Genetic polymorphisms of the renin-angiotensin-aldosterone system in Chinese patients with end-stage renal disease secondary to IgA nephropathy.
Genetic variability in the renin-angiotensin-aldosterone system may modify renal responses to injury and disease progression. The angiotensin I-converting enzyme (ACE) gene insertion/deletion (I/D), the angiotensinogen (AGT) gene, M235T, the aldosterone synthase (CYP11B2) gene, C-344T, and the angiotensin II type 1 receptor (AT1R) gene, A1166C, have been shown to be associated with IgA nephropathy (IgAN) and its progression. We determined the presence of these polymorphisms in 130 Chinese patients with IgAN, including 47 patients with end-stage renal disease (ESRD) and 120 healthy Chinese subjects, to assess their impact on the susceptibility to disease and the liability of progression to ESRD. Genotyping was performed with DNA isolated from peripheral leucocytes using polymerase chain reaction amplification of the polymorphic sequence, restriction enzyme digestion, and separation and identification of DNA fragments. Clinical data from renal biopsies were collected. ACE, AGT, CYP and AT1R genotype distributions were similar in patients with IgAN and in controls. Comparing patients with ESRD (IgAN-ESRD) and those without ESRD (IgAN-non ESRD), there was a significant increase only in the ACE DD genotype (P < 0.05) among the four gene polymorphisms. There was significant dominance of the male (P < 0.05), more marked hypertension (P < 0.01), proteinuria (P < 0.01) and increased serum creatinine during renal biopsy (P < 0.01) in the IgAN-ESRD group. Among the ACE, AGT, AT1R and CYP gene polymorphisms, only the DD genotype may predispose the individual to increased risk of progression to ESRD in the Chinese population.


Complete Genome Sequences of the Plant Pathogens Dickeya solani RNS 08.23.3.1.A and Dickeya dianthicola RNS04.9.
Dickeya spp. are bacterial pathogens causing soft-rot and blackleg diseases on a wide range of ornamental plants and crops. In this paper, we announce the PacBio complete genome sequences of the plant pathogens Dickeya solani RNS 08.23.3.1.A (PRI3337) and Dickeya dianthicola RNS04.9.


Influence of acute melatonin treatment and light on the circadian melatonin rhythm in the Djungarian hamster.
The present study tested the hypothesis that acute melatonin treatment affects the biological clock mechanism controlling the circadian melatonin rhythm. Adult Djungarian hamsters were raised in LD 16:8 (lights-on from 0300 to 1900 hr). Pineal and serum melatonin concentrations were assessed at specific clock times during the subsequent LD cycle (day 1) and afterwards in hamsters that remained in constant darkness (day 2), to assess the effects of treatment on the circadian melatonin rhythm. In untreated controls (n = 76), melatonin increased in the pineal and in circulation within the first hour after lights-off (day 1) or subjective night (day 2); melatonin concentrations remained elevated for up to 7 hr. A single melatonin injection (5 micrograms/0.2 ml saline, s.c.), administered in the morning (0900 hr, n = 80) or late afternoon (1600 hr, n = 74), transiently increased in circulation but not in the pineal gland. In constant darkness (day 2), the circadian melatonin rhythm in both the pineal gland and circulation was the same as that in untreated controls. No significant differences were found among the three groups in the mean concentration during the day or night; the rise, fall, peak time, peak amplitude, and duration of increased melatonin were also unchanged. The ability of melatonin to override the effect of a light pulse on the circadian melatonin rhythm was also tested. The 5-min light pulse at night (2300-2305 hr of day 1, n = 64) delayed the rise and shortened the duration of increased melatonin in both pineal gland and serum by as much as 3 hr (day 2); these light effects were more pronounced on the pineal than on the serum melatonin rhythm. Injection with melatonin prior to the light pulse (5 micrograms/0.2 ml saline at 2245 hr, n = 64) failed to alter the inhibitory effects of light on the circadian melatonin rhythm. These data suggest that the biological clock mechanism controlling the circadian melatonin rhythm in the Djungarian hamster in long days is responsive to the phase-shifting effects of light, but resistant to the influence of acute melatonin treatment.


Cognitive functioning related to quality of life in schizophrenia.
The present study compared the cognitive function of patients with schizophrenia to that of healthy subjects, and investigated the relationships between cognitive function and quality of life (QOL). Participants consisted of 53 patients meeting DSM-IV criteria for schizophrenia and 31 normal controls. All participants completed a neuropsychological test battery assessing executive function, verbal memory, and social knowledge. QOL was rated using the Schizophrenia Quality of Life Scale. Patients with schizophrenia showed lower performance across various cognitive measures of memory, including the Sentence Memory Test, the Verbal Learning Test, and the Script Test, as well as the Rule Shift Cards Test of executive function. Multiple regression analyses were used to evaluate the neuropsychological measures and clinical symptoms to predict QOL. The QOL total score, the social initiative score or the empathy score were significantly predicted by the Script or/and the Sentence Memory. Neuropsychological functioning was unrelated to most QOL scores in the presence of clinical symptoms, while ability of empathy in the QOL was predicted by performance of the Sentence Memory Test. These results demonstrated patients with schizophrenia have deficits in executive function, memory and learning, and social knowledge, and that social knowledge and memory are related to QOL. Thus, in patients with schizophrenia, deficits in social knowledge appear to be associated with current QOL in general, and specifically with the capacity for empathy and social initiative.


Functional Impairment Variability in Children With ADHD Due to Emotional Impulsivity.
The present study utilized ecological momentary assessment (EMA) to examine the effects of emotional impulsivity on overall functional impairment and functional impairment variability (FIV) of children with and without ADHD. Parents of 74 children, 8- to 12-year-olds (42 with ADHD, 32 without ADHD), completed EMA assessment protocol ratings of their child's mood (3 times daily) and functional impairment (1 time daily) over the course of 28 days. Hierarchical regression analyses supported the interaction of ADHD diagnostic status and greater EMA-derived emotional impulsivity in the estimation of total functional impairment (Total FI) and FIV. Thus, greater emotional impulsivity was found to be related to greater Total FI and FIV among children with ADHD but not among children without ADHD. This study suggests that children with ADHD and greater emotional impulsivity demonstrate greater overall levels of functional impairment, with the severity of their impairment varying significantly over time.


Rapid evolution of pandemic noroviruses of the GII.4 lineage.
Over the last fifteen years there have been five pandemics of norovirus (NoV) associated gastroenteritis, and the period of stasis between each pandemic has been progressively shortening. NoV is classified into five genogroups, which can be further classified into 25 or more different human NoV genotypes; however, only one, genogroup II genotype 4 (GII.4), is associated with pandemics. Hence, GII.4 viruses have both a higher frequency in the host population and greater epidemiological fitness. The aim of this study was to investigate if the accuracy and rate of replication are contributing to the increased epidemiological fitness of the GII.4 strains. The replication and mutation rates were determined using in vitro RNA dependent RNA polymerase (RdRp) assays, and rates of evolution were determined by bioinformatics. GII.4 strains were compared to the second most reported genotype, recombinant GII.b/GII.3, the rarely detected GII.3 and GII.7 and as a control, hepatitis C virus (HCV). The predominant GII.4 strains had a higher mutation rate and rate of evolution compared to the less frequently detected GII.b, GII.3 and GII.7 strains. Furthermore, the GII.4 lineage had on average a 1.7-fold higher rate of evolution within the capsid sequence and a greater number of non-synonymous changes compared to other NoVs, supporting the theory that it is undergoing antigenic drift at a faster rate. Interestingly, the non-synonymous mutations for all three NoV genotypes were localised to common structural residues in the capsid, indicating that these sites are likely to be under immune selection. This study supports the hypothesis that the ability of the virus to generate genetic diversity is vital for viral fitness.


[Changes of cellular hydroxyl proline and some other parameters of rats in early bronchoalveolar lavage treated with quartz dust].
The changes of cellular hydroxyl proline (Hyp) and some other parameters in bronchoalveolar lavage (BAL) induced by different doses of quartz dust (5, 10, 20, or 40mg/per rat) were studied. Quartz dust was administered intratracheally and the rats were killed two weeks after quartz administration. The results showed that the differential count of polymorphonuclear leukocytes (PMN) in BAL, the concentrations of Hyp and total lipids in BAL cells, and the levels of total lipids, total protein, lactic dehydrogenase (LDH) and ceruloplasmin in BAL supernatant all changed significantly in quartz treated groups compared with the control group. Further investigation revealed that the cellular Hyp correlated best with total lung collagen (r = 0.834). This indicated that Hyp might be a specific and important parameter reflecting early increase of total lung collagen after quartz dust administration.


Development, implementation, and early results of a 4-year interprofessional education curriculum.
This article seeks to outline the implementation of a longitudinal interprofessional education (IPE) program in the predoctoral curriculum at a U.S. dental school. The challenges of implementing the curriculum in a complex environment are reviewed, and an overview of the 4-year curriculum is offered, including exposure, immersion, and clinical readiness components. Results of developmental evaluations are reviewed. Respondents to surveys regarding the capstone case conference experiences overwhelmingly suggest the conferences were educationally rewarding as well as enriching for each of the health professions represented. While response was limited, alumni surveys also indicate satisfaction with the IPE experience. A discussion of challenges and suggestions regarding successful implementation and expansion of IPE programs from didactic to clinical settings are also included.


Anchoring Platinum Clusters onto Oxygen Vacancy-Modified In2O3 for Ultraefficient, Low-Temperature, Highly Sensitive, and Stable Detection of Formaldehyde.
To avoid carcinogenicity, formaldehyde gas, currently being only detected at higher operating temperatures, should be selectively detected in time with ppb concentration sensitivity in a room-temperature indoor environment. This is achieved in this work through introducing oxygen vacancies and Pt clusters on the surface of In2O3 to reduce the optimal operating temperature from 120 to 40 °C. Previous studies have shown that only water participates in the competitive adsorption on the sensor surface. Here, we experimentally confirm that the adsorbed water on the fabricated sensor surface is consumed via a chemical reaction due to the strong interaction between the oxygen vacancies and Pt clusters. Therefore, the long-term stability of formaldehyde gas detection is improved. The results of theoretical calculations in this work reveal that the excellent formaldehyde gas detection of Pt/In2O3-x originates from the electron enrichment due to the surface oxygen vacancies and the molecular adsorption and activation ability of Pt clusters on the surface. The developed Pt/In2O3-x sensor has potential use in the ultraefficient, low-temperature, highly sensitive, and stable detection of indoor formaldehyde at an operating temperature as low as room temperature.


Use of a visual feedback-equipped reacher in reach-to-grasp movements.
[Purpose] The purpose of this study was to investigate the effectiveness of using a visual feedback-equipped reacher when performing reach-to-grasp tasks. [Subjects and Methods] Seventeen healthy participants with no illnesses or physical disabilities were selected for this study. Activation of the flexor digitorum superficialis and extensor digitorum muscles was assessed using electromyography. Wrist and shoulder momentums were calculated using a three-axis acceleration sensor. Participants were instructed to move 10 ears of plastic corn from right to left using a reacher with and without visual feedback. [Results] Comparison of muscle activity under the two conditions revealed a statistically significant reduction in the activity of the FDS and ED with feedback compared to without. The three-axis accelerometer values showed that wrist momentum decreased significantly with visual feedback compared to without feedback. [Conclusion] The results showed that using the vision-assisted reacher affected upper limb muscle activation and momentum. It is important that assistive devices be developed for effective energy use. Here, providing visual feedback during reacher use was shown to reduce users' physical fatigue.


Dyshidrotic eczema: relevance to the immune response in situ.
Pompholyx (called dyshidrosis by some) is one of the most common conditions and its immune response is presently poorly understood. We describe a 58 year old African American female with a clinical history of rheumatoid arthritis and type II diabetes who presented a chronic five-year, itchy vesicular/blistering rash involving her hands and feet. A lesional skin biopsy was taken for hematoxylin and eosin (H & E) analysis. In addition, a multicolor direct immunofluorescence (MDIF) and immunohistochemistry (IHC) studies were performed. The major findings to be reported were: the H & E examination revealed spongiotic dermatitis and pompholix. IHC and MDIF studies demonstrated focally deposits of positive CD45, CD3, CD8, anti myeloperoxidase (MPO), and anti-human IgE, C3C, C3D and anti-human-fibrinogen within the epidermal spongiotic process, as well as around the blood vessels surrounding the inflammatory process especially at the sweat glands and respective ductus. The patient began mycophenolate mofetil therapy, with successful clearing of the palms and soles. The significance of our findings indicates a complex immunological process including complement, MPO and T-cell immune response. In addition, possibly a secondary allergic process for the presence of IgE immune response and possibly aggravation by application of other medicines. Further immunological studies on pompholyx are needed. (Abreu-Velez AM, Pinto FJ, Howard MS. North Am J Med Sci 2009; 1: 117-120).


The sequencing of psychiatric recommendations. Concordance during the process of a psychiatric consultation.
Whether or not medical staff follow through with the recommendations of the consultation-liaison (C-L) psychiatrist, a process referred to as concordance, is an important factor that influences the outcome of C-L interventions. Previous research has demonstrated that process variables have the greatest effect on concordance. This study extends earlier research by examining the relationship of the timing of various recommendation types and concordance. In this study, the authors found that during the first two weeks of a case, psychosocial diagnostic recommendations were closely followed (most concordant) when given later in the consultation. However, concordance was better when discharge recommendations were given earlier. The findings reveal an interaction between the type of recommendation and its timing in the consultation in predicting concordance.


[Genetic polymorphism of the metabolism of drugs used in cardiac diseases].
The genetic determinants of the metabolism of certain drugs used in cardiology is one predictable cause of variability in their pharmacokinetics and effects. Genetic polymorphism of the metabolism of drugs is characterised by the existence of several metabolic phenotypes, usually 2, which allow distinction between fast and slow metabolisers. Clinical identification of these phenotypes is relatively simple. The enzymatic deficiency in slow metabolisers concerns a specific metabolic pathway responsible for the biotransformation of the drug but it respects other eventual metabolic pathways. For a given drug and a given metabolic pathway, slow metabolisers are unable to eliminate the parent product by hepatic metabolism. When the drug is given orally, the plasma concentrations of the parent product in slow metabolisers are 5 to 25 times higher than those observed in fast metabolisers. Depending on the given drug, doses usually well tolerated by fast metabolisers may cause excessive effects in slow metabolisers. The pharmacodynamic consequences of genetic polymorphism on the metabolism of drugs depend essentially on the therapeutic index of the drug concerned and on the activity of the metabolites formed by the genetically determined pathway of the parent product. The pharmacokinetic and pharmacodynamic consequences of the two main genetic polymorphisms concerning drugs used in cardiology are discussed: the polymorphism of N acetylation and that of cytochrome P-450 IID6.


Independent associations and effect modification between lifetime substance use and recent mood disorder diagnosis with household food insecurity.
Poor mental health and substance use are associated with food insecurity, however, their potential combined effects have not been studied. This study explored independent associations and effect modification between lifetime substance use and mood disorder in relation to food insecurity. Poisson regression analysis of data from British Columbia respondents (n = 13,450; 12 years+) in the 2007/08 Canadian Community Health Survey was conducted. Measures included The Household Food Security Survey Module (7.3% food insecure), recent diagnosis of a mood disorder (self-reported; 9.5%), lifetime use of cannabis, cocaine/crack, ecstasy, hallucinogens, and speed, any lifetime substance use, sociodemographic covariates, and the interaction terms of mood disorder by substance. For those with recent diagnosis of a mood disorder the prevalence of lifetime substance use ranged between 1.2 to 5.7% and were significantly higher than those without recent mood disorder diagnosis or lifetime use of substances (p's < 0.05). For respondents with a recent mood disorder diagnosis or who used cannabis, food insecurity prevalence was higher compared to the general sample (p < 0.001); prevalence was lower for cocaine/crack use (p < 0.05). Significant effect modification was found between mood disorder with cannabis, ecstasy, hallucinogen and any substance use over the lifetime (PRs 0.51 to 0.64, p's 0.022 to 0.001). Independent associations were found for cocaine/crack and speed use (PRs 1.68, p's < 0.001) and mood disorder (PRs 2.02, p's < 0.001). Based on these findings and the existing literature, future study about coping and resilience in the context of substance use, mental health, and food insecurity may lead to the development of relevant interventions aimed at mental well-being and food security.


Mössbauer investigation of the photoexcited spin states and crystal structure analysis of the spin-crossover dinuclear complex [{Fe(bt)(NCS)(2)}(2)bpym] (bt=2,2'-bithiazoline, bpym=2,2'-bipyrimidine).
The crystal structure of the complex [{Fe(bt)(NCS)(2)}(2)bpym] (1) (bt=2,2'-bithiazoline, bpym=2,2'-bipyrimidine) has been solved at 293, 240, 175 and 30 K. At all four temperatures the crystal remains in the P space group with a=8.7601(17), b=9.450(2), c=12.089(3) A, alpha=72.77(2), beta=79.150(19), gamma=66.392(18) degrees , V=873.1(4) Angstrom(3) (data for 293 K structure). The structure consists of centrosymmetric dinuclear units in which each iron(II) atom is coordinated by two NCS(-) ions in the cis position and two nitrogen atoms of the bridging bpym ligand, with the remaining positions occupied by the peripheral bt ligand. The iron atom is in a severely distorted octahedral FeN(6) environment. The average Fe--N bond length of 2.15(9) Angstrom indicates that compound 1 is in the high-spin state (HS-HS) at 293 K. Crystal structure determinations at 240, 175 and 30 K gave a cell comparable to that seen at 293 K, but reduced in volume. At 30 K, the average Fe--N distance is 1.958(4) Angstrom, showing that the structure is clearly low spin (LS-LS). At 175 K the average Fe--N bond length of 2.052(11) Angstrom suggests that there is an intermediate phase. Mössbauer investigations of the light-induced excited spin state trapping (LIESST) effect (lambda=514 nm, 25 mW cm(-2)) in 1 (4.2 K, H(ext)=50 kOe) show that the excited spin states correspond to the HS-HS and HS-LS pairs. The dynamics of the relaxation of the photoexcited states studied at 4.2 K and H(ext)=50 kOe demonstrate that HS-HS pairs revert with time to both HS-LS and LS-LS configurations. The HS-LS photoexcited pairs relax with time back to the ground LS-LS configuration. Complex [{Fe(0.15)Zn(0.85)(bt)(NCS)(2)}(2)bpym] (2) exhibits a continuous spin transition centred around 158 K in contrast to the two-step transition observed for 1. The different spin-crossover behaviour observed for 2 is due to the decrease of cooperativity (intermolecular interactions) imposed by the matrix of Zn(II) ions. This clearly demonstrates the role of the intermolecular interactions in the stabilization of the HS-LS intermediate state in 1.


Self-consistent Ornstein-Zernike approximation for molecules with soft cores.
The self-consistent Ornstein-Zernike approximation (SCOZA) is an accurate liquid state theory. So far it has been tied to interactions composed of hard core repulsion and long-range attraction, whereas real molecules have soft core repulsion at short distances. In the present work, this is taken into account through the introduction of an effective hard core with a diameter that depends upon temperature only. It is found that the contribution to the configurational internal energy due to the repulsive reference fluid is of prime importance and must be included in the thermodynamic self-consistency requirement on which SCOZA is based. An approximate but accurate evaluation of this contribution relies on the virial theorem to gauge the amplitude of the pair distribution function close to the molecular surface. Finally, the SCOZA equation is transformed by which the problem is reformulated in terms of the usual SCOZA with fixed hard core reference system and temperature-dependent interaction.


Signaling silence--breaking ground and spreading out.
Among the persistent mysteries in epigenetics are the criteria by which specific regions of the genome are chosen for deposition of distinguishing chromatin marks. Once a particular region is modified, will the newly acquired epigenetic state spill onto neighboring regions of the genome or be confined to tidy patches? The report by Henderson and Jacobsen in the the previous issue of Genes & Development (1597-1606) addresses these questions while providing insight into the utility of DNA methylation for a eukaryotic genome.


Inhibition of the cellular secretion of cholesteryl ester transfer protein by a variant protein formed by alternative splicing of mRNA.
Alternative splicing of mRNA is often used as a regulatory switch, determining whether a functional protein is made or not. The plasma cholesteryl ester transfer protein (CETP) mediates the transfer of cholesteryl esters from high density lipoproteins to other lipoproteins. In addition to the mRNA encoding plasma CETP, human tissues contain an alternatively spliced variant in which exon 9-derived sequences are omitted. To determine a possible regulatory role of alternative splicing, COS cells were co-transfected with full-length and exon 9-deleted cDNAs. The exon 9-deleted protein was poorly secreted and inhibited the secretion of full-length CETP, due to formation of an intracellular heteromeric complex between full-length and exon 9-deleted proteins. The findings suggest a novel use of alternative splicing to generate a poorly secreted protein variant, which complexes with the active form and prevents its secretion by cells.


Disparities in pulmonary function in healthy children across the Indian urban-rural continuum.
Marked socioeconomic health-care disparities are recognized in India, but lung health inequalities between urban and rural children have not been studied. We investigated whether differences exist in spirometric pulmonary function in healthy children across the Indian urban-rural continuum and compared results with those from Indian children living in the UK. Indian children aged 5 to 12 years were recruited from Indian urban, semiurban, and rural schools, and as part of the Size and Lung Function in Children study, London. Anthropometric and spirometric assessments were undertaken. Acceptable spirometric data were obtained from 728 (58% boys) children in India and 311 (50% boys) UK-Indian children. As an entire group, the India-resident children had significantly lower z FEV1 and z FVC than UK-Indian children (P < 0.0005), when expressed using Global Lung Function Initiative-2012 equations. However, when India-resident children were categorized according to residence, there were no differences in z FEV1 and z FVC between Indian-urban and UK-Indian children. There were, however, significant reductions of ∼ 0.5 z scores and 0.9 z scores in both FEV1 and FVC (with no difference in FEV1/FVC) in Indian-semiurban and Indian-rural children, respectively, when compared with Indian-urban children (P < 0.0005). z Body mass index, socioeconomic circumstances, tobacco, and biomass exposure were individually significantly associated with z FEV1 and z FVC (P < 0.0005). The presence of an urban-rural continuum of lung function within a specific ethnic group emphasizes the impact of environmental factors on lung growth in emerging nations such as India, which must be taken into account when developing ethnic-specific reference values or designing studies to optimize lung health.


Does neutrophil-to-lymphocyte ratio predict 1-year mortality in patients with primary biliary cholangitis? Results from a retrospective study with validation cohort.
Neutrophil-to-lymphocyte ratio (NLR) has been used to predict prognosis in various liver diseases, but its role in primary biliary cholangitis (PBC) is not clarified. We aimed to investigate the prognostic usefulness of NLR for 1-year mortality in PBC. The study recruited a retrospective cohort with 88 patients with PBC and a prospective validation cohort with 63 participants who were followed-up for 1 year. NLR and other laboratory measurements were analysed by multivariate regression model for identifying independent factors for early mortality. The cut-off threshold of NLR was determined by calculating the area under the receiver operating characteristics curve (AUROC) and used in a subsequent Kaplan-Meier survival analysis. Univariate and multivariate analyses showed that Mayo Risk Score (MRS), serum creatinine and NLR were independent indicators for mortality. NLR yielded significantly higher AUROC (0.86) than those of platelet-to-lymphocyte ratio (0.58, p=0.03), but comparable with MRS (0.87, p=0.88). Spearman's correlation analysis represented a positive correlation between escalating NLR and aggravating Child-Pugh grade (r=0.44, p<0.001). Patients with NLR <2.18 exhibited higher survival (with 100% sensitivity and 67.1% specificity) within 1 year follow-up duration, and NLR ≥2.18 was indicative of higher mortality (log-rank test, p<0.001). In addition, these results were internally confirmed by a validation cohort. NLR is closely related to short-term mortality in patients with PBC.


[Development of auxiliary early predicting model for human brucellosis using machine learning algorithm].
Using machine learning algorithms to construct an early prediction model of brucellosis to improve the diagnosis efficiency of Brucellosis. This study was a case-control study. 2 381 brucellosis patients from Beijing Ditan Hospital affiliated to Capital Medical University were retrospectively collected as case group, and healthy people from Beijing Chaoyang Hospital affiliated to Capital Medical University were collected as control group from May 9, 2011 to November 29, 2021. The relevant clinical information and full blood count results of 13 257 data were collected and five algorithms of machine learning were used to construct an early predication model of brucellosis by using machine learning: random forest, Naive Bayes, decision tree, logistic regression and support vector machine;14 074 data (2 143 cases incase group and 11 931 cases in control group) were used to establish the early predication model of brucellosis, and 1 564 (238 cases in case group and 1 326 cases in control group) data were used to test the predication efficiency of the brucellosis model. The results showed that the support vector machine algorithm has the best predication performance by comparing the five machine learning models. The area under receiver curve (AUC) of receiver operating characteristic (ROC) was 0.991, and the accuracy, precision, specificity and Recall were 95.6%, 95.5%, 95.4% and 95.9%, respectively. Based on the SHAP plot, platelet distribution width (PDW) and basophil relative value (BASO%) results were low, and men with high coefficient of variation (R-CV), erythrocyte hemoglobin concentration (MCHC), and platelet volume (MPV) were predicted to be at high risk of brucellosis. Platelet distribution width (PDW) contributed the most to the prediction model, followed by red blood cell distribution width coefficient of variation (R-CV). In conclusion, the establishment of a high-precision early predication method of brucellosis based on machine learning may be of great significance for the early detection and treatment of brucellosis patients.


Integration of a rapid scanning technique into THz time-domain spectrometers for nonlinear THz spectroscopy measurements.
We have implemented a rapid scanning technique into THz time-domain spectrometers using an oscillating frictionless delay line, especially adapted for nonlinear THz experiments. Thereby we were able to increase the dynamic range of THz measurements in the frequency range from 40 to 200 cm-1 by up to 24 dB and reduce the scanning time by up to a factor of 200. We report here test measurements on TDS-setups at repetition rates of 80 MHz and 5 kHz. The dynamic range exceeds 64 dB, which allows to record even small changes in the THz absorption upon optical excitation by a THz probe, covering the frequency range of the intermolecular modes and the phonon bands. We demonstrate the potential of this technique for optical-pump THz-probe experiments using a 70 μm thick high-resistivity silicon, excited by 400 nm, ∼50 fs pulses as a sample.


Global and regional changes in exposure to extreme heat and the relative contributions of climate and population change.
The frequency and intensity of extreme heat wave events have increased in the past several decades and are likely to continue to increase in the future under the influence of human-induced climate change. Exposure refers to people, property, systems, or other elements present in hazard zones that are thereby subject to potential losses. Exposure to extreme heat and changes therein are not just determined by climate changes but also population changes. Here we analyze output for three scenarios of greenhouse gas emissions and socio-economic growth to estimate future exposure change taking account of both climate and population factors. We find that for the higher emission scenario (RCP8.5-SSP3), the global exposure increases nearly 30-fold by 2100. The average exposure for Africa is over 118 times greater than it has been historically, while the exposure for Europe increases by only a factor of four. Importantly, in the absence of climate change, exposure is reduced by 75-95% globally and across all geographic regions, as compared with exposure under the high emission scenario. Under lower emission scenarios RCP4.5-SSP2 and RCP2.6-SSP1, the global exposure is reduced by 65% and 85% respectively, highlighting the efficacy of mitigation efforts in reducing exposure to extreme heat.


An unusual degenerative disorder of neurons associated with a novel intranuclear hyaline inclusion (neuronal intranuclear hyaline inclusion disease). A clinicopathological study of a case.
A 21-year-old woman with an unusual, progressive, degenerative neurological disorder is described. The disorder is characterized clinically by behavioral abnormality, peculiar involuntary movements, and ataxia starting in early childhood and subsequent development of dementia, choreoathetosis, rectal and bladder incontinence, bulbar and spinal muscular weakness, pes cavus, kyphoscoliosis, and generalized seizures. The clinical manifestations are correlated, with widespread pathological changes affecting almost all neuronal systems. The pathological changes are discussed in relation to the wide spectrum of "multisystem atrophies." Particular attention is directed to the ubiquitous occurrence of a novel intranuclear, eosinophilic, hyaline inclusion in almost all types of central, peripheral, and autonomic neurons. The ubiquitous neuronal involvement seems to explain the diffuse multiple system degeneration. The pathogenesis of the neuronal inclusions is unknown, but it is speculated that the disorder may represent a metabolic abnormality affecting the nuclear protein of neurons, rather than a viral infection. The pathological features, consisting of the neuronal intranuclear hyaline inclusions associated with multiple system atrophy, have not hitherto been described, and "neuronal intranuclear hyaline inclusion disease" is proposed as a name for the disorder. Rectal biopsy demonstrating the intranuclear hyaline inclusions in ganglion cells of the hyenteric plexuses may serve as a diagnostic procedure for the disorder.


Felodipine inhibits intimal lesion formation in the hypercholesterolemic rabbit: differential effects on endothelial and monocyte determinants of atherogenesis.
The purpose of this study was to determine if the calcium entry antagonist felodipine inhibited intimal lesion formation in hypercholesterolemic rabbits, and to determine if this was due to an effect upon monocyte and/or endothelial determinants of this interaction. Twenty-three male New Zealand White rabbits received the following treatment regimen for 10 weeks: normal chow (NP, n = 3); normal chow with felodipine infusion (NF, n = 6); 0.5% cholesterol chow (CP, n = 7); or 0.5% cholesterol chow and felodipine infusion (CF, n = 7). After 10 weeks blood was collected for biochemical measurements and mononuclear cell binding assays, and thoracic aortae were harvested for vascular reactivity studies and histomorphometry. In the animals receiving normal chow, felodipine did not significantly affect blood pressure, plasma cholesterol levels, binding studies, vascular reactivity, or structure; therefore these animals were analyzed as one group (N). Plasma cholesterol levels were significantly elevated in groups receiving the 0.5% cholesterol diet (N, 29 +/- 3 mg/dl; CP, 1221 +/- 73 mg/dl; CF, 979 +/- 108 mg/dl). High-density lipoprotein cholesterol was not different between the groups (25 +/- 4 vs 23 +/- 4 vs 27 +/- 4 mg/dl; N vs CF vs CP respectively; p = NS). Cholesterol feeding markedly augmented the adhesiveness of mononuclear cells, as demonstrated by a 250% increase in cell binding. Felodipine did not alter the adhesiveness of mononuclear cells in hypercholesterolemic animals. Cholesterol feeding significantly impaired endothelium-dependent relaxations. Endothelium-dependent relaxations were restored by felodipine treatment as reflected by the maximal responses to acetylcholine (40 +/- 7% vs 58 +/- 4% vs 67 +/- 5%; CP vs CF vs N respectively). The improvement in endothelium-dependent relaxation in the felodipine-treated animals was associated with a 2.2-fold reduction in lesion surface area of the thoracic aorta (8.2 +/- 6.3% vs 18.2 +/- 9.5%; CF vs CP; p < 0.01). Moreover, the intima/media ratio reflecting lesion thickness was substantially reduced by felodipine treatment (0.05 +/- 0.02 vs 0.20 +/- 0.07; CF vs CP; p = 0.006). Ex vivo studies revealed that felodipine inhibited the adhesiveness of vascular endothelium, but not mononuclear cells, derived from hypercholesterolemic animals. Low-dose felodipine appears to inhibit monocyte-endothelial interaction, as indicated by a reduction in the formation of lesions in hypercholesterolemic animals. This effect is not due to an alteration in adhesiveness of mononuclear cells. The salutary effect of felodipine is associated with an increase in vascular nitric oxide activity which may reduce endothelial adhesiveness.


Progress in the Total Synthesis of Antitumor Tetrahydroisoquinoline Alkaloids.
Among the tetrahydroisoquinoline(THIQ) of natural products, a family of THIQ alkaloids has the characteristics of similar biosynthetic pathway. Such THIQ alkaloids family mainly include Renieramycins, Ecteinasicdins, Tetrazaomine, Lemonomycin, etc. Most of these natural compounds have strong antitumor activities, and its family member Ecteinasicdins743 (ET-743, Trabectedin) has been marketed in the European Union and the United States for the treatment of advanced soft tissue tumors and ovarian cancer. Because of the excellent biological activity and complex chemical structure of this kind of THIQ products, it has aroused great interest of biologists and chemists, and many synthetic chemists have paid considerable efforts to their total synthesis over the past decade. Based on this, the recent advances in the total synthesis of such THIQ alkaloids are reviewed.


Complement-mediated cytotoxic effects of islet cell surface antibodies in non-diabetic subjects with antecedent mumps infection and diabetic risk.
We studied sera of 24 selected non-diabetic subjects in whom an antecedent mumps infection with either complications and/or with onset at older age occurred 10-27 month ago regarding the capability to lyse rat islets of Langerhans in vitro. Thirteen subjects were characterized by diabetes associated HLA antigens DR3 and/or DR4 whereas 11 of them had none of these HLA antigens. Islet cell surface antibodies (ICSA) could be detected in 11 out of 24 subjects. Isolated pancreatic islets from 8-10 days old Wistar rats were incubated in freshly prepared human serum. The insulin leakage under the conditions of pharmacologic blockade of insulin secretion by means of epinephrine and propranolol provides a measure of complement-mediated cytotoxicity of human serum against rats islets in vitro. Out of a total of 24 subjects the sera of 11 of them exhibited cytotoxicity. Mean cytolytic insulin leakage was significantly higher in subjects with DR3 and/or DR4 in comparison with subjects without these HLA antigens (6.82 +/- 0.77% vs 3.90 +/- 0.48%; p less than 0.05). Ten out of the 11 subjects with cytotoxic sera had HLA DR3 and/or DR4 whereas DR3 was present in three out of 13 subjects with non-cytotoxic sera. There was no relationship between beta cell function in vivo (fasting C-peptide concentration and insulin response to oral glucose challenge) and the capability of patients sera to damage islet cells in vitro. In conclusion the pathogenetic role of mumps virus and cytotoxic ICSA and their possible relation to slow progressive beta-cell destruction has still to be ascertained.


Regulation of retrotranslocation by p97-associated deubiquitinating enzyme ataxin-3.
Misfolded proteins of the endoplasmic reticulum undergo retrotranslocation to enter the cytosol where they are degraded by the proteasome. Retrotranslocation of many substrates requires an ATPase complex consisting of the p97 ATPase and a dimeric cofactor, Ufd1-Npl4. We report that efficient elimination of misfolded ER proteins also involves ataxin-3 (atx3), a p97-associated deubiquitinating enzyme mutated in type-3 spinocerebellar ataxia. Overexpression of an atx3 mutant defective in deubiquitination inhibits the degradation of misfolded ER proteins and triggers ER stress. Misfolded polypeptides stabilized by mutant atx3 are accumulated in part as polyubiquitinated form, suggesting an involvement of its deubiquitinating activity in ER-associated protein degradation regulation. We demonstrate that atx3 transiently associates with the ER membrane via p97 and the recently identified Derlin-VIMP complex, and its release from the membrane appears to be governed by both the p97 ATPase cycle and its own deubiquitinating activity. We present evidence that atx3 may promote p97-associated deubiquitination to facilitate the transfer of polypeptides from p97 to the proteasome.


Strategic considerations for invasive species managers in the utilization of environmental DNA (eDNA): steps for incorporating this powerful surveillance tool.
Invasive species surveillance programs can utilize environmental DNA sampling and analysis to provide information on the presence of invasive species. Wider utilization of eDNA techniques for invasive species surveillance may be warranted. This paper covers topics directed towards invasive species managers and eDNA practitioners working at the intersection of eDNA techniques and invasive species surveillance. It provides background information on the utility of eDNA for invasive species management and points to various examples of its use across federal and international programs. It provides information on 1) why an invasive species manager should consider using eDNA, 2) deciding if eDNA can help with the manager's surveillance needs, 3) important components to operational implementation, and 4) a high-level overview of the technical steps necessary for eDNA analysis. The goal of this paper is to assist invasive species managers in deciding if, when, and how to use eDNA for surveillance. If eDNA use is elected, the paper provides guidance on steps to ensure a clear understanding of the strengths and limitation of the methods and how results can be best utilized in the context of invasive species surveillance.


Factors for progression of periodontal diseases.
Progression factors for periodontal diseases have been suggested by in vitro study of peripheral blood and gingival cells; however, those factors are not established in vivo. This investigation assessed biopsies of three groups of gingival tissues: those adjacent to a 1) < or =3 mm (normal), 2) 4-6 mm, and 3) >6 mm gingival sulcus, to determine changes in the gingival microenvironment coincident to the progression of periodontal disease. Superoxide dismutase (SOD) and catalase activity, and IL-12 and bcl-2 levels, were decreased at >6 mm; total protein and IL-6 concentrations were increased adjacent to >6 mm, as compared to < or =3 and 4-6 mm, sites. Apoptotic cells were evident only within gingiva adjacent to >6 mm sites. These data suggest that IL-12 is an important factor in the shift from a TH1 to TH2 cell profile and that a favorable gingival microenvironment for hyperinflammation may develop coincident to progression of periodontal diseases due to decreased bcl-2 and increased IL-6 concentrations within gingiva. These changes in the gingival microenvironment could impair apoptosis and promote enhanced release of reactive oxygen species (ROS) by phagocytes; decreased catalase and SOD activity could promote accumulation of ROS and result in additional tissue destruction.


Autogenous bone grafts in cervical vertebrectomy and fusion practice for injuries.
Among the patients with a cervical injury admitted to our clinic between 1980 and 1988, 18 cases underwent a ventral fusion operation (Cloward) and 8 of them needed additional vertebrectomy. The injury in all of these cases was due to falls and presented with major compression fractures. In each case the vertebral body was resected and replaced by a "T" shaped iliac bone graft. The graft was fixated by a screw or wire when necessary, than the patients were immobilized by a bed rest for 2 weeks duration. During the follow-up period, cervical alignment was found to be stable in all patients. The radiological characteristics of the lesions, intraoperative surgical modifications for specific aspects of the lesion, other technical availabilities and the results are discussed.


The Gads (GrpL) adaptor protein regulates T cell homeostasis.
Little is known about the role of the Gads (GrpL) adaptor protein in mature T cell populations. In this study we show that the effects of Gads deficiency on murine CD4(+) and CD8(+) T cells are markedly different. Gads(-/-) CD4(+) T cells were markedly deficient in the spleen and had an activated phenotype and a rapid turnover rate. When transferred into a wild-type host, Gads(-/-) CD4(+) T cells continued to proliferate at a higher rate than wild-type CD4(+) T cells, demonstrating a defect in homeostatic proliferation. Gads(-/-) CD8(+) T cells had a memory-like phenotype, produced IFN-gamma in response to ex vivo stimulation, and underwent normal homeostatic proliferation in wild-type hosts. Gads(-/-) T cells had defective TCR-mediated calcium responses, but had normal activation of ERK. Gads(-/-) CD4(+) T cells, but not CD8(+) T cells, had a severe block of TCR-mediated proliferation and a high rate of spontaneous cell death and were highly susceptible to CD95-induced apoptosis. This suggests that the rapid turnover of Gads(-/-) CD4(+) T cells is due to a defect in cell survival. The intracellular signaling pathways that regulate homeostasis in CD4(+) and CD8(+) T cells are clearly different, and the Gads adaptor protein is critical for homeostasis of CD4(+) T cells.


Predictive accuracy of Static-99R across different racial/ethnic groups: A meta-analysis.
The overrepresentation of numerous racial/ethnic groups in the criminal legal system warrants examination of the cross-cultural applicability of risk assessment tools. Static-99R is a tool used in diverse countries to assess sexual recidivism risk. We conducted a meta-analysis on the predictive accuracy of Static-99R across different racial/ethnic groups. No hypotheses were made regarding discrimination, given that past research could support hypotheses of differential or equivalent accuracy. We hypothesized that Indigenous individuals would score higher on Static-99R than non-Indigenous or White individuals. Our search identified 18 eligible documents (from 17 distinct studies) with 41 nonoverlapping effect sizes. These 17 studies examined the predictive accuracy of Static-99R with racially/ethnically diverse men charged with or convicted of sexually motivated offenses. We report analyses using both fixed-effect and random-effects meta-analysis. Indigenous and Black individuals scored significantly higher on Static-99R than their non-Indigenous or White counterparts, with small effect sizes. For discrimination, area under the curve (AUC) values were generally moderate-to-large and statistically significant for all groups in both fixed-effect and random-effects analyses. Within-study subgroup analyses indicated significantly lower accuracy for Indigenous and Hispanic individuals compared with White/non-Indigenous samples (though for Hispanic individuals, this finding was significant only in the fixed-effect analyses). No statistically significant differences in accuracy were found between White and Black individuals. Static-99R significantly predicted recidivism with large effect sizes across two samples of Asian individuals. Two studies supported calibration across Black, White, and Hispanic individuals. Two studies examining calibration of Static-99R for Indigenous individuals had mixed findings. Given a small number of studies and limitations with both the fixed- and random-effects analyses, readers should interpret findings regarding Hispanic individuals with caution. The analyses clearly found significant but lower accuracy for Static-99R with Indigenous individuals. Potential reasons for this differential accuracy are discussed, along with limitations of the meta-analysis and suggestions for research and practice. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Fall concern about older persons shifts to carers as changing health policy focuses on family, home-based care.
With the Singaporean population ageing at an exponential rate, home carers are increasingly becoming essential partners in fall prevention and care delivery for older persons living at home and in the community. Singapore, like other Asian countries, regards the family as the main support structure for the older person, and national policies have been implemented to support this cultural expectation. Family carers experience similar concerns as older persons with regard to fall risk, and identifying and addressing these concerns can potentially lower fall risk and improve fall prevention for older persons. It is timely to remind ourselves - as concern about falls in older persons begins to shift to carers - to incorporate the influence of Asian cultural values and unique family dynamics of outsourcing family caregiving, in the management of older persons' fall risk in the community.


DMSO induces reactivation of cytomegalovirus in vitro from spleens of latently infected mice. Brief report.
Reactivation of murine cytomegalovirus in spleen explant cultures from latently infected CD 1 mice was studied. A significant increase in the incidence of reactivation was observed when 200 mM DMSO was included in the culture medium. Virus could also be reactivated from the bone marrow of some mice.


[The dynamic hip screw in fractures of the median femoral neck].
Since 1983 we have treated 19 cases of medial neck of femur fracture by using the dynamic hip screw. A follow-up of these patients has shown bad result in 12 cases. We have abandoned the indications for implantation of DHS.


Effect of tryptophan hydroxylase gene polymorphism on aggression in major depressive disorder and undifferentiated somatoform disorder.
Aggression and anger have been linked with depression, and anger suppression has been linked with somatic symptoms of somatoform disorders. However, the relationship between aggression or anger and genes in patients with depression and somatoform disorders has not been clearly elucidated. The objective of this study was to examine the effect of serotonin-related gene polymorphism on aggression in depressive disorders and somatoform disorders. A serotonin-related polymorphic marker was assessed by using single nucleotide polymorphism (SNP) genotyping. 106 outpatients with major depressive disorder (MDD), 102 outpatients with undifferentiated somatoform disorder, and 133 healthy subjects were enrolled between October 2005 and May 2008. Diagnoses were made according to the Korean version of the Structured Clinical Interview Schedule for DSM-IV. The allele and genotype frequencies of tryptophan hydroxylase-1 (TPH1) A218C were compared between groups. The Hamilton Depression Rating Scale and the Aggression Questionnaire were used for psychological assessment. Each of the 2 disorder groups scored significantly higher on all the Aggression Questionnaire subscales and on the total Aggression Questionnaire score than the healthy subjects (P < .001). Patients with MDD had significantly higher frequencies of TPH1 C allele (P = .0002) and CC homozygote (P = .0003) than healthy subjects, regardless of sex and age. However, no significant differences were found in TPH1 C allele and CC homozygote frequencies between the undifferentiated somatoform disorder patients and the healthy subjects. TPH1 CC homozygote in the MDD group scored significantly higher in terms of verbal aggression (P = .03) and total Aggression Questionnaire score (P = .04) than A-carrier genotypes, regardless of sex and age. However, no significant differences were found in the scores of all the Aggression Questionnaire subscales and the total Aggression Questionnaire score between TPH1 CC homozygote and A-carrier genotypes in the undifferentiated somatoform disorder group and the control group, respectively. Aggression in MDD patients is more susceptible to an excess of TPH1 CC homozygote than in undifferentiated somatoform disorder patients, though the 2 disorders are high risk groups for aggression. In addition, TPH1 gene is most likely to have a shared effect on aggression and MDD.


Breast Cancer Screening in the High-risk Population.
The risk for developing breast cancer can be influenced by a number of critical factors. An individual's age, gender, personal and family health history, nutritional status, level of physical activity, environmental exposures, and substance use can significantly shift the recommended screening guidelines format from the general risk population to a high-risk population. It is essential for health-care providers to become proficient in obtaining a complete cancer genetic risk assessment to accurately identify those who may be at high risk. There are a number of evidence-based risk models that can be utilized by providers to determine if an individual is indeed at a higher risk to develop breast cancer. In addition, there are evidence-based guidelines for breast cancer screening and possible recommendations for medical management/risk reduction that are appropriate to discuss for those high-risk individuals.


Rate of gastric emptying influences dietary cholesterol absorption efficiency in selected inbred strains of mice.
This study compared the physiological process of cholesterol absorption in different strains of inbred mice with the goal of identifying novel mechanism(s) by which cholesterol absorption can be controlled. The rate and amount of cholesterol absorption were evaluated based on [14C]cholesterol appearance in plasma after feeding a meal containing [14C]cholesterol and by the percentage of [14C]-cholesterol absorbed over a 24 h period. Results showed that the rate of [14C]cholesterol appearance in plasma was slower in 129P3/J mice than in SJL/J mice. However, more dietary cholesterol was absorbed over a 24 h period by 129P3/J mice than by SJL/J mice. In both strains of mice, cholesterol delivered with medium-chain triglyceride was absorbed less efficiently than cholesterol delivered with olive oil. The strain- and vehicle-dependent differences in cholesterol absorption efficiency correlated negatively with stomach-emptying rates. Furthermore, inhibition of gastric emptying with nitric oxide synthase inhibitor increased cholesterol absorption efficiency in SJL/J mice. These results document that stomach-emptying rate contributes directly to the rate of dietary cholesterol absorption, which is inversely correlated with the total amount of cholesterol absorbed from a single meal. Additionally, genetic factor(s) that influence gastric emptying may be an important determinant of cholesterol absorption efficiency.


Serum Osteoprotegerin Is a Potential Biomarker of Insulin Resistance in Chinese Postmenopausal Women with Prediabetes and Type 2 Diabetes.
The aim of this study is to investigate the circulating OPG levels in postmenopausal women with diabetes and prediabetes and explore the relationships between serum OPG and insulin resistance. A total of 271 unrelated Chinese postmenopausal women were recruited in this study. The subjects were divided into type 2 diabetes mellitus (T2DM) group (n = 93), impaired glucose regulation (IGR) (n = 90), and normal glucose regulation group (NGR) (n = 88), according to different glucose regulation categories. Serum OPG levels were measured by enzyme-linked immunosorbent assay. The serum OPG concentration in NGR group, 151.00 ± 45.72 pg/mL, was significantly lower than that in IGR group (169.28 ± 64.91 pg/mL) (p = 0.031) and T2DM group (183.20 ± 56.53 pg/mL) (p < 0.01), respectively. In multiple linear regression analysis, HOMA-IR, age, 2hPG, AST, ALP, and eGFR were found to be independent predictors of OPG. Increased serum OPG levels (OR = 1.009, p = 0.006) may be a risk factor for insulin resistance. The present study suggests that OPG might be implicated in the pathogenesis of diabetes and is a potential biomarker of insulin resistance in subjects with diabetes and prediabetes.


Improving community acceptance of breastfeeding in public: a collaborative approach.
This project, conducted from 2001 to 2003, reports the results of an action research plan aimed to improve community acceptability of breastfeeding in public through the accreditation and promotion of breastfeeding-friendly venues in Australia. The Australian Breastfeeding Association (ABA) along with other breastfeeding support groups, the media, community groups and organisations have collaborated on this project to promote and distribute over 17 000 'Breastfeeding Welcome Here' kits. The strong links established with ABA and the use of their logo have assisted in promotion of the kit and enabled the initiative to be sustainable beyond the project. The identification of breastfeeding-friendly venues has provided more places for mothers to breastfeed in a welcoming environment when out of the home, while at the same time communicating to the community that breastfeeding is acceptable anywhere. Information about the national kit and how to obtain copies is located on the ABA website: www.breastfeeding.asn.au.


Aetiology and clinical characteristics of uveitic glaucoma in Turkish patients.
To investigate the types, frequency and clinical profiles of uveitic glaucoma seen at a tertiary care center and also to have an idea about the distribution of uveitic glaucoma types in Turkish population. Consecutive case notes of all patients attending a specialized uveitis clinic over a 3-month period were reviewed retrospectively. One hundred and seven eyes of 96 patients were included. Sixty-five of the eyes had anterior, one intermediate, nine posterior uveitis while 32 of them had panuveitis. Twenty-three eyes had acute, 52 chronic and 32 recurrent uveitis. Herpes virus associated iridocyclitis was the leading cause of anterior uveitis-associated uveitic glaucoma followed by cytomegalovirus (CMV) associated anterior uveitis; while steroid-induced glaucoma accounted for the majority of chronic uveitis with glaucoma followed by Fuchs' uveitis syndrome (FUS). The most common causes of glaucoma among the cases were steroid-induced in 30 eyes (28%), Herpes virus anterior uveitis in 24 eyes (22%), CMV anterior uveitis in 20 eyes (18%), FUS in 15 eyes (14%), ocular toxoplasmosis in 5 eyes (4%). Behçet's uveitis was the most common (n = 11, 36%) cause of steroid-induced glaucoma. The need for surgical intervention was 23.32% (n = 25; 12 of them were FUS, 8 steroid-dependent, 1 HSV and 3 CMV anterior uveitis and 1 angle closure glaucoma with idiopathic uveitis) in our cases. Uveitic glaucoma is a common complication in a tertiary clinic. The most common causes are steroid-induced, FUS, viral anterior uveitis. The most common disease causing steroid induced glaucoma was Behçet's disease. Glaucoma surgery is required in a significant number of cases.


Biomarker interactions are better predictors of spontaneous preterm birth.
The objective of this study was to assess the role of biomarker interactions as predictors of spontaneous preterm birth (PTB) using multifactor dimensionality reduction (MDR) analysis. With MDR, a nonparametric, unsupervised, model-free approach, we tested for biomarker interactions within maternal-fetal compartments in 2 racial groups: African Americans (AA) and Caucasians (C). A total of 36 biomarkers from maternal plasma (MP), cord plasma (CP), and amniotic fluid (AF) were analyzed from 191 patients. The MDR combined attribute selection, construction, and classification to detect biomarker interactions that were assessed for generality and significance using 10× cross-validation and permutation testing. Selected significant interactive models were replicated with additional samples. The interactive model containing interleukin (IL)-2, angiopoietin 2 (ANGPT-2), and IL-6 receptor was significant in AA MP. In AA CP, the IL-8 and tumor necrosis factor (TNF) receptor 1 model was significant. In AA AF, the ANGPT-2 and macrophage inflammatory protein 1 alpha model was significant. Replication of the AA MP model using 54 additional AA MP samples confirmed predictability of these biomarkers. In C AF, interaction was observed between ANGPT-2, monocyte chemotactic protein 3, and TNF-α, but no other interactions were significant in C. Using MDR, we identified biomarker interactions that are predictors of PTB even in the absence of a main effect with a single biomarker.


[Development of a replication-incompetent adenovirus vector derived from subgroup B adenovirus serotype 35].
Properties of gene delivery vehicles, including gene transfer efficiencies and toxicities, are a key parameter for successful gene therapy. Among various types of gene delivery vehicles that have been developed so far, adenovirus (Ad) vectors have promising potentials as a vector for gene therapy because they can easily be grown to high titers and can efficiently deliver genes to both dividing and non-dividing cells. However, recent studies demonstrated some drawbacks of conventional Ad vectors, which are composed of subgroup C Ad serotype 5 (Ad5). First, Ad5 vectors poorly transduce cells lacking the primary receptor for Ad5, coxsackievirus and adenovirus receptor (CAR). Second, majority of adults have neutralizing antibodies to Ad5. In order to overcome these drawbacks, we developed a novel Ad vector which is fully composed of subgroup B Ad serotype 35 (Ad35). Ad35 vectors can infect a variety of human cells because the primary receptor for Ad35, CD46, is ubiquitously expressed in human cells. Furthermore, Ad35 vectors efficiently transduce in the presence of anti-Ad5 antibodies, and seroprevalence of Ad35 in adults is much lower than that of Ad5. In the current review, I introduce our recent work on development and evaluation of Ad35 vectors, and I also discuss the potential of Ad35 vectors as gene delivery vehicles.


Contactless impedance sensors and their application to flow measurements.
The paper provides a critical discussion of the present state of the theory of high-frequency impedance sensors (now mostly called contactless impedance or conductivity sensors), the principal approaches employed in designing impedance flow-through cells and their operational parameters. In addition to characterization of traditional types of impedance sensors, the article is concerned with the use of less common sensors, such as cells with wire electrodes or planar cells. There is a detailed discussion of the effect of the individual operational parameters (width and shape of the electrodes, detection gap, frequency and amplitude of the input signal) on the response of the detector. The most important problems to be resolved in coupling these devices with flow-through measurements in the liquid phase are also discussed. Examples are given of cell designs for continuous flow and flow-injection analyses and of detection systems for miniaturized liquid chromatography and capillary electrophoresis. New directions for the use of these sensors in molecular biology and chemical reactors and some directions for future development are outlined.


Aesthetic Effect of Autologous Fat Transplantation on Frontotemporal Depression Filling and Its Influence on SCL-90 and SES of Patients.
This study aimed to study the aesthetic effect of autologous fat transplantation in frontotemporal depression filling as well as the influence on the Symptom Checklist 90 (SCL-90) and the Rosenberg Self-Esteem Scale (SES) score of patients. A total of 100 patients with frontotemporal depression admitted to the outpatient department of burn and plastic surgery in our hospital were selected as the observation group, and all of them received autologous fat transplantation. The filling effect of patients in the observation group was discussed. Simultaneously, 50 volunteers were selected as the control group to compare the SCL-90 and SES scores of the observation group and the control group. ① A total of 100 patients with frontotemporal depression were treated with autologous fat transplantation, and the secondary autologous fat transplantation rate was 10%; two cases of fat absorption occurred during the 12-month follow-up after surgery; on the 7th day, 6 months, and 12 months after the operation, the satisfaction rate of the patients who visited the doctor was 96.00%, 97%, and 92.00%; the satisfaction rate of the plastic surgeon was 94.00%, 96%, and 90.00%; the satisfaction rate of the third party was 96.00%, 98%, and 92.00%. ② The preoperative scores of somatization, obsessive-compulsive, interpersonal sensitivity, depression, anxiety, hostility, terror, paranoia, and psychotic factor scores in the observation group were higher than those in the control group (P < 0.05). The scores of somatization, obsessive-compulsive, interpersonal sensitivity, depression, anxiety, hostility, terror, paranoia, and psychotic factor scores in the observation group at 6 months after the operation were lower than those before operation (P < 0.05). The preoperative SES score of the observation group (28.51 ± 9.81) was significantly lower than that of the control group (32.47 ± 5.39) (P < 0.05). The SES score (34.17 ± 9.81) in the observation group at 6 months after the operation was significantly higher than that before the operation (P < 0.05). The aesthetic effect of autologous fat transplantation in frontotemporal depression filling is good and safe. Simultaneously, it can improve the mental health and self-esteem of patients and has high clinical value.


A concept for classification of optimal breathing pattern for use in radiotherapy tracking, based on respiratory tumor kinematics and minimum jerk analysis.
During radiotherapy, maintaining the patient in a relaxed and comfortable state helps ensure respiratory regularity and reproducibility, thereby supports accurate respiratory tracking/gating treatment. Criteria to evaluate respiratory naturalness, regularity, and phase robustness are therefore needed to aid for the treatment system numerically and medical observers visually. This study introduces a new concept of respiratory tumor kinematics that describes the trajectory of tumor motion with respiration, leading to the minimum jerk theory. Using this theory, this study proposes novel respiratory criteria for respiratory naturalness, regularity, and phase robustness. According to respiratory tumor kinematics, tumor motion follows the minimum curvature/jerk trajectory in 4D spacetime. Using this theory, the following three respiratory criteria are proposed: (1) respiratory naturalness Us, the residual sum of the squared difference between the normalized average free respiratory wave (single inhalation/exhalation averaged over each 10 phases) and the normalized minimum jerk theoretical respiratory wave; (2) respiratory regularity Cj16, the cumulative jerk squared cost function sampling every 0.2 s with a peak adjustment coefficient, 16; and (3) respiratory phase robustness (LΔ), a second-order partial differential in the respiratory position for regarded Cj16 as the respiratory position function. To verify these respiratory criteria, values obtained from CyberKnife tracking marker log data for 15 patients were compared with regard to the correlation error between the correlation model and the imaged tumor position, as well as with the number of remodels. The Cj16 growth curve was also compared between 15 patients and 15 healthy volunteers. In the 15 patients, data with Us < 1 and Cj16(60 s) < 10 000 satisfied average/maximum correlation errors of less than 1/3 mm. Data with higher Us values (less respiratory naturalness) and higher Cj16(60 s) values (less respiratory regularity) demonstrated more than 3 mm average/5 mm maximum correlation errors and an increased number of remodels. The data for the 15 patients and 15 volunteers demonstrated that the Cj16 growth curve over 120 s from the start of sampling indicated patient-specific respiratory trends and that the distribution of LΔ clearly showed the respiratory phase shift. In 22 of 30 subjects, the degree of change in the Cj growth curve trends from 60 to 120 s was 22% ± 13% (average ± SD). In contrast, the residual data observed when Cj16 > 1000 showed minimum and mean changes of 91% and 180%, respectively. The authors developed and verified novel respiratory criteria for respiratory naturalness, regularity, and phase robustness obtained using respiratory tumor kinematics and minimum jerk analysis. These criteria should be useful in monitoring respiratory trends on a real-time basis during treatment, as well as in selecting optimal breathing for tracking/gating radiation treatment and defining numerical goals for respiratory training/gating.


Presentation and management of nervous system cavernous malformations in children: A systematic review and case report.
Cerebral cavernous malformations (CMs) are slow-flow vascular lesions that affect up to 0.5% of the pediatric population. These lesions are at risk for hemorrhage, causing seizures, and leading to neurological deficits. Here, we conduct a literature review and then present a report of a supratentorial CM in a 2-year-old patient with no significant past medical history who presented at our institution with 1 month of eye twitching. We performed a literature search of five databases of all articles published before 2020. Our inclusion criteria included cohort and case series of children with mean age under 12 years. Our search yielded 497 unique articles, of which 16 met our inclusion criteria. In our pooled literature analysis, a total of 558 children were included, 8.3% of which had a positive family history and 15.9% had multiple CMs. About 46.1% of the children had seizures, and 88.4% of those who underwent surgery had a total resection. About 85.1% of those with epilepsy were Engel Class 1 postsurgery. Over a mean follow-up of 4.1 years, 3.4% of patients had additional neurological deficits, including paresis and speech deficits. Our analysis of published literature shows surgical intervention should be considered first-line therapy for patients who are symptomatic from CM, present with seizure, and have surgically accessible lesions. Additional work is needed on outcomes and long-term effects of minimally invasive treatments, including radiosurgery and laser ablation, in pediatric populations.


Use of Pantoea agglomerans ASB05 as a biocontrol agent to inhibit the growth of Salmonella enterica on intact cantaloupe melons.
To identify biocontrol agents to prevent the growth of Salmonella serotype Enterica on cantaloupe melons during the pre- and postharvest periods. We created a produce-associated bacterial library containing 8736 isolates and screened it using an in-vitro fluorescence inhibition assay to identify bacteria that inhibit the growth of S. Enterica. One isolate, Pantoea agglomerans ASB05, was able to grow, persist, and inhibit the growth of S. Enterica on intact cantaloupe melons under simulated pre- and postharvest conditions. We also demonstrated that the growth inhibition of S. Enterica by P. agglomerans ASB05 was due to the production of a phenazine type antibiotic. Pantoea agglomerans ASB05 is an effective biocontrol agent for the prevention of S. Enterica growth on intact cantaloupe melons in both the pre- and postharvest environments.


CHARACTER DISCRIMINATORY POWER, CHARACTER-SET CONGRUENCE, AND THE CLASSIFICATION OF INDIVIDUALS FROM HYBRID ZONES: AN EXAMPLE USING STONE CRABS (MENIPPE).
Many investigators categorize individuals from hybrid zones to facilitate comparisons among genotypic classes (e.g., parental, F1 , backcross) for comparative studies in which components of fitness or geographic variation are being analyzed. Frequently, multiple character sets representing genetically independent traits are used to classify these individuals and various methodologies are employed to combine the classifications obtained from the different character sets. We adapted the principles of total evidence and taxonomic congruence (two formalized approaches used by systematists in formulating phylogenetic hypotheses) to address the problem of discriminating hybridizing species and classifying individuals from hybrid zones. As our model, we used two morphological (coloration and morphometric) and two molecular (allozyme and mitochondrial DNA restriction-fragment-length polymorphism) character sets that differentiate two stone crab species (Menippe adina and M. mercenaria). Using principal-components analysis, we determined that combining character sets and eliminating characters or character sets that did not have large eigenvector coefficients for the principal component that best separated the two species yielded the highest level of discrimination between species and allowed us to classify a broad range of morpho-genotypes as hybrids. For the stone crabs, three diagnostic allozyme loci and five diagnostic coloration characters best separated the species. The two character sets were not completely congruent, but they agreed in their classification of 50% of the individuals from the hybrid zone and rarely strongly disagreed in their classifications. Classification discrepancies between the two character sets probably represent variation between traits in interspecific gene flow rather than intraspecific, ecologically mediated variation. Our results support the assertions of previous investigators who espoused the benefits associated with using multiple character sets to classify individuals from hybrid zones and demonstrate that, if character sets are reasonably congruent and numerically balanced, combining diagnostic characters from multiple character sets (a total-evidence approach) can enhance discriminatory power between species and facilitate the assignment of hybrid-zone individuals to genotypic classes. On the contrary, classifying hybrid-zone individuals using character sets separately (a taxonomic-congruence approach) provides the opportunity to compare levels of introgression between species and to assess reasons for discordance among the data sets.


Chronic paroxysmal hemicrania and hemicrania continua: lack of efficacy of sumatriptan.
Attacks of chronic paroxysmal hemicrania are prevented by the continuous administration of indomethacin. Sumatriptan, an agonist of 5-HT1-like receptors, has proven effective in the treatment of cluster headache attacks. There are clear clinical similarities between chronic paroxysmal hemicrania and cluster headache. A natural consequence of these considerations would be to establish whether chronic paroxysmal hemicrania also responds similarly to sumatriptan. Since hemicrania continua is another unilateral headache responsive to indomethacin, it would be meaningful to also include hemicrania continua in such a study. Sumatriptan, 6 mg subcutaneous, was tried in an open fashion in 7 patients (6 women and 1 man) with chronic paroxysmal hemicrania and 7 patients (5 women and 2 men) with hemicrania continua. In chronic paroxysmal hemicrania, the mean interval between the last three attacks prior to sumatriptan treatment (40 +/- 23 minutes) was not statistically different from the mean interval between the three attacks subsequent to sumatriptan treatment of an attack (32 +/- 20 minutes). In none of the patients did the mean duration of the "test attack" decrease as compared to the attacks antedating the test attack (25 +/- 11 minutes and 19 +/- 9 minutes, respectively) (P = 0.027, Wilcoxon). In 2 patients with chronic paroxysmal hemicrania, placebo (saline) administration did not lead to any change in the interval between attacks. There was a mild, but statistically significant reduction in visual analog scale values for headache intensity in hemicrania continua (P = 0.04, Wilcoxon). There was no clear, i.e., clinically meaningful, reduction in visual analog scale values in any particular patient with hemicrania continua. Taken together, these results seem to show that sumatriptan is of no benefit in chronic paroxysmal hemicrania, but may have a partial efficacy in hemicrania continua. However, the latter effect is clinically unimportant. This minor difference in regard to the clinical effect may, nevertheless, be of some interest pathogenetically, indicating minor differences between the two headaches. The lack of sumatriptan effect in chronic paroxysmal hemicrania clearly and markedly strengthens the nonalignment concept in regard to chronic paroxysmal hemicrania and cluster headache.


A revision of PassifloraL.subgenusDecaloba(DC.) Rchb.supersectionCieca (Medik.) J. M. MacDougal & Feuillet (Passifloraceae).
PassiflorasubgenusDecalobasupersectionCieca is a monophyletic group of herbaceous to woody climbers found in subtropical and tropical regions of the world. The 19 species recognized here are primarily distributed in the southern United States, Mexico, Central America, South America, and the Caribbean. Two species, Passiflorasuberosa and Passiflorapallida, are also naturalized in various regions of the Old World. The species of the supersection are recognized by their small, apetalous, usually greenish flowers with the filaments of the corona mostly in two series. The plants commonly lack c-glycosylflavones but possess flavonol 3-O-glycosides. The supersection contains two problematic species complexes, Passiflorasuberosa and Passifloracoriacea. Phylogenetic relationships within supersection Cieca are investigated by means of phenetic and cladistic analyses of morphological and molecular (ITS 1 & 2) characters. The morphological and molecular data sets were analyzed separately because of incongruity due to taxon sampling and the complicated evolutionary history of entities within the Passiflorasuberosa complex. All analyses confirm the monophyly of the supersection. They also show that the Passiflorasuberosa complex is a non-monophyletic group of cryptic species, and inter-taxic hybridization and polyploidy have contributed to the confusing and complex pattern of variation evident within the group. Four taxa that were formerly included in this complex are recognized: Passiflorapallida, Passiflorasuberosasubsp.suberosa, Passiflorasuberosasubsp.litoralis, and Passifloratridactylites. On the basis of molecular and morphological data, three species from the Passifloracoriacea complex are recognized: Passifloracoriacea, Passiflorasexocellata, and Passifloramegacoriacea. A key, detailed descriptions, distribution maps, and illustrations are included in the revision. Pollination, dispersal, and herbivory of the group are reviewed. The distribution and ecology of the species within the supersection are also discussed.


Research on social attention in autism and the challenges of the research domain criteria (RDoC) framework.
The fuzzy nature of categories of psychopathology, such as autism, leads to significant research challenges. Alternatively, focusing research on the study of a common set of important and well-defined psychological constructs across psychiatric conditions may make the fundamental etiological processes of psychopathology easier to discern and treat (Cuthbert, 2022). The development of the research domain criteria (RDoC) framework is designed to guide this new research approach (Insel et al., 2010). However, progress in research may be expected to continually refine and reorganize the understanding of the specifics of these mental processes (Cuthbert & Insel, 2013). Moreover, knowledge gleaned from the study of both normative and atypical development can be mutually informative in the evolution of our understanding of these fundamental processes. A case in point is the study of social attention. This Autism 101 commentary provides an educational summary of research over the last few decades indicates that social attention is major construct in the study of human social-cognitive development, autism and other forms of psychopathology. The commentary also describes how this research can inform the Social Process dimension of the RDoC framework.


Using Conjoint Analysis to Investigate Hospital Directors' Preference in Adoption of an Evidence-based Intervention.
This study used conjoint analysis, a marketing research technique, to investigate hospital stakeholders' decision-making in adoption of evidence-based interventions (EBI). An efficacious hospital-based stigma-reduction intervention was used as a "product" to study adoption of EBI. Sixty hospital directors in Fujian, China evaluated the likelihood of adopting the EBI in their hospitals by rating across eight hypothetical scenarios with preferred and non-preferred levels of seven attributes, including 1) administrative support, 2) cost, 3) personnel involvement, 4) format, 5) duration, 6) technical support, and 7) priority alignment with the hospital. A hierarchical generalized linear model was fit to the likelihood of intervention adoption for the eight scenarios, with the seven attributes served as independent variables. Monetary cost of intervention implementation (impact score=2.12) had the greatest impact on the directors' reported likelihood of adopting the EBI, followed by duration of the intervention (impact score=0.88), availability of technical support (impact score=0.69), and flexibility of format (impact score=0.36). The impact scores of other attributes were not statistically significant. Conjoint analysis was feasible in modeling hospital directors' decision-making in adoption of EBI. The findings suggested the importance of considering cost, duration, technical support, and flexibility of format in development and dissemination of interventions in healthcare settings.


A halogen-bonding bis-triazolium rotaxane for halide-selective anion recognition.
A systematic study on the anion-binding properties of acyclic halogen- and hydrogen-bonding bis-triazolium carbazole receptors is described. The halide-binding potency of halogen-bonding bis-iodotriazolium carbazole receptors was found to be far superior to their hydrogen-bonding bis-triazolium-based analogues. This led to the synthesis of a mixed halogen- and hydrogen-bonding rotaxane host containing a bis-iodotriazolium carbazole axle component. The rotaxane's anion recognition properties, determined by (1)H NMR titration experiments in a competitive aqueous solvent mixture, demonstrated the preorganised halogen-bonding interlocked host cavity to be halide-selective, with a strong binding affinity for bromide.


Is the Lateralized Categorical Perception of Color a Situational Effect of Language on Color Perception?
This study investigated whether and how a person's varied series of lexical categories corresponding to different discriminatory characteristics of the same colors affect his or her perception of colors. In three experiments, Chinese participants were primed to categorize four graduated colors-specifically dark green, light green, light blue, and dark blue-into green and blue; light color and dark color; and dark green, light green, light blue, and dark blue. The participants were then required to complete a visual search task. Reaction times in the visual search task indicated that different lateralized categorical perceptions (CPs) of color corresponded to the various priming situations. These results suggest that all of the lexical categories corresponding to different discriminatory characteristics of the same colors can influence people's perceptions of colors and that color perceptions can be influenced differently by distinct types of lexical categories depending on the context.


A road map for navigating end-of-life care.
As nurses begin to develop the sensitivities and skills necessary to preserve the integrity of clinical care and professional life, they must recognize the legitimacy of their perspectives and the value and consequences they have for the well-being of patient and family care. Nurses have much to contribute to the development of ethical practice environments for patients, families, multidisciplinary team members, and themselves. The frenzied, and at times anesthetized, culture of clinical settings can mitigate against the kind of deliberate reflection that is necessary if nurses are to act with ethical integrity. Knowing the rules of the road for end-of-life care and being attentive to common warning signs and addressing them proactively, enables nurses to provide patients and families with the highest quality care at the end of life.


Audiovisual resources for learning--a brave new world unrealized?
Sir Brynmor Jones, who was Vice-Chancellor of the University of Hull from 1956 until 1972, died on the 16 July 1989 at the age of 85. He will perhaps be most widely remembered for his Chairmanship of a Committee which reported, in 1965, on Audiovisual Aids in Higher Scientific Education. The Brynmor Jones Report, as it became known, was published during an expansion of higher education and its recommendations mirror the sense of optimism and enthusiasm that prevailed at that time. The report urged a corresponding expansion in the use of audiovisual aids and, while the recommendations initiated interest and approval and were acted on to some extent, they have had comparatively little impact on the delivery of teaching and learning, particularly in medical education.


Alterations in visually related eye movements following left pulvinar damage in man.
This case study presents evidence for two subtle types of eye movement abnormalities following surgical resection of the left posterior pulvinar in man. First, visual fixations during vertical pattern matching are on average both increased in number and prolonged in duration compared to controls, although normal fixation durations also occur. Second, unilateral deficiencies during search and scanning performance are associated with eye movements directed into the hemifield contralateral to the lesion. Although direct damage to parietal cortex and indirect damage to other visually related structures cannot be ruled out as other explanations for these deficits, these findings are consistent with recent electrophysiological and behavioral studies of the pulvinar in both human and non-human primates, and suggests a fruitful area for further investigation of pulvinar function.


Intramuscular sedation technique.
A sedative technique with meperidine hydrochloride and promethazine hydrochloride via an intramuscular injection is presented. We believe this is an excellent technique because of the safety to the patient and the ease of administration. Like any technique using potentially dangerous medications, practitioners and their staff must be familiar with and prepared for possible complications. When the technique is mastered, it will be a valuable addition for treatment of certain mentally and physically handicapped patients.


Prostate-derived Ets factor is overexpressed in serous epithelial ovarian tumors.
The frequent overexpression of prostate-derived Ets factor (PDEF) mRNA in ovarian cancer has been previously reported. The aim of this study was to evaluate PDEF protein expression in ovarian cancer and how this expression might vary at different stages of epithelial ovarian tumors in comparison to normal ovary. A new rabbit polyclonal antibody to PDEF was prepared, and immunohistochemistry was performed on tissue sections from 12 normal ovaries, 10 cases of benign serous cystadenoma, 17 cases of low malignant potential tumor, 19 cases of stage 1, and 15 cases of advanced stage primary epithelial (serous) ovarian carcinomas and their peritoneal metastases. Expression levels were assessed based on the percentage of positively staining cells and the intensity of staining. All 12 normal ovary and 10 benign serous cystadenoma cases were negative for PDEF expression. In contrast, 6 of 17 (35%) low malignant potential tumors, 5 of 19 (27%) stage 1, and 5 of 15 (33%) advanced stage ovarian tumors stained positive for PDEF expression. Together, these results show frequent overexpression of PDEF protein in epithelial ovarian tumors and its lack of expression in normal ovary and cystadenomas, and this supports a role for PDEF in ovarian tumorigenesis. Furthermore, these results suggest that PDEF is a potential marker and target in ovarian cancer.


Successful atrioventricular valve repair improves long-term outcomes in children with unbalanced atrioventricular septal defect.
Atrioventricular valve regurgitation is a significant cause of morbidity and mortality in patients with unbalanced atrioventricular septal defect. However, knowledge of the outcomes of atrioventricular valve repair in children with unbalanced atrioventricular septal defect and univentricular physiology is limited. We conducted a retrospective review of all patients with unbalanced atrioventricular septal defect treated with single-ventricle palliation who underwent atrioventricular valve surgery at The Royal Children's Hospital. Between 1976 and 2016, 139 children with unbalanced atrioventricular septal defect underwent single-ventricle palliation, of whom 31.7% (44/139) required atrioventricular valve surgery. Repair of the atrioventricular valve was attempted in 97.7% (43/44) of patients, of whom 4.7% (2/43) were converted to replacement during the initial operation. Replacement of the atrioventricular valve without attempted repair was performed in 2.3% (1/44) of patients. Early mortality was 18.2% (8/44). Freedom from death or transplantation at 10 years was 66.0% (95% confidence interval, 49.1-78.5) and at 20 years was 53.3% (95% confidence interval, 32.1-70.6). In multivariable analysis, significant predischarge atrioventricular valve regurgitation (hazard ratio, 6.4; P = .002), age less than 1 year (hazard ratio, 8.3; P = .01), and repair before stage II palliation (hazard ratio, 3.4; P = .04) were associated with death. Freedom from reoperation at 10 years was 61.9% (95% confidence interval, 41.9-76.8) and at 20 years was 56.3% (95% confidence interval, 35.3-72.8). Moderate or greater atrioventricular valve regurgitation at discharge was associated with an increased risk of reoperation (hazard ratio, 1.8; P = .03). Of transplant-free survivors, atrioventricular valve regurgitation was less than moderate in 60.0% (15/25) at the most recent follow-up. Atrioventricular valve surgery in patients with unbalanced atrioventricular septal defect is associated with substantial mortality and a high rate of reoperation. Successful atrioventricular valve repair is associated with better survival and freedom from reoperation.


High Spatial Resolution Multi-Organ Finite Element Modeling of Ventricular-Arterial Coupling.
While it has long been recognized that bi-directional interaction between the heart and the vasculature plays a critical role in the proper functioning of the cardiovascular system, a comprehensive study of this interaction has largely been hampered by a lack of modeling framework capable of simultaneously accommodating high-resolution models of the heart and vasculature. Here, we address this issue and present a computational modeling framework that couples finite element (FE) models of the left ventricle (LV) and aorta to elucidate ventricular-arterial coupling in the systemic circulation. We show in a baseline simulation that the framework predictions of (1) LV pressure-volume loop, (2) aorta pressure-diameter relationship, (3) pressure-waveforms of the aorta, LV, and left atrium (LA) over the cardiac cycle are consistent with the physiological measurements found in healthy human. To develop insights of ventricular-arterial interactions, the framework was then used to simulate how alterations in the geometrical or, material parameter(s) of the aorta affect the LV and vice versa. We show that changing the geometry and microstructure of the aorta model in the framework led to changes in the functional behaviors of both LV and aorta that are consistent with experimental observations. On the other hand, changing contractility and passive stiffness of the LV model in the framework also produced changes in both the LV and aorta functional behaviors that are consistent with physiology principles.


Identification of a receptor required for the anti-inflammatory activity of IVIG.
The anti-inflammatory activity of intravenous Ig (IVIG) results from a minor population of the pooled IgG molecules that contains terminal alpha2,6-sialic acid linkages on their Fc-linked glycans. These anti-inflammatory properties can be recapitulated with a fully recombinant preparation of appropriately sialylated IgG Fc fragments. We now demonstrate that these sialylated Fcs require a specific C-type lectin, SIGN-R1, (specific ICAM-3 grabbing non-integrin-related 1) expressed on macrophages in the splenic marginal zone. Splenectomy, loss of SIGN-R1(+) cells in the splenic marginal zone, blockade of the carbohydrate recognition domain (CRD) of SIGN-R1, or genetic deletion of SIGN-R1 abrogated the anti-inflammatory activity of IVIG or sialylated Fc fragments. Although SIGN-R1 has not previously been shown to bind to sialylated glycans, we demonstrate that it preferentially binds to 2,6-sialylated Fc compared with similarly sialylated, biantennary glycoproteins, thus suggesting that a specific binding site is created by the sialylation of IgG Fc. A human orthologue of SIGN-R1, DC-SIGN, displays a similar binding specificity to SIGN-R1 but differs in its cellular distribution, potentially accounting for some of the species differences observed in IVIG protection. These studies thus identify an antibody receptor specific for sialylated Fc, and present the initial step that is triggered by IVIG to suppress inflammation.


Treatment of depression in Parkinson's disease with moclobemide: A pilot open-label study.
Moclobemide, a potent reversible monoamine-oxidase A (MAO-A) inhibitor, is an effective antidepressant that does not cause impairment of cognitive function in elderly patients and might be beneficial to motor deficits in Parkinson's disease (PD). In a 12-week open-label prospective study, we administered moclobemide (300-600 mg day(-1)) as an add-on medication to twelve PD patients who met DSM-III-R criteria for depressive illness. There were two early drop-outs due to subjective worsening of Parkinsonism associated with insomnia and anorexia, respectively. The Beck Depression Inventory score decreased significantly in the ten patients who completed the study, and clinical global assessment of efficacy recorded 'good' or 'excellent' responses or in nine of the ten patients. Mean parkinsonian disability, as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) and Schwab-England Daily Life Activities scales, remained unchanged throughout the study in the group as a whole. However, worsening or onset of resting tremor occurred in five patients and the UPDRS tremor subscore in the group overall was significantly higher by week 8 (p = 0.03) when dose titration was optimal. There was a trend toward improvement in UPDRS bradykinesia subscores that did not attain statistical significance. Compared to baseline, patients complained more often of insomnia, anorexia, increased perspiration, and restlessness. Though these preliminary results need to be replicated in a large controlled trial, we suggest that moclobemide may be an effective alternative in the treatment of PD associated depression.


Characterization of viral pathogens associated with symptomatic upper respiratory tract infection in adults during a low COVID-19 transmission period.
The epidemiology of respiratory tract infections (RTI) has dramatically changed over the course of the COVID-19 pandemic. A major effort in the clinical management of RTI has been directed toward diagnosing COVID-19, while the causes of other, common community RTI often remain enigmatic. To shed light on the etiological causes of RTI during a low COVID-19 transmission period in 2021, we did a pilot study using molecular testing for virologic causes of upper RTI among adults with respiratory symptoms from Almaty, Kazakhstan. Adults presenting at two public hospitals with respiratory symptoms were screened using SARS-CoV-2 PCR on nasopharyngeal swabs. A subset of RTI+, COVID-19-negative adults (n = 50) was then tested for the presence of common RTI viruses and influenza A virus (IAV). Next generation virome sequencing was used to further characterize the PCR-detected RTI pathogens. Of 1,812 symptomatic adults, 21 (1.2%) tested SARS-CoV-2-positive. Within the COVID-19 negative outpatient subset, 33/50 subjects (66%) had a positive PCR result for a common community RTI virus, consisting of human parainfluenza virus 3-4 (hPIV 3-4) in 25/50 (50%), rhinovirus (hRV) in 2 (4%), hPIV4-hRV co-infection in four (8%) and adenovirus or the OCR43/HKU-1 coronavirus in two (4%) cases; no IAV was detected. Virome sequencing allowed to reconstruct sequences of most PCR-identified rhinoviruses and hPIV-3/human respirovirus-3. COVID-19 was cause to a low proportion of symptomatic RTI among adults. Among COVID-negative participants, symptomatic RTI was predominantly associated with hPIV and hRV. Therefore, respiratory viruses other than SARS-CoV-2 should be considered in the clinical management and prevention of adult RTI in the post-pandemic era.