Cardiac autonomic control in high level Brazilian power and endurance track-and-field athletes.
The autonomic nervous system (ANS) has an important role in physical performance. However, the cardiac ANS activity in high-level track and field athletes has been poorly explored. Thus, we tested the hypothesis that endurance and power athletes would present a markedly different cardiac autonomic control at rest. We analyzed the cardiac ANS by means of time and frequency domains heart rate variability (HRV) analyses and by symbolic analysis. Endurance athletes showed higher pulse interval than power athletes (1,265±126 vs. 1,031±98 ms respectively; p<0.05). No differences were found in time and frequency domains between the groups. However, the LF%, HF% and LF/HF ratio presented high effect sizes (1.46, 1.46 and 1.30, respectively). The symbolic analysis revealed that endurance athletes had higher 2V parasympathetic modulation (36±6.5) than power athletes (24±9.3; p<0.05). A reduced 0V sympathetic modulation was observed in endurance athletes (21±9.9) compared to power athletes (33±11; p<0.05 and ES=1.30). Our results suggest greater parasympathetic modulation and less sympathetic modulation in endurance athletes compared to power athletes. Additionally, the type of HRV analysis needs to be chosen with well-defined criteria and caution because their use in assessing cardiac autonomic modulation can interfere with the interpretation of results. In practical terms, symbolic analysis appears to better discriminate between cardiac autonomic activities of athletes with different training backgrounds than frequency domain analysis.


Reduced β-catenin expression affects patterning of bone primordia, but not bone maturation.
Wnt/β-catenin signaling is involved in patterning of bone primordia, but also plays an important role in the differentiation of chondrocytes and osteoblasts. During these processes the level of β-catenin must be tightly regulated. Excess β-catenin leads to conditions with increased bone mass, whereas loss of β-catenin is associated with osteoporosis or, in extreme cases, the absence of limbs. In this study, we examined skeletogenesis in mice, which retain only 25% of β-catenin. These embryos showed severe morphological abnormalities of which the lack of hindlimbs and misshaped front paws were the most striking. Surprisingly however, calcification of bone primordia occurred normally. Moreover, the Wnt-dependent regulatory network of transcription factors driving the differentiation of cartilage and bone, as well as the expression of extracellular matrix components, were preserved. These findings show that 25% β-catenin is insufficient for the correct patterning of bone primordia, but sufficient for their mineralization. Our approach helps to identify bone morphogenetic processes that can proceed normally even at low β-catenin levels, in contrast to those that require high β-catenin dosages. This information could be exploited to improve the treatment of bone diseases by fine-tuning the individual β-catenin dosage requirements.


A misdiagnosed patient: 16 years of locked-in syndrome, the influence of rehabilitation.
LiS can be mistakenly recognized as a vegetative state, minimally conscious state or akinetic mutism. It can be caused by isolated lesions--bilateral infarction, vertebrobasilar artery osslusion, haemorrhage or tumor of the ventral portion of the basis pontis or midbrain. The case of a 65-year-old patient with a brain tumor localized in the posterior part of the posterior commissure of the brain was presented. He lost consciousness in 1991, was diagnosed as being at a terminal stage and from 2005 he started to improve. In MRI brain tumor stated in 1989 with the same localization and size in 2007 without any disturbance in cerebral fluid flow. The patients remained in this condition for 14 years without any rehabilitation, because he was diagnosed as a terminal stage, a non-operative stage. When exercises were introduced in 2005 the patient started to recover. In 2007 he was conscious with quadriplegia, a neuropsychological test showed memory problems, without any dementia. After intensive rehabilitation functional improvement and speech improvement was observed, GOS (4), Ranczo Los Amigos Scale (6), DRS (18). It is important to carry out full diagnostics before determining a terminal stage and to continue a rehabilitation program and multisensory stimulation. Even after 16 year of lying in bed without communication there is a chance in LiS to witness improvement after stimulation, without any signs of dementia.


Activation and Loading of the Starter Unit during Thiocoraline Biosynthesis.
The initiation of the nonribosomal peptide synthetase (NRPS) assembly of the bisintercalator natural product thiocoraline involves key enzymatic steps for AMP activation and carrier protein loading of the starter unit 3-hydroxyquinaldic acid (3HQA). Gene cluster data combined with protein sequence homology analysis originally led us to propose that TioJ could be responsible for the AMP activation step, whereas TioO could act as the thiolation (T) domain, facilitating the transfer of 3HQA to the next NRPS module, TioR. Herein, we confirmed the involvement of TioJ in thiocoraline biosynthesis by tioJ knockout and in vitro activation of 3HQA studies. However, we demonstrated that TioJ-activated 3HQA is not loaded onto the T domain TioO, as originally believed, but instead onto a fatty acid synthase (FAS) acyl carrier protein (ACP) domain FabC, which is located outside of the thiocoraline gene cluster. We showed a strong interaction between TioJ and FabC. By generating TioJ point mutants mimicking the active site of highly homologous enzymes activating different molecules, we showed that the identity of the substrate activated by adenylation domains such as TioJ is not determined by only the active site residues that directly interact with the substrate. The insights gained from these enzymatic transformations are valuable in the efforts toward deciphering the complete biosynthetic pathway of thiocoraline and bisintercalators in general.


Extracting dominant textures in real time with multi-scale hue-saturation-intensity histograms.
It is very important to extract high quality texture features from images. This is, however, often laborious, because the randomness in the color distribution patterns for texture elements makes texture measurement very difficult, despite these elements having a very similar visual appearance. In this paper, we propose the use of multi-scale color histograms to measure the effect of color distribution patterns efficiently and without having to compute the actual patterns, which saves considerable effort. Meanwhile, the hue-saturation-intensity color model is mainly adopted to take the advantage of human visual experiences in texture recognition. We discuss and validate the effectiveness and efficiency of our method by applying to various benchmarks. The results show that we can extract quality dominant textures automatically in real time, and faster by several orders of magnitude than existing methods.


Treacher Collins syndrome: current evaluation, treatment, and future directions.
Treacher Collins syndrome (TCS) is an inherited disorder in which there are general bilateral symmetric anomalies of the structures within the first and second branchial arches. In general, there is complete penetrance and variable expressivity of the trait. The craniofacial rehabilitation of a child with TCS is tailored to the extent of the deformities involved: the orbitozygomatic region, the maxillomandibular region, the nose, facial soft tissues, and external and middle ear structures. This article reviews the range of clinical features and specific dysmorphology observed in TCS. Functional and aesthetic objectives are discussed, and a comprehensive staged reconstructive approach is outlined, which may be used as a roadmap for treatment planning.


Development of a Brief Psychological Trauma Intervention for Child Sexual Abuse in India.
Despite the alarming increase in incidences of child sexual abuse (CSA) in India, intervention research remains preliminary and generic. Although Cognitive Behavior Therapy (CBT) has been found to be consistently effective in addressing the adverse consequences of CSA, none of the cultural adaptations of CBT have been evidenced in India so far. Hence, the present study was conceived to develop a CSA-focused brief CBT intervention for children between 7 and 13 years of age. Intervention development progressed through four steps: 1) a systematic review of literature; 2) a qualitative study, including focused group discussions, conducted with 19 mental health professionals; 3) development of the intervention; 4) expert evaluation and finalization. We developed the intervention with three key elements: restoring the child's functioning, assisting the child in processing, and managing trauma effectively and initiating the process of growth. The intervention predominantly followed the CBT framework while integrating culturally specified techniques. The intervention contains 8 modules and 18 sub-modules structured around three phases of intervention. The intervention is spread across a minimum of 6 required sessions and a maximum of 12 session held twice weekly for approximately 90-120 min duration. A list of 35 activities corresponding to each phase and sub-module of the present intervention has been designed as an intervention workbook. In conclusion, the newly developed intervention is a manualised, culturally competent, psychological intervention developed within the CBT framework for children aged 7-13 years with experience of CSA. The next phases include piloting intervention for feasibility.


Assessment of cardiac status in hypertensive patients.
Evaluation of cardiac participation in hypertension includes much more than determination of the presence or absence of left ventricular hypertrophy by chest X-ray or electrocardiography. Chest X-ray has not proved very useful in the work-up of hypertensive patients in contrast with electrocardiography. Although electrocardiography is highly specific for left ventricular hypertrophy, it is not sensitive enough for many cases nor does it allow functional assessment of cardiac performance. Echocardiography, on the other hand, is a much more powerful tool for the evaluation of both the anatomical and functional aspects of cardiac performance. However, although it cannot be recommended as yet for routine evaluation of all patients, it is rapidly becoming an important examination for many patients. It allows not only quantitative estimate of left ventricular hypertrophy (LVH), but will also determine the distribution of hypertrophy, its effects on both systolic and diastolic functions of the heart and its alteration with therapy. As regards specific tests for myocardial perfusion, coronary reserve and ventricular volume analysis, these techniques are indicated more for clinical research or very special circumstances than for routine use. In summary assessment of cardiac status of a hypertensive patient should include the following: a precise diagnosis of LVH, estimate of cardiac performance, both systolic and diastolic, evaluation of cardiac factors in resistance to antihypertensive therapy and follow-up of regression of structural alterations during antihypertensive treatment.


[Methods of histological treatment of the labyrinth].
The otic labyrinth presents one of the most difficult objects for histological investigations as it is situated in the thick layer of the temporal bone and has a very complex structure. At the same time, a method for treating this object is not given in general hand-books on pathological techniques. The methods for histological treatment of the otic labyrinth elaborated by Wittmaack and later on modified are presented in the article. Methods for fixation, vital fixation including, decalcination, dehydratation and saturation of the objects prepared for histological investigation are described in details. Methods for the temporal bone orientation in order to obtain sections of the internal otic structures in the most advantageous plane depending on the purpose and aim of the investigation are recommended.


Neotropical ant gardens : I. Chemical constituents.
In ant gardens of lowland Amazonia, parabiotic ant speciesCamponotus femoratus andCrematogaster cf.limata parabiotica cultivate a taxonomically diverse group of epiphytic plants, whose establishment is restricted to arboreal carton ant nests. Epiphyte seeds are collected by workers ofCa. femoratus, the larger of the two ants, and stored unharmed in brood chambers where they subsequently germinate. Although seeds of some ant-garden epiphytes bear nutritional rewards, previous studies have shown that these rewards are not sufficient to explain the pattern of ant attraction to seeds. Five aromatic compounds occur frequently in and on the seeds of most ant-garden epiphytes and may be chemical cues by which ants recognize propagules of their symbiotic plants. The most widely distributed of these is methyl 6-methylsalicylate [6-MMS]1, previously reported as a major mandibular gland product in relatedCamponotus species and present in trace quantities inCa. femoratus males. (-)-Citronellol6 (previously unreported inCamponotus) was the principal volatile constituent in extracts of male heads, and (-)-mellein7 was present in small quantities. Discovery of 6-MMS inside the mandibular glands of maleCa. femoratus (and its presence in analogous glands of related ants) offers preliminary support for Ule's (1906) hypothesis that seeds attract ants by mimicking ant brood. In addition, the likely fungistatic activity of seed compounds suggests that they could retard microbial pathogens of ants and plants in the organic detritus of nest gardens. While the presence of identical seed compounds in so many unrelated plant lineages might represent a remarkable case of convergent evolution, other interpretations are possible.


Detection of small lesions of the large bowel; barium enema versus double contrast.
Roentgen study with the so-called opaque barium enema with some modifications is superior to double contrast study as the primary means of demonstrating polyps in the colon as well as other lesions. The method described combines fluoroscopy, high kilovoltage radiography, fluoroscopically aimed "spot films" taken with compression, suction and evacuation studies. In this way unsuspected as well as suspected polyps can be demonstrated, particularly if attention is directed to the region where polyps are most likely to be found-namely, the distal third of the large bowel. Double contrast study is quite valuable as a supplement to the modified "single contrast" barium enema, but it has not been sufficiently perfected to replace the modified opaque barium enema as a primary procedure. In many instances a combination of methods will, of course, be required.


Reorientational dynamics of water confined in zeolites.
We present a detailed molecular-dynamics study of water reorientation and hydrogen-bond dynamics in a strong confinement situation, within the narrow pores of an all-silica Linde type A (LTA) zeolite. Two water loadings of the zeolite are compared with the bulk case. Water dynamics are retarded in this extreme hydrophobic confinement and the slowdown is more pronounced at higher water loading. We show that water reorientation proceeds mainly by large-amplitude angular jumps, whose mechanism is similar to that determined in the bulk. The slowdown upon hydrophobic confinement arises predominantly from an excluded-volume effect on the large fraction of water molecules lying at the interface with the zeolite matrix, with an additional minor contribution coming from a structuring effect induced by the confinement.


The actor's insight: Actors have comparable interoception but better metacognition than nonactors.
Both accurately sensing our own bodily signals and knowing whether we have accurately sensed them may contribute to a successful emotional life, but there is little evidence on whether these physiological perceptual and metacognitive abilities systematically differ between people. Here, we examined whether actors, who receive substantial training in the production, awareness, and control of emotion, and nonactor controls differed in interoceptive ability (the perception of internal bodily signals) and/or metacognition about interoceptive accuracy (awareness of that perception), and explored potential sources of individual differences in and consequences of these abilities including correlational relationships with state and trait anxiety, proxies for acting ability, and the amount of acting training. Participants performed a heartbeat detection task in which they judged whether tones were played synchronously or delayed relative to their heartbeats, and then rated their metacognitive confidence in that judgment. Cardiac interoceptive accuracy and metacognitive awareness of interoceptive accuracy were independent, and while actors' and controls' interoceptive accuracy was not significantly different, actors had consistently superior metacognitive awareness of interoception. Exploratory analyses additionally suggest that this metacognitive ability may be correlated with measures of acting ability, but not the duration of acting training. Interoceptive accuracy and metacognitive insight into that accuracy appear to be separate abilities, and while actors may be no more accurate in reading their bodies, their metacognitive insight means they know better when they're accurate and when they're not. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


[Changes in functional activity of granulocytopoiesis in patients with rheumatoid arthritis].
Thirty-five RA patients with the disease history from 3 months to 15 years were examined. Seropositive RA was diagnosed in 19 patients, seronegative in 16 ones. A control group comprised 14 subjects aged 18-29. The marrow cells culturing occurred in the system agar drop-liquid. Compared to the reference group, in RA patients' precursor cells of granulomonocytopoiesis there was inhibited capacity for colony and cluster formation and predominance of small-size cell colonies. Colony-formation of marrow cells from seropositive RA patients was less active than in seronegative RA variant. Morphologic evaluation of the agar cultures showed prevalence of neutrophil colonies in the marrow cultures, though RA samples differed from those of healthy controls by a trend to a decline in the number of monocyte-macrophage cellular aggregates against similar proportions of eosinophilic colonies and clusters.


Prevalence and correlates of alcohol use and DSM-IV alcohol dependence in the United States: results of the National Longitudinal Alcohol Epidemiologic Survey.
The purpose of this study was to present updated estimates of the prevalence of, and to examine the correlates of, alcohol use and DSM-IV alcohol dependence in a representative sample of the U.S. population. This study was based on the National Institute on Alcohol Abuse and Alcoholism's National Longitudinal Alcohol Epidemiologic Survey (NLAES), a representative sample (N = 42,862) of the United States population aged 18 years and older. The prevalence of lifetime alcohol use was 66.0%, with 44.4% of the respondents reporting alcohol use during the past 12 months. Lifetime and 12-month prevalences of alcohol dependence were estimated at 13.3% and 4.4%, respectively. Men were significantly more likely than women to use alcohol, and alcohol use and dependence were much more common among cohorts born after Prohibition and after World War II. Members of the youngest cohorts, between the ages of 18 and 24 years at the time of the interview, were more likely to use drugs, to become dependent and to persist in dependence compared to the older cohorts. In addition, the conditional probability of dependence among users was greatest in Cohort 1 (born between 1968 and 1974) after early adolescence compared to Cohort 2 (born between 1958 and 1967), despite the finding that the probability of lifetime use was lower in Cohort 1 compared to Cohort 2. The sociodemographic correlates of first use, onset of dependence and persistence of dependence varied as a function of the stage of progression. Implications of these findings are discussed in terms of changes over time in drinking patterns, dependence liability and vulnerability among recent alcohol users.


XacFhaB adhesin, an important Xanthomonas citri ssp. citri virulence factor, is recognized as a pathogen-associated molecular pattern.
Adhesion to host tissue is one of the key steps of the bacterial pathogenic process. Xanthomonas citri ssp. citri possesses a non-fimbrial adhesin protein, XacFhaB, required for bacterial attachment, which we have previously demonstrated to be an important virulence factor for the development of citrus canker. XacFhaB is a 4753-residue-long protein with a predicted β-helical fold structure, involved in bacterial aggregation, biofilm formation and adhesion to the host. In this work, to further characterize this protein and considering its large size, XacFhaB was dissected into three regions based on bioinformatic and structural analyses for functional studies. First, the capacity of these protein regions to aggregate bacterial cells was analysed. Two of these regions were able to form bacterial aggregates, with the most amino-terminal region being dispensable for this activity. Moreover, XacFhaB shows features resembling pathogen-associated molecular patterns (PAMPs), which are recognized by plants. As PAMPs activate plant basal immune responses, the role of the three XacFhaB regions as elicitors of these responses was investigated. All adhesin regions were able to induce basal immune responses in host and non-host plants, with a stronger activation by the carboxyl-terminal region. Furthermore, pre-infiltration of citrus leaves with XacFhaB regions impaired X. citri ssp. citri growth, confirming the induction of defence responses and restraint of citrus canker. This work reveals that adhesins from plant pathogens trigger plant defence responses, opening up new pathways for the development of protective strategies for disease control.


MRI measurement of regional lung deposition in mice exposed nose-only to nebulized superparamagnetic iron oxide nanoparticles.
Superparamagnetic iron oxide nanoparticles show potential in magnetic targeting of inhaled aerosols to localized sites within the lung. These particles are also used as contrast agents in magnetic resonance imaging (MRI). In the present work, we examine the feasibility of measuring regional lung deposition of iron oxide nanoparticles using MRI. Mice were exposed nose-only to nebulized superparamagnetic iron oxide nanoparticles. The droplet size distribution in the inhalation chamber was measured using a time-of-flight device. Regional concentrations of iron in the left and right lung were assessed with MRI by measuring the longitudinal relaxation times (T(1)) of the lung tissue in exposed mice, compared to a baseline group. Regional concentrations of iron in the lungs of the mice ranged from 1.1 +/- 0.8 microg/cm(3) (mean +/- one standard deviation, n = 6) in peripheral lung regions to 2.7 +/- 1.4 microg/cm(3) in the central lung, with no significant difference between the left and right lung. The nebulized droplets in the inhalation chamber had mass median aerodynamic diameter (MMAD) of 5.6 +/- 0.8 microm, with a geometric standard deviation (GSD) of 1.30 +/- 0.03 (both values expressed as mean +/- one standard deviation, n = 6). MRI shows promise for in vivo measurement of regional lung concentrations of superparamagnetic iron oxide nanoparticles, and may be useful in studies of lung deposition and clearance.


Genetic control of susceptibility to Cryptococcus neoformans in mice.
Inbred mice injected intravenously with 5 x 10(6) cells of Cryptococcus neoformans showed two patterns of survival: sensitive (A/WySn, A.BY, A/J, DBA/2J, NZB/B1NJ, and SWR/J) and resistant [C57BL/10Sn, B10.A, B10.A (2R), B10.S (7R),C57BR/cdJ, C58/J, C3H/HeJ, BALB/c, DBA/1J, and SJL/J]. Relative susceptibility based on survival time was shown to correspond to differences obtained for 50% lethal dose values. Either decreasing the dose of organisms or changing to the intraperitoneal route of inoculation resulted in prolonged survival times, but neither change affected the observed patterns of survival. F1 hybrids between different sensitive strains were also sensitive, whereas F1 hybrids between sensitive and resistant strains were resistant, indicating a dominant mode of inheritance. Sensitivity and resistance were shown to be under single gene control by segregation analysis in F2 progeny produced by inbreeding (B10.A x A/WySn)F1 hybrids and in (F1 x A/WySn) backcross progeny. Blood obtained from parental strains, F1, F2, and backcross hybrids was tested for the presence or absence of hemolytic complement. Mice lacking hemolytic complement activity in their sera are homozygous for the Hc(0) allele at the Hc locus on chromosome 2 and are deficient in the complement component C5. A 1:1 correspondence was found between C5 deficiency and sensitivity to C. neoformans. Resistance was shown to cosegregate with the presence of hemolytic complement in the F2 and the backcross progenies.


[Model of a chronic Vibrio cholerae carrier based on gnotobiotic rats].
Germ-free monoflora (contaminated with nonpathogenic spore-bearing bacillus) and common albino rats (OFA) were infected with V. cholera El Tor, of Ogava and Inaba serological types (6 milliard microbial cells per 1.5 ml of physiological solution per rat). Approximately one week after the infection the number of vibrios reached hundreds of millions per 1 g of feces and persisted at this level for over 100 days (observation period). Newborn rats were infected by natural way from adult vibrio carriers and also became vibrio-carriers. The number of vibrios excretedby the animals which were germ-free and monoflora before the infection was approximately the same. Cholera vibrios perished completely in the enteric tract and were never revealed in the feces of common (control) rats.


Characteristics, primary treatment, and survival of MDS/MPN with neutrophilia: a population-based study.
MDS/ MPN with neutrophilia, until recently called atypical chronic myeloid leukemia (aCML), being part of the myelodysplastic/myeloproliferative neoplasms is a very rare disease with poor prognosis. Although emerging data reveal its cytogenetic and molecular profile, integrated survival and treatment data remain scarce. We analyzed a cohort of 347 adult patients diagnosed with MDS/ MPN with neutrophilia, registered in the Netherlands Cancer Registry between 2001 and 2019. Our demographic baseline data align with other cohorts. We observed cytogenetic aberrations exclusively in patients aged >65 years, with trisomy 8 being the most common abnormality. We identified 16 distinct molecular mutations, with some patients (16/101) harboring up to 3 different mutations; ASXL1 being the most frequent one (22%). In a multivariable Cox regression analysis, only age, hemoglobin level and allogeneic hematopoietic stem cell transplant (alloHSCT) were associated with overall survival (>65 years of age HR 1.85, P=0.001 and alloHSCT HR 0.51, P=0.039). As no other treatment modality, seemed to impact survival and might cause toxicity, we propose that all patients eligible for alloHSCT should whenever possible receive an allogeneic transplant. It is imperative that we strive to improve outcomes for patients not eligible for alloHSCT. Tackling this challenge requires international collaborative efforts to conduct prospective intervention studies.


Generation of mouse induced pluripotent stem cells from different genetic backgrounds using Sleeping beauty transposon mediated gene transfer.
Induced pluripotent stem (iPS) cell technology involves reprogramming somatic cells to a pluripotent state. The original technology used to produce these cells requires viral gene transduction and results in the permanent integration of exogenous genes into the genome. This can lead to the development of abnormalities in the derived iPS cells. Here, we report that non-viral transfection of a Sleeping Beauty (SB) transposon containing the coding sequences Oct3/4 (Pouf1), Sox-2, Klf-4 and c-Myc (OSKM) linked with 2A peptides, can reprogram mouse fibroblasts. We have established reprogrammed mouse cell lines from three different genetic backgrounds: (1) ICR-outbred, (2) C57BL/6-inbred and (3) F1-hybrid (C57BL/6 x DBA/2J), with parallel robust expression of all exogenous (Oct3/4, Sox-2, Klf-4, and c-Myc) and endogenous (e.g. Oct3/4 and Nanog) pluripotency genes. The iPS cell lines exhibited characteristics typical for undifferentiated embryonic stem (ES) cell lines: ES cell-like morphology, alkaline phosphatase (ALP) positivity and gene expression pattern (shown by reverse transcription PCR, and immunofluorescence of ES cell markers-e.g. Oct3/4, SSEA1, Nanog). Furthermore, cells were able to form embryoid bodies (EBs), to beat rhythmically, and express cardiac (assayed by immunofluorescence, e.g. cardiac Troponin T, desmin) and neuronal (assayed by immunofluorescence e.g. nestin, Tuj1) markers. The in vitro differentiation potential was found to be the highest in the ICR-derived iPS lines (ICR-iPS). Interestingly, the ICR-iPS lines had even higher differentiation potential than the ICR-ES cell lines: the rate of EBs forming rhythmically beating cardiomyocytes was 4% in ICR-ES and 79% in ICR-iPS cells, respectively. In vivo, the ICR and F1 hybrid iPS cells formed chimeras and one of the iPS cells from the F1 hybrid background transmitted to the germline. Our results suggest that iPS technology may be useful for generating pluripotent stem cells from genetic backgrounds of which good quality ES cell generation is difficult. These studies provide insights into viral-free iPS technology and may contribute towards defining future cell-based therapies, drug-screening methods and production of transgenic animals using genetically modified iPS cells.


Nonspecific complement activation by streptococcal structures. II. Properdin-independent initiation of the alternate pathway.
Complement consumption by isolated membranes and walls from Group A streptococci and various other gram-positive microbes has been tested. These microbial structures were found to activate the alternate complement pathway. However, unlike endotoxin, inulin, or other plant polysaccharides, activation of complement by our material was found to bypass properdin. The activating factor(s) also differs from cobra venom in its/their requirement for factor D. Preliminary experiments suggest this factor isolated from membranes to be a protein and to have a mol wt greater than 40-60,000 daltons. Our studies have led us to speculate that the phylogenetic role of the alternate complement pathway may be the primordial nonspecific defense system which has retained certain fundamental aspects up to the present time.


Depression Status Is Associated with Functional Decline Over 1-Year Following Acute Stroke.
We investigated the independent association of depression status at 3 and 12 months after stroke and functional decline. Data were obtained as part of the multicenter Adherence eValuation After Ischemic stroke Longitudinal (AVAIL) registry. Depression was assessed with the Patient Health Questionnaire-8 (depression, PHQ-8 ≥ 10), and functional status was assessed with the modified Rankin score (mRS) at 3 and 12 months following hospitalization for ischemic stroke. We used logistic regression analyses to evaluate the independent association between the change in depression rating and the change in mRS. Among 1444 patients, 75% did not have depression at either time point, 9.2% had persistent depression, 8.7% had resolving depression, and 7% had incident depression at 12 months. After covariate adjustment, depression status at 3 and 12 months remained associated with worsening mRS (P = .01). Compared with patients without depression, those with resolving depression were less likely to have a worsening mRS (odds ratio [OR] = .49, 95% confidence interval [CI]: .29-0.83). There was no difference in functional decline between those with no depression and those with persistent depression; however, those with persistent depression had worse mRS at both time points (median mRS: 2.5 [Q1-Q3: 2-3] at 3 months; 2 [2-3] at 12 months) than those with no depression (mRS: 1 [0-2] at both 3 and 12 months), P < .0001. Patients with resolving depression in the first year after stroke were less likely to have functional deterioration than those without depression. Greater functional impairment was present in the setting of depression.


The effects of various diets on glycemic outcomes during pregnancy: A systematic review and network meta-analysis.
Evidence to support dietary modifications to improve glycemia during pregnancy is limited, and the benefits of diet beyond limiting gestational weight gain is unclear. Therefore, a systematic review and network meta-analysis of randomized trials was conducted to compare the effects of various common diets, stratified by the addition of gestational weight gain advice, on fasting glucose and insulin, hemoglobin A1c (HbA1c), and homeostatic model assessment for insulin resistance (HOMA-IR) in pregnant women. MEDLINE, EMBASE, Cochrane database, and reference lists of published studies were searched through April 2017. Randomized trials directly comparing two or more diets for ≥2-weeks were eligible. Bayesian network meta-analysis was performed for fasting glucose. Owing to a lack of similar dietary comparisons, a standard pairwise meta-analysis for the other glycemic outcomes was performed. The certainty of the pooled effect estimates was assessed using the GRADE tool. Twenty-one trials (1,865 participants) were included. In general, when given alongside gestational weight gain advice, fasting glucose improved in most diets compared to diets that gave gestational weight gain advice only. However, fasting glucose increased in high unsaturated or monounsaturated fatty acids diets. In the absence of gestational weight gain advice, fasting glucose improved in DASH-style diets compared to standard of care. Although most were non-significant, similar trends were observed for these same diets for the other glycemic outcomes. Dietary comparisons ranged from moderate to very low in quality of evidence. Alongside with gestational weight gain advice, most diets, with the exception of a high unsaturated or a high monounsaturated fatty acid diet, demonstrated a fasting glucose improvement compared with gestational weight gain advice only. When gestational weight gain advice was not given, the DASH-style diet appeared optimal on fasting glucose. However, a small number of trials were identified and most dietary comparisons were underpowered to detect differences in glycemic outcomes. Further studies that are high in quality and adequately powered are needed to confirm these findings. PROSPERO CRD42015026008.


[The mean timing of periodontic care rendering].
The time-studies demonstrated that the periodontologist spend 30.3 +/- 2.6 minutes on the primary ambulatory visit of patient and 16.4 +/- 0.9 minutes on the revisit of patient (non-registering time spending on preventive and curative activities). Time spending on curative preventive activities in each group of patients with periodontal diseases depended on both the severity of inflammatory destructive processes in periodontium and therapy stage.


Genetic and clinical characteristics of PROM1-related retinal degeneration in Korean.
This scientific report aims to comprehensively describe the genetic and clinical characteristics of PROM1-related retinal degeneration in Korean patients. Medical records of patients diagnosed with retinal dystrophy who underwent comprehensive ophthalmologic examination and genetic testing at Samsung Medical Center between January 2016 and April 2023 were retrospectively reviewed. Genetic testing included targeted gene panel sequencing and Sanger sequencing, with diagnosis based on the presence of a "Likely Pathogenic" or "Pathogenic Variant" in the PROM1 gene, as determined by the ACMG criteria. The study identified seven patients from five unrelated families with PROM1-related retinal degeneration, all carrying the autosomal dominant variant PROM1 p.R373C; no other PROM1 gene variants were detected. All patients exhibited degenerative retinal area within the macula, with peripheral retinal degeneration observed in five patients. Substantial interfamilial and intrafamilial variability was observed in the extent of macular and peripheral degeneration. Ultra-widefield autofluorescence imaging and fluorescein angiography aided in the detection of mild peripheral degeneration in one case. In conclusion, the autosomal dominant variant PROM1 p.R373C constitutes a significant proportion of PROM1-related retinal degeneration cases in the Korean population. The observed clinical heterogeneity may suggests the potential influence of additional genetic, epigenetic, and environmental factors on disease phenotypes.


Comparative Study of Auto Plan and Manual Plan for Nasopharyngeal Carcinoma Intensity-Modulated Radiation Therapy.
Auto planning might reduce the manual time required for the optimization and could also potentially improve the overall plan quality. The aim of this study is to demonstrate the statistical comparison of automatic (AU) and manually (MA) generated nasopharyngeal carcinoma (NPC) intensity-modulated radiation therapy (IMRT) plans. The study included 105 nasopharyngeal carcinoma patients, admitted to our hospital. The patients underwent IMRT treatments. The clinically delivered plans were performed with Eclipse (Version 11.0) using manual optimization. The same plans were optimized successively in PinnacleTM3 (version 9.10) treatment planning system using the auto plan software package module. D95 (dose of 95% volume) and D98 (dose of 98% volume) were calculated for the targets and maximum dose (Dmax) and mean dose (Dmean) for the organ at risks (OARs); moreover, the average doses of each target and OARs for 105 patients were evaluated. There is no significant difference in the homogeneity of the target between AU and MA treatment plans, while a significant difference is observed for what is concerning the OARs or most of OARs in 105 patients, OAR doses were significantly reduced in AU plan. For OARs which have no significant difference between AU and MA plans are highlighted, the mean dose of OARs in AU plans was at least not higher than MA plans. Nasopharyngeal carcinoma IMRT plans made by an automatic planning tool met the clinical requirements for target prescription dose; moreover, the dose of normal tissues was lower than in MA plans. Clinical physicists' time can be saved and the influence of factors such as the lack of experience in treatment planning can be avoided.


Self-assembled wiggling nano-structures and the principle of maximum entropy production.
While behavior of equilibrium systems is well understood, evolution of nonequilibrium ones is much less clear. Yet, many researches have suggested that the principle of the maximum entropy production is of key importance in complex systems away from equilibrium. Here, we present a quantitative study of large ensembles of carbon nanotubes suspended in a non-conducting non-polar fluid subject to a strong electric field. Being driven out of equilibrium, the suspension spontaneously organizes into an electrically conducting state under a wide range of parameters. Such self-assembly allows the Joule heating and, therefore, the entropy production in the fluid, to be maximized. Curiously, we find that emerging self-assembled structures can start to wiggle. The wiggling takes place only until the entropy production in the suspension reaches its maximum, at which time the wiggling stops and the structure becomes quasi-stable. Thus, we provide strong evidence that maximum entropy production principle plays an essential role in the evolution of self-organizing systems far from equilibrium.


Integrated Polypyrrole@Sulfur@Graphene Aerogel 3D Architecture via Advanced Vapor Polymerization for High-Performance Lithium-Sulfur Batteries.
Although lithium-sulfur batteries have been regarded as the most promising candidates for next-generation energy storage devices with high specific capacity, their rapid capacity decay, mainly caused by volume expansion and dissolution of polysulfides, has limited their practical applications. Aiming at these issues, herein, we have designed an ideal three-dimensional (3D)-structured polypyrrole@sulfur@graphene aerogel (PPy@S@GA) as an efficient sulfur host via advanced pyrrole vapor polymerization. GA with an interconnected 3D porous structure provides an excellent conductive network for electrons and a channel for ion transfer, as well as a physical barrier or absorber for the polysulfides. In addition, physical confinement and chemical adsorption are further strengthened by the PPy coating layer with polar nitrogen. The electrode with the PPy@S@GA 3D structure delivered a superior initial discharge specific capacity of 1135 mA h g-1 and a capacity of 741 mA h g-1 after 500 cycles at a rate of 0.5 C, with capacity fading as low as 0.031% per cycle, superior to both a sulfur electrode and a S@GA electrode. These results demonstrate that GA as a sulfur host further coated with PPy is a promising cathode for pursuing high-performance Li-S batteries.


Epidemiologic background of hand hygiene and evaluation of the most important agents for scrubs and rubs.
The etiology of nosocomial infections, the frequency of contaminated hands with the different nosocomial pathogens, and the role of health care workers' hands during outbreaks suggest that a hand hygiene preparation should at least have activity against bacteria, yeasts, and coated viruses. The importance of efficacy in choosing the right hand hygiene product is reflected in the new Centers for Disease Control and Prevention guideline on hand hygiene (J. M. Boyce and D. Pittet, Morb. Mortal. Wkly. Rep. 51:1-45, 2002). The best antimicrobial efficacy can be achieved with ethanol (60 to 85%), isopropanol (60 to 80%), and n-propanol (60 to 80%). The activity is broad and immediate. Ethanol at high concentrations (e.g., 95%) is the most effective treatment against naked viruses, whereas n-propanol seems to be more effective against the resident bacterial flora. The combination of alcohols may have a synergistic effect. The antimicrobial efficacy of chlorhexidine (2 to 4%) and triclosan (1 to 2%) is both lower and slower. Additionally, both agents have a risk of bacterial resistance, which is higher for chlorhexidine than triclosan. Their activity is often supported by the mechanical removal of pathogens during hand washing. Taking the antimicrobial efficacy and the mechanical removal together, they are still less effective than the alcohols. Plain soap and water has the lowest efficacy of all. In the new Centers for Disease Control and Prevention guideline, promotion of alcohol-based hand rubs containing various emollients instead of irritating soaps and detergents is one strategy to reduce skin damage, dryness, and irritation. Irritant contact dermatitis is highest with preparations containing 4% chlorhexidine gluconate, less frequent with nonantimicrobial soaps and preparations containing lower concentrations of chlorhexidine gluconate, and lowest with well-formulated alcohol-based hand rubs containing emollients and other skin conditioners. Too few published data from comparative trials are available to reliably rank triclosan. Personnel should be reminded that it is neither necessary nor recommended to routinely wash hands after each application of an alcohol-based hand rub. Long-lasting improvement of compliance with hand hygiene protocols can be successful if an effective and accessible alcohol-based hand rub with a proven dermal tolerance and an excellent user acceptability is supplied, accompanied by education of health care workers and promotion of the use of the product.


Role of protocol ultrasonography for detecting biliary stricture in adult living donor liver transplantation recipients.
The role of protocol ultrasonography (US) in detecting biliary stricture (BS) after adult living donor liver transplantation (ALDLT) remains to be clarified. We reviewed 268 ALDLT cases with BS to assess the role of protocol US. The sensitivity and specificity of serum values of gamma-glutamyl transpeptidase (G-GTP) and alkaline phosphatase (ALP) as indicators of BS were evaluated and compared with the US findings. Diagnosis of BS was made by drip-infusion cholangiography or direct endoscopic retrograde cholangiography. Fifty patients (19%) developed BS; anastomotic stricture in 46 and non-anastomotic in 4. The incidence of BS was not affected by the method of bile duct reconstruction or the type of graft. Protocol US detected dilated bile ducts (>or= 3 mm) in 45 cases (90%) with BS. The mean diameter of bile ducts in the BS group was 5 +/- 2 mm, which was greater than that of patients without BS (2 +/- 1 mm, P < 0.001). When the bile duct diameter was over 3 mm, the sensitivity and specificity of protocol US for the diagnosis of BS was 96% and 91%, respectively, whereas those of G-GTP were 60% and 74% when the values were more than 5-fold greater than the upper normal limit, and those of ALP were 56% and 62% when the values were 3-fold greater than the upper normal limit. The bile duct diameter and the G-GTP and ALP values did not correlate. US might be a useful and efficient imaging method to follow-up patients after ALDLT.


Regular and frequent feedback of specific clinical criteria delivers a sustained improvement in the management of diabetic ketoacidosis .
Efficient management of diabetic ketoacidosis (DKA) improves outcomes and reduces length of stay. While clinical audit improves the management of DKA, significant and sustained improvement is often difficult to achieve. We aimed to improve the management of DKA in our trust through the implementation of quality improvement methodology. Five specific targets (primary drivers: fluid prescription, fixed rate intravenous insulin infusion, glucose measurement, ketone measurement and specialist referral) were selected following a baseline audit. Interventions (secondary drivers) were developed to improve these targets and included monthly feedback to departments of emergency medicine, acute medicine, and diabetes. Following our intervention, the mean average duration of DKA reduced from 22.0 hours to 10.2 hours. We demonstrate that regular audit cycles with interventions introduced through the plan-do-study-act model is an effective way to improve the management of DKA.


Using distance transform based algorithms for extracting measures of the fiber network in volume images of paper.
Nowadays volume images are frequently used in many applications. Volume images of paper can be analyzed to increase the understanding of the complexity of the fiber network in paper and its effect on the optical and mechanical properties of paper. We show how curve and surface representations of the fiber, the fiber wall, and the fiber lumen can be computed using distance transform based algorithms. These representations are used for easy computation of wall thickness, degree of collapse, fiber length, slenderness ratio, fiber curl, and torsional resistance for the fibers. Free-fiber segments are identified, again using a distance transform based algorithm. Finally, we show tools for qualitative visual inspection of the fibers. The methods are evaluated and illustrated using both sets of synthetic and of real data. In addition to the analysis of the fiber network in paper, they can be used in many other applications where shape analysis of elongated objects is to be performed.


Functional modules distinguish human induced pluripotent stem cells from embryonic stem cells.
It has been debated whether human induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs) express distinctive transcriptomes. By using the method of weighted gene co-expression network analysis, we showed here that iPSCs exhibit altered functional modules compared with ESCs. Notably, iPSCs and ESCs differentially express 17 modules that primarily function in transcription, metabolism, development, and immune response. These module activations (up- and downregulation) are highly conserved in a variety of iPSCs, and genes in each module are coherently co-expressed. Furthermore, the activation levels of these modular genes can be used as quantitative variables to discriminate iPSCs and ESCs with high accuracy (96%). Thus, differential activations of these functional modules are the conserved features distinguishing iPSCs from ESCs. Strikingly, the overall activation level of these modules is inversely correlated with the DNA methylation level, suggesting that DNA methylation may be one mechanism regulating the module differences. Overall, we conclude that human iPSCs and ESCs exhibit distinct gene expression networks, which are likely associated with different epigenetic reprogramming events during the derivation of iPSCs and ESCs.


Health effects of Vaccinium myrtillus L.: evaluation of efficacy and technological strategies for preservation of active ingredients.
Bilberries are a rich dietary source of various phytonutrients, including anthocyanins which contribute greatly to their antioxidant capacity and have demonstrated a broad spectrum of biomedical functions. These include protection against cardiovascular disorders, age-induced oxidative stress, inflammatory responses and several degenerative diseases. Berry anthocyanins also improve neuronal and cognitive brain functions, ocular health as well as protecting genomic DNA integrity. In recent years, sales of many dietary supplements/pharmaceutical products containing anthocyanins in various dosages and formulations have been made by advertising their wide range of beneficial effects. However, there is a heightened risk of distributing deteriorated formulations to consumers due to lax regulations, in particular those applicable to phytochemical characterization and extract standardization, and in terms of quality regarding the stability of anthocyanins. Anthocyanin pigments readily degrade during industrial processing and this can have a dramatic impact on color quality and may also affect nutritional/pharmaceutical properties. This review aims to summarize the main health effects of bilberry extract used in several food supplements/pharmaceutical formulations focusing on some important aspects of anthocyanin degradation during processing and storage. It will also describe the main technological strategies which can give active ingredients greater stability, solubility and dispersibility in order to enhance formulation quality which is of great interest to the consumer and industry due to its direct and indirect impact on consumer health.


Analysis of the sakacin P gene cluster from Lactobacillus sake Lb674 and its expression in sakacin-negative Lb. sake strains.
Sakacin P is a small, heat-stable, ribosomally synthesized peptide produced by certain strains of Lactobacillus sake. It inhibits the growth of several Gram-positive bacteria, including Listeria monocytogenes. A 7.6 kb chromosomal DNA fragment from Lb. sake Lb674 encompassing all genes responsible for sakacin P production and immunity was sequenced and introduced into Lb. sake strains Lb790 and Lb706X which are bacteriocin-negative and sensitive to sakacin P. The transformants produced sakacin P in comparable amounts to the parental strain, Lb674. The sakacin P gene cluster comprised six consecutive genes: sppK, sppR, sppA, spiA, sppT and sppE, all transcribed in the same direction. The deduced proteins SppK and SppR resembled the histidine kinase and response regulator proteins of bacterial two-component signal transducing systems of the AgrB/AgrA-type. The genes sppA and spiA encoded the sakacin P preprotein and the putative immunity protein, respectively. The predicted proteins SppT and SppE showed strong similarities to the proposed transport proteins of several other bacteriocins and to proteins implicated in the signal-sequence-independent export of Escherichia coli haemolysin A. Deletion and frameshift mutation analyses showed that sppK, sppT and sppE were essential for sakacin P production in Lb706X. The putative SpiA peptide was shown to be involved in immunity to sakacin P. Analogues of sppR and spiA were found on the chromosomes of Lb. sake Lb706X and Lb790, indicating the presence of an incomplete spp gene cluster in these strains.


Degenerative Lumbar Spine Disease: Estimating Global Incidence and Worldwide Volume.
Meta-analysis-based calculation. Lumbar degenerative spine disease (DSD) is a common cause of disability, yet a reliable measure of its global burden does not exist. We sought to quantify the incidence of lumbar DSD to determine the overall worldwide burden of symptomatic lumbar DSD across World Health Organization regions and World Bank income groups. We used a meta-analysis to create a single proportion of cases of DSD in patients with low back pain (LBP). Using this information in conjunction with LBP incidence rates, we calculated the global incidence of individuals who have DSD and LBP (ie, their DSD has neurosurgical relevance) based on the Global Burden of Disease 2015 database. We found that 266 million individuals (3.63%) worldwide have DSD and LBP each year; the highest and lowest estimated incidences were found in Europe (5.7%) and Africa (2.4%), respectively. Based on population sizes, low- and middle-income countries have 4 times as many cases as high-income countries. Thirty-nine million individuals (0.53%) worldwide were found to have spondylolisthesis, 403 million (5.5%) individuals worldwide with symptomatic disc degeneration, and 103 million (1.41%) individuals worldwide with spinal stenosis annually. A total of 266 million individuals (3.63%) worldwide were found to have DSD and LBP annually. Significantly, data quality is higher in high-income countries, making overall quantification in low- and middle-income countries less complete. A global effort to address degenerative conditions of the lumbar spine in regions with high demand is important to reduce disability.


Vaping product exposure system (VaPES): a novel in vitro aerosol deposition system.
Due to recent increases in the use of vaping devices, there is a high demand for research addressing the respiratory health effects of vaping products. Given the constantly changing nature of the vaping market with new devices, flavors, metals, and other chemicals rapidly emerging, there is a need for inexpensive and highly adaptable vaping device exposure systems. Here, we describe the design and validation of a novel in vitro aerosol exposure system for toxicity testing of vaping devices. We developed an inexpensive, open-source in vitro vaping device exposure system that produces even deposition, can be adapted for different vaping devices, and allows for experiments to be performed under physiological conditions. The system was then validated with deposition testing and a representative exposure with human bronchial epithelial cells (hBECs). The Vaping Product Exposure System (VaPES) produced sufficient and uniform deposition for dose-response studies and was precise enough to observe biological responses to vaping exposures. VaPES was adapted to work with both pod and cartridge-based vaping devices. We have designed and validated a novel vaping device exposure system that will eliminate the need to use high-cost commercial exposure systems, lowering the barrier to entry of physiologically relevant vaping studies.


[Patterns of maternal behavior of rats genetically selected for opposite coping styles].
Maternal behavior of Koltushi High- and Low-avoidance (KHA and KLA) rats strains was assessed over the prewealing period (days 6-21). Ten litters of each strain were observed during the light phase of the light/dark cycle. In a series of experiments, rat pups were taken from the maternal nest and placed into the opposite corner of the cage. The following parameters of the maternal behavior were recorded: the latency of the first contact with the pups, pup licking, latency of carrying/retrieval of the first pup back to the nest, time of returning to the nest of the whole litter, and mother's spontaneous behavior (grooming and locomotion time) over the course of 10 min of observation. KLA mothers stayed with their pups and took care of them more frequently than KHA mothers during the light phase of the circadian cycle. Time of self-grooming was significantly higher in KHA rats. The highest levels of self-grooming of mothers was registered on the first day of testing. The latency of the first coming to pups after their removal from the nest was lower in KHA rats, but they needed more time to returned all pups to the nest. The experimental evidence suggests that the KHA but not KLA rats with the active coping style and higher stress reactivity display disorders in maternal behavior in a novel situation.


Expression of activated Notch3 in transgenic mice enhances generation of T regulatory cells and protects against experimental autoimmune diabetes.
Thymic-derived dysregulated tolerance has been suggested to occur in type 1 diabetes via impaired generation of CD4(+)CD25(+) T regulatory cells, leading to autoimmune beta cell destruction. In this study, we demonstrate that Notch3 expression is a characteristic feature of CD4(+)CD25(+) cells. Furthermore, streptozotocin-induced autoimmune diabetes fails to develop in transgenic mice carrying the constitutively active intracellular domain of Notch3 in thymocytes and T cells. The failure to develop the disease is associated with an increase of CD4(+)CD25(+) T regulatory cells, accumulating in lymphoid organs, in pancreas infiltrates and paralleled by increased expression of IL-4 and IL-10. Accordingly, CD4(+) T cells from Notch3-transgenic mice inhibit the development of hyperglycemia and insulitis when injected into streptozotocin-treated wild-type mice and display in vitro suppressive activity. These observations, therefore, suggest that Notch3-mediated events regulate the expansion and function of T regulatory cells, leading to protection from experimental autoimmune diabetes and identify the Notch pathway as a potential target for therapeutic intervention in type 1 diabetes.


Use of special education services among children with and without congenital gastrointestinal anomalies.
Our objective was to evaluate the relationship between congenital gastrointestinal anomalies requiring neonatal surgery and neurodevelopmental outcome. Among the children born in metropolitan Atlanta during 1982-2001 who survived to age 1 year (N = 762,824), we identified children with congenital gastrointestinal anomalies via linkage with the Metropolitan Atlanta Congenital Defects Program and children who received special education services via linkage with the Special Education Database of Metropolitan Atlanta. Several modest increases in special education service use were observed among children with isolated congenital gastrointestinal anomalies; no association was statistically significant. Among children with Hirschsprung disease, gastroschisis, esophageal atresia, intestinal malrotation, bowel atresia, or imperforate anus who had multiple anomalies, we observed statistically significant increases in special education service use.


Probabilistic cell/domain-type assignment of spatial transcriptomics data with SpatialAnno.
In the analysis of both single-cell RNA sequencing (scRNA-seq) and spatially resolved transcriptomics (SRT) data, classifying cells/spots into cell/domain types is an essential analytic step for many secondary analyses. Most of the existing annotation methods have been developed for scRNA-seq datasets without any consideration of spatial information. Here, we present SpatialAnno, an efficient and accurate annotation method for spatial transcriptomics datasets, with the capability to effectively leverage a large number of non-marker genes as well as 'qualitative' information about marker genes without using a reference dataset. Uniquely, SpatialAnno estimates low-dimensional embeddings for a large number of non-marker genes via a factor model while promoting spatial smoothness among neighboring spots via a Potts model. Using both simulated and four real spatial transcriptomics datasets from the 10x Visium, ST, Slide-seqV1/2, and seqFISH platforms, we showcase the method's improved spatial annotation accuracy, including its robustness to the inclusion of marker genes for irrelevant cell/domain types and to various degrees of marker gene misspecification. SpatialAnno is computationally scalable and applicable to SRT datasets from different platforms. Furthermore, the estimated embeddings for cellular biological effects facilitate many downstream analyses.


MCF7/LCC9: an antiestrogen-resistant MCF-7 variant in which acquired resistance to the steroidal antiestrogen ICI 182,780 confers an early cross-resistance to the nonsteroidal antiestrogen tamoxifen.
Acquired resistance to antiestrogens is a major problem in the clinical management of initially endocrine responsive metastatic breast cancer. We have shown previously that estrogen-independent and -responsive MCF7/LCC1 human breast cancer cells selected for resistance to the triphenylethylene tamoxifen produce a variant (MCF7/LCC2) that retains sensitivity to the steroidal antiestrogen ICI 182,780 (N. Brunner et al., Cancer Res., 53: 3229-3232, 1993). We have now applied stepwise selections in vitro from 10 pM to 1 microM ICI 182,780 against MCF7/LCC1 and obtained a stable ICI 182,780-resistant variant designated MCF7/LCC9. In contrast to 4-hydroxytamoxifen-selected MCF7/LCC2 cells, MCF7/LCC9 cells exhibit full cross-resistance to tamoxifen, despite never having been exposed to this drug. Significantly, tamoxifen cross-resistance arose early in the selection, appearing following selection against only 0.1 nM ICI 182,780. Although limited resistance to ICI 182,780 also was observed, full ICI 182,780 resistance was not detected until the selective pressure increased to 100 nM ICI 182,780. Cross-resistance to tamoxifen persisted throughout these additional selections. Despite their antiestrogen cross-resistance, MCF7/LCC9 cells retain a level of estrogen receptor expression comparable to that of their parental MCF7/LCC1 cells. Whereas MCF7/LCC1 cells retain an estrogen-inducible expression of progesterone receptors, MCF7/LCC9 cells exhibit an up-regulated expression of both progesterone receptor mRNA and protein that is no longer estrogen responsive. Estrogen-independent and -responsive components of the MCF7/LCC9 phenotype are apparent in vivo. These cells form slowly growing tumors in ovariectomized athymic nude mice but respond mitogenically upon estrogenic supplementation. The in vivo growth of MCF7/LCC9 tumors is not affected by treatment with ICI 182,780. Although there is some evidence of tamoxifen stimulation of tumor growth, this did not reach statistical significance. If this pattern of cross-resistance occurs in some breast cancer patients, administering triphenylethylene antiestrogens as a first-line therapy with a cross-over to steroidal compounds upon recurrence may be advantageous.


A systematic review of contrast-enhanced computed tomography calcium scoring methodologies and impact of aortic valve calcium burden on TAVI clinical outcomes.
Different methodologies have been used to assess the role of AV calcification (AVC) on TAVI outcomes. This systematic review aims to describe the burden of AVC, synthesize the different methods of calcium score quantification, and evaluate the impact of AVC on outcomes after TAVI. We included studies of TAVI patients who had reported AV calcium scoring by contrast-enhanced multidetector CT and the Agatston method. The impact of calcification on TAVI outcomes without restrictions on follow-up time or outcome type was evaluated. Results were reported descriptively, and a meta-analysis was conducted when feasible. Sixty-eight articles were included, with sample sizes ranging from 23 to 1425 patients. Contrast-enhanced calcium scoring was reported in 30 studies, calcium volume score in 28 studies, and unique scoring methods in two. All studies with calcium volume scores had variable protocols, but most utilized a modified Agatston method with variable attenuation threshold values of 300-850 HU. Eight studies used the Agatston method, with the overall mean AV calcium score in studies published from 2010 to 2012 of 3342.9 AU [95%CI: 3150.4; 3535.4, I2 = 0%]. The overall mean score was lower and heterogenous in studies published from 2014 to 2020 (2658.9 AU [95% CI: 2517.3; 2800.5, I2 = 79%]. Most studies reported a positive association between calcium burden and increased risk of adverse outcomes, including implantation of permanent pacemaker (7/8 studies), paravalvular leak (13/13 studies), and risk of aortic rupture (2/2 studies). AVC quantification methodology with contrast-enhanced CT is still variable. AVC negatively impacts TAVI outcomes independently of the quantification method.


Ten questions worth asking about mobile computing.
"Mobile," or perhaps "nomadic," are the watchwords for the style of information management fast coming to the healthcare sector. No, mobile technology in healthcare is not to be confused with cellular-phones. Mobile computing goes where the user goes ... to the patient.


Outcomes after listing for primary transplantation for infants with unoperated-on non-hypoplastic left heart syndrome congenital heart disease: a multi-institutional study.
Although heart transplantation has been used as the primary therapy for congenital heart lesions in infants other than hypoplastic left heart syndrome (HLHS), the outcomes in this group of patients have not been determined. We used the Pediatric Heart Transplant Study database (1993 to 2006) to compare outcomes of 388 infants aged < 6 months listed for HLHS, 161 with other congenital heart diseases (non-HLHS), and 145 with cardiomyopathy in early (1993 to 1999) and recent (2000 to 2006) eras. The cardiomyopathy group was significantly (p < 0.001) different from the HLHS and non-HLHS groups at listing: more girls, older age, and a greater need for high-dose inotropes, mechanical ventilation, and/or mechanical circulatory support. Survival after listing was similar among the groups in the early era. Although outcomes after listing in HLHS and cardiomyopathy patients improved in the recent era, outcomes in non-HLHS patients did not. Survival at 1 and 5 years after listing was significantly worse (p < 0.001) for non-HLHS patients (51%, 48%) vs HLHS (71%, 61%), with age- and sex-adjusted hazard ratio (HR) of 1.79 (95% confidence interval, 1.15-2.77, p = 0.009) and CM (80%, 74%; HR, 2.72; 95% confidence interval, 1.59-4.67, p < 0.001) in the recent era. Post-transplant survival in both eras was not significantly different among the groups. Use of heart transplantation as primary therapy for non-HLHS infants has not improved over time and currently is associated with significantly poorer results vs HLHS and cardiomyopathy due to a higher risk for death before transplant.


Heterogeneity of pollen food allergy syndrome in seven Southern European countries: The @IT.2020 multicenter study.
Pollen food allergy syndrome (PFAS) is a frequently underdiagnosed disease due to diverse triggers, clinical presentations, and test results. This is especially relevant in geographic areas with a broad spectrum of pollen sensitization, such as Southern Europe. To elucidate similarities and differences of PFAS in nine Southern European centers and identify associated characteristics and unique markers of PFAS. As part of the @IT.2020 Multicenter Study, 815 patients with seasonal allergic rhinitis (SAR), aged 10-60 years, were recruited in seven countries. They completed questionnaires regarding SAR, comorbidities, family history, and PFAS, and underwent skin prick testing (SPT) and serum IgE testing. Of the 815 patients, 167 (20.5%) reported PFAS reactions. Most commonly, eliciting foods were kiwi (58, 34.7%), peach (43, 25.7%), and melon (26, 15.6%). Reported reactions were mostly local (216/319, 67.7%), occurring within 5 min of contact with elicitors (209/319, 65.5%). Associated characteristics included positive IgE to at least one panallergen (profilin, PR-10, or nsLTP) (p = 0.007), maternal PFAS (OR: 3.716, p = 0.026), and asthma (OR: 1.752, p = 0.073). Between centers, heterogeneity in prevalence (Marseille: 7.5% vs. Rome: 41.4%, p < 0.001) and of clinical characteristics was apparent. Cypress played a limited role, with only 1/22 SPT mono-sensitized patients reporting a food reaction (p < 0.073). PFAS is a frequent comorbidity in Southern European SAR patients. Significant heterogeneity of clinical characteristics in PFAS patients among the centers was observed and may be related to the different pollen sensitization patterns in each geographic area. IgE to panallergen(s), maternal PFAS, and asthma could be PFAS-associated characteristics.


Risk factors for acute myocardial infarction in Indians: a case-control study.
South Asians who have settled overseas and those in urban India have an increased risk of ischaemic heart disease (IHD). Reasons for this increased risk are unclear. Most studies have been based on migrants to western nations, so their findings may not apply to most south Asians, who live in their own countries. Therefore, we assessed the relative importance of risk factors for IHD among South Asians in Bangalore, India. We conducted a prospective hospital-based case-control study of 200 Indian patients with a first acute myocardial infarction (AMI) and 200 age and sex matched controls. We recorded prevalence of the following risk factors for IHD: diet, smoking, alcohol use, socioeconomic status, waist to hip ratio (WHR), blood glucose, serum insulin, oral glucose tolerance test, and lipid profile. The most important predictor of AMI was current smoking (odds ratio [OR] 3.6, p < 0.001) of cigarettes or beedis (a local form of tobacco), with individuals who currently smoked 10 or more per day having an OR of 6.7 (p < 0.001). History of hypertension and of overt diabetes mellitus were also independent risk factors (OR 2.69 [p = 0.001] and 2.64 [p = 0.004], respectively). Among all individuals, fasting blood glucose was a strong predictor of risk over the entire range, including at values usually regarded as normal (OR adjusted for smoking, hypertension, and WHR 1.62 for 1 SD increase, p < 0.001). Abdominal obesity (as measured by WHR) was also a strong independent predictor across the entire range of measures (OR adjusted for smoking, hypertension, and blood glucose 2.24 for 1 SD increase; p < 0.001). Compared with individuals with no risk factors, individuals with multiple risk factors had greatly increased risk of AMI (eg, OR of 10.6 for the group with smoking and elevated glucose). Lipid profile was not associated with AMI. In univariate analyses, higher socioeconomic (income) status (OR 0.32, p = 0.005 highest vs lowest; OR 0.75 middle vs lowest) and vegetarianism (OR = 0.55, p = 0.006), seemed to be protective. The impact of vegetarianism was closely correlated with blood glucose and WHR. Smoking cessation, treatment of hypertension, and reduction in blood glucose and central obesity (perhaps through dietary modification) may be important in preventing IHD in Asian Indians.


[Auto-immune encephalitis in psychiatric practice].
Our knowledge about auto-immune limbic encephalitis is increasing rapidly and it is now evident that patients with this disease can present with psychiatric symptoms. To propose practical guidelines for the recognition and diagnosis of an underlying auto-immune limbic encephalitis in patients with acute psychiatric symptoms. We studied recent reviews on the topic and had discussions with psychiatrists, a neurologist and a neuroimmunologist in order to reach consensus. Auto-immune limbic encephalitis is a rather rare but important diagnostic consideration in patients with acute psychiatric symptoms. We describe the different steps in the diagnostic work-up and mention features that can point to an underlying auto-immune encephalitis. These include atypical psychiatric symptoms, seizures, movement disorders and autonomic instability. Since patients with autoimmune limbic encephalitis often present with psychiatric symptoms, curative treatment is often available and the prognosis depends on the delay from presentation to treatment, psychiatrists should be aware of the signs of an underlying autoimmune encephalitis which have been described in this article.


Fungal endophytes vary by species, tissue type, and life cycle stage in intertidal macroalgae.
Fungal symbionts of terrestrial plants are among the most widespread and well-studied symbioses, relatively little is known about fungi that are associated with macroalgae. To fill the gap in marine fungal taxonomy, we combined simple culture methods with amplicon sequencing to characterize the fungal communities associated with three brown (Sargassum muticum, Pelvetia canaliculata, and Himanthalia elongata) and two red (Mastocarpus stellatus and Chondrus crispus) macroalgae from one intertidal zone. In addition to characterizing novel fungal diversity, we tested three hypotheses: fungal diversity and community composition vary (i) among species distributed at different tidal heights, (ii) among tissue types (apices, mid-thallus, and stipe), and (iii) among "isomorphic" C. crispus life cycle stages. Almost 70% of our reads were classified as Ascomycota, 29% as Basidiomycota, and 1% that could not be classified to a phylum. Thirty fungal isolates were obtained, 18 of which were also detected with amplicon sequencing. Fungal communities differed by host and tissue type. Interestingly, P. canaliculata, a fucoid at the extreme high intertidal, did not show differences in fungal diversity across the thallus. As found in filamentous algal endophytes, fungal diversity varied among the three life cycle stages in C. crispus. Female gametophytes were also compositionally more dispersed as compared to the fewer variable tetrasporophytes and male gametophytes. We demonstrate the utility of combining relatively simple cultivation and sequencing approaches to characterize and study macroalgal-fungal associations and highlight the need to understand the role of fungi in near-shore marine ecosystems.


Prevention of Esophageal Stricture after Endoscopic Submucosal Dissection with an Autologous Esophageal Epithelial Cell Suspension: An Animal Study.
Severe esophageal stricture decreases patient's quality of life after circumferential endoscopic submucosal dissection (ESD). We aimed to evaluate the efficacy of autologous esophageal epithelial cell suspensions in preventing esophageal stricture after circumferential ESD. Twelve male mini-pigs underwent circumferential ESD and were randomized into four groups: G1 (control), G2 (esophageal stent), G3 (autologous esophageal epithelial cell suspension), and G4 (autologous esophageal epithelial cell suspension combined with esophageal stent). Post-ESD status was observed in each group, and endoscopy was performed weekly. Esophageal stents were removed 3 weeks after ESD. The esophageal stricture rates and histologic characteristics were assessed 4 weeks after ESD. G1 showed the greatest weight loss (p < 0.05). Dysphagia scores were not significantly different among the groups. The esophageal mucosal stricture rates were 77.7 ± 2.9%, 74.2 ± 1.9%, 69.2 ± 3.8% and 65.9 ± 1.9% in G1-4, respectively; with the highest in G1 (G1 vs. G3, p = 0.005; G1 vs. G4, p = 0.001). The regenerated epithelium lengths were 4.408 ± 1.980 mm, 8.319 ± 0.857 mm, 11.801 ± 2.455 mm and 12.353 ± 1.111 mm in G1-4, respectively. The lowest degree of re-epithelialization was observed in G1, followed by G2, with the highest degrees in G3 and G4 (G1 vs. G3, p = 0.001; G1 vs. G4, p = 0.000). The maximum wound fibrosis thicknesses were 2.546 ± 0.389 mm, 2.136 ± 0.231 mm, 1.126 ± 0.211 mm and 1.131 ± 0.438 mm in G1-4, respectively, with higher degrees in G1 and G2 than in G3 and G4 (G1 vs. G3, p = 0.001; G1 vs. G4, p = 0.001). Autologous esophageal epithelial cell suspensions can promote re-epithelialization and reduce fibrosis, thus decreasing esophageal stricture severity after ESD.


Two cases of cytomegalovirus infection revealed by hearing loss in HIV-infected patients.
Neurological complications are particularly common during HIV infection. Among various opportunistic diseases, cytomegalovirus (CMV) is one of the most frequent causes of central and peripheral neurological manifestations. Previously, there have been several reports of cranial nerve infection by CMV, but to our knowledge, no cases of auditory nerve involvement have been described. We report two cases in which CMV infection was revealed by involvement of the VIIIth cranial nerves. Cytomegalovirus (CMV) infection is frequent in severely immunodeficient patients infected by human immunodeficiency virus (HIV). The main targets of CMV are the retina, gastrointestinal tract and central nervous system. We describe two cases in which neurologic CMV infection was revealed by hearing loss.


Antibacterial effects of glass ionomers.
Glass ionomer cements have been shown to possess antimicrobial activity. Proposed mechanisms of action include acidity and fluoride. It was the purpose of this study to determine the antimicrobial effect of 11 glass ionomer cements, their individual powder and liquid components and one resin-bonded liner containing high fluoride ionomer glass against Streptococcus mutans #6715. The role of fluoride and pH in the antibacterial activity was also studied. Using agar diffusion assay methodology, the following results were obtained. All of the glass ionomer cements were inhibitory against S. mutans. The antibacterial cements and slurries that were tested for fluoride, released the ion in excess of reported minimum inhibitory values. The antimicrobial activity of the liquid components, that were tested for the effects of pH changes, was totally lost when the pH was adjusted to 5. The resin bonded liner was inactive against S. mutans and did not release inhibitory concentrations of fluoride. These results indicate that freshly-mixed glass ionomer cements are antimicrobial against S. mutans and that the mechanism of action is probably a function of both fluoride and pH although additional factors may be involved.


Automated administration of lidocaine for the treatment of ventricular arrhythmias.
An automated lidocaine infusion system has been developed for the treatment of ventricular arrhythmias. A drug serum concentration which is in the therapeutic range is initially achieved and maintained by an open-loop infusion regimen. The lidocaine infusion rate is then adjusted using closed-loop control to regulate the rate of premature ventricular contractions (PVC rate) at a setpoint. The major system components are a portable computer, a computer-controlled drug infusion pump, and an arrhythmia monitor which is used to measure the PVC rate. During closed-loop control, the drug infusion rate is constrained to keep the predicted serum concentration below an upper limit (ceiling concentration) so that toxic serum concentrations are avoided. The infusion rate is also constrained to keep the predicted serum concentration above a minimum value (floor concentration) to ensure the maintenance of a therapeutic serum level during closed-loop control. The system has been evaluated in initial clinical trials.


3 alpha, 17 beta-androstanediol glucuronide in plasma. A marker of androgen action in idiopathic hirsutism.
Biologically active androgens and peripheral androgen metabolites in plasma were measured in 25 women with idiopathic hirsutism (IH). Plasma testosterone was not significantly elevated. Free testosterone however was increased although the elevation was not impressive (10.9 +/- 6.6 SD vs. 3.3 +/- 1.5 ng/dl) and one-fourth of the cases had normal unbound testosterone. Dihydrotestosterone (DHT) values were elevated (23.5 +/- 14 vs. 12.5 +/- 3.59) but again over half of the values were within the normal range. In our series of mild to moderate cases, 3 alpha-diol was not at all discriminatory. However, plasma 3 alpha-diol glucuronide was markedly increased (604 +/- 376 vs. 40 +/- 10 ng/dl), and elevated in all but one mild case. Previous studies document that DHT is the important androgen in skin and formation of DHT and 3 alpha-diol is markedly increased in vitro in IH. Since 3 alpha-diol glucuronide is derived largely from extrasplanchnic events, beta-glucuronidase is present in skin, and androgen stimulates formation of the enzyme in extrasplanchnic tissue, we conclude that 3 alpha-diol glucuronide is a marker of peripheral androgen action and markedly elevated in IH.


Public Awareness of Knowledge, Belief, and Attitude Regarding Organ Donation and Organ Transplantation: A National Survey From the United Arab Emirates.
Organ donation in the United Arab Emirates (UAE) was restricted until recently to living donation. This survey was conducted to explore the public knowledge, belief, and attitude regarding donation during life and after death. A 31-item survey was distributed among 900 participants (UAE residents) of whom 495 completed the forms and were considered for further analysis. Among the participants, 293 (59.2%) were women and 202 (40.1%) were men. With 8 items as the highest possible score, the mean score of knowledge was 4.42 (SD = 1.54) and 436 (88%) of the participants knew about a brain-dead condition. However, their awareness on organ donation and transplantation legislation in the UAE was not consistent, and less than 198 (40%) had correct knowledge in this regard. Religious belief regarding organ donation was scored at 80 and the mean of the beliefs score obtained was 56.56 (SD = 6.39). Together, 369 (74.6%) of the participants had positive religious sentiments regarding the issue. Participants' attitude toward organ donation and transplantation was scored at 14.7 out of 20 possible score (SD = 2.46) with 396 (80%) acknowledging the fact that organ donation and transplantation prolongs and improves recipient's quality of life. The small number of respondents (n = 495) in the survey was a limitation of the study. The population of the UAE was moderately well informed and motivated about organ donation and transplantation. Although a knowledge gap about the current legislation prevailed, the majority of the participants were knowledgeable, they nurtured positive beliefs, and had compassionate attitude regarding lawful organ transplantation.


13 Reasons Why: Perceptions and Correlates of Media Influence in Psychiatrically Hospitalized Adolescents.
The Netflix series 13 Reasons Why (13RW) has sparked controversy due to graphic depictions of youth suicide, bullying, and sexual assault. However, further research is needed examining experiences of the show among youth with psychiatric illness. This exploratory, mixed-methods study examines adolescents' perceptions of 13RW and associations among viewership, suicide-related media influence processes, and self-injurious thoughts and behaviors (SITBs). Participants were 242 adolescents hospitalized in a psychiatric inpatient facility; 60.7% female, 30.2% male, 9.1% other genders; ages 11 to 18; and 74.3% White, 7.5% Black, and 21.8% Hispanic. Participants completed measures of series viewership, media message processing, and SITBs. Participants who watched completed open-ended questions regarding beliefs and opinions about the series. In all, 50.4% of participants watched 13RW, with girls (63.3%) more likely to have watched than boys (26.0%). More than half (55.9%) of youth expressed negative reactions to the show, while approximately one-third (33.8%) expressed positive reactions. Having watched the series was associated with greater likelihood of past-year non-suicidal self-injury (NSSI), but not with suicidal ideation or past-year suicide attempts. Youth's interpretation of media messages in 13RW, including greater identification with and perceived likeability of the main character, were associated with suicidal ideation and past-year NSSI. Findings suggest high rates of 13RW viewership among psychiatrically hospitalized youth, particularly girls, and provide insight into factors that may affect youths' vulnerability to suicide-related media effects.


A Review of the Use of Ultrasound for Skin Tightening, Body Contouring, and Cellulite Reduction in Dermatology.
Ultrasound (US) technology uses acoustic waves to heat tissue, resulting in thermal damage and coagulative necrosis leading to the renewal of skin elasticity, body contouring, and destruction of cellulite. This review will discuss the use of US for skin tightening, body contouring/sculpting, and cellulite reduction. A literature search identified studies using US for skin tightening, body contouring/sculpting, and cellulite reduction. Two hundred thirty-one studies were identified using US technology. Twenty studies each were identified addressing body contouring/sculpting and skin tightening, and 2 studies for cellulite reduction. Ultrasound is efficacious for skin rejuvenation, body contouring, and reduction of cellulite of the face, décolletage, abdomen, and thighs. Ultrasound lipolysis results in a 2- to 4.6-cm decrease in abdominal circumference. Ultrasound is safe and can be used in all skin types with minimal concern for postinflammatory hyperpigmentation. Ultrasound seems to be an efficacious, effective, and safe modality for correction of skin laxity, lipolysis, and decrease the appearance of cellulite. Adverse effects are minimal including procedural pain, postprocedure erythema, and swelling. Clinicians and patients are both satisfied with results after treatment. In this review, the authors will provide an update on the use of US in the dermatologic field.


On the necessity of improving the environmental impacts of furniture and appliances in net-zero energy buildings.
There is now clear evidence regarding the extensive use of furniture and appliances in daily human life, but there is less evidence of their impact on the environment. Responding to this gap in knowledge, this study focuses on an assessment of the environmental impacts of furniture and appliances as used in highly energy efficient buildings. Their primary energy, non-renewable energy and global warming potential indicators have been assessed by extending the boundaries of the Life Cycle Assessment (LCA) study beyond the building itself. In conclusion, we found that furniture and appliances were responsible for around 30% of greenhouse gas emissions and non-renewable energy consumption and 15% of primary energy consumption comparing to the overall impacts of the building. Since embodied impacts represent the largest values, the process for labelling the appliances' energy efficiency should encompass a life-cycle point of view, not just a usage point of view as the case currently. Among office appliances, computer equipment was ranked as the highest impacting element, especially laptops and monitors. As for domestic appliances, refrigerators and electric ovens had the biggest impacts. Concerning furniture, the greatest impacts were from office and kitchen cabinets.


Malignant hyperthermia: update on susceptibility testing.
Malignant hyperthermia (MH) is a pharmacogenetic clinical syndrome that manifests as a hypermetabolic crisis when a susceptible individual is exposed to an anesthetic triggering agent. Clinical signs include unexplained elevation of end-tidal carbon dioxide, muscle rigidity, acidosis, tachycardia, tachypnea, hyperthermia, and evidence of rhabdomyolysis. This process is a result of an abnormally increased release of calcium from the sarcoplasmic reticulum, which is often caused by an inherited mutation in the gene for the ryanodine receptor (RYR1) that resides in the membrane of the sarcoplasmic reticulum. The gold standard for determination of MH susceptibility is the caffeine-halothane contracture test. However, it is invasive, requiring skeletal muscle biopsy and is not widely available. Researchers have begun to map mutations within the ryanodine receptor gene (chromosome 19q13.1) responsible for conferring MH susceptibility. Ryanodine receptor mutations are found in at least 25% of known MH susceptible individuals in North America. Mutation analysis has recently become available in the United States and is expected to play an integral role in the diagnosis of MH susceptibility in the future.


Antigenicity of Leishmania braziliensis histone H1 during cutaneous leishmaniasis: localization of antigenic determinants.
The humoral immune response against Leishmania braziliensis histone H1 by patients with cutaneous leishmaniasis is described. For this purpose, the protein was purified as a recombinant protein in a prokaryotic expression system and was assayed by enzyme-linked immunosorbent assay (ELISA) with a collection of sera from patients with cutaneous leishmaniasis and Chagas' disease. The assays showed that L. braziliensis histone H1 was recognized by 66% of the serum samples from patients with leishmaniasis and by 40% of the serum samples from patients with Chagas' disease, indicating that it acts as an immunogen during cutaneous leishmaniasis. In order to locate the linear antigenic determinants of this protein, a collection of synthetic peptides covering the L. braziliensis histone H1sequence was tested by ELISA. The experiments showed that the main antigenic determinant is located in the central region of this protein. Our results show that the recombinant L. braziliensis histone H1 is recognized by a significant percentage of serum samples from patients with cutaneous leishmaniasis, but use of this protein as a tool for the diagnosis of cutaneous leishmaniasis is hampered by the cross-reaction with sera from patients with Chagas' disease.


Conflicting effects of atazanavir therapy on atherosclerotic risk factors in stable HIV patients: A randomized trial of regimen switch to atazanavir.
Bilirubin acts as a potent endogenous antioxidant, with higher concentrations associated with lower rates of CVD; the antiretroviral drug atazanavir (ATV) increases bilirubin levels but may also increase von Willebrand factor levels. We tested the hypothesis that increasing endogenous bilirubin using ATV would improve cardiometabolic risk factors and vascular function in older patients with HIV. Ninety participants were enrolled in two study protocols. In protocol 1, we evaluated markers of inflammation, thrombosis, and conduit artery endothelial function in subjects on non-ATV containing regimens. Participants were randomly assigned to continue baseline treatment or switch to an ATV-based regimen. Measurements were made at baseline and 28 days. In the protocol 2, we enrolled 30 subjects who received atazanavir for more than one year and were compared to the aim 1 protocol subjects at baseline. 60 subjects were enrolled in the first protocol (mean age 53, +/- 6 years), with 31 randomized to ATV and 29 continuing baseline treatment. Atazanavir significantly increased serum total bilirubin levels (p<0.001) and acutely but not chronically plasma total antioxidant capacity (p<0.001). An increase in von Willebrand Factor (p<0.001) and reduction in hs-CRP (p = 0.034) were noted. No changes were seen in either flow-mediated endothelium-dependent or vasodilation. In cross-sectional analysis (second protocol), similar findings were seen in the baseline attributes of non-atazanavir-based and long-term atazanavir users. Increasing serum bilirubin levels with atazanavir in subjects with HIV reduces hs-CRP, temporarily reduces oxidative stress, but increases von Willebrand Factor. Atazanavir does not improve endothelial function of conduit arteries. ClinicalTrials.gov NCT03019783.


[Study on quality of sleep and mental health in patients with hyperthyroidism].
Sleep quality and psychical health were investigated with Pittsburgh Sleeping Quality Index (PSQI) and SCL-90 in 128 patients with hyperthyroidism. The results showed that: 1. The PSQI scores of the patients with ages over 35 years old were higher than that less than 35 years old (P < 0.05). 2. Sleep problems occurred in 87.55% of the patients. Sleep quality of 9.38% of patients were worse. The sleep quality of the female patients were better than the male (P < 0.05). 3. Apart from interpersonal sensitivity, paranoid ideation and psychoticism, scores of the rest were higher than the general people (P < 0.05). 10.2% of the patients with hyperthyroidism had psychical problems. 4. Apart from sleep time and using sleep pill, there was a high correlation between the scores of SCL-90 and PSQI (P < 0.05-P < 0.001). The results showed that sleep problems of the patients with hyperthyroidism affected their psychical health. Lower sleep quality was a main dangerous factor which affected psychical health of the patients with hyperthyroidism.


Two histological methods for recognition and study of cortical microinfarcts in thick sections.
Cortical microinfarcts are the most widespread form of brain infarction but frequently remain undetected by standard neuroimaging protocols. Moreover, microinfarcts are only partially detectable in hematoxylin-eosin-stained (H and E) 4-10 µm paraffin sections at routine neuropathological examination. In this short report, we provide two staining protocols for visualizing cortical microinfarcts in 100-300 µm sections. For low-power microscopy, the first protocol combines aldehyde fuchsine staining for detection of lipofuscin granules and macrophages with Darrow red counterstaining for Nissl material. The second protocol combines collagen IV immunohistochemistry with aldehyde fuchsine/Darrow red or with erythrosin-phosphotungstic acid-aniline blue staining for detailed study of the capillary network. In the first protocol, microinfarcts are recognizable as radially-oriented funnel-like accumulations of aldehyde fuchsine-positive macrophages. The second protocol recognizes microinfarcts and alterations of the capillary network, at whose center accumulations of dead neurons and aldehyde fuchsine-positive macrophages cluster. In addition, the second protocol permits visualization of abnormalities within the capillary network associated with more recent microinfarcts. Both protocols can be useful for comparing MRI datasets with cortical microinfarcts in corresponding whole brain sections of 100-300 µm thickness.


Aspirin Use and Awareness for Cardiovascular Disease Prevention Among Hispanics: Prevalence and Associations with Health Behavior Beliefs.
Cardiovascular disease (CVD) persists as the leading cause of death and disability in many Americans including Hispanics. Primary prevention for CVD may be achieved through regular aspirin use in high risk individuals. This study examined regular aspirin use and specific attitudes and social norms toward CVD and aspirin use within an urban Hispanic population in Minnesota. A sample of primary prevention Hispanics aged 45-79 years were surveyed about CVD history and risk factors, aspirin use, demographic characteristics, and health beliefs and social norms in relation to CVD and aspirin. Relative risk estimation using Poisson regression with robust error variance was used to examine associations with aspirin use. In this sample of 152 Hispanics (55% women), the mean age was 53 years, 70% had a regular healthcare provider, and 22% used aspirin. Aspirin discussions with a regular healthcare provider were strongly associated with aspirin use (adjusted risk ratio 3.02, 95% CI 1.20-7.60). There was a positive association between health beliefs and social norms that affirm preventive behaviors and aspirin use (adjusted linear risk ratio 1.23, 95% CI 1.04-1.45) while uncertainty about the role of aspirin for individual use and in the community was negatively associated with aspirin use (adjusted linear risk ratio 0.85, 95% CI 0.70-1.03). This growing population may benefit from health education about CVD risk and the role of aspirin in prevention.


The role of context in establishing university clinics.
Healthcare systems have a vested interest in employing work-ready graduates. The challenge for universities is to find ways to provide workplace learning that incorporates student education and high quality patient care. Inland areas of Australia, similar to other rural locations globally, experience additional challenges including a relatively high incidence of ill health, increasing demand for health services, chronic workforce shortages and ageing of the existing rural health workforce. In this paper, we conceptualise and describe the research findings related to context from a consultative enquiry into university clinics conducted in 2008. Interview participants were drawn from twenty university clinics in Australia and New Zealand. A consistent theme throughout the interviews was tensions that arose between the role of education and healthcare provision within university clinics. Many interview participants described ways they managed these tensions to meet the expectations of students, educators and the community. The patient supply is the most critical factor in the context of university clinic operations. It is vital to both the educator and the healthcare provider roles. In inland areas with sparse populations a number of strategies, such as outreach clinics, hospital or health centre- based clinics and multi-disciplinary sites, will have to be developed if university clinics are to operate effectively for students and patients.