Understanding and predicting future relapse in depression from resting state functional connectivity and self-referential processing.
The recurrent nature of Major Depressive Disorder (MDD) asks for a better understanding of mechanisms underlying relapse. Previously, self-referential processing abnormalities have been linked to vulnerability for relapse. We investigated whether abnormalities in self-referential cognitions and functioning of associated brain-networks persist upon remission and predict relapse. Remitted recurrent MDD patients (n = 48) and never-depressed controls (n = 23) underwent resting-state fMRI scanning at baseline and were additionally assessed for their implicit depressed self-associations and ruminative behaviour. A template-based dual regression approach was used to investigate between-group differences in default mode, cingulo-opercular and frontoparietal network resting-state functional connectivity (RSFC). Additional prediction of relapse status at 18-month follow-up was investigated within patients using both regression analyses and machine learning classifiers. Remitted patients showed higher rumination, but no implicit depressed self-associations or RSFC abnormalities were observed between patients and controls. Nevertheless, relapse was related to i) baseline RSFC between the ventral default mode network and the precuneus, dorsomedial frontal gyrus, and inferior occipital lobe, ii) implicit self-associations, and iii) uncontrollability of ruminative thinking, when controlled for depressive symptomatology. Moreover, preliminary machine learning classifiers demonstrated that RSFC within the investigated networks predicted relapse on an individual basis. Remitted MDD patients seem to be commonly characterized by abnormal rumination, but not by implicit self-associations or abnormalities in relevant brain networks. Nevertheless, relapse was predicted by self-related cognitions and default mode RSFC during remission, suggesting that variations in self-relevant processing play a role in the complex dynamics associated with the vulnerability to developing recurrent depressive episodes. Netherlands Trial Register, August 18, 2015, trial number NL53205.042.15.


Stability of IgG solutions, especially anti-D gammaglobulin, with special reference to measured proteolytic activity and degradation.
The stability of IgG solutions during the dating period can be predicted by measuring the degree of degradation after elevated storage conditions at +37 degrees C with added streptokinase. The measurement of proteolytic activity with a synthetic substrate correlates with the results obtained by SDS-disc gel electrophoresis and gel filtration. IgG molecules having Anti-D activity were observed to be essentially more sensitive to proteolytic degradation by plasmin than IgG molecules in general. It seems, therefore, that the methods which are suitable for the study of the stability of normal IgG preparations are not sufficient to predict the stability of anti-D gammaglobulin preparations.


Myelin breakdown and elimination in the posterior funiculus of the adult cat after dorsal rhizotomy: a light and electron microscopic qualitative and quantitative study.
Adult cats were subjected to unilateral dorsal L6, L7, and S1 rhizotomy. After survival times of 1-1,552 days the degeneration of axons and myelin sheaths and the elimination of degenerating myelin was studied qualitatively and quantitatively with light and electron microscopy and in Marchi-stained sections in the posterior funiculus in T12-L2. Degeneration was first observed as swollen or shrunken nerve fibers. Somewhat later there was an increased occurrence of collapsed myelin sheaths. The latter lost their myelin periods and appeared to be transformed into myelin bodies. The occurrence of myelin bodies coincided temporally with the presence of many Marchi-positive bodies. Later, an increasing number of intracellularly located lipid droplets occurred, paralleled by the occurrence of a great number of Marchi-positive granules and crystalline structures. Profiles of collapsed myelin sheaths, myelin bodies, and lipid droplets were frequently seen in the cytoplasm of microglial cells. Later, astrocytes and perivascular cells became filled with numerous lipid droplets. The findings suggest that microglial cells take up collapsed myelin sheaths and within these cells the sheaths become transformed into myelin bodies and subsequently into lipid droplets. These two products of myelin disintegration appear to correspond to the Marchi-positive structures seen during the degeneration process. The lipid droplets appear to be transported to astrocytes and perivascular cells.


COVID-19 diagnostics: Molecular biology to nanomaterials.
The SARS-CoV-2 pandemic has claimed around 6.4 million lives worldwide. The disease symptoms range from mild flu-like infection to life-threatening complications. The widespread infection demands rapid, simple, and accurate diagnosis. Currently used methods include molecular biology-based approaches that consist of conventional amplification by RT-PCR, isothermal amplification-based techniques such as RT-LAMP, and gene editing tools like CRISPR-Cas. Other methods include immunological detection including ELISA, lateral flow immunoassay, chemiluminescence, etc. Radiological-based approaches are also being used. Despite good analytical performance of these current methods, there is an unmet need for less costly and simpler tests that may be performed at point of care. Accordingly, nanomaterial-based testing has been extensively pursued. In this review, we discuss the currently used diagnostic techniques for SARS-CoV-2, their usefulness, and limitations. In addition, nanoparticle-based approaches have been highlighted as another potential means of detection. The review provides a deep insight into the current diagnostic methods and future trends to combat this deadly menace.


The effect of shift work on burnout and occupational fatigue among clinical faculty members during the COVID-19 pandemic.
Shift work of clinical faculty members in the COVID-19 pandemic may cause burnout and occupational fatigue and as a result, may reduce the quality of student education and disrupt the treatment of patients, so this study was conducted to evaluate this case. The statistical population of this cross-sectional research included all clinical faculty members of Ahvaz Jundishapur University of Medical Sciences in southwestern Iran, who experienced a shift work system (night shift from 8 p.m. to 8 a.m.) during the COVID-19 pandemic, and finally, 71 of them participated in it. The sampling method was also available. Two inventories were used to collect data, namely the Maslach Burnout Inventory [MBI-HSS (MP)] and the Swedish Occupational Fatigue Inventory (SOFI-20). The self-reported burnout of faculty members was high (mean ± SD = 98.18 ± 17.18), which was graded into the range of emotional exhaustion (38.01 ± 10.2), range of personal accomplishment, (33.75 ± 6.75), and the range of depersonalization (26.42 ± 3.5), respectively. Perceived occupational fatigue of faculty members was also high (M ± SD = 82.25 ± 34.79), which included the dimensions of lack of motivation (18.69 ± 8.65), drowsiness (17.43 ± 8.7), lack of energy (16.33 ± 7.67), physical discomfort (15.65 ± 8.62), and physical stress (13.51 ± 6.9), respectively. In terms of demographic characteristics, occupational fatigue was significantly more common among women. The self-reported burnout and occupational fatigue of clinical faculty members due to shift work were reported to be high in this study. Although our knowledge of burnout has advanced in recent years, many gaps in our knowledge still remain. In order for clinical faculty members to properly fulfill their mission to treat patients, educate students, and promote public health, it is necessary to provide all the necessary conditions for their effective activity. Some interventions, such as improving organizational strategies and providing technical solutions, incentives, and occupational facilities, can help reduce or eliminate these problems.


Complete genome sequence of datura leaf curl virus, a novel begomovirus infecting Datura innoxia in Sudan, related to begomoviruses causing tomato yellow leaf curl disease.
Several species in the genus Datura (family Solanaceae) are hosts for begomoviruses (family Geminiviridae), both in the New World and the Old World. Here, we report the genome characterization of two isolates of a novel Old World monopartite begomovirus infecting Datura innoxia in Sudan, which we propose to be named "datura leaf curl virus" (DaLCV). Pairwise sequence comparisons and phylogenetic analysis showed that DaLCV isolates are related to begomoviruses causing tomato yellow leaf curl disease, a global menace for tomato crops. Thus, the novel begomovirus could pose an additional threat to tomato cultivation in Africa.


Adding the Coping Power Programme to parent management training: the cost-effectiveness of stacking interventions for children with disruptive behaviour disorders.
Parent management training (PMT) programmes and child cognitive behavioural therapy are recommended approaches for treatment of oppositional defiant disorder in children, and combining these may be effective. However, little is known regarding the economic efficiency of this additive effect. A within-trial cost-effectiveness analysis was carried out in Sweden including 120 children aged 8-12 who screened positive for disruptive behaviour disorders, within a psychiatric care setting, and their parents. They were randomly assigned to either the Swedish group-based PMT Comet, or to an enhanced version, where an additional child component was provided, the Coping Power Programme (CPP). Child behaviour problems as well as healthcare and educational resource use were measured at baseline, post-test and at two-year follow-up. A net benefit regression framework was used to estimate differences in costs and health outcomes between the two intervention arms during the two-year period. Comet with CPP cost on average 820 EURO more per family than Comet only. At the 2-year follow-up, there were 37% recovered cases of ODD in Comet with CPP, in comparison to 26% in the Comet only arm. At a willingness-to-pay of approximately 62,300 EURO per recovered case of ODD, Comet with CPP yielded positive net benefits, in comparison to Comet only. Offering children the CPP simultaneously as their parents receive PMT, in comparison to only providing PMT, yields clinically relevant gains. Despite the relatively small cost for CPP, investment in combining PMT and CPP should be guided by resource prioritisation. Trial registration number: ISRCTN10834473, date of registration: 23/12/2015.


Deletions of the long arm of chromosome 6: two new cases and review of the literature.
Seven terminal deletions and four interstitial deletions of 6q have been reported. We present the clinical and cytogenetic findings of these cases and of two new patients with different interstitial deletions of 6q. Although there are too few cases of interstitial deletions to identify one or more clinical syndromes associated with monosomies of the more proximal regions of 6q, a terminal 6q deletion syndrome is proposed. Its major components are microcephaly with mental retardation, strabismus, apparently low-set malformed ears, a broad nasal bridge, micrognathia, apparently short neck, congenital heart defect, abnormal palmar creases, and various hand abnormalities.


Evaluation of 9-cis retinoic acid for a new remedy of human retinoblastoma.
We investigated the effect of two isomers of retinoic acid (RA), all-trans RA and 9-cis RA, on the proliferation of Y79 human retinoblastoma cells. The two isomers inhibited the cell proliferation in a concentration-dependent manner. The IC50 for this inhibition by all-trans RA and 9-cis RA was 1.50 and 0.15 microM, respectively. The inhibitory effect of 9-cis RA on Y79 cell growth was observed within 24 hr, thereafter the cell number was gradually decreased. In contrast, no inhibition by all-trans RA of Y79 cell growth was observed within 24 hr, thereafter the cell number was slightly increased. In these cases, the cell viability at 4 days after the addition of 9-cis RA and all-trans RA was more than 90% and 95%, respectively. These results indicate that the two RA inhibit the proliferation of Y79 human retinoblastoma cells without inducing the cell death and that the effect of 9-cis RA on the inhibition of Y79 cell growth is much greater than that of all-trans RA.


Four-membered heterocycles-containing 4-anilino-quinazoline derivatives as epidermal growth factor receptor (EGFR) kinase inhibitors.
We report herein the design and synthesis of novel azaspirocycle or azetidine substituted 4-anilinoquinazoline derivatives. The EGFR inhibitory activities and in vitro antitumor potency of these newly synthesized compounds against two lung cancer cell lines HCC827 and A549 were evaluated. Most of the target compounds possess good inhibitory potency. In particular, compounds 21g with 2-oxa-6-azaspiro[3.4]octane substituent was found to possess higher EGFR inhibitory activities and similar antitumor potency comparing to the lead compound gefitinib with improved water solubility.


Effect of pH and water-soluble polymers on the aqueous solubility of nimesulide in the absence and presence of beta-cyclodextrin derivatives.
The aqueous solubility of nimesulide in the absence and presence of beta-cyclodextrin (beta-CD) and its alkyl derivatives hydroxypropyl-beta-CD and methyl-beta-CD was studied. We also investigated the effect of water-soluble polymers, hydroxypropylmethyl-cellulose, sodium-carboxymethyl-cellulose, polyvinylpyrrolidone and polyethyleneglycol on the solubilization efficacy and complexation ability of cyclodextrins with nimesulide. The solubility of nimesulide in the absence and presence of cyclodextrins and polymers was studied using a phase solubility technique combined with a spectrophotometric method. The study was carried out at 25 degrees C and pH values of 6.0 and 7.0. Conditions in terms of polymer concentration and polymer heating with and without sonication were optimized. Values of the solubility enhancement factor of nimesulide in the presence of each cyclodextrin and in the absence and presence of each polymer were determined and the formation constants, K, of the inclusion complexes formed calculated. beta-CDs increased the aqueous solubility of nimesulide in the following order: methyl-beta-CD > beta-CD > hydroxypropyl-beta-CD. Addition of hydroxypropylmethyl-cellulose at a concentration of 0.1% (w/v) had the greatest influence on complexation of all three beta-CDs with nimesulide, while preheating of the polymer at 70 degrees C under sonication resulted in an additional two-fold increase in the aqueous solubility of the drug. Sodium-carboxymethyl-cellulose, polyvinylpyrrolidone and polyethyleneglycol had minor effects on the aqueous solubility of nimesulide. Thus beta-CD, hydroxypropyl-beta-CD and methyl-beta-CD are proposed as good solubilizing agents for nimesulide in the presence and absence of hydroxypropylmethyl-cellulose in order to enhance its oral bioavailability.


Effects of a community-level intervention on maternal health care utilization in a resource-poor setting of Northern Ghana.
This study aimed to assess the effects of health education and community-level participatory interventions at the community level and the use of community maternal health promoters on the utilization of maternal health care services in poor rural settings of northern Ghana. A randomized controlled survey design was conducted from June 2019 to July 2020 in two rural districts of northern Ghana. A multistage cluster sampling technique was used to select the participants. Data were collected from a repeated cross-sectional household survey. Descriptive analysis, bivariate and covariates adjusted simple logistic regression analyses were performed using STATA version 16 statistical software. At post-intervention, the two groups differed significantly in terms of ANC (p = 0.001), skilled delivery (SD) (p = 0.003), and PNC (p < 0.0001). Women who received health education on obstetric danger signs had improved knowledge by 50% at the end of the study. Women who received the health education intervention (HEI) on practices related to ANC and skilled delivery had increased odds to utilize ANC (AOR = 4.18; 95% CI = 2.48-7.04) and SD (AOR = 3.90; 95% CI = 1.83-8.29) services. Institutional delivery and PNC attendance for at least four times significantly increased from 88.5 to 97.5% (p < 0.0001), and 77.3-96.7% (p < 0.0001) respectively at postintervention. Women who had received the HEI were significantly more likely to have good knowledge about obstetric danger signs (AOR = 10.17; 95% CI = 6.59-15.69), and BPCR (AOR = 2.10; 95% CI = 1.36-3.24). Women who had obtained tertiary education were significantly more likely to make at least four visits to ANC (AOR = 2.38; 95% CI = 0.09-1.67). This study suggests that the use of health education and participatory sessions led by community-based facilitators could be a potentially effective intervention to improve the knowledge of women about obstetric danger signs and encourage the uptake of maternity care services in resource-poor settings of Ghana.


Vaginal metastasis and thrombocytopenia from renal cell carcinoma.
Vaginal cancer represents approximately 1-2% of genital tract malignancies. Most cases represent metastasis from the cervix, endometrium, or colon. Metastasis of renal cell carcinoma to the vagina is extremely rare. A 58-year-old female presented with a bleeding vaginal lesion. Laboratory studies revealed severe thrombocytopenia, and radiological studies revealed a left renal mass; excision was consistent with metastatic renal cell carcinoma. A subsequent nephrectomy confirmed renal cell carcinoma. Postoperatively, the patient underwent immunotherapy and the thrombocytopenia resolved. We report the first case of metastatic renal cell carcinoma presenting as a vaginal metastasis with thrombocytopenia as a paraneoplastic manifestation. Renal cell carcinoma must be in the differential diagnosis of a clear cell neoplasm in a postmenopausal woman, particularly with systemic symptoms suggestive of a paraneoplastic syndrome.


Development of a deep learning model for safe direct optical trocar insertion in minimally invasive surgery: an innovative method to prevent trocar injuries.
Direct optical trocar insertion is a common procedure in laparoscopic minimally invasive surgery. However, misinterpretations of the abdominal wall anatomy can lead to severe complications. Artificial intelligence has shown promise in surgical endoscopy, particularly in the employment of deep learning models for anatomical landmark identification. This study aimed to integrate a deep learning model with an alarm system algorithm for the precise detection of abdominal wall layers during trocar placement. Annotated bounding boxes and assigned classes were based on the six layers of the abdominal wall: subcutaneous, anterior rectus sheath, rectus muscle, posterior rectus sheath, peritoneum, and abdominal cavity. The cutting-edge YOLOv8 model was combined with a deep learning detector to train the dataset. The model was trained on still images and inferenced on laparoscopic videos to ensure real-time detection in the operating room. The alarm system was activated upon recognizing the peritoneum and abdominal cavity layers. We assessed the model's performance using mean average precision (mAP), precision, and recall metrics. A total of 3600 images were captured from 89 laparoscopic video cases. The proposed model was trained on 3000 images, validated with a set of 200 images, and tested on a separate set of 400 images. The results from the test set were 95.8% mAP, 89.8% precision, and 91.7% recall. The alarm system was validated and accepted by experienced surgeons at our institute. We demonstrated that deep learning has the potential to assist surgeons during direct optical trocar insertion. During trocar insertion, the proposed model promptly detects precise landmark references in real-time. The integration of this model with the alarm system enables timely reminders for surgeons to tilt the scope accordingly. Consequently, the implementation of the framework provides the potential to mitigate complications associated with direct optical trocar placement, thereby enhancing surgical safety and outcomes.


New 4-[(5-arylidene-2-arylimino-4-oxo-3-thiazolidinyl)methyl]benzoic acids active as protein tyrosine phosphatase inhibitors endowed with insulinomimetic effect on mouse C2C12 skeletal muscle cells.
In pursuing our research targeting the identification of potent inhibitors of PTP1B and LMW-PTP, we have identified new 4-[(5-arylidene-2-arylimino-4-oxo-3-thiazolidinyl)methyl]benzoic acids endowed with interesting in vitro inhibitory profiles. Most compounds proved to be inhibitors of PTP1B and LMW-PTP isoform IF1. The tested inhibitors also showed selectivity towards PTP1B over the closely related TC-PTP. These compounds were found to activate the insulin-mediated signalling on mouse C2C12 skeletal muscle cells by increasing the phosphorylation levels of the insulin receptor and promoting cellular 2-deoxyglucose uptake. Interestingly, 4-{[5-(4-benzyloxybenzylidene)-2-(4-trifluoromethylphenylimino)-4-oxo-3-thiazolidinyl]methyl}benzoic acid (7d), the best in vitro inhibitor of PTP1B and the isoform IF1 of LMW-PTP, provided the highest activation level of the insulin receptor and was found to be endowed with an excellent insulinomimetic effect on the selected cells. This compound therefore represents an interesting lead compound for developing novel PTP1B and LMW-PTP inhibitors which could be achieved by improving both its pharmacological profile and its potentiating effects on insulin signalling.


Isoflurane modulates excitability in the mouse thalamus via GABA-dependent and GABA-independent mechanisms.
GABAergic neurons in the reticular thalamic nucleus (RTN) synapse onto thalamocortical neurons in the ventrobasal (VB) thalamus, and this reticulo-thalamocortical pathway is considered an anatomic target for general anesthetic-induced unconsciousness. A mutant mouse was engineered to harbor two amino acid substitutions (S270H, L277A) in the GABA(A) receptor (GABA(A)-R) alpha1 subunit; this mutation abolished sensitivity to the volatile anesthetic isoflurane in recombinant GABA(A)-Rs, and reduced in vivo sensitivity to isoflurane in the loss-of-righting-reflex assay. We examined the effects of the double mutation on GABA(A)-R-mediated synaptic currents and isoflurane sensitivity by recording from thalamic neurons in brain slices. The double mutation accelerated the decay, and decreased the (1/2) width of, evoked inhibitory postsynaptic currents (eIPSCs) in VB neurons and attenuated isoflurane-induced prolongation of the eIPSC. The hypnotic zolpidem, a selective modulator of GABA(A)-Rs containing the alpha1 subunit, prolonged eIPSC duration regardless of genotype, indicating that mutant mice incorporate alpha1 subunit-containing GABA(A)-Rs into synapses. In RTN neurons, which lack the alpha1 subunit, eIPSC duration was longer than in VB, regardless of genotype. Isoflurane reduced the efficacy of GABAergic transmission from RTN to VB, independent of genotype, suggesting a presynaptic action in RTN neurons. Consistent with this observation, isoflurane inhibited both tonic action potential and rebound burst firing in the presence of GABA(A)-R blockade. The suppressed excitability in RTN neurons is likely mediated by isoflurane-enhanced Ba(2+)-sensitive, but 4-aminopyridine-insenstive, potassium conductances. We conclude that isoflurane enhances inhibition of thalamic neurons in VB via GABA(A)-R-dependent, but in RTN via GABA(A)-R-independent, mechanisms.


Compartmental flux and in situ methods underestimate total feed nitrogen as judged by the omasal sampling method due to ignoring soluble feed nitrogen flow.
The objective of the present study was to estimate ruminal feed N outflow in lactating cows using the omasal sampling, compartmental flux or in situ method. A total of five ruminally fistulated Finnish Ayrshire dairy cows were used in a 5 × 5 Latin square study with 21 d periods. Experimental silages of grass or red clover harvested at two stages of maturity in addition to a supplement of 9·0 kg concentrate/d were fed to the cows. In vivo omasal N flow was determined using the omasal sampling technique. Ruminal in situ N flow was calculated from N intake and degradability (38 μm nylon bags). The samples of ruminal contents and faeces were divided into seven particle-size fractions by wet sieving; the concentrations of indigestible neutral-detergent fibre and N were used to calculate N flow in the compartmental flux method. In vivo omasal N flow was greater for the red clover silage diets than for the grass silage diets. The N flow calculated using the compartmental flux technique and that calculated using the in situ technique were highly correlated, but both were less than and poorly correlated with the in vivo N flow. In both in situ and compartmental flux techniques, forage maturity increased the particle-associated N flow, with the increase being significantly greater for the red clover diets than for the grass silage diets. In conclusion, the compartmental flux and in situ methods described the N flow associated with the particle fractions rather than the total ruminal outflow of feed N.


CT and MR imaging in atypical teratoid/rhabdoid tumors of the central nervous system.
Atypical teratoid/rhabdoid tumors (ATRT) are rare aggressive neoplasms of the CNS affecting predominantly very young children. We retrospectively reviewed the imaging findings of 9 CT and 32 MR examinations of the brain and spine of 33 children. Of the 33 tumors, 11 were located in the infratentorial compartment, 16 in the supratentorial compartment, 5 in both cranial compartments, and 1 in the lower thoracic spinal cord. The mean age of the children with infratentorial or infra- and supratentorial tumors was significantly lower than the mean age of the children with purely supratentorial tumors. Heterogeneity on imaging, large size and high tumor stages are striking features reflecting the aggressive nature of this histopathological entity. Although not present in the majority of children, a distinct and unusual pattern of a wavy band-like enhancement surrounding a central hypointensity was present in 12 of 32 children (38%) in whom contrast medium was used. To the best of our knowledge this is the largest number of imaging examinations of ATRTs so far reported. A rather unusual pattern of contrast enhancement may be typical of ATRTs.


Production of fructo-oligosaccharides from molasses by Aureobasidium pullulans cells.
Three different strains of Aureobasidium pullulans were grown in batch cultures to compare their abilities for the production of fructo-oligosaccharides. Specific intracellular enzyme activity was the highest with strain KCCM 12017 and enzyme production was closely coupled to growth. Using A. pullulans cells, 166 g/l fructo-oligosaccharides was produced from 360 g/l molasses sugar as sucrose equivalent at 55 degrees C and pH 5.5 after 24 h incubation.


[Life cycle and nucleic acid distribution in the endogenous development stages of coccidia (Coccidiida, Eimeriidae) of the Vinogradov gerbil].
Studies were undertaken of the life cycles of three intestinal coccidia: Eimeria arabiana, E. bistratum and E. poljanski, parasites of meriones vinogradovi. The number of the asexual generations, the period of appearance of the endogenous stages and the first oocysts, localization were determined. The successive phases of the growth and development of schizonts of different generations, macrogametes and microgametocytes were described. The distribution of DNA and RNA in different endogenous stages of three kinds of coccidia were studied by methods of cytochemistry.


Death due to dextropropoxyphene: Copenhagen experiences.
A review of 323 fatal poisonings with dextropropoxyphene is presented. The falling tendency of the poisoning in question and the National Board of Health's attention towards it are discussed.


The unusual rps3-like orf712 is functionally essential and structurally conserved in Chlamydomonas.
The Chlamydomonas reinhardtii chloroplast orf712 is a previously described open reading frame that lacks a detectable transcript but potentially encodes a polypeptide with sequence similarities to ribosomal protein Rps3 only at its N- and C-termini. Here we report that orf712 is an essential gene, as demonstrated through gene disruption by particle gun-mediated chloroplast transformation. We also show that an orf712 is present and structurally conserved in all of the two or three major Chlamydomonas lineages. Our results suggest that orf712 is an unusual rps3 gene that contains a large translated intervening sequence.


Purification and characterization of aldehyde dehydrogenase from human brain.
Aldehyde dehydrogenase (EC 188.8.131.52) has been purified from human brain; this constitutes the first purification to homogeneity from the brain of any mammalian species. Of the three isozymes purified two are mitochondrial in origin (Peak I and Peak II) and one is cytoplasmic (Peak III). By comparison of properties, the cytoplasmic Peak III enzyme could be identified as the same as the liver cytoplasmic E1 isozyme (N.J. Greenfield and R. Pietruszko (1977) Biochim. Biophys. Acta 483, 35-45). The Peak I and Peak II enzymes resemble the liver mitochondrial E2 isozyme, but both have properties that differ from those of the liver enzyme. The Peak I enzyme is extremely sensitive to disulfiram while the Peak II enzyme is totally insensitive; liver mitochondrial E2 isozyme is partially sensitive to disulfiram. The specific activity is 0.3 mumol/mg/min for the Peak I and 3.0 mumol/mg/min for the Peak II enzyme; the specific activity of the liver mitochondrial E2 isozyme is 1.6 mumol/min/mg under the same conditions. The Peak I enzyme is also inhibited by acetaldehyde at low concentrations, while the Peak II enzyme and the liver mitochondrial E2 isozyme are not inhibited under the same conditions. The precise relationship of brain Peak I and II enzymes to the liver E2 isozyme is not clear but it cannot be excluded at the present time that the two brain mitochondrial enzymes are brain specific.


Identification of 5,6-dimethoxyindolyl-2-carboxylic acid in melanotic urine.
5,6-dimethoxyindolyl-2-carboxylic acid was identified in urine of patients with malignant melanoma by means of gas chromatography - mass spectrometry. Its presence supports the concept of the existence of an efficient methylating activity in melanoma tissue.


Characterization of the dynamics of Plasmodium falciparum deoxynucleotide-triphosphate pool in a stage-specific manner.
Understanding and characterizing the molecular background of the maintenance of genomic integrity might be a major factor in comprehending the exceptional ability of the malaria parasite, Plasmodium falciparum to adapt at a fast pace to antimalarials. A balanced nucleotide pool is an essential factor for high-fidelity replication. The lack of detailed studies on deoxynucleotide-triphosphate (dNTP) pools in various intraerythrocytic stages of Plasmodium falciparum motivated our present study. Here, we focused on the building blocks of DNA and utilized an EvaGreen-based dNTP incorporation assay to successfully measure the temporal dynamics of dNTPs in every intraerythrocytic stage and in drug-treated trophozoites. Our findings show that the ratio of dNTPs in the ring-stage parasites significantly differs from the more mature trophozoite and schizont stages. We were also able to detect dGTP levels that have never been shown before and found it to be the least abundant dNTP in all stages. Treatment with WR99210, a TS-DHFR inhibitor drug, affected not only dTTP, but also dGTP levels, despite its presumed selective action on pyrimidine biosynthesis. Results from our studies might assist in a better understanding of genome integrity mechanisms and may potentially lead to novel drug related aspects involving purine and pyrimidine metabolic targets.


Factors affecting pain intensity in a pain model based upon tonic intranasal stimulation in humans.
The present publication describes an inflammatory pain model based on an air-stream introduced in the nasal cavity. The aim of the present study was to investigate the influence of flow, humidity and temperature of the air-stream on the intensity of the evoked pain sensations. Six healthy volunteers participated in the study. Pain was produced by a stream of air introduced to the nasal cavity at different flow rates (5, 6 and 81/min), humidity (20 and 80% relative humidity) and temperature (16, 24, and 32 degrees C). The evoked pain was quantified by means of visual analogue scales. The air-stream induced a dull and burning painful sensation. The intensity of pain was found to be related to the air-stream's humidity and temperature. Specifically, a dry air-stream (20% relative humidity) evoked significantly stronger pain than a humidified air-stream (80% relative humidity). Pain was significantly greater at a temperature of 32 degrees C than at 24 degrees and 16 degrees C, while the temperatures of 16 and 24 degrees C did not differ with respect to pain intensity. In contrast, a tendency towards stronger pain produced by a flow of 81 compared to that with 51 could not be statistically justified within the present study. The non-invasive pain stimulus was found to be easily applicable and the evoked pain sensation could be modified by variation of humidity and temperature of the air-stream.


Genome-wide association study identifies novel single nucleotide polymorphisms having age-specific effect on prostate-specific antigen levels.
Testing for prostate-specific antigen (PSA) levels in blood are widely used and associated with prostate cancer risk and outcome. After puberty, PSA levels increase by age and multiple single nucleotide polymorphisms (SNPs) have been found to be associated with PSA levels. However, the relationship between the effects of SNPs and age on PSA remains unknown. To test for SNP × age interaction, we conducted a genome-wide association study using 2394 men without prostate cancer diagnosis from Malmö, Sweden as a discovery set and 2137 men from the eMERGE study (USA) for validation. Linear regression was used to identify significant interactions between SNP and age (p < 1 × 10-4 for discovery, p < .05 for validation). The 15 SNPs from three different loci (8p11.22, 8p12, 3q25.31) are found to have age-specific effect on PSA levels. Expression quantitative trait loci (eQTLs) analysis shows that 12 SNPs from 3q25.31 locus affect the expression level of three genes: KCNAB1, SLC33A1, PLCH1. Our results suggest that SNPs may have age-specific effect on PSA levels, which provides new direction to study genetic markers for PSA.


Demographic, Hematologic, and Clinical Features of Myelodysplastic Syndrome Patients: Results from the First Polish Myelodysplastic Syndrome Registry.
Epidemiological studies on myelodysplastic syndromes (MDS) in Middle-Eastern Europe are scarce. No data about the demographic, clinical, and laboratory features of Polish MDS patients have been published. The aim of this study was to assess the epidemiological data and toxic exposure of Polish MDS patients and their association with hematological parameters and clinical outcomes. For 15 months, 966 living MDS patients were enrolled at 24 centers (12 university and 12 community hospitals). Follow-up was conducted for the next 55 months. The percentage of patients older than 80 years (16%) was between the values for Eastern and Western countries. In patients younger than 55 years, a female predominance was observed (male/female ratio 0.70:1 vs. 1.29:1; p < 0.001). Female patients had higher platelet counts (160 × 10⁹/l vs. 111 × 10⁹/l; p < 0.001). Patients exposed to chemicals were younger than patients without such exposure; their median age at MDS diagnosis was 66 vs. 70 years (p = 0.037). Smokers had significantly lower hemoglobin concentrations (8.6 vs. 9.1 g/dl; p = 0.032) and lower platelet counts (99 × 10⁹/l vs. 137 × 10⁹/l; p < 0.001) than nonsmokers. We provide the first description of the characteristics of Polish MDS patients. Females predominated in the group aged <60 years and they had higher platelet counts. The course of the disease is affected by toxic exposure and smoking.


Calcium chelation improves spatial learning and synaptic plasticity in aged rats.
Impaired regulation of intracellular calcium is thought to adversely affect synaptic plasticity and cognition in the aged brain. Comparing young (2-3 months) and aged (23-26 months) Fisher 344 rats, stratum radiatum-evoked CA1 field EPSPs were smaller and long-term potentiation (LTP) was diminished in aged hippocampal slices. Resting calcium, in presynaptic axonal terminals in the CA1 stratum radiatum area, was elevated in aged slices. Loading the slice with the calcium chelator, BAPTA-AM, depressed LTP in young slices, but enhanced this plasticity in old slices. Forty-five minutes following LTP-inducing high frequency stimulation, resting calcium levels were significantly increased in both young and old presynaptic terminals, and significantly reduced by pretreatment with BAPTA-AM. In vivo, intraperitoneal administration of BAPTA-AM prior to training in the reference memory version of the Morris water maze test, significantly improved the acquisition of spatial learning in aged animals, without a significant effect in young rats. These results support the hypothesis that increasing intracellular neuronal buffering power for calcium in aged rats ameliorates age-related impaired synaptic plasticity and learning.


(Re)thinking the Residential in Residency: Modern Surgical Practice Continues to Move Away From the Inpatient Setting.
Despite the overall shift in care delivery to an ambulatory setting, the majority of general surgical education still relies on the experience of caring for inpatients. We aimed to investigate how the inpatient practice patterns of newly minted general surgeons (GS) have changed since 2008, in order to better inform education policies regarding both training approach and setting for modern surgical trainees. State discharge data from NY and FL (2008-2017) were linked to data on GS from the American Medical Association Masterfile, and to hospital data from the American Hospital Association annual survey. Mean annual inpatient case volume (CV) and case type breadth (CB) were compared between surgeons who were new-to-practice (0-3 years of experience) in 2008 and in 2013. Each new surgeon cohort was followed for 5 years. Case type was classified by organ system. The 2008 cohort included 328 GS with a mean age of 37.1, 79.6% male and 94.2% board-certified. The 2013 cohort included 359 GS with a mean age of 36.2, 73.0% male and 93.9% board-certified. CV was higher among the 2008 cohort than the 2013 cohort for each year of practice in the study period. CB included at least 4 organ system types for all new GS with greater breadth among the 2008 cohort for each year in the study period. Declining rates of inpatient surgery affect general surgeons who were new-to-practice in 2013 significantly more than those entering practice only 5 years ahead of them. New surgeons continue to start their practices broadly, suggesting a need to continue broad training while expanding formal educational policies to include the full spectrum of ambulatory surgery.


Ultrastructural changes in the thymus of the turtle Mauremys caspica in relation to the seasonal cycle.
Changes in the ultrastructure of the thymus of the turtle Mauremys caspica, with special reference to its non-lymphoid components, were studied in relation to the seasonal cycle. The thymic cortex contains framework-forming epithelial-reticular cells and free macrophages, while the medulla includes, in addition, mature and presumptive pro-interdigitating cells. The ultrastructural features of these cells are generally similar to those described for non-lymphoid components of the mammalian thymus. The turtle thymus undergoes cortical involution in spring, with recovery periods in May-June and during autumn. A moderate involution occurs in winter. At the beginning of spring, cortical (but not medullary) epithelial-reticular cells show degenerative changes, probably related to high levels of circulating testosterone. In spring and autumn, mature interdigitating cells are absent, but macrophages, monocytes, and pro-interdigitating cells are found. During May-June, the cortical epithelial-reticular population recovers and macrophages, monocytes, and interdigitating cells are actively phagocytic. In summer, the epithelial-reticular cells in both cortex and medulla display normal ultrastructural features; mature and immature interdigitating cells are absent and some macrophages are detected occasionally. The results suggest that non-lymphoid components of the reptilian thymus can play a role in governing T-lymphocyte differentiation, and that the thymic cortex and medulla exhibit different cycles of seasonal activity.


Arthroscopic management of the thrower's shoulder: internal impingement.
Our understanding of internal impingement in the overhand athlete is an evolving body of knowledge. More recent improved understanding of the pathophysiology of events that leads to the spectrum of injury has caused us to refine our techniques of treatment. Improved surgical techniques and instrumentation have made refinement of our approach to treatment possible. Only time will tell whether the perceived understanding of these disorders, resulting in alteration of our treatment methods, is making our treatment outcomes more successful.


Zbtb4 represses transcription of P21CIP1 and controls the cellular response to p53 activation.
In response to stimuli that activate p53, cells can undergo either apoptosis or cell cycle arrest, depending on the precise pattern of p53 target genes that is activated. We show here that Zbtb4, a transcriptional repressor protein, associates with the Sin3/histone deacetylase co-repressor and represses expression of P21CIP1 as part of a heterodimeric complex with Miz1. In vivo, expression of ZBTB4 is downregulated in advanced stages of multiple human tumours. In cell culture, depletion of ZBTB4 promotes cell cycle arrest in response to activation of p53 and suppresses apoptosis through regulation of P21CIP1, thereby promoting long-term cell survival. Our data suggest that Zbtb4 is a critical determinant of the cellular response to p53 activation and reinforce the notion that p21Cip1 can provide an essential survival signal in cells with activated p53.


Measurements of urinary leptin and capillary leptin: alternative tools for the assessment of the leptin status?
The aim of this study was to check whether leptin is reliably measurable in urine samples of children, adolescents, and adults and to examine whether capillary leptin measurements can be utilized as an alternative tool to assess the leptin status. Two studies were performed. In both studies, leptin was quantified by an ultrasensitive and highly specific enzyme immunoassay (ELISA; R & D Systems). Anthropometric measures were taken from all study subjects, and body fat was calculated using skinfold thickness measurements. In study 1, leptin was analyzed in 24-hour urine samples of 155 healthy children and adolescents and 26 healthy adults after a methodological modification of the assay necessary for urine analysis. In study 2, venous and capillary blood samples were collected in 26 healthy adults within 10 min on the same day. After adapting the assay system to urine matrix, the detection range was 20-160 pg/ml. Only in 2 of 181 urine samples reproducibly measurable urinary leptin concentrations in the lowest detection range were found. In study 2, a close correlation was found between log capillary and log venous leptin concentrations (r = 0.98, p < 0.001) and between log capillary as well as log venous leptin levels and percent body fat (r = 0.86, p < 0.001). Our results based on one of the most specific and sensitive ELISAs currently available show that leptin is generally undetectable in the urine from healthy children, adolescents and adults. Thus, urinary leptin excretion cannot be used as a noninvasive marker of the leptin status. Our findings in healthy adults show that the merely moderately invasive determination of capillary leptin allows a reliable assessment of the individual leptin status and may be used instead of venous leptin as a biochemical indicator of body fatness.


Overexpression of the maize γ-tocopherol methyltransferase gene (ZmTMT) increases α-tocopherol content in transgenic Arabidopsis and maize seeds.
The vitamin E family includes tocopherols and tocotrienols, which are essential lipid-soluble antioxidants necessary for human and livestock health. The seeds of many plant species, including maize, have high gamma (γ)-tocopherol but low alpha (α)-tocopherol contents; however, α-tocopherol is the most effective antioxidant. Therefore, it is necessary to optimize the tocopherol composition in plants. α-Tocopherol is synthesized from γ-tocopherol by γ-tocopherol methyltransferase (γ-TMT, VTE4) in the final step of the tocopherol biosynthetic pathway. In the present study, the full-length coding sequence (CDS) of γ-TMT was isolated from Zea mays, named ZmTMT. The ZmTMT CDS was 1059 bp in size, encoding 352 amino acids. Recombinant ZmTMT was expressed in Escherichia coli and the purified protein effectively converted γ-tocopherol into α-tocopherol in vitro. A comparison of enzyme activities showed that the activity of ZmTMT was higher than that of GmTMT2a (Glycine max) and AtTMT (Arabidopsis thaliana). Overexpression of ZmTMT increased the α-tocopherol content 4-5-fold in transgenic Arabidopsis and around 6.5-fold in transgenic maize kernels, and increased the α-/γ-tocopherol ratio to approximately 15 and 17, respectively. These results show that it is feasible to overexpress ZmTMT to optimize the tocopherol composition in maize; such a corn product might be useful in the feed industry in the near future.


Exploring QSPR models for predicting PUF-air partition coefficients of organic compounds with linear and nonlinear approaches.
Partition coefficients are important parameters for measuring the concentration of chemicals by passive sampling devices. Considering the wide application of the polyurethane foam (PUF) in passive air sampling, an attempt for developing several quantitative structure-property relationship (QSPR) models was made in this work, to predict PUF-air partition coefficients (KPUF-air) using linear (multiple linear regression, MLR) and non-linear (artificial neural network, ANN and support vector machine, SVM) methods by machine learning. All of the developed models were performed on a dataset of 170 compounds comprising 9 distinct classes. A series of statistical parameters and validation results showed that models had good prediction ability, robustness and goodness-of-fit. Furthermore, the underlying mechanisms of molecular descriptors emphasized that ionization potential, molecular bond, hydrophilicity, size of molecule and valence electron number had dominating influence on the adsorption process of chemicals. Overall, the obtained models were all established on the extensive applicability domains, and thus can be used as effective tools to predict the KPUF-air of new organic compounds or those have not been synthesized yet which, in turn, could help researchers better understand the mechanistic basis of adsorption behavior of PUF.


Interpretation and Implications of Lognormal Linear Regression Used for Bacterial Enumeration.
Bacterial enumeration data are typically log transformed to realize a more normal distribution and stabilize the variance. Unfortunately, statistical results from log transformed data are often misinterpreted as data within the arithmetic domain. To explore the implication of slope and intercept from an unweighted linear regression and compare it to the results of the regression of log transformed data. Mathematical formulae inferencing explained using real dataset. For y=Ax+B+ε, where y is the recovery (CFU/g) and x is the target concentration (CFU/g) with error ε homogeneous across x. When B=0, slope A estimates percent recovery R. In the regression of log transformed data, logy=αlogx+β+εz (equivalent to equation y=Axα·ω), it is the intercept β=logyx=logA that estimates the percent recovery in logarithm when slope α=1, which means that R doesn't vary over x. Error term ω is multiplicative to x, while εz or log(ω) is additive to log(x). Whether the data should be transformed or not is not a choice, but a decision based on the distribution of the data. Significant difference was not found between the five models (the linear regression of log transformed data, three generalized linear models and a nonlinear model) regarding their predicted percent recovery when applied to our data. An acceptable regression model should result in approximately the best normal distribution of residuals. Statistical procedures making use of log transformed data should be studied separately and documented as such, not collectively reported and interpreted with results studied in arithmetic domain. The way to interpret statistical results developed from arithmetic domain does not apply to that of the log transformed data.


Clinical outcomes of definitive chemoradiation followed by intracavitary pulsed-dose rate image-guided adaptive brachytherapy in locally advanced cervical cancer.
To report the outcomes and late toxicities of patients with locally advanced cervical cancer treated with concomitant chemoradiation (CRT) followed by intracavitary image-guided adaptive brachytherapy (IGABT). Data from consecutive patients with histologically proven stage IB-IVA cervical cancer treated with curative intent in a single institution were analyzed. After pelvic +/- para-aortic external-beam radiation therapy, they received pulsed-dose rate IGABT following GEC-ESTRO recommendations. Two hundred and twenty-five patients were enrolled. Sixty-five percent were stage≥IIB according to FIGO classification. Ninety-five percent received CRT. Mean D90 to HR and IR-CTV were 80.4+/-10.3Gy and 67.7+/-6.1Gy. After a median follow-up of 38.8months, 3-year local control and overall survival rates were 86.4% and 76.1%, respectively. A trend for a detrimental effect of tumor stage on local control rates was observed with 3-year local control rates of 100% for stages IB1 and IIA, 90.5 for IB2, 85.8% for IIB, 50% for IIIA, 77.1 for IIIB, and 66.7% for IVA tumors (p=0.06). Local control rates at 3years were 95.6% in the group of patients with D90 of HR-CTV≥85Gy, 88.8% in those with D90 between 80 and 85Gy, and 80% when D90<80Gy (p=0.018). Eighteen severe late gastrointestinal and urinary effects affecting 14 patients were reported corresponding with a crude incidence of 6.6%. CRT followed by IGABT provides high local control rates with limited toxicity. Reaching high doses is mandatory to achieve local control and interstitial brachytherapy is necessary in advanced diseases.


Dopamine blockade of the thyroliberin -- induced cyclic AMP accumulation in rat anterior pituitary.
Effects of dopamine and thyroliberin on the cyclic AMP concentration in the rat anterior pituitary gland were investigated in vitro. Dopamine by itself had no effect on the anterior pituitary cAMP concentration but inhibited the cAMP-accumulating effect of thyroliberin.


Built environment effects on cyclist injury severity in automobile-involved bicycle crashes.
This analysis uses a generalized ordered logit model and a generalized additive model to estimate the effects of built environment factors on cyclist injury severity in automobile-involved bicycle crashes, as well as to accommodate possible spatial dependence among crash locations. The sample is drawn from the Seattle Department of Transportation bicycle collision profiles. This study classifies the cyclist injury types as property damage only, possible injury, evident injury, and severe injury or fatality. Our modeling outcomes show that: (1) injury severity is negatively associated with employment density; (2) severe injury or fatality is negatively associated with land use mixture; (3) lower likelihood of injuries is observed for bicyclists wearing reflective clothing; (4) improving street lighting can decrease the likelihood of cyclist injuries; (5) posted speed limit is positively associated with the probability of evident injury and severe injury or fatality; (6) older cyclists appear to be more vulnerable to severe injury or fatality; and (7) cyclists are more likely to be severely injured when large vehicles are involved in crashes. One implication drawn from this study is that cities should increase land use mixture and development density, optimally lower posted speed limits on streets with both bikes and motor vehicles, and improve street lighting to promote bicycle safety. In addition, cyclists should be encouraged to wear reflective clothing.


The effects of early postnatal dexamethasone therapy on pulmonary outcome in premature infants with respiratory distress syndrome: a two-year follow-up study.
To evaluate the pulmonary outcome at corrected age of 2 y on preterm infants who participated in a double-blind trial of early postnatal dexamethasone therapy (< 12 h after birth) for the prevention of chronic lung disease. Clinical respiratory status, blood gases, acid-base balance and pulmonary function were evaluated at corrected age of 2 y in 116 preterm infants (59 infants in the control group; 57 in the dexamethasone-treated group). In the dexamethasone-treated group, dexamethasone was administered intravenously every 12 h in tapering doses: 0.25 mg/kg on days 1 through 7, 0.12 mg/kg on days 8 through 14, 0.05 mg/kg on days 15 through 21, and 0.02 mg/kg on days 21 through 28. The clinical and laboratory characteristics in the perinatal period were comparable between the groups. At the time of follow-up (mean +/- SD corrected age was 25.1 +/- 4.8 mo for the control group and 24.6 +/- 5.1 mo for the dexamethasone-treated group), there was a slightly lower mean body weight and body length, and a lower psychomotor developmental index in the dexamethasone-treated group than in the control group (10.9 +/- 2.1 vs 11.5 +/- 1.9 kg, 84.4 +/- 6.1 vs 85.9 +/- 5.8 cm, and 82 +/- 24 vs 89 +/- 26, respectively); however, these differences were not statistically significant. There were no significant differences between the control and dexamethasone-treated groups in clinical respiratory status, blood gases, acid-base balance or in lung mechanics (V(T): 9.5 +/- 2.0 vs 9.4 +/- 1.9 ml/kg; V(min): 0.23 +/- 0.04 vs 0.23 +/- 0.03 l/min/kg; C(RS): 13.1 +/- 3.9 vs 12.6 +/- 3.6 ml/kPa/kg; R(RS): 1.56 +/- 0.64 vs 1.62 +/- 0.58 kPa/l/s, respectively). There was no apparent adverse respiratory outcome associated with early postnatal dexamethasone therapy.


Autoantibodies against dsDNA measured with nonradioactive Farr assay-an alternative for routine laboratories.
Autoantibodies against dsDNA are utilized for the diagnosis and prognosis of SLE as they are highly specific and correlate with disease activity/renal involvement. However, different detection methods are used in routine diagnostic laboratories. Farr radioimmunoassay (Farr-RIA) has been designated as the preferred method, since it provides very specific and at the same time quantitative results, enabling follow-up of level variations over time. Using intercalating fluorescent dsDNA dye would enable all the benefits of Farr-RIA without the radioactive material and organic solvents. To develop a modified fluorescent Farr method (Farr-FIA) and compare it to the classical Farr-RIA in regard to laboratory parameters, as well as clinical utility. Assays were tested on sera of 70 SLE patients, 78 other autoimmune patients, and 145 healthy blood donors. DNA for Farr-FIA was isolated from healthy donor, for Farr-RIA, 14C-labeled dsDNA from E. coli was used and mixed with sera in borate-buffered saline, followed by precipitation with saturated ammonium sulfate solution and centrifugation. The supernatant (S) was separated from the precipitate (P), and content of dsDNA was measured with PicoGreen (Invitrogen) in Farr-FIA or radioactive isotope in scintillation solution in Farr-RIA. The results were calculated as a ratio (P-S)/(P+S). Farr-FIA has a diagnostic sensitivity of 53% and diagnostic specificity of 100% (ROC AUC 0.781). Good correlation and agreement were shown between Farr-RIA and Farr-FIA. Also, there is good correlation between Farr-FIA and SLEDAI, comparable to that of Farr-RIA. Farr-FIA differs from Farr-RIA in the changed detection system yielding comparable results and thus could represent a nonradioactive replacement for Farr-RIA.


Limited value of arthroscopic evaluation and treatment of painful knee prostheses: a retrospective study of 27 cases.
Twenty-seven painful knee replacements were evaluated arthroscopically. The diagnostic and therapeutic value of these arthroscopic procedures was studied retrospectively. In 5 of the 27 cases, the arthroscopy revealed no diagnosis for the pain. Some form of arthroscopic treatment was performed in 20 cases; in 6 of these 20 cases, however, the treatment did not reduce the pain. Based on these findings, we conclude that the indications for arthroscopic evaluation and treatment of painful knee prostheses are limited.


[Transitional psychiatric needs and identity development of adolescents in Tyrol].
Due to the structural separation of child and adolescent psychiatric treatment and adult psychiatric treatment, a switch between these two systems upon the age of 18 is necessary. Considering the importance of an organized transition, patients from an age of 17 were asked about their transition needs and aspects of their identity development. Thus future improvements in the treatment structures in this sensitive phase should derive. With the help of the Transition Readiness and Appropriateness Measure (TRAM), the transition-specific needs of 17 to 24-year-old patients (N = 42) at the Clinic for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy in Hall in Tirol were surveyed. In addition, the connection between identity development and transition was examined using the Assessment of Identity Development in Adolescence (AIDA). Almost 80% of the patients stated that they needed further care. 'Patient-related factors' and 'family support' were described as barriers to the willingness to transition. A significant connection was found between identity development and the willingness or need for transition (r = 0.431, p < 0.01), although this was more pronounced in relation to the need for transition (r = 0.821 p < 0.01). In addition, those affected stated that they were frequently and severely burdened by stress, 45% reported self-injurious behavior, 48% suicidal thoughts or behavior in the last six months. In terms of psychopathology, anxiety and depression were among the most common symptoms. In terms of functional impairment, the 'relationships' area was the most affected. The study provides initial insights into the transition-specific characteristics and needs of patients in transition age. The integration of standardized measuring instruments in institutional care systems, which individually record the transition-related needs, the willingness and need of young people in transition age, can facilitate targeted and needs-based treatment or transition. Interdisciplinary cooperation between child and adolescent psychiatry and adult psychiatry as well as a continuous transfer of the therapeutic relationships in the transition process should also be guaranteed.


Glycogen storage diseases of muscle.
Ten specific enzyme defects of glycogen metabolism affect skeletal muscle alone or in combination with other tissues. The newest addition to this group of disorders is the defect of aldolase A (glycogenosis type XII), a block in terminal glycolysis associated with myopathy and a hemolytic trait. The muscle glycogenoses cause two major syndromes, one characterized by exercise intolerance, cramps, and myoglobinuria, and the other dominated by fixed, often progressive weakness. This review considers sequentially recent advances in the following: clinical features or clinical variants, including a brief description of glycogenosis type XII; animal models, both spontaneous and genetically engineered; physiopathologic mechanisms, especially of the exercise intolerance and myoglobinuria; biochemical and molecular features--molecular defects are just beginning to be discovered for some glycogenoses (e.g. phosphorylase-b-kinase deficiency or branching enzyme deficiency), whereas they form long lists for others, such as acid maltase deficiency and myophosphorylase deficiency; and therapeutic approaches, including enzyme replacement and gene therapy.


Phase-locked responses in the Limulus lateral eye. Theoretical and experimental investigation.
The 1:1 phase locking of the neural discharge to sinusoidally modulated stimuli was investigated both theoretically and experimentally. On the theoretical side, a neural encoder model, the self-inhibited leaky integrator, was considered, and the phase of the locked impulse was computed for each frequency in the locking range by imposing the condition that the "leaky integral" u(t) of the driving signal should reach the threshold for the first time one stimulus period after the preceding impulse. As u(t) can be a nonmonotonic function, this approach leads to results that sometimes differ from those reported in the literature. It turns out that the phase excursion is often much smaller than the values of about 180 degrees predicted from previous analysis. Moreover, our analysis shows a peculiar effect; the phase locking frequency range narrows when the input modulation depth increases. The theoretical predictions are then compared with phase-locked discharge patterns recorded from visual cells of the Limulus lateral eye, stimulated by sinusoidally modulated light or depolarizing current. The phases of the locked spikes at each of a number of modulation frequencies have been measured. The predictions offered by the model fit the experimental data, although there are some difficulties in determining the effective driving signal.


Mucosal transferrin and ferritin factors in the regulation of iron absorption.
1. A standardized decompensation and recompensation of iron homeostasis has been produced by a change-over from normal to iron deficiency and back. 2. Under these conditions the 59Fe uptake into transferrin and ferritin of the mucosal "cytosol" and SDS treated "membrane" fraction has been measured together with the 59Fe amount transferred into the body. 3. The increase of the intestinal 59Fe absorption due to a progressive iron deficiency is associated with an increase of the 59Fe uptake into the mucosal transferrin of the "cytosol" and the "membrane" fraction; the reverse is observed with regard to mucosal ferritin. 4. Three days after the re-establishment of normal conditions the 59Fe absorption was lowered to normal values, while the 59Fe uptake into mucosal ferritin achieved again normally high values. 5. The high apparent rate of absorption in iron deficient animals decreased during the last 50 min after injection of the 59Fe labelled test dose. The 59Fe content in the ferritin fraction increased simultaneously, whereas the 59Fe content in the transferrin fraction remained the same. 6. The conclusion is drawn that the intestinal iron absorption is regulated by both mucosal iron binding proteins. Mucosal transferrin is responsible for the increase of absorption in iron deficiency while mucosal ferritin is responsible for the inhibition of iron absorption when the iron homeostasis recompensats.


Novel AP2238-clorgiline hybrids as multi-target agents for the treatment of Alzheimer's disease: Design, synthesis, and biological evaluation.
Cholinesterase and monoamine oxidase are potential targets for the therapy of Alzheimer's disease. A series of novel AP2238-clorgiline hybrids as multi-target agents were designed, synthesized and investigated in vitro for their inhibition of cholinesterases and monoamine oxidases. Many compounds displayed balanced and good inhibitory activity against AChE, BuChE and MAO-B with an obvious selective inhibitory effect on MAO-B. Among them, Compound 5l showed the most balanced potency to inhibit ChEs (eeAChE: IC50 = 4.03 ± 0.03 μM, eqBuChE: IC50 = 5.64 ± 0.53 μM; hAChE: IC50 = 8.30 ± 0.04 μM, hBuChE: IC50 = 1.91 ± 0.06 μM) and hMAO-B (IC50 = 3.29 ± 0.09 μM). Molecular modeling and kinetic studies showed that 5l was a mixed inhibitor for both AChE and BuChE, and a competitive MAO-B inhibitor. Compound 5l exhibited no toxicity to PC12 and BV-2 cells at 12.5 μM and no acute toxicity at a dosage of 2500 mg/kg. Moreover, 5l can improve the memory function of mice with scopolamine-induced memory impairment and have an excellent ability to cross the blood-brain barrier. Overall, these findings suggested that compound 5l could be deemed as a promising, balanced multi-target drug candidate against Alzheimer's disease.


Lemon juice improved color acceptance of aronia (Aronia melanocarpa) pound cake by copigmentation.
Anthocyanins can be changed into dark purplish color during pound cake preparation due to high temperature and alkaline baking soda, which lowers color acceptance by consumers. To stabilize a red color of anthocyanins in pound cake enriched with aronia (Aronia melanocarpa) powder, lemon juice was added to contain final concentrations of 0, 1, 2, and 3% (w/w) in the pound cake, which were assigned as control, PL1%, PL2%, and PL3%, respectively. As lemon juice amount increased, redness (a*) and sensory color perception as well as overall acceptance were enhanced, whereas hardness, gumminess, and chewiness decreased in texture profile analysis. In a model system, the addition of lemon juice to aronia solution caused bathochromic shift and hyperchromic effect in UV-Vis absorption spectrum, which are typical phenomena of copigmentation derived from interactions between anthocyanins and copigments. The results indicate that lemon juice improved color acceptance for aronia pound cake by copigmentation. The online version contains supplementary material available at 10.1007/s10068-023-01286-1.


The association between intolerance of uncertainty and Internet addiction during the second wave of the coronavirus disease 2019 pandemic: A multiple mediation model considering depression and risk perception.
Repeated outbreaks of coronavirus disease 2019 (COVID-19) have forced people to shift most of their work and life activities from offline to online, leading to a growing problem of Internet dependence and even Internet addiction. However, the mechanism of the association between COVID-19-related intolerance of uncertainty (COVID-19 IU) and Internet addiction during the second wave of COVID-19 is still unclear. The current study explored the association between COVID-19 IU and Internet addiction as mediated by depression and risk perception based on the Uncertainty-Depression-Perception-Addiction model (UDPA). A total of 1,137 adult participants were recruited, and COVID-19 IU, depression, risk perception, Internet addiction, and demographic variables were analyzed. The results showed that COVID-19 IU was significantly and positively associated with Internet addiction and that this relationship was mediated in parallel by depression and risk perception. Our findings further extend the Interaction of Person-Affect-Cognition-Execution (I-PACE) model from the perspective of applicability in the unique context of COVID-19. Furthermore, the study suggests that individuals could decrease their dependence on the Internet to prevent Internet addiction during the second wave of the pandemic through effective interventions that include lowering COVID-19 IU, improving emotion regulation, and developing reasonable perceptions of risk.


Germ line control of female sex determination in zebrafish.
A major transition during development of the gonad is commitment from an undifferentiated "bi-potential" state to ovary or testis fate. In mammals, the oogonia of the developing ovary are known to be important for folliculogenesis. An additional role in promoting ovary fate or female sex determination has been suggested, however it remains unclear how the germ line might regulate this process. Here we show that the germ line is required for the ovary versus testis fate choice in zebrafish. When the germ line is absent, the gonad adopts testis fate. These germ line deficient testes have normal somatic structures indicating that the germ line influences fate determination of surrounding somatic tissues. In germ line deficient animals the expression of the ovary specific gene cyp19a1a fails to be maintained whereas the testis genes sox9a and amh remain expressed. Furthermore, we observed decreased levels of the ovary specific genes cyp19a1a and foxL2 in germ line deficient animals prior to morphological sex differentiation of the gonad. We propose that the germ line has a common role in female sex determination in fish and mammals. Additionally, we show that testis specification is sufficient for masculinization of the fish pointing to a direct role of hormone signaling from the gonad in directing sex differentiation of non-gonadal tissues.


HFIP Promoted Low-Temperature SNAr of Chloroheteroarenes Using Thiols and Amines.
A highly efficient and an unprecedented hexafluoro-2-propanol, promoting low-temperature aromatic nucleophilic substitutions of chloroheteroarenes, has been performed using thiols and (secondary) amines under base-free and metal-free conditions. The developed protocol also provides excellent regio-control for the selective functionalization of dichloroheteroarenes, while the utility of the protocol was demonstrated by the modification of a commercially available drug ceritinib.


Investigational therapies for psoriasis.
As the pathogenesis of psoriasis is better understood, specific targeted therapies are being developed. In addition to alefacept, etanercept, efaluzimab, and infliximab, discussed in separate articles in this issue, numerous other investigational therapies are currently in clinical trials, some of which will likely be approved in the future. We review the most promising of these therapies and their mechanisms of action.


Systematic characterization of the branch point binding protein, splicing factor 1, gene family in plant development and stress responses.
Among eukaryotic organisms, alternative splicing is an important process that can generate multiple transcripts from one same precursor messenger RNA, which greatly increase transcriptome and proteome diversity. This process is carried out by a super-protein complex defined as the spliceosome. Specifically, splicing factor 1/branchpoint binding protein (SF1/BBP) is a single protein that can bind to the intronic branchpoint sequence (BPS), connecting the 5' and 3' splice site binding complexes during early spliceosome assembly. The molecular function of this protein has been extensively investigated in yeast, metazoa and mammals. However, its counterpart in plants has been seldomly reported. To this end, we conducted a systematic characterization of the SF1 gene family across plant lineages. In this work, a total of 92 sequences from 59 plant species were identified. Phylogenetic relationships of these sequences were constructed, and subsequent bioinformatic analysis suggested that this family likely originated from an ancient gene transposition duplication event. Most plant species were shown to maintain a single copy of this gene. Furthermore, an additional RNA binding motif (RRM) existed in most members of this gene family in comparison to their animal and yeast counterparts, indicating that their potential role was preserved in the plant lineage. Our analysis presents general features of the gene and protein structure of this splicing factor family and will provide fundamental information for further functional studies in plants.


Pre- Versus Post-Procedure Health Care Resource Utilization in Patients Undergoing Commercial Transcatheter Mitral Valve Repair.
The aim of this study was to assess the real-world impact of transcatheter mitral valve repair (TMVR) on hospitalizations and Medicare costs pre- versus post-TMVR. TMVR is effective in degenerative mitral regurgitation (MR) and appropriately selected patients with functional MR with high surgical risk. Patients undergoing TMVR in the Society of Thoracic Surgeons/American College of Cardiology TVT (Transcatheter Valve Therapy) Registry from 2013 to 2018 were linked to Medicare claims data. Rates of hospitalizations, hospitalized days, and Medicare costs were compared 1-year pre-TMVR to 1-year post-TMVR. Across 246 sites, 4,970 patients with a median age of 83 years (interquartile range: 77 to 87 years) were analyzed. The TMVR indication was degenerative MR in 77.5% and functional MR in 16.7%. From pre- to post-TMVR, heart failure (HF) hospitalization rates (479 vs. 370 hospitalizations/1,000 person-years; rate ratio [RR]: 0.77) and cardiovascular hospitalizations (838 vs. 632; RR: 0.75) decreased significantly (p < 0.001 for all). Similarly, the rates of hospitalized days decreased for HF and cardiovascular causes (p < 0.05 for all). Following TMVR, the odds of having no Medicare costs for HF hospitalizations increased (69% vs. 79%; odds ratio: 1.67; p < 0.001). However, the average total Medicare costs per day alive among patients with any HF hospitalizations after TMVR increased significantly (p < 0.001). The HF hospitalization rates decreased for patients with functional MR (683 vs. 502; RR: 0.74) and those with degenerative MR (431 vs. 337; RR: 0.78) (p < 0.001). TMVR is associated with a decrease in cardiovascular and HF hospitalizations and a greater likelihood of having no HF Medicare costs in the year after TMVR, regardless of MR etiology. Further work is necessary to elucidate the reasons for increased costs among patients with HF hospitalizations post-TMVR.


Detection and changes of nucleotide pyrophosphotransferase activity of Streptomyces griseus strains in submerged culture.
Nucleotide pyrophosphotransferase (NPT) activity of two Streptomyces griseus strains was studied in submerged culture during their life cycle. NPT activity could be detected only in the culture filtrate but not in the membrane fraction or in cell extract of the sporulating (streptomycin-non-producing) S. griseus No. 45-H. No enzyme could be detected in the non-sporulating (streptomycin-producing) S. griseus No 52--1 cultures.


Retracted: A Secure Private Cloud Storage Platform for English Education Resources Based on IoT Technology.
[This retracts the article DOI: 10.1155/2022/8453470.].


Cinnarizine: A Contemporary Review.
Cinnarizine, is approved for nausea, vomiting, motion sickness, inner ear disorders and is considered as first-line pharmacotherapy for management of vertigo. It acts by anti-vasoconstrictor activity, reducing blood viscosity and reducing nystagmus in labyrinth. Lack of adequate literature on clinical evidence of cinnarizine and its combination (dimenhydrinate) in vertigo management prompted this review. A specific MEDLINE literature search strategy was designed combining Medical Subject Headings, free-text keywords (like cinnarizine and vertigo) using Boolean operators (1970-2016) for clinical studies, clinical reviews and meta-analyses of cinnarizine. Analyses of studies validated cinnarizine's efficacy in peripheral and central vertigo versus placebo or other therapies, and was well-tolerated by the patients recruited across different studies. Cinnarizine and/ or its combinations are favorable in management of vestibular disorders wherein cinnarizine acts predominantly peripherally on labyrinth and dimenhydrinate acts centrally on vestibular nuclei and associated centers in brainstem. Combination therapy of cinnarizine and/ or its combinations demonstrated a better safety profile than either of the mono-components, offering a viable therapeutic option in vertigo management.


Novel dual inhibitor for targeting PIM1 and FGFR1 kinases inhibits colorectal cancer growth in vitro and patient-derived xenografts in vivo.
Colorectal cancer (CRC) is the second most common cause of cancer-related death in the world. The pro-viral integration site for Moloney murine leukemia virus 1 (PIM1) is a proto-oncogene and belongs to the serine/threonine kinase family, which are involved in cell proliferation, migration, and apoptosis. Fibroblast growth factor receptor 1 (FGFR1) is a tyrosine kinase that has been implicated in cell proliferation, differentiation and migration. Small molecule HCI-48 is a derivative of chalcone, a class of compounds known to possess anti-tumor, anti-inflammatory and antibacterial effects. However, the underlying mechanism of chalcones against colorectal cancer remains unclear. This study reports that HCI-48 mainly targets PIM1 and FGFR1 kinases, thereby eliciting antitumor effects on colorectal cancer growth in vitro and in vivo. HCI-48 inhibited the activity of both PIM1 and FGFR1 kinases in an ATP-dependent manner, as revealed by computational docking models. Cell-based assays showed that HCI-48 inhibited cell proliferation in CRC cells (HCT-15, DLD1, HCT-116 and SW620), and induced cell cycle arrest in the G2/M phase through modulation of cyclin A2. HCI-48 also induced cellular apoptosis, as evidenced by an increase in the expression of apoptosis biomarkers such as cleaved PARP, cleaved caspase 3 and cleaved caspase 7. Moreover, HCI-48 attenuated the activation of downstream components of the PIM1 and FGFR1 signaling pathways. Using patient-derived xenograft (PDX) murine tumor models, we found that treatment with HCI-48 diminished the PDX tumor growth of implanted CRC tissue expressing high protein levels of PIM1 and FGFR1. This study suggests that the inhibitory effect of HCI-48 on colorectal tumor growth is mainly mediated through the dual-targeting of PIM1 and FGFR1 kinases. This work provides a theoretical basis for the future application of HCI-48 in the treatment of clinical CRC.


Calcaneocuboid arthrodesis.
The calcaneocuboid joint is stable, although multiple conditions might affect the joint, including arthritis, fracture, subluxation, and dislocation. Calcaneocuboid arthrodesis is more commonly performed as an adjunct procedure with other rearfoot procedures such as triple arthrodesis and is less used as isolated fusion. This article reviews the main conditions of the lateral column and calcaneocuboid joint in particular. The surgical technique for isolated calcaneocuboid arthrodesis is discussed.


Uses and limitations of exercise Doppler echocardiography in the diagnosis of ischemic heart disease.
This study tested the hypothesis that coronary artery disease might be identified by a decrease in Doppler measurements of flow velocity and acceleration. The response of aortic blood flow velocity and acceleration to exercise was determined in 102 subjects (28 young control subjects and 74 older patients) who underwent continuous wave Doppler echocardiographic examination before, during and immediately after near maximal treadmill exercise. Patients were grouped according to the results of thallium perfusion imaging: Group I = normal, Group II = ischemia with or without prior infarction and Group III = prior infarction only. A significant decrease in the level of velocity and acceleration achieved with exercise was observed both in patients in Group I (normal thallium study) (1.2 +/- 0.3 m/s and 36.8 +/- 14 m/s per s, p less than or equal to 0.005) and in patients in Group II (ischemia) (1.1 +/- 0.3 m/s and 27.7 +/- 11 m/s per s, p less than or equal to 0.0005) compared with values in young control subjects (1.4 +/- 0.2 m/s and 52.7 +/- 16 m/s per s). When groups of patients of similar age who differed in the presence (Group II) or absence (Group I) of ischemia on thallium scintigraphy were compared, no difference was found for maximal velocity (1.1 +/- 0.3 versus 1.2 +/- 0.3 m/s, p = NS), but acceleration was significantly lower in Group II (27.7 +/- 11 versus 36.8 +/- 14 m/s per s, p less than or equal to 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Nitric oxide affects trypomastigote to amastigote differentiation in Trypanosoma cruzi.
Trypanosoma cruzi is the etiologic agent of Chagas disease. Two main distinct forms are present in the mammalian host: trypomastigote, an infective form, and the amastigote, a typical replicative form. Succeeding the host cell invasion, trypomastigotes differentiate to amastigotes, a process known as amastigogenesis. Amastigogenesis is characterized by parasite body remodeling, with drastic reduction of flagellum, and changes in protein profile and energetic metabolism. Our aim is to explore the role of nitric oxide as a signaling molecule during the amastigogenesis process, which must be strictly regulated. We report herein that acid pH (6.0) is essential for T. cruzi amastigogenesis. Also, during amastigogenesis there is a progressive solubilization of the paraflagellar protein, a flagellum marker. Moreover, the process is dependent on (•)NO concentration, since it is suppressed by 1mM SNAP, a (•)NO donor, and favored by 10mM L-NAME, a NOS inhibitor. Accordingly, S-nitrosylation of selective proteins occurs in amastigogenesis. Additionally, amastigogenesis is affected by IBMX (PDE inhibitor) treatment, suggesting the importance of cyclic nucleotides signaling. Furthermore, tubulin stability is also affected by the (•)NO availability. Along amastigogenesis, flagellum disassembling is accompanied by changes in a-tubulin tyrosylation and polyglutamylation levels. Taken together, these results suggest (•)NO participation in trypomastigote differentiation to amastigotes in T. cruzi.


NEAT1 contributes to ox-LDL-induced inflammation and oxidative stress in macrophages through inhibiting miR-128.
Long noncoding RNAs (lncRNA) have been recognized as significant regulators in the progression of atherosclerosis (AS). Oxidized low-density lipoprotein (ox-LDL) can induce macrophage inflammation and oxidative stress, that serves important roles in AS. However, the exact function of lncRNA NEAT1 and its possible molecular mechanism in AS remain unclear. Here, we concentrated on the roles and molecular mechanisms of NEAT1 in AS development. In our current study, we observed that NEAT1 was elevated by ox-LDL in a dose-dependent and time-dependent manner. RAW264.7 cell survival was greatly enhanced, and cell apoptosis was significantly inhibited by LV-shNEAT1 transfection. In addition, knockdown of NEAT1 in RAW264.7 cells repressed CD36 expression and foam cell formation while NEAT1 overexpression shown an opposite process. Moreover, NEAT1 downregulation inhibited inflammation molecules including IL-6, IL-1β, and TNF-α. Meanwhile, silencing of NEAT1 can also suppress reactive oxygen species (ROS) and malondialdehyde (MDA) levels with an enhancement of superoxide dismutase (SOD) activity in RAW264.7 cells. MicroRNAs are some short RNAs, and they can regulate multiple biological functions in many diseases including AS. Here, we found that miR-128 expression was remarkably decreased in ox-LDL-incubated RAW264.7 cells. Interestingly, miR-128 mimics was able to reverse AS-correlated events induced by overexpression of NEAT1. By using bioinformatics analysis, miR-128 was predicted as a target of NEAT1 and the correlation between them was validated in our study. Taken these together, it was implied that NEAT1 participated in ox-LDL-induced inflammation and oxidative stress in AS development through sponging miR-128.


Publisher Correction: Alloying conducting channels for reliable neuromorphic computing.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Enhanced adenoviral-vector mediated gene transfer using human albumin solder.
Laser tissue welding with human albumin solder (HAS) has been used as an alternative method of wound closure. Adenoviral vectors have been used to introduce various cytokine genes into wounds to accelerate wound closure. In the present study, we were interested in the effect of HAS on adenoviral vector transfer of the beta-galactosidase (beta-gal) gene in vitro and in vivo. 3T3 fibroblasts were used to study the effect of HAS on beta-gal gene transfer in vitro. The presence of beta-gal was determined by Western blot, and its activity by a colorimetric assay. A punch biopsy model of wound healing in pigs was used for in vivo experiments. HAS increased the efficiency of adenoviral-mediated beta-gal transduction and stabilized the adenovirus at room temperature. HAS protected adenovirus from inactivation by laser, both in vitro and in vivo. HAS may stabilize adenoviral vectors to deliver cytokine genes in future wound healing experiments.


Combined fractionated CO2 and low-power erbium:YAG laser treatments.
This article addresses the use of fractionated CO(2) laser and erbium:YAG laser for facial rejuvenation. Outcomes and limitations of these techniques are discussed, along with a stepwise summary of techniques as they are used in clinical practice. An evaluation of patient satisfaction is presented for a group of patients who underwent combined fractional CO(2) and erbium:YAG facial resurfacing.


Taxonomic notes on the predatory mite genus Proparholaspulus Ishikawa, 1980 and the first description of the male of Proparholaspulus ishikawai Liang amp; Hu, 1993 (Acari: Parholaspididae).
This study provides the first description of the male of Proparholaspulus ishikawai Liang Hu, 1993, on the basis of specimens from the south of China. The leg chaetotaxy of Proparholaspulus is described for the first time. A key for all recognisable species of Proparholaspulus is provided.


Histochemical evaluation of glutathione in brain.
Glutathione (GSH) is a ubiquitous cellular sulfhydryl compound with a variety of essential functions. A histochemical method that was developed by others for the localization of GSH in tissue sections was used to study the localization of GSH in rodent and primate brain. Sections of freshly frozen tissue were stained for 4 min with Mercury orange dissolved in toluene, and viewed by fluorescence microscopy for the product of the reaction with soluble sulfhydryl compounds. Soluble sulfhydryl compounds are comprised almost exclusively of GSH. Although the brain exhibits strong staining characteristics, reflecting the millimolar levels of GSH that are detected by chemical assay, very little stain is seen in neuronal somata. Pretreatment of animals with diethyl maleate resulted in depletion of GSH from brain (measured by high performance liquid chromatography), as well as decreased Mercury orange staining. The staining pattern observed in the brain may indicate that GSH is primarily localized to non-neuronal elements, such as glia, and/or in axons and nerve terminals.


EUS-guided cholecystenterostomy: a new technique (with videos).
The cornerstone of management for acute cholecystitis is cholecystectomy. However, surgical intervention is contraindicated in the occasional patient. EUS-guided transduodenal gallbladder drainage may represent an effective minimally invasive alternative. To describe a new technique, EUS-guided cholecystenterostomy. A single-center retrospective case series. Three patients with severe acute cholecystitis unresponsive to conservative management who were deemed unfit for cholecystectomy. Under combined EUS and fluoroscopic guidance, cholecystenterostomy was performed via needle puncture, guidewire insertion, cystoenterostome passage, and stent placement. Technical success, clinical progress, immediate and long-term complications, and recurrence of cholecystitis. Pilot series. Cholecystenterostomy was performed successfully in all patients. Rapid improvement in clinical status and inflammatory parameters ensued. A minor intraprocedural bile leak occurred in 1 patient, without significant clinical sequelae. Cholecystitis did not recur in any patient. EUS-guided cholecystenteric drainage is technically feasible and appears to be a safe and effective procedure. Via this technique, gallbladder drainage and resolution of related sepsis may be achieved in patients with acute cholecystitis who are unfit for surgery.


Prevalence of staphylococcal zoonosis in pyogenic skin infections.
S. aureus aetiology was found in 76.47% of the 102 pyoderma cases under study, with a high frequency of incidence in children below 5 years of age. The majority of the S. aureus isolates was nontypable (50.0%) and among the typable strains, phage group-III (31.0%), Group-I (20.7%) and a mixed phage group (34.5%) were predominant. 28.2% of the isolates were S. aureus var. bovis and 2.6% were S. aureus var. canis subgroups. Zoonoses in staphylococcal pyogenic skin infections were proved in 9 of the cases, which showed the history of direct animal contact supported by the isolation of S. aureus of animal host origin. Dogs, cattle and poultry were found to be the most important reservoirs transmitting S. aureus to humans, with folliculitis, furunculosis, impetigo as the frequent clinical manifestations.


Healthcare-Associated Meningitis or Ventriculitis in Older Adults.
Healthcare-associated meningitis or ventriculitis (HCAMV) is a serious and life-threatening complication of invasive neurosurgical procedures or penetrating head trauma. Older adults are at higher risk of adverse outcomes in community-acquired meningitis but studies of HCAMV are lacking. Therefore, we perform the study to define the differences in clinical outcomes between older and younger adults with HCAMV. Retrospective study. A large tertiary care hospital in Houston, Texas, from July 2003 to November 2014. Adults with a diagnosis of HCAMV (N = 160) aged ≥65 (n = 35), aged 18-64 (n = 125). Demographic characteristics, clinical presentation, laboratory results, treatments, and outcomes (Glasgow Outcome Scale). Older adults had more comorbidities and CSF abnormalities [pleocytosis, high cerebrospinal fluid (CSF) protein, low CSF glucose) and were more likely to have altered mental status than younger adults (P < .05). An adverse clinical outcome was seen in 142 participants (89%) (death (n = 18, 11%), persistent vegetative state (n = 26, 16%), severe disability (n = 68, 43%), moderate disability (n = 30, 19%). There was no difference in adverse outcomes between older (97%) and younger (86%) adults (P = .13). On logistic regression analysis, abnormal neurological examination (adjusted odds ratio (aOR) = 7.13, 95% confidence interval (CI) = 2.15-23.63, P = .001) and mechanical ventilation (aOR = 11.03, 95% CI = 1.35-90.51, P = .02) were associated with adverse clinical outcomes. Older adults with HCAMV have more comorbidities and CSF abnormalities and are more likely to have altered mental status than younger adults but have similar high rates of adverse clinical outcomes.


Feedback regulation of apical progenitor fate by immature neurons through Wnt7-Celsr3-Fzd3 signalling.
Sequential generation of neurons and glial cells during development is critical for the wiring and function of the cerebral cortex. This process requires accurate coordination of neural progenitor cell (NPC) fate decisions, by NPC-autonomous mechanisms as well as by negative feedback from neurons. Here, we show that neurogenesis is protracted and gliogenesis decreased in mice with mutations of genes Celsr3 and Fzd3. This phenotype is not due to gene inactivation in progenitors, but rather in immature cortical neurons. Mutant neurons are unable to upregulate expression of Jag1 in response to cortical Wnt7, resulting in blunted activation of Notch signalling in NPC. Thus, Celsr3 and Fzd3 enable immature neurons to respond to Wnt7, upregulate Jag1 and thereby facilitate feedback signals that tune the timing of NPC fate decisions via Notch activation.


Long noncoding RNA ANRIL up-regulates CCND1 via sponging miR-98-5p to promote TGF-β1-induced human airway smooth muscle cell proliferation, migration, and extracellular matrix deposition.
Excessive proliferation and migration of airway smooth muscle cell (ASMC) contribute to asthma pathogenesis. Long noncoding RNAs (lncRNAs) are reported to take part in asthma pathogenesis. This study is targeted at deciphering the role of the lncRNA antisense noncoding RNA in the INK4 locus (ANRIL) in ASMC proliferation, migration and extracellular matrix (ECM) deposition. qRT-PCR was performed to determine ANRIL, miR-98-5p, and cyclin D1 (CCND1) mRNA expression levels in transforming growth factor-β1 (TGF-β1)-treated ASMCs. CCK-8 and Transwell assays were employed to examine ASMC proliferation and migration, respectively. Dual-luciferase reporter gene assay and RNA immunoprecipitation assay were carried out for analyzing the targeted relationship of miR-98-5p with ANRIL or CCND1 mRNA 3'-UTR. The levels of CCND1 and ECM proteins (such as fibronectin, COL3A1, and COL1A2) in ASMCs were detected through Western blot. In this work, we found that ANRIL and CCND1 were up-regulated in TGF-β1-treated ASMCs, whereas miR-98-5p was down-regulated. ANRIL overexpression facilitated the proliferation, ECM deposition and migration of TGF-β1-induced ASMCs, while knocking down ANRIL had the opposite effect. Furthermore, ANRIL targeted miR-98-5p directly, and CCND1 was miR-98-5p's downstream target. ANRIL indirectly increased CCND1 expression in ASMCs via competitively binding to miR-98-5p. MiR-98-5p inhibition or CCND1 overexpression counteracted the inhibiting effect that ANRIL knockdown had on TGF-β1-stimulated ASMC proliferation, migration and ECM deposition. In conclusion, ANRIL indirectly up-regulates CCND1 expression by targeting miR-98-5p to promote ASMC proliferation, migration and ECM deposition, thus facilitating the pathogenesis of asthma.


Natural antibodies against the carcinoembryonic antigen (CEA) and a related antigen, NCA, in human sera.
Natural antibodies directed against CEA and a related antigen, NCA, have been demonstrated in all normal and pathological sera using an EIA, although they have never been detected by RIA. These antibodies are not anti-blood group antibodies, as their titer was decreased only slightly by absorption with blood group substances. The study of their reactivity with deglycosylated antigens demonstrated that they were directed against peptidic epitopes. Antibodies against NCA or CEA, purified using specific immunosorbents, cross-reacted with all the antigens of the "CEA family" but not or only weakly with unrelated antigens.


Erector spinae plane block versus retrolaminar block for postoperative analgesia after breast surgery: a randomized controlled trial.
The newly introduced erector spinae plane block (ESPB) has given anesthesiologists an alternative regional anesthetic technique for thoracic analgesia. Although ESPB and retrolaminar block (RLB) have similar puncture sites, no clinical study comparing ESPB and RLB has been reported. The aim of this study was to compare ESPB and RLB in terms of analgesic efficacy in the context of multimodal analgesia following breast surgery. Fifty female patients undergoing breast surgery under general anesthesia were randomly allocated to receive either ultrasound-guided ESPB or RLB with 20 mL of 0.375% levobupivacaine for postoperative analgesia. The primary outcome was analgesic efficacy in terms of time to first postoperative rescue analgesic after the block procedure. The secondary outcomes were consumption of remifentanil during anesthesia, pain intensity at rest for 24 h postoperatively, and occurrence of postoperative nausea and vomiting (PONV). After excluding five patients, 45 patients (22 and 23 patients in the ESPB and RLB group, respectively) were analyzed. Median time until the first postoperative rescue analgesic after the block procedure in the ESPB group was not significantly longer than that in the RLB group (8.6 [range 2.7-24] vs. 4.8 [3.0-24] h; P = 0.83). There was no significant difference in the consumption of remifentanil during anesthesia, pain intensity at rest for 24 h postoperatively, and occurrence of PONV between the two groups. ESPB is equivalent, and not superior, to RLB for postoperative analgesia after breast surgery when 20 mL of 0.375% levobupivacaine is injected at the fourth thoracic vertebra.


A diabetic patient presenting with stiff hand following fasciectomy for Dupuytren's contracture: A case report.
Reported is the case of a 68-year-old male presenting with severe wrist and hand stiffness following surgery for a Dupuytren's contracture. Complications of surgery or rehabilitation and complex regional pain syndrome were excluded as factors explaining this stiffness. Given the patient's diabetes mellitus and the striking similarity with the typical diabetic stiff hand, it is suggested that diabetes may have contributed to the development of the complication.