[Single ruptured pelvic hydatid cyst as an unusual manifestation of secondary peritoneal echinococcosis].
The authors report the case of a large pelvic tumour compressing the bladder, the ureters and the recto-sigmoid junction. Its sudden rupture into the peritoneum led to an emergency operation and the discovery of a hydatid cyst ruptured into the pouch of Douglas and a hepatic cyst. The most frequent presentation of peritoneal echinococcosis, peritoneal cysts are metastases from a hepatic or splenic cyst which has ruptured into the peritoneum. They are usually multiple. Single pelvic lesions are rare, their hydatid nature is in the absence of a past history of hydatid disease difficult to suspect before operation. The object of the latter is to treat in one stage the primary cyst and its peritoneal metastases. The narrow vascular connections of the pelvic cysts render cystectomy dangerous and make one prefer removal of the germinal membrane followed by marsupialisation or drainage of the remaining cavity. In the long term, the frequency of peritoneal recurrences makes prolonged supervision necessary.


Electroencephalographic brain dynamics of memory encoding in emotionally arousing context.
Emotional content/context enhances declarative memory through modulation of encoding and retrieval mechanisms. At encoding, neurophysiological data have consistently demonstrated the subsequent memory effect in theta and gamma oscillations. Yet, the existing studies were focused on the emotional content effect and let the emotional context effect unexplored. We hypothesized that theta and gamma oscillations show higher evoked/induced activity during the encoding of visual stimuli when delivered in an emotionally arousing context. Twenty-five healthy volunteers underwent evoked potentials (EP) recordings using a 21 scalp electrodes montage. They attended to an audiovisual test of emotional declarative memory being randomly assigned to either emotionally arousing or neutral context. Visual stimulus presentation was used as the time-locking event. Grand-averages of the EP and evoked spectral perturbations were calculated for each volunteer. EP showed a higher negative deflection from 80 to 140 ms for the emotional condition. Such effect was observed over central, frontal and prefrontal locations bilaterally. Evoked theta power was higher in left parietal, central, frontal, and prefrontal electrodes from -50 to 300 ms in the emotional condition. Evoked gamma power was higher in the emotional condition with a spatial distribution that overlapped at some points with the theta topography. The early theta power increase could be related to expectancy induced by auditory information processing that facilitates visual encoding in emotional contexts. Together, our results suggest that declarative memory enhancement for both emotional content and emotional context are supported by similar neural mechanisms at encoding, and offer new evidence about the brain processing of relevant environmental stimuli.


Regression of grade III astrocytoma during the treatment of CML with imatinib mesylate.
Astrocytomas are central nervous system neoplasms, which are derived predominately from astrocytes. On the basis of the histopathologic characteristics astrocytomas are graded from I to IV. The cells that demonstrate the greatest degree of anaplasia are used to determine the histologic grade of the tumor. The mean age of survival are approximately 10 years from the time of diagnosis for pilocystic astrocytomas (World Health Organization grade I), more than 5 years for patients with low-grade diffuse astrocytomas (WHO grade II), 2 to 5 years for those with anaplastic astrocytomas (WHO grade III), and less than 1 year for patients with glioblastoma (WHO grade IV). The treatment is a combination of surgery, radiation, and chemotherapy depending of the grade of astrocytoma. We present a case of 31-year-old man with grade III astrocytoma with subsequent chronic myelogenous leukemia treated with imatinib mesylate as part of his chronic myelogenous leukemia treatment failing to show recurrence of the astrocytoma 10 years after standard treatment for astrocytoma.


A positron-probe system for arterial input function quantification for positron emission tomography in humans.
We developed an intra-arterial positron-probe (beta(+)-probe) system to measure the arterial time-activity concentration in humans for quantitative compartmental modeling of positron emission tomography studies. Performance was characterized in vitro, by using a uniform phantom to calculate dead time, linearity, and absolute detector sensitivity. In vitro evaluations in a uniform phantom showed a system dead time of 2.5 micros, linear regression between measured and true count rates with R(2)=0.999, and detector sensitivity of 6.9-7.0 counts/s kBq(-1) ml. These met or exceeded values of previously reported systems.


Brief stimuli localization in visual periphery.
Experiments were carried out to establish the effect of stimulus eccentricity and the kind of reference structure on the localization of brief stimuli in the visual periphery. In Experiment 1 the effect of eccentricities up to 55 degrees to the left and to the right of the fixation point on stimulus localization was studied. Systematic errors were obtained, the stimuli being mislocated nearer the fixation point than they were actually presented. The angular size of errors increased with the increase of stimulus eccentricity. In Experiment 2 the subjects had to localize the stimuli against three different background structures (scales). The results showed that error magnitude decreased when scales with clearly visible cues were used. The possible involvement of stimulus direction perception and of the identification of the scale element nearest to the perceived event is discussed.


Influence of binder droplet dimension on granulation rate during fluidized bed granulation.
Here, we statistically identified the critical factor of the granulation rate during the fluidized bed granulation process. Lactose was selected as the excipient and was granulated with several binders, including hydroxypropyl cellulose, hydroxypropyl methyl cellulose, and polyvinylpyrrolidone. The viscosity, density, and surface tension of the binder solution, contact angle, and the work done during adhesion and cohesion between the binder and lactose, mist diameter, Stokes number, and the dimension of the droplet were considered. The Stokes number was defined as the ratio of the inertial force to the viscous-damping force of a particle. We confirmed that droplet diameter after adhesion had the highest correlation coefficient with the granulation rate constant in our investigated parameters. Partial least squares regression revealed two critical principal components of the granulation rate: one relating to the droplet dimension, which is composed of mist diameter and diameter and thickness of the droplet after adhesion of the binder to the lactose surface; and the other relating to wettability, which involves the work done during adhesion and cohesion, surface tension, and the thickness of the droplet after adhesion of the binder to the lactose surface.


Use of rare-earth elements in the phyllosphere colonizer Methylobacterium extorquens PA1.
Until recently, rare-earth elements (REEs) had been thought to be biologically inactive. This view changed with the discovery of the methanol dehydrogenase XoxF that strictly relies on REEs for its activity. Some methylotrophs only contain xoxF, while others, including the model phyllosphere colonizer Methylobacterium extorquens PA1, harbor this gene in addition to mxaFI encoding a Ca2+ -dependent enzyme. Here we found that REEs induce the expression of xoxF in M. extorquens PA1, while repressing mxaFI, suggesting that XoxF is the preferred methanol dehydrogenase in the presence of sufficient amounts of REE. Using reporter assays and a suppressor screen, we found that lanthanum (La3+ ) is sensed both in a XoxF-dependent and independent manner. Furthermore, we investigated the role of REEs during Arabidopsis thaliana colonization. Element analysis of the phyllosphere revealed the presence of several REEs at concentrations up to 10 μg per g dry weight. Complementary proteome analyses of M. extorquens PA1 identified XoxF as a top induced protein in planta and a core set of La3+ -regulated proteins under defined artificial media conditions. Among these was a REE-binding protein that is encoded next to a gene for a TonB-dependent transporter. The latter was essential for REE-dependent growth on methanol indicating chelator-assisted uptake of REEs.


Sex hormone-binding globulin and serum testosterone are inversely associated with C-reactive protein levels in postmenopausal women at high risk for cardiovascular disease.
C-reactive protein (CRP), androgens, and menopausal loss of endogenous estrogens are associated with cardiovascular disease (CVD). We hypothesized that high androgens, low estradiol, and low sex hormone-binding globulin (SHBG) would be associated with high CRP in postmenopausal women. CRP, SHBG, estradiol, and total testosterone were measured using baseline bloods of 221 hormone therapy (HT)-nonusers and 162 HT-users from a cross-sectional analysis in a nested case-control sample of the Women's Health Study. Hormones and CRP were ln-transformed and relationships were assessed with Spearman correlations and linear regression. ln-SHBG (beta=-0.40; p<0.01) and ln-testosterone (beta=-0.24; p=0.04) were the only independent hormonal predictors of ln-CRP among HT-nonusers after adjusting for age, hypertension, smoking, body mass index, diabetes, exercise, HDL cholesterol, alcohol intake, and CVD occurrence during follow-up. Upon stratification, the association between ln-SHBG and ln-CRP persisted among HT nonusers who subsequently developed CVD (beta=-0.55; p=0.01), but not among women who remained CVD-free (p=0.28). The inverse relationship between ln-SHBG and ln-CRP was strongest among the leanest women. None of the sex-hormones predicted ln-CRP among HT-users. SHBG and total testosterone were inversely associated with CRP among HT nonusers in this study. The relationship between SHBG and CRP was more strongly inverse among leaner women.


Pulmonary arterial hypertension (PAH) in connective tissue diseases.
Pulmonary arterial hypertension (PAH) is characterized by progressive obliteration of the small pulmonary vascular bed as a result of vascular proliferation and remodelling of the vessel wall leading to permanently increased pulmonary vascular resistance and elevated pulmonary artery pressures, which result in right heart failure and premature death. Pathologic processes behind the complex vascular changes associated with PAH include vasoconstrictor/vasodilator imbalance, thrombosis, misguided angiogenesis and inflammation. Besides idiopathic PAH, it can also occur in association with portal hypertension, HIV infection, congenital cardiac left-to-right shunts and connective tissue diseases (CTD). Unfortunately, despite recent major improvements in PAH treatment, no current therapy can yet cure this devastating condition. This review will briefly highlight epidemiology, pathogenesis, and diagnostic and treatment options known so far for PAH occurring in connection with CTD.


[Research progress of different minimally invasive spinal decompression in lumbar spinal stenosis].
To review the application and progress of different minimally invasive spinal decompression in the treatment of lumbar spinal stenosis (LSS). The domestic and foreign literature on the application of different minimally invasive spinal decompression in the treatment of LSS was extensively reviewed, and the advantages, disadvantages, and complications of different surgical methods were summarized. At present, minimally invasive spinal decompression mainly includes microscopic bilateral decompression, microendoscopic decompression, percutaneous endoscopic lumbar decompression, unilateral biportal endoscopy, and so on. Compared with traditional open surgery, different minimally invasive spinal decompression techniques can reduce the operation time, intraoperative blood loss, and postoperative pain of patients, thereby reducing hospital stay and saving treatment costs. The indications of different minimally invasive spinal decompression are different, but there are certain advantages and disadvantages. When patients have clear surgical indications, individualized treatment plans should be formulated according to the symptoms and signs of patients, combined with imaging manifestations.


Differences and Similarities in Forgiveness Seeking Across Childhood and Adolescence.
The current study examines age-related differences and similarities in forgiveness seeking. Students in third, seventh, and 12th grade imagined themselves committing various transgressions and the characteristics of these transgression (e.g., severity of consequences, type of offense) were manipulated. Across the age groups, forgiveness seeking was predicted by guilt, whereas withdrawal was predicted by shame. For all age groups, forgiveness seeking was more likely to occur when the offense was an active one rather than a failure to act. However, age differences were found in how offense severity affected forgiveness seeking. Older students were more likely to seek forgiveness when the offense was high rather than low in severity, but younger students did not show this difference. Age differences were also found in the motivations for seeking forgiveness. Finally, teacher ratings of students' overall prosocial behavior were positively correlated with forgiveness seeking.


Anatomy of the shaken baby syndrome.
Shaken baby syndrome refers to the constellation of nonaccidental injuries occurring in infants and young children as a consequence of violent shaking. The typical victim of shaken baby syndrome is a male infant younger than six months of age who is alone with the perpetrator at the time of injury. Occurrence of the syndrome is unrelated to race, gender, socioeconomic status, or education. The characteristic injuries observed in shaken baby syndrome include subdural hemorrhages, retinal hemorrhages, and fractures of the ribs or long bones. Although each of these injuries may result from violent shaking of the victim, the most severe brain injuries result from the addition of a forceful impact of the infant's or child's head against a firm surface. The unique anatomic features of the infant's head and skeletal system, which account for the type and pattern of injuries observed in shaken baby syndrome, are emphasized in this article.


Stepwise introduction of thiolates in copper-indium binuclear complexes.
We report the synthesis and characterization of copper-indium binuclear I-III complexes composing the series (Ph(3)P)(2)CuIn(SEt)(x)Cl(4-x) (1-5; 0 < or = x < or = 4). Members of the series, which are prepared by variations in the stoichiometry, are compared in terms of their solid-state structures, spectroscopic features, and suitability as precursors for CuInS(2) materials. The regiochemistry of thiolate substitution, the preference for monomeric versus dimeric (eight-membered ring) structures, and new synthetic strategies informed by this series are all discussed.


Occult cardiac contractile dysfunction in dystrophin-deficient children revealed by cardiac magnetic resonance strain imaging.
Duchenne muscular dystrophy (DMD) is an inherited disease characterized by early onset of skeletal muscle degeneration and progressive weakness. Although dilated cardiomyopathy may occur during adolescence, it is often undetected early in its course because of physical inactivity and generalized debilitation. The purpose of this study was to apply the technique of cardiac magnetic resonance (CMR) tagging to detect occult cardiac dysfunction in young subjects with DMD by measuring myocardial strain and torsion. Thirteen DMD pediatric subjects without clinically apparent heart disease and 9 age-matched healthy males were recruited. Each was scanned on a 1.5-T clinical scanner to acquire contiguous short-axis planes from the apex to the mitral valve plane and then 3 tagged images at base, midventricle, and apex. Global and segmental myocardial net twist and circumferential strain were computed with the use of 2D homogeneous strain analysis. Ventricular torsion was computed by normalizing net twist by the distance from apex to mitral valve plane. DMD patients exhibited normal left ventricular volumes and ejection fractions but manifested reduced midventricular and basal cross-sectional global circumferential strain compared with the reference group (P<0.005). These alterations also appeared in segmental analyses in the septal, anterior, lateral, and inferior walls (P<0.05). In patients predisposed to cardiomyopathies because of dystrophinopathy, occult regional cardiac dysfunction can be diagnosed with CMR tagging. This method of strain imaging analysis may offer a sensitive approach for delineating the presence and progression of cardiovascular disease and for assessing therapies designed to modulate the onset and course of heart failure.


Clinical use of and experience with neutral-pH solutions.
New peritoneal dialysis solutions with neutral pH and lactate bicarbonate, or combinations of both buffer bases, have been clinically tested in various countries. The experience is most encouraging and consistent with the laboratory data generated in animals and tissue cultures. The available studies suggest improvement in cellular function and viability and better biocompatibility. However the reported studies do not define the specific contributions of neutral pH per se versus those of bicarbonate or reduction in glucose degradation products. Studies designed to address this important question are required.


The Incidences and Characteristics of Various Cancers in Patients on Dialysis: a Korean Nationwide Study.
The numbers of patients on dialysis and their life expectancies are increasing. Reduced renal function is associated with an increased risk of cancer, but the cancer incidence and sites in dialysis patients compared with those of the general population require further investigation. We investigated the incidences of various cancers in dialysis patients in Korea and used national health insurance data to identify cancers that should be screened in dialysis clinics. We accessed the Korean National Health Insurance Database and excerpted data using the International Classification of Disease codes for dialysis and malignancies. We included all patients who commenced dialysis between 2004 and 2013 and selected the same number of controls via propensity score matching. A total of 48,315 dialysis patients and controls were evaluated; of these, 2,504 (5.2%) dialysis patients and 2,201 (4.6%) controls developed cancer. The overall cancer risk was 1.54-fold higher in dialysis patients than in controls (adjusted hazard ratio, 1.71; 95% confidence interval, 1.61-1.81). The cancer incidence rate (incidence rate ratio [IRR], 3.27) was especially high in younger dialysis patients (aged 0-29 years). The most common malignancy of end-stage renal disease patients and controls was colorectal cancer. The major primary cancer sites in dialysis patients were liver and stomach, followed by the lung, kidney, and urinary tract. Kidney cancer exhibited the highest IRR (6.75), followed by upper urinary tract (4.00) and skin cancer (3.38). The rates of prostate cancer (0.54) and oropharyngeal cancer (0.72) were lower than those in the general population. Dialysis patients exhibited a higher incidence of malignancy than controls. Dialysis patients should be screened in terms of colorectal, liver, lung, kidney and urinary tract malignancies in dialysis clinics.


Short-term relevance of lower respiratory viral coinfection in inpatients under 2 years of age.
Advances in molecular diagnosis have made it possible to detect previously unknown viral agents as causative agents of lower respiratory tract infections (LRTI). The frequency and relevance of viral coinfections is still debatable. Compare clinical presentation and severity between single virus infection and viral coinfection in children admitted for LRTI. A 3-year period observational study (2012-2015) included children younger than two years admitted for LRTI. Viral identification was performed using PCR technique for 16 viruses. Clinical data and use of health resources was gathered during hospital stay using a standard collection form and we compared single virus infection and viral coinfections. The study included 524 samples (451 patients); 448 (85.5%) had at least one virus identified. Viral coinfections were found in 159 (35.5%). RSV and HRV were the most commonly identified virus; bronchiolitis and pneumonia the most frequent diagnosis. Patients with viral coinfections were older, attended day-care centers, had previous recurrent wheezing more frequently and were more symptomatic at admission. These patients did not have more complementary exams performed but were prescribed medications more often. Viral coinfection group did not show longer length of hospital stay and oxygen need, more need for ICU nor ventilatory support. Our study showed a significant proportion of viral coinfections in young infants admitted with LRTI and confirmed previous data showing that prescription was more frequent in inpatients with viral coinfections, without an association with worst clinical outcome.


Frontal eye field microstimulation induces task-dependent gamma oscillations in the lateral intraparietal area.
Macaque frontal eye fields (FEF) and the lateral intraparietal area (LIP) are high-level oculomotor control centers that have been implicated in the allocation of spatial attention. Electrical microstimulation of macaque FEF elicits functional magnetic resonance imaging (fMRI) activations in area LIP, but no study has yet investigated the effect of FEF microstimulation on LIP at the single-cell or local field potential (LFP) level. We recorded spiking and LFP activity in area LIP during weak, subthreshold microstimulation of the FEF in a delayed-saccade task. FEF microstimulation caused a highly time- and frequency-specific, task-dependent increase in gamma power in retinotopically corresponding sites in LIP: FEF microstimulation produced a significant increase in LIP gamma power when a saccade target appeared and remained present in the LIP receptive field (RF), whereas less specific increases in alpha power were evoked by FEF microstimulation for saccades directed away from the RF. Stimulating FEF with weak currents had no effect on LIP spike rates or on the gamma power during memory saccades or passive fixation. These results provide the first evidence for task-dependent modulations of LFPs in LIP caused by top-down stimulation of FEF. Since the allocation and disengagement of spatial attention in visual cortex have been associated with increases in gamma and alpha power, respectively, the effects of FEF microstimulation on LIP are consistent with the known effects of spatial attention.


The jugular bulb in otologic surgery: anatomic, clinical, and surgical considerations.
The jugular bulb varies widely in position and dimensions. In certain pathologic conditions there is an increased incidence of jugular bulb enlargement, but such enlargement also occurs without an obvious underlying cause. Jugular bulb enlargment may lead to clinical symptoms for the patient and particular difficulties for the otologic surgeon, not only in the middle ear but also in neurotologic approaches. The different clinical aspects and problems associated with jugular bulb enlargement are discussed with illustrative cases and temporal bone histologic findings.


Rapid detection of specific genes from human genomic DNA using the microbead-quantum dot complexes in microfluidic chip.
In the clinic, it is important to prepare for single stranded DNA from genomic DNA to detect the target gene. In this study, we have investigated the detection of single stranded DNA (ssDNA) obtained by ultrasonication of human genomic DNA via fluorescence quenching on microfluidic chip with pillars at the channel to entrap the microbead-QD complexes (MQCs). The QDs with carboxyl group bind to microbeads with amine group by EDC/NHS coupling reaction. The thiolated probe DNA conjugates strongly with the metal ions on the surface of QDs. The MQCs were packed into a chamber on the channel blocked by pillars. ssDNA and TOTO-3 (intercalating dye) were introduced into the microchannel. After hybridization of probe DNA and target DNA, fluorescence quenching was observed at the surface of the MQDs by FRET between QD and TOTO-3. This experiment shows the possibility of rapid detection of genomic DNA from clinical samples via microbead-QD complexs on microfluidic chip.


Diastereoselective oxidative carbon-carbon bond formation via silyl bis-enol ethers.
Diisopropylsilyl bis-enol ethers are shown to be powerful intermediates for the diastereoselective dimerization and cross-coupling of cyclic ketones. The trends observed for the oxidative coupling of a range of different dialkylsilyl bis-enol ethers derived from cyclohexanone are rationalized by invoking a stereochemical model based on a Thorpe-Ingold effect.


Calcium crystals in osteoarthritis.
Osteoarthritis is the most common form of arthritis in adults and its incidence increases with age. More than 50% of people aged 65 and older have radiographic changes of knee osteoarthritis. Calcium crystals, including calcium pyrophosphate dihydrate and basic calcium phosphate crystals, are also common in the elderly. Not surprisingly, osteoarthritis and crystal arthropathy frequently coexist. The question of a role for calcium crystals in causing or worsening osteoarthritis has been pondered for many years. Progress in understanding the interrelationships between calcium crystals and osteoarthritis has been slowed by our limited knowledge of the pathogenesis of both osteoarthritis and calcium crystal-induced arthritis and our limited ability to accurately detect calcium crystals. Nonetheless, there are good data from clinical and laboratory studies supporting an important role for calcium crystals in osteoarthritis.


Evaluation of the association between atypical bacteria infections and respiratory tract diseases with emphasis on bronchial asthma exacerbations in children.
Mycoplasma pneumoniae and Chlamydia pneumonie are important etiological agents responsible for human respiratory tract diseases. Recently, these atypical microorganisms received much attention regarding their role in bronchial asthma pathogenesis, which is one of the most frequent chronic diseases in children. The aim of the study was to investigate the association between infections caused by these pathogens and respiratory tract diseases in children. Levels of M. pneumoniae and C. pneumoniae-specific antibodies were determined in serum samples obtained from 30 patients suffering from bronchial asthma exacerbations, 10 patients with pneumonia, 28 patients with chronic otitis media with effusion (COME) and 22 sinusitis patients. Specific anti-M. pneumoniae antibodies were detected more frequently in the patients enrolled in the study than in control subjects. The highest percentage of the serum samples, which demonstrated the presence of M. pneumoniae-specific antibodies was demonstrated in patients with asthma (60%) and it was twofold higher than in control subjects. Serologic profile of 26.6% patients with asthma, 50% of patients with pneumonia, 39.2% of patients with COME, 45.4% of patients with sinusitis and 10% of control subjects was consistent with a possible acute infection caused by M. pneumoniae. The presence of specific anti-C. pneumoniae antibodies was demonstrated in a smaller percentage of patients--in 13.3% of children with asthma, 10% of children with pneumonia and in 7.1% of patients with COME; the level of specific antiobodies was suggestive of acute chlamydial infection only in COME patients. Analysis of serologic markers for atypical bacteria infections indicates a possible association between infections caused by M. pneumoniae and bronchial asthma exacerbations and other respiratory tract disorders including pneumonia, sinusitis and COME.


Reporting child abuse in Belgium.
Belgian society has become increasingly aware of the problem of abuse and neglect of children. Recent changes to both Belgian Penal Law and the Code of Medicine now allows dentists to report suspected cases of abuse to provincial trust centres or official authorities, bypassing issues of professional confidentiality. Data on different kinds of child abuse and neglect are presented for the Dutch and French-speaking parts of Belgium for 2001-2002. An increase in notified cases for both regions is noted, along with apparent differences in the type of abuse reported.


Monocyte-mediated tumoricidal activity via the tumor necrosis factor-related cytokine, TRAIL.
TRAIL (tumor necrosis factor [TNF]-related apoptosis-inducing ligand) is a molecule that displays potent antitumor activity against selected targets. The results presented here demonstrate that human monocytes rapidly express TRAIL, but not Fas ligand or TNF, after activation with interferon (IFN)-gamma or -alpha and acquire the ability to kill tumor cells. Monocyte-mediated tumor cell apoptosis was TRAIL specific, as it could be inhibited with soluble TRAIL receptor. Moreover, IFN stimulation caused a concomitant loss of TRAIL receptor 2 expression, which coincides with monocyte acquisition of resistance to TRAIL-mediated apoptosis. These results define a novel mechanism of monocyte-induced cell cytotoxicity that requires TRAIL, and suggest that TRAIL is a key effector molecule in antitumor activity in vivo.


Effects of semantic predictability and regional dialect on vowel space reduction.
This study explored the interaction between semantic predictability and regional dialect variation in an analysis of speech produced by college-aged female talkers from the Northern, Midland, and Southern dialects of American English. Previous research on the effects of semantic predictability has shown that vowels in high semantic predictability contexts are temporally and spectrally reduced compared to vowels in low semantic predictability contexts. In the current study, an analysis of vowel duration confirmed temporal reduction in the high predictability condition. An analysis of vowel formant structure and vowel space dispersion revealed overall spectral reduction for the Southern talkers. For the Northern talkers, more extreme Northern Cities shifting occurred in the high predictability condition than in the low predictability condition. No effects of semantic predictability were observed for the Midland talkers. These findings suggest an interaction between semantic and indexical factors in vowel reduction processes.


Liquid-phase mass transfer coefficients in bioreactors.
Liquid-phase mass transfer coefficient in bioreactors have been examined. A theoretical model based on the surface renewal concept has been developed. The predicted liquid-phase mass transfer coefficients are compared with the experimental data for a mycelial fermentation broth (Chaetomium cellulolyticum) and model media (carboxymethyl cellulose) in a bench-scale bubble column reactor. The liquid-phase mass transfer coefficient is evaluated by dividing the volumetric mass transfer coefficient obtained experimentally by the specific surface area estimated using the available correlations. The available literature data in bubble column and stirred tank bioreactors is also used to test the validity of the proposed model. A reasonable agreement between the model and the experimental data is found.


Association between epithelial-mesenchymal transition and cancer stemness and their effect on the prognosis of lung adenocarcinoma.
The epithelial-mesenchymal transition (EMT) and cancer stemness (CS) are reported to be pivotal phenomena involved in metastasis, recurrence, and drug-resistance in lung cancer; however, their effects on tumor malignancy in clinical settings are not completely understood. The mutual association between these factors also remains elusive and are worthy of investigation. The purpose of this study was to elucidate the association between EMT and CS, and their effect on the prognosis of patients with lung adenocarcinoma. A total of 239 lung adenocarcinoma specimens were collected from patients who had undergone surgery at Kyoto University Hospital from January 2001 to December 2007. Both EMT (E-cadherin,vimentin) and CS (CD133, CD44, aldehyde dehydrogenase) markers were analyzed through immunostaining of tumor specimens. The association between EMT and CS as well as the patients' clinical information was integrated and statistically analyzed. The molecular expression of E-cadherin, vimentin, and CD133 were significantly correlated with prognosis (P = 0.003, P = 0.005, and P < 0.001). A negative correlation was found between E-cadherin and vimentin expression (P < 0.001), whereas, a positive correlation was found between vimentin and CD133 expression (P = 0.020). CD133 was a stronger prognostic factor than an EMT marker. Elevated CD133 expression is the signature marker of EMT and CS association in lung adenocarcinoma. EMT and CS are associated in lung adenocarcinoma. Importantly, CD133 is suggested to be the key factor that links EMT and CS, thereby exacerbating tumor progression.


Helicobacter pylori-related host gene polymorphisms associated with susceptibility of gastric carcinogenesis: a two-stage case-control study in Chinese.
Stomach carcinogenesis progresses stepwise from normal mucosa/superficial gastritis, atrophic gastritis (GA) to gastric cancer (GC). Host factors independent of or combined with Helicobacter pylori infection may modulate the carcinogenesis process. In this two-stage study, we selected 24 putative functional tag single-nucleotide polymorphisms (tagSNPs) for six H.pylori-related host genes, MUC1, toll-like receptor 4 (TLR4), protein tyrosine phosphatase, non-receptor type 11 (PTPN11), IL-1B, PGC and PGA3-5, and analyzed their influence and interaction with H.pylori on the GA and GC risks. Using high-throughput genotyping, the 24 tagSNPs were preliminarily assessed in a screening population of 552 controls, 254 GA and 236 GC subjects; subsequently, five candidate tagSNPs for gastric diseases risk in the TLR4, PGC and PTPN11 genes were re-evaluated in a larger population of 1276 controls, 907GA and 714 GC subjects. We observed that PGC rs6458238, PGC rs4711690 and PTPN11 rs12229892 were associated with susceptibilities to GA and/or GC. Moreover, rs4711690 and rs12229892 and H.pylori demonstrated significant interaction effects on GA risk. In gastric cancerous specimens, we observed significantly higher messenger RNA level in the subjects carrying the PGC rs6458238 GA genotype than that in subjects with the common GG genotype. These findings indicated that genetic variations of two crucial H.pylori-related host genes, H.pylori's mucosal effecter PGC gene and H.pylori's cellular messenger PTPN11 gene, either dependent or independent of interaction with H.pylori, were associated with the risks of GC and/or GA that precede carcinoma. Functional studies and further independent large-scale studies especially in other ethnic populations are still needed to confirm our results.


Medication Histories in Critically Ill Patients Completed by Pharmacy Personnel.
Although critically ill adults often have extended hospital lengths of stay and are at high risk of having medication-related adverse events, the value of medication histories in these patients remains underreported. To assess the feasibility of performing medication histories in critically ill adults and to establish the frequency of and characterize identified discrepancies. This prospective study included patients admitted to 4 intensive care units (ICUs) in a large academic medical center and was conducted in 2 phases. In phase 1, medication histories were conducted over a 5-week period by clinical pharmacists to assess feasibility. In phase 2, medication histories were conducted over a 3-week period by a pharmacy technician. Medication discrepancies, defined as any difference between the documented and pharmacy personnel-identified home medication list, were aggregated in both phases and adjudicated for severity. In phase 1, 127 medication histories were completed (42.3% of admitted patients). Impaired cognition was the most common barrier encountered; however, 76% of patients were able to have a history completed if an attempt was made. In phase 2, a medication history was completed for 176 patients (58.9% of admitted patients). In aggregate, 1155 discrepancies were identified, with 78.2% of patients having a discrepancy. The median number of discrepancies per patient was 3 (interquartile range = 1-5); 11 life-threatening, 101 serious, and 326 significant discrepancies were identified. Conclusion and Relevance: A pharmacy personnel-based medication history program in the ICU is feasible and assists in the discovery of medication discrepancies with the potential for patient harm.


Thyroid replacement in thyroparathyroidectomized dogs.
The thyroparathyroidectomized dog is an important experimental model of hypoparathyroidism and has been widely utilized for acute and chronic studies of the physiologic role of parathyroid hormone on systemic and renal acid-base, electrolyte and vitamin D physiology. Despite widespread use of this model, the appropriate thyroid hormone replacement dose necessary for achievement of postoperative euthyroidism has not been established for this species. Accordingly, serum thyroxine (T4) concentration was measured prior to and following chronic thyroparathyroidectomy in dogs given thyroid hormone replacement at different doses and routes of administration: sodium levothyroxine, 2.4 micrograms/kg daily in one or two divided subcutaneous doses (group I, n = 9), 20 micrograms/kg daily in two divided oral doses (group II, n = 8), and a wide range of intravenous doses (group III, n = 3). Group I dosage was based on the reported T4 production rate in dogs and is slightly greater than the reported production rate in man. Group II dosage was based on published clinically derived estimates of required replacement amounts. With subcutaneous replacement (group I) serum T4 concentration decreased from a preoperative value of 1.80 +/- 0.20 to 0.60 +/- 0.10 microgram/100 ml (p less than 0.001) following thyroparathyroidectomy. With oral replacement (group II), serum T4 concentration after thyroparathyroidectomy was not significantly changed from control (1.88 +/- 0.22 vs. 1.66 +/- 0.43 microgram/100 ml). Group III studies revealed that both total and free serum T4 concentration could be normalized after thyroparathyroidectomy with an intravenous dose of 10 micrograms/kg daily. As found with subcutaneous administration, intravenous replacement with lesser amounts of T4 than 10 micrograms/kg daily (i.e. 2.5 micrograms/kg) resulted in significant decreases in serum T4 concentration from control.(ABSTRACT TRUNCATED AT 250 WORDS)


Hypertension in African Americans: evaluation and treatment issues.
The evaluation and treatment of hypertension in the African-American patient with an elevated blood pressure presents a diagnostic challenge. We are less able to rely on young age and resistance to treatment as indications for more extensive evaluation of secondary causes of hypertension; thus, greater reliance on history, physical examination, and clinical judgment is required if we are to identify potentially treatable causes. The treatment of hypertension in the African-American patient also presents a therapeutic challenge. Thiazide diuretics remain the drugs of first choice for treating hypertension in the African-American hypertensive. The calcium channel blockers (CCBs) are attractive alternatives to thiazides in patients uncontrolled by or intolerant of thiazides or who have specific indications for these agents (eg, angina, severe diastolic dysfunction). Beta-blockers should not be denied to African-American hypertensives if indications for their use exist. Although beta-blockers may be less effective as monotherapy, 50% of African-American hypertensives can be so controlled. Resistance to beta-blockers may be eliminated by administering them with a diuretic. The angiotensin converting enzyme inhibitors (ACEIs), like CCBs, are well tolerated, but also lack long-term primary prevention data. As is the case with beta-blockers, ACEIs are less effective in African-American hypertensives when used as monotherapy. ACEIs have particular value in therapy for African-American hypertensives with concomitant congestive heart failure and may protect against progression of diabetic nephropathy. Finally, all hypertensives, especially African-American hypertensives, should have access to treatment prior to the development of end organ damage. The cost of early intervention is minimal compared with the economic consequences of neglect.


Molecular analysis of patients with synostotic frontal plagiocephaly (unilateral coronal synostosis).
Mutations in genes known to be responsible for most of the recognizable syndromes associated with bilateral coronal synostosis can be detected by molecular testing. The genetic alterations that could cause unilateral coronal synostosis are more elusive. It is recognized that FGFR and TWIST mutations can give rise to either bilateral or unilateral coronal synostosis, even in the same family. The authors undertook a prospective study of patients presenting with synostotic frontal plagiocephaly (unilateral coronal synostosis) to Children's Hospital Boston during the period from 1997 to 2000. Mutational analysis was performed on all patients and on selected parents whenever familial transmission was suspected. Intraoperative anthropometry was used in an effort to differentiate those patients in whom a mutation was detected from those in whom it was not. The anthropometric measures included bilateral sagittal orbital-globe distance, inter medial canthal distance, and nasal angulation. Macrocephaly and palpebral angulation were also considered possible determinants. There was a 2:1 female preponderance in 47 patients with synostotic frontal plagiocephaly. Mutations were found in eight of 47 patients: two patients with different single-amino-acid changes in FGFR2, three patients with FGFR3 Pro250Arg, and three patients with TWIST mutations. Another patient had craniofrontonasal syndrome for which a causative locus has been mapped to chromosome X, although molecular testing is not yet available. Two features were strongly associated with a detectable mutation in patients with synostotic frontal plagiocephaly: asymmetrical brachycephaly (retrusion of both supraorbital rims) and orbital hypertelorism. Other abnormalities in the craniofacial region and extremities were clues to a particular mutation in FGFR2, FGFR3, TWIST, or the X-linked mutation. Neither macrocephaly nor degree of nasal angulation nor relative vertical position of the lateral canthi correlated with mutational detection. An additional four patients in this study had either unilateral or bilateral coronal synostosis in an immediate relative and had anthropometric findings that predicted a mutation, and yet no genetic alteration was found. This suggests either that the authors' screening methods were not sufficiently sensitive or that perhaps there are other unknown pathogenic loci. Nevertheless, molecular testing is recommended for infants who have unilateral coronal synostosis, particularly if there are the anthropometric findings highlighted in this study or an otherwise suspicious feature in the child or a parent. Infants with either an identified or a suspected mutation usually need bilateral asymmetric advancement of the bandeau and may be more likely to require frontal revision in childhood.


A study on the effectiveness of DOTS on tuberculosis patients treated under RNTCP.
A total of 88 Tuberculosis patients who registered for treatment were followed up until their completion. These patients were given treatment under the Government of India implemented RNTCP in the year 1999-2000 in a Tuberculosis unit in Bangalore Mahanagara Palike. Majority of the patients were male and from lower middle class In the present study the cure rate was 72.00 %, treatment completion was 80.55%, default patients were 22.72% and chronic cases were 6.25%.


Responses of lactating ewes to exogenous growth hormone: short- and long-term effects on productivity and tissue utilization of key metabolites.
Responses to daily injections of bovine growth hormone (GH, 0.15 mg kg-1 liveweight), beginning on day 10 of lactation, were measured in lactating ewes. Milk yields of GH-treated ewes increased soon after commencement of injections and continued to increase for some 25 days before reaching plateau levels. By comparison, yields of ewes injected with excipient (controls) decreased over the experiment. There was a tendency for contents of milk fat to be higher and milk protein to be lower for GH-treated than for control ewes during the first 15-20 days after injections were started. At the beginning and over the first 15-20 days of the experiment feed intakes of both groups of ewes were similar, but thereafter intakes of GH-treated ewes gradually increased to reach plateau levels some 200-300 g day-1 higher than for control ewes by about day 35. Liveweights of both groups of ewes decreased during the first 2 weeks of treatment then increased, with GH-treated ewes losing, then gaining, more weight than control ewes. The efficiency of food utilization for milk production was higher for GH-treated than control ewes throughout the experiment but digestibility of food organic matter was not different during the eighth week of the experiment. At the end of the experiment, body composition, assessed by dilution of tritiated water, was similar for both groups of ewes. Differences in milk production were not sustained after withdrawal of GH injections. Measurements of tissue uptake of key metabolites were made on days 3 and 45 of GH treatment. On day 3, GH lowered uptake of glucose and non-esterified fatty acids by leg muscle tissue and increased mammary uptake of non-esterified fatty acids. By day 45 there were no apparent differences of tissue uptake of key metabolites. The results indicate that there is a biphasic response to exogenous GH in the lactating ruminant. It appears that initially GH affects nutrient partition thereby increasing supplies to the mammary gland of key nutrients for milk synthesis. In the longer term, GH increases feed intake, which provides sufficient nutrients to sustain increased milk production and also liveweight gain.


Physiology-informed toxicokinetic model for the zebrafish embryo test developed for bisphenols.
Zebrafish embryos (ZFE) is a widely used model organism, employed in various research fields including toxicology to assess e.g., developmental toxicity and endocrine disruption. Variation in effects between chemicals are difficult to compare using nominal dose as toxicokinetic properties may vary. Toxicokinetic (TK) modeling is a means to estimate internal exposure concentration or dose at target and to enable extrapolation between experimental conditions and species, thereby improving hazard assessment of potential pollutants. In this study we advance currently existing TK models for ZFE with physiological ZFE parameters and novel experimental bisphenol data, a class of chemicals with suspected endocrine activity. We developed a five-compartment model consisting of water, plastic, chorion, yolk sack and embryo in which surface area and volume changes as well as the processes of biotransformation and blood circulation influence mass fluxes. For model training and validation, we measured internal concentrations in ZFE exposed individually to BPA, bisphenol AF (BPAF) and Z (BPZ). Bayesian inference was applied for parameter calibration based on the training data set of BPZ. The calibrated TK model predicted internal ZFE concentrations of the majority of external test data within a 5-fold error and half of the data within a 2-fold error for bisphenols A, AF, F, and tetrabromo bisphenol A (TBBPA). We used the developed model to rank the hazard of seven bisphenols based on predicted internal concentrations and measured in vitro estrogenicity. This ranking indicated a higher hazard for BPAF, BPZ, bisphenol B and C (BPB, BPC) than for BPA.


EUS versus percutaneous management of postoperative pancreatic fluid collection: A systematic review and meta-analysis.
Postoperative pancreatic fluid collection (POPFC) is an important complication following abdominal surgery. POPFC causes significant morbidity and mortality. Management options are time-consuming and severely affect patient's quality of life. Surgical and/or percutaneous drainage (PCD) is the traditional mainstay of treatment. Studies have shown that EUS could have a role to play in the management of POPFC. Data are limited in the comparison of clinical outcomes with EUS as compared to PCD to this end. We conducted a comprehensive search of multiple electronic databases and conference proceedings including PubMed, EMBASE, Google Scholar, LILACS, and Web of Science databases (earliest inception through September 2018) to identify studies that reported on the clinical outcomes of EUS and PCD in the management of POPFC. The goals were to estimate and compare the pooled rates of technical success, clinical success, adverse events, and POPFC recurrence with EUS and PCD. A total of 13 studies were included in the analysis. Ten studies (239 patients) used EUS and 6 studies (267 patients) used PCD in the management of POPFC. The pooled rate of clinical success with EUS was 93.2% (95% confidence interval [CI] 88.2-96.2, I2 = 0) and with PCD was 79.8% (95% CI 70-87, I2 = 74). The difference was statistically significant, P = 0.002. Recurrence rate was significantly lower with EUS as compared to PCD (9.4%: 95% CI 5.2-16.5 vs. 25.7%: 95% CI 24.3-41.7; P = 0.02). Pooled rates of technical success and adverse events were similar with EUS and PCD. Our meta-analysis shows that EUS has significantly better clinical outcomes, in terms of clinical success and disease recurrence, in the management of POPFC as compared to PCD.


[Origin of low molecular weight protein in amniotic fluid].
This study was designed to clarify the origin of some low molecular weight (M.W.) proteins in amniotic fluid. Fragments of amniotic membrane were incubated in Krebs solution for six hours. During the incubation period, 2 ml samples of solution were collected at 5, 15, 30, 60, 120, 180, 360 minutes. The protein concentration of samples was measured with a LASER"NEPHELOMETER. The protein concentration increased significantly from 1.25 +/- 0.21 mg/g.w.w. at 60 minutes to 2.33 +/- 0.67 mg/g.w.w. of amniotic membrane at 360 minutes (p less than 0.001). Samples were also analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Proteins of M.W. less than 56 X 10(3) formed several bands, including band 15 (M.W. = 38 X 10(3)), bands 18-19 (M.W. = 23-25 X 10(3)) and band 21-23 (M.W. = 13-19 X 10(3)). Neonatal saliva and urine were also analyzed by SDS-PAGE. The saliva contained proteins of bands 15 and 20 (M.W. = 22 X 10(3)), and the urine a protein of band 14-15 (M.W. = 38-45 X 10(3)). Although the protein of band 20 was the greatest percentage of total protein in saliva samples, it could not be detected in amniotic fluid. Therefore, saliva was probably not a source of low M.W. proteins in amniotic fluid. Amniotic fluid proteins of band 15 probably originated from fetal urine. And proteins of band 21-23 were probably synthesized by the amniotic membrane.


Insights into the binding mode of sulphamates and sulphamides to hCA II: crystallographic studies and binding free energy calculations.
Sulphamate and sulphamide derivatives have been largely investigated as carbonic anhydrase inhibitors (CAIs) by means of different experimental techniques. However, the structural determinants responsible for their different binding mode to the enzyme active site were not clearly defined so far. In this paper, we report the X-ray crystal structure of hCA II in complex with a sulphamate inhibitor incorporating a nitroimidazole moiety. The comparison with the structure of hCA II in complex with its sulphamide analogue revealed that the two inhibitors adopt a completely different binding mode within the hCA II active site. Starting from these results, we performed a theoretical study on sulphamate and sulphamide derivatives, demonstrating that electrostatic interactions with residues within the enzyme active site play a key role in determining their binding conformation. These findings open new perspectives in the design of effective CAIs using the sulphamate and sulphamide zinc binding groups as lead compounds.


Synthetic peptides containing T and B cell epitopes from human immunodeficiency virus envelope gp120 induce anti-HIV proliferative responses and high titers of neutralizing antibodies in rhesus monkeys.
We have previously described a synthetic peptide (T1-SP10) derived from two noncontiguous regions of HTLVIIIB envelope gp120 (T1, amino acids 428-443; SP10, amino acids 303-321) that induced type-specific anti-HIV neutralizing antibodies and T cell proliferative responses against native HIV gp120 when used as a carrier-free immunogen in goats. In this study, HTLVIIIB T1-SP10 synthetic peptides were used to immunize rhesus monkeys to determine if the peptides were capable of eliciting HIV-specific neutralizing antibody and proliferative responses in primates. Four compounds (alum, polyA:polyU, threonyl-muramyldipeptide (MDP) and IFA) were also compared for efficacy as adjuvants in this system. Rhesus monkeys immunized with T1-SP10 peptides generated high titers of antibodies against the immunogens and also against HTLVIIIB gp120. Sera from all four animals given T1-SP10 in IFA or threonyl-MDP neutralized infection by HTLVIIIB and blocked virus-dependent cell fusion events. A peak neutralization titer of 1:940 was seen in one animal given IFA (19600) and a titer of 1:900 was seen in one of the monkeys (17371) given threonyl-MDP. Proliferative responses of immune rhesus PBMC to T1-SP10 appeared after the first injection. After eight immunizations, two of eight monkeys (one injected with peptides in threonyl-MDP and one given peptides in IFA) had PBMC proliferative responses to native HTLVIIIB gp120. These data demonstrate that the carrier-free T1-SP10 synthetic peptide construct can induce high titers of neutralizing anti-HIV antibody responses and PBMC proliferative responses to HIV in primates.


Twelve tips for creating a multicultural mindfulness-based intervention in diverse healthcare settings.
High levels of stress and burnout, low help-seeking behaviour and unhealthy coping in healthcare professionals (HCPs), are a critical concern globally. Mindfulness-based interventions (MBIs) reduce stress, are a healthy coping mechanism and have become increasingly popular among HCPs, especially during the Covid-19 pandemic. Nevertheless, HCPs' busy schedules require the intervention to be accessible, pragmatic, and context specific. Key to this goal is approaching mindfulness from a multicultural perspective, especially in diverse settings such as Africa. This paper aims to provide practical tips to ensure that the MBI offered is effective with multicultural HCPs during intense stress. Four tips each discuss the curriculum, implementation, and sustainability, respectively. The tips are elucidated by practical examples of regulating stress in healthcare settings and to offer a guideline to help structure future MBIs to be culturally and context appropriate.


Amyloid peptide hydrogels via formation of coordination polymers with Ag+ by its core peptide equipped with a C-cysteine.
We report that the core sequence of amyloid β (Aβ) peptide, KLVFF, when equipped with a C-terminal cysteine residue, exhibited an extremely low minimum hydrogelation concentration of 0.05 wt% in the presence of Ag+ in pH 5 buffer, with this concentration 2 orders of magnitude lower than that of the pentapeptide itself. The CD signal of the Ag+-L-KLVFFC hydrogel was observed to be sensitive to the early-stage aggregation of amyloid β peptide.


A molecular platinum cluster junction: a single-molecule switch.
We present a theoretical study of electron transport through single-molecule junctions incorporating a Pt(6) metal cluster bound within an organic framework. The insertion of this molecule between a pair of electrodes leads to a fully atomically engineered nanometallic device with high conductance at the Fermi level and two sequential high on/off switching states. The origin of this property can be traced back to the existence of a degenerate HOMO consisting of two asymmetric orbitals with energies close to the Fermi level of the metal leads. The degeneracy is broken when the molecule is contacted to the leads, giving rise to two resonances that become pinned to the Fermi level and display destructive interference.


Characterization of bropirimine O-glucuronidation in human liver microsomes.
1. The antitumour agent bropirimine undergoes significant Phase II conjugation in vivo. Incubation of [14C]bropirimine with human liver microsomes resulted in the formation of a single product peak (M1) using high-performance liquid chromatography with radiochemical detection and was tentatively assigned as bropirimine glucuronide based on sensitivity to beta-glucuronidase and by obtaining the expected mass of 442/444 amu with liquid chromatography/mass spectrometry. Following metabolite isolation, the structure of M1 was established as bropirimine O-glucuronide by 1H-nuclear magnetic spectroscopy. 2. Studies aimed at identifying the human liver UDP-glucuronosyltransferase (UGT) enzyme(s) involved in the glucuronidation of bropirimine were carried out using recombinant human UGTs and it was determined that glucuronidation of bropirimine was catalysed by UGT1A1, UGT1A3 and UGT1A9. Bropirimine O-glucuronidation followed Michaelis-Menten kinetics and the Km and Vmax (mean +/- SD; n = 3) were 1217 +/- 205 microM and 667 +/- 188 pmol min(-1) mg(-1), respectively. 3. The activity of bropirimine O-glucuronidation by human liver microsomes was inhibited by bilirubin (40%) and with mefenamic acid (80%). Although buprenorphine extensively inhibited the activity of bropirimine O-glucuronidation by UGT1A3, the inhibition profile did not parallel that observed in HLMs. 4. The results demonstrate that UGT1A9 and to a lesser extent UGT1A1 are responsible for the majority of bropirimine O-glucuronidation in man.


Fetal megacystis-microcolon: Genetic mutational spectrum and identification of PDCL3 as a novel candidate gene.
Megacystis-microcolon-intestinal-hypoperistalsis syndrome (MMIHS) is a severe congenital visceral myopathy characterized by an abdominal distension due to a large non-obstructed urinary bladder, a microcolon and intestinal hypo- or aperistalsis. Most of the patients described to date carry a sporadic heterozygous variant in ACTG2. More recently, recessive forms have been reported and mutations in MYH11, LMOD1, MYLK and MYL9 have been described at the molecular level. In the present report, we describe five patients carrying a recurrent heterozygous variant in ACTG2. Exome sequencing performed in four families allowed us to identify the genetic cause in three. In two families, we identified variants in MMIHS causal genes, respectively a nonsense homozygous variant in MYH11 and a previously described homozygous deletion in MYL9. Finally, we identified compound heterozygous variants in a novel candidate gene, PDCL3, c.[143_144del];[380G>A], p.[(Tyr48Ter)];[(Cys127Tyr)]. After cDNA analysis, a complete absence of PDLC3 expression was observed in affected individuals, indicating that both mutated transcripts were unstable and prone to mediated mRNA decay. PDCL3 encodes a protein involved in the folding of actin, a key step in thin filament formation. Presumably, loss-of-function of this protein affects the contractility of smooth muscle tissues, making PDCL3 an excellent candidate gene for autosomal recessive forms of MMIHS.


Importance of the global regulators Agr and SaeRS in the pathogenesis of CA-MRSA USA300 infection.
CA-MRSA infection, driven by the emergence of the USA300 genetic background, has become epidemic in the United States. USA300 isolates are hypervirulent, compared with other CA- and HA-MRSA strains, in experimental models of necrotizing pneumonia and skin infection. Interestingly, USA300 isolates also have increased expression of core genomic global regulatory and virulence factor genes, including agr and saeRS. To test the hypothesis that agr and saeRS promote the observed hypervirulent phenotype of USA300, isogenic deletion mutants of each were constructed in USA300. The effects of gene deletion on expression and protein abundance of selected downstream virulence genes were assessed by semiquantitative real-time reverse-transcriptase PCR (qRT-PCR) and western blot, respectively. The effects of gene deletion were also assessed in mouse models of necrotizing pneumonia and skin infection. Deletion of saeRS, and, to a lesser extent, agr, resulted in attenuated expression of the genes encoding α-hemolysin (hla) and the Panton-Valentine leukocidin (lukSF-PV). Despite the differences in hla transcription, the toxin was undetectable in culture supernatants of either of the deletion mutants. Deletion of agr, but not saeRS, markedly increased the expression of the gene encoding protein A (spa), which correlated with increased protein abundance. Each deletion mutant demonstrated significant attenuation of virulence, compared with wild-type USA300, in mouse models of necrotizing pneumonia and skin infection. We conclude that agr and saeRS each independently contribute to the remarkable virulence of USA300, likely by means of their effects on expression of secreted toxins.


Clinical Outcomes of Mitral Annuloplasty with Flexible Bands in Ischemic Mitral Regurgitation.
In this study, we present the outcomes of 53 patients with concomitant coronary artery disease and ischemic mitral regurgitation (IMR)who underwent coronary bypass grafting (CABG) plus mitral repair (flexible posterior band annuloplasty). A total of 53 patients with concomitant ischemic mitral regurgitation and coronary artery disease underwent CABG plus posterior mitral band annuloplasty between June 2008 and June 2015. Flexible Duran AnCore® annuloplasty band (Medtronic) was used in all patients. Transesophageal echocardiography (TEE) was intraoperatively performed in all patients. A transthoracic (TTE) follow-up examination was performed at postoperative months 1, 3, 6, and 12. The average cross-clamp and cardiopulmonary bypass times were 85.11 ± 5.79 and 105.98 ± 6.14 minutes, respectively. Postoperatively, there was an improvement in the grade of mitral regurgitation from 3.8 to 0.7 and in the NYHA class from 3.1 ± 0.5 to 0.5 ± 0.6 (both P < .001). In addition, statistically significant reductions in LVEDD, LVESD, and PAP were observed (P < .001). Ejection fraction rose from 39 ± 10% to 45 ± 8% (P < .01). Early mortality rate was 7.5% (n = 4). Mean follow-up was at 16 months. Late mortality occurred in one patient. During the follow-up period, reoperation was required in 2 patients. Only 2 parameters, redo surgery (P = .030) and IABP use (P = .021), were found related to mortality (P < .001). Cox regression analysis showed that redo surgery and postoperative bleeding increased mortality by 14.731 times (odds ratio: 14.731; 95% confidence interval [CI]: 1.530-141.852) and 23.839 times (odds ratio: 23.839; 95% CI: 1.478-348.641). In patients with IMR, mitral band annuloplasty performed in conjunction with CABG was associated with an increase in functional capacity and ejection fraction as well as a reduction in LVEDD and LVESD. This approach represents a feasible alternative with low mortality and prevents future development of mitral regurgitation and the need for redo surgery.


Description of plerocerci and adults of a new species of Grillotia (Cestoda: Trypanorhyncha) in teleosts and elasmobranchs from the Patagonian shelf off Argentina.
A new species of Grillotia was found from teleosts and elasmobranchs along the Patagonian shelf off Argentina. Grillotia patagonica n. sp. is described from plerocerci recovered from gadiform (Moridae) and perciform fish (Cheilodactylidae, Bovichtidae, and Nototheniidae) and adults from the smallthorn sand skate Psammobatis rudis (Rajiformes, Rajidae). Grillotia patagonica most closely resembles species in the Grillotia erinaceus species complex (viz., Grillotia borealis, Grillotia brayi, Grillotia dollfusi, G. erinaceus, and Grillotia musculara) in having 4 hooks per principal row and 2 or more intercalary rows in the metabasal region, a band of hooks on the external surface of the tentacle, numerous proglottids, a hermaphroditic sac, internal and external seminal vesicles, uterine pore, and attachment of the retractor muscle in the mid region of the tentacular bulb. Grillotia patagonica n. sp. is unique among all valid species in the genus by having the hooks on the first row reduced and of a different shape from the rest of the metabasal rows. Despite the diversity of elasmobranchs that are available as definitive hosts for species in Grillotia, most species (10/14) are oioxenous or mesostenoxenous. The specificity for the last intermediate host is variable among species of Grillotia, with most plerocerci being oioxenous (5/15) or euryxenous (8/15). Host specificity is higher for the adult stage in the definitive host (mean HS(S) = 4.07) than for the plerocerci (mean HS(S) = 7.30). All the species with oioxenous specificity (either larvae or adults) have limited geographic distributions. Some previous records of species of Grillotia from fishes caught off Argentina require reconsideration, i.e., G. erinaceus, Grillotia minuta (reported as Grillotia bothridiopunctata) and G. borealis . An updated host-parasite checklist for the valid species of Grillotia is also presented along with new host records for Grillotia carvajalregorum.


Validation of reference genes for quantitative gene expression analysis in experimental epilepsy.
To grasp the molecular mechanisms and pathophysiology underlying epilepsy development (epileptogenesis) and epilepsy itself, it is important to understand the gene expression changes that occur during these phases. Quantitative real-time polymerase chain reaction (qPCR) is a technique that rapidly and accurately determines gene expression changes. It is crucial, however, that stable reference genes are selected for each experimental condition to ensure that accurate values are obtained for genes of interest. If reference genes are unstably expressed, this can lead to inaccurate data and erroneous conclusions. To date, epilepsy studies have used mostly single, nonvalidated reference genes. This is the first study to systematically evaluate reference genes in male Sprague-Dawley rat models of epilepsy. We assessed 15 potential reference genes in hippocampal tissue obtained from 2 different models during epileptogenesis, 1 model during chronic epilepsy, and a model of noninjurious seizures. Reference gene ranking varied between models and also differed between epileptogenesis and chronic epilepsy time points. There was also some variance between the four mathematical models used to rank reference genes. Notably, we found novel reference genes to be more stably expressed than those most often used in experimental epilepsy studies. The consequence of these findings is that reference genes suitable for one epilepsy model may not be appropriate for others and that reference genes can change over time. It is, therefore, critically important to validate potential reference genes before using them as normalizing factors in expression analysis in order to ensure accurate, valid results.


Effects of aminoguanidine on structural alterations of microvessels in peripheral nerve of streptozotocin diabetic rats.
This study was designed to explore the effect of aminoguanidine (AG) on the structural abnormalities of microvessels in the sural nerve of streptozotocin-induced diabetic rats. Diabetic rats were treated with AG (25 mg/ kg, sc) for 16 weeks, a dose high enough to prevent glycation but also inhibit inducible nitric oxide synthase. Non-treated diabetic rats and normal Wistar rats were used for comparison. Morphometric analysis disclosed an expansion of vascular and luminal areas of endoneurial microvessels in diabetic rats, particularly of large size, compared to control rats. These changes were partially but significantly corrected by AG treatment. There was no closure of microvessels in diabetic rats. The mean ratio of basement membrane area to vascular area was significantly smaller in diabetic rats than that in normal control rats and basement membrane was not thickened in diabetic rats. The mean ratio of endothelial cell area to vascular area was smaller in diabetic rats than that in nondiabetic control rats, and it was not influenced by AG treatment. Numbers of microvessels per unit endoneurial area in diabetic rats were not different from those of control rats. These findings in conjunction with previous reports suggest that alterations of nerve blood flow detected in diabetic peripheral nerve may be relevant to structural alterations of endoneurial microvessels, which may be an early sign of endoneurial microangiopathy. We also consider that AG treatment is beneficial for experimental diabetic neuropathy, partially through the correction of endoneurial microcirculation.


Increased CCL-5 (RANTES) Gene Expression in the Choroid Plexus of Dogs with Canine Leishmaniosis.
Visceral canine leishmaniasis (CanL) can cause several clinical manifestations, including neurological lesions. Few reports have characterized the lesions observed in the central nervous system (CNS) during CanL; however, its pathogenesis remains unclear. The choroid plexus (CP) is a specialized structure responsible for the production and secretion of cerebrospinal fluid (CSF) and considered an interface between the peripheral immune system and CNS. It can allow the passage of inflammatory cells or pathogens and has the potential to act as a source of inflammatory mediators in several diseases. Thus, this study aimed to evaluate the role of CP as a possible route of inflammatory cells in the development of brain lesions in dogs with CanL, as well as its association with blood-CSF barrier (BCSFB) dysfunction. Samples were collected from 19 dogs that were naturally infected with CanL. We evaluated the histopathological lesions in the brain and investigated the gene expression of the cytokines. Capture enzyme-linked immunosorbent assay (ELISA) was used to evaluate the presence of the same cytokines in the CSF. Biochemical analysis was performed to compare the presence of albumin in the serum and CSF. Indirect ELISA was performed to measure the presence of anti-Leishmania antibodies in the CSF, which would suggest the disruption of the BCSFB. Histopathological evaluation of the dogs' brains revealed mild-to-severe inflammatory infiltrates, mainly in the CP and meninges. We also detected the presence of anti-Leishmania antibodies and albumin in the CSF, as well as Leishmania DNA in the CP. The gene expression of CCL-5 was increased in the CP of infected dogs compared with that of controls, and there was a tendency for the increase in the gene expression of CXCL-10. Thus, our findings confirm the disfunction of the BCSFB during CanL and suggest that the chemokines CCL-5 and CXCL-10 can be responsible for the recruitment of inflammatory cells found in CP.


[Vaporization of urethral stenosis using the KTP 532 laser].
The authors treated 16 patients presenting with a total of 20 anterior urethral strictures using the KTP 16 Laser. The aetiology was iatrogenic in 50% of cases, infectious in 20% of cases, traumatic in 20% of cases and unknown in 10% of cases. The stricture was situated in the bulbous urethra (80%), membranous urethra (10%) or penil urethra (10%). Laser vaporization of the urethral stricture was performed over the entire circumference of the urethra when necessary, followed by bladder drainage by urethral catheter for 24 hours. All patients were prospectively reviewed at 3 weeks, 3 months and 6 months (clinical symptoms, uroflowmetry, cystourethrography). A complete symptom and urodynamic success was obtained in 13 patients (81%) at 3 and 6 months. The stricture recurred in 4 patients, but only three of them (19%) required treatment (reoperation of repeat dilatations). The mean maximum flow rate increased from 6 mL/s to 20 mL/s at 3 months and was maintained at 19 mL/s at 6 months. No intraoperative or postoperative complications were observed. In conclusion, our results confirm that KTP 532 laser urethral strictures is a reliable and effective method in the medium term. These good results also suggest an advantage in terms of the recurrence rate in comparison with internal urethrotomy. However, our series needs to be evaluated with a longer follow-up and prospective, randomized trials comparing the two methods need to be conducted.


Radiological prediction of tumor invasiveness of lung adenocarcinoma on thin-section CT.
To evaluate thin-section computed tomography (CT) (TSCT) features that differentiate adenocarcinoma in situ (AIS), minimally invasive adenocarcinoma (MIA), and invasive adenocarcinoma (IVA), and to determine the size of solid portion on CT that correlates to pathological invasive components. Forty-eight patients were included. Nodules were classified into ground-glass nodule (GGN), part-solid, solid, and heterogeneous. Visual density of GGNs was subjectively evaluated using reference standard images: faint GGN (Ga), <-700 Hounsfield unit (HU); intermediate GGN (Gb), from -700 to -400 HU; dense GGN (Gc), >-400 HU; and mixed (Ga + Gb, Ga + Gc, and Gb + Gc). The evaluated TSCT findings included margin of nodule, distribution of solid portion, distribution of air bronchiologram, and pleural indentation. The longest diameters of the solid portion and the entire tumor were measured. Invasive diameters were measured in pathological specimens. Twenty-two AISs (16 GGNs [7 Ga, 5 Gb, 2 Gc, 1 Ga + Gc, 1 Gb + Gc], 4 part-solids, and 2 heterogeneous), 6 MIAs (1 GGN [Gb + Gc], 3 part-solids, and 2 solids), and 20 IVAs (1 GGN [Gb], 3 part-solids, and 16 solid) were found. The longest diameter (mean ± standard deviation) of the solid portion and total tumor were 9.7 ± 9.7 and 18.9 ± 5.6 mm, respectively. Significant differences in TSCT findings between AIS and IVA were margin of nodule (Pearson chi-squared test, P = 0.004), distribution of air bronchiologram (P = 0.0148), and pleural indentation (P = 0.0067). A solid portion >5.3 mm on TSCT indicated MIA or IVA, and >7.3 mm indicated IVA (receiver operating characteristic analysis, P < 0.0001). Irregular margin, air bronchiologram with disruption and/or irregular dilatation, and pleural indentation may distinguish IVA from AIS. A 5.3 to 7.3 mm solid portion on TSCT indicates MIA/IVA, and a solid portion >7.3 mm on TSCT indicates IVA.


Clinical characterization and differentiation of B-SNIP psychosis Biotypes: Algorithmic Diagnostics for Efficient Prescription of Treatments (ADEPT)-1.
Clinically defined psychosis diagnoses are neurobiologically heterogeneous. The B-SNIP consortium identified and validated more neurobiologically homogeneous psychosis Biotypes using an extensive battery of neurocognitive and psychophysiological laboratory measures. However, typically the first step in any diagnostic evaluation is the clinical interview. In this project, we evaluated if psychosis Biotypes have clinical characteristics that can support their differentiation in addition to obtaining laboratory testing. Clinical interview data from 1907 individuals with a psychosis Biotype were used to create a diagnostic algorithm. The features were 58 ratings from standard clinical scales. Extremely randomized tree algorithms were used to evaluate sensitivity, specificity, and overall classification success. Biotype classification accuracy peaked at 91 % with the use of 57 items on average. A reduced feature set of 28 items, though, also showed 81 % classification accuracy. Using this reduced item set, we found that only 10-11 items achieved a one-vs-all (Biotype-1 or not, Biotype-2 or not, Biotype-3 or not) area under the sensitivity-specificity curve of .78 to .81. The top clinical characteristics for differentiating psychosis Biotypes, in order of importance, were (i) difficulty in abstract thinking, (ii) multiple indicators of social functioning, (iii) conceptual disorganization, (iv) severity of hallucinations, (v) stereotyped thinking, (vi) suspiciousness, (vii) unusual thought content, (viii) lack of spontaneous speech, and (ix) severity of delusions. These features were remarkably different from those that differentiated DSM psychosis diagnoses. This low-burden adaptive algorithm achieved reasonable classification accuracy and will support Biotype-specific etiological and treatment investigations even in under-resourced clinical and research environments.


Solidarity, citizenship and social justice: perceptions of social actors about public responses to COVID-19.
This qualitative study aimed to analyze the social actors' perceptions of public responses during the COVID-19 pandemic. We conducted semi-structured interviews with eleven civil society representatives and social movement leaders. We also performed triangulation based on the systematization of opinion papers authored by humanitarian organizations and civil society leaders and published in large-circulation newspapers. Our analysis was inspired by the ethical principles of social justice, solidarity, and citizenship. Two main themes emerged from the thematic analysis: 1) disproportionately affected populations remain invisible to care and protection; 2) there is an intentional project to annihilate "undesirable" populations. Community movements must be incorporated as an essential part of the responses to provide care and protection and mitigate the effects during health emergencies. Care, solidarity, and social participation are central to building health protection responses within the framework of social justice. The responses to transforming the future in the aftermath of the pandemic will occur through the initiatives of civil society and community leaders within the territories.


Immunoregulatory effects of the traditional Dai prescription Yajieshaba on food allergic mice.
The Dai prescription Yajieshaba is widely used in Traditional Dai Medicine to treat food allergies and intolerance. However, information on the active chemical ingredients, effects and mechanisms of action of Yajieshaba is limited. The present study aimed to elucidate the effects and underlying mechanisms of Yajieshaba in the treatment of food allergies. Liquid chromatography with a diode array detector was used to measure the levels of palmatine and berberine, the active ingredients of Yajieshaba. A food allergy model was established in female BALB/c mice by three injections of ovalbumin (OVA) at 0, 48, and 96 h. OVA-sensitized mice recieved no treatments (control), Yajieshaba, loratadine, palmatine or berberine. The scratching frequency, serum immunoglobulin (Ig)G, IgE, interleukin (IL)-4, IL-10, IL-17, IL-21, interferon-γ and tumor necrosis factor-α levels were assessed at 50 and 98 h. The percentage of regulatory T cells (Tregs) was evaluated by flow cytometry at 98 h. The scratching frequency induced by OVA was significantly suppressed in mice treated with loratadine, palmatine, berberine or 3.50 and 4.70 g/kg Yajieshaba. The frequency of CD4+CD25+Treg in the spleen increased from 6.80% in mice in the control group to 12.50% in mice treated with 4.70 g/kg body weight Yajieshaba. Mice treated with palmatine or 4.70 g/kg body weight Yajieshaba had increased forkhead box p3 expression compared with those in the control group. Treatment with Yajieshaba decreased the scratching frequency and increased CD4+CD25+Foxp3+ Treg frequency in the spleen. This indicated that symptoms of allergic reaction were alleviated following Yajieshaba treatment. Palmatine was identified as one of the major active components of Yajieshaba. The present study identified the possible mechanism through which Yajieshaba treatment may alleviate food allergy symptoms.


Effects of combined radiosurgery and temozolomide therapy on epidermal growth factor receptor and variant III in glioblastoma multiforme.
Glioblastoma multiforme (GBM) is a highly malignant and notably aggressive primary tumour. Variant III of the epidermal growth factor receptor (EGFRvIII) is one of the most common types of variants in GBM, and serves an important role in tumour invasion, proliferation and treatment resistance. In the present study, statistical analyses were performed on data from 57 patients with GBM, and polymerase chain reaction detection was conducted on the tumour tissues from 32 of these patients. The results indicated that the EGFRvIII mutation was significantly associated with tumour malignancy. Human GBMU87-EGFRvIII cell lines were cultured and treated with radiosurgery and temozolomide individually, or with combined radiosurgery and temozolomide treatment. In vitro and in vivo experimental methods were used to detect the expression levels of Ki-67 and EGFRvIII. As verified in the present study, the EGFRvIII mutation is positively correlated with the malignancy of tumours, and combined radiosurgery and temozolomide therapy may inhibit the invasion and proliferation abilities of U87-EGFRvIII more effectively than treatment alone.


Oxidative stress and hepatotoxicity in the frog, Rana chensinensis, when exposed to low doses of trichlorfon.
Trichlorfon is an organophosphate insecticide that is widely used in aquaculture and agriculture against parasitic infestations and has caused aquatic toxicity to non-target organisms. To evaluate the effects of low doses of trichlorfon on the oxidative stress and hepatotoxicity in amphibians, Chinese brown frogs (Rana chensinensis) were exposed to trichlorfon at concentrations of 0, 0.01, 0.1, and 1.0 mg/L for 2 and 4 weeks. Then, the activities of superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), and the content of malondialdehyde (MDA) in hepatic tissue were examined to evaluate the effects of oxidative stress and lipid peroxidation. The histopathological alternations to the liver were observed through light and transmission electron microscopy (TEM). The results showed that SOD and CAT activities were increased in the livers of frogs exposed to various concentrations of trichlorfon. The GST activity showed no significant changes at any concentration after 2 weeks of exposure, whereas there was an initial increase after exposure to 0.1 mg/L of trichlorfon at 4 weeks. The content of MDA revealed a significant decrease after exposure. Histopathological and ultrastructural studies showed that trichlorfon induced hyalinization, vacuolation, nucleus necrosis, and cellular swelling in hepatocytes. These results suggest that low doses of trichlorfon could induce oxidative stress, lipid peroxidation, and hepatic lesions in frogs, which shows that even lower, non-lethal doses of trichlorfon are potentially toxic to amphibians.


Self-expandable metal stent placement for treatment of severe sphincterotomy bleeding.
One of the most frequent complications of endoscopic sphincterotomy (ES) is bleeding. When post-ES bleeding does not respond to the use of typical endoscopic therapy, the only alternative is angiography or surgery. A 82-year-old female was admitted for jaundice. A RMN-cholangiography revealed multiple stones in the common bile duct (CBD). She underwent endoscopic retrograde cholangiopancreatography (ERCP). The papilla major was located between two large periampullary diverticula. During the ES, a severe bleeding was observed from the upper part of the biliary cut. Several methods of hemostasis (injection of adrenaline, thermal methods and balloon tamponate) were performed without efficacy. A partially covered metallic stent was placed across the biliary orifice, in order to compress mechanically the bleeding site archiving the hemostasis.


Assessment of Patients with Hirschsprung Disease and the Use of Laparoscopy.
This study aims to evaluate patients who were diagnosed and treated due to Hirschsprung disease (HD) in our clinic. We retrospectively evaluated the demographic and clinical findings of the patients with HD, who were operated in our clinic between January 2010 and December 2015. During study period, 28 patients (19 male 9 female) were found to be operated due to HD in our clinic. Mean age was 16.8 months (1-168). "Transanal Endorectal Pull-through (TERPT)" was performed to 20 of them, Duhamell procedure to five and Soave procedure to three of them. TERPT was applied as laparoscopy assisted in four of them and biopsies were taken laparoscopically preoperatively from one of the patients from each group. Soave procedure was performed in three patients; one had anal stenosis and history of recurrent enterocolitis after TERPT procedure and pathologic analysis revealed neuronal intestinal dysplasia and the other one had total colonic HD and performed Soave procedure with colonic patch. Seven (25%) patients had enterocolitis. Frequencies of enterocolitis were three in two patients, two in two patients and one in three patients. Broad spectrum anibiotics and rectal washouts were supplied to these patients. Five of the seven patients with enterocolitis were operated with TERPT; two patients were operated with Duhamell procedure. Only one of them had total colonic HD. Three patients had total colonic HD diagnosis. Two of them were operated with Duhamell-Martin procedure and one was with Soave procedure with colonic patch according to Kimura technique. Anal stenosis developed in two patients after TERPT and treated with dilatations. Soiling rate was 3% (1/28) and this single patient was treated with laxatives and toilet training. Mean duration of hospitalization was 8.75 (2-14) days. Mean length of the removed intestinal segment was 23.6 (5-38) cm. Mean follow-up was for 35.5 (2-56) months. Neither of the patients was followed in the intensive care unit postoperatively nor died. TERPT procedure win priority in HD, but other procedures keep importance. Recently, laparoscopy-assisted TERPT is preferred in our clinic in HD therapy due to easy biopsy, full exposure to the transitional zone, the advantage of meso preparation of colon and prevention of strained anastomosis.


Omp85 from the thermophilic cyanobacterium Thermosynechococcus elongatus differs from proteobacterial Omp85 in structure and domain composition.
Omp85 proteins are essential proteins located in the bacterial outer membrane. They are involved in outer membrane biogenesis and assist outer membrane protein insertion and folding by an unknown mechanism. Homologous proteins exist in eukaryotes, where they mediate outer membrane assembly in organelles of endosymbiotic origin, the mitochondria and chloroplasts. We set out to explore the homologous relationship between cyanobacteria and chloroplasts, studying the Omp85 protein from the thermophilic cyanobacterium Thermosynechococcus elongatus. Using state-of-the art sequence analysis and clustering methods, we show how this protein is more closely related to its chloroplast homologue Toc75 than to proteobacterial Omp85, a finding supported by single channel conductance measurements. We have solved the structure of the periplasmic part of the protein to 1.97 A resolution, and we demonstrate that in contrast to Omp85 from Escherichia coli the protein has only three, not five, polypeptide transport-associated (POTRA) domains, which recognize substrates and generally interact with other proteins in bigger complexes. We model how these POTRA domains are attached to the outer membrane, based on the relationship of Omp85 to two-partner secretion system proteins, which we show and analyze. Finally, we discuss how Omp85 proteins with different numbers of POTRA domains evolved, and evolve to this day, to accomplish an increasing number of interactions with substrates and helper proteins.


Uterine Sensitization-Associated Gene-1 in the Progression of Kidney Diseases.
Uterine sensitization-associated gene-1 (USAG-1), originally identified as a secretory protein preferentially expressed in the sensitized rat endometrium, has been determined to modulate bone morphogenetic protein (BMP) and Wnt expression to play important roles in kidney disease. USAG-1 affects the progression of acute and chronic kidney damage and the recovery of allograft kidney function by regulating the BMP and Wnt signaling pathways. Moreover, USAG-1 has been found to be involved in the process of T cell immune response, and its ability to inhibit germinal center activity and reduce humoral immunity is of great significance for the treatment of autoimmune nephropathy and antibody-mediated rejection (AMR) after renal transplantation. This article summarizes the many advances made regarding the roles of USAG-1 in the progression of kidney disease and outlines potential treatments.


The psychological effects of vasectomy for American men.
Evidence concerning the psychological effects of vasectomy for American men was reviewed. Surveys of postoperative sexual behavior, satisfaction, and/or happiness suggest that the effects of vasectomy are generally positive. Data from studies employing clinical interviews and/or psychological tests, however, support a very different conclusion. These investigations which are generally superior in methodology and measurement techniques to the survey studies indicate that (a) although men in general verbally express satisfaction with vasectomy, many men are probably describing feelings which have been distorted as part of an attempt to cope with their private concerns about the consequences of the operation; and (b) many men experience some difficulty in adjusting to the psychological consequences of vasectomy. Implications for future research are discussed.


A study of the growth changes in the maxillofacial skeleton of females with reversed occlusion: investigation by means of lateral x-ray cephalogram.
321 females with reversed occlusion from the ages of 6 to 20 were classified into 15 groups according to chronological age, and the changes of maxillofacial skeleton accompanying growth were investigated. Lateral cephalometric roentgenogram before treatment of the subjects were used for analyses and measurements of maxillofacial skeleton and overjet. The cephalometric analysis was standardized on the S-N plane, and 5 angular items and 6 linear distances were examined. The results of the investigation are summarized as follows: (1) angle ANB, the relationship between the upper and lower jaws, deteriorated to a minus degree from the age of 9 and became -3.3 degrees at the age of 14. Skeletal convexity became negative from the same age and was -7.3 degrees at the age of 14. Thus, the abnormal skeletal features progressed in this condition. (2) The Ar-Gn distance measurement gradually increased from the age of 6 to 18. The increase was 16.2 mm from 7 to 12, an increase of 3.2 mm yearly. (3) A high correlation (r = 0.99) was observed between angle ANB and Convexity. As well, a high coefficient of correlation (r = 0.87) was observed between skeletal convexity and soft tissue convexity. The change in soft tissue convexity may occur 3-4 years later than that of skeletal convexity. (4) The growth curve of Ar-Gn became a logistic curve with the point of deflection at the age of 10.87. The growth curves of S-Gn and N-Me became logistic curves in the same way.


Organisation of the 5S RNA genes in flax.
The 5S RNA genes of flax [Linum usitatissimum] are arranged as tandem arrays of a 0.35 - 0.37kb repeating sequence. The 5S DNA is extensively methylated at CCGG and CCGG. In contrast to the rDNA, the 5S DNA sequences exhibit both length and sequence heterogeneity. The number of copies of this sequence varies between 117,000 and 49,600 per 2C nucleus in different lines of flax, and does not correlate with the number of rRNA genes.


Low-density lipoprotein receptor-related protein 8 gene association with egg traits in dwarf chickens.
Low-density lipoprotein receptor-related protein 8 (LRP8), a member of the low-density lipoprotein receptor gene family with a role in clusterin processing, was investigated as a candidate gene for egg quality-related traits. One SNP from C to T at position 1623 of the open reading frame of LRP8 was identified and genotyped by a high-throughput genotyping method, matrix-assisted laser desorption-ionization time-of-flight mass spectrometry in 747 egg-type dwarf layers from 44 sire families. There were no significant differences among genotypes for any interior egg traits measured, except for yolk color, in which color was deeper for the TT genotype than CC or CT (P < 0.05). For shell traits, strength and thickness were greater for TT than CC (P < 0.05), with CT intermediate and not different from either. Shape index was lower for CT than either TT or CC, which did not differ, whereas for shell color, CT was intermediate to the homozygotes, which differed (CC > TT). The present results indicated that LRP8, as a new member of eggshell matrix protein, may be a candidate gene associated with eggshell traits.


DNA electroporation in rabbits as a method for generation of high-titer neutralizing antisera: examples of the botulinum toxins types A, B, and E.
Raising high titer antibodies in animals is usually performed by protein immunization, which requires the long and sometimes difficult step of production of the recombinant protein. DNA immunization is an alternative to recombinant proteins, only requiring the building of an eukaryotic expression plasmid. Thanks to efficient DNA delivery techniques such as in vivo electroporation, DNA vaccination has proven useful the last few years. In this work, we have shown that it is possible to raise very high antibody titers in rabbit by DNA electroporation of an antigen encoding plasmid in the skeletal muscle with the right set of electrodes and rabbit strain. In a model of botulinum toxins types A and E, the neutralizing titers obtained after three treatments were high enough to fit the European Pharmacopeia, while it did not for type B toxin. Furthermore, the raised antibodies have high avidity and are suitable for in vitro and in vivo immunodetection of proteins.


Genome-wide imputation study identifies novel HLA locus for pulmonary fibrosis and potential role for auto-immunity in fibrotic idiopathic interstitial pneumonia.
Fibrotic idiopathic interstitial pneumonias (fIIP) are a group of fatal lung diseases with largely unknown etiology and without definitive treatment other than lung transplant to prolong life. There is strong evidence for the importance of both rare and common genetic risk alleles in familial and sporadic disease. We have previously used genome-wide single nucleotide polymorphism data to identify 10 risk loci for fIIP. Here we extend that work to imputed genome-wide genotypes and conduct new RNA sequencing studies of lung tissue to identify and characterize new fIIP risk loci. We performed genome-wide genotype imputation association analyses in 1616 non-Hispanic white (NHW) cases and 4683 NHW controls followed by validation and replication (878 cases, 2017 controls) genotyping and targeted gene expression in lung tissue. Following meta-analysis of the discovery and replication populations, we identified a novel fIIP locus in the HLA region of chromosome 6 (rs7887 P meta = 3.7 × 10(-09)). Imputation of classic HLA alleles identified two in high linkage disequilibrium that are associated with fIIP (DRB1*15:01 P = 1.3 × 10(-7) and DQB1*06:02 P = 6.1 × 10(-8)). Targeted RNA-sequencing of the HLA locus identified 21 genes differentially expressed between fibrotic and control lung tissue (Q < 0.001), many of which are involved in immune and inflammatory response regulation. In addition, the putative risk alleles, DRB1*15:01 and DQB1*06:02, are associated with expression of the DQB1 gene among fIIP cases (Q < 1 × 10(-16)). We have identified a genome-wide significant association between the HLA region and fIIP. Two HLA alleles are associated with fIIP and affect expression of HLA genes in lung tissue, indicating that the potential genetic risk due to HLA alleles may involve gene regulation in addition to altered protein structure. These studies reveal the importance of the HLA region for risk of fIIP and a basis for the potential etiologic role of auto-immunity in fIIP.


LEUKEMIA, MULTIPLE MYELOMA, AND APLASTIC ANEMIA IN AMERICAN RADIOLOGISTS.
A survey of 425 death certificates of radiologists dying between the ages of 35 and 74 during the years 1948 to 1961 reveals a statistically highly significant excess of deaths from leukemia, multiple myeloma, and aplastic anemia. That this excess is due to radiation exposure (or to some factor acting in a similar manner), rather than to an artifact of diagnosis is suggested by the absence of deaths ascribed to chronic lymphatic leukemia.