinase inhibitors, also diminished the expression of progranulin in both cell lines. In addition, LY294002 treatment produced a significant reduction in cell viability. Inhibition of protein kinase A, P38, extracellular signal-regulated kinase, and Akt did not affect progranulin protein expression. These results suggest that the PKC signaling is involved in the regulation of progranulin protein expression in 2 different ovarian cancer cell lines. Inhibiting these intracellular signal transduction pathways may provide a future therapeutic target for hindering the cellular proliferation and invasion in ovarian cancer produced by progranulin.


Survival outcomes of patients with colorectal liver metastases following hepatic resection or ablation in the era of effective chemotherapy.
The outcome of patients with colorectal liver metastases (CLM) undergoing surgical resection in the era of effective chemotherapy is not widely reported. In addition, factors associated with disease-specific survival (DSS) in a contemporary series of patients are not well defined. Clinical, pathologic, and outcome data for 64 patients with CLM treated by a single surgeon in a multidisciplinary setting from February 2002 to October 2007 were examined. Hepatic resection was combined with radiofrequency ablation (RFA) in 23 (36%) cases. Secondary or tertiary resection was undertaken in 12 (19%) patients. Synchronous CLM were noted in 25 (39%) cases. Neoadjuvant chemotherapy was given to 41 (64%) patients. Following hepatic resection, adjuvant chemotherapy was administered in 52 (81%) cases. There was one (2%) operative mortality. One or more complications were noted in 24 (38%) patients. Median length of hospital stay was 7 (2-7) days. Five-year DSS and overall survival were 72% and 69%, respectively. Bilobar disease (p < 0.001), local tumor extension (p = 0.02), response to neoadjuvant chemotherapy (p = 0.005), preoperative portal vein embolization (p = 0.05), number of hepatic lesions (p = 0.03), positive resection margin (p < 0.001), and node-positive primary disease (p = 0.001) were prognostically significant factors on univariate analysis. On multivariate analysis, bilobar disease (p = 0.02) and local tumor extension (p = 0.02) were the only two independent prognostic factors. We conclude that, in patients with CLM, a multidisciplinary approach encompassing an aggressive surgical policy achieves excellent 5-year survival results with acceptable operative morbidity and mortality. Bilobar disease and local extrahepatic extension of cancer appear to be independent prognostic factors for long-term survival.


Nonaxisymmetric magnetorotational instabilities in cylindrical Taylor-Couette flow.
We study the stability of cylindrical Taylor-Couette flow in the presence of azimuthal magnetic fields, and show that one obtains nonaxisymmetric magnetorotational instabilities, having azimuthal wave number m=1. For Omega{o}/Omega{i} only slightly greater than the Rayleigh value (r{i}/r{o}){2}, the critical Reynolds and Hartmann numbers are Re{c} approximately 10{3} and Ha{c} approximately 10{2}, independent of the magnetic Prandtl number Pm. These values are sufficiently small that it should be possible to obtain these instabilities in the Potsdam Rossendorf Magnetic Instability Experiment.


Application of Fundamental Chemical Principles for Solvation Effects: A Unified Perspective for Interaction Patterns in Solution.
We demonstrate the utility of basic chemical principles like the "|Δμ| big is good" (DMB) rule for the study of solvation interactions between distinct solutes such as ions and solvents. The corresponding approach allows us to define relevant criteria for maximum solvation energies of ion pairs in different solvents in terms of electronegativities and chemical hardnesses. Our findings reveal that the DMB principle culminates into the strong and weak acids and bases concept as recently derived for specific ion effects in various solvents. The further application of the DMB approach highlights a similar condition for the chemical hardnesses with a reminiscence to the hard/soft acids and bases principle. Comparable conclusions can also be drawn with regard to the change of the solvent. We show that favorable solvent interactions are mainly driven by low chemical hardnesses as well as high electronegativity differences between the ions and the solvent. Our findings highlight that solvation interactions are governed by basic chemical principles, which demonstrates the close similarity between solvation mechanisms and chemical reactions.


Holding power of different screws in the femoral head. A study in human cadaver hips.
The holding power of four different bone screws was measured by a pull-out test in 40 cadaver hips from 10 females and 10 males over 70 years of age. Each femoral head was used to test a 6.5 mm cancellous bone screw and a 12.7 mm hip compression screw. The holding power was higher in screws with a long or wide thread. Generally, the holding power in bones from females was about 70 per cent of that in bones from males.


Capillary electrophoresis separation in the presence of an immiscible boundary for droplet analysis.
This paper demonstrates the ability to use capillary electrophoresis (CE) separation coupled with laser-induced fluorescence for analyzing the contents of single femtoliter-volume aqueous droplets. A single droplet was formed using a T-channel (3 microm wide by 3 microm tall) connected to microinjectors, and then the droplet was fluidically moved to an immiscible boundary that isolates the CE channel (50 microm wide by 50 microm tall) from the droplet generation region. Fusion of the aqueous droplet with the immiscible boundary effectively injects the droplet content into the separation channel. In addition to injecting the contents of droplets, we found aqueous samples can be introduced directly into the separation channel by reversibly penetrating and resealing the immiscible partition. Because droplet generation in channels requires hydrophobic surfaces, we have also investigated the advantages to using all hydrophobic channels versus channel systems with patterned hydrophobic and hydrophilic regions. To fabricate devices with patterned surface chemistry, we have developed a simple strategy based on differential wetting to deposit selectively a hydrophilic polymer (poly(styrenesulfonate)) onto desired regions of the microfluidic chip. Finally, we applied our device to the separation of a simple mixture of fluorescein-labeled amino acids contained within a approximately 10-fL droplet.


Can Condylectomy Alone Achieve Facial Symmetry in Patients With Hemimandibular Hyperplasia (Condylar Hyperplasia Type 2)?
The purpose of the present study was to evaluate the 3-dimensional orofacial changes occurring after proportional condylectomy in patients with unilateral condylar hyperplasia type 2 (hemimandibular hyperplasia). Eight patients underwent proportional condylectomy that was not followed by orthognathic surgery or orthodontic treatment for at least 1 year. The precondylectomy and postcondylectomy photographs and radiographs were analyzed cephalometrically and compared. The average length of the condylar segment removed was 13 mm and this resulted in almost equal heights of the ramus-condyle units of both sides. Evaluations in the vertical plane improved after surgery; however, when the preoperative asymmetry was significant, the residual asymmetry continued to be notable after condylectomy. Transverse plane evaluations improved after condylectomy, and chin position was satisfactorily centralized in all patients. In the horizontal plane, mandibular setback occurred, and this was considered favorable when the preoperative skeletal profile was class III, whereas the opposite was when the patient was class I before surgery. The occlusion improved gradually over the postoperative months by the intrusion on the affected side and extrusion on the unaffected side into a bilaterally balanced posterior contacts with residual anterior open bite. In conclusion, condylar hyperplasia type 2 patients with mild asymmetry and low esthetic demands can benefit from proportional condylectomy as the sole treatment to both stop the hyperplastic condylar growth and improve the asymmetry to some extent. Surgeons should be able to predict the change that is expected to occur after proportional condylectomy and discuss this with the patient before surgery.


Transgenic expression of the proneural transcription factor Ascl1 in Müller glia stimulates retinal regeneration in young mice.
Müller glial cells are the source of retinal regeneration in fish and birds; although this process is efficient in fish, it is less so in birds and very limited in mammals. It has been proposed that factors necessary for providing neurogenic competence to Müller glia in fish and birds after retinal injury are not expressed in mammals. One such factor, the proneural transcription factor Ascl1, is necessary for retinal regeneration in fish but is not expressed after retinal damage in mice. We previously reported that forced expression of Ascl1 in vitro reprograms Müller glia to a neurogenic state. We now test whether forced expression of Ascl1 in mouse Müller glia in vivo stimulates their capacity for retinal regeneration. We find that transgenic expression of Ascl1 in adult Müller glia in undamaged retina does not overtly affect their phenotype; however, when the retina is damaged, the Ascl1-expressing glia initiate a response that resembles the early stages of retinal regeneration in zebrafish. The reaction to injury is even more pronounced in Müller glia in young mice, where the Ascl1-expressing Müller glia give rise to amacrine and bipolar cells and photoreceptors. DNaseI-seq analysis of the retina and Müller glia shows progressive reduction in accessibility of progenitor gene cis-regulatory regions consistent with the reduction in their reprogramming. These results show that at least one of the differences between mammal and fish Müller glia that bears on their difference in regenerative potential is the proneural transcription factor Ascl1.


Intracytoplasmic sperm injection combined with preimplantation genetic diagnosis for the prevention of recurrent gestational trophoblastic disease.
A strategy for the prevention of repeated molar pregnancies by using intracytoplasmic sperm injection (ICSI) coupled with preimplantation genetic diagnosis (PGD) with fluorescence in-situ hybridization (FISH) was developed. In this approach, complete moles which arise from dispermic fertilization are avoided by the use of ICSI. ICSI is followed by preimplantation selection against the transfer of 46,XX embryos, thus preventing complete moles resulting from a fertilization of an inactive oocyte, by a haploid X-bearing spermatozoon which subsequently duplicates. Triploid partial moles which arise mainly from dispermic fertilization may also be prevented by ICSI. The preimplantation confirmation of diploidy by FISH guards against triploid partial moles which may result from mechanisms other than dispermic fertilization. The employment of this strategy in an attempt to prevent a repeated event of molar pregnancy in a patient with a history of two previous episodes of gestational trophoblastic disease is reported.


Prevalence of cancer in relation to signs of periodontal inflammation.
We investigated the associations between periodontal inflammation (gingivitis and periodontitis) and all-kind malignancies, specifically breast and prostate cancer, in a cohort followed-up for 30 years. The study hypothesis was based on the oral inflammation vs. systemic health paradigm. A sample of 2,168 subjects from an original cohort of 105,718 individuals from the greater Stockholm area in Sweden that had been followed since 1985 was investigated. Swedish national health registers were used in the study. Chi-square tests and logistic multiple regression analyses were conducted. The results showed that periodontitis was significantly associated with any cancer after adjusting for gender, age, income, and education (p = 0.015). The probability of getting cancer increased on average by 38% if the patient had periodontitis vs. had not; the odds ratio was 1.380 (95% confidence interval l.066-1.786). No significant association was observed between periodontitis and breast cancer (p = 0.608), while the association between periodontitis and prostate cancer tended towards significance (p = 0.082). However, no statistically significant difference was found between the observed and the calculated distribution of any cancer in gingivitis groups (p = 0.079). Thus, the study hypothesis was partly confirmed by showing a statistically significant association between periodontitis and any cancer.


Adaptive indirectly cooled monochromator crystals at HASYLAB.
The high-heat-load monochromator, based on the HASYLAB (Hamburger Synchrotronstrahlungslabor) 'Torii' design, has been used successfully for 2 years at the BW2 wiggler beamline. The bowing of the reflecting surface induced by the heat load and water pressure is compensated mechanically. This is achieved by mounting the specially shaped crystal in a bending mechanism and by heat transfer from the directly water-cooled crystal. We present the latest step in the development of this design. The piezoceramic-driven actuators are replaced by actuators based on the thermal expansion of copper rods. The direct water cooling of the crystal is replaced by a safer indirect water-cooling scheme. Characterization results of the crystal are presented. The Si(111) rocking-curve width at 9.5 keV was measured to be 8.3 arcsec under 500 W heat load.


Metabolomics of Pregnancy Complications: Emerging Application of Maternal Hair.
In recent years, the study of metabolomics has begun to receive increasing international attention, especially as it pertains to medical research. This is due in part to the potential for discovery of new biomarkers in the metabolome and to a new understanding of the "exposome", which refers to the endogenous and exogenous compounds that reflect external exposures. Consequently, metabolomics research into pregnancy-related issues has increased. Biomarkers discovered through metabolomics may shed some light on the etiology of certain pregnancy-related complications and their adverse effects on future maternal health and infant development and improve current clinical management. The discoveries and methods used in these studies will be compiled and summarized within the following paper. A further focus of this paper is the use of hair as a biological sample, which is gaining increasing attention across diverse fields due to its noninvasive sampling method and the metabolome stability. Its significance in exposome studies will be considered in this review, as well as the potential to associate exposures with adverse pregnancy outcomes. Currently, hair has been used in only two metabolomics studies relating to fetal growth restriction (FGR) and gestational diabetes mellitus (GDM).


Investigation of Psychophysiological and Subjective Effects of Long Working Hours - Do Age and Hearing Impairment Matter?
Following current prognosis, demographic development raises expectations of an aging of the working population. Therefore, keeping employees healthy and strengthening their ability to work, becomes more and more important. When employees become older, dealing with age-related impairments of sensory functions, such as hearing impairment, is a central issue. Recent evidence suggests that negative effects that are associated with reduced hearing can have a strong impact at work. Especially under exhausting working situations such as working overtime hours, age and hearing impairment might influence employees' well-being. Until now, neither the problem of aged workers and long working hours, nor the problem of hearing impairment and prolonged working time has been addressed explicitly. Therefore, a laboratory study was examined to answer the research question: Do age and hearing impairment have an impact on psychophysiological and subjective effects of long working hours. In total, 51 white-collar workers, aged between 24 and 63 years, participated in the laboratory study. The results show no significant effects for age and hearing impairment on the intensity of subjective consequences (perceived recovery and fatigue, subjective emotional well-being and physical symptoms) of long working hours. However, the psychophysiological response (the saliva cortisol level) to long working hours differs significantly between hearing impaired and normal hearing employees. Interestingly, the results suggest that from a psychophysiological point of view long working hours were more demanding for normal hearing employees.


[Responses of enterometasympathetic neurons to transmural electric stimulation].
Transmural electrical stimulation evokes a multicomponent response in the enterometasympathetic ganglion, the response consisting of early low-amplitude APs and late single AP or bursts of APs. Some of the neurons developed a high-amplitude antidromic spike following the stimulation. Application of ganglio-blocking agent hexonium (10(-6) g/ml), solutions with high magnesium concentration (up to 10 mM) and high-frequency stimulation (30 Hz) led to disappearance of single APs but not the bursts of APs. This suggests that some components of the response are synaptically evoked in ortho- and antidromic stimulations. The remaining spikes reflect conduction of excitation along continuous nerve fibers. Transmural electrical stimulation leads to either increase or decrease in the spontaneous firing rate of neurons except the cells generating stable burst-like firing. Reasons and significance of these changes are discussed.


DFT Investigation of the Mechanism of Action of Organoiridium(III) Complexes As Anticancer Agents.
The potential use of synthetic metal complexes able to catalyze chemical transformations in living organisms is currently attracting a great deal of attention. Recently, organometallic ruthenium and iridium complexes have revealed an unexpected ability to modulate the redox status of cancer cells. In particular, half-sandwich organoiridium(III) cyclopentadienyl complexes of general formula [(η(5)-Cp(x))Ir(III)(X(∧)Y)Z](0/+), where Cp(x) = Cp*, Cp(xph) (tetramethyl-(phenyl)cyclopentadienyl) or Cp(xbiph) (tetramethyl(biphenyl)-cyclopentadienyl), X(∧)Y = bidentate ligand with nitrogen, oxygen, and/or carbon donor atoms, and Z = Cl, H2O, or pyridine (py) have shown promising antiproliferative activity toward cancer cells, higher potency than cisplatin, and a different mechanism of action due to the increase of the oxidative stress in cells. As such, complexes can belong to the class of DNA interacting compounds and attack on DNA can represent a secondary mechanism of action. We have explored here by means of density functional calculations (M06-L) and with the support of experimental observations for both [(η(5)-Cp(xbiph))Ir-(phpy) (Cl)], 1-Cl, and [(η(5)-Cp(xbiph))Ir-(phpy) (py)], 1-py, complexes the mechanistic aspects of the hydrolysis reaction, H2O2 ROS production by assisted hydride transfer from NADH to molecular oxygen, interaction with purine nucleobases adenine and guanine as well as gluthatione, that is highly abundant in cells, alongside the reaction mechanism for the oxidation of the formed sulfur-coordinated thiolate to the corresponding sulfenato complex. The comparison between kinetic and thermodynamic parameters calculated for all the involved processes shows that, according to the hypothesis based on experimental findings, the interaction with the tripeptide glutathione causes deactivation of 1-Cl, whereas 1-py, in both its aquated and nonaquated form, can induce cell apoptosis in a dual manner: DNA damage and H2O2 ROS production to increase oxidative stress.


Globulixanthones A and B, two new cytotoxic xanthones with isoprenoid groups from the root bark of Symphonia globulifera.
Bioassay-guided fractionation of a root bark extract of Symphonia globulifera has yielded, in addition to stigmasterol, two new xanthones with isoprenoid units, named globulixanthones A (1) and B (2). The structures of these compounds have been elucidated by spectroscopic means. They possess significant cytotoxicity in vitro against the KB cell line.


SPEQTACLE: An automated generalized fuzzy C-means algorithm for tumor delineation in PET.
Accurate tumor delineation in positron emission tomography (PET) images is crucial in oncology. Although recent methods achieved good results, there is still room for improvement regarding tumors with complex shapes, low signal-to-noise ratio, and high levels of uptake heterogeneity. The authors developed and evaluated an original clustering-based method called spatial positron emission quantification of tumor-Automatic Lp-norm estimation (SPEQTACLE), based on the fuzzy C-means (FCM) algorithm with a generalization exploiting a Hilbertian norm to more accurately account for the fuzzy and non-Gaussian distributions of PET images. An automatic and reproducible estimation scheme of the norm on an image-by-image basis was developed. Robustness was assessed by studying the consistency of results obtained on multiple acquisitions of the NEMA phantom on three different scanners with varying acquisition parameters. Accuracy was evaluated using classification errors (CEs) on simulated and clinical images. SPEQTACLE was compared to another FCM implementation, fuzzy local information C-means (FLICM) and fuzzy locally adaptive Bayesian (FLAB). SPEQTACLE demonstrated a level of robustness similar to FLAB (variability of 14% ± 9% vs 14% ± 7%, p = 0.15) and higher than FLICM (45% ± 18%, p < 0.0001), and improved accuracy with lower CE (14% ± 11%) over both FLICM (29% ± 29%) and FLAB (22% ± 20%) on simulated images. Improvement was significant for the more challenging cases with CE of 17% ± 11% for SPEQTACLE vs 28% ± 22% for FLAB (p = 0.009) and 40% ± 35% for FLICM (p < 0.0001). For the clinical cases, SPEQTACLE outperformed FLAB and FLICM (15% ± 6% vs 37% ± 14% and 30% ± 17%, p < 0.004). SPEQTACLE benefitted from the fully automatic estimation of the norm on a case-by-case basis. This promising approach will be extended to multimodal images and multiclass estimation in future developments.


Psychometric properties and relations with coping and family strain of the Health Services and Caregiver Experience questionnaire (HSCE): an outcome measure of informal caregivers' experience for inpatient care in Italy.
In the last decade, the number of patients supported by informal caregivers has substantially increased. In the Italian healthcare context, informal caregivers' experience of care is a new under-recognized construct, and no assessment tool is available. Measuring caregivers' experience is important since in Italy the relationship between doctors and patients/relatives is still considered asymmetrical. The current study presented development and initial psychometric properties of the Health Services and Caregiver Experience questionnaire (HSCE), a self-report tool of caregivers' global experience for inpatient clinical care, including factor structure, reliability and its relations with measures of coping strategies and family strain. The HSCE was administered to a total of 503 informal caregivers of inpatients admitted at an Italian University Hospital (mean age = 48.08 years, SD = 14.82, females = 61.40%). Family Strain Questionnaire-Short Form (FSQ-SF) and Coping Orientations to Problems Experience-New Italian Version (COPE-NVI) were administered to a subgroup of participants. First-grade relatives were 73.10%, whereas 13.20% were second-grade relatives and 13.70% were home-watch caregivers. Exploratory and confirmatory factor analyses showed a structure with a single factor, which explained 64.80% of the total variance. All the items had salient loadings. In the two subsamples, HSCE had excellent internal consistency (Cronbach's alpha = 0.95-0.97). Positive moderate correlations were found between HSCE and FSQ-SF scores (r = 0.45, p < .05), between HSCE and COPE-NVI scale scores, including COPE-NVI positive attitude and COPE-NVI problem solving scores (rs' range = 0.51-0.57, p < .05). Moreover, a positive large correlation between HSCE and COPE-NVI social support scores emerged (r = 0.72, p < .05). Correlations were not significant between HSCE scores and COPE-NVI turning to religion and avoidance strategies. The HSCE resulted to have good psychometric properties. Better caregivers' experience correlated with stronger family strain but also with better problem solving and social support. The study expanded knowledge on caregiver's experience in Italy and indicated that HSCE is a valid and reliable tool to measure this under-recognized construct in Italy.


Extraintestinal campylobacteriosis in rhesus macaques (Macaca mulatta).
Two cases of clinical disease associated with extraintestinal Campylobacter infection were recently encountered in rhesus macaques (Macaca mulatta). The first case was that of a 3-y-old, male, rhesus macaque experimentally infected with SIV, who presented with abdominal pain and a midabdominal mass and was euthanized. Pathology findings included an abscess within the median liver lobe, fibrinopurulent peritonitis, and intestinal serositis with isolation of Campylobacter fetus from the blood, liver, and the hepatic abscess. The second case was that of a 1-mo-old, female, rhesus macaque who died with no apparent history of illness. Gross pathology findings included thin body condition and diarrheic staining of the perineum; histologically, acute multifocal hepatitis with intralesional bacteria was noted. Campylobacter coli was isolated from the liver and colon. Extraintestinal Campylobacter infection is uncommon in humans, usually occurring in immunocompromised subjects and most commonly manifesting as bacteremia. Extraintestinal Campylobacter infections in animals are rare but have been associated with bacteremia and cholecystitis. The macaques presented here were either immunocompromised due to SIV infection (case 1) or more vulnerable due to young age (case 2). These factors likely contributed to the extraintestinal spread of Campylobacter.


Antiviral and Immunomodulatory Activities of Clinacanthus nutans (Burm. f.) Lindau.
Clinacanthus nutans (Burm. f.) Lindau has been used as a traditional herbal medicine for treating snake bites, scalds, burns, and viral and bacterial infections. It has been attracting an increasing amount of attention because of its biological activities, including its antidiabetic, antioxidant, antibacterial, anticancer, anti-inflammatory, antiviral, and immunoregulatory activities. Here, we conducted a panoramic survey of the literature regarding the immunoregulatory, anti-inflammatory, and antiviral activities of C. nutans. We discovered that C. nutans extracts have virucidal activities against herpes simplex virus types 1 and 2, varicella-zoster virus, cyprinid herpesvirus 3, porcine reproductive and respiratory syndrome virus, mosquito-borne chikungunya virus, and potentially SARS-CoV-2; such activities likely result from C. nutans interfering with the entry, penetration, infection, and replication of viruses. We also reviewed the phytochemicals in C. nutans extracts that exhibit anti-inflammatory and immunoregulatory activities. This updated review of the antiviral, anti-inflammatory, and immunoregulatory activities of C. nutans may guide future agricultural practices and reveal clinical applications of C. nutans.


Identification of the binding sites for ubiquinone and inhibitors in the Na+-pumping NADH-ubiquinone oxidoreductase from Vibrio cholerae by photoaffinity labeling.
The Na+-pumping NADH-quinone oxidoreductase (Na+-NQR) is the first enzyme of the respiratory chain and the main ion transporter in many marine and pathogenic bacteria, including Vibrio cholerae The V. cholerae Na+-NQR has been extensively studied, but its binding sites for ubiquinone and inhibitors remain controversial. Here, using a photoreactive ubiquinone PUQ-3 as well as two aurachin-type inhibitors [125I]PAD-1 and [125I]PAD-2 and photoaffinity labeling experiments on the isolated enzyme, we demonstrate that the ubiquinone ring binds to the NqrA subunit in the regions Leu-32-Met-39 and Phe-131-Lys-138, encompassing the rear wall of a predicted ubiquinone-binding cavity. The quinolone ring and alkyl side chain of aurachin bound to the NqrB subunit in the regions Arg-43-Lys-54 and Trp-23-Gly-89, respectively. These results indicate that the binding sites for ubiquinone and aurachin-type inhibitors are in close proximity but do not overlap one another. Unexpectedly, although the inhibitory effects of PAD-1 and PAD-2 were almost completely abolished by certain mutations in NqrB (i.e. G140A and E144C), the binding reactivities of [125I]PAD-1 and [125I]PAD-2 to the mutated enzymes were unchanged compared with those of the wild-type enzyme. We also found that photoaffinity labeling by [125I]PAD-1 and [125I]PAD-2, rather than being competitively suppressed in the presence of other inhibitors, is enhanced under some experimental conditions. To explain these apparently paradoxical results, we propose models for the catalytic reaction of Na+-NQR and its interactions with inhibitors on the basis of the biochemical and biophysical results reported here and in previous work.


Management of radiation-induced early nasal adhesion after radiotherapy for nasopharyngeal carcinoma.
This study investigates the conservative management of radiation-induced early nasal adhesion after radiotherapy for nasopharyngeal carcinoma (NPC). From June 2008 to June 2010, patients with bilateral or unilateral early nasal adhesion after radiotherapy for NPC were selected. All patients received endoscopic management and then nasal irrigation daily and nasal steroids spray for at least 3 months. All of the clinical data and follow-up endoscopy were analyzed. There were 40 patients enrolled. The mean follow-up period was 19.6 months (range, 12-24 months) after procedure. Thirty-eight patients (95%) had patent nasal cavity during follow-up. Two patients (5%) had not received endoscopy regularly and developed severe fibrosis. For the whole group, nasal obstruction, rhinorrhea, hyposmia, and xerostomia all were improved from before management according to visual analog score (p < 0.05). Therapeutic endoscopy in combination with nasal steroid sprays and nasal irrigation provides a convenient, simple, effective, and minimally invasive therapy to treat early radiation-induced nasal adhesion patients.


Delusional Disorder, Erotomanic Type, Exacerbated by Social Media Use.
Erotomania is an uncommon form of delusional disorder in which an individual has an unfounded belief that another is in love with him. Previous case reports have shown that social media networks may play a role in worsening delusional beliefs. We report the case of a 24-year-old male college student that utilized social media to stalk a female college student, resulting in his suspension from school and hospitalization. The student was diagnosed with delusional disorder, erotomanic type, and started on risperidone. He showed little improvement and was transferred to another facility. This is the first identified case of social media triggering or exacerbating delusional disorder. We recommend increasing education on the ramifications of sharing personal information on social media.


Patient costs for prevention of mother-to-child HIV transmission and antiretroviral therapy services in public health facilities in Zimbabwe.
Zimbabwe has made large strides in addressing HIV. To ensure a continued robust response, a clear understanding of costs associated with its HIV program is critical. We conducted a cross-sectional evaluation in 2017 to estimate the annual average patient cost for accessing Prevention of Mother-To-Child Transmission (PMTCT) services (through antenatal care) and Antiretroviral Treatment (ART) services in Zimbabwe. Twenty sites representing different types of public health facilities in Zimbabwe were included. Data on patient costs were collected through in-person interviews with 414 ART and 424 PMTCT adult patients and through telephone interviews with 38 ART and 47 PMTCT adult patients who had missed their last appointment. The mean and median annual patient costs were examined overall and by service type for all participants and for those who paid any cost. Potential patient costs related to time lost were calculated by multiplying the total time to access services (travel time, waiting time, and clinic visit duration) by potential earnings (US$75 per month assuming 8 hours per day and 5 days per week). Mean annual patient costs for accessing services for the participants was US$20.00 [standard deviation (SD) = US$80.42, median = US$6.00, range = US$0.00-US$12,18.00] for PMTCT and US$18.73 (SD = US$58.54, median = US$8.00, range = US$0.00-US$ 908.00) for ART patients. The mean annual direct medical costs for PMTCT and ART were US$9.78 (SD = US$78.58, median = US$0.00, range = US$0.00-US$ 90) and US$7.49 (SD = US$60.00, median = US$0.00) while mean annual direct non-medical cost for US$10.23 (SD = US$17.35, median = US$4.00) and US$11.23 (SD = US$25.22, median = US$6.00, range = US$0.00-US$ 360.00). The PMTCT and ART costs per visit based on time lost were US$3.53 (US$1.13 to US$8.69) and US$3.43 (US$1.14 to US$8.53), respectively. The mean annual patient costs per person for PMTCT and ART in this evaluation will impact household income since PMTCT and ART services in Zimbabwe are supposed to be free.


Translation and cross language validation of human immunodeficiency virus stigma scale in a Pakistani context.
To evaluate the translation and validation of human immunodeficiency virus stigma scale in Urdu language. The evaluation study was conducted in Lahore, Kasur, Gujranwala and Faisalabad from January 2019 to June 2019. Forward-backward translation method was used to translate the human immunodeficiency virus stigma scale from English to Urdu. Additionally, inter-correlation among variables was assessed by using correlation to determine the psychometric properties. Exploratory factor analysis of the scale was done followed by confirmatory factor analysis for establishing a good model fit. Cronbach's alpha coefficient was 0.95. There was high correlation among the sub-components of the scale, ranging from 0.38 to 0.80 (p<0.001). Confirmatory factor analysis depicted good model fit. The Urdu version of the human immunodeficiency virus stigma scale was found to be a valid and reliable tool to measure personal stigma, disclosure concern, concerns about public attitude and negative self-image.


Nursing care of the patient with hydrocephalus.
Hydrocephalus is a neurological disorder seen frequently in the pediatric population and less frequently in adults. Treatment is directed toward removing the lesion causing the obstruction. Frequently a shunting device is needed to restore and/or maintain CSF flow. The prognosis of these patients is based on a variety of factors. Nursing observations and intervention are of the utmost importance to recognize and/or prevent serious complications postoperatively. Long-term studies to evaluate the prognosis of these patients are limited.