Chemical and environmental implications of visible and near-infrared spectral features of salt crusts formed from different brines.
This work describes a laboratory experiment intended to study the formation and spectral reflectance properties of stratified salt crusts that cause severe environmental degradations to soil and water resources in arid regions. Salt crusts were prepared by evaporating three types of saline solutions consisting of i) NaCl - Na2SO4, ii) Na2SO4 - MgSO4, and iii) NaCl - MgSO4 at an initial concentrations of 50 mmol L(-1). They were examined for evaporite mineralogy using X-ray diffraction, optical and reflected microscopes, and for spectral reflectance with a high-resolution spectroradiometer (GER 3700) in the visible and near-infrared regions (400-2500 nm). The study documented chemical and environmental implications of the spectral properties of salt formed from the studied saline-systems. The reported results can be used to understand remotely sensed signatures of salt crusts and their implications.


Establishing Reliability and Validity of the FACE-Q Craniofacial Module for Pediatric Head and Neck Cancer.
Purpose: We aimed to establish content validity and assess the psychometric properties of the FACE-Q Craniofacial Module, a patient-reported outcome measure, for use in pediatric and adolescent patients with head and neck cancer (HNC). Methods: To establish content validity (Part 1), between June 2017 and August 2019, cognitive interviews were conducted with survivors of pediatric HNC (n = 15), and input was obtained from clinical experts (n = 21). To examine item and scale performance (Part 2), Rasch Measurement Theory (RMT) analysis was performed using data from two international studies (n = 121). Results: Part 1: Qualitative data from 15 survivors and input from 21 experts provided evidence to support the use of the FACE-Q Craniofacial Module in pediatric HNC. Part 2: The field-test study sample included 121 survivors of pediatric HNC. RMT analysis provided evidence of reliability and validity for 10 FACE-Q scales. Data for each scale fit the RMT model. Scale reliability was high, with Person Separation Index and Cronbach's alpha values ≥0.82 for 9 scales. Mean scores on the Appearance, Psychological, and Social scales were higher for those who liked aspects of their face more. For participants with (vs. without) a facial difference, mean scores were lower for the Face, Jaws, Psychological, and Social scales. Conclusion: The FACE-Q Craniofacial Module evidenced reliability and validity for HNC survivors aged 8-29 years and can be used in research and clinical care to measure quality of life of pediatric survivors with HNC.


Does calprotectin level identify a subgroup among patients suffering from irritable bowel syndrome? Results of a prospective study.
Irritable bowel syndrome is a multifactorial disease. Although faecal calprotectin has been shown to be a reliable marker of intestinal inflammation, its role in irritable bowel syndrome remains debated. The aims of this prospective study were to select a subgroup of irritable bowel syndrome patients and to characterise those patients with high faecal calprotectin by systematic work-up. Calprotectin levels were determined by enzyme-linked immunosorbent assay test in consecutive irritable bowel syndrome patients fulfilling Rome III criteria in whom normal colonoscopy and appropriate tests had excluded organic disease. Calprotectin levels were compared in irritable bowel syndrome patients, healthy controls and patients with active and quiescent Crohn's disease. When the calprotectin level was higher than 50 µg/g, the absence of ANCA/ASCA antibodies and a normal small bowel examination were required to confirm irritable bowel syndrome diagnosis. Additional explorations included assessment of irritable bowel syndrome severity, anxiety and depression, impact on quality of life, glucose and fructose breath tests, rectal distension test by barostat and quantitative and qualitative assessment of inflammation on colonic biopsies. Among the 93 irritable bowel syndrome patients (73% women; 66.7% with diarrhoea) recruited, 34 (36.6%) had reproducibly elevated calprotectin. Although they tended to be older than those with normal calprotectin (P = 0.06), there were no other differences between the two groups. When elevated, calprotectin was correlated with age (P = 0.03, r = 0.22). Elevated faecal calprotectin was observed in one third of patients in this series, without any significant association with a specific clinical phenotype (except age) or specific abnormalities.


Osteonecrosis of the femoral head caused by bone marrow blockage: a case report.
Interruption of the blood flow may occur in intra-osseous arteries within the femoral head. We report a 72-year-old woman who developed osteonecrosis of the femoral head 11 months after surgery involving massive cementing of a segmental distal femoral rotating hinge prosthesis to treat nonunion of the distal femur. The bone cement filled the cavity up to the femoral neck and the superolateral portion of the femoral head, blocking the bone marrow.


High Throughput NPY-Venus and Serotonin Secretion Assays for Regulated Exocytosis in Neuroendocrine Cells.
Here we describe two assays to measure dense core vesicle (DCV) exocytosis-mediated cargo secretion in neuroendocrine cells. To conduct siRNA screens for novel genes in regulated DCV exocytosis, we developed a plate reader-based secretion assay using DCV cargo, NPY-Venus, and an orthogonal 3H-serotonin secretion assay. The NPY-Venus secretion assay was successfully used for a high throughput siRNA screen, and the serotonin secretion assay was used to validate hits identified from the screen (Sorensen, 2017; Zhang et al., 2017).


Guanidine hydrochloride can induce amyloid fibril formation from hen egg-white lysozyme.
The formation of amyloid fibrils is an intractable problem in which normally soluble protein polymerizes and forms insoluble ordered aggregates. Such aggregates can range from being a nuisance in vitro to being toxic in vivo. The latter is true for lysozyme, which has been shown to form toxic deposits in humans. In the present study, the effects of partial denaturation of hen egg-white lysozyme via incubation in a concentrated solution of the denaturant guanidine hydrochloride are investigated. Results show that when lysozyme is incubated under moderate guanidine hydrochloride concentrations (i.e., 2-5 M), where lysozyme is partially unfolded, fibrils form rapidly. Thioflavin T, Congo red, X-ray diffraction, transmission electron microscopy, atomic force microscopy, and circular dichroism spectroscopy are all used to verify the production of fibrils under these conditions. Incubation at very low or very high guanidine hydrochloride concentrations fails to produce fibrils. At very low denaturant concentrations, the structure of lysozyme is fully native and very stable. On the other hand, at very high denaturant concentrations, guanidine hydrochloride is capable of dissolving and dis-aggregating fibrils that are formed. Raising the temperature and/or concentration of lysozyme accelerates fibril formation by further adding to the concentration of partially unfolded species. The addition of preformed fibrils also accelerates fibril formation but only under partially unfolding conditions. The results presented here provide further evidence that partial unfolding is a prerequisite to fibril formation. Partial denaturation can accelerate fibril formation in much the same way that mutations have been shown to accelerate fibril formation.


Electrochemical Characterization of Graphene and MWCNT Screen-Printed Electrodes Modified with AuNPs for Laccase Biosensor Development.
The aim of this work is to show how the integration of gold nanoparticles (AuNPs) into multi-wall-carbon-nanotubes (MWCNTs) based screen-printed electrodes and into graphene-based screen-printed electrodes (GPHs) could represent a potential way to further enhance the electrochemical properties of those electrodes based on nanoparticles. Laccase from Trametes versicolor (TvL) was immobilized over MWCNTs and GPH previously modified with AuNPs (of 5 and 10 nm). The characterization of the modified electrode surface has been carried out by cyclic voltammetry. The results showed that the use of AuNPs for modification of both graphene and MWCNTs screen-printed electrode surfaces would increase the electrochemical performances of the electrodes. MWCNTs showed better results than GPH in terms of higher electroactive area formation after modification with AuNPs. The two modified nanostructured electrodes were successively proven to efficiently immobilize the TvL; the electrochemical sensing properties of the GPH- and MWCNT-based AuNPs-TvL biosensors were investigated by choosing 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic-acid diammonium salt (ABTS), catechol and caffeic acid as laccase mediators; and the kinetic parameters of the laccase biosensor were carefully evaluated.


Effect modification of kitchen ventilation on the associations of solid fuel use and long-duration cooking with the increased prevalence of depressive and anxiety symptoms: The Henan Rural Cohort Study.
Although solid fuel use for cooking is linked to an increased risk for depression, there is limited evidence on the effects of cooking duration and kitchen ventilation on these associations in rural areas. Among 29 903 participants from the Henan Rural Cohort, the independent and combined associations of cooking fuel type, cooking duration, and kitchen ventilation with depressive and anxiety symptoms were examined by logistic regression models and restricted cubic spline. The adjusted odds ratios (aORs) and 95% confidence intervals (CIs) of solid fuel use for depressive and anxiety symptoms were 1.237 (1.041, 1.469) and 1.384 (1.153, 1.662), respectively. Increased cooking duration was associated with an increased prevalence of depressive symptoms (aOR: 1.098, 95% CI: 1.033, 1.166) and anxiety symptoms (aOR: 1.074, 95% CI: 1.009, 1.144). Solid fuel use and long-duration cooking associated with increased prevalence of depressive and anxiety symptoms were only observed in individuals without kitchen ventilation. Kitchen ventilation may attenuate the positive associations of solid fuel use and long-duration cooking with the prevalence of depressive and anxiety symptoms, which suggested popularizing clean fuel and promoting kitchen ventilation may be effective strategies to improve mental health related to household air pollution sourced from solid fuel use and long-duration cooking.


Laser wavelength- and power-dependent plasmon-driven chemical reactions monitored using single particle surface enhanced Raman spectroscopy.
Plasmon-driven chemical reaction of p-nitrothiophenol (pNTP) dimerizing into p,p'-dimercaptoazobenzene (DMAB) has been monitored using single particle surface enhanced Raman spectroscopy, which provides laser wavelength- and power-dependent conversion rates of the reaction.


Impact of Repeated Influenza Immunization on Respiratory Illness in Children With Preexisting Medical Conditions.
Annual influenza immunization in medical risk groups is recommended in many countries. Recent evidence suggests that repeated inactivated influenza vaccine (IIV) immunization throughout childhood may impair long-term immunity against influenza. We assessed whether prior immunization altered the effect of IIV in children with preexisting medical conditions on primary care-diagnosed respiratory illness (RI) episodes during the influenza season. Electronic records of IIV-immunized children who met the criteria for annual IIV immunization according to Dutch guidelines were extracted from a primary care database from 2004 to 2015. For each year, we collected information on IIV immunization status, primary care-attended RI episodes (including influenza-like illness, acute RI, and asthma exacerbation), and potential confounders. Generalized estimating equations were used to model the association between prior IIV and occurrence of at least one RI episode during the influenza season, with "current year immunized but without IIV history" as reference group. A total of 4,183 children (follow-up duration: 11,493 child-years) were IIV immunized at least once. Adjusted estimates showed lower odds for RI in current year-immunized children with prior IIV compared with those without (odds ratio [OR] = 0.61; 95% CI, 0.47-0.78 for "current year immunized and one IIV in previous 2 years"; OR = 0.85; 95% CI, 0.68-1.07 for "current year immunized and ≥2 IIVs in previous 3 years, including prior year"). Repeated IIV immunization in children with preexisting medical conditions has no negative impact on, and may even increase, long-term protection against RI episodes diagnosed during the influenza season in primary care.


[Stress fracture after changing to barefoot running].
Barefoot running is increasing in popularity but little is known about the implications in respect to injuries. It has been proposed that barefoot running is associated with a decrease in running injuries as it represents a more natural way of running. A 50-year-old runner with a weekly running distance of 50 km presented suffering from a stress fracture of the second metatarsal after six weeks of intensive barefoot running.


Abnormal SDS-PAGE migration of cytosolic proteins can identify domains and mechanisms that control surfactant binding.
The amino acid substitution or post-translational modification of a cytosolic protein can cause unpredictable changes to its electrophoretic mobility during SDS-PAGE. This type of "gel shifting" has perplexed biochemists and biologists for decades. We identify a mechanism for "gel shifting" that predominates among a set of ALS (amyotrophic lateral sclerosis) mutant hSOD1 (superoxide dismutase) proteins, post-translationally modified hSOD1 proteins, and homologous SOD1 proteins from different organisms. By first comparing how 39 amino acid substitutions throughout hSOD1 affected SDS-PAGE migration, we found that substitutions that caused gel shifting occurred within a single polyacidic domain (residues ~80-101), and were nonisoelectric. Substitutions that decreased the net negative charge of domain 80-101 increased migration; only one substitution increased net negative charge and slowed migration. Capillary electrophoresis, circular dichroism, and size exclusion chromatography demonstrated that amino acid substitutions increase migration during SDS-PAGE by promoting the binding of three to four additional SDS molecules, without significantly altering the secondary structure or Stokes radius of hSOD1-SDS complexes. The high negative charge of domain 80-101 is required for SOD1 gel shifting: neutralizing the polyacidic domain (via chimeric mouse-human SOD1 fusion proteins) inhibited amino acid substitutions from causing gel shifting. These results demonstrate that the pattern of gel shifting for mutant cytosolic proteins can be used to: (i) identify domains in the primary structure that control interactions between denatured cytosolic proteins and SDS and (ii) identify a predominant chemical mechanism for the interaction (e.g., hydrophobic vs. electrostatic).


Reproductive consequences of an X-autosome translocation in a swine herd.
A survey was conducted on the chromosome makeup and breeding data of pigs housed at the Arkell Research Station, University of Guelph, to determine the reproductive impact of a reciprocal translocation previously identified as t(Xp+;14q-). Blood samples were cultured and chromosome spreads were examined to identify carriers in the herd. Gonadal features of carrier boars and piglets and their age-matched normal counterparts were studied, and the reproductive history of carrier sows, including the number of breedings required for conception, mean litter size, prevalence of still births and malformations, and sex distribution among the piglets, was compared with that of normal (noncarrier) sows. Our observations on testicular histology confirmed that X-autosome translocation-carrier boars are sterile, and the analysis of reproductive data showed that the most striking effects of t(Xp+;14q-) on sows are the 50% increase in the number of breedings required for conception and the over 25% reduction in litter size compared with that of normal sows. The reproductive impact of this and similar translocations on the herd and on the swine industry in general is discussed.


Personal genomes in progress: from the human genome project to the personal genome project.
The cost of a diploid human genome sequence has dropped from about $70M to $2000 since 2007--even as the standards for redundancy have increased from 7x to 40x in order to improve call rates. Coupled with the low return on investment for common single-nucleotide polylmorphisms, this has caused a significant rise in interest in correlating genome sequences with comprehensive environmental and trait data (GET). The cost of electronic health records, imaging, and microbial, immunological, and behavioral data are also dropping quickly. Sharing such integrated GET datasets and their interpretations with a diversity of researchers and research subjects highlights the need for informed-consent models capable of addressing novel privacy and other issues, as well as for flexible data-sharing resources that make materials and data available with minimum restrictions on use. This article examines the Personal Genome Project's effort to develop a GET database as a public genomics resource broadly accessible to both researchers and research participants, while pursuing the highest standards in research ethics.


Tyrosine-directed conjugation of large glycans to proteins via copper-free click chemistry.
We have demonstrated that the insertion of alkyne-containing bifunctional linkers into the tyrosine residues of the carrier protein, followed by the copper mediated azide-alkyne [3 + 2] cycloaddition of carbohydrates, is a robust approach for the preparation of glycoconjugates with defined glycans, carrier, and connectivity. Conjugation of Group B Streptococcus (GBS) capsular polysaccharides to streptococcal pilus protein could extend the vaccine coverage to a variety of strains. Application of our protocol to these large charged polysaccharides occurred at low yields. Herein we developed a tyrosine-directed conjugation approach based on the copper-free click chemistry of sugars modified with cyclooctynes, which enables efficient condensation of synthetic carbohydrates. Most importantly, this strategy was demonstrated to be more effective than the corresponding copper catalyzed reaction for the insertion of GBS onto the tyrosine residues of GBS pilus proteins, previously selected as vaccine antigens through the so-called reverse vaccinology. Integrity of protein epitopes in the modified proteins was ascertained by competitive ELISA, and conjugation of polysaccharide to protein was confirmed by SDS page electrophoresis and immunoblot assays. The amount of conjugated polysaccharide was estimated by high-performance anion-exchange chromatography coupled with pulsed amperometric detection (HPAEC-PAD). The described technology is particularly suitable for proteins used with the dual role of vaccine antigen and carrier for the carbohydrate haptens.


Immunotherapy of colon cancer: prospects for developing immunogenic vaccines based on autologous serological typing.
Exploration of specific immunization as a means of cancer therapy has been hampered by the lack of knowledge of human cancer antigens. Recent progress in the serological definition of cell surface antigens of malignant melanomas, renal cancers, and astrocytomas provides a new basis for the construction of immunogenic vaccines and their clinical testing. Application of the same approach to colon cancer depends on the development of methods which permit continuous growth of colon cancer cells in tissue culture.


Improving safety management in health care organizations.
This article explores reducing workplace accidents and resulting injuries through the introduction of better safety management programs in health care organizations. It examines the benefits of such programs and discusses causes of accidents. It presents components considered necessary for inclusion in an effective accident prevention program.


Validation of the Chinese version of the Schizophrenia Quality of Life Scale Revision 4 (SQLS-R4) in Taiwanese patients with schizophrenia.
We tested the reliability, sensitivity, and validity of a Chinese translation of the Schizophrenia Quality of Life Scale Revision 4 (SQLS-R4). One hundred Taiwanese individuals with schizophrenia were recruited. The internal consistency reliability was satisfactory for both the psychosocial and vitality domains (Cronbach's alpha = 0.92, 0.84). The test-retest reliability was also high (psychosocial: ICC = 0.84, vitality: ICC = 0.84) for those individuals whose psychological conditions remained stable between the two-week interval. However, the responsiveness coefficient for those with considerable changes in psychological conditions ranged from very small to moderate, suggesting either low responsiveness for the vitality domain or a complex relationship between the change of psychological conditions and quality of life, and the need to estimate responsiveness more conclusively in a future intervention study. The convergent validity was supported by moderate-to-large correlations between domains measuring related constructs of the SQLS-R4 and SF-36 (r = -0.65 to -0.67). Overall, the results of this study provide preliminary evidence for the reliability and validity of the SQLS-R4 used in Taiwanese individuals with schizophrenia. This study provides a common ground for international researchers to understand quality of life in Taiwanese patients with schizophrenia.


Optical immunobiosensor assay for determining enrofloxacin and ciprofloxacin in bovine milk.
A rapid, sensitive optical immunobiosensor assay was developed and used to determine enrofloxacin and its main metabolite, ciprofloxacin, in milk from healthy cows and cows with clinical signs of mastitis after intramuscular administration of enrofloxacin. Liquid chromatography (LC) was used to confirm results of the biosensor assay. Despite incomplete cross-reactivity between polyclonal enrofloxacin antibodies and ciprofloxacin, the biosensor assay could be used for semiquantitative analysis of the sum of the 2 substances. LC analysis showed that ciprofloxacin persisted at levels exceeding the expected future maximum residue limit in milk for several days after the end of the withdrawal period.


Development of nerves expressing P2X3 receptors in the myenteric plexus of rat stomach.
Development of neurones and fibres expressing P2X3 receptors in the myenteric plexus of rat stomach and coexistence of the P2X3 receptor with calbindin, calretinin and NOS during postnatal development, were investigated with immunostaining methods. Extrinsic nerves expressing P2X3 receptors appeared as early as E12 and were localised in the trunk and branches of the vagus nerve, which extended rapidly onto the whole rat stomach from E12 to E14. Intrinsic neurone cell bodies with P2X3-immunoreactivity in the myenteric ganglia were first demonstrated postnatally at P1, and at P14, when the number of neurones expressing the P2X3 receptor peaked at 45%. P2X3 receptor-immunoreactivity decreased subsequently, and at P60 only about 11% were P2X3-immunoreactive. Intraganglionic laminar nerve endings and intramuscular arrays were first demonstrated postnatally at P1 and P7, respectively. In the early postnatal days, there were many growth cone-like structures with strong P2X3 immunostaining associated with these endings and arrays. Double-immunostaining showed that 9-15% of P2X3-immunoreactive neurones in the gastric myenteric plexus expressed calbindin D-28 k only in the early postnatal days, while 14-21% of neurones from P1 to P60 increasingly expressed calretinin. About 20% of neurones with P2X3 immunoreactivity coexpressed NOS throughout perinatal development.


Predictors of appropriate use of interpreters: identifying professional development training needs for labor and delivery clinical staff serving Spanish-speaking patients.
Assuring quality health care services to limited English proficient patients requires certain skills, including the ability to communicate through interpreters. This study identifies predictors of appropriate use of interpreters by maternal labor and delivery service providers. Clinical labor and delivery staff (N=200) at five hospitals in an Eastern U.S. city completed a survey about providing care to Latinas. Multivariate logistic regression identified significant predictors for appropriate use of interpreters. The strongest association with appropriately using interpreters was relying less often on general mass media for medical information (OR=2.25; p=.03). Other statistically significant variables included agreeing that learning about Latino history and culture could improve quality of care (OR=2.07; p=02) and seeking medical information from colleagues at the same hospital (OR=1.83; p=.03). Study findings have implications for training professionals about working with interpreters.


Direct influence of temperature on the semicircular canal receptor.
Effect of thermal stimulus on the vestibular receptor was studied using the isolated frog semicircular canal. The posterior (PSC) and lateral semicircular canals (LSC) were placed in the horizontal plane in frog Ringer's solution. The ampullary nerve was sucked into a glass suction electrode to record compound potentials. The steel thermal probe was positioned next to the ampullary surface to give thermal stimuli. When the PSC ampulla was cooled, the spontaneous discharge markedly increased. When the PSC ampulla was warmed, the discharge decreased. When the LSC ampulla was cooled, the discharge increased in the same manner as in the PSC. Also, warming of the LSC decreased the discharge in the same manner as in the PSC. The cupula was removed from the crista in order to eliminate the effect of volume change of the endolymph. The results were comparable to those with intact cupula in both the PSC and LSC. Cooling increased, while warming decreased the discharge. These responses are possibly due to a mechanism other than mechanical volume change, because the PSC and LSC yielded the same type of responses. Direct temperature reaction of the vestibular hair cell was suggested.


Impact of sex education on knowledge and attitude of adolescent school children of Loni village.
Reproductive capability is now established at earlier age. But the subject of adolescent sexuality is taboo in most societies. There is widespread ignorance about risks of unprotected sex, problems among adolescents. Unfortunately need of sex education is not perceived and fulfilled in India especially in rural areas. The present study was conducted to assess the need and demonstrate the impact of sex education among adolescent school children. The impact of sex education workshop was tested by analysing pre- and postintervention questionnaire. The felt need of sex education increased considerably and the knowledge regarding contraceptives increased from manifolds after the intervention. There was significant increase in knowledge about menstrual hygiene, sexually transmitted diseases, etc, after sex education workshop. This study concludes that there is intense need of sex education and it has significant impact on knowledge of adolescent school children.


Real-time monitoring of mycobacterium genomic DNA with target-primed rolling circle amplification by a Au nanoparticle-embedded SPR biosensor.
In this study, we developed a surface plasmon resonance (SPR) DNA biosensor array based on target-primed rolling circle amplification (RCA) for isothermal and rapid detection of two pathogenic mycobacteria, Mycobacterium tuberculosis complex (MTBC) and Mycobacterium avium complex (MAC).The species-specific padlock probe (PLP) was designed to target the sequence in 16S-23S rRNA gene internal transcribed spacer (ITS). After ligation, the circularized PLP could be primed by the target sequence to initial RCA. The RCA performed simultaneously with the cleavage reaction to produce small fragments of single strand DNA which immediately hybridized with the probe immobilized on the sensor chip without denaturation. This process caused SPR angle changes on the chip surface, which made the detection for analysis from the solution achievable, and dynamic real-time RCA monitoring of mycobacterium possible. Besides, Au nanoparticles (AuNPs) were directly assembled onto the surface of the sensor chip via hexanedithiol (HDT) for the enhancement of sensitivity as a label-free detection system. Experimental results show that the signal enhancement by the target-primed RCA together with AuNPs-embedded surface caused at least10-fold increased sensitivity as compared with conventional RCA on bare SPR chip method. Within 40min amplification duration as low as 20amol of synthetic targets and 10(4)CFUmL(-1) of genomic DNA from clinical samples can be detected. The proposed method not only provides a simple design idea for liquid-phase amplification monitoring, but also apply it in clinical pathogen detection, which holds great promise in ultrasensitive bioassay in the future.


A new digital image analysis system useful for surface assessment of vitiligo lesions in transplantation studies.
So far there is no uniformity in the evaluation methods used in the assessment of treatment outcome in vitiligo studies. The ability to objectively measure surfaces of vitiligo lesions is important for both clinical practice and research. Our objective was to assess the reproducibility, accuracy, user-friendliness and time effectiveness of a new digital image analysis system for surface measurement of vitiligo lesions. Three different observers performed both a visual estimation and a digital image analysis on 30 images of 10 vitiligo lesions. Inter- and intra-observer variation were evaluated and results were compared with the 2D gold standard measurements and a 3D measurement. A high inter- and intra-observer variability was observed for the visual estimation of surfaces. With the digital image analysis system a significant improvement of the reproducibility was achieved (p = 0.01). Moreover, results were accurate and the measurement procedure was user-friendly. Importantly, a systematic underestimation was demonstrated when comparing the 2D with the 3D measurements. We introduced an objective measurement method that might be useful in the future for consistently measuring surfaces of selected vitiligo lesions both before and after different therapeutic modalities.


Timeless Is a Novel Estrogen Receptor Co-activator Involved in Multiple Signaling Pathways in MCF-7 Cells.
Activation of estrogen receptor α (ERα) stimulates cell division and tumor growth by modulating the expression of ERα target genes. This activation involves the recruitment of specific proteins with activities that are still not fully understood. Timeless, the human homolog of the Drosophila gene involved in circadian rhythm, was previously shown to be a strong predictor of tamoxifen relapse, and is involved in genomic stability and cell cycle control. In this study, we investigated the interplay between Timeless and ERα, and showed that human Timeless is an ERα coactivator. Timeless binds to ERα and enhances its transcriptional activity. Overexpressing Timeless increases PARP1 expression and enhances ERα-induced gene regulation through the proximal LXXLL motif on Timeless protein and ERα PARylation. Finally, Timeless is recruited with ERα on the GREB1 and cMyc promoters. These data, the first to link Timeless to steroid hormone function, provide a mechanistic basis for its clinical association with tamoxifen resistance. Thus, our results identify Timeless as another key regulator of ERα in controlling ERα transactivation.


Chronic renal disease in Kuwaiti nationals: a prospective study during the past 4 years.
Our study is a prospective one conducted at Al-Amiri Hospital and including all new cases of chronic renal disease (CRD) seen at the capital area of Kuwait between 1 January 1999 and 30 December 2003. Diagnosis of CRD was based on clinical, laboratory, and radiological features. Kidney biopsies were done when indicated. A total of 271 cases of chronic renal failure (CRF) were diagnosed, of whom 143 were women. The median age was 40 years (range, 5 to 80 years; mean +/- SD: 40 +/- 14). The most common cause of CRF was glomerulonephritis (32%), of which systemic lupus erythematosis and vasculitis constituted 5% and 4%, respectively. Diabetic glomerulosclerosis was the second leading cause of CRD (24%), followed by tubulointerstitial disease (11%) and nephroangiosclerosis (10%). Less frequent causes included renovascular/ischemic disease (6%), obstructive nephropathy (3%), and adult polycystic kidney disease (3%). One hundred and seven patients had 121 incidents of acute deterioration of underlying renal disease. This was mostly due to drugs (22%), infection (21%), and volume depletion (13%). Antiinflammatory drugs were the most common drugs (63%) responsible for the acute decline in renal function. By the end of the study, 18 (7%) patients died, 55 (20%) required maintenance dialysis, and 40 (15%) had received a kidney allograft. Diabetic patients did not differ from nondiabetic with regard mortality, although had more renal replacement therapy (p = .002). Using the Cox regression model, analysis of the relative risk factors likely to contribute to mortality, viz. age, gender, original kidney disease, fitness for transplantation, and mode of presentation, did not show significant factors except for less hazard to death in those diagnosed early with CRD (i.e., on routine testing; relative risk 0.06, p = .01). In conclusion, our study indicates that early diagnosis and management of CRD can improve the patient's quality of life and decrease the cost of frequent hospitalization, morbidity, and even mortality associated with end-stage renal disease.


Two fractions staged Gammaknife radiosurgery for "large" cerebral metastases.
Gammaknife radiosurgery (GKRS) is a valuable option to control cerebral metastases. However, the risk (adverse radiation effect (ARE))-benefit (local control (LC)) ratio switches when the target is too large. In order to balance this ratio, two fractions staged GKRS protocol was conducted for "large" cerebral metastases. The aim of this study is to evaluate the outcome (LC, ARE). A total of 39 large cerebral metastases in 35 patients were treated. The initial mean tumor volume was 14.6 cc [6.1; 35.8]. The prescription margin dose was 12 Gy on the 50% isodose line, with 2 weeks between them. A majority of primary cancer were from lung (43%), melanoma (20%) or breast (17%) origin. The mean age was 63 years old (31-89). Mean Graded Prognostic Assessment (GPA) was 2. At the second fraction, mean tumor volume was 10.3 cc [1.9-27.4]. The mean percentage of volume variation for decreasing lesions was 29%. At last follow-up, mean tumor volume was 7.4 cc [0-25.2]; 34 lesions decreased volume (mean 35%). A decreased volume of more than 45% after first stage GKRS was able to predict a long-term local response to staged GKRS treatment. Local control rate at 6 months and 1 year was 87.3% and 75% respectively. The rate of ARE was 7.7%. No predictive factor of local control or ARE was found in a univariate analysis. The new 2-fractions-dose-staged GKRS concept seems to be a well-tolerated and effective treatment option for large cerebral metastases.


Predicting of diabetic retinopathy development stages of fundus images using deep learning based on combined features.
The number of diabetic retinopathy (DR) patients is increasing every year, and this causes a public health problem. Therefore, regular diagnosis of diabetes patients is necessary to avoid the progression of DR stages to advanced stages that lead to blindness. Manual diagnosis requires effort and expertise and is prone to errors and differing expert diagnoses. Therefore, artificial intelligence techniques help doctors make a proper diagnosis and resolve different opinions. This study developed three approaches, each with two systems, for early diagnosis of DR disease progression. All colour fundus images have been subjected to image enhancement and increasing contrast ROI through filters. All features extracted by the DenseNet-121 and AlexNet (Dense-121 and Alex) were fed to the Principal Component Analysis (PCA) method to select important features and reduce their dimensions. The first approach is to DR image analysis for early prediction of DR disease progression by Artificial Neural Network (ANN) with selected, low-dimensional features of Dense-121 and Alex models. The second approach is to DR image analysis for early prediction of DR disease progression is by integrating important and low-dimensional features of Dense-121 and Alex models before and after PCA. The third approach is to DR image analysis for early prediction of DR disease progression by ANN with the radiomic features. The radiomic features are a combination of the features of the CNN models (Dense-121 and Alex) separately with the handcrafted features extracted by Discrete Wavelet Transform (DWT), Local Binary Pattern (LBP), Fuzzy colour histogram (FCH), and Gray Level Co-occurrence Matrix (GLCM) methods. With the radiomic features of the Alex model and the handcrafted features, ANN reached a sensitivity of 97.92%, an AUC of 99.56%, an accuracy of 99.1%, a specificity of 99.4% and a precision of 99.06%.


Is the priority review voucher program stimulating new drug development for tropical diseases?
Congress created the tropical disease priority review voucher program to stimulate new drug development for tropical diseases. An analysis of the pharmaceutical pipeline indicates that the development of drugs for these tropical diseases has increased. However, the effects of the program are not uniform across all diseases, as malaria and tuberculosis have seen significant new drug development, while other diseases have not.


Antigenic and biochemical characterization of poliovirus type 1 isolates.
By the introduction of Sabin oral poliovirus vaccine, the circulation of wild type polioviruses has virtually disappeared in Japan. However, an outbreak of poliomyelitis associated with sporadic transmission of type 1 wild strain occurred in Nagano in 1980. Furthermore, we found that some type 1 wild strains were introduced into Japan from abroad in 1981. In recent surveys, the two poliovirus type 1 isolates which have non-vaccine-like antigenic character were detected in Aichi. Then, an investigation to trace the origin of these strains was performed, by using intratypic serodifferentiation and biochemical techniques. Electrophoretic migration patterns of their structural polypeptides were quite different from the vaccine virus. In the oligonucleotide mapping, however, one of them gave patterns very similar to those of the vaccine virus. We could conclude that one originated most probably from wild strains, and the other was an antigenic variant derived from the vaccine virus. It showed that oligonucleotide mapping was a very useful method for identification of antigenic modified Sabin type 1 derivatives.


Acute kidney injury-attributable mortality in critically ill patients with sepsis.
To assess whether acute kidney injury (AKI) is independently associated with hospital mortality in ICU patients with sepsis, and estimate the excess AKI-related mortality attributable to AKI. We analyzed adult patients from two distinct retrospective critically ill cohorts: (1) Medical Information Mart for Intensive Care IV (MIMIC IV; n = 15,610) cohort and (2) Wenzhou (n = 1,341) cohort. AKI was defined by Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We applied multivariate logistic and linear regression models to assess the hospital and ICU mortality, hospital length-of-stay (LOS), and ICU LOS. The excess attributable mortality for AKI in ICU patients with sepsis was further evaluated. AKI occurred in 5,225 subjects in the MIMIC IV cohort (33.5%) and 494 in the Wenzhou cohort (36.8%). Each stage of AKI was an independent risk factor for hospital mortality in multivariate logistic regression after adjusting for baseline illness severity. The excess attributable mortality for AKI was 58.6% (95% CI [46.8%-70.3%]) in MIMIC IV and 44.6% (95% CI [12.7%-76.4%]) in Wenzhou. Additionally, AKI was independently associated with increased ICU mortality, hospital LOS, and ICU LOS. Acute kidney injury is an independent risk factor for hospital and ICU mortality, as well as hospital and ICU LOS in critically ill patients with sepsis. Thus, AKI is associated with excess attributable mortality.


Using protein-binding microarrays to study transcription factor specificity: homologs, isoforms and complexes.
Protein-DNA binding is central to specificity in gene regulation, and methods for characterizing transcription factor (TF)-DNA binding remain crucial to studies of regulatory specificity. High-throughput (HT) technologies have revolutionized our ability to characterize protein-DNA binding by significantly increasing the number of binding measurements that can be performed. Protein-binding microarrays (PBMs) are a robust and powerful HT platform for studying DNA-binding specificity of TFs. Analysis of PBM-determined DNA-binding profiles has provided new insight into the scope and mechanisms of TF binding diversity. In this review, we focus specifically on the PBM technique and discuss its application to the study of TF specificity, in particular, the binding diversity of TF homologs and multi-protein complexes.


Validity of body mass index compared with other body-composition screening indexes for the assessment of body fatness in children and adolescents.
Validation studies of height- and weight-based indexes of body fatness in children and adolescents have examined only small samples of school-age children. The objective was to validate the performance of age- and sex-specific body mass index (BMI) compared with the Rohrer index (RI) and weight-for-height in screening for both underweight and overweight in children aged 2-19 y. Data from the third National Health and Nutrition Examination Survey (n = 11096) and a pooled data set from 3 studies that used dual-energy X-ray absorptiometry (n = 920) were examined. The receiver operating characteristic curve was used to characterize the sensitivity and specificity of these 3 indexes in classifying both underweight and overweight. Percentage body fat and total fat mass were determined by dual-energy X-ray absorptiometry. Subcutaneous fat was assessed on the basis of the average of triceps and subscapular skinfold thicknesses. For children aged 2-19 y, BMI-for-age was significantly better than were weight-for-height and RI-for-age in detecting overweight when average skinfold thicknesses were used as the standard, but no differences were found in detecting underweight. When percentage body fat or total fat mass was used as the standard, BMI-for-age was significantly better than was RI-for-age in detecting overweight in children aged 3-19 y. No differences were found between BMI-for-age and weight-for-height in detecting overweight or underweight. For children and adolescents aged 2-19 y, the performance of BMI-for-age is better than that of RI-for-age in predicting underweight and overweight but is similar to that of weight-for-height.


Effects of Extraction Methods on Phytochemicals of Rice Bran Oils Produced from Colored Rice.
Rice bran oil (RBO) especially from colored rice is rich in phytochemicals and has become popular in food, cosmetic, nutraceutical and pharmaceutical applications owing to its offering health benefits. This study determined the contents of phytochemicals including oryzanols, phytosterols, tocopherols (Toc) and tocotrienols (T3) in RBOs extracted using different methods namely cold-press extraction (CPE), solvent extraction (SE) and supercritical CO2 extraction (SC-CO2). Two colored rice, Red Jasmine rice (RJM, red rice) and Hom-nin rice (HN, black rice), were studied in comparison with the popular Thai fragrant rice Khao Dawk Mali 105 (KDML 105, white rice). RBOs were found to be the rich source of oryzanols, phytosterols, Toc and T3. Rice varieties had a greater effect on the phytochemicals concentrations than extraction methods. HN rice showed the significantly highest concentration of all phytochemicals, followed by RJM and KDML 105 rice, indicating that colored rice contained high concentration of phytochemicals in the oil than non-colored rice. The RBO samples extracted by the CPE method had a greater concentration of the phytochemicals than those extracted by the SC-CO2 and SE methods, respectively. In terms of phytochemical contents, HN rice extracted using CPE method was found to be the best.


Impact of pre-analytical handling on bone marrow mRNA gene expression.
Large clinical trials on leukaemia, require the transport of bone marrow (BM) from participating clinics to central diagnostic laboratories. We have investigated the impact of RNA extraction protocols and time delays between sample aspiration and RNA extraction on RNA quality and gene expression profiles. Intact RNA can be extracted from BM samples stored at room temperature for up to 48 h. Gene expression analyses using Affymetrix U95Av2 GeneChips and a custom-designed cDNA array in parallel showed that even short-term storage of BM has dramatic effects on mRNA expression of individual transcripts. Many probe sets/genes showed either reproducible deregulation (18.8%, analysis of variance <0.05), or inconsistent expression that differed from patient to patient (38.4%). Moderate alterations were observed in 42.8% genes, with a maximum fold change <2.0 in all experiments and at all time points. These profound effects complicate the use of unstabilized, shipped BM samples for gene expression analyses. The comparison of a variety of RNA stabilization reagents (e.g. PAXgene) resulted in partial conservation of the mRNA expression patterns. Immediate density centrifugation or erythrocyte lysis and freezing at -80 degrees C represent simple procedures that reliably preserved mRNA gene expression patterns in BM.


A qualitative analysis of life course adjustment to multiple morbidity and disability.
The accumulation of limitations over the life course requires that women readapt to environmental barriers they encounter over time. The purpose of this qualitative case study was to detail the life experiences associated with living with mobility, cognitive, and sensory loss experienced by a woman and her sister who participated in an ongoing ethnographic study of mobility impairment in women. In-depth interviews were subjected to thematic, life course analysis. A family case study was interpreted as an exemplar for aging with early-onset disability into multiple morbidity, which was described as a series of loss, recovery, and reengagement. Within the case study, the participant suggested that because her functional limitations were not accommodated earlier in life due to societal and family-level disadvantage, these limitations were more difficult to adjust to in later years.


Parametric study of a Hill-type hyperelastic skeletal muscle model.
Hill's one-dimensional three-element model has often been used for formulating a three-dimensional skeletal muscle constitutive model, which generally involves several material parameters. However, only few of these parameters have physical meanings and can be experimentally determined. In this paper, a parametric study of a Hill-type hyperelastic skeletal muscle model is performed. First, the Hill-type hyperelastic skeletal muscle model is formulated, containing 13 material parameters. The values or value ranges of these parameters are discussed. The muscle model is then used to predict the behaviour of New Zealand white rabbit hind leg muscle tibialis anterior and a sensitivity study of several parameters is performed. Results show that some parameters in the muscle model can be experimentally determined, some parameters have their own value ranges and the muscle model can predict the experimental data by tuning the parameters within their value ranges. The results from the sensitivity study can help understand how some parameters influence the total muscle stress.


Treatment of cerebellar ataxia with 5-HT1A agonist.
Effective, pharmacologic approaches to the treatment of cerebellar ataxia are lacking or inadequate. We recently reported preliminary evidence that tandospirone citrate (tandospirone), a 5-HT1A agonist, improved cerebellar ataxia in patients with Machado-Joseph disease (MJD). In the course of that study, we found that such treatment also alleviated the pain associated with cold sensations in the legs, insomnia, anorexia, and depression, all of which are thought to be mediated through activation of the 5-HT1A receptor. In this paper, we reviewed the few published clinical trials that involved the use of 5-HT1A receptor agonists for the treatment of cerebellar ataxia, and discussed the current theories regarding their mechanism of action. Cortical cerebellar atrophy (CCA) was reported, in a double-blind study, to be amenable to treatment with tandospirone. Other types of spinocerebellar degeneration (SCD) i.e., olivopontocerebellar atrophy (OPCA) and Machado-Joseph disease (MJD) have also been reported to respond to the drug, but these have been small studies. Responsive patients exhibited only mild ataxia. The doses of 5-HT1A agonists that have been used successfully ranged from 12.5 mg/day to 60 mg/day (or 1 mg/kg), and were well tolerated by most patients.


The UL24 protein of herpes simplex virus 1 affects the sub-cellular distribution of viral glycoproteins involved in fusion.
Mutations in UL24 of herpes simplex virus type 1 can lead to a syncytial phenotype. We hypothesized that UL24 affects the sub-cellular distribution of viral glycoproteins involved in fusion. In non-immortalized human foreskin fibroblasts (HFFs) we detected viral glycoproteins B (gB), gD, gH and gL present in extended blotches throughout the cytoplasm with limited nuclear membrane staining; however, in HFFs infected with a UL24-deficient virus (UL24X), staining for the viral glycoproteins appeared as long, thin streaks running across the cell. Interestingly, there was a decrease in co-localized staining of gB and gD with F-actin at late times in UL24X-infected HFFs. Treatment with chemical agents that perturbed the actin cytoskeleton hindered the formation of UL24X-induced syncytia in these cells. These data support a model whereby the UL24 syncytial phenotype results from a mislocalization of viral glycoproteins late in infection.


Does aluminium bind to histidine? An NMR investigation of amyloid β12 and amyloid β16 fragments.
Aluminium and zinc are known to be the major triggering agents for aggregation of amyloid peptides leading to plaque formation in Alzheimer's disease. While zinc binding to histidine in Aβ (amyloid β) fragments has been implicated as responsible for aggregation, not much information is available on the interaction of aluminium with histidine. In the NMR study of the N-terminal Aβ fragments, DAEFRHDSGYEV (Aβ12) and DAEFRHDSGYEVHHQK (Aβ16) presented here, the interactions of the fragments with aluminium have been investigated. Significant chemical shifts were observed for few residues near the C-terminus when aluminium chloride was titrated with Aβ12 and Aβ16 peptides. Surprisingly, it is nonhistidine residues which seem to be involved in aluminium binding. Based on NMR constrained structure obtained by molecular modelling, aluminium-binding pockets in Aβ12 were around charged residues such as Asp, Glu. The results are discussed in terms of native structure propagation, and the relevance of histidine residues in the sequences for metal-binding interactions. We expect that the study of such short amyloid peptide fragments will not only provide clues for plaque formation in aggregated conditions but also facilitate design of potential drugs for these targets.


Brent Technique of Repair Versus Nagata Auricular Reconstruction for Microtia Reconstruction: A Systematic Review and Meta-Analysis.
Up to 17.4 in every 10,000 births are affected by microtia, but no consensus exists on a gold standard technique for autogenous repair. In this study, the authors compare 2 common methods-the Brent and Nagata autogenous costal cartilage ear reconstruction techniques. A systematic review of the literature and a quantitative meta-analysis to compare the outcomes of these 2 approaches were performed. The outcomes analyzed included rates of infection, necrosis, cartilage exposure, cartilage resorption, hematoma, wire extrusion, and hypertrophic scar. A MEDLINE database systematic review with the following keywords: microtia, Brent, and Nagata was performed. Case reports and articles without original data or patient outcomes were excluded. Inclusion methods for study selection are outlined in Supplemental Digital Content 1, http://links.lww.com/SCS/F461, below. The prevalence of outcomes for each study was analyzed through meta-analysis of proportions using Stata. A total of 536 potential studies were retrieved for review. Twelve of these studies met inclusion criteria. Four studies utilized the Brent method of repair with the inclusion of 563 ear reconstructions. Nine studies implemented the Nagata technique in 2304 reconstructions. Two studies directly compared the Brent (327 ears) and Nagata (471 ears) techniques. The calculated rate and 95% confidence intervals are summarized in Supplemental Digital Content 2, http://links.lww.com/SCS/F461. There were no statistically significant differences in complication rates between the Brent and Nagata microtic reconstruction techniques identified in this study. The Brent and Nagata microtia reconstruction techniques have no difference in the risk of infection, necrosis, cartilage exposure, cartilage resorption, hematoma, wire extrusion, or hypertrophic scars.


Successful treatment of pure red cell aplasia because of ABO major mismatched stem cell transplant.
Pure red cell aplasia (PRCA) is a well-documented potential side effect of ABO major mismatched allogeneic hematopoietic stem cell transplants. This side effect may be self-limiting, but is sometimes treated using modalities such as steroids, antithymocyte globulin, donor lymphocyte infusions, rituximab, or plasma exchanges. Another well-documented cause of pure red cell aplasia is a chronic parvovirus B19 infection, which may be seen in immunocompromised hosts. The treatment of this cause of PRCA includes removal of immunosuppression, intravenous immunoglobulin (IVIg), or rituximab; however, this condition may also be self-limiting. We show a case of a patient with PRCA who had previously received an ABO major mismatched allogeneic hematopoietic stem cell transplant, but also had an identified source of parvovirus B19 in his marrow post-transplant. He underwent several various treatments for his PRCA, including rituximab, bortezomib, and then plasma exchange. Anti-A IgM and IgG titers were drawn throughout his treatment course, and fell from 512 (anti-A IgM) and 1024 (anti-A IgG) to 2 (anti-A IgM) and 8 (anti-A IgG). After his last plasma exchange procedure, the patient's hemoglobin and reticulocyte count rose from 6.6 g/dL and 12.5 × 109 /L (respectively) at the onset of the PRCA diagnosis to 9.6 g/dL and 138.1 × 109 /L after a series of 14 plasma exchanges. This demonstrates a case of PRCA caused by an ABO major mismatched allogeneic hematopoietic stem cell transplant that was potentially complicated by a parvovirus infection, which was treated with multiple therapeutic interventions including a series of therapeutic plasma exchanges, rituximab, and bortezomib. Successful resolution of the patient's PRCA was achieved.


Hepatic gene expression of apolipoprotein B100 during early lactation in underfed, high producing dairy cows.
The hepatic gene expression of apolipoprotein B, the major protein of very low density lipoproteins in plasma, was studied using 8 Holstein x Friesian cows during the first 12 wk of lactation. Cows were fattened during gestation and were underfed just after parturition to increase fat mobilization and subsequent hepatic steatosis. Intracellular concentrations of apolipoprotein B and apolipoprotein B mRNA and control parameters (albumin, total lipids, RNA, and proteins) were determined in liver samples obtained by biopsy from each cow on four occasions at 1, 2, 4, and 12 wk after calving. Results were compared with those obtained from 5 dry cows in late pregnancy and 4 dry nonpregnant cows. The hepatic concentration of apolipoprotein B was lower (approximately 25%) during wk 1, 2, and 4 after calving, a period of intense liver steatosis (44.2 to 95.7 mg of triglycerides/g of fresh tissue), than for nonsteatotic dry cows (pregnant or nonpregnant); hepatic concentrations were also lower than those during wk 12. In contrast, hepatic concentrations of mRNA coding for apolipoprotein B, total proteins, RNA, and albumin did not vary significantly during early lactation. These results suggested that synthesis of apolipoprotein B during early lactation is specifically regulated at a posttranscriptional level by a decrease in the rate of translation, or by a higher rate of intracellular degradation of apolipoprotein B, or both.


Expedient synthesis of α-heteroaryl piperidines using a Pd-catalyzed Suzuki cross-coupling-reduction sequence.
A method for the modular synthesis of α-heteroaryl piperidines is reported. The two-step procedure consists of an initial Pd-catalyzed Suzuki cross-coupling of the heteroaryl bromide with a boronate ester derived from N-Boc piperidone, followed by subsequent tetrahydropyridine reduction. Using this method, α-heteroaryl piperidine products featuring a broad range of pharmaceutically relevant azine and diazine substitutions have been prepared.


Specific inhibition of macrophage antibody-dependent endocytosis by p-chloromercuribenzenesulphonic acid: identification of sensitive membrane proteins.
Murine macrophage Fc receptor function has been studied with the membrane-impermeable sulphydryl-blocking reagent p-chloromercuribenzenesulphonic acid (PCMBSA). Antibody-dependent endocytosis of fluorescein-labelled immune complexes was studied with video intensification microscopy. PCMBSA was found to inhibit the endocytosis of immune complexes at 10 nM. Control experiments indicate that the inhibition is due to an effect upon the cell, not the immune complex. Furthermore, specificity is suggested by the fact that complement-mediated and latex bead phagocytosis were not affected. 203Hg-PCMBSA labelled three macrophage proteins of molecular weight (MW) 25,000, 35,000 and 50,000. A 25,000 MW PCMBSA-binding protein has been found that is specifically immunoprecipitated by an anti-Fc receptor antibody. These studies suggest that perturbation of a cell surface sulphydryl group(s) of one of the three major PCMBSA binding membrane proteins, possibly an Fc receptor-associated protein, blocks a molecular signal required for antibody-dependent endocytosis.


Consciousness weaves our internal view of the outside world.
Low-level consciousness is fundamental to our understanding of the world. Within the conscious field, the constantly changing external visual information is transformed into stable, object-based percepts. Remarkably, holistic objects are perceived while we are cognizant of all of the spatial details comprising the objects and of the relationship between individual elements. This parallel conscious association is unique to the brain. Conscious contributions to motor activity come after our understanding of the world has been established.


Bone diseases of the jaws.
Lesions specific for the jaws and not occurring in any other bones mostly are related to the teeth or to odontogenic tissues. Moreover, the jaws may harbor nonodontogenic bone lesions not seen in any other part of the skeleton. This paper pays attention to the diseases that are specific for the jaws, odontogenic as well as nonodontogenic. Both neoplastic and nonneoplastic entities will be discussed.


Machine learning to predict progression of non-alcoholic fatty liver to non-alcoholic steatohepatitis or fibrosis.
Non-alcoholic fatty liver (NAFL) can progress to the severe subtype non-alcoholic steatohepatitis (NASH) and/or fibrosis, which are associated with increased morbidity, mortality, and healthcare costs. Current machine learning studies detect NASH; however, this study is unique in predicting the progression of NAFL patients to NASH or fibrosis. To utilize clinical information from NAFL-diagnosed patients to predict the likelihood of progression to NASH or fibrosis. Data were collected from electronic health records of patients receiving a first-time NAFL diagnosis. A gradient boosted machine learning algorithm (XGBoost) as well as logistic regression (LR) and multi-layer perceptron (MLP) models were developed. A five-fold cross-validation grid search was utilized for hyperparameter optimization of variables, including maximum tree depth, learning rate, and number of estimators. Predictions of patients likely to progress to NASH or fibrosis within 4 years of initial NAFL diagnosis were made using demographic features, vital signs, and laboratory measurements. The XGBoost algorithm achieved area under the receiver operating characteristic (AUROC) values of 0.79 for prediction of progression to NASH and 0.87 for fibrosis on both hold-out and external validation test sets. The XGBoost algorithm outperformed the LR and MLP models for both NASH and fibrosis prediction on all metrics. It is possible to accurately identify newly diagnosed NAFL patients at high risk of progression to NASH or fibrosis. Early identification of these patients may allow for increased clinical monitoring, more aggressive preventative measures to slow the progression of NAFL and fibrosis, and efficient clinical trial enrollment.


Humanized NOD/SCID/IL2rγnull (hu-NSG) Mouse Model for HIV Replication and Latency Studies.
Ethical regulations and technical challenges for research in human pathology, immunology, and therapeutic development have placed small animal models in high demand. With a close genetic and behavioral resemblance to humans, small animals such as the mouse are good candidates for human disease models, through which human-like symptoms and responses can be recapitulated. Further, the mouse genetic background can be altered to accommodate diverse demands. The NOD/SCID/IL2rγnull (NSG) mouse is one of the most widely used immunocompromised mouse strains; it allows engraftment with human hematopoietic stem cells and/or human tissues and the subsequent development of a functional human immune system. This is a critical milestone in understanding the prognosis and pathophysiology of human-specific diseases such as HIV/AIDS and aiding the search for a cure. Herein, we report a detailed protocol for generating a humanized NSG mouse model (hu-NSG) by hematopoietic stem cell transplantation into a radiation-conditioned neonatal NSG mouse. The hu-NSG mouse model shows multi-lineage development of transplanted human stem cells and susceptibility to HIV-1 viral infection. It also recapitulates key biological characteristics in response to combinatorial antiretroviral therapy (cART).


lncRNA-PCAT1 rs2632159 polymorphism could be a biomarker for colorectal cancer susceptibility.
Background: Single-nucleotide polymorphisms (SNPs) in lncRNAs could be biomarkers for susceptibility to colorectal cancer (CRC), but the association of PCAT1 polymorphisms and CRC susceptibility is yet to be studied. Methods: Five tagSNPs covering the PCAT1 gene were detected through Kompetitive Allele-Specific PCR among 436 CRC patients and 510 controls. An expression quantitative trait locus (eQTL) bioinformatic analysis was then performed. Results: In the present study, PCAT1 rs2632159 polymorphism increased CRC risk by 1.37-fold and 2.19-fold in the dominant and recessive models, respectively (P=0.040 and 0.041). When the CRC cases were divided into colon cancer and rectal cancer, we found that this polymorphism affected colon cancer risk under the dominant model (P=0.022, OR = 1.51) and affected rectal cancer susceptibility under the recessive model (P=0.009, OR = 3.03). A more pronounced effect was observed in the male subgroup in that PCAT1 rs2632159 SNP increased rectal cancer risk by 3.97-fold (P=0.017). When PCAT1 rs2632159 was present, epistatic effects were observed with rs1902432 and rs785005 (P=0.011 and 0.008, respectively). eQTL analysis showed that rs2632159 could influence binding with the transcription factors EBF, LUN-1, and TCF12. Conclusion:PCAT1 rs2632159 SNP could be a biomarker for CRC risk. And the rs1902432 SNP might only have potential to be a biomarker for colon cancer risk.


Vibrational sum-frequency spectroscopy for trace chemical detection on surfaces at stand-off distances.
Vibrational sum-frequency spectroscopy (VSFS) has been used for some time as a laboratory-based surface chemical analytical tool. Here, theoretical considerations in applying the method as a remote-sensing probe for detecting trace levels of chemicals adsorbed on surfaces are presented. Additionally, a VSFS instrument is configured to operate at a stand-off distance of 2.2 m using near-nadir incidence angles. This system was used to measure VSFS spectra for films of pure 1-amino-4-nitrobenzene (p-nitroaniline, PNA) and pure 2-hydroxy-1,3,5-trinitrobenzene (picric acid, PA) adsorbed on polished T-6061 aluminum alloy. These spectra are used to investigate the effect of optical polarization on the sum-frequency response of these compounds at nadir optical geometries. Detection limits for each compound are also estimated and found to be 0.51 μg cm(2) for PNA and 0.89 μg cm(2) for PA. The implications of these results regarding remote sensing applications of VSFS are discussed.


A Review of NEPA, a Novel Fixed Antiemetic Combination with the Potential for Enhancing Guideline Adherence and Improving Control of Chemotherapy-Induced Nausea and Vomiting.
Combination antiemetic regimens targeting multiple molecular pathways associated with emesis have become the standard of care for prevention of chemotherapy-induced nausea and vomiting (CINV) related to highly and moderately emetogenic chemotherapies. Antiemetic consensus guidelines from several professional societies are widely available and updated regularly as new data emerges. Unfortunately, despite substantial research supporting the notion that guideline conformity improves CINV control, adherence to antiemetic guidelines is unsatisfactory. While studies are needed to identify specific barriers to guideline use and explore measures to enhance adherence, a novel approach has been taken to improve clinician adherence and patient compliance, with the development of a new combination antiemetic. NEPA is an oral fixed combination of a new highly selective NK1 receptor antagonist (RA), netupitant, and the pharmacologically and clinically distinct 5-HT3 RA, palonosetron. This convenient antiemetic combination offers guideline-consistent prophylaxis by targeting two critical pathways associated with CINV in a single oral dose administered only once per cycle. This paper will review and discuss the NEPA data in the context of how this first combination antiemetic may overcome some of the barriers interfering with adherence to antiemetic guidelines, enhance patient compliance, and offer a possible advance in the prevention of CINV for patients.


Sleep-promoting and hypothermic effects of daytime melatonin administration in humans.
Sleep-promoting and hypothermic effects of orally administered melatonin during the daytime were assessed using a placebo-controlled, double-blind, cross-over design. Following a 7-hour nighttime sleep opportunity, healthy young male subjects (n = 8) were given either a placebo or one of three doses of melatonin (1 mg, 10 mg, and 40 mg) at 1000 hours. Sleep was polygraphically assessed in a 4-hour sleep opportunity from 1200 to 1600 hours. All doses of melatonin significantly shortened the latency to sleep onset. Melatonin also significantly increased total sleep time and decreased wake after sleep onset (WASO). Sleep following melatonin administration contained significantly more stage 2 and less stage 3-4, while stage 1 and rapid eye movement (REM) sleep were unaffected. In addition to the sleep-promoting effects, melatonin completely suppressed the normal diurnal rise of core body temperature. These data suggest that melatonin may be an effective method of promoting sleep for individuals attempting to sleep during their subjective day, such as shiftworkers and individuals rapidly traveling across multiple time zones.


Withdrawal of nutritional support in the terminally ill.
The technological advances of recent years have placed an increasingly troublesome burden on healthcare practitioners. When the focus of patient care becomes supportive in nature and not curative, decisions to withhold or withdraw medical treatment become important. The purpose of this article is to allow the reader to explore their own personal reasoning for their continued use of or withdrawal of nutritional support. Legal/ethical principles and approaches to withdraw treatment will be discussed and help guide providers in care options.


Endotracheal tuberculous stenosis: ventilation rescue and bronchography guided stenting.
We present the case of a 16-year-old female patient who presented with dyspnoea, cough and noisy breathing that progressed further in hospital with the development of stridor and severe respiratory compromise requiring mechanical ventilatory support. Investigations were consistent with a diagnosis of endotracheal tuberculosis with tracheal and bronchial stenosis. Despite adequate anti-tuberculous therapy and ventilation the patient had high airway pressures, low tidal volumes and hypercapnia, which prevented weaning from mechanical ventilation. Balloon dilatation and stenting of the 4.5cm long, 2.3mm diameter stenotic tracheal segment was performed under radiological guidance. The patient was weaned successfully from the ventilator post-procedure. This report illustrates the successful management of an uncommon presentation of a common disease with modern endoscopic therapy.


Differences in prolactin receptor (PRLR) in mouse and human fallopian tubes: evidence for multiple regulatory mechanisms controlling PRLR isoform expression in mice.
The anterior pituitary-derived hormone prolactin (PRL) signals through the PRL receptor (PRLR) and is important for female reproductive function in mammals. In contrast to the extensive studies of PRLR expression and regulation in human and mouse ovary and uterus, the mechanisms controlling the regulation of PRLR isoform expression in the fallopian tube are poorly understood. Because dynamic interaction of hormonal signaling in gonadal tissue and the pituitary or in gonadal tissues themselves in mammals suggests endocrine or paracrine regulation of PRLR expression, we questioned whether differential regulation of PRLR isoforms by PRL ovarian-derived estrogen (E(2)) and progesterone (P(4)) exists in the fallopian tube and pituitary of prepubertal female mice. Western blot analysis showed distinct molecular separation of PRLR isoforms in mouse and human fallopian tubes, and cellular localization was found in mouse and human tubal epithelia but not in mouse tubal smooth muscle cells. These data support the concept of an isoform- and cell type-specific expression of PRLR in human and mouse fallopian tubes. Moreover, expression of the long form of PRLR decreased after PRL treatment and increased after blockage of endogenous PRL secretion by bromocriptine (an inhibitor of PRL secretion) in a time-dependent manner in mouse fallopian tube. The opposite regulation was observed in the pituitary. Treatment with exogenous E(2) or P(4) led to changes in PRLR expression in the fallopian tube similar to those of PRL treatment. However, E(2) and P(4) did not affect PRLR expression in the pituitary. Estrogen had no effect on the long form of PRLR expression, whereas P(4) regulated the long form of PRLR in the fallopian tube, as did PRL. Taken together, the data from our comparative study provide evidence that PRLR can be regulated by an interplay of two different mechanisms, PRL or ovarian steroid hormones independently or in combination in a tissue-specific manner. Furthermore, we found that ovarian steroid hormones selectively suppress the expression of PRLR isoforms in mouse fallopian tubes. These findings may contribute to our understanding of the mechanisms controlling PRLR isoform expression in the fallopian tube (in addition to ovary and uterus), with implications for female reproduction.


Phosphinoyl Radical-Initiated 1,2-Bifunctional Thiocyanodiphenylphosphinoylation of Alkenes.
1,2-Bifuctional thiocyanodiphenylphosphinoylation of alkenes is established through the phosphinoyl radical addition followed by Cu-catalyzed thiocyanation. This one-pot reaction is applicable to a range of aromatic, aliphatic, and cyclic alkenes to afford thiocyanodiphenylphosphinoylated compounds in satisfactory yields.


Validation of a virtual source model of medical linac for Monte Carlo dose calculation using multi-threaded Geant4.
The use of phase space in medical linear accelerator Monte Carlo (MC) simulations significantly improves the execution time and leads to results comparable to those obtained from full calculations. The classical representation of phase space stores directly the information of millions of particles, producing bulky files. This paper presents a virtual source model (VSM) based on a reconstruction algorithm, taking as input a compressed file of roughly 800 kb derived from phase space data freely available in the International Atomic Energy Agency (IAEA) database. This VSM includes two main components; primary and scattered particle sources, with a specific reconstruction method developed for each. Energy spectra and other relevant variables were extracted from IAEA phase space and stored in the input description data file for both sources. The VSM was validated for three photon beams: Elekta Precise 6 MV/10 MV and a Varian TrueBeam 6 MV. Extensive calculations in water and comparisons between dose distributions of the VSM and IAEA phase space were performed to estimate the VSM precision. The Geant4 MC toolkit in multi-threaded mode (Geant4-[mt]) was used for fast dose calculations and optimized memory use. Four field configurations were chosen for dose calculation validation to test field size and symmetry effects, [Formula: see text] [Formula: see text], [Formula: see text] [Formula: see text], and [Formula: see text] [Formula: see text] for squared fields, and [Formula: see text] [Formula: see text] for an asymmetric rectangular field. Good agreement in terms of [Formula: see text] formalism, for 3%/3 mm and 2%/3 mm criteria, for each evaluated radiation field and photon beam was obtained within a computation time of 60 h on a single WorkStation for a 3 mm voxel matrix. Analyzing the VSM's precision in high dose gradient regions, using the distance to agreement concept (DTA), showed also satisfactory results. In all investigated cases, the mean DTA was less than 1 mm in build-up and penumbra regions. In regards to calculation efficiency, the event processing speed is six times faster using Geant4-[mt] compared to sequential Geant4, when running the same simulation code for both. The developed VSM for 6 MV/10 MV beams widely used, is a general concept easy to adapt in order to reconstruct comparable beam qualities for various linac configurations, facilitating its integration for MC treatment planning purposes.


ACUTE MYOCARDIAL INFARCTION IN A 58-YEAR-OLD FEMALE WITH ANOMALOUS ORIGIN OF THE LEFT CORONARY ARTERY FROM THE RIGHT SINUS OF VALSALVA.
We report a case of a 58-year-old female with a history of hypertension, hypercholesterolemia and diabetes type 2, who was admitted to the coronary care unit with continuous substernal severe chest pain persisting for two hours. Her electrocardiogram showed ST-elevation acute myocardial infarction. ST-segment elevation was noted in leads I and aVL and ST-segment depression in leads II, III and V3-V5. The troponin-I level was elevated (1.97 ng/L). Coronary angiography showed anomalous origin of the left coronary artery from the right sinus of Valsalva and subocclusion in the proximal portion of the diagonal branch. In conclusion, primary percutaneous coronary intervention (PCI) of diagonal branch was performed with balloon dilatation and thrombolysis in myocardial infarction TIMI 3 flow was achieved. After PCI, she had no chest pain. At 5-year clinical follow-up, the patient was asymptomatic.


Daily oral administration of chlorogenic acid prevents the experimental carrageenan-induced oxidative stress.
Inflammation and oxidative stress are interrelated processes, during which many pathological processes lead to the reactive oxygen species (ROS) and the cytokines release. The aim of this experimental study was to analyse the effects of chlorogenic acid, in oral daily administration, against the oxidative stress and oedema development in experimental carrageenan-induced rat paw inflammation. The oxidative stress parameters were investigated after a paw inflammation was produced in rats that previoulsy received, for 14 days, either chlorogenic acid (100 mg/day or 150 mg/day) or indomethacin (1 mg/kg/day). The paw oedema was measured through plethysmometry made at 2, 6 and 24 hours after carrageenan injection. The oxidative stress was investigated through spectrophotometry. Blood samples, paw skin and kidneys were collected to investigate malondialdehyde (MDA), glutathione (GSH) and oxidized glutathione (GSSG). The protein expression of oxidative stress-related pathways was analysed in skin and kidneys through Western blot. The present study showed that indomethacin and both doses of chlorogenic acid, after 14 days of oral administration, exerted antioedematous effects during the inflammation development after carrageenan local injection. Compared to the group that received only carrageenan injection, significant decreases of the inflamed paw volume were shown in the treated groups (P < 0.001), in all inflammation phases. The lipid peroxidation was significantly decreased by both doses of chlorogenic acid in inflamed skin (P < 0.0001) and kidney (P < 0.0001). In serum, it was significantly inhibited by indomethacin (P < 0.01) and by 100 mg/day of chlorogenic acid (P < 0.05). The antioxidant protection, evaluated through the ratio GSH/GSSG, was significantly increased by chlorogenic acid in inflamed skin (P < 0.0001) and kidney (100 mg/day, P < 0.01; 150 mg/day, P < 0.0001). In serum, only indomethacin administration produced significant increases of the antioxidant protection (P < 0.05). Western blot analysis showed significant decreases of COX-2 in inflamed skin and kidney in the groups of rats that received indomethacin or 100 mg/day of chlorogenic acid. The effects of chlorogenic acid on NF-κB and pNF-κB were dose-dependent.


The importance of the doctor-patient relationship in adherence to HIV/AIDS treatment: a case report.
In this case report, which includes a statement related by the patient himself, the authors also discuss the importance of a good doctor-patient relationship in treating HIV patients and in assuring the patient's adherence to his treatment. Related issues, such as the importance of treating psychiatric comorbidities, of preserving the patient's hope and motivation, and of giving him an adequate amount of information regarding the disease and its treatment, are also discussed.


Rates of Influenza-Associated Hospitalization, Intensive Care Unit Admission, and In-Hospital Death by Race and Ethnicity in the United States From 2009 to 2019.
Racial and ethnic minority groups, such as Black, Hispanic, American Indian or Alaska Native, and Asian or Pacific Islander persons, often experience higher rates of severe influenza disease. To describe rates of influenza-associated hospitalization, intensive care unit (ICU) admission, and in-hospital death by race and ethnicity over 10 influenza seasons. This cross-sectional study used data from the Influenza-Associated Hospitalization Surveillance Network (FluSurv-NET), which conducts population-based surveillance for laboratory-confirmed influenza-associated hospitalizations in selected counties, representing approximately 9% of the US population. Influenza hospitalizations from the 2009 to 2010 season to the 2018 to 2019 season were analyzed. Data were analyzed from October 2020 to July 2021. The main outcomes were age-adjusted and age-stratified rates of influenza-associated hospitalization, ICU admission, and in-hospital death by race and ethnicity overall and by influenza season. Among 113 352 persons with an influenza-associated hospitalization (34 436 persons [32.0%] aged ≥75 years; 61 009 [53.8%] women), 70 225 persons (62.3%) were non-Hispanic White (White), 24 850 persons (21.6%) were non-Hispanic Black (Black), 11 903 persons (10.3%) were Hispanic, 5517 persons (5.1%) were non-Hispanic Asian or Pacific Islander, and 857 persons (0.7%) were non-Hispanic American Indian or Alaska Native. Among persons aged younger than 75 years and compared with White persons of the same ages, Black persons were more likely to be hospitalized (eg, age 50-64 years: rate ratio [RR], 2.50 95% CI, 2.43-2.57) and to be admitted to an ICU (eg, age 50-64 years: RR, 2.09; 95% CI, 1.96-2.23). Among persons aged younger than 50 years and compared with White persons of the same ages, American Indian or Alaska Native persons were more likely to be hospitalized (eg, age 18-49 years: RR, 1.72; 95% CI, 1.51-1.96) and to be admitted to an ICU (eg, age 18-49 years: RR, 1.84; 95% CI, 1.40-2.42). Among children aged 4 years or younger and compared with White children, hospitalization rates were higher in Black children (RR, 2.21; 95% CI, 2.10-2.33), Hispanic children (RR, 1.87; 95% CI, 1.77-1.97), American Indian or Alaska Native children (RR, 3.00; 95% CI, 2.55-3.53), and Asian or Pacific Islander children (RR, 1.26; 95% CI, 1.16-1.38), as were rates of ICU admission (Black children: RR, 2.74; 95% CI, 2.43-3.09; Hispanic children: RR, 1.96; 95% CI, 1.73-2.23; American Indian and Alaska Native children: RR, 3.51; 95% CI, 2.45-5.05). In this age group and compared with White children, in-hospital death rates were higher among Hispanic children (RR, 2.98; 95% CI, 1.23-7.19), Black children (RR, 3.39; 95% CI, 1.40-8.18), and Asian or Pacific Islander children (RR, 4.35; 95% CI, 1.55-12.22). Few differences were observed in rates of severe influenza-associated outcomes by race and ethnicity among adults aged 75 years or older. For example, in this age group, compared with White adults, hospitalization rates were slightly higher only among Black adults (RR, 1.05; 95% CI 1.02-1.09). Overall, Black persons had the highest age-adjusted hospitalization rate (68.8 [95% CI, 68.0-69.7] hospitalizations per 100 000 population) and ICU admission rate (11.6 [95% CI, 11.2-11.9] admissions per 100 000 population). This cross-sectional study found racial and ethnic disparities in rates of severe influenza-associated disease. These data identified subgroups for whom improvements in influenza prevention efforts could be targeted.


Bisphenol A induces COX-2 through the mitogen-activated protein kinase pathway and is associated with levels of inflammation-related markers in elderly populations.
Bisphenol A (BPA) is a well-known endocrine-disrupting chemical, and it is one of the highest volume chemicals produced worldwide. Even though several in vivo and in vitro studies showed positive associations of BPA exposure with pro-inflammatory cytokines such as tumor necrosis factor-α and interleukin (IL)-6, the mechanism by which BPA induces inflammation is unclear. We investigated the mechanism by which BPA induces inflammation (expression of inflammation-related genes, changes in oxidative stress, and cell proliferation and migration) and evaluated the effect of BPA exposure on inflammation-related markers in epidemiologic studies using repeat urine and serum samples from elderly subjects. BPA induced COX-2 expression via nuclear translocation of NF-κB and activation of mitogen-activated protein kinase (MAPK) by phosphorylation of ERK1/2 and enhanced the migration of lung cancer A549 and breast cancer MDAMB-231 cells. In two epidemiologic studies, we detected associations of BPA with six inflammation-related markers (WBC, CRP, IL-10, ALT, AST, and γ-GTP levels). Our findings probably suggest that BPA exposure induces inflammation and exacerbates tumorigenesis.


Gene expression analysis of parthenogenetic embryonic development of the pea aphid, Acyrthosiphon pisum, suggests that aphid parthenogenesis evolved from meiotic oogenesis.
Aphids exhibit a form of phenotypic plasticity, called polyphenism, in which genetically identical females reproduce sexually during one part of the life cycle and asexually (via parthenogenesis) during the remainder of the life cycle. The molecular basis for aphid parthenogenesis is unknown. Cytological observations of aphid parthenogenesis suggest that asexual oogenesis evolved either through a modification of meiosis or from a mitotic process. As a test of these alternatives, we assessed the expression levels and expression patterns of canonical meiotic recombination and germline genes in the sexual and asexual ovaries of the pea aphid, Acyrthosiphon pisum. We observed expression of all meiosis genes in similar patterns in asexual and sexual ovaries, with the exception that some genes encoding Argonaute-family members were not expressed in sexual ovaries. In addition, we observed that asexual aphid tissues accumulated unspliced transcripts of Spo11, whereas sexual aphid tissues accumulated primarily spliced transcripts. In situ hybridization revealed Spo11 transcript in sexual germ cells and undetectable levels of Spo11 transcript in asexual germ cells. We also found that an obligately asexual strain of pea aphid produced little spliced Spo11 transcript. Together, these results suggest that parthenogenetic oogenesis evolved from a meiosis-like, and not a mitosis-like, process and that the aphid reproductive polyphenism may involve a modification of Spo11 gene activity.


[The neuroanatomy of attention deficit hyperactivity disorder in adults: structural and functional neuroimaging findings].
The objective of this work is to review the existing literature on findings from structural and functional magnetic resonance and connectivity. For a long time it was thought that children 'grew out' of attention deficit hyperactivity disorder (ADHD) on reaching adolescence. Yet, it is now known that up to 70% of children who present ADHD in childhood go on to present symptoms in the behavioural and cognitive sphere in adulthood. Neuroimaging studies conducted in adults with ADHD have shown alterations in the brain at the structural and functional levels, and also in terms of connectivity. These findings have been observed mainly in the inferior frontal and dorsolateral prefrontal cortex, as well as in striatal, anterior cingulate, parietotemporal and cerebellar regions. However, certain inconsistencies have also been found, which may be related with the presence of comorbidity, a history of medication, gender-related differences and the small size of the sample used in some studies. Differences have also been noted in relation to studies carried out in children with ADHD. Hence the importance for future studies of avoiding the existence of variables that can affect the findings in ADHD in adults and, moreover, of being able to determine whether the anatomical and functional deficits continue into adulthood.


A rare case: the medical cord of the brachial plexus sandwiched between the axillary and superficial brachial arteries.
We encountered a rare anomaly in the cadaver of a Japanese woman in the medical cord of the brachial plexus including the ulnar nerve and the medical root of the median nerve was sandwiched with the axillary and the superficial brachial arteries. The axillary artery passed inferior and dorsal to the medial cord, branching off the subscapular, anterior circumflex humeral arteries, and the common trunk of the posterior circumflex humeral and profunda brachii arteries, and ended as the inferior ulnar collateral artery. The superficial brachial artery descended ventral to the median nerve and divided into the radial and ulnar arteries in the cubital fossa. We discuss the developmental formation of this anomaly.


Rapid changes in mucociliary transport in the tracheal epithelium caused by unconditioned room air or nebulized hypertonic saline and mannitol are not determined by frequency of beating cilia.
Inspired air is heated and humidified in the nose before it reaches lower airways. This mechanism is bypassed during tracheostomy, directly exposing the airways to colder and drier air from the environment, known to negatively affect mucociliary transport; however, little is known about how quickly mucociliary transport deteriorates. This study determines the short-term effect of flowing room air and nebulized hypertonic saline and mannitol on mucociliary transport in the trachea. In an ovine perfused in vitro tracheal model (N = 9) the epithelium was exposed to 25 L/min of flow, heated to lamb body temperature (38 °C) and fully saturated with water vapor as the control, followed by either room air (22 °C and 50% relative humidity) or nebulized solutions of NaCl 7% and mannitol 20% up to 1 min for a short duration, until mucociliary transport had visually changed. Mucus transport velocity (MTV) and cilia beat frequency (CBF) were continuously measured with video-microscopy. Exposing the tracheal epithelium to air heated to body temperature and fully humidified had stable MTV 9.5 ± 1.1 mm/min and CBF 13.4 ± 0.6 Hz. When exposed to flow of room air, MTV slowed down to 0.1 ± 0.1 mm/min in 2.0 ± 0.4 s followed by a decrease in CBF to 6.7 ± 1.9 Hz, after 2.3 ± 0.8 s. Both MTV and CBF recovered to their initial state when heated and humidified air-flow was re-introduced. Exposing the tracheal epithelium to nebulized hypertonic saline and nebulized mannitol for 1 min increased MTV without a subsequent increase in CBF. This study demonstrates mucociliary transport can deteriorate within seconds of exposing the tracheal epithelium to flowing room air and increase rapidly when exposed to nebulized hypertonic solutions. The reduction in MTV precedes slowing of CBF with room air and MTV increases without a subsequent increase in CBF during the nebulization. Their relationship is non-linear and a minimum CBF of approximately 6 Hz is required for MTV > 0, while MTV can reach 10.9 mm/min without CBF increasing. Clinically these findings indicate a potential rapid detrimental effect of breathing with non-humidified air via bypassed upper airways and the short-term effects of nebulized osmotic agents that increase MTV.


[Accuracy of the measurements of left ventricular volume and ejection fraction determined by multigated blood pool tomography].
Accuracy of the measurements of LV volumes and ejection fraction determined from multigated blood pool tomography (MGBPT) was tested in 23 patients with various heart diseases who underwent cineventriculography (CV). Preliminary phantom studies showed that a 42% threshold value was found to provide the best relationship between measured and actual volumes (r = 0.99, standard error of the estimate (SEE) = 4.7 ml). The patients studies were performed at 16 frames/cardiac cycle at 18 angles over a 180 degrees rotation for one minute per angle. Long-axis horizontal views were reconstructed. The numbers of LV voxel with counts above the threshold value were summed and multiplied by the known volume of a voxel. Measurements of LV volume (r = 0.82, SEE = 29 ml), end-systolic LV volume (r = 0.83, SEE = 25 ml), end-diastolic LV volume (r = 0.68, SEE = 33 ml), and ejection fraction (r = 0.73, SEE = 10%) determined from MGBPT correlated well with those determined by CV. However, the ratios (Y) of the difference of the MGBPT-volume from the CV-volume to the CV-volume were decreased progressively and negatively as the CV-volumes (X) were smaller (Y = 38-3,996/X). Thus, we conclude that the determinations of volume by MGBPT would lead to more errors with the smaller volumes.


Meta-analysis and systematic review of liver transplantation as an ultimate treatment option for secondary sclerosing cholangitis.
Secondary sclerosing cholangitis (SSC) is a chronic cholestatic biliary disease, characterized by inflammation, obliterative fibrosis of the bile ducts, stricture formation, and progressive destruction of the biliary tree, which leads to biliary cirrhosis. In recent years, the development of secondary sclerosing cholangitis in critically ill patients (SSC-CIP) has increasingly been perceived as a separate disease entity. To perform a systematic review and meta-analysis of secondary sclerosing cholangitis and ischaemic cholangiopathy in post organ transplant patients and intensive care unit (ICU). A comprehensive search strategy using the PubMed, Biosis, and EMBASE databases was designed to retrieve relevant clinical data from the published literature up to 2020. Demographic characteristics, laboratory, transplantation, mortality rate, and follow-up data undergoing liver transplantation were extracted from the inclusion studies. We used DerSimonian-Laird random-effects meta-analysis. Analysis was carried out using R statistical software version 4.02. A total of 862 patients with SSC-CIP were extracted from 16 studies. Eighteen studies were searched for the meta-analysis, out of which 16 studies were eligible for the meta-analysis and 2 were excluded. A proportion meta-analysis was performed on liver transplant patients with SSC-CIP and on mortality rate. Significant results were found (Prop = 0.30, 95% CI: 0.12-0.49, p < 0.01), with high heterogeneity among the studies (I 2 = 98%, p < 0.01) and (Prop = 0.45; 95% CI: 0.35-0.56 with I 2 = 80, p < 0.01), respectively. No indication of publication bias, as confirmed by the funnel plot and the risk of bias in the included studies, shows that the study reporting is adequate to judge that no major or minor sources of bias are likely to influence results. The systematic review and meta-analysis show that liver transplantation is a valid option for patients with SSC-CIP, with excellent long-term outcome and improvement of quality of life.


Transient Neonatal Myasthenia Gravis: A Case Report.
Transient neonatal myasthenia gravis (TNMG) is a neuromuscular disorder that occurs in infants born from mothers with myasthenia gravis (MG) due to transplacental transfer of antibodies against the acetylcholine receptor. TNMG is a rare form occurring in 10-15% of infants born from mothers with MG. We present a case of a newborn with TNMG with generalized hypotonia and respiratory distress. The newborn shows symptoms of hypotonia, weakened reflexes, poor crying, difficult sucking and potentiated tachydyspnea after 24 hours of birth and needs of assisted mechanical ventilation. Based on the mother's positive history of MG and the high titer of mother's (8.43nmol/l) and newborn's (9.088nmol/l) anti-AChR antibodies, TNMG was diagnosed. The baby was treated with assisted mechanical ventilation and neostig-mine until the anti-AChR antibody titer was negative. Adequate management of the newborn resulted in a positive outcome and evident withdrawal of the symptoms. Although TNMG is one of the rare neuromuscular disorders in newborns that can be treated, a multidisciplinary approach in the management of pregnant women with MG and newborns through timely diagnosis and early appropriate treatment, results in successful resolution of this condition.


From disks to channels: dynamics of active nematics confined to an annulus.
Confinement can be used to systematically tame turbulent dynamics occurring in active fluids. Although periodic channels are the simplest geometries to study confinement numerically, the corresponding experimental realizations require closed racetracks. Here, we computationally study 2D active nematics confined to such a geometry-an annulus. By systematically varying the annulus inner radius and channel width, we bridge the behaviors observed in the previously studied asymptotic limits of the annulus geometry: a disk and an infinite channel. We identify new steady-state behaviors, which reveal the influence of boundary curvature and its interplay with confinement. We also show that, below a threshold inner radius, the dynamics are insensitive to the presence of the inner hole. We explain this insensitivity through a simple scaling analysis. Our work sheds further light on design principles for using confinement to control the dynamics of active nematics.


Perinephric transplant fluid collection approach and management.
Renal transplant is the treatment of choice for end-stage renal disease. Perirenal fluid collections are a common surgical complication postrenal transplant that may lead to early graft loss, considerable morbidity, and excess financial loss, if not diagnosed and managed early. The causes of posttransplant fluid collections are urinary leak, lymphocele, hematoma, and seroma, which can be further complicated by abscess formation if becomes infected. Urine leak is considered the most common urological complication postrenal transplant. Diagnosis can be made by biochemical analysis of the fluid drainage with the simultaneous comparison to that of serum. Radiological imaging is also essential for confirming the diagnosis of urinary leak that may not necessarily identify the site of the leak. The management of urinary leak is usually surgical unless the leak is small. The choice of surgery depends on the location of the leak, the vascularization of the involved ureter, and the presence of any complications caused by the leak. This article reviews the differential diagnoses of perirenal fluid collections in postrenal transplant period and focuses on the clinical assessment of urinoma and management options according to the latest evidence-based medicine.