Brain death in the newborn.
The clinical courses of 18 preterm and term infants less than 1 month of age in whom brain death was diagnosed were retrospectively reviewed. Clinical diagnosis was determined neurologically and included (1) coma, (2) apnea, manifested by inability to sustain respiration, and (3) absent brainstem reflexes. Electroencephalograms were performed in all patients; 17 patients had adequate cerebral blood flow as estimated by radionuclide imaging. The results indicate that (1) neurodiagnostic tests such as electroencephalograms and radionuclide scanning reconfirmed clinically determined brain death in only one half to two thirds of patients; (2) electrocerebral silence in the absence of barbiturates, hypothermia, or cerebral malformations during 24 hours was confirmatory of brain death if the clinical findings remained unchanged; (3) absence of radionuclide uptake associated with initial electrocerebral silence was associated with brain death; (4) term infants clinically brain dead for 2 days and preterm infants brain dead for 3 days did not survive despite electroencephalogram or cerebral blood flow status; and (5) phenobarbital levels greater than 25 micrograms/mL may suppress electroencephalographic activity in this age group. The findings suggest that determination of brain death in the newborn can be made solely by using clinical criteria. Confirmatory neurodiagnostic studies are of value because they can potentially shorten the period of observation.


Design of "Turn On" fluorometric nanoprobe based on nitrogen doped graphene quantum dots modified with β-cyclodextrin and vitamin B6 cofactor for selective sensing of dopamine in human serum.
Herein, a novel and rapid fluorometric nanoprobe was constructed for quantitation of dopamine (DA) in presence of biologically interfering compounds. The nanoprobe based on synthesis of yellow emissive nitrogen doped graphene quantum dots (N@GQDs) by advanced thermal driven oxidation. After that, the synthesized N@GQDs was capped with β-cyclodextrin (β-CD), followed by interaction with pyridoxal (PYL) vitamin B6 cofactor. This interaction resulted in diminishing the yellow fluorescence of β-CD/N@GQDs, and appearance of blue emission peak at 420 nm. Upon addition of DA, the blue emission of β-CD/N@GQDs was increased after excitation at λ = 330 nm. Under optimum conditions, the nanoprobe exhibited a linear range of 0.36-400 nM with limit of detection (LOD) of 0.117 nM. In addition, the fluorescent nanoprobe shows high selectivity and can be used for detection of DA in complicated biological matrices and human serum. This strategy might provide a potential tool for clinical diagnosis and biomedical research for DA related diseases.


HSP27 phosphorylation is correlated with ADP-induced platelet granule secretion.
Adenosine diphosphate (ADP) plays a crucial role in hemostasis and thrombosis by activating platelets. ADP has been reported to induce heat-shock protein (HSP) 27 phosphorylation in human platelets. However, the exact role of HSP27 phosphorylation in human platelets has not yet been clarified. In the present study, we investigated the mechanisms and the roles of ADP-induced HSP27 phosphorylation in human platelets. We showed for the first time that both of decreased phosphorylation levels of HSP27 by PD98059, a MEK1/2 inhibitor and SB203580, a p38 MAPK inhibitor were correlated with the suppressed levels of platelet granule secretion but not with platelet aggregation. Furthermore, the inhibition of either the p44/p42 MAPK or p38 MAPK pathways had no effect on ADP-induced platelet aggregation. These results strongly suggest that the ADP-induced phosphorylation of HSP27 via p44/p42 MAPK and/or p38 MAPK is therefore sufficient for platelet granule secretion but not for platelet aggregation in humans.


Relationships Among Motor, First, and Second Language Skills Among Bilingual Children With Language Disorders.
The purpose of this study was to determine the significance and directions of the relationships among oral and manual fine motor skills and language abilities among Spanish-English bilingual children. If such relationships exist, this would support a shared biological influence on motor and language development. Participants included 56 bilingual children, 24 of whom met criteria for developmental language disorder (DLD), recruited based on teacher concern for language and/or reading comprehension abilities. Students participated in a battery of baseline tests to determine motor, language, and cognitive abilities. Correlations among all variables were examined for direction of relationships. Regression models explored the predictive power of motor skills with Spanish and English language ability as the outcome measure. Oral fine motor abilities (diadochokinetic rate productions of /pa/ and /pata/) predicted Spanish (but not English) oral language abilities in the expected direction (i.e., faster rates were associated with better language). Manual fine motor performance on computer tapping tasks was not related to performance in either language. Oral fine motor abilities are related to language abilities in bilingual children, but only for the native language. We did not find reliable differences in oral and manual fine motor skills between groups of bilingual children with and without DLD. These findings support a limited role of shared biological influences on motor and language development.


Application of Magnetic Force Microscopy for Investigation of Epitaxial Ferro- and Antiferromagnetic Structures.
Growing of epitaxial Fe50Mn50/Fe/Mo/R-sapphire films was performed with a new configuration of two in-plane easy axes of Fe(001)-layer magnetization in which application of annealing in a magnetic field forms an unidirectional anisotropy. The microstructures made from these films exhibited an exchange bias 25-35 G along an exchange field generated at antiferromagnet/ferromagnet (AFM/FM) interface. Magnetic force microscopy (MFM) experiments supported by micromagnetic calculations and magneto-resistive measurements allowed interpretation of the magnetic states of the Fe layer in these microstructures. The magnetic states of the iron layer are influenced more by crystallographic anisotropy of the Fe-layer than by unidirectional exchange anisotropy.


A 300-kb microduplication of 7q36.3 in a patient with triphalangeal thumb-polysyndactyly syndrome combined with congenital heart disease and optic disc coloboma: a case report.
Triphalangeal thumb-polysyndactyly syndrome (TPT-PS) is a rare well-defined autosomal dominant disorder characterized by long thumbs with three phalanges combined with pre- and postaxial polydactyly/syndactyly of limbs. By now, the syndrome has been reported in several large families from different ethnic backgrounds, with a high degree of inter- and intrafamilial variability. The genome locus responsible for TPT-PS has been mapped to the 7q36.3 region harboring a long-range sonic hedgehog (SHH) regulatory sequence (ZRS). Both single-nucleotide variants and complete duplications of ZRS were shown to cause TPT-PS and similar limb phenotypes. TPT-PS usually forms as isolated limb pathology not associated with additional malformations, in particular, with cardiovascular abnormalities. Here we report on a rare Russian neonatal case of TPT-PS combined with severe congenital heart disease, namely double outlet right ventricle, and microphthalmia with optic disc coloboma. Pedigree analysis revealed TPT-PS of various expressivity in 10 family members throughout five generations, while the cardiac defect and the eye pathology were detected only in the proband. To extend the knowledge on genotype-phenotype spectrum of TPT-PS, the careful clinical and genomic analysis of the family was performed. High-resolution array-based comparative genomic hybridization (array-CGH) revealed a ~ 300 kb microduplication of 7q36.3 locus (arr[GRCh37] 7q36.3(156385810_156684811) × 3) that co-segregated with TPT-PS in the proband and her mother. The duplication encompassed three genes including LMBR1, the intron 5 of which is known to harbor ZRS. Based on whole-exome sequencing data, no additional pathogenic mutations or variants of uncertain clinical significance were found in morbid cardiac genes or genes associated with a microphthalmia/anophthalmia/coloboma spectrum of ocular malformations. The results support the previous data, indicating that complete ZRS duplication underlies TPT-PS, and suggest a broader phenotypic impact of the 7q36.3 microduplication. Potential involvement of the 7q36.3 microduplication in the patient's cardiac and eye malformations is discussed. However, the contribution of some additional genetic/epigenetic factors to the complex patient`s phenotype cannot be excluded entirely. Further comprehensive functional studies are needed to prove the possible involvement of the 7q36.3 locus in congenital heart disease and eye pathology.


Visual evoked potentials to light flash in cats: is a frontal sinus reference electrode truly indifferent?
In flaxedilized cats, visual cortex evoked potentials (VEPs) to an intensity series of brief light flashes were recorded differentially using either a screw over frontal sinus or an insect pin in neck muscle as the reference electrode. At the same time EPs from the cornea (the ERG) and frontal sinus were recorded differentially against the neck muscle electrode. The EP recorded from the frontal sinus screw was a miniature of the ERG recorded from the cornea, with the same latencies and shape as the ERG but only 10-30% of its amplitude. At a fast presentation rate (1/sec) the amplitude of the ERG, and consequently the frontal sinus potential, decreased with increasing intensity of light flash, whereas at a slow presentation rate (1/3 or 1/5 sec) the ERG and frontal sinus potential increased in response to all but the highest intensities. The location of the reference electrode and the rate of light flash presentation had the following effects on visual cortex EP amplitudes. A frontal sinus reference increased the amplitudes of early components (less than 100 msec) of the VEP. Also, VEP amplitudes as a function of flash intensity yielded slopes which tended to be positive at a slow presentation rate and negative at a fast presentation rate. This effect is in accord with the rate dependent slopes of the frontal sinus potential.


Differential polarized phase fluorometric studies of phospholipid bilayers under high hydrostatic pressure.
Differential polarized phase fluorometry was used to quantify the rotational rate (R) and limiting anisotropy (r infinity) of the membrane probe diphenylhexatriene (DPH) in solvents and lipid vesicles exposed to hydrostatic pressures ranging from 1 bar to 2 kbar. These measurements reveal the effect of pressure on the phase-transition temperatures of the phosphatidylcholine vesicles, and the effects of pressure on order parameter of the acyl side-chain region of the membranes, the latter as indicated by r infinity. In addition to the well-known elevation of the transition temperature (Tc) with pressure, our results demonstrate that increased pressure restores the order of the bilayers to that representative of temperatures below the transition temperature. We also found that solvents which allowed free isotropic rotation of DPH at 1 bar no longer allowed free rotation when sufficiently compressed; moreover, the apparent DPH rotational rate increased with r infinity. Pressure studies using both DPH and the charged DPH analogue, trimethylammonium DPH (TMA-DPH) indicated that the Tc of dipalmitoylphosphatidylcholine vesicles increased 23 K/kbar and an apparent volume change of 0.036 ml/mol lipid at the phase transition. Assuming, as has been proposed, that TMA-DPH is localized near the glycerol backbone region of the bilayers, these results indicate a similar temperature- and pressure-dependent phase transition in this region and the acyl side-chain region of the membrane.


Nur77 ameliorates age-related renal tubulointerstitial fibrosis by suppressing the TGF-β/Smads signaling pathway.
Nerve growth factor-induced gene B (Nur77) has been shown to ameliorate several biological processes in chronic diseases, including inflammatory response, cellular proliferation, and metabolism. Chronic kidney disease (CKD) is characterized by tubulointerstitial fibrosis for which no targeted therapies are available as yet. In this study, we performed in vivo and in vitro experiments to demonstrate that Nur77 targets fibrosis signals and attenuates renal tubulointerstitial fibrosis during the aging process. We observed that the TGF-β/Smads signal pathway was significantly suppressed by Nur77, suggesting that Nur77 controlled the activation of key steps in TGF-β/Smads signaling. We further showed that Nur77 interacted with Smad7, the main repressor of nuclear translocation of Smad2/3, and stabilized Smad7 protein homeostasis. Nur77 deficiency resulted in Smad7 degradation, aggravating Smad2/3 phosphorylation, and promoting transcription of its downstream target genes, ACTA2 and collagen I. Our findings demonstrate that Nur77 is a potential therapeutic target for age-related kidney diseases including CKD. Maintenance of Nur77 may be an effective strategy for blocking renal tubulointerstitial fibrosis and improving renal function in the elderly.


Validation of the French Version of Conners' Parent Rating Scale Revised, Short Version: Factorial Structure and Reliability.
Attention-deficit hyperactivity disorder is one of the most frequent neurodevelopmental disorders. Its diagnosis requires reference questionnaires such as the Conners' Parent Rating Scale (CPRS). Presently, in French-speaking countries, a few translations of the revised short CPRS have been put to use without previous formal validation. We sought here for the validation of a French version (Lausanne, Switzerland) of the revised short CPRS regarding construct validity, internal consistency, and item reliability in a sample of French schoolchildren. The study involved 795 children and adolescents aged 9 to 19 years from a single school. The factorial structure and item reliability were assessed with a confirmatory factor analysis for ordered categorical variables. The dimension internal consistency was assessed with Guttman's lambda 6 coefficient. The results confirmed the original and strong 3-dimensional factorial structure (Oppositional, Cognitive Problems/Inattention, and Hyperactivity), showed satisfactory item reliability, and indicated a good dimension internal consistency (Guttman's lambda 6 coefficient: 0.87, 0.90, and 0.82, respectively, to the 3 dimensions). Thus, the Lausanne French version of the revised short CPRS may be considered validated regarding construct validity and item and dimension reliability; it can be now more confidently used in clinical practice.


Local Therapy Decision-Making and Contralateral Prophylactic Mastectomy in Young Women with Early-Stage Breast Cancer.
Rates of contralateral prophylactic mastectomy (CPM) have increased in the United States, with younger women with breast cancer the most likely to have CPM. As part of an ongoing cohort study of young women diagnosed with breast cancer at age ≤40 years, we conducted multinomial logistic regression of data from 560 women with unilateral Stage I-III disease to identify factors associated with: (1) CPM versus unilateral mastectomy (UM); (2) CPM versus breast-conserving surgery (BCS). Median age at diagnosis was 37 years; 66 % of women indicated that their doctor said that BCS was an option or was recommended. Of all women, 42.9 % had CPM, 26.8 % UM, and 30.4 % BCS. Among women who said the surgical decision was patient-driven, 59.9 % had CPM, 22.8 % BCS, and 17.3 % UM. Clinical characteristics associated with CPM versus BCS included HER2 positivity, nodal involvement, larger tumor size, lower BMI, parity, and testing positive for a BRCA mutation. Emotional and decisional factors associated with CPM versus UM and BCS included anxiety, less fear of recurrence, and reporting a patient-driven decision. Women who reported a physician-driven decision were less likely to have had CPM than both of the other surgeries, whereas higher confidence with the decision was associated with having CPM versus BCS. Many young women with early-stage breast cancer are choosing CPM. The association between CPM and emotional and decisional factors suggest that improved communication together with better psychosocial support may improve the decision-making process.


Immediate bonding properties of universal adhesives to dentine.
To evaluate the dentine microtensile bond strength (μTBS), nanoleakage (NL), degree of conversion (DC) within the hybrid layer for etch-and-rinse and self-etch strategies of universal simplified adhesive systems. forty caries free extracted third molars were divided into 8 groups for μTBS (n=5), according to the adhesive and etching strategy: Clearfil SE Bond [CSE] and Adper Single Bond 2 [SB], as controls; Peak Universal Adhesive System, self-etch [PkSe] and etch-and-rinse [PkEr]; Scotchbond Universal Adhesive, self-etch [ScSe] and etch-and-rinse [ScEr]; All Bond Universal, self-etch [AlSe] and etch-and-rinse [AlEr]. After restorations were constructed, specimens were stored in water (37°C/24h) and then resin-dentine sticks were prepared (0.8mm(2)). The sticks were tested under tension at 0.5mm/min. Some sticks from each tooth group were used for DC determination by micro-Raman spectroscopy or nanoleakage evaluation (NL). The pH for each solution was evaluated using a pH metre. Data were analyzed with one-way ANOVA and Tukey's test (α=0.05). For μTBS, only PkSe and PkEr were similar to the respective control groups (p>0.05). AlSe showed the lowest μTBS mean (p<0.05). For NL, ScEr, ScSe, AlSe, and AlEr showed the lowest NL similar to control groups (p<0.05). For DC, only ScSe showed lower DC than the other materials (p<0.05). Performance of universal adhesives was shown to be material-dependent. The results indicate that this new category of universal adhesives used on dentine as either etch-and-rinse or self-etch strategies were inferior as regards at least one of the properties evaluated (μTBS, NL and DC) in comparison with the control adhesives (CSE for self-etch and SB for etch-and-rinse).


Role of fluid replacement, increased oxygen availability by perfluorochemicals and enhanced RES function in the treatment of mesenteric occlusion shock.
Experiments were carried out on 183 rats to study the effect of a complex therapy for treatment of mesenteric shock. The superior mesenteric artery (SMA) was temporarily ligated for 90 min under ether anesthesia; this was followed by an analgesic treatment. After release of the ligated artery, fluid therapy was instituted by administering the equivalent of 7.5% of body weight of one of three different solutions: ringer lactate (RL), hydroxyethyl starch (HES) in RL, and perfluorochemicals (PFC, 4 g/kg b.wt. in RL with HES), the latter with the aim to improve the oxygen transport to the tissue. The same fluid therapy was carried out on rats pretreated with E. coli endotoxin. Endotoxin pretreatment was chosen to compensate the negative effect of PFC on the reticuloendothelial system (RES) as shown in previous studies. Survival time and survival rate were recorded as well as hematocrit values at different times before and after treatment. Experimental groups were: (1) SMA occlusion without release; (2) 90-min occlusion without therapy. Treated animals: (3) RL therapy; (4) therapy with HES in RL; (5) therapy with PFC in RL and HES; (6), (7), and (8) identical therapies as Groups 3, 4, and 5, respectively, but with endotoxin pretreatment. Survival time increased to the same extent if HES or PFC were added to RL. There was a further increase both in survival times and rates with endotoxin pretreatment (Groups 6, 7, and 8 vs. Groups 3, 4, and 5). The highest survival time and rate were obtained in Group 8, which received PFC therapy with endotoxin pretreatment. There was a slight negative correlation between survival time and hematocrit values if all groups were considered together.(ABSTRACT TRUNCATED AT 250 WORDS)


Multicore disease. Report of a case with lack of fibre type differentiation.
A six year old boy had congenital hypotonia and nonprogressive proximal muscular weakness, with mild abnormalities in the E. M. G. and normal serum enzyme levels. There was lack of fibre type differentiation in the quadriceps muscle biopsy. The fibres had high oxidative enzyme activity and low ATPase 9.4 activity. In almost every fibre there were multiple areas of focal decrease of oxidative enzyme activity, resembling in few of them the lesion described in Central Core Disease. There was abscence of mitochondria and disorganization of the sarcomere with streaming of the Z line within the lesions. The clinical and histological observations have close similarity to the cases first described by A. G. Engel et al. in 1971 as "Multicore Diseases" and to other similar reported cases.


Copper transfer through the intestinal wall. Serosal release of metallothionein.
The elucidation of the molecular side of copper transport in biological systems is a promising task. In this context the transfer of ingested copper into the portal blood plasma was examined. Intralumenal addition of 200 microM copper caused the release of Cu-thionein into the venous effluent. This Cu-thionein became detectable after prior perfusion of the porcine small bowel using a modified isotonic phosphate-buffered saline (Pi/NaCl) medium. The protein was characterized by gel chromatography, luminescence, electronic absorption and immunological identification. ELISA and immunoblotting employing a murine monoclonal antibody to rat liver metallothionein-I proved to be most convenient. Using buffer-loaded sacs of porcine jejunum into which Cu2+, Zn2+ and Cd2+ were added, the release of metallothionein into the serosal fluid was successfully seen by ELISA. The observed excretion of metallothionein into the portal compartment may be a genuine metal transport system for many biochemically active metals.


Compassionate Use of REGEN-COV® in Patients With Coronavirus Disease 2019 (COVID-19) and Immunodeficiency-Associated Antibody Disorders.
Patients with immunodeficiency-associated antibody disorders are at a higher risk of prolonged/persistent COVID-19 infection, having no viable treatment options. A retrospective analysis of patients with primary and/or secondary immunodeficiency-associated antibody disorders who received casirivimab and imdevimab (REGEN-COV®) under emergency compassionate use. Objective were to describe safety and response to REGEN-COV, focusing on the subset of patients who had COVID-19 duration ≥21 days before treatment. Quantitative (change in oxygenation status and/or viral load) and/or qualitative (physician-reported clinical status) outcomes data are reported from 64 patients. Improvement in ≥1 outcome was observed in 90.6% of the overall patient group. Thirty-seven of these had COVID-19 duration ≥21 days before treatment; median time from diagnosis to REGEN-COV treatment was 60.5 days. Of the 29 patients with COVID-19 duration ≥21 days before treatment and available outcome data, 96.6% showed improvement in ≥1 outcome. In the 14 patients with post-treatment reverse transcription-polymerase chain reaction (RT-PCR) results available, 11 (78.6%) reported a negative RT-PCR following treatment, with 5 (45.5%) and 8 (72.7%) patients reporting a negative RT-PCR within 5 days and 21 days of treatment, respectively. Ten of 85 patients (11.8%) experienced serious adverse events; only one was an infusion-related reaction, possibly related to REGEN-COV. Two deaths were reported; neither were attributed to REGEN-COV. In this retrospective analysis of immunodeficient patients granted REGEN-COV under emergency compassionate use, REGEN-COV treatment was associated with rapid viral clearance and clinical improvement in patients with longstanding COVID-19. Adverse events were consistent with COVID-19 and its associated complications, and due to patients' concurrent medical conditions.


A cDNA encoding a plant homologue to animal HMG box proteins involved in structure-specific recognition of DNA (SSRP family).
We report a cDNA encoding a 71-kDa protein with a single high-mobility group (HMG) box and two nuclear localization signals from the higher plant Catharanthus roseus (Madagascar periwinkle). The protein had 40% amino acid identity with animal DNA-binding proteins of the SSRP (structure-specific recognition protein) family that recognize bent, unwound DNA structures. Genomic Southern analysis suggested the presence of two genes.


A new class of highly potent matrix metalloproteinase inhibitors based on triazole-substituted hydroxamates: (radio)synthesis and in vitro and first in vivo evaluation.
In vivo imaging of MMPs is of great (pre)clinical interest and can potentially be realized with modern three-dimensional and noninvasive in vivo molecular imaging techniques such as positron emission tomography (PET). Consequently, MMP inhibitors (MMPIs) radiolabeled with positron emitting nuclides (e.g., (18)F) represent a suitable tool for the visualization of activated MMPs with PET. On the basis of our previous work and results regarding radiolabeled and unlabeled derivatives of the nonselective MMPIs, we discovered a new class of fluorinated MMPIs with a triazole-substituted hydroxamate substructure. These novel MMPIs are characterized by an increased hydrophilicity compared with the lead structures and excellent MMP inhibition potencies for MMP-2, MMP-8, MMP-9, and MMP-13 (IC(50) = 0.006-107 nM). Therefore, one promising fluorinated triazole-substituted hydroxamate (30b) was selected and resynthesised as its (18)F-labeled version to yield the potential PET radioligand [(18)F]30b. The biodistribution behavior of this novel compound was investigated with small animal PET.


A caprine pneumonia outbreak associated with caprine herpesvirus and Pasteurella haemolytica respiratory infections.
In a field disease outbreak, 60 female goats died over a 2-3 week period. Necropsies of seven of these does revealed that six had an acute exudative necrotising broncho-pneumonia, and moderate to high numbers of Pasteurella haemolytica were isolated from their lungs. Caprine herpesvirus, identified as Bovid herpesvirus type 6, was isolated from the lungs of two of these does, including one with pneumonia, and from nasal swabs of in-contact goats. Clinical disease was only observed in does, and deaths began 3 weeks after the introduction of a mob of goat hoggets from another farm.


Nerves in northern Norway: the communication of emotions, illness experiences, and health-seeking behaviors.
The nature of nerves is the subject of a growing and dynamic body of anthropological research. The term nerves is often conceptualized as hard to define. Its meaning carries ambiguities, inconsistencies, and variation, although it is connected to reactions to the hardships of life. In the West, it is often associated with psychiatric problems. In this study, the researcher unveiled peoples' pragmatic use of the term nerves through diverse social settings in a coastal community in Northern Norway. The term was connected to psychological or psychiatric problems, privacy, and stigma, but had the capacity to communicate a continuum from normal emotional problems to severe mental illness. This study also showed the effect of the term in encounters between patients and professional health workers.


Co-occurrence patterns of cavity-nesting birds in cottonwood-willow communities.
We studied the covariation of six species of cavity-nesting birds to determine the extent to which species' co-occurrence patterns were attributable to interspecific relations. We tested two null hypotheses: (1) inverse relations did not exist among potential competitors for nest trees or nest cavities, and (2) there were no positive relations among potential commensals for nest cavities. Statistical power analyses, and simple, partial, and multiple partial correlation and regression analyses provided little evidence of species-species or higher-order inverse or positive relations. Most of the variation in co-occurrence patterns was associated with stand characteristics. Collectively, an abundance of nest trees and nest cavities, differences among species in acceptable nest-tree and nest-cavity dimensions, and different periods of peak nesting activity appear to be responsible for the lack of negative relations among potential competitors. Positive relations among potential commensals were weak presumably because (1) secondary cavity nesters (SCNs) frequently used cavities that originated from wind-, lightning-, and/or disease-damaged limbs and were thus not dependent completely on primary cavity nesters for cavities, and (2) the lag time for cavity use by SCNs is often two or more seasons. Interspecific relations were apparently not major determinants of community structure during our investigation; assemblages of cavity nesters appeared instead to be influenced more by independent species-specific habitat responses.


The hygiene hypothesis and psychiatric disorders.
The hygiene hypothesis proposes that several chronic inflammatory disorders (allergies, autoimmunity, inflammatory bowel disease) are increasing in prevalence in developed countries because a changing microbial environment has perturbed immunoregulatory circuits which normally terminate inflammatory responses. Some stress-related psychiatric disorders, particularly depression and anxiety, are associated with markers of ongoing inflammation, even without any accompanying inflammatory disorder. Moreover, pro-inflammatory cytokines can induce depression, which is commonly seen in patients treated with interleukin-2 or interferon-alpha. Therefore, some psychiatric disorders in developed countries might be attributable to failure of immunoregulatory circuits to terminate ongoing inflammatory responses. This is discussed in relation to the effects of the immune system on a specific group of brain serotonergic neurons involved in the pathophysiology of mood disorders.


An enzymatic assay for the MAO-B inhibitor selegiline in plasma.
A sensitive fluorimetric assay based on inhibition of rat brain monoamine oxidase-B (MAO-B) in vitro has been described. The procedure measures the inhibition of MAO activity produced by the addition of selegiline extracted from human plasma. This method uses the substrate kynuramine which is converted by MAO to the product 4-hydroxyquinoline which fluoresces in alkaline solution. Human plasma (500 microliters) containing different concentrations of selegiline was deproteinized and extracted with ethyl acetate-butyl chloride. After reconstitution with 200 microliters phosphate buffer, 50 microliters of rat brain homogenate was added to study the MAO-B inhibition. Selegiline metabolites, amphetamine and methamphetamine (50 ng ml-1), and desmethylselegiline (20 ng ml-1), showed no inhibitory effect on MAO-B inhibition. Selegiline concentrations as low as 0.25 ng ml-1 can be detected. The standard curve was linear from 125 pg (0.25 ng ml-1) to 4000 pg (8.0 ng ml-1) in the incubation tube. This method should be helpful to determine pharmacokinetic parameters of selegiline after i.v. or oral dosing.


A review of various techniques of mouse liver transplantation.
Liver transplantation in a mouse model is a valuable tool for studying transplantation immunobiology and clinic-relevant issues. However, the successful establishment is highly technical and demanding, impeding its widespread use. Herein, the aims of this study were to review and analyze the various techniques of liver transplantation in mice to circumvent pitfalls and minimize the incidence of complications. A search of PubMed was made by using the key words "mouse liver transplantation" for articles published between January 1973 and July 2012. Of the 473 publications identified, 14 were shown to be closely associated with mouse liver transplantation and 4 articles discussed specific microsurgical techniques. Through reviewing these articles, a series of potential factors were collected and analyzed in combination with other murine transplantation models, which might influence successfully establishing a mouse model for liver transplantation. A mouse liver transplantation model is feasible and practical for experimental studies. Mouse strain, type of anesthesia, type of perfusion and storage solution, and reconstruction of bile duct are relevant factors but not determinants for a successful transplantation. Cold and warm ischemia time should be less than 4.0 hours and 20 minutes, respectively. The cuff preparation, reconstruction of the hepatic artery, and length of the anhepatic phase play critical roles in successfully establishing a liver transplantation model in mice.


A technique to repair type I left ventricular rupture following mitral valve replacement.
Rupture of the posterior left ventricle is a serious complication following mitral valve replacement. A successful method of repair is illustrated. The causes, other methods of repair, and means to prevent this complication are discussed.


An institutional quality improvement initiative for pain management for pediatric cancer inpatients.
Health care institutions must use the principles of quality improvement to demonstrate appropriate assessment and effective management of pain. Here, we describe the quality improvement initiative implemented at our pediatric institution to improve the quality of pain management. We conducted chart audits for the previous 24 hours during which patients received inpatient care. Over six years, 2,478 charts were audited for 87 24-hour periods (average 1.2 days/month) to answer the following: (1) Was pain intensity assessed as per the institutional pain standard of care, (2) What proportion of audited inpatients had significant pain (>or=5/10), and (3) When significant pain (>or=5/10) occurred, was treatment effective (pain score <or=4/10) within one hour of an intervention? Data were analyzed for quarterly time periods (n=24). Compliance with pain assessment guidelines improved from 77% initially to consistently greater than 90%. The mean proportion of patients with significant pain each quarter was 21%. Sixty-six percent of patients with significant pain had pain treated effectively within one hour of intervention. Lack of documentation of pain reassessment within one hour of the intervention was consistent throughout the study period (overall frequency 22%). Comprehensive pain management guidelines have been established. Leaders of health care organizations need to provide the support and resources needed to incorporate these guidelines and standards into institutional culture. We present a simple quality improvement approach to patient care that can be modified to fit the unique aspects of other institutions.


The function of dreams (REM sleep): roles for the hippocampus, melatonin, monoamines, and vasotocin.
Rapid eye movement (REM) sleep is suggested to play a role in the storage of memory, resolution of emotional experiences, and erasure of memory (forgetting). Plasticity of hippocampal physiology, morphology, and chemistry seems to be evidence for new memory formation. REM sleep, melatonin, and monoamines may be involved in the transfer of memory from the intermediate-term high-capacity buffer in the hippocampus into long-term memory storage in the neocortex. Vasotocin, which is released by melatonin, could be an amnestic agent that erases recent memory from the hippocampal-entorhinal complex during dreams.


Analysis of driver characteristics, self-reported psychology measures and driving performance measures associated with aggressive driving.
Whereas aggressive driving mainly causes speed-related crashes, aggressive driving may be reduced to improve road safety by identifying aggressive driving behaviour, aggressive drivers' characteristics, and their underlying motivational and psychological processes. Previous studies show that both driving performance and self-reported measures of aggressive driving are effective means to identify aggressive drivers. However, these studies assessed aggressive driving patterns across only a limited number of events, did not relate driver characteristics to aggressive driving in each event, and used chiefly vehicle kinematics variables (e.g., mean speed), but not vehicle dynamics variables (e.g., brake pedal force) which better capture driver reaction and decision-making. To address these limitations, this study assessed driver characteristics, self-reported psychological measures, and driving performance measures associated with aggressive driving among 55 drivers' behaviours in 9driving events using a driving simulator and survey responses. The results of structural equation models showed that unique aggressive driving patterns and driver characteristics related to aggressive driving vary among different driving events. As such, we recommend road safety policies to reduce aggressive driving based on the findings in this study.


Survival and differentiation of oligodendrocytes from neural tissue transplanted into new-born mouse brain.
Fragments of new-born mouse central nervous system have been transplanted into new-born mice host brains, under conditions in which the myelin synthesized by the oligodendrocytes included in the graft, could be distinguished from the host myelin. The work demonstrates that transplanted oligodendrocytes survive in the host brain, migrate out of the graft and synthesize myelin. No sign of rejection was observed during the time of the experiment.


Pulmonary aspergillosis and aflatoxins in chronic lung diseases.
Fungal infections of lung have become increasingly common during the last few decades. Aspergillosis and the role of aflatoxins in various chronic lung diseases have not been extensively studied. Bronchoalveolar lavage (BAL) samples and sera from 40 patients of chronic lung diseases were analyzed for galactomannan antigen (GM) and aflatoxin by enzyme-linked immunosorbent assay. Direct microscopy and culture of BAL samples were also done to detect the Aspergillus species. Results revealed that 15 (37.5 %) of the 40 patients had growth of Aspergillus on BAL culture. Out of these culture-positive cases, 13 (86.7 %) patients were positive for galactomannan antigen also. About 62.5 % cases did not show growth of Aspergillus in BAL culture. However, galactomannan antigen could be detected in 20 % of these patients. Overall, 20 % patients were diagnosed as proven invasive fungal disease (IFD), 32.5 % were of probable IFD, 17.5 % of possible IFD. Aspergillus growth was observed in 100 % of proven and 53.8 % of probable IFD cases. Galactomannan antigen was found in 100 % cases of proven and 76.9 % of probable IFD. Ten (25 %) patients were found to be positive for aflatoxins. It was detected in 6 (40 %) of culture-positive cases. About 62.5 % of the cases with proven IFD and 46.1 % of probable IFD had aflatoxin in their samples. Aflatoxin positivity was found to be more in patients with proven IFD than in probable IFD, and higher level of aflatoxins was detected in cases with proven IFD. Significant difference was observed in aflatoxin positivity among food grain workers when compared to other occupations.


Regulator of G-Protein Signaling 7 Regulates Reward Behavior by Controlling Opioid Signaling in the Striatum.
Morphine mediates its euphoric and analgesic effects by acting on the μ-opioid receptor (MOR). MOR belongs to the family of G-protein coupled receptors whose signaling efficiency is controlled by the regulator of G-protein signaling (RGS) proteins. Our understanding of the molecular diversity of RGS proteins that control MOR signaling, their circuit specific actions, and underlying cellular mechanisms is very limited. We used genetic approaches to ablate regulator of G-protein signaling 7 (RGS7) both globally and in specific neuronal populations. We used conditioned place preference and self-administration paradigms to examine reward-related behavior and a battery of tests to assess analgesia, tolerance, and physical dependence to morphine. Electrophysiology approaches were applied to investigate the impact of RGS7 on morphine-induced alterations in neuronal excitability and plasticity of glutamatergic synapses. At least three animals were used for each assessment. Elimination of RGS7 enhanced reward, increased analgesia, delayed tolerance, and heightened withdrawal in response to morphine administration. RGS7 in striatal neurons was selectively responsible for determining the sensitivity of rewarding and reinforcing behaviors to morphine without affecting analgesia, tolerance, and withdrawal. In contrast, deletion of RGS7 in dopaminergic neurons did not influence morphine reward. RGS7 exerted its effects by controlling morphine-induced changes in excitability of medium spiny neurons in nucleus accumbens and gating the compositional plasticity of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid and N-methyl-D-aspartate receptors. This study identifies RGS7 as a novel regulator of MOR signaling by dissecting its circuit specific actions and pinpointing its role in regulating morphine reward by controlling the activity of nucleus accumbens neurons.


Potassium bromide for treatment of malignant migrating partial seizures in infancy.
The syndrome of malignant migrating partial seizures in infancy is a rare epileptic syndrome with a devastating course characterized by early onset of continuous pharmacoresistent multifocal seizures arising from multiple independent sites of both hemispheres with unknown etiology. A 2-month-old boy with the characteristic clinical and electroencephalograph pattern of migrating partial seizures in infancy was treated with potassium bromide. His seizures were unresponsive to the conventional and new generation antiepileptic drugs. The seizure frequency was reduced markedly with potassium bromide. Potassium bromide, an old antiepileptic drug, is useful in the treatment of malignant migrating partial seizures in infancy.


Capillary electrophoresis coupled to mass spectrometry for the determination of anthelmintic benzimidazoles in eggs using a QuEChERS with preconcentration as sample treatment.
Benzimidazoles (BZDs) are anthelmintic agents widely used in veterinary medicine. Their use in food-producing animals increases the possibility of residues appearing in animal tissues and products. Most analytical procedures reported for the determination of BZDs have been developed based on liquid chromatography (LC) because of their polar nature - zwitterionic - and thermal lability. To our knowledge, the determination of these compounds by capillary electrophoresis coupled to mass spectrometry (CE-MS) has not yet been described. In this work CE-MS is proposed for the identification and simultaneous quantification of several benzimidazoles in egg samples. The target compounds were 2-aminobenzimidazole, carbendazim, albendazole-2-aminosulphone, 5-hydroxy-thiabendazole, oxibendazole, albendazole, fenbendazole, oxfendazole, albendazole-sulphone, fenbendazole-sulphone. Optimization of the composition and nature - organic/aqueous - of both the electrophoretic separation buffer and the injection medium was carried out with a view to obtaining the best sensitivity and separation efficiency for the CE-MS coupling. A comparative study was carried out on different sample treatments for analyte extraction from egg samples. Two of them comprised a solvent extraction step followed by clean-up using a new commercial polymeric sorbent (Evolute ABN(©)), and the third was a particularization of the general extractive method so called Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS). Different modifications of the QuEChERS method were assayed, which included a later preconcentration step based on either SPE with MCX(©) sorbents or evaporation. The whole optimized method (QuEChERS with preconcentration prior to CE-MS) was validated according to the 2002/657/EC decision obtaining a CE-MS method sufficiently reliable and robust to determine residues of these compounds in egg samples of different origins with limits of detection between 3 and 51 μgL(-1) (S/N=3) and recoveries in the 74-112% range.


Two cases of primary neuroblastoma of the kidney in adults.
Primary neuroblastoma of the kidney in adults is an extremely rare neoplasm that had not been described in the literature until 1986. The diagnosis can be made by histopathological examination only. We report 2 unusual cases of neuroblastoma of the kidney in adults. In both patients right nephrectomy was performed after the diagnosis of right renal cell carcinoma was made. Histological examination revealed the tumors to be primary neuroblastomas of the right kidney. In the first patient cobalt therapy was administered to the tumor bed and para-aortic area. Followup at 5 years revealed no sign of tumor recurrence. Progressive disseminated disease has been documented in the second patient despite postoperative adjuvant chemotherapy with combined cis-platinum and epipodophyllotoxin, and combined vincristine, cyclophosphamide, doxorubicin and dimethyl-tri-azeno imidazole carboxamine.


Applying Cultural Intelligence to Improve Vaccine Hesitancy Among Black, Indigenous, and People of Color.
Despite the overwhelming evidence to support the benefits of vaccines for preventable diseases and improving health outcomes throughout the world, vaccine hesitancy and resistance continues to be a concern during the COVID-19 pandemic. Although Black, Indigenous, and People of Color (BIPOC) experience the highest rates of morbidity and mortality from COVID-19, mistrust and historical unethical research and medical practices continue to preclude this population from getting the vaccine. This article urges clinicians to subscribe to development and application of cultural intelligence to understand the impact of structural racism and cultural considerations of BIPOC to partner in strategy development.


Marked synergism between mutant SOD1 and glutamate transport inhibition in the induction of motor neuronal degeneration in spinal cord slice cultures.
Loss of astrocytic glutamate transport capacity in ALS spinal cord supports an excitotoxic contribution to motor neuron (MN) damage in the disease, and dominant gain of function mutations in Cu/Zn superoxide dismutase (SOD1) cause certain familial forms of ALS. We have used organotypic slice cultures from wild type and G93A SOD1 mutant rat spinal cords to examine interactions between excitotoxicity and the presence of mutant SOD1 in the induction of MN degeneration. Slice cultures were prepared from 1 week old pups, and after an additional week in vitro, some were exposed to either a low level (30 μM) of the glutamate uptake inhibitor, trans-pyrrolidine-2,4-dicarboxylic acid (PDC) for 3 weeks, or a higher level (50 μM) for 48 h, followed by histochemical labeling to assess MN injury. In wild type animals these exposures caused relatively little MN degeneration. Similarly, little MN degeneration was seen in slices from SOD1 mutant animals that were not exposed to PDC. However, addition of PDC to SOD1 mutant slices resulted in substantial MN injury, which was markedly attenuated by a Ca2+ permeable AMPA-type (Ca-AMPA) glutamate channel blocker, or by a nitric oxide synthase antagonist. These observations illustrate the utility of the organotypic culture model for the investigation of intracellular interactions underlying MN degeneration in ALS, and support the hypothesis that activation of Ca-AMPA channels on MNs provides a metabolic burden that synergizes with deleterious effects of mutant SOD1 in the induction of MN injury.


Author Correction: Chimpanzee ethnography reveals unexpected cultural diversity.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Utility of CD229 as novel marker in measurable residual disease assessment in multiple myeloma-An evidence-based approach.
CD229 has been found to be a useful plasma cell (PC) gating marker in multiple myeloma (MM). This study analyses the expression profile of CD229 on various bone marrow compartments namely, PC, non-PC and hematogones (HGs) using Multiparameter flow cytometry (MFC). Furthermore, it evaluates the ability of CD229 to delineate normal PC (NPC) from aberrant PC (APC) in measurable residual disease assessment (MRD) in MM. Bone marrow aspirates from patients diagnosed with MM (per standard IMWG criteria) were collected in EDTA and processed for MFC using a single tube 14-color antibody panel as per standard operating procedure. A total of 74 patients with a diagnosis of MM (26 treatment naïve and 48 on therapy) were evaluated. The expression of CD229 was homogenous on both the PC and HG compartments as compared to CD138 and CD38. On comparing the expression of individual markers, it was found to be statistically significant between PC, HGs and non-PC for all three markers (p < 0.001). APC showed lower median expression of CD38 and higher median expression of CD138 and CD229 as compared to NPC and was found to be statistically significant for all markers (p < 0.001). In terms of differential expression on NPC and APC; CD38 was found to be the most aberrantly expressed (70%; 52/74) followed by CD229 (7%; 5/74) and CD138 (5%; 4/74). CD229 can be used for the identification of PC and due to relatively homogenous expression; it can be used as a suitable marker for targeted therapies. However, precise discrimination of NPC from APC cannot be reliably achieved with CD229, limiting its utility as a useful marker of diagnostic relevance and MRD assessment in MM.


Developmental perspectives on neurocranial proportions in Japan.
This study employs juvenile cranial data derived from collections dating to between about 5000 years ago and the present in order to investigate how differences in cranial growth trajectories contributed to inter-group variation in cranial shape among temporally defined Japanese populations. As gene influx from the Asian mainland was insignificant after the Yayoi period (c. CE 300), differences in adult cranial shape among later assemblages from Japan are probably related to developmental adaptations to environmental change. Comparing cranial growth trajectories among groups from different time periods allows indirect testing of several hypotheses about secular changes in cranial growth, including thermoregulatory adaptation, change in levels of masticatory stress, and change in levels of physiological stress. Differences in neurocranial proportions among groups with contrasting adult cranial shapes were found to be already pronounced for the infant cohort (0-3 years of age) and actually tended to decline slightly within later age ranges; differences in mandibular shape were unremarkable early in life, but became more pronounced after infancy. Consequently, changes in chewing stress are unlikely to have been the principal factor driving inter-group differences in cranial proportions. The cranial growth pattern reconstructed from a Medieval Japanese skeletal series showed the greatest magnitude of difference from those reconstructed for other time periods. Unlike in the other groups, there was no marked decline of cephalic index with age for the Medieval series. The unusual trajectory of cranial growth evident in the Medieval sample may result from a high degree of physiological stress due to overall poor nutrition.


The DUBA-SLC7A11-c-Myc axis is critical for stemness and ferroptosis.
Ferroptosis is characterized by the accumulation of lipid peroxidation as a unique iron-dependent cell death. However, the interplay between stemness and ferroptosis remains unknown. Here, we demonstrate that undifferentiated cells are more sensitive to ferroptosis than differentiated cells, and cystine transporter SLC7A11 protein is highly up-regulated by deubiquitinase DUBA in differentiated cells. Additionally, DUBA promotes stemness by deubiquitinating SLC7A11. Moreover, SLC7A11 drastically increases the expression of c-Myc through cysteine, the combination of sorafenib and c-Myc inhibitor EN4 has a synergetic effect on cancer therapy. Together, our results reveal that enhanced stemness increases the susceptibility to ferroptosis, and the DUBA-SLC7A11-c-Myc axis is pivotal for differentiated cancer stem cells (CSCs) resistant to ferroptosis, providing a promised targets to eradicate CSCs through ferroptosis.


Embryonic heart mesenchymal cell migration in laminin.
Laminin, a large glycoprotein and major component of basement membranes, influences cell adhesion, migration, morphology, and differentiation. A peptide sequence, YIGSR, from the B1 chain of laminin has been found to correspond to an active site for cell adhesion. We report here that cardiac mesenchymal cells migrate vigorously within three-dimensional gels of laminin and that the YIGSR peptide will completely abolish this migratory activity. In contrast, migration of the mesenchymal cells into three-dimensional gels composed of collagen or collagen + laminin is not effected by YIGSR or other peptides (GRGDS, GRGDTP) reported to mediate cellular adhesion.


Effect of bilateral sagittal split ramus osteotomy setback on the soft palate and pharyngeal airway space.
To evaluate the effect of bilateral sagittal split ramus osteotomy setback on the morphology of the pharyngeal airway, especially the structures of the soft palate and pharyngeal airway space (PAS), lateral cephalograms obtained from 49 women before treatment and 1 year after surgery were traced and compared. All patients underwent this osteotomy to correct mandibular hyperplasia. The data were corrected with the use of regression equations for the PAS, taking into account head posture. On average, the SNB angle decreased by 3.9 degrees, resulting in an increase of 4.1 degrees in OPT/NSL (head posture, defined as the craniocervical angulation at the uppermost part of the cervical spine). The morphology of the PAS and soft palate changed significantly (p<0.01). The mean reduction in the PAS was 2.6mm retropalatinally and 4.0mm retrolingually. On average, the soft-palate length increased by 3.2mm and the soft-palate angle increased by 4 degrees. These results show that mandibular setback surgery markedly decreases the PAS and changes the morphology of the soft palate.


High-throughput single nucleotide polymorphism typing by fluorescent single-strand conformation polymorphism analysis with capillary electrophoresis.
In this study, we performed high-throughput and precise single nucleotide polymorphism (SNP) typing by fluorescent capillary electrophoresis single-strand conformation polymorphism (CE-SSCP) analysis. A system composed of a multicapillary DNA analyzer, a newly developed sieving matrix, four different colors of fluorescent labels, and a multiplex polymerase chain reaction (PCR) enabled low-cost and highly reliable SNP typing. Moreover, this system enabled the estimation of SNP allele frequencies using pooled DNA samples, which should be beneficial for large-scale association studies. Thus, fluorescent CE-SSCP analysis is a useful method for large-scale SNP typing.


Analgesia and chemical restraint for the emergent veterinary patient.
Frequently, analgesics are withheld in the emergent patient based on common misconceptions. Concerns expressed are that analgesics "mask" physiologic indicators of patient deterioration or that potential toxicity and adverse reactions associated with drug administration outweigh the benefits gained. Appropriate selection of drugs and doses as described in this article allow the veterinarian to achieve analgesia, in addition to sedation or restraint when needed, without unwarranted fears. Guidelines are provided for typical situations encountered in trauma patients to provide a safe starting point for providing analgesia. Caution required in these cases is also discussed, with emphasis on individualization of the approach to analgesia and chemical restraint.


Interfacial Properties of Chitosan in Interfacial Shear and Capsule Compression.
The time-dependent behavior of surface-active adsorption layers at the oil/water interface can dictate emulsion behavior at both the micro- and macroscale. In addition, self-healing behavior of the adsorption layer may benefit emulsion stability subject to large deformation under processing or during final application. We explore the behavior of chitosan, a known hydrophilic emulsifier, which forms nanoparticle aggregates when the concentration of acetate buffer exceeds 0.3 M. We observe a Pickering adsorption layer building and strain-dependent behavior of the chitosan at the medium chain triglyceride oil/water interface. We compare this to the behavior of identical chitosan layers coated on oil droplets via atomic force microscopy colloidal probe compression in both linear and oscillatory compressions. In both interfacial shear rheometry and the capsule compression, a thick, elastic layer with strong time-dependent recovery behavior is observed, suggesting that the layer has some self-healing capabilities.


Response of phosphorus fractionation in lake sediments to anthropogenic activities in China.
In this study, geochemical fractionation is used to establish the relationship between sediment phosphorus (P) pools and anthropogenic activities based on the dated sediment from a suite of lakes in China. Our extraction results showed that the inorganic P fractions, including Ca-P (46% of TP) and Fe/Al-P (24%), constitute most of the P in sediments. Soil erosion dynamics and geographic location are the dominant factors controlling the historical distribution and partitioning of Ca-P in sediments, while over the last few decades, industrial and domestic effluents were the leading factor controlling Fe/Al-P. The organic P (Po) fractions, NaHCO3-Po, HCl-Po, and Ful-Po accounted for only 11%, 16% and 12% of Po on average, respectively, whereas Hum-Po and Res-Po made up the dominant Po fraction (59%) and were the main factors controlling Po dynamics due to fertilizer and livestock breeding. Thus, the historical fraction of P in the sediment core can be used as an indicator of anthropogenic activities. Ca-P decreased in the top layers of the cores because of the implementation of the Soil and Water Conservation Law in China since 1991. However, Fe/Al-P and Po continuously increased in the lakes from the economic backward area over the last few decades, which is largely due to enhanced point sources of pollution and an increase in the intensity of agricultural practices. As a potential P source, the massive accumulation of Fe/Al-P and Po would be released into the overlying water to further facilitate eutrophication via increasing pH and alkaline phosphatase and decreasing in the dissolved oxygen concentration. Therefore, in order to control eutrophication more effectively and efficiently, it is essential that the accumulation of sediment Fe/Al-P and Po be decreased immediately and domestic wastewater, poultry excreta, and fertilizer loss must be more carefully controlled, especially in economically backward areas.


Obesity and the risk of prostate cancer (United States).
The role of obesity in prostate cancer etiology remains controversial. A recent report suggested that obese men younger than age 60 may have a lower risk of developing prostate cancer than men the same age who are not obese. The current study used a nested, matched case-control study design and data collected in the General Practice Research Database between January 1991 and December 2001 to assess the association between body mass index (BMI) and the risk of incident prostate cancer. Seven hundred and thirty cases of prostate cancer with adequate information on BMI were identified and matched to 2740 controls on age, sex, general practice, and index date. Obese men (BMI > or = 30.0 kilograms [kg]/square of height in meters [m(2)]) were at lower risk of developing prostate cancer (AOR=0.78, 95% CI: 0.56, 1.09) compared to normal weight men (BMI=23.0-24.9 kg/m(2)), and the data best fit an inverse quadratic model for the relation between BMI and the risk of prostate cancer. This study provides modest support for a protective association between obesity and the risk of incident prostate cancer.


The development of independence in adolescents with cystic fibrosis.
This study assessed the development of independence and its interaction with some biologic factors. Sixty-four adolescents with cystic fibrosis (CF) were compared with 36 adolescents with bronchial asthma, 47 healthy but small adolescents, and 71 normal healthy controls. A structured interview was designed to measure eight elements of independence. Adolescents with CF showed less responsibility for their own body hygiene and a delay in intimacy and sexuality, both correlated with puberty not yet having started. They also took less part in a number of social activities outside the home. There were minimal or no differences between ill and healthy adolescents for four elements. The results indicated that in future research, different types of independence should be taken into account. The correspondences between the chronically ill and the healthy adolescents prevailed over the differences. The main differences could be interpreted in terms of realistic coping with the illness and maintaining hope for the future.


Suppressive effects of a novel antioxidant compound on human T cell functions in vitro.
The use of antioxidant compounds with differing modes of action has clearly demonstrated involvement of oxidative processes in the activation of T lymphocytes. In this paper, we show that a novel antioxidant (lazaroid U75412E, a free radical scavenger) suppressed mitogen-induced T cell proliferation in vitro. Similar results were obtained with diphenylene iodonium (DPI), a known inhibitor of NADPH oxidase. The lazaroid was further shown to inhibit IL 2 production but to be less potent in suppressing IL 2 receptor expression. Thus, scavenger-type antioxidants act on T cells primarily by blocking a signal necessary for the induction of IL 2 synthesis such as the activation of NF kappa B. Furthermore, the potent inhibition of lymphocyte responses caused by the specific enzyme inhibitor DPI provides direct proof of the source of the oxidants involved in these processes.


Corrigendum: The Role of Toll-Like Receptor-2 in Clostridioides difficile Infection: Evidence From a Mouse Model and Clinical Patients.
[This corrects the article DOI: 10.3389/fimmu.2021.691039.].


Effect of fenoterol hydrobromide and sodium cromoglycate individually and in combination on postexercise asthma.
A double-blind trial involving 20 asthmatic patients was carried out to test the effect of fenoterol and sodium cromoglycate alone and in combination on ventilatory function one hour after medication. The results show that fenoterol, whether alone or in combination with sodium cromoglycate, can increase the forced expiratory volume in one second (FEV1) by up to 25% both after rest and after exercise. No patient suffered a decrease in FEV1 using fenoterol, and at least 80% of them recorded an increase in ventilatory ability. Sodium cromoglycate was of no benefit in eliminating early reaction to exercise-induced asthma.


Antipsychotics promote the differentiation of oligodendrocyte progenitor cells by regulating oligodendrocyte lineage transcription factors 1 and 2.
Oligodendrocyte/myelin abnormalities may be an important component of the pathogenesis found in schizophrenia. The aim of this current study was to examine the possible effects of the antipsychotic drugs (APDs) haloperidol (HAL), olanzapine (OLA), and quetiapine (QUE) on the development of oligodendroglial lineage cells. CG4 cells, an oligodendrocyte progenitor cell line, were treated with various concentrations of HAL, OLA, or QUE for specific periods. The proliferation and differentiation of the CG4 cells were measured. The regulation of CG4 cell differentiation by oligodendrocyte lineage transcription factors 1 and 2 (Olig1 and Olig2) was examined. The APDs used in this study had no effect on the proliferation of CG4 cells. The APDs elevated the expression of 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP), a specific marker of oligodendrocytes, and promoted the CG4 cells to differentiate into CNP positive oligodendrocytes. QUE and OLA increased the expression of both Olig1 and Olig2 whereas HAL only increased the expression of Olig2. Our findings suggest that oligodendrocyte development is a target of HAL, OLA, and QUE and provide further evidence of the important role of oligodendrocytes in the pathophysiology and treatment of schizophrenia. They also indicate that the expression level of oligodendrocyte/myelin-related genes could be profoundly affected by APDs, which should be considered in future studies aiming to measure the oligodendrocyte/myelin-related gene expressions in schizophrenia patients.


DFT and QSAR studies of PTFE/ZnO/SiO2 nanocomposite.
Polytetrafluoroethylene (PTFE) is one of the most significant fluoropolymers, and one of the most recent initiatives is to increase its performance by using metal oxides (MOs). Consequently, the surface modifications of PTFE with two metal oxides (MOs), SiO2 and ZnO, individually and as a mixture of the two MOs, were modeled using density functional theory (DFT). The B3LYPL/LANL2DZ model was used in the studies conducted to follow up the changes in electronic properties. The total dipole moment (TDM) and HOMO/LUMO band gap energy (∆E) of PTFE, which were 0.000 Debye and 8.517 eV respectively, were enhanced to 13.008 Debye and 0.690 eV in the case of PTFE/4ZnO/4SiO2. Moreover, with increasing nano filler (PTFE/8ZnO/8SiO2), TDM changed to 10.605 Debye and ∆E decreased to 0.273 eV leading to further improvement in the electronic properties. The molecular electrostatic potential (MESP) and quantitative structure activity relationship (QSAR) studies revealed that surface modification of PTFE with ZnO and SiO2 increased its electrical and thermal stability. The improved PTFE/ZnO/SiO2 composite can, therefore, be used as a self-cleaning layer for astronaut suits based on the findings of relatively high mobility, minimal reactivity to the surrounding environment, and thermal stability.


Artificial intelligence and Bayesian decision theory in the prediction of chemical carcinogens.
Two procedures for predicting the carcinogenicity of chemicals are described. One of these (CASE) is a self-learning artificial intelligence system that automatically recognizes activating and/or deactivating structural subunits of candidate chemicals and uses this to determine the probability that the test chemical is or is not a carcinogen. If the chemical is predicted to be carcinogen, CASE also projects its probable potency. The second procedure (CPBS) uses Bayesian decision theory to predict the potential carcinogenicity of chemicals based upon the results of batteries of short-term assays. CPBS is useful even if the test results are mixed (i.e. both positive and negative responses are obtained in different genotoxic assays). CPBS can also be used to identify highly predictive as well as cost-effective batteries of assays. For illustrative purposes the ability of CASE and CPBS to predict the carcinogenicity of a carcinogenic and a non-carcinogenic polycyclic aromatic hydrocarbon is shown. The potential for using the two methods in tandem to increase reliability and decrease cost is presented.


Orbital subperiosteal hematoma, cholesterol granuloma, and infection. Evaluation with MR imaging and CT.
Orbital subperiosteal space, a potential space, is an important entity due to its unique anatomy and susceptibility to various pathologic processes. CT scan and MR imaging are important tools in the diagnosis of orbital subperiosteal hematomas, cholesterol granulomas, and infections. MR imaging has emerged as the modality of choice in the evaluation of hematomas and infections of this space due to its multiplanar capability and various imaging sequences giving better information. High-resolution CT scan offers good differentiation in most of these cases. Osseous changes in a cholesterol granuloma is better seen in CT scan, although MR imaging offers better differentiation from epidermoid or dermoid cysts and other subperiosteal process, as well as lacrimal fossa lesions. Subperiosteal abscesses are best evaluated using MR imaging.


Forearm oxygen consumption and forearm blood flow in healthy children and adolescents measured by near infrared spectroscopy.
The assessment of forearm oxygen consumption (VO(2)) and forearm blood flow (FBF) by means of near infrared spectroscopy has become widespread in adults, whereas in children and adolescents no data are available. The aim of the present study was to analyze VO(2) and FBF in healthy children and adolescents. In a prospective cohort study, 20 male and 20 female healthy children and adolescents were investigated. The measurements of VO(2) and FBF were performed by means of near infrared spectroscopy in combination with the venous occlusion method. Mean VO(2) was 0.08 +/- 0.04 ml 100 g(-1) min(-1) in male and 0.09 +/- 0.05 ml 100 g(-1) min(-1) in female subjects. Mean FBF was 1.95 +/- 1.25 ml 100 g(-1) min(-1) in male and 1.82 +/- 0.98 ml 100 g(-1) min(-1) in female subjects. No significant difference was found between male and female subjects. A significant negative correlation of VO(2) and FBF to age was observed in both groups. In the present study we were able to show that VO(2) and FBF decreased with increasing age in children and adolescents without significant differences between male and female subjects.


Long term follow-up of bifurcation aneurysms treated with braided stent assisted coiling and complex T- and Y- stent constructs.
Stent assisted coil embolization (SACE) of bifurcation aneurysms is challenging. Heterogeneous results have been achieved to date, but largely for laser cut stents. While braided stents offer multiple technical advantages, their long term efficacy has yet to be validated. To report the first long term 18 month results for the durability of bifurcation aneurysms treated with braided stents. Over a 4 year period, 59 consecutive patients with 60 bifurcation aneurysms underwent elective braided SACE across three Australian neurovascular centers. 17 of these aneurysms underwent T- or Y-shaped stent constructs. All patients had immediate, 6 month and 18 month clinical and radiological follow-up. Radiological assessment was made on modified Raymond-Roy occlusion scores while clinical assessment was based on the modified Rankin Scale. Subgroup analysis of 17 aneurysms treated with multi-stent constructs was conducted. 6 month follow-up data were available for 59 aneurysms and 18 month follow-up data for 58 aneurysms. Satisfactory aneurysm occlusion was achieved in 97% at inception and at 6 months, and 98% at 18 months. Good neurological outcomes were achieved in 95% at 18 months. Similar satisfactory results were achieved with the multi-stent construct cohort. Intraprocedural thromboembolic events were recorded in 5% and delayed events in 2%. Technical complications were found in 5%. All complication rate was 13%. Braided SACE was safe, efficacious, and durable at the long term 18 month follow-up, including for multi-stent constructs. Preliminary results indicate favorable clinical and radiological outcomes compared with laser cut stents.


Cellular responses to increasing Cd concentrations in the freshwater crab, Potamonautes warreni, harbouring microbial gill infestations.
We investigated the uptake, transport, storage and defence mechanisms in the freshwater crab, Potamonautes warreni, harbouring microbial gill infestations and exposed to increasing chronic (0.2, 0.5, 1.0 mg l(-1)) and acute (2.0 mg l(-1)) cadmium (Cd) concentrations under controlled laboratory conditions over a period of 21 days. Transmission electron microscopy and X-ray microanalysis revealed that the microbial gill fauna was eliminated on exposure to 0.2 mg Cd(2+) l(-1) and that Cd became increasingly adsorbed and incorporated into lamellar crystal deposits and permeated the cuticle of the gills of P. warreni. Degeneration of the apical membrane infoldings and vacuolation of epithelial cells occurred concurrently with pinocytosis, endocytosis and pronounced phagocytotic activity in the epithelia and haemal canal of the gills. Elevated Cd exposures (0.5 or 1.0 mg l(-1)) resulted in the swelling and dissociation of mitochondrial outer membranes together with an increase in transport of Cu, Cl and S by haemocytes in the haemal canal to epithelial tissues depleted in these elements. Cd also accumulated in tightly coiled concentric membrane whorls in the haemal canal, whereas the highest concentrations of Cd were found within aggregates of lysosome-like bodies in cuticulin-secreting cells of the gill stem. Chronic exposure to Cd induced increased fatigue and mild uncoordinated motor activity. In contrast, at an acute exposure of 2.0 mg l(-1) over 48 h, P. warreni showed a time-specific rapid loss of motor function, although only mild cellular lesions occurred in the gill tissues. The significance of cellular changes in the gill epithelia and altered motor activity of P. warreni with increased waterborne Cd are discussed as potential biomarker responses in monitoring aquatic pollution.


The 5alpha-reductase type II A49T and V89L high-activity allelic variants are more common in men with prostate cancer compared with the general population.
To compare men with prostate disease with those from the general population regarding polymorphisms in the androgen receptor gene and in the 5alpha-reductase II (SRD5A2) gene. The SRD5A2 polymorphisms A49T, V89L and R227Q, the androgen receptor CAG and GGN repeats and sex hormone status was investigated in men with prostate cancer (CaP) (n=89), benign prostate hyperplasia (n=45) and healthy military conscripts (n=223). The SRD5A2 high-activity allele variants A49T AT and V89L LL were more frequent in CaP-patients compared to general population, p=0.026 and p=0.05, respectively. CaP progression was, however, independent of SRD5A2 variants. In contrary, men with GGN<23 had a higher risk of dying from the disease than their counterparts with longer repeats. Men with CaP were more often genetically predisposed to a higher enzymatic activity in the turn over from T to DHT compared to the general population. In our population, androgen receptor genotype affected CaP outcome.


The Effect of Supportive Counseling on Mother Psychological Reactions and Mother-Infant Bonding Following Traumatic Childbirth.
Women experienced traumatic childbirth talk about the lack of opportunity to express their worries and stresses. However, providing psychological support to reduce the long-term and severe consequences is essential. The present study aimed to determine the effect of supportive counseling on mother psychological reactions and mother-infant bonding following traumatic childbirth. This quasi experimental study was performed on 166 postpartum women with psychological birth trauma admitted to public hospitals in Arak, Iran. Postpartum bonding questionnaire was filled before hospital discharge. The women were randomly assigned into the intervention and control groups. The intervention group (n = 83) received individual supportive counseling for two in-person sessions before hospital discharge, and 10-15 days after delivery and a telephone consultation during 4-6 weeks after delivery. The data were collected using Edinburgh Postnatal Depression Scale, Post-Traumatic Stress Disorder checklist for DSM-5 (PCL-5), and the postpartum bonding questionnaire, after 2 months. The data were analyzed using SPSS21 software and chi-square, t-test, and ANCOVA were used. The mean score of postpartum depression (PPD) symptoms in the intervention group was significantly lower than that in the control group (MD: -13.40, 95% CI: -10.66 to -16.15, P < 0.001). The severity of the PTSD symptoms in the intervention group was significantly lower than that in the control group (MD: -6.37, 95% CI: -3.55 to -9.18, P = 0.04). The mean (SD) of mother-infant bonding after controlling the effect of baseline score indicated a significant difference between the two groups (MD: -7.82, 95% CI: -6.53 to -9.11, P < 0.001). The supportive counseling seems to be effective in reducing PPD and PTSD symptoms, and improving postpartum bonding after traumatic childbirth. The use of group supportive counseling with other time intervals and long follow-up period is recommended. Further, other intervention approaches should be used for preventing the progression of psychological birth trauma toward PTSD.


Controlled Cavity-Free, Single-Photon Emission and Bipartite Entanglement of Near-Field-Excited Quantum Emitters.
We report theoretical statistics of 1- and 2-qubit (bipartite) systems, namely, photon antibunching and entanglement, of near-field excited quantum emitters. The sub-diffraction focusing of a plasmonic waveguide is shown to generate enough power over a sufficiently small region (<50 × 50 nm2) to strongly drive quantum emitters. This enables ultrafast (10-14 s) single-photon emission as well as creates entangled states between two emitters when performing a controlled-NOT operation. A comparative analysis of silicon and near-zero index materials demonstrates advantages and uncovers challenges of embedding quantum emitters for single-photon emission and for bipartite entanglement. The use of a movable plasmonic waveguide, in lieu of stationary nanostructures, allows high-speed rasterization between sets of qubits and enables spatially flexible data storage and quantum information processing. Furthermore, the sub-diffraction focusing of the waveguide is shown to achieve cavity-free dynamic entanglement. This greatly reduces fabrication constraints and increases the speed and scalability of nanophotonic quantum devices.


Variations in internal iliac veins detected using multidetector computed tomography.
Anatomical variations of the internal iliac veins (IIV), which have the potential to cause problems during related surgery, are not uncommon and are not fully appreciated. To determine the types and prevalence rates of anatomical variations of the IIV using multidetector computed tomography (MDCT). IIV variations in 63 patients who underwent contrast-enhanced MDCT were interpreted and classified by two radiologists retrospectively. The prevalence rates (with 95% confidence intervals [CIs]) were calculated. IIV variations were classified into six types: normal (n=45, 69.8%; 95% CI 59–81%); left IIV connecting with the left external iliac veins centrally (n=5, 7.9%; 95% CI 1–15%); separated trunk of the left IIV draining into the central left common iliac veins(CIV; n=3, 4.8%; 95% CI 0–10%); right IIV draining into the central left CIV (n=7,11.1%; 95% CI 3–19%); right IIV draining into the central right CIV (n=1, 1.6%; 95% CI 0–5%); and the bilateral IIVs connecting with each other before draining into the central left CIV (n=3, 4.8%; 95% CI 0–10%). MDCT demonstrates six types of IIV variations; the prevalence rate of IIV anomalies is not low.


Prospective study of voice outcomes and patient tolerance of in-office percutaneous injection laryngoplasty.
In-office percutaneous injection laryngoplasty is a common treatment for glottal insufficiency. Our objective was to prospectively study voice outcomes and patient tolerance of the procedure. Prospective case series. Consecutive adult patients undergoing awake injection laryngoplasty were recruited. Voice Handicap Index (VHI)-30; Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V); and vocal Grade, Roughness, Breathiness, Asthenia and Strain (GRBAS) were evaluated prior to injection and 2 months postinjection. Visual analog scale (VAS) was completed by the patient before and after the procedure to quantify the amount of discomfort. Thirty-five subjects enrolled; 26 (15 male, 11 female; mean age 61.6 ± 13.2 years) had complete data. All components of VHI improved significantly: functional (P=0.0006), emotional (P=0.0004), physical (P=0.009), and total (P=0.0006). CAPE-V also improved significantly (P=0.003). All components of GRBAS, except for roughness, improved significantly: grade (P=0.004), roughness (P=0.718), breathiness (P=0.023), asthenia (P=0.023), and strain (P=0.03). Patient expectations on the tolerance of the procedure was similar to what they reported immediately afterward (P=0.803). Injection laryngoplasty is an effective method of treating glottal insufficiency, as measured by voice outcomes. Patients have realistic expectations on the procedure experience and find it tolerable. This is the first prospective study of injection laryngoplasty outcomes.


Biotin-thiamine responsive basal ganglia disease in the era of COVID-19 outbreak diagnosis not to be missed: A case report.
Biotin-thiamine-responsive basal ganglia disease (BTRBGD) is a rare treatable autosomal recessive neurometabolic disorder characterized by progressive encephalopathy that eventually leads to severe disability and death if not treated with biotin and thiamine. BTRBGD is caused by mutations in the SLC19A3 gene on chromosome 2q36.6, encoding human thiamine transporter 2 (hTHTR2). Episodes of BTRBGD are often triggered by febrile illness. The patient was 2 years 10 months old male child presented with fever and progressive acute encephalopathy associated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) virus infection. MRI revealed bilateral symmetrical high signal involving both basal ganglia and medial thalami which is swollen with central necrosis, initially diagnosed as acute necrotizing encephalomyelitis with increased severity. Genetic analysis revealed BTRBGD. BTRBGD requires high index of suspicion in any patient presenting with acute encephalopathy, characteristic MRI findings (that are difficult to differentiate from necrotizing encephalopathy), regardless of the existence of a proven viral infection.


Sub-national climate change risk assessment: A case analysis for Tibet and its prefecture-level cities.
Avoiding climate change from exceeding its critical threshold is a serious challenge facing humanity at present and in the future. As the mode of global cooperative action is stranded, multi-center and multi-level efforts are needed to deal with global warming in the future. In order to provide information for the formulation of low-carbon development policies, it is essential to assess the maintain or cross of climate change threshold on different scales. In this study, the carbon footprint calculated based on the process coefficient approach is systematically integrated with the climate change indicator of the planetary boundaries framework improved with the goals of the Paris Agreement to identify the climate change risks of Tibet and its prefecture-level cities from 2000 to 2017. Moreover, the main driving factors behind carbon footprint were analyzed. The findings showed that: (1) Since 2000, Tibet's CO2 emissions have demonstrated steady and rapid increase. The sector composition is dominated by cement production-related and transportation sector-related emissions. The type composition is dominated by diesel-related, process-related, and coal-related emissions. There are significant differences in CO2 emissions among all prefecture-level cities, with Lhasa having the largest contribution. (2) Except for Lhasa and Shannan's CO2 emissions that have crossed their critical threshold of climate change and are in an unsafe state, Tibet and other prefecture-level cities have not yet crossed their critical threshold. (3) Except for Ngari, per capita GDP, energy intensity, population size, and carbon intensity positively affect the increase of CO2 emissions in Tibet and its prefecture-level cities. Our study helps actors at less aggregated scales to determine appropriate policy strengths based on globally agreed goals and ambitions in the process of responding to global warming in a bottom-up manner.


Dietary networks identified by Gaussian graphical model and general and abdominal obesity in adults.
Gaussian graphical model (GGM) has been introduced as a new approach to identify patterns of dietary intake. We aimed to investigate the link between dietary networks derived through GGM and obesity in Iranian adults. A cross-sectional study was conducted on 850 men and women (age range: 20-59 years) who attended the local health centers in Tehran. Dietary intake was evaluated by using a validated food frequency questionnaire. GGM was applied to identify dietary networks. The odds ratios (ORs) and 95% confidence intervals (CIs) of general and abdominal adiposity across tertiles of dietary network scores were estimated using logistic regression analysis controlling for age, sex, physical activity, smoking status, marital status, education, energy intake and menopausal status. GGM identified three dietary networks, where 30 foods were grouped into six communities. The identified networks were healthy, unhealthy and saturated fats networks, wherein cooked vegetables, processed meat and butter were, respectively, central to the networks. Being in the top tertile of saturated fats network score was associated with a higher likelihood of central obesity by waist-to-hip ratio (OR: 1.56, 95%CI: 1.08, 2.25; P for trend: 0.01). There was also a marginally significant positive association between higher unhealthy network score and odds of central obesity by waist circumference (OR: 1.37, 95%CI: 0.94, 2.37; P for trend: 0.09). Healthy network was not associated with central adiposity. There was no association between dietary network scores and general obesity. Unhealthy and saturated fat dietary networks were associated with abdominal adiposity in adults. GGM-derived dietary networks represent dietary patterns and can be used to investigate diet-disease associations.


The oncology drug elesclomol selectively transports copper to the mitochondria to induce oxidative stress in cancer cells.
Elesclomol is an investigational drug that exerts potent anticancer activity through the elevation of reactive oxygen species (ROS) levels and is currently under clinical evaluation as a novel anticancer therapeutic. Here we report the first description of selective mitochondrial ROS induction by elesclomol in cancer cells based on the unique physicochemical properties of the compound. Elesclomol preferentially chelates copper (Cu) outside of cells and enters as elesclomol-Cu(II). The elesclomol-Cu(II) complex then rapidly and selectively transports the copper to mitochondria. In this organelle Cu(II) is reduced to Cu(I), followed by subsequent ROS generation. Upon dissociation from the complex, elesclomol is effluxed from cells and repeats shuttling elesclomol-Cu complexes from the extracellular to the intracellular compartments, leading to continued copper accumulation within mitochondria. An optimal range of redox potentials exhibited by copper chelates of elesclomol and its analogs correlated with the elevation of mitochondrial Cu(I) levels and cytotoxic activity, suggesting that redox reduction of the copper triggers mitochondrial ROS induction. Importantly the mitochondrial selectivity exhibited by elesclomol is a distinct characteristic of the compound that is not shared by other chelators, including disulfiram. Together these findings highlight a unique mechanism of action with important implications for cancer therapy.


Alteration in Rab11-mediated endocytic trafficking of LDL receptor contributes to angiotensin II-induced cholesterol accumulation and injury in podocytes.
Exposure of podocytes to angiotensin II (Ang II) enhances the abundance of the cell surface glycoprotein, low-density lipoprotein receptor (LDLR) and promotes significant changes in the cellular cholesterol content. Recent investigation provides evidence that the small GTPase Rab11 is involved in the regulation of LDLR, but the exact mechanisms remain unknown. In this study, the role of Rab11 in post-transcriptional regulation of LDLR was evaluated to investigate potential mechanisms of podocyte cholesterol dysregulation in chronic kidney disease. Cholesterol content, LDLR and Rab11 expression were assessed in podocytes from Ang II-infused mice. In vitro, the intracellular localization of LDLR was detected under different conditions. Rab11 expression was modulated and we then explored the effect of anti-lipid cytotoxicity by detecting LDLR expression and trafficking, cholesterol content and apoptosis in podocytes. Cholesterol accumulation, upregulated expression of LDLR and Rab11 were discovered in podocytes from Ang II-infused mice. Ang II enhanced the co-precipitation of LDLR with Rab11 and accelerated the endocytic recycling of LDLR to the plasma membrane. Additionally, silencing Rab11 promoted lysosomal degradation of LDLR and alleviated Ang II-induced cholesterol accumulation and apoptosis in podocytes. Conversely, overexpression of Rab11 or inhibition of lysosomal degradation up-regulated the abundance of LDLR and aggravated podocyte cholesterol deposition. Rab11 triggers the endocytic trafficking and recycling of LDLR; overactivation of this pathway contributes to Ang II-induced podocyte cholesterol accumulation and injury.


Association of MicroRNA-146a with autoimmune diseases.
MicroRNAs (miRNAs) are a group of approximately 20-22-nucleotide-long non-coding RNAs that repress target gene expression through mRNA degradation and translation inhibition. MiRNA (miR)-146a, located in the second exon of the LOC285628 gene on human chromosome 5, is a negative regulator in immune and inflammatory responses. Studies have indicated that miR-146a is associated with the pathogenesis of several autoimmune diseases, such as systemic lupus erythematosus, rheumatoid arthritis, and Sjögren's syndrome. In this review, emphasis will be laid on the recent progress in the functional roles of miR-146a in these autoimmune diseases.


Coexistence of five autoimmune diseases: diagnostic and therapeutic difficulties.
We report the case of coexistence of five autoimmune diseases in a 36-year-old woman, who initially developed psoriasis. Several years later, the patient was diagnosed with a mixed connective tissue disease and primary biliary cirrhosis (PBC). On admission to the Department of Rheumatology and Connective Tissue Diseases, the patient fulfilled classification criteria of an overlap syndrome systemic lupus erythematosus (SLE) with secondary antiphospholipid syndrome/systemic sclerosis (SSc)/Sjogren's syndrome (SS) with coexisting PBC and psoriasis. The SLE symptoms included discoid lupus erythematosus, arthritis, pancytopenia, antinuclear antibodies and anticardiolipin antibodies. Moreover, the patient met the criteria of antiphospholipid syndrome diagnosed based on preterm delivery before week 34, and high values of anticardiolipin antibodies were found at repeated determinations. The SSc symptoms included sclerodactyly, pulmonary fibrosis with pulmonary hypertension and esophageal dysfunction. The SS syndrome involved xerostomia, xerophthalmia, the positive Schirmer's test and presence of anti-SS antibodies. The literature reports overlap syndromes in various combinations; however, the coexistence of five autoimmune diseases is extremely rare.


Increased apoptotic chondrocytes in articular cartilage from adult heterozygous SirT1 mice.
A growing body of evidence indicates that the protein deacetylase, SirT1, affects chondrocyte biology and survival. This report aims to evaluate in vivo attributes of SirT1 in cartilage biology of 129/J murine strains. Heterozygous haploinsufficient (SirT1(+/-)) and wild-type (WT; SirT1(+/+)) 129/J mice aged 1 or 9 months were systematically compared for musculoskeletal features, scored for osteoarthritis (OA) severity, and monitored for chondrocyte apoptosis in articular cartilage. Sections of femorotibial joints were stained for type II collagen and aggrecan. Protein extracts from articular chondrocytes were isolated and immunoblotted for SirT1 and active caspase 3. Phenotypic observations show that, at 1 month of age, SirT1(+/-) mice were smaller than WT and showed a significant decrease in full-length SirT1 (FLSirT1; 110 kDa) protein levels. Levels of FLSirT1 were further decreased in both strains at 9 months. Immunoblot assays for 9-month-old strains revealed the presence of the inactive cleaved SirT1 variant (75 SirT1; 75 kDa) in WT mice, which was undetected in age-matched SirT1(+/-) mice. Nine-month-old SirT1(+/-) mice also showed increased OA and increased levels of apoptosis compared with age-matched WT mice. The data suggest that the presence of 75 SirT1 may prolong viability of articular chondrocytes in adult (9-month-old) mice.


Effects of resistance training on the physical symptoms and functional capacity of patients with fibromyalgia: a systematic review and meta-analysis of randomized clinical trials.
Resistance training (RT) has become an important topic for the treatment of fibromyalgia (FM); however, there are still controversies regarding its ability to significantly improve physical symptoms and a lack of adequate recommendations for evidence-based practice. The aim of this study is to analyze the effects of RT on the physical symptoms of patients with FM through a systematic review with meta-analysis. We conducted a systematic review of randomized controlled trials in June 2022, according to PRISMA recommendations. The searches were carried out on the databases PubMed, Embase, Science Direct, Web of Science, PEDro, CINAHL, SciELO, and Google Scholar for gray literature, and the protocol was recorded in PROSPERO. Studies that evaluated patients with FM undergoing an RT program lasting more than 2 weeks and that analyzed physical health were selected. To carry out the meta-analysis, the recommendations of the Cochrane Handbook for Systematic Reviews of Interventions were followed. In total, 13 studies were included for qualitative analysis and nine for meta-analysis. Regarding meta-analysis, a favorable improvement was found for pain ([MD = - 10.22 (95% CI: - 18.86 to - 1.58; I2: 64%; P for heterogeneity: 0.003)]; very low quality of evidence {QoE}), fatigue ([SMD = - 0.39 (95% CI: - 0.61 to - 0.17; I2: 0%; P = 0.91)]; moderate QoE), and muscle strength ([SMD = 0.94 (95% CI: 0.02 to 1.85; I2: 93%; for heterogeneity: < 0.0001)]; very low QoE) and improvement in functional capacity ([MD = 18.75 (95% CI: 4.27 to 33.22; I2: 39%; P = 0.19)]; low QoE), in the general comparison. RT was effective in reducing pain and fatigue and increasing strength and functional capacity; however, due to the quality of the evidence, more studies are needed.


Increased levels of nuclear androgen receptors in hyperplastic prostate of aging men.
Several publications indicate the dihydrotestosterone content of hyperplastic prostatic tissue from man and dog is increased. There is limited information concerning an abnormality in the androgen receptor content in this disorder. In men, we determined the androgen receptor concentration in cytosol, nuclei, the nuclear matrix, and nuclease solubilized salt extract fractions from benign prostatic hyperplasia (BPH) and normal prostate. Nine BPH cases (age 61 +/- 7, mean +/- SD) and seven controls (age 29 +/- 10.6) were compared. Prostates were obtained during autopsy performed within 12 h after death and frozen at -70 degrees C until analysis. Four grams of tissue were homogenized and centrifuged for separation of nuclei and cytosol. Androgen receptors were estimated with an improved assay procedure. The androgen receptor content per mg of DNA in whole nuclei and in the salt extract fraction (P less than 0.01 and less than 0.05 respectively) was higher in BPH cases than in controls. Cytosol did not show a significant difference. For both groups, receptors were undetectable in the nuclear matrix. We speculate that increased androgen receptor bound to chromatin of hyperplastic tissue may be causally related to the development of BPH in aging man.


Cycloartane triterpenes from Euphorbia tuckeyana.
Investigation of the acetone extract of the whole plant of Euphorbia tuckeyana afforded a new cycloartane-type triterpene named as cyclotucanol. Its structure was established as cycloartane-24-methylene-3beta,25-diol (1). The known cycloartane triterpenes cycloeucalenol (2), 3beta-hydroxycycloart-25-en-24-one (3), cycloart-25-ene-3beta,24-diol (4), 25,26,27-trisnor-3beta-hydroxycycloartan-24-al (5) and cycloart-23-ene-3beta,25-diol (6) were also isolated and identified.


IMB-SD62, a triazolothiadiazoles derivative with promising action against tuberculosis.
One lead 3,6-disubstituted 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole was identified as an inhibitor of shikimate dehydrogenase with antitubercular activity. Following up this compound, we optimized the lead through systematic modification of the 3 and 6 positions. The antitubercular activities in vitro, shikimate dehydrogenase inhibitory activities and cytotoxicity of derivatives were determined. We found IMB-SD62 with lower cytotoxicity and better activity. Thus, we studied the in vivo efficacy of IMB-SD62 against Mycobacterium tuberculosis and pharmacokinetics of IMB-SD62. In vivo acute M. tuberculosis H37Rv infection assay, IMB-SD62 showed antitubercular activity with the mean lung CFU counts decreasing 1.7 lg. The plasma pharmacokinetics study in rats showed that the oral bioavailability of IMB-SD62 was 14% and the half time was 1.05 h. The results of tissue distribution indicated that IMB-SD62 was mainly absorbed by liver and lung. In vitro metabolism study suggested that the metabolic ways of IMB-SD62 were dealkylated, oxidized and demethylated. CYP enzyme inhibition of IMB-SD62 in human liver microsomes was also evaluated. IMB-SD62 showed barely inhibition on CYP3A4 and CYP2D6. The excretion study manifested that IMB-SD62 was mainly eliminated by fecal excretion in rats. We concluded that based on these pharmaceutical properties, IMB-SD62 has the potential to be developed into new TB drug.