Mapping protein collapse with single-molecule fluorescence and kinetic synchrotron radiation circular dichroism spectroscopy.
We have used the combination of single-molecule Förster resonance energy transfer and kinetic synchrotron radiation circular dichroism experiments to probe the conformational ensemble of the collapsed unfolded state of the small cold shock protein CspTm under near-native conditions. This regime is physiologically most relevant but difficult to access experimentally, because the equilibrium signal in ensemble experiments is dominated by folded molecules. Here, we avoid this problem in two ways. One is the use of single-molecule Förster resonance energy transfer, which allows the separation of folded and unfolded subpopulations at equilibrium and provides information on long-range intramolecular distance distributions. From experiments with donor and acceptor chromophores placed at different positions within the chain, we find that the distance distributions in unfolded CspTm agree surprisingly well with a Gaussian chain not only at high concentrations of denaturant, where the polypeptide chain is expanded, but also at low denaturant concentrations, where the chain is collapsed. The second, complementary approach is synchrotron radiation circular dichroism spectroscopy of collapsed unfolded molecules transiently populated with a microfluidic device that enables rapid mixing. The results indicate a beta-structure content of the collapsed unfolded state of approximately 20% compared with the folded protein. This suggests that collapse can induce secondary structure in an unfolded state without interfering with long-range distance distributions characteristic of a random coil, which were previously found only for highly expanded unfolded proteins.


An adolescent with significant emotional and medically unexplained complaints: case report and proposal of an intervention.
Ethiopia is a country in which child and adolescent mental health needs are often not met. In order to promote capacity building, a Collaborative International Exchange Programme has been established between Jimma University at Jimma, Ethiopia, and Ludwig-Maximilian University in Munich, Germany. The programme focuses on training non-physician health professionals in mental health speciality. One of the courses in the training programme, child psychiatry, involves a child psychiatrist and a children's nurse supporting the management of a patient described in this case report. Its conceptual framework is based on the section "significant emotional and medically unexplained complaints" of the "WHO mental health GAP intervention guide for mental, neurological and substance use disorders in non-specialized health settings". The purpose of this case report is to promote confidence in mental health professionals when managing patients with similar conditions, and to stimulate further evaluation of the conceptual approach in developing countries. The subject of this case report is a 14-year-old adolescent girl admitted to the psychiatric clinic at Jimma University Teaching Hospital. She was admitted for intractable retching, inability to eat, weight loss, and inability to walk. Challenges included the combination of medical and psychiatric symptoms, and the significant impairment of functioning in this adolescent. The first aim in the management of this patient was to guarantee vital functions. In a problem-oriented approach, different domains were addressed to restore nutritional, social, emotional, and motor functions. Treatment consisted of various elements of psychosocial interventions. The patient improved in 2 weeks and the final diagnosis was conversion disorder. Psychosocial interventions can be developed in cooperation, and applied in a setting where little child mental health expertise is available. Case-based learning relying on local expertise is suitable in meeting local needs and in developing mental health services for children and adolescents.


[Clinical application of intraoperative ultrasonography for bilateral multilocular cystic renal cell carcinoma: a case report].
A 45-year-old man was referred to our department for further examination of the renal complicated cyst which was found incidentally by ultrasonography. Another complicated cyst in the left kidney was detected by subsequent dynamic CT and ultrasonography, which suggested bilateral cystic renal cell carcinoma. Bilateral partial nephrectomy was performed. Intraoperative ultrasonography was useful for diagnosis of multilocular cystic renal cell carcinoma (MCRCC). It disclosed multiple septa of the right renal complicated cyst which were not revealed by any preoperative examinations. It was also a useful adjunct to partial nephrectomy. It helped to identify the extent of deep intra-parenchymal lesions. The final diagnosis was bilateral synchronous multilocular cystic renal cell carcinoma. This is the second case of bilateral synchronous multilocular cystic renal cell carcinoma reported in Japan. We reviewed the clinical characteristics of 59 cases of MCRCC in the Japanese literature including the present case.


[Possible relation between viruses and oromaxillofacial tumors. V. Demonstration of hemagglutination-inhibiting anti-BK virus antibodies in patients with tumors of the parotid gland].
Anti-BK-virus hemagglutination inhibiting antibodies were revealed in 81.8% of the patients with parotid gland tumors. Results of the investigations conducted on oromaxillofacial tumors including the parotid gland ones are discussed from the point of view of the presence of viral antigens (herpes-, SV40 and BK-viruses) and of specific antibodies. Possible implication of the papova viruses in the etiopathogenesis of the parotid gland tumors in humans are also discussed.


Impact of emotional distress and pain-related fear on patients with chronic pain: Subgroup analysis of patients referred to multimodal rehabilitation.
Multimodal rehabilitation programmes (MMRP) for chronic pain could be improved by determining which patients do not benefit fully. General distress and pain-related fear may explain variations in the treatment effects of MMRP. Cohort study with a cross-sectional, prospective part. Chronic musculoskeletal pain patients referred to 2 hospital-based pain rehabilitation clinics. The cross-sectional part of this study cluster analyses patients (n = 1,218) with regard to distress and pain-related fear at first consultation in clinical pain rehabilitation and describes differences in external variables between clusters. The prospective part follows the subsample of patients (n = 260) participating in MMRP and describes outcome post-treatment. Four distinct subgroups were found: (i) those with low levels of distress and pain-related fear; (ii) those with high levels of pain-related fear; (iii) those with high levels of distress; and (iv) those with high levels of distress and pain-related fear. These subgroups showed differences in demogra-phics, pain characteristics, quality of life, and acceptance, as well as the degree of MMRP participation and MMRP outcome. Among patients with chronic pain referred to MMRP there are subgroups with different profiles of distress and pain-related fear, which are relevant to understanding the adaptation to pain and MMRP outcome. This knowledge may help us to select patients and tailor treatment for better results.


Cephalic tetanus: demonstration of a dual lesion.
A clinical and electrophysiological study of 15 cases of cephalic tetanus is reported. This condition is a form of local tetanus which commonly follows an injury to the face or head. It is characterised by muscle paralysis which is maximal close to the site of injury, while spasm is evident at mroe distant sites. As muscle paralysis improves with time it is succeeded by spasm. It is argued that paralysis is due to high local concentrations of toxin in the brainstem while lesser concentrations cause spasm by abolishing inhibition. Electrophysiological studies indicate that paralysis is of lower motor neurone type with denervation potentials, hyperirritability, loss of motor units, and marginally increased distal latencies being the features recorded.


A comprehensive analysis of gut and skin microbiota in canine atopic dermatitis in Shiba Inu dogs.
Like its human counterpart, canine atopic dermatitis (cAD) is a chronic relapsing condition; thus, most cAD-affected dogs will require lifelong treatment to maintain an acceptable quality of life. A potential intervention is modulation of the composition of gut microbiota, and in fact, probiotic treatment has been proposed and tried in human atopic dermatitis (AD) patients. Since dogs are currently receiving intensive medical care, this will be the same option for dogs, while evidence of gut dysbiosis in cAD is still missing, although skin microbial profiling in cAD has been conducted in several studies. Therefore, we conducted a comprehensive analysis of both gut and skin microbiota in cAD in one specific cAD-predisposed breed, Shiba Inu. Additionally, we evaluated the impact of commonly used medical management on cAD (Janus kinase; JAK inhibitor, oclacitinib) on the gut and skin microbiota. Furthermore, we genotyped the Shiba Inu dogs according to the mitochondrial DNA haplogroup and assessed its association with the composition of the gut microbiota. Staphylococcus was the most predominant bacterial genus observed in the skin; Escherichia/Shigella and Clostridium sensu stricto were highly abundant in the gut of cAD-affected dogs. In the gut microbiota, Fusobacteria and Megamonas were highly abundant in healthy dogs but significantly reduced in cAD-affected dogs. The abundance of these bacterial taxa was positively correlated with the effect of the treatment and state of the disease. Oclacitinib treatment on cAD-affected dogs shifted the composition of microbiota towards that in healthy dogs, and the latter brought it much closer to healthy microbiota, particularly in the gut. Additionally, even within the same dog breed, the mtDNA haplogroup varied, and there was an association between the mtDNA haplogroup and microbial composition in the gut and skin. Dysbiosis of both the skin and the gut was observed in cAD in Shiba Inu dogs. Our findings provide a basis for the potential treatment of cAD by manipulating the gut microbiota as well as the skin microbiota. Video Abstract.


Genetic counseling in Angelman syndrome: the challenges of multiple causes.
The causal heterogeneity of Angelman syndrome (AS) makes providing information regarding recurrence risk both important and challenging, and may have a dramatic impact on reproductive decision-making for the nuclear and extended family. Most cases of AS result from typical large de novo deletions of 15q11-q13, and are expected to have a low (<1%) risk of recurrence. AS due to paternal uniparental disomy (UPD), which occurs in the absence of a parental translocation, is likewise expected to have a <1% risk of recurrence. Parental transmission of a structurally or functionally unbalanced chromosome complement can lead to 15q11-q13 deletions or to UPD and will result in case-specific recurrence risks. In instances where there is no identifiable large deletion or UPD, the risk for recurrence may be as high as 50% as the result of either a maternally inherited imprinting center (IC) mutation or a ubiquitin-protein ligase (UBE3A) gene mutation. Individuals with AS who have none of the above abnormalities comprise a significant proportion of cases, and some may be at a 50% recurrence risk. Misdiagnoses, as well, can be represented in this group. In light of the many conditions which are clinically similar to AS, it is essential to address the possibility of diagnostic uncertainty and potential misdiagnosis prior to the provision of genetic counseling. Summaries of the different causal classes of AS as an algorithm for determination of recurrence risks are presented.


The isolation of wool keratin messenger RNA from sheep.
A method for the isolation of polysomal RNA from plucked wool follicle tissue is described. When translated in a reticulocyte lysate cell-free system, the products encoded by the RNA are electrophoretically identical to the low-sulfur and high-sulfur wool keratins. Since non-keratin translation products were not detected, the keratin mRNA species appear to be the predominant messenger component of the polysomal RNA. Sucrose gradient fractionation of the polysomal RNA gave rise to 2 discrete peaks of keratin mRNA, with mean sizes of 21S and 11S. The 21S fraction coded for the low-sulfur and larger high-sulfur wool keratins, while the 11S fraction coded for proteins smaller than about 20000 daltons, possibly the high-tyrosine keratins and smaller high-sulfur keratins. The keratin mRNA can be separated from the bulk ribosomal RNA by oligo(dT) cellulose chromatography, and hence is presumed to contain a terminal poly(rA) tract.


Transcription by T7 RNA polymerase is not zinc-dependent and is abolished on amidomethylation of cysteine-347.
T7 RNA polymerase has been purified to homogeneity from an overproducing clone of Escherichia coli containing pAR1219. Preparations have a zinc content as low as 0.01 mol/mol of enzyme and a high specific activity, 300 000-500 000 units/mg. There are no intrinsic zinc sites. Furthermore, extrinsic Zn2+ does not function as an activator. Supplementation of the assay mix with up to 5 mM ethylenediaminetetraacetic acid has little effect on activity while added Zn2+ is strongly inhibitory at concentrations above 10 microM. This monomeric RNA polymerase is not a zinc metalloenzyme, unlike its multimeric bacterial counterparts. Titration of the urea-denatured protein with 5,5'-dithiobis(2-nitrobenzoic acid) reveals that all 12 Cys residues are present in the free sulfhydryl form, 5 of which are readily accessible to reagent in the native enzyme. More preferential labeling of the sulfhydryls can be achieved with low concentrations of [14C]iodoacetamide, where inactivation of the enzyme proceeds with incorporation of approximately 1.2 mol of [14C]iodoacetamide/mol of polymerase. Amidomethylation primarily occurs at Cys-347, with lesser reaction at Cys-723 and Cys-839. Cys-347 and Cys-723 are in segments of the primary sequence containing numerous basic residues. These same segments have previously been implicated in promoter binding, suggesting that both residues are located within or near the active site region.


Solvent Organization and Rate Regulation of a Menshutkin Reaction by Oriented External Electric Fields are Revealed by Combined MD and QM/MM Calculations.
When and how do external electric fields (EEFs) lead to catalysis in the presence of a (polar or nonpolar) solvent? This is the question that is addressed here using a combination of molecular dynamics (MD) simulations, quantum mechanical/molecular mechanical calculations with EEF, and quantum mechanical/(local) electric field calculations. The paper focuses on a model reaction, the Menshutkin reaction between CH3I and pyridine in three solvents of varying polarity. Using MD simulations, we find that the EEF causes the solvent to undergo organization; the solvent molecules gradually align with the applied field as the field strength increases. The collective orientation of the solvent molecules modifies the electrostatic environment around the Menshutkin species and induces a global electric field pointing in the opposite direction of the applied EEF. The combination of these two entangled effects leads to partial or complete screening of the EEF, with the extent of screening being proportional to the polarity/polarizability of the solvent. Nevertheless, we find that catalysis of the Menshutkin reaction inevitably emerges once the EEF exceeds the opposing field of the organizing solvent, i.e., once polarization of the Menshutkin complex is observed to set in. Overall, our analysis provides a lucid and pictorial interpretation of the behavior of solutions in the presence of EEFs and indicates that EEF-mediated catalysis should, in principle, be feasible in bulk setups, especially for nonpolar and mildly polar solvents. By application of the charge-transfer paradigm, it is shown that the emergence of OEEF catalysis in solution can be generalized to other reactions as well.


KIF1A mediates axonal transport of BACE1 and identification of independently moving cargoes in living SCG neurons.
Neurons rely heavily on axonal transport to deliver materials from the sites of synthesis to the axon terminals over distances that can be many centimetres long. KIF1A is the neuron-specific kinesin with the fastest reported anterograde motor activity. Previous studies have shown that KIF1A transports a subset of synaptic proteins, neurofilaments and dense-core vesicles. Using two-colour live imaging, we showed that beta-secretase 1 (BACE1)-mCherry moves together with KIF1A-GFP in both the anterograde and retrograde directions in superior cervical ganglions (SCG) neurons. We confirmed that KIF1A is functionally required for BACE1 transport by using KIF1A siRNA and a KIF1A mutant construct (KIF1A-T312M) to impair its motor activity. We further identified several cargoes that have little or no co-migration with KIF1A-GFP and also move independently from BACE1-mCherry. Together, these findings support a primary role for KIF1A in the anterograde transport of BACE1 and suggest that axonally transported cargoes are sorted into different classes of carrier vesicles in the cell body and are transported by cargo-specific motor proteins through the axon.


Not all imatinib resistance in CML are BCR-ABL kinase domain mutations.
Point mutations within the ABL kinase domain of the BCR-ABL gene are associated with clinical resistance to imatinib mesylate in chronic myeloid leukemia (CML). To obtain more information about the association between BCR-ABL mutations and type of imatinib resistance, we studied 30 early chronic phase (CP) CML patients, commencing imatinib therapy, using a conventional sequencing technique. Seven patients treated in late CP and three patients treated in the accelerated phase were included for comparison. Blood samples were collected before and every third month during imatinib therapy. Mutations were not seen in any blood sample collected before start of therapy. During imatinib treatment, 2 of the 30 early CP patients acquired point mutations and both of them had other signs of imatinib resistance. None of the five early CP patients with a complete hematologic response (HR), but no cytogenetic response at 12 months, displayed any missense mutation. Likewise, none of 12 early CP patients with detectable BCR-ABL transcripts but in complete hematologic and cytogenetic remission at 12 months displayed any mutation. We conclude that screening early CP patients for BCR-ABL mutations before start of imatinib therapy is not cost-effective. BCR-ABL kinase domain mutations do not appear to explain cytogenetic or molecular (detectable BCR-ABL transcripts by polymerase chain reaction) disease persistence in patients otherwise in stable disease. However, in patients with signs of expanding disease burden, a search for BCR-ABL mutations is warranted.


Perinatal diagnosis and management of early-onset Marfan syndrome: case report and systematic review.
Early onset Marfan syndrome is the most severe form of Marfan syndrome diagnosed during perinatal period. Early onset Marfan syndrome is associated with high mortality rates, usually within the first 2 years of life. First, we present a case of prenatally diagnosed early onset Marfan syndrome in a dichorionic diamniotic twin pregnancy, where suspicion was raised at 35 weeks of gestation. Ultrasound and fetal magnetic resonance imaging were used to assess prenatal findings in the affected fetus. She presented right diaphragmatic eventration, elongation of humerus and femur and subluxation of the crystalline lens. She died 3 months after birth. Secondly, we present a PubMed-based review of the published articles on early onset Marfan syndrome, with pre- or postnatal suspicion or diagnosis. We found 39 articles published between 1981 and 2017, arising information on 55 cases. Including ours, early onset Marfan syndrome was prenatally diagnosed in 34.54% of the cases. In these cases, the most frequent prenatal findings were cardiomegaly, dilatation of the great vessels and mitral or tricuspid regurgitation. Mortality rate during the first 15 months after birth was 73.68%. In the postnatally diagnosed cases, the most frequent findings were arachnodactyly, dilatation of the great vessels and mitral or tricuspid regurgitation. Mortality rate was 61.11%. Overall genetic confirmation was performed in 67.27% of the cases. Prenatal diagnosis of early onset Marfan syndrome is challenging but of utmost importance, since management should take place in a tertiary care center, by a multidisciplinary team. Differential diagnosis is essential in order to perform an adequate genetic counseling.


Role of plasmapheresis in preparing myasthenic patients for thymectomy: initial results.
Between 1976 and 1981, one of the authors operated on 16 patients for myasthenia gravis. Plasmapheresis was carried out preoperatively on seven patients, while nine patients were operated upon without previous plasmapheresis. The seven patients who underwent plasmapheresis had a smooth course pre- and postoperatively. In the other group, there were two postoperative myasthenic complications. Both patients improved with medication and plasmapheresis. Also, the degree of myasthenia gravis was slightly more severe in this group. From their experience, the authors conclude that plasmapheresis is a worthwhile and safe adjuvant in the preparation of myasthenic patients for thymectomy, especially those in Osserman class IV.


The role of a semi-automated NanoVelcro system in capturing circulating tumor cells and evaluating their prognostic value for gestational choriocarcinoma.
To investigate whether circulating tumor cells (CTCs) are detectable in patients with gestational choriocarcinoma (GC) and evaluate the prognostic value of CTC enumeration. In this multicenter study, the presence of CTCs was examined in 180 GC patients using a semi-automated NanoVelcro system, among whom 106 patients underwent CTC re-evaluation after one cycle of chemotherapy. Approximately 96% of the GC patients contained ≥2 CTCs in 7.5 mL of blood. The number of CTCs per 7.5 mL of blood was much higher in patients with distant metastases (n = 95; range, 0 to 104) than in patients without distant metastases (n = 85; range, 0 to 6). Applying a 90-patient training and 90-patient validation cohort, a cutoff value of ≥6 CTCs was defined as the prognostic threshold for progression-free survival (PFS) and overall survival (OS). The presence of ≥6 CTCs was significantly associated with worse PFS and OS (both P < 0.001). A multivariate analysis showed that the CTC number (≥6 CTCs) was the strongest predictor of OS (hazard ratio [HR], 15.8; 95% confidence interval [CI], 4.3-57.9; P < 0.001). The number of CTCs decreased after one cycle of chemotherapy; univariate analyses demonstrated that the CTC count after the first chemotherapy cycle was a strong predictor of OS (HR, 36.1; 95% CI, 4.8-271.5; P < 0.001). CTCs are a promising prognostic factor for GC. The absolute CTC count after one cycle of chemotherapy in the context of this disease is a strong predictor of chemotherapy response.


Airway toxicity of house dust and its fungal composition.
House dust is an important source of different toxic metabolites as well as allergens, including those of fungal origin, in the indoor environment. A bio-assay employing 1-day-old chick tracheas was used to characterize airway effects of 2-butanone and dimethylsulphoxide (Me2SO) extracts of 23 dust samples collected from water damaged (13) and control (10) Danish schools. Direct microscopical analysis of samples, followed by cultivation on dichloran 18 % glycerol agar at 25 degrees C for 10 days to establish their mycoflora, was performed. The in vitro ciliostatic potential of the chloroform-extractable endo- and exometabolites of 41 representative fungal isolates was determined. Nine dust extracts in 2-butanone (2 from damp rooms) or 10 (6) in Me(2)SO showed some ciliostatic activity in the 3-days' experiment. Fungal composition of dust from buildings with leakage was almost identical with that from undamaged houses, as well as the fungal colony counts from the damp schools and the control samples. Aspergillus spp. were prevalent in the samples - 31 or 40 % of all fungi, followed by Penicillium spp. and Cladosporium cladosporioides. Alternaria spp., Chaetomium spp., Mucor spp., Mycelia sterilia, Paecilomyces variotii, Rhizopus sp., Ulocladium sp. and yeasts were each isolated in less than 8 % of the fungal content. No Aspergillus flavus isolate (8 in total) was aflatoxigenic,em>in vitro. Alternaria spp., Aspergillus spp., Botrytis cinerea, Penicillium spp., C. cladosporioides, Chaetomium spp. and Ulocladium sp.; in total, 88 % of all fungi tested, produced ciliostatically active metabolites. These toxigenic strains were also present in 4 dust samples from controls and 5 dust samples from water damaged buildings. Extracts of these dust samples were also toxic in bioassay. There were bio-detectable concentrations (10-20 microg of extracts/ml of the organ culture medium) of toxic compounds in house dust. Contribution of fungal metabolites to its toxic effect should be studied further.


Definition of sizes for the design of school furniture for Bogotá schools based on anthropometric criteria.
The current paper deals with the definition of sizes for the design of school furniture for schools in Bogotá, Colombia, based on an analysis of available anthropometric data on Latin American children. State-of-the-art anthropometric, national and international standards were considered, in order to define the anthropometric variables that were to be used for defining the furniture. Matrices relating age and specific anthropometric dimensions were constructed, as a visualization method for establishing the dimensional differences between children of the same age and the ranges that should be covered by the items of furniture. Dimensional data were grouped by establishing the minimum sizes and general dimensions of furniture needed to cover the 5-95th percentile of school children between the ages of 5 and 18 years. The distribution of the furniture in the different school grades was also indicated. Apart from the need for an adequate match between child anthropometry and school furniture dimensions, this study shows the importance of a proper distribution of furniture sizes in the different school grades, as a complementary and decisive aspect to be considered in order to meet the heterogenic, anthropometrical requirements of children of the same age and school grade.


Semiparametric multivariate joint model for skewed-longitudinal and survival data: A Bayesian approach.
Joint models and statistical inference for longitudinal and survival data have been an active area of statistical research and have mostly coupled a longitudinal biomarker-based mixed-effects model with normal distribution and an event time-based survival model. In practice, however, the following issues may standout: (i) Normality of model error in longitudinal models is a routine assumption, but it may be unrealistically violating data features of subject variations. (ii) Data collected are often featured by the mixed types of multiple longitudinal outcomes which are significantly correlated, ignoring their correlation may lead to biased estimation. Additionally, a parametric model specification may be inflexible to capture the complicated patterns of longitudinal data. (iii) Missing observations in the longitudinal data are often encountered; the missing measures are likely to be informative (nonignorable) and ignoring this phenomenon may result in inaccurate inference. Multilevel item response theory (MLIRT) models have been increasingly used to analyze the multiple longitudinal data of mixed types (ie, continuous and categorical) in clinical studies. In this article, we develop an MLIRT-based semiparametric joint model with skew-t distribution that consists of an extended MLIRT model for the mixed types of multiple longitudinal data and a Cox proportional hazards model, linked through random-effects. A Bayesian approach is employed for joint modeling. Simulation studies are conducted to assess performance of the proposed models and method. A real example from primary biliary cirrhosis clinical study is analyzed to estimate parameters in the joint model and also evaluate sensitivity of parameter estimates for various plausible nonignorable missing data mechanisms.


Mechanistic investigation on the hydrogenation of imines by[p-(Me2CH)C6H4Me]RuH(NH2CHPhCHPhNSO2C6H4-p-CH3). Experimental support for an ionic pathway.
The need for acidic activation in the stoichiometric hydrogenation of benzyl-[1-phenyl-ethylidene]-amine (6a) or [1-(4-methoxy-phenyl)-ethylidene]-methyl-amine (6b) by Noyori's catalyst [p-Me2CH)C6H4Me]RuH(NH2CHPhCHPhNSO2C6H4-p-CH3) (2) is inconsistent with the proposed concerted mechanism and supports an ionic mechanism.


Metabolism in atherosclerotic plaques: immunoregulatory mechanisms in the arterial wall.
Over the last decade, there has been a growing interest to understand the link between metabolism and the immune response in the context of metabolic diseases but also beyond, giving then birth to a new field of research. Termed 'immunometabolism', this interdisciplinary field explores paradigms of both immunology and metabolism to provided unique insights into different disease pathogenic processes, and the identification of new potential therapeutic targets. Similar to other inflammatory conditions, the atherosclerotic inflammatory process in the artery has been associated with a local dysregulated metabolic response. Thus, recent studies show that metabolites are more than just fuels in their metabolic pathways, and they can act as modulators of vascular inflammation and atherosclerosis. In this review article, we describe the most common immunometabolic pathways characterised in innate and adaptive immune cells, and discuss how macrophages' and T cells' metabolism may influence phenotypic changes in the plaque. Moreover, we discuss the potential of targeting immunometabolism to prevent and treat cardiovascular diseases (CVDs).


Mega clinical trials which have shaped the RAS intervention clinical practice.
Following extensive clinical research, drugs affecting the renin-angiotensin system have been used for the treatment of patients with congestive heart failure, myocardial infarction, hypertension, diabetic nephropathy, chronic renal failure and for reducing the risk of developing major cardiovascular (CV) events. This review examines all mega trials (those involving >1000 patients) and smaller pivotal trials involving angiotensin-converting enzyme inhibitors (ACE-Is; 25 mega trials) and angiotensin receptor blockers (ARBs; 27 mega trials) to provide perspective on the huge database of evidence that has accumulated on the use of these drugs. Our review demonstrates that ACE-Is and ARBs are generally as effective as conventional therapies in the treatment of hypertension, but offer additional cardioprotective benefits in patients with heart failure, and in those who have experienced myocardial infarction. Also, both ACE-Is and ARBs are capable of renal protection in addition to their blood-pressure-lowering effects. Although ACE-Is and ARBs provide major benefits to CV patients, doubts remain over the concept of blood-pressure-independent CV protection offered by both classes of drugs. ACE-Is and ARBs appear to be equally effective with respect to morbidity and mortality endpoints, but ARBs are better tolerated. Considering the available evidence, the combined use of an ACE-I and ARB should be avoided and full doses of either ACE-I or ARB should be aimed for as evidence suggests they provide a greater prognostic benefit.


Electronically Pure Single-Chirality Semiconducting Single-Walled Carbon Nanotube for Large-Scale Electronic Devices.
Single-walled carbon nanotube (SWCNT) networks deposited from a purple single chirality (6,5) SWCNT aqueous solution were electrically characterized as pure semiconductors based on metal/semiconductor/metal Schottky contacts using both complex instruments and a portable device. Both air-stable PMOS (p-type metal-oxide-semiconductor) and NMOS (n-type metal-oxide-semiconductor, resembling amorphous silicon) thin film transistors were fabricated on (6,5) SWCNT in large scale showing the characteristics of fA off current and ION/IOFF ratio of >1 × 10(8). CMOS (complementary metal-oxide-semiconductor) SWCNT inverter was demonstrated by wire-bonding PMOS (6,5) SWCNT TFT and NMOS (6,5) SWCNT TFT together to achieve the voltage gain as large as 52.


Lateral and medial amygdala of anuran amphibians and their relation to olfactory and vomeronasal information.
The amygdala of anurans is currently considered as a complex of nuclei that share many features with their counterparts in amniotes. In the present study, the subdivisions of the amygdala that are directly related to olfactory and vomeronasal information, were investigated in the anurans Rana perezi and Xenopus laevis. In particular, the connectivity of the main and accessory olfactory bulbs and their related amygdaloid nuclei was studied by means of in vivo and in vitro tract-tracing with dextran amines. The projections observed from the main olfactory bulb clearly innervate the newly redefined lateral amygdala within the ventral pallium and, to a lesser extent, the rostral portion of the medial amygdala. Injections into the accessory olfactory bulb exclusively revealed projections to the medial amygdala. Tracer applications into the lateral and medial nuclei revealed abundant intra-amygdaloid connections. The dual flow of olfactory and vomeronasal projections throughout the telencephalon was not strictly segregated since the lateral pallium and the lateral amygdala, both receiving olfactory information, were found to project to the medial amygdala (the only target of vomeronasal information), which in turn projects to the lateral amygdala. Additionally, both the lateral and the medial amygdala strongly project to the hypothalamus through the anuran equivalent of the stria terminalis. The main hodological features found in the present study suggest that forerunners of the olfactory and vomeronasal amygdaloid nuclei can be distinguished in anurans. This supports the notion that all tetrapods share a common pattern of organization of the amygdaloid complex, which links environmental (olfactory/vomeronasal) information and the behavioural response of the animal.


Direct observation of reductive elimination of methyl iodide from a rhodium(III) pincer complex: the importance of sterics.
A rare case of directly observed alkyl halide reductive elimination from rhodium is reported. Treatment of the naphthyl-based PCP-type Rh(III) methyl complexes 2a,b [(C10H5(CH2PR2)2)Rh(CH3)(I)] (R = iPr 2a, R = tBu 2b) with CO resulted in facile reductive elimination of methyl iodide in the case of 2b, yielding the Rh(I) carbonyl complex [(C10H5(CH2PR2)2)Rh(CO)] 3b (R = tBu), while the less bulky 2a formed CO adducts and did not undergo reductive elimination, contrary to expectations based on electron density considerations. Moreover, 3b oxidatively added methyl iodide, while 3a did not. CD3I/CH3I exchange studies in the absence of CO indicate that reversible formation of (ligated) methyl iodide takes place in both systems. Subsequently, when CO is present, it displaces methyl iodide in the bulkier tBu system, whereas with the iPr system formation of the Rh(III) CO adducts is favored. Iodide dissociation followed by its attack on the rhodium-methyl group is unlikely.


Fibroblast growth factor 23 in acute myocardial infarction complicated by cardiogenic shock: a biomarker substudy of the Intraaortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II) trial.
Cardiogenic shock (CS) is the leading cause of death in patients hospitalized with acute myocardial infarction (AMI). Biomarkers might help in risk stratification and understanding of pathophysiology. Preliminary data suggests that patients with CS face a profound increase in the osteocyte-derived hormone fibroblast growth factor 23 (FGF-23), which acts as a negative regulator of serum phosphate levels. The present study aimed to assess the predictive role of FGF-23 for clinical outcome in a large cohort of CS patients with and without renal dysfunction. In the randomized Intraaortic Balloon Pump in Cardiogenic Shock II (IABP-SHOCK II) trial, 600 patients with CS complicating AMI were assigned to therapy with or without IABP. Our predefined biomarker substudy included 182 patients. Blood sampling was performed in a standardized procedure at three different time points (day 1 (day of admission), day 2 and day 3). Differences in outcome of patients with FGF-23 levels<and>median were compared by log-rank testing. Stepwise logistic regression modeling was performed to identify predictors of death at 30 days and Cox regression analysis for time to death during the first year. At all three time points, nonsurvivors had significantly higher FGF-23 levels compared to survivors (P<0.001 for all). Patients with FGF-23 levels above the median (395 RU/mL [interquartile range 102;2,395]) were characterized by an increased 30-day mortality and 1-year mortality. In multivariable analysis FGF-23 levels remained independent predictors for 30-day (odds ratio per 10log 1.80, 95% confidence interval (CI) 1.11 to 2.92; P=0.02) and 1-year mortality (hazard ratio 1.50, 95% CI 1.11 to 2.04, P=0.009). After stratifying the patients according to their baseline serum creatinine levels, the negative prognostic association of increased FGF-23 was only significant in those with serum creatinine greater than median. In CS, high levels of FGF-23 are independently related to a poor clinical outcome. However, this prognostic association appears only to apply in patients with impaired renal function. ClinicalTrials.gov NCT00491036. Registered 22 June 2007.


Mechanism of polymeric nanoparticle-based drug transport across the blood-brain barrier (BBB).
In 1995 it was reported for the first time that nanoparticles could be used for the delivery of drugs across the blood-brain barrier (BBB) following intravenous injection. In vitro and in vivo experiments show that the underlying mechanism is receptor-mediated endocytosis followed by transcytosis. No opening of the tight junctions was observed. Due to the overcoating of the nanoparticles with polysorbate 80 or poloxamers 188, apolipoproteins A-I and/or E are adsorbed from the blood on to the particle surface after injection. These apolipoproteins mediate the interaction with LDL or scavenger receptors on the BBB followed by the above brain uptake processes. Likewise, covalent attachment of these apolipoproteins or of transferrin, insulin or antibodies against the respective receptors also enables a similar nanoparticle-mediated drug transport across the BBB. From these results it can be concluded that the nanoparticles act as "Trojan Horses" taking advantage of physiological receptor-mediated transport processes across the BBB.


Enzyme and nucleic acid formation during synchronous growth of Rhodopseudomonas spheroides.
The synthesis of various cell components was examined during the anaerobic photosynthetic growth of synchronous populations of Rhodopseudomonas spheroides. Net deoxyribonucleic acid (DNA), ribonucleic acid (RNA), and protein increased continuously as did the rate of incorporation of radioactive precursors into protein. The rates of incorporation of radioactive precursors into RNA and DNA were marked by abrupt discontinuities. It is not clear whether these discontinuities represent changes in rates of synthesis or fluctuations in precursor pools. Although the synthesis of bacteriochlorophyll occurred in a continuous manner, those enzymes examined which are involved in the synthesis of tetrapyrroles, i.e., succinyl CoA thiokinase, delta-aminolevulinic acid synthetase, and delta-aminolevulinic acid dehydrase, increased discontinuously. Two other enzymes not involved in tetrapyrrole biosynthesis were examined. Alkaline phosphatase increased in a stepwise manner during the division cycle, whereas the synthesis of ornithine transcarbamylase increased rapidly before leveling off for a period of time until synthesis began again. In each instance of discontinuous enzyme synthesis, increases occurred at regular and characteristic times during the division cycle. Ammonium sulfate precipitation was employed to remove low molecular weight end product inhibitors from enzyme preparations. These studies suggested that the stepwise increases in enzyme activity observed in the present investigation were not affected by periodic end product inhibition. A temporal map of enzyme synthesis during the division cycle was constructed. Both delta-aminolevulinic acid synthetase and delta-aminolevulinic acid dehydrase appeared early in the division cycle, whereas alkaline phosphatase and succinyl CoA thiokinase appeared later on.


White matter in the older brain is more plastic than in the younger brain.
Visual perceptual learning (VPL) with younger subjects is associated with changes in functional activation of the early visual cortex. Although overall brain properties decline with age, it is unclear whether these declines are associated with visual perceptual learning. Here we use diffusion tensor imaging to test whether changes in white matter are involved in VPL for older adults. After training on a texture discrimination task for three daily sessions, both older and younger subjects show performance improvements. While the older subjects show significant changes in fractional anisotropy (FA) in the white matter beneath the early visual cortex after training, no significant change in FA is observed for younger subjects. These results suggest that the mechanism for VPL in older individuals is considerably different from that in younger individuals and that VPL of older individuals involves reorganization of white matter.


Reconstitution of high-grade serous ovarian carcinoma from primary fallopian tube secretory epithelial cells.
Fallopian tube secretory epithelial cells (FTSECs) have been suggested to be the source of high-grade serous ovarian carcinoma (HGSOC). Although several genetic alterations are known to be involved in HGSOC development, the minimal requirements remain unclear. We aimed to identify oncogenic mutations indispensable for HGSOC development in a stepwise model, using immortalized FTSECs. FTSECs were isolated from clinical samples and immortalized by overexpression of cyclin D1, CDK4R24C, and hTERT. Oncogenic mutations in the p53, c-Myc, and RAS/PI3K pathways were mimicked by lentiviral transduction. We found two distinct patterns of gene alteration essential for HGSOC development: p53/KRAS/AKT and p53/KRAS/c-Myc. Dominant-negative p53, alone or combined with oncogenic KRAS (KRASV12), constitutively active AKT (CA-AKT), and c-Myc, did not induce tumorigenesis in immortalized cells; however, overexpression of CA-AKT or c-Myc, along with dominant-negative p53 and KRASV12, conferred tumorigenic potential. Transformed FTSECs formed tumors in nude mice that were grossly, histologically, and immunohistochemically similar to human HGSOCs. Interestingly, mice harboring tumors with c-Myc amplifications displayed extensive metastases, consistent with the increased dissemination in their human counterparts. Thus, aberrant p53/KRASV12/c-Myc or p53/KRASV12/PI3K-AKT signaling was the minimum requirement for FTSEC carcinogenesis. The model based on this evidence could shed light on the early stages of HGSOC development.


EVOLUTION OF BASAL METABOLIC RATE AND ORGAN MASSES IN LABORATORY MICE.
Animal species of similar body mass vary widely in basal metabolic rate (BMR). A central problem of evolutionary physiology concerns the anatomical/physiological origin and functional significance of that variation. It has been hypothesized that such interspecific differences in wild animals evolved adaptively from differences in relative sizes of metabolically active organs. In order to minimize confounding phenotypic effects and maximize relevant genetic variation, we tested for intraspecific correlations between body-mass-corrected BMR and masses of four organs (heart, kidney, liver, and small intestine) among six inbred strains of mice. We found significant differences between strains in BMR and in masses of all four organs. Strains with exceptionally high (or low) BMR tended to have disproportionately large (or small) organs. The mass of each organ was correlated with the masses of each of the other three organs. Variation in organ masses accounted for 52% of the observed variation in BMR, of which 42% represented between-strain variation, and 10% represented within-strain variation. This conclusion is supported by published measurements of metabolic rates of tissue slices from the four organs. The correlation between BMR and intestine or heart mass arose exclusively from differences between strains, while the correlation between BMR and liver or kidney mass also appeared in comparing individual mice within the same strain. Thus, even though the masses of the four examined organs account for no more than 17% of total body mass, their high metabolic activities or correlated factors account for much of the variation in BMR among mice. We suggest that large masses of metabolically active organs are subject to natural selection through evolutionary trade-offs. On the one hand, they make possible high-energy budgets (advantageous under some conditions), but on the other hand they are energetically expensive to maintain.


The PROTEIN PHOSPHATASE4 Complex Promotes Transcription and Processing of Primary microRNAs in Arabidopsis.
PROTEIN PHOSPHATASE4 (PP4) is a highly conserved Ser/Thr protein phosphatase found in yeast, plants, and animals. The composition and functions of PP4 in plants are poorly understood. Here, we uncovered the complexity of PP4 composition and function in Arabidopsis (Arabidopsis thaliana) and identified the composition of one form of PP4 containing the regulatory subunit PP4R3A. We show that PP4R3A, together with one of two redundant catalytic subunit genes, PROTEIN PHOSPHATASE X (PPX)1 and PPX2, promotes the biogenesis of microRNAs (miRNAs). PP4R3A is a chromatin-associated protein that interacts with RNA polymerase II and recruits it to the promoters of miRNA-encoding (MIR) genes to promote their transcription. PP4R3A likely also promotes the cotranscriptional processing of miRNA precursors, because it recruits the microprocessor component HYPONASTIC LEAVES1 to MIR genes and to nuclear dicing bodies. Finally, we show that hundreds of introns exhibit splicing defects in pp4r3a mutants. Together, this study reveals roles for Arabidopsis PP4 in transcription and nuclear RNA metabolism.


Genetic evidence that brassinosteroids suppress pistils in the maize tassel independent of the jasmonic acid pathway.
The developmental genetics of reproductive structure control in maize must consider both the staminate florets of the tassel and the pistillate florets of the ear synflorescences. Pistil abortion takes place in the tassel florets, and stamen arrest is affected in ear florets to give rise to the monoecious nature of maize. Gibberellin (GA) deficiency results in increased tillering, a dwarfed plant syndrome, and the retention of anthers in the ear florets of maize. The silkless1 mutant results in suppression of silks in the ear. We demonstrate in this study that jasmonic acid (JA) and GA act independently and show additive phenotypes resulting in androecious dwarf1;silkless1 double mutant plants. The persistence of pistils in the tassel can be induced by multiple mechanisms, including JA deficiency, GA excess, genetic control of floral determinacy, and organ identity. The silkless1 mutant can suppress both silks in the ear and the silks in the tassel of JA-deficient and AP2 transcription factor tasselseed mutants. We previously demonstrated that GA production was required for brassinosteroid (BR) deficiency to affect persistence of pistils in the tassel. We find that BR deficiency affects pistil persistence by an independent mechanism from the silkless1 mutant and JA pathway. The silkless1 mutant did not prevent the formation of pistils in the tassel by nana plant2 in double mutants. In addition, we demonstrate that there is more to the silkless1 mutant than just a suppression of pistil growth. We document novel phenotypes of silkless1 mutants including weakly penetrant ear fasciation and anther persistence in the ear florets. Thus, the JA/AP2 mechanism of pistil retention in the tassel and silk growth in the ear are similarly sensitive to loss of the SILKLESS1 protein, while the BR/GA mechanism is not.


The cerebral cortex origin of enflurane-induced generalized seizure in cats.
The role of sensorimotor cortex (anterior and posterior sigmoid gyri) as the origin of enflurane-induced generalized seizures was examined and compared to that of lidocaine-induced seizures in cats. The inhaled enflurane concentration was adjusted at 3.5% in oxygen, the maximum potency to induce generalized seizures. Repetitive electrical stimulation with supramaximum intensity at a forepaw (2 Hz, 0.5 ms, 10 V) induced generalized seizures, which ended with a sudden appearance of isoelectricity in the electroencephalogram (EEG), the so-called "postictal depression." Repetitive auditory stimuli also induced similar grand mal-type EEGs. Unilateral ablation of the sensorimotor cortex completely blocked the induction of generalized seizures by contralateral somatosensory stimuli. However, it had little effect on the induction of seizures by ipsilateral somatosensory stimuli or bilateral auditory stimuli. In contrast, bilateral ablation of the sensorimotor cortex did not have a significant effect on the lidocaine-induced seizures. These findings indicate that the involvement of the sensorimotor cortex is essential for the development of enflurane-induced but not lidocaine-induced seizures.


Revisiting the Mechanisms of CNS Immune Privilege.
Whereas the study of the interactions between the immune system and the central nervous system (CNS) has often focused on pathological conditions, the importance of neuroimmune communication in CNS homeostasis and function has become clear over that last two decades. Here we discuss the progression of our understanding of the interaction between the peripheral immune system and the CNS. We examine the notion of immune privilege of the CNS in light of both earlier findings and recent studies revealing a functional meningeal lymphatic system that drains cerebrospinal fluid (CSF) to the deep cervical lymph nodes, and consider the implications of a revised perspective on the immune privilege of the CNS on the etiology and pathology of different neurological disorders.


Static and dynamic postural control: Comparison between community old adults and people with Parkinson's disease.
To compare the static and dynamic postural control of people with Parkinson's disease and community old adults. Thirty-five people were in the Parkinson's disease group (PDG; 12 women, 62.4 ± 11.0 years, 77.9 ± 15.6 kg, 166.5 ± 11.0 cm, 27.9 ± 3.8 kg/m2 , 1.9 ± 0.5 Hoehn & Yahr) and 32 were in the old adults group (OAG; 13 women, 69.5 ± 6.0 years, 74.2 ± 12.3 kg, 165.0 ± 8.3 cm, 27.2 ± 4.0 kg/m2 ). The static balance was measured on a force platform, three 30-s trials in four conditions: feet side-by-side (FSBS) and semi-tandem stance (ST) positioning, eyes open (EO) and eyes closed (EC). The total sway path length (SPL), sway area (SA), anterior-posterior (APSR) and medial-lateral (MLSR) sway range of the centre of pressure were obtained. Dynamic balance was assessed using the timed-up-and-go test (TUG). For comparison between groups and repeated-measures, a mixed-design ANOVA was carried out and the Mann-Whitney U test to compare TUG between groups. The significance level was set at p ≤ .05. Between groups, PDG presented higher mean values for SPL, APSR and SA in feet side-by-side eyes open compared to the OAG, for SPL in feet side-by-side eyes closed, for SPL and SA in STEO. For repeated-measures, both groups had higher mean values in the EC condition compared to EO and MLSR compared to APSR. No significant difference was found between groups for TUG. Balance disorders are found early in people with Parkinson's disease compared to healthy older adults. Thus, Parkinson's disease seems to advance the process of alterations in the postural control system.


The postnatal development of blood vessels in the optic nerve of normotensive and hypertensive rats.
The blood vessels in the optic nerve of normotensive and hypertensive rats have been examined at 2, 4, 8 and 12 weeks of age. The pattern of development was found to be different in the two strains, with the number of blood vessels in the hypertensive rat optic nerve being lower at 2 weeks, but greater at 12 weeks than the normotensive rat. There appeared to be no correlation between vascularity and either myelination or changes in the fibre diameter spectrum at the ages studied. It is concluded that while the cause of the increased vascularity of the optic nerve in hypertensive rats is not known, it appears to be without effect in the structural development of the optic nerve.


Unresolved issues in the future of pharmacy.
The effect of the major forces shaping pharmacy's future--technology, economics, and social values--is discussed. Pharmacy can best respond to these forces by expanding the informational component of pharmacy practice and by returning to its fundamental relationship with society--that is, by accepting responsibility for drug-use control. To accomplish this, pharmacy must go through a process of occupational reconstruction and self-renewal. Technological forces shaping pharmacy practice include computers and robotics, communications, and therapeutics. Regarding economic changes, medical-care decisions are shifting away from individuals toward "third parties." This factor, combined with output-based payment systems, may lead to a consolidation of service providers. Marketing pharmaceutical services and organizing pharmacy's internal structure will become important. Some of the social forces affecting pharmacy's future include the aging population, the weakening of professional authority, and pharmacy's public image. Just as society goes through the "information revolution," pharmacy will need to undergo a "reprofessionalization." Pharmacy's societal function should involve "pharmaceutical care," a concept that includes both drug-product control and clinical pharmacy services. Pharmacy should return to its preindustrial origins in valued, complex, specific, and committed public service if it wishes a happy postindustrial future.


Delayed visuomotor development in children born to adolescent mothers.
The objective of the present study was to determine visuomotor development of children born to adolescent mothers and to compare it with that observed in those born to adult mothers. The sample included 59 urban Mestizo children, 7-8 years of age, who were born to adolescent mothers, and 73 urban Mestizo children of the same age, who were born to adult mothers (>20 years). Visuomotor development was assessed using the Bender test. Children born to adolescent mothers had a higher number of errors in the Bender Gestalt scores compared to those obtained by children born to adult mothers. Items of perseverance and integration in the Bender-Gestalt test were the most affected in children born to adolescent mothers. Of the children born to adolescent mothers, 13.8% repeated a school grade compared to 4.3% of children born to adult mothers (P < 0.01). Differences in sociocultural circumstances between the adolescent and adult mothers may have influenced the results. Nevertheless, children born to adolescent mothers have delayed visuomotor maturation and a low performance at school. Am. J. Hum. Biol. 9:717-723, 1997. © 1997 Wiley-Liss, Inc.


Novel approaches and hurdles to somatic cloning in cattle.
The overall efficiency of somatic cloning in cattle is still low. Many factors are necessary for successful birth of live offspring. Among them, the source of donor cells reveals the importance of the donor genotype but also the influence of the cell line itself. The cell cycle stage has been intensively investigated, and recent results indicate that, in cattle, the G0 stage of the donor nuclei is not a prerequisite for reprogramming, as highly proliferating cultured fibroblasts also result in live offspring after nuclear transfer. A technical approach using direct microinjection of fibroblast nuclei, instead of fusion of the whole cell, has proved to result in high in vitro development rates in cattle. However, full-term development of somatic cloned embryos is still limited by long-lasting effects and a high incidence of losses at periimplantation time (as well as in late gestation and around calving).


A PstI restriction fragment length polymorphism in the 5' untranslated region of DRD4 is not associated with schizophrenia.
We detected a PstI restriction fragment length polymorphism in the 5'-non-coding region of the dopamine D4 receptor gene (DRD4), making it the seventh known polymorphism for DRD4. DNA polymorphisms in the putative regulatory region of DRD4 are of interest because of the reported six-fold increase in D4 receptors in post-mortem schizophrenic brain tissue [Seeman P, Guan HC, Van Tol HHM (1993) Nature, 365, 441-445]. We found no difference in the PstI allele frequencies between DSM-III-R schizophrenia patients (0.76 and 0.24, n = 41), and matched control Caucasians (0.77 and 0.23, n = 46). The PstI DRD4 polymorphism has potential use in linkage and association studies with neuropsychiatric and cardiovascular disorders.


Impact of Functional Hepatic Venous Outflow Obstruction on Perioperative Outcome After Living-Donor Liver Transplant.
An optimal initial graft function after living-donor liver transplant depends on optimal graft hemodynamics. Nonmechanical impediments to free hepatic venous outflow, due to elevated central venous pressure, may obstruct the "functional" hepatic venous outflow. Here, we evaluated whether central venous pressure affected early graft function and outcomes in adult living-donor liver transplant recipients. This prospective observational study included 61 living-donor liver transplant recipients without technical complications who received transplants from August 2013 to November 2014. Hemodynamic variables were measured preoperatively, at anhepatic phase, 30 minutes postreperfusion, at end of surgery, and during postoperative days 1-5. Patients with high central venous pressure showed functional hepatic venous outflow obstruction, which caused delayed recovery of graft function. Although postoperative central venous pressure was the only identified independent risk factor for mortality, all 5 deaths in our study group occurred in those who had high central venous pressure at the anhepatic, postreperfusion, end of surgery, and postoperative phases. A postoperative central venous pressure value of ~11 mm Hg was determined to be the cutoff for high-risk mortality, with area under the curve of 0.859 (sensitivity of 80%, specificity of 68%). Increased central venous pressure was associated with increased portal venous pressure (increase of 45%, range, 28%-89%; P = .001). Central venous pressure at end of surgery (r = 0.45, P ≤ .001) and at posttransplant time points (r = 0.29, P = .02) correlated well with portal venous pressure at end of surgery. Other risk factors for early allograft dysfunction were Model for End-Stage Liver Disease and cardiac output posttransplant. High central venous pressure, modulating portal venous pressure, can result in functional hepatic venous outflow obstruction, causing delayed graft function recovery and increased risk of mortality. Maintaining a central venous pressure below 11 mm Hg is beneficial.


Psychometric evaluation of the eating disorder examination adapted for children.
The Eating Disorder Examination adapted for children (ChEDE) is the child version of the semi-structured gold standard eating disorder interview for adults. This study was a comprehensive test statistic evaluation of the German ChEDE in a large sample of children and adolescents with anorexia nervosa, binge eating disorder, loss of control eating, overweight and obesity, as well as non-eating-disordered and chronically ill control probands (n = 352). Excellent inter-rater reliability, adequate internal consistency and satisfactory stability of ChEDE indicators were demonstrated. ChEDE indicators discriminated between diverse forms of eating and weight disturbances and normative eating and were significantly correlated with conceptually related measures. Factorial validity was not convincing; a brief eight-item scale showed the best fit. Item statistics were mostly acceptable. Overall, the ChEDE's German translation reliably and validly assesses psychopathology across the eating and weight disorder spectrum and facilitates international comparison of eating disorder research.


Association between multimorbidity patterns and chronic pain in elderly primary care patients: a cross-sectional observational study.
Multimorbidity is a highly prevalent health problem, which may reduce adherence, produce conflicts in treatment, and is not yet supported by evidence-based clinical recommendations. Many older people suffer from more than one chronic disease as well as from chronic pain. There is some evidence that disease management can become more complex if multimorbid patients suffer from chronic pain. In order to better consider the patients' comorbidity spectrum in clinical pain treatment recommendations, evidence is needed regarding which disease combinations are frequently related with the presence of chronic pain. Therefore, our aim is to identify diseases and disease combinations in a multimorbid population, which are associated with the patient-reported presence of chronic pain. Analyses are based on cross-sectional data of the MultiCare Cohort Study, an observational cohort study based on interviews with 3189 multimorbid patients aged 65+, randomly selected from 158 practices, and their GPs. The response rate was 46.2 %. Data were collected in GP interviews and comprehensive patient interviews. Diseases and disease combinations associated with chronic pain were identified by CART (classification and regression tree) analyses performed separately for both genders. 46 chronic conditions were used as predictor variables and a dichotomized score from the Graded Chronic Pain Scale was used as outcome variable. About 60 % of the study participants were female. Women more often reported chronic pain than men. The most important predictor of a higher pain level in the female population was chronic low back problems, especially if combined with chronic gastritis, hyperuricemia/gout, cardiac insufficiency, neuropathies or depression. Regarding the pain level the male population was also divided best by chronic low back problems, especially if combined with intestinal diverticulosis, neuropathies or chronic ischemic heart disease. Our analyses are a first step in identifying diseases and disease combinations that are related to chronic pain. The most important condition seems to be low back problems. Back pain and pain in other body regions seems to be interrelated with cardiometabolic conditions. In women, psychosocial issues like depression also seem to be relevant. ISRCTN89818205 .


A population balance model of enzymatic lysis of microbial cells.
A model is proposed for enzymatic lysis of microbial cells based on number balances over the distribution of cell-wall mass in a population of cells. Analytical solutions to the population balance equations were obtained by the method of characteristics for simple reaction kinetics. The model has been used to analyze the following cases of lysis in a nonhomogeneous cell population: wall hydrolysis with cell rupture and product release, the effect of a distribution of lysis rates, and lysis of two-layer cell walls. Rate expressions for the reactions of lysis can be derived from bulk-phase experiments; the distributions of cell size and product content can be measured independently by flow cytometric techniques. The population model also provides an explanation for the initial lag seen in lysis kinetics for virtually any initial distribution. The model demonstrates patterns of lysis and product recovery for heterogeneous populations of cells and also applies to the more general problem of soluble-enzyme reactions with heterogeneous solid substrates.


ABF1 Positively Regulates Rice Chilling Tolerance via Inducing Trehalose Biosynthesis.
Chilling stress seriously limits grain yield and quality worldwide. However, the genes and the underlying mechanisms that respond to chilling stress remain elusive. This study identified ABF1, a cold-induced transcription factor of the bZIP family. Disruption of ABF1 impaired chilling tolerance with increased ion leakage and reduced proline contents, while ABF1 over-expression lines exhibited the opposite tendency, suggesting that ABF1 positively regulated chilling tolerance in rice. Moreover, SnRK2 protein kinase SAPK10 could phosphorylate ABF1, and strengthen the DNA-binding ability of ABF1 to the G-box cis-element of the promoter of TPS2, a positive regulator of trehalose biosynthesis, consequently elevating the TPS2 transcription and the endogenous trehalose contents. Meanwhile, applying exogenous trehalose enhanced the chilling tolerance of abf1 mutant lines. In summary, this study provides a novel pathway 'SAPK10-ABF1-TPS2' involved in rice chilling tolerance through regulating trehalose homeostasis.


Suicidal ideation in university students in Lithuania amid the COVID-19 pandemic: A prospective study with pre-pandemic measures.
We aimed to identify patterns of changes in suicidal ideation among university students six months after the COVID-19 outbreak, in comparison to the pre-pandemic suicidal ideation. Furthermore, we explored the links among these patterns and mental health indicators. 474 university students participated in the study in October-December 2019 and October-December 2020. The latent class change analysis revealed four groups: no-ideation (68.1%), stable low ideation (16.2%), increased ideation (8.9%), and decreased ideation (6.8%). Increased, in comparison to decreased ideation, was positively linked to changes in depression, stress, and anxiety. More loneliness during the pandemic was related to higher suicidal ideation.


Wearables in cardiology: Here to stay.
The adoption of wearables in medicine has rapidly expanded worldwide. New generations of wearables are emerging, driven by consumers' demand to monitor their own health. With the ongoing development of new features capable of assessing real-time biometric data, the impact of wearables on cardiovascular management has become inevitable. Smartwatches, among other wearable devices, offer a user-friendly noninvasive approach to continuously monitor for health parameters. With advancements in artificial intelligence, the photoplethysmography-generated pulse waveform has the potential to accurately detect episodes of atrial fibrillation and one day could replace conventional diagnostic and long-term monitoring methods. Clinical benefits that could arise from the use of such devices include refining stroke prevention strategies, personalizing AF management, and optimizing the patient-physician relationship. Wearables are changing not only the way clinicians conduct research but also the future of cardiovascular preventive and therapeutic care. As such, wearables are here to stay.


Baroreflex sensitivity, blood pressure buffering, and resonance: what are the links? Computer simulation of healthy subjects and heart failure patients.
The arterial baroreflex buffers slow (<0.05 Hz) blood pressure (BP) fluctuations, mainly by controlling peripheral resistance. Baroreflex sensitivity (BRS), an important characteristic of baroreflex control, is often noninvasively assessed by relating heart rate (HR) fluctuations to BP fluctuations; more specifically, spectral BRS assessment techniques focus on the BP-to-HR transfer function around 0.1 Hz. Skepticism about the relevance of BRS to characterize baroreflex-mediated BP buffering is based on two considerations: 1) baroreflex-modulated peripheral vasomotor function is not necessarily related to baroreflex-HR transfer; and 2) although BP fluctuations around 0.1 Hz (Mayer waves) might be related to baroreflex BP buffering, they are merely a not-intended side effect of a closed-loop control system. To further investigate the relationship between BRS and baroreflex-mediated BP buffering, we set up a computer model of baroreflex BP control to simulate normal subjects and heart failure patients. Output variables for various randomly chosen combinations of feedback gains in the baroreflex arms were BP resonance, BP-buffering capacity, and BRS. Our results show that BP buffering and BP resonance are related expressions of baroreflex BP control and depend strongly on the sympathetic gain to the peripheral resistance. BRS is almost uniquely determined by the vagal baroreflex gain to the sinus node. In conclusion, BP buffering and BRS are unrelated unless coupled gains in all baroreflex limbs are assumed. Hence, the clinical benefit of a high BRS is most likely to be attributed to vagal effects on the heart instead of to effective BP buffering.


Epstein-Barr virus (EBV) gene expression in lymphoid B cells during acute infectious mononucleosis (IM) and clonality of the directly growing cell lines.
We examined the patterns of viral gene expression in acute infectious mononucleosis (IM) patients and the clonality of the directly growing EBV-carrying cell lines. Both low- and high-density EBV-carrying B cells obtained from the patients' tonsils expressed EBNA1, EBNA2 and LMP1. Like LCLs and immunoblastic B-cell lymphomas, the in vivo EBV-carrying low-density cells used only the latency III program for viral gene expression. The in vivo EBV-carrying high-density B cells used both the latency I program, as indicated by the QUK-, and the latency III program, as indicated by the YUK-EBNA1. This suggests that the lymphoid tissues contained not only proliferating immunoblasts but also cells programmed for latent viral persistence in vivo. EBV-carrying cells that grew directly into permanent cell lines in the presence of virus-neutralizing antibody and a late viral inhibitor were polyclonal, as indicated by JH rearrangement. Two of the high-density-derived lines had identical JH and TR patterns, indicating a common parental origin. Our investigation indicates that EBV-carrying cells divide and survive in a fully competent immune system during the outbreak of acute IM.


Denaturing gradient gel method for mapping single base changes in human mitochondrial DNA.
A denaturing gradient gel electrophoresis (DGGE) method is described that detects even single base pair changes in mitochondrial DNA (mtDNA). In this method, restriction fragments of mtDNA are electrophoresed in a urea/formamide gradient gel at 60 degrees C. Migration distance of each mtDNA fragment in the gel depends on melting behavior which reflects base composition. Fragments are located by Southern blotting with specific mtDNA probes. With just four carefully chosen restriction enzymes and as little as 50-100 ng of mtDNA, the method covers almost the entire human mitochondrial genome. To demonstrate the method, human mtDNA was analyzed. In six normal individuals, DGGE revealed melting behavior polymorphisms (MBPs) in mtDNA fragments that were not detected by restriction fragment length polymorphism (RFLP) analysis in agarose gels. Another individual, shown to have a melting behavior polymorphism in the cytochrome b coding region, was studied in detail. By mapping, the mutation was deduced to lie between nt 14905 and 15370. The affected fragment was amplified by PCR and sequenced. Specific base changes were identified in the region predicted by the gel result. This method will be especially useful as a diagnostic tool in mitochondrial disease for rapid localization of mtDNA mutations to specific regions of the genome, but DGGE also could complement RFLP analysis as a more sensitive method to follow maternal lineage in human and animal populations in a variety of research fields.


[Synthesis of Cu2O-Ag-AgBr/MA visible photocatalyst and its performance in degradation of 2-chlorophenol].
Cu2O-Ag-AgBr/MA plasmon photocatalyst was prepared by the co-deposition of Cu2O and Ag-AgBr nanoparticles on mesoporous alumina (MA). The samples were characterized by means of X-ray diffraction (XRD) ,X-ray photoelectron spectroscopy (XPS) and diffuse reflectance UV-vis spectra (UV-vis DRS). The results showed that both Ag+ and Ag0 existed on the surface. The photocatalytic activity of the samples prepared were evaluated by degradation of 2-chlorophenol (2-CP) under visible light (λ >420 nm) irradiation. The results showed that the catalyst had high photocatalytic activity for the degradation of 2-CP. Meanwhile, the doping of Cu2O nanoparticles significantly inhibited the release of silver ions during the photocatalytic reaction, which improved the photostability of the catalyst. Analyses on the effects of various scavengers showed that h+ , O2- and OH radicals were the primary active species.


Specific activation of transcription initiation by the sequence-specific DNA-binding agents distamycin A and netropsin.
A series of promoters with nine base-pair substitutions in the spacer DNA separating the -10 and -35 regions was used to demonstrate that Escherichia coli RNA polymerase is sensitive to events affecting the spacer DNA--a region not directly contacted by the enzyme. The drugs distamycin A and netropsin specifically enhanced the rate of functional complex formation at a promoter bearing a substitution of nonalternating A-T base pairs. The effect is exerted at an early step in the RNA polymerase-promoter interaction. We hypothesize that a drug-induced structural alteration in the spacer DNA occurs, similar to that normally resulting from RNA polymerase binding. These findings are relevant to an understanding of potential mechanisms of transcription activation.


Point: "bring those 'outside' observers in".
A teaching hospital is frequently overwhelmed by the number of people who want to observe a working therapeutic group; therefore the need to provide and enhance this experience for group members and leaders led us to try a new approach. After some initial experimentation, the technique of an observer participating through feedback sessions within the group made a major impact on members, leaders, and observers. Observers were held accountable for the privilege of joining the group experience, and the passiveness, which usually accompanies non-participation, decreased notably. And last, but certainly not least in our experience, patients felt less exploited when the unseen people shared their observations with them. Bringing these outside observers in helped the group's potential to develop more fully.


Exercise Test Predicts Both Noncardiovascular and Cardiovascular Death in a Primary Prevention Population.
To identify specific causes of death and determine the prevalence of noncardiovascular (non-CV) deaths in an exercise test referral population while testing whether exercise test parameters predict non-CV as well as CV deaths. Non-imaging exercise tests on patients 30 to 79 years of age from September 1993 to December 2010 were reviewed. Patients with baseline CV diseases and non-Minnesota residents were excluded. Mortality through January 2016 was obtained through Mayo Clinic Records and the Minnesota Death Index. Exercise test abnormalities included low functional aerobic capacity (ie, less than 80%), heart rate recovery (ie, less than 13 beats/min), low chronotropic index (ie, less than 0.8), and abnormal exercise electrocardiogram (ECG) of greater than or equal to 1.0 mm ST depression or elevation. We also combined these four abnormalities into a composite exercise test score (EX_SCORE). Statistical analyses consisted of Cox regression adjusted for age, sex, diabetes, hypertension, obesity, current and past smoking, and heart rate-lowering drug. The study identified 13,382 patients (females: n=4736, 35.4%, 50.5±10.5 years of age). During 12.7±5.0 years of follow-up, there were 849 deaths (6.3%); of these 162 (19.1%) were from CV; 687 (80.9%) were non-CV. Hazard ratios for non-CV death were significant for low functional aerobic capacity (HR, 1.42; 95% CI, 1.19 to 1.69; P<.0001), abnormal heart rate recovery (HR, 1.36; 95% CI, 1.15 to 1.61; P<.0033), and low chronotropic index (HR, 1.49; 95% CI, 1.26 to 1.77; P<.0001), whereas abnormal exercise ECG was not significant. All exercise test abnormalities including EX_SCORE were more strongly associated with CV death versus non-CV death except abnormal exercise ECG. Non-CV deaths predominated in this primary prevention cohort. Exercise test abnormalities not only predicted CV death but also non-CV death.


Hepatic artery chemoembolization with distal transradial access for primary hepatocellular carcinoma: a novel interventional therapy for peripheral tumors.
To investigate the feasibility and safety of hepatic artery chemoembolization via the distal transradial access (dTRA). The clinical data of 130 patients with primary hepatocellular carcinoma treated in The First Hospital of Jilin University between August 1, 2020 and December 31, 2020, were retrospectively analyzed. Patients were confirmed to have primary hepatocellular carcinoma by preoperative imaging or pathology, with Child-Pugh Grade A or B and persistently palpable distal radial pulses. After a negative Allen test, patients underwent transcatheter arterial chemoembolization (TACE) via dTRA. The puncture success rate, the average number of needles, puncture time, distal radial occlusion and wrist hematoma were used to evaluate the treatment efficacy in the patients. All the punctures were performed using 21G steel needles. 5F sheaths were used for 84 cases, and 4F sheaths for 46 cases. The total was 130 cases. Among the 130 cases, 112 cases (86.2%) were successful in the puncture, 18 cases (13.8%) failed in the puncture. The success rate of the descending aorta selection using an MPA1 catheter (Cordis, Santa Clara, CA, USA) was 96.2% (125/130). In the remaining 5 cases, the selection succeeded after a 5F pigtail catheter was used instead. The success rate of the celiac trunk or superior mesenteric artery selection using an MPA1 catheter was 100%. No bleeding or hematoma occurred after 2-4 hours of compression following distal radial artery puncture, and both distal and proximal radial artery pulses were palpable. No arterial dissection or pseudoaneurysm was found, and there was no distal radial artery occlusion. Fourteen patients underwent 2 sessions of distal radial artery punctures, and no vascular occlusion was found in these patients either. TACE via the dTRA is feasible and safe for primary hepatocellular carcinoma.


Fabry disease in mice protects against lethal disease caused by Shiga toxin-expressing enterohemorrhagic Escherichia coli.
Fabry disease is an X-linked recessive disorder in which affected persons lack alpha-galactosidase A (alpha -GalA), which leads to excess glycosphingolipids in tissues, mainly globotriaosylceramide (Gb3). Gb3 is the cellular receptor for Shiga toxin (Stx), the primary virulence factor of enterohemorrhagic Escherichia coli. alpha-GalA-knockout mice were significantly protected against lethal intraperitoneal doses of Stx2 or oral doses of Stx2-expressing bacteria, compared with wild-type (wt) control mice. Kidneys of moribund wt mice revealed tubular necrosis, but no histopathologic changes were observed in Gb3-overexpressing mice. Reducing Gb3 levels in alpha-GalA-knockout mice by the intravenous injection of recombinant human alpha-GalA restored the susceptibility of knockout mice to lethal doses of Stx2. These results suggest that excess amounts of Gb3 in alpha-GalA-deficient mice may impair toxin delivery to susceptible tissues.


Prevalence and characterization of novel pANCA, antibodies to the high mobility group non-histone chromosomal proteins HMG1 and HMG2, in systemic rheumatic diseases.
To determine the immunodiagnostic value of antibodies to the high mobility group non-histone chromosomal proteins HMG1 and HMG2, which have been identified as novel target antigens of perinuclear antineutrophil cytoplasmic antibodies (pANCA), in sera from patients with systemic rheumatic diseases. Anti-HMG1 or HMG2 antibody was assayed by ELISA and Western blotting in sera from patients with systemic rheumatic diseases. These antibodies were analyzed for the relationship with pANCA detected by indirect immunofluorescence in these diseases, and with clinical features in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Anti-HMG1 or HMG2 antibody was frequently detected in sera from patients with RA (48%), SLE (45%), Sjögren's syndrome (SS) (44%), and systemic sclerosis (SSc) (41%). In these diseases, anti-HMG1 antibody was detected more frequently than anti-HMG2 antibody. In sera from patients with RA, the positivity for anti-HMG1 and HMG2 antibodies was significantly correlated with the positivity for pANCA (p < 0.0001). Anti-HMG1/HMG2 antibodies were associated with some disease activity variables, e.g., erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, joint score and hand grip strength in RA, and CH50, C3, C4, and IgG in SLE. Anti-HMG1/HMG2 antibodies are detected commonly in systemic rheumatic diseases, particularly in RA, SLE, SS, and SSc. HMGI and HMG2 seem to be the significant target antigens of pANCA in RA. These antibodies are significantly associated with disease activity indices in RA and SLE.


Cardiopulmonary response in obese children using treadmill exercise testing.
Obesity impairs performance in most athletic events. The prevalence of obesity in Taiwan has increased over the past decades. It is important to understand any alterations in cardiopulmonary responses to exercise in obese children. The purpose of this study is to evaluate the cardiorespiratory response to graded treadmill exercise testing protocol in obese children. Twenty obese and 10 control children between 8 to 12 years of age were recruited among patients at Pediatric Clinics. The treadmill was set at a grade of 10% to perform continuous treadmill walking. Measures of cardiopulmonary responses were recorded. Height, weight and body mass index were determined before testing. Cardiopulmonary responses including heart rate (HR), systolic pressure (SP), rate-pressure product (RPP) and forced vital capacity (FVC) were significantly different between obese children and normal children during and after exercise. The correlations of cardiopulmonary function to age, sex, height, body weight, triceps and biceps skinfold thickness were assessed, and a significant correlation was found between HR and age (r = 0.5, p < 0.05), as well as biceps skinfold thickness (r = 0.5, p < 0.05). There was also a good correlation between predicted values of FVC and age (r = -0.5, p < 0.05). The HR (r = 0.79, p < 0.05) was in correlation with tricep skinfold thickness in normal healthy children. In conclusion, there appears to show a relatively less efficient cardiopulmonary response in obese children. Regular exercise that improves fitness and body composition should have a favorable effect on obese children.


[Hydronephrosis presenting as the first sign of malignant lymphoma of the small intestine: report of a case].
A 45-year-old man was admitted to hospital on November 26, 1985 with the chief complaint of left hypochondrial pain. Excretory and retrograde pyelography revealed left hydronephrosis due to extrinsic obstruction of ureter. Computerized tomography and angiography revealed that a tumor of the small intestine was the cause of ureteral obstruction. In addition to the presence of a tumor, a fistula in the small intestine was disclosed on the upper gastrointestinal series. During the operation, a large mass which involved several organs was identified without mobility. The sophisticated operation was composed of wide resection of small intestine including the tumor, left hemicolectomy, left nephroureterectomy, splenectomy, partial pancreatectomy, duodeno-ileostomy and transverse sigmoidostomy was done on December 19, 1985. Pathological diagnosis was malignant lymphoma, diffuse small cell type infiltrating ureter, kidney and perirenal connective tissue. Because of poor postoperative course systemic chemotherapy was not performed and he died of disseminated intravascular coagulation on April 2, 1986.


Reproduction on the edge: large-scale patterns of individual performance in a marine invertebrate.
Reproductive output is a central attribute of life history, providing a measure of individual and population performance. The fields of ecology, biogeography, and evolutionary biology take disparate approaches in addressing spatial variation in reproduction, and thus we lack clear predictions for how reproductive output should vary geographically. We empirically investigate these contrasting theoretical approaches by determining geographic patterns in reproductive output for intertidal populations of the purple sea urchin, Strongylocentrotus purpuratus, at 15 sites spanning a large geographic distance (9 degrees span of latitude) from central California, USA, to Baja California, Mexico. Contrary to predictions from biogeography, some of the highest values of reproductive output are at sites near the species' southern range boundary. Additionally, sea urchins do not exhibit a latitudinal gradient in reproduction, but rather show considerable mesoscale variation in reproductive output. Spatial analyses reveal that this variation is correlated with coastal topographic features that are known to influence the pattern of nearshore nutrient flux and circulation. We hypothesize that urchins' reproductive output may be driven by the spatial distribution of their food supply, drift macroalgae, the abundance of which is influenced by both nutrient supply and alongshore transport processes that are coupled to topographic features. Large-scale studies such as this provide valuable insight into the causes of species' range limits, population connectivity, habitat reserve design, and forecasting the effects of climate change on species' distributions.


Comprehensive investigation on the power scaling of a tapered Yb-doped fiber-based monolithic linearly polarized high-peak-power near-transform-limited nanosecond fiber laser.
An all-fiberized linearly polarized nanosecond master oscillator power amplifier based on polarization-maintaining large-mode-area Yb-doped tapered double cladding fiber (T-DCF) is comprehensively investigated. Firstly, excellent performance of the Yb-doped T-DCF for suppressing nonlinear effects, including stimulated Brillouin scattering (SBS) effect and spectral broadening effects, is experimentally demonstrated and qualitatively analyzed. An SBS-free average output power of 8.8 W is obtained under pulse duration of 3.8 ns and repetition frequency of 80 kHz, with peak power of ∼30 kW, pulse energy of 110 µJ and nearly transform-limited linewidth of < 283.8 MHz respectively. The polarization extinction ratio is > 16 dB and near-diffraction-limited beam quality with M2 factor of 1.2 is maintained at the maximal output power. Moreover, the discussion on the optimization of the system for further power scaling is carried out based a nonlinear dynamic model that is capable of simultaneously evaluating the time-domain and frequency-domain evolution properties of the narrow-linewidth linearly-polarized pulsed laser, and meaningful conclusion is obtained.


Effect of Childhood Adversity and Positive Psychological Resources on Stress Response-Comparison Between Depressed and Nondepressed Young Adults.
The purpose of this study was to explore the relationship between stress response, childhood adversity, and positive psychological resources in young adults, to investigate the mediation effect of positive psychological resources, and to compare the moderated mediation effects between depressed and non-depressed groups. A total of 360 young adults (165 outpatients diagnosed with depression and 195 non-depressed participants) were recruited. Data were collected using the Adverse Childhood Events questionnaire, Positive Resources Test, and Stress Response Inventory. Models 4 and 14 of the PROCESS macro were used to test the mediating and moderated mediating effects. In both groups, the stress response was negatively correlated with positive psychological resources and positively correlated with childhood adversity. Positive psychological resources mediated childhood adversity and depression. In the depression group, positive resources had a moderated mediation effect on the relationship between childhood adversity, positive psychological resources, and stress response. The findings suggest the importance of enhancing positive psychological resources, especially in patient groups, to help overcome childhood adversity and cope with stress more effectively.


In Vivo Evaluation of the Toxic Effect of Ethyl Acetate Extracts of Marine Antibiotic Resistance Pseudomonas Species Derived from the Red Sea.
Eighty-nine cultured Pseudomonas species isolated from the sediment and water samples collected from five industrial Red Sea regions that have been affected by petroleum and industry. Genotypic (exoT, exoS, exoU, exoY, lasA, lasB, rhlA, rhlB, Pf1, PAGI-1, -2, and -3) and phenotypic (DNase, elastase, lipase, protease, siderophore, antibiotic resistance patterns) characteristics were determined. Out of these isolates, nine Pseudomonas isolates were selected as the hyperactive virulence factors producers along with highly resistant pattern against all antibiotics of different classes included in this study. They were subjected to phenotypic and chemotypic characterization as well as molecular identification through 16S rRNA gene amplification and sequencing. The bioactive metabolites of these nine strains were extracted by ethyl acetate followed by evaluating their cytotoxic activity toward liver tissues, kidney tissues, and other biochemical activities in rat. Both EGY6 and EGY8 caused the highest significant reduction in the levels of packed cell volume (PCV), red blood cell count (RBC), and hemoglobin (Hb), which indicate that these Pseudomonas strain metabolites could cause anemia and toxic effects on hematological values in animals that were infected with them. Rats treated with the most toxic extract, EGY8, showed severe histopathological alterations in liver and kidney.


The effect of acute alcohol ingestion on systemic hemodynamics and sleep architecture in young, healthy men.
Objective Heightened nocturnal blood pressure (BP) may be attributed to the disruption of sleep, a condition worsened by alcohol ingestion. This study investigated the effects of acute alcohol ingestion on hemodynamics and sleep architecture in a young, healthy cohort of male. METHODS: Subjects (n = 17) underwent acute alcohol ingestion reaching a breath alcohol content of 0.08. Each subject endured a battery of hemodynamic tests and had their sleep architecture and nocturnal blood pressure monitored pre- and post-ingestion. Results: Systolic blood pressure (SBP) increased both 30 minutes and 12 hours after alcohol. Ambulatory nocturnal SBP significantly increased after alcohol compared to baseline measures. Minutes of total, rapid eye movement, and light sleep all increased after alcohol ingestion, while a decrease was observed for sleep latency. Conclusions: An acute bout of heavy alcohol consumption may attenuate nocturnal BP dipping that, in turn, may hasten the progression of hypertension-related cardiovascular disease.


Determination of Intermolecular Interactions Using Polarization Compensated Heteronuclear Overhauser Effect of Hyperpolarized Spins.
The nuclear Overhauser effect (NOE) has long been used as a selective indicator for intermolecular interactions. Due to relatively small changes of signal intensity, often on the order of several percent, quantitative NOE measurements can be challenging. Hyperpolarization of nuclear spins can dramatically increase the NOE intensity by increasing population differences, but poses its own challenge in quantifying the original polarization level. Here, we demonstrate a method for the accurate measurement of intermolecular heteronuclear cross-relaxation rates by simultaneous acquisition of signals from both nuclei. Using this method, we measure cross-relaxation rates between water protons and (19)F of trifluoroacetic acid at concentrations ranging from 23 to 72 mM. A concentration-independent value of 2.46 × 10(-4) ± 1.02 × 10(-5) s(-1) M(-1) is obtained at a temperature of 301 K and validated using a nonhyperpolarized measurement. In a broader context, accurate measurement of heteronuclear cross-relaxation rates may enable the study of intermolecular interactions including those involving macromolecules where (19)F atoms can be introduced as site-selective labels.


Severe bilateral atrophy of the spinati muscles in a cadaver.
During the routine dissection of a 62-year-old male cadaver, bilateral atrophy of the supra and infraspinatus muscles was observed. The suprascapular nerves, cervical spinal cord and surrounding muscles were found to be normal. We propose that, in the face of normal histology and other normal shoulder girdle muscles and normal nerves, this case represents an instance of Parsonage-Turner syndrome. To our knowledge, this is the first report of bilateral spinati atrophy in a cadaver.


Strengthening Renal Registries and ESRD Research in Africa.
In Africa, the combination of noncommunicable diseases, infectious diseases, exposure to environmental toxins, and acute kidney injury related to trauma and childbirth are driving an epidemic of chronic kidney disease and end-stage renal disease (ESRD). Good registry data can inform the planning of renal services and can be used to argue for better resource allocation, audit the delivery and quality of care, and monitor the impact of interventions. Few African countries have established renal registries and most have failed owing to resource constraints. In this article we briefly review the burden of chronic kidney disease and ESRD in Africa, and then consider the research questions that could be addressed by renal registries. We describe examples of the impact of registry data and summarize the sparse primary literature on country-wide renal replacement therapy in African countries over the past 20 years. Finally, we highlight some initiatives and opportunities for strengthening research on ESRD and renal replacement therapy in Africa. These include the establishment of the African Renal Registry and the availability of new areas for research. We also discuss capacity building, collaboration, open-access publication, and the strengthening of local journals, all measures that may improve the quantity, visibility, and impact of African research outputs.


Long-term effectiveness of lithium in bipolar disorder: a multicenter investigation of patients with typical and atypical features.
Poor response to long-term lithium treatment has been reported to be associated with atypical features of bipolar disorder. The purpose of this study was to investigate the influence of atypical symptoms on the effectiveness and stability of long-term lithium treatment in a prospective, multicenter cohort of bipolar patients in a naturalistic setting. Patients were initially selected according to International Classification of Diseases, 8th Revision, criteria for bipolar disorder and required long-term treatment. Their diagnoses were reconfirmed according to DSM-IV upon its publication. They were prospectively followed for an approximately 20-year period ending in 2004 in 5 centers participating in the International Group for the Study of Lithium-Treated Patients. Examinations included a comprehensive psychiatric evaluation, an assessment of typical and atypical features on an 8-item scale, and an evaluation of clinical course using the morbidity index. Unbalanced repeated-measures regression models with structured covariance matrices were used to assess the extent to which the morbidity index was influenced by atypical symptoms, duration of treatment, and pretreatment features. A total of 242 patients were followed for a mean period of 10 years. In 142 patients, the number of typical features was greater than the number of atypical features, whereas in 100 patients the number of atypical features was greater than or equal to the number of typical features. The mean morbidity index remained stable over a period of 20 years in both groups of patients and was not significantly associated with the presence of atypical features, the duration of lithium treatment, the number or frequency of episodes, or latency from the onset of bipolar disorder to the start of lithium treatment. Our study suggests that long-term response to lithium maintenance treatment is stable both in patients with typical and in patients with atypical features. The predominance of either typical or atypical features did not result in different responses to long-term lithium treatment in this sample of bipolar patients.