Normal bone marrow hematopoietic stem cell reserves and normal stromal cell function support the use of autologous stem cell transplantation in patients with multiple sclerosis.
Bone marrow (BM) stem cell reserves and function and stromal cell hematopoiesis supporting capacity were evaluated in 15 patients with multiple sclerosis (MS) and 61 normal controls using flow cytometry, clonogenic assays, long-term BM cultures (LTBMCs) and enzyme-linked immunosorbent assays. MS patients displayed normal CD34+ cell numbers but a low frequency of colony-forming cells (CFCs) in both BM mononuclear and purified CD34+ cell fractions, compared to controls. Patients had increased proportions of activated BM CD3+/HLA-DR+ and CD3+/CD38+ T cells that correlated inversely with CFC numbers. Patient BM CD3+ T cells inhibited colony formation by normal CD34+ cells and patient CFC numbers increased significantly following immunomagnetic removal of T cells from BMMCs, suggesting that activated T cells may be involved in the defective clonogenic potential of hematopoietic progenitors. Patient BM stromal cells displayed normal hematopoiesis supporting capacity indicated by the CFC number in the nonadherent cell fraction of LTBMCs recharged with normal CD34+ cells. Culture supernatants displayed normal stromal derived factor-1 and stem cell factor/kit ligand but increased flt-3 ligand levels. These findings provide support for the use of autologous stem cell transplantation in MS patients. The low clonogenic potential of BM hematopoietic progenitors probably reflects the presence of activated T cells rather than an intrinsic defect.


ProSeg: a database of local structures of protein segments.
Integration of knowledge on the sequence-structure correlation of proteins provides a basis for the structural design of artificial novel proteins. As one of strategies, it is effective to consider a short segment, whose size is in between an amino acid and a domain, as a correlation unit for exploring the structure-to-sequence relationship. Here we report the development of a database called ProSeg, which consists of two sub-databases, Segment DB and Cluster DB. Segment DB contains tens of thousands of segments that were prepared by dividing the primary sequences of 370 proteins using a sliding L-residue window (L = 5, 9, 11, 15). These segments were classified into several thousands of clusters according to their three-dimensional structural resemblance. Cluster DB contains much cluster-related information, which includes image, rank, frequency, secondary structure assignment, sequence profile, etc. Users can search for a suitable cluster by inputting an appropriate parameter (i.e., PDB ID, dihedral angles, or DSSP symbols), which identifies the backbone structure of a query segment. Analogous to a language, ProSeg could be regarded as a 'structure-sequence dictionary' that contains over 10,000 'protein words'. ProSeg is freely accessible through the Internet ( http://riodb.ibase.aist.go.jp/proseg/ ).


Liquid chromatography/atmospheric pressure chemical ionization ion trap mass spectrometry of terpene lactones in plasma of animals.
Liquid chromatography/atmospheric pressure chemical ionization ion trap mass spectrometry (LC/APCI-ITMS) was applied to evaluate the bioavailibility of two different forms (free and complexed with soy phospholipids) of pure bilobalide and ginkgolide B in rats after acute administration. The same technique was used to measure the levels of ginkgolide A, B and bilobalide in plasma of guinea pigs fed Ginkgo biloba extract enriched in terpene lactones after chronic administration. The ratio R(P)/R(A) increased two to four times after the administration in the phytosomic form, where R(P) and R(A) represent the percentage ratio between the concentration of each terpene lactone in plasma and in the administrated form, respectively.


Monoclonal antibody raised against tetrodonic acid, a derivative of tetrodotoxin.
Tetrodonic acid, a relatively non-toxic derivative of tetrodotoxin, was conjugated with bovine serum albumin and injected i.p. to BALB/c mice. After several injections, spleen cells were isolated, fused with myeloma cells X63-Ag8-6.5.3. and cloned by the limiting dilution method. The monoclonal antibody produced in ascites fluid in the mouse by the cloned cell showed an increasing reactivity with tetrodotoxin at concentrations ranging from 0.03 to 100 micrograms per well.


Early diversification and permeable species boundaries in the Mediterranean firs.
Inferring the evolutionary relationships of species and their boundaries is critical in order to understand patterns of diversification and their historical drivers. Despite Abies (Pinaceae) being the second most diverse group of conifers, the evolutionary history of Circum-Mediterranean firs (CMFs) remains under debate. We used restriction site-associated DNA sequencing (RAD-seq) on all proposed CMF taxa to investigate their phylogenetic relationships and taxonomic status. Based on thousands of genome-wide single nucleotide polymorphisms (SNPs), we present here the first formal test of species delimitation, and the first fully resolved, complete species tree for CMFs. We discovered that all previously recognized taxa in the Mediterranean should be treated as independent species, with the exception of Abies tazaotana and Abies marocana. An unexpectedly early pulse of speciation in the Oligocene-Miocene boundary is here documented for the group, pre-dating previous hypotheses by millions of years, revealing a complex evolutionary history encompassing both ancient and recent gene flow between distant lineages. Our phylogenomic results contribute to shed light on conifers' diversification. Our efforts to resolve the CMF phylogenetic relationships help refine their taxonomy and our knowledge of their evolution.


Strategies of Drug Delivery for Deep Fungal Infection: A Review.
The deep fungal infection poses serious threats to human health, mainly due to the increase in the number of immunocompromised individuals. Current first-line antifungal agents such as Amphotericin B, Fluconazole and Itraconazole, may decrease the severity of fungal infection to some extent, but the poor drug bioavailability, drug toxicity and poor water solubility seriously restrict their clinical utility. This review focuses on the study of drug delivery strategies for the treatment of deep fungal infections. We summarize the drug delivery strategies recently reported for the treatment of deep fungal infection, and explain each part with research examples. We discuss the use of pharmaceutical approaches to improve the physicochemical properties of the antifungal drugs to provide a basis for the clinical application of antifungal drugs. We then highlight the strategies for targeting drug delivery to the infection sites of fungi and fungal surface moieties, which have the potential to get developed as clinically relevant targeted therapies against deep fungal infections. It is worth noting that the current research on fungal infections still lags behind the research on other pathogens, and the drug delivery strategy for the treatment of deep fungal infections is far from meeting the treatment needs. Therefore, we envision the potential strategies inspired by the treatment of diseases with referential pathology or pathophysiology, further enriching the delivery of antifungal agents, providing references for basic research of fungal infections. Lay Summary: The deep fungal infections pose serious threats to the health of immunodeficiency patients. It is worth noting that the current research on fungi is still lagging behind that on other pathogens. The drug delivery strategies for the treatment of deep fungal infections are far from meeting the treatment needs. We summarize the recently reported drug delivery strategies for treating deep fungal infection, and envision the potential strategies to further enrich the delivery of antifungal agents.


[Is there a correlation between C-reactive protein and calcification inhibitors with cardiovascular parameters and risk factors in hemodialysis patients?].
Patients on hemodialysis exhibit a drastically increased cardiovascular mortality. Inflammation, hyperphosphatemia and lack of calcification inhibitors are uremia-associated risk factors for vascular calcification. Functional and morphological vascular parameters are used to assess cardiovascular risk. The aim of our study was to analyse the relation between pulse wave velocity (PWV) and intima-media-thickness (IMT) with calcification inhibitors. A cohort of 97 hemodialysis patients was consecutively selected and investigated (age 56 +/- 9 years). Carotid-femoral PWV, carotid IMT, left ventricular ejection fraction and septum thickness were determined. These parameters were correlated with serum levels of CRP and calcification inhibitors (fetuin-A and osteoprotegerin [OPG]). Both PWV and IMT showed a positive correlation with age and systolic blood pressure and a negative correlation with Kt/V (dialysis efficiency). Additionally, fetuin-A was negatively associated with CRP and positively with cholesterol and triglycerides. Serum levels of the calcification inhibitors fetuin-A and OPG were not correlated to PWV or IMT. The lack of correlation of calcification inhibitors with PWV and IMT means that functional and morphological measurements of vascular properties can not necessarily be replaced by analysing "biomarkers".


Integrated Fluidic Circuits (IFCs) for digital PCR.
The Fluidigm Digital Array IFC is a nanofluidic biochip where digital PCR reactions can be performed with isolated individual DNA template molecules. This chip is part of a family of integrated fluidic circuits (IFC) and contains a network of fluid lines, NanoFlex™ valves and chambers. NanoFlex™ valves are made of an elastomeric material that deflects under pressure to create a tight seal and are used to regulate the flow of liquids in the IFC. Digital Arrays have enabled a different approach to digital PCR, by partitioning DNA molecules instead of diluting them. Single DNA molecules are randomly distributed into nanoliter volume reaction chambers and then PCR amplified in the presence of a fluorophore-containing probe. Positive fluorescent signal indicates the presence of a DNA molecule in a reaction chamber, while negative chambers are blank. IFC technology enables the delivery of very precise volumes of solutions in a simple, fast procedure, utilizing a minimum of sample and assay reagents. The development of the IFC technology and the Digital Array chip has revolutionized the field of biology, and has been utilized in gene copy number studies, absolute quantitation (molecule counting) of genomic DNA and cDNA, rare mutation detection, and digital haplotyping.


Genetic associations with resistance to Meloidogyne enterolobii in guava (Psidium sp.) using cross-genera SNPs and comparative genomics to Eucalyptus highlight evolutionary conservation across the Myrtaceae.
Tropical fruit tree species constitute a yet untapped supply of outstanding diversity of taste and nutritional value, barely developed from the genetics standpoint, with scarce or no genomic resources to tackle the challenges arising in modern breeding practice. We generated a de novo genome assembly of the Psidium guajava, the super fruit "apple of the tropics", and successfully transferred 14,268 SNP probesets from Eucalyptus to Psidium at the nucleotide level, to detect genomic loci linked to resistance to the root knot nematode (RKN) Meloidogyne enterolobii derived from the wild relative P. guineense. Significantly associated loci with resistance across alternative analytical frameworks, were detected at two SNPs on chromosome 3 in a pseudo-assembly of Psidium guajava genome built using a syntenic path approach with the Eucalyptus grandis genome to determine the order and orientation of the contigs. The P. guineense-derived resistance response to RKN and disease onset is conceivably triggered by mineral nutrients and phytohormone homeostasis or signaling with the involvement of the miRNA pathway. Hotspots of mapped resistance quantitative trait loci and functional annotation in the same genomic region of Eucalyptus provide further indirect support to our results, highlighting the evolutionary conservation of genomes across genera of Myrtaceae in the adaptation to pathogens. Marker assisted introgression of the resistance loci mapped should accelerate the development of improved guava cultivars and hybrid rootstocks.


An experimental evaluation of nucleotide enhancement techniques for kidney transplantation.
The effect of various nucleotide-enhancing agents on renal function and intracellular nucleotide levels was evaluated in a canine autotransplant model. Thirty-five dogs (18-28 kg) underwent left nephrectomy and 30 min of warm ischemia followed by Collins C-4 flush and 24 hr of cold-storage preservation. Heterotopic autotransplantation and immediate contralateral nephrectomy was then performed. Seven equal groups were evaluated: group A--controls, group B--adenosine pretreatment (1.0 g), group C--dipyridamole pretreatment (10 mg), group D--adenosine (1.0 g), and dipyridamole (10 mg) pretreatment, group E--adenosine (200 mg) and EHNA (2.5 mg/kg) pretreatment, group F--adenosine (200 mg) and EHNA (2.5 mg/kg) in the Collins C-4 flush, and group G--adenosine (200 mg) and EHNA (2.5 mg/kg) at the time of autotransplantation. All kidneys underwent cortical biopsies at the end of preservation and 1 hr after restoration of blood flow for determinations of AMP, ADP, and ATP. In the pretreatment groups (groups B through E) there was 60% graft survival whereas the controls (group A) and the groups treated after ischemia (groups F and G) had 0, 0, and 20% graft survival, respectively. In groups B and E, ATP levels were greater than controls after preservation and 1 hr after restoration of blood flow. Group C AMP and ADP levels and group D energy charge were greater than controls in the post-transplantation biopsies. Administration of adenosine and EHNA after ischemia was not associated with increased intracellular nucleotide levels. One hour post-transplantation biopsies demonstrated greater ability to regenerate cortical nucleotides in the surviving animals but no absolute value could be identified as a predictor of viability. In conclusion, pretreatment with adenosine, dipyridamole, and EHNA alone and in combination is beneficial in ischemically injured kidneys undergoing cold-storage preservation.


Radical prostatectomy for high-risk prostate cancer.
Consensus recommendations for the identification and treatment of men whose apparent organ confined prostate cancer has high risk features are lacking. Despite ongoing refinements in surgical technique and improvements in morbidity and functional outcomes, the tradition of steering high-risk patients away from radical prostatectomy (RP) remains steadfast. We performed a medical literature search in English using MEDLINE/PubMed that addressed high risk prostate cancer. We analyzed the literature with respect to the historical evolution of this concept, current risk stratification schemes and treatment guidelines and related short and long term outcomes following RP. Contemporary evidence suggest that patients classified with high-risk prostate cancer by commonly used definitions do not have a uniformly poor prognosis after RP. Many cancers categorized clinically as high risk are actually pathologically confined to the prostate, and most men with such cancers who undergo RP are alive and free of additional therapy long after surgery. RP in the high-risk setting appears to be associated with a similar morbidity as in lower-risk patients. Men with clinically localized high-risk prostate cancer should not be categorically disqualified from local definitive therapy with RP. With careful attention to surgical technique, cancer control rates should improve further, and adverse effects on quality of life after RP should continue to decrease.


Use of an innovative cuff pressure control and subglottic secretions drainage system in COVID-19 ARDS patients undergoing pronation.
We conducted a proof of concept study where Anapnoguard endotracheal tubes and its control unit were used in 15 patients with COVID-19 acute respiratory distress syndrome. Anapnoguard system provides suction, venting, rinsing of subglottic space and controls cuff pressure detecting air leakage through the cuff. Alpha-amylase and pepsin levels, as oropharyngeal and gastric microaspiration markers, were assessed from 85 tracheal aspirates in the first 72 h after connection to the system. Oropharyngeal microaspiration occurred in 47 cases (55%). Episodes of gastric microaspiration were not detected. Patient positioning, either prone or supine, did not affect alpha-amylase and pepsin concentration in tracheal secretions. Ventilator-associated pneumonia (VAP) rate was 40%. The use of the AG system provided effective cuff pressure control and subglottic secretions drainage. Despite this, no reduction in the incidence of VAP has been demonstrated, compared to data reported in the current COVID-19 literature. The value of this new technology is worth of being evaluated for the prevention of ventilator-associated respiratory tract infections.


Electron probe analysis of maturation ameloblasts of the rat incisor and calf molar.
Rapidly frozen upper incisor teeth of rats and molar teeth of calves were freeze fractured, freeze dried and dry dissected in preparation for energy dispersive x-ray emission microanalysis in the scanning electron microscope. Successive zones of ameloblasts adjacent to maturing rat incisor enamel were examined, beginning with cells adjacent to the least mature enamel and progressing to cells over increasingly more mature enamel. Pronounced Kalpha1,2 x-ray peaks were obtained for P, S, Cl, K and Fe but not for Ca. Ca levels were also very low compared with P, S, Cl and K in calf molar maturation ameloblasts, whereas they were high in the distal poles of the secretory odontoblasts in the same specimens. The findings indicate that both intra- and extracellular Ca levels are extremely low in maturation ameloblasts. It is concluded that Ca is neither stored nor concentrated in large amounts by the maturation ameloblasts prior to its entry into the enamel. The suggestion is made that the maturation ameloblasts might regulate entry of calcium into enamel by serving as a selective barrier.


UCSF Chimera, MODELLER, and IMP: an integrated modeling system.
Structural modeling of macromolecular complexes greatly benefits from interactive visualization capabilities. Here we present the integration of several modeling tools into UCSF Chimera. These include comparative modeling by MODELLER, simultaneous fitting of multiple components into electron microscopy density maps by IMP MultiFit, computing of small-angle X-ray scattering profiles and fitting of the corresponding experimental profile by IMP FoXS, and assessment of amino acid sidechain conformations based on rotamer probabilities and local interactions by Chimera.


Cochlear Implantation in Patients With Intracochlear and Intralabyrinthine Schwannomas.
Schwannomas may arise primarily within the inner ear, or invade the cochlea or labyrinth from the distal internal auditory canal through transmodiolar or transmacular extension, respectively. To date, very limited data exists regarding cochlear implant (CI) outcomes in this unique population. Retrospective case review. Ten ears (nine patients) with inner ear schwannomas that underwent CI at a single tertiary referral center. Cochlear implantation. Surgical approach, CI performance. Ten ears (nine patients) were implanted with conventional CI arrays. Three cases had primary inner ear schwannomas, while seven were in patients with neurofibromatosis type 2 (NF2) having transmodiolar invasion of the inner ear from a vestibular schwannoma (VS). In all cases, intracochlear tumor was left in situ to preserve cochlear anatomy and a full electrode insertion was achieved. Use of a styleted electrode with late deployment aided advancement through the intracochlear tumor. In all cases, the ipsilateral internal auditory canal and inner ear could be visualized on postoperative magnetic resonance imaging (MRI) for tumor surveillance. Eight ears achieved good open-set word recognition (median, Consonant-Nucleus-Consonant [CNC] 50% [range, 28-88%], median, AzBio 73% [range, 60-91%]); two patients with NF2 and prolonged deafness (15 and 22 years) received limited benefit. Cochlear implantation in patients with inner ear schwannomas and an intact cochlear nerve is feasible. Leaving intracochlear schwannoma in situ preserves cochlear architecture and use of a styleted electrode may aid in achieving a full insertion when obstructing tumor is present. Postoperative MRI surveillance is still adequate after CI and a high percentage of patients achieve good open-set speech perception performance.


Genetic and environmental influences on body fat and blood pressure in African-American adult twins.
African Americans have a particularly high prevalence of excessive body fat and high blood pressure. Genetic and environmental influences may be implicated for both of these risk factors. We investigated the potential for common genetic and environmental influences on body fat (waist circumference (WC), body mass index (BMI)) and blood pressure measures (systolic and diastolic pressure (SBP, DBP)) among African-American male and female subjects. Measurements were taken as part of the Carolina African-American Twin Study of Aging (CAATSA). The CAATSA sample contains 217 same-sex African-American male and female twins with average age of 47 years. This analysis included 39 monozygotic male pairs (MZ), 43 dizygotic male pairs (DZ); 63 MZ female pairs, and 72 DZ female pairs. Maximum likelihood quantitative genetic analyses were used. The total genetic variance for SBP was 22% in male subjects and 40.1% in female subjects. Of this total variance, 3.1% was in common with BMI in male subjects and 6% was in common with BMI in female subjects. After controlling for the effects of BMI, WC had less than 1% of its variance in common with SBP in male and female subjects. For DBP, the total genetic variance was 16.9% in male and 38.7% in female subjects. Of this total variance 6.1% was in common with BMI in male subjects and 3.7% was in common in female subjects. Again, WC had less than 1% of its genetic variance in common with DBP in both male and female subjects. The environmental variance common among these measures was also very small. The remaining variance was primarily accounted for by genetic and environmental effects unique to each measure as well as age. Based on the very small common genetic variance for BMI, SBP, and DBP as well as WC and the blood pressure measures, our results suggest that searching for common genes among these measures may be inconclusive.


Hierarchical electrodeposition of methylene blue on ZnO nanocrystals thin films layered on SnO2/F electrode for in vitro sensing of anti-thalassemic drug.
Zinc oxide nanocrystals-methylene blue nanocomposites were developed by electrodeposition of methylene blue onto the thin films of zinc oxide nanocrystals deposited onto SnO2/F coated glass substrates for in vitro sensing of anti-thalassemic drug i.e. deferiprone. Detailed morphological, electrochemical, structural and optical characterizations of ZnONC-MB/FTO electrode were done using XRD, SEM, EIS, FTIR, LSV, and CV and show quick response time (within 5 s), linearity as 1 × 10(-3) to 10(3) μM and shelf life of about 10 weeks under refrigerated conditions. Attempts have been made to utilize this electrode for estimation of deferiprone in urine samples. The developed sensor exhibited high reproducibility and good storage stability.


The aetiology and maintenance of social anxiety disorder: A synthesis of complimentary theoretical models and formulation of a new integrated model.
Within maintenance models of social anxiety disorder (SAD), a number of cognitive and behavioural factors that drive the persistence of SAD have been proposed. However, these maintenance models do not address how SAD develops, or the origins of the proposed maintaining factors. There are also models of the development of SAD that have been proposed independently from maintenance models. These models highlight multiple factors that contribute risk to the onset of SAD, but do not address how these aetiological factors may lead to the development of the maintaining factors associated with SAD. A systematic review of the literature was conducted to identify aetiological and maintenance models of SAD. We then united key factors identified in these models and formulated an integrated aetiological and maintenance (IAM) model of SAD. A systematic review of the literature was then conducted on the components of the IAM model. A number of aetiological and maintaining factors were identified in models of SAD. These factors could be drawn together into the IAM model. On balance, there is empirical evidence for the association of each of the factors in the IAM model with social anxiety or SAD, providing preliminary support for the model. There are relationships between components of the IAM model that require empirical attention. Future research will need to continue to test the IAM model. The IAM model provides a framework for future investigations into the development and persistence of SAD.


Atrial size and transport function after the Maze III procedure for paroxysmal atrial fibrillation.
The Maze procedure is a curative surgical therapy for atrial fibrillation, restoring sinus rhythm and improving quality of life. Because the procedure results in tissue scarring, the atrial transport function is most likely affected. Seventeen patients with paroxysmal atrial fibrillation underwent the Maze III procedure without any concomitant valve operation. Atrial size and transport function were measured before and at 2, 6, and 24 months after operations with two-dimensional echocardiography and pulsed-wave Doppler. Fifteen patients (88%) had signs of left atrial contractions as shown by the presence of a transmitral atrial filling wave on Doppler echocardiography at 6 months follow-up. The transmitral early filling wave and atrial filling wave were measured to calculate the early filling/atrial filling wave ratio, which increased from 1.2 before to 1.9 at 2 months after the Maze procedure (nonsignificant), and further to 2.8 at 24 months (p = 0.02). A decrease in the right and left atrial size was seen at 2 months after an operation, but no further decrease occurred. In patients with paroxysmal atrial fibrillation, there is a progressive increase in the transmitral early filling/atrial filling wave ratio after the Maze procedure, consistent with a gradual decrease in the left atrial transport function.


Histochemical changes in protein disulphide bonds in rat liver and kidney after chronic cadmium administration, and the possible relation to metallothionein.
After chronic exposure to low doses of CdCl2 an increase in disulphide bonds has been established in rat liver using a specific staining method for disulphide bonds and cytophotometric quantitation. This increase is dependent on doses and length of exposure time. Evidence is presented that this increase might be related to the accumulation of metallothionein or some other cadmium binding protein. Using the same staining method after long exposure to low doses of CdCl2 a large number of large dark blue stained granules were observed in the proximal tubule cells, with blue stained deposits in the lumen of the proximal and some renal medulla tubules of the kidney. Evidence is presented that this staining pattern corresponds to the destruction of the proximal tubule cell by the cadmium thionein complex.


Increased polymorphonuclear leukocyte cGMP levels induced by the human lympholine, leukocyte migration inhibitory factor (LIF).
The possible involvement in vitro of 3', t'-cyclic GMP (cGMP) in the mechanism of action of the lymphokine, leukocyte migration inhibitory factor (LIF), was investigated. Partially purified LIF-rich supernatants, but not their control counterparts, induced a 2-fold increase in the cGMP levels of purified human polymorphonuclear (NMN) leukocytes. The effect was no influenced by heat-inactivated horse serum; it was manifested within 3 min of exposure to LIF and it subsided within 180 min. LIF and the supernatant factor responsible for the cGMP-generating effect were both rendered inactive by treatment with the serine esterase and protease inhibitor, phenylmethylsulfonyl fluoride, indicating that these factors are closely related, if not identical. A potent phosphodiesterase inhibitor, dipyridamole (2 x 10(-4) M), induced a 3- to 5-fold increase in PMN leukocyte cGMP levels, but combined treatment with purified LIF and dipyridamole did not add to this effect. This suggests that the cGMP-generating factor acts on the biochemical pathway that degrades cGMP.


Growth of human bone marrow in vitro.
Attempts were made to establish human bone marrow (HBM) culture. Cell proliferation was triggered by medium conditioned by acute myelocytic leukemic (AML) cells exposed to 12-0-tetradecanoyl-phorbol-13-acetate (TPA). A 6-15 fold multiplication of myelomonocytic cells was obtained in tissue culture from HBM cells. Proliferation of granulocyte-macrophage colony forming cells (CFC-GM) occurred up to 30-fold. The morphology of the cells and cytochemical markers were investigated at all stages of the culture.


Relationship between milk urea content and important milk traits in Holstein cattle.
Breeding cattle with low nitrogen emissions has been proposed as a countermeasure against eutrophication due to dairy production. Milk urea content (MU) could potentially serve as a new readily measured indicator trait for nitrogen emissions by cows. Therefore, we estimated genetic parameters related to MU and its relationship with other milk traits. We analysed 4 178 735 milk samples collected between January 2008 and June 2019 from 261 866 German Holstein dairy cows during their first, second, and third lactations. Restricted maximum likelihood estimation was conducted using univariate and bivariate random regression sire models in WOMBAT. We obtained moderate average daily heritability estimates for the daily MU of 0.24 in first lactation cows, 0.23 in second lactation cows, and 0.21 in third lactation cows with average daily genetic SDs of 25.16 mg/kg, 24.93 mg/kg, and 23.75 mg/kg, respectively. Averaged over days in milk, the repeatability estimates were low at 0.41 in first, second, and third lactation cows. A strong positive genetic correlation was found between MU and milk urea yield (MUY; 0.72 on average). In addition, 305-day heritabilities were estimated as 0.50, 0.52, and 0.50 in first, second, and third lactation cows, respectively, with genetic correlations of 0.94 or higher for MU in different lactations. By contrast, the averaged estimates of the genetic correlations between MU and other milk traits were low (-0.07 to 0.15). Moderate heritability estimates clearly allow the possible selection for MU, and the near-zero estimates of genetic correlations indicate no risk of undesired correlated selection responses in other milk traits. However, a relationship still needs to be established between MU as an indicator trait and the target trait, defined as total individual nitrogen emissions.


IL-30 protects against sepsis-induced myocardial dysfunction by inhibiting pro-inflammatory macrophage polarization and pyroptosis.
Cardiac dysfunction is a well-recognized complication of sepsis and seriously affects the prognosis of sepsis patients. IL-30 has been reported to exert anti-inflammatory effects in various diseases. However, the role of IL-30 in sepsis-induced myocardial dysfunction (SIMD) remains unclear. Here, we explored the protective role of IL-30 in cecum ligation and puncture (CLP)-induced SIMD mice. IL-30 expression increased in the cardiac tissues of septic mice and was mainly derived from macrophages. IL-30 deletion or neutralization aggravated sepsis-induced cardiac dysfunction and injury, whereas recombinant IL-30 treatment significantly ameliorated it. Mechanistically, IL-30 deficiency exerts pro-inflammatory effects by promoting Ly6Chigh macrophage polarization and pyroptosis. Inhibiting NLRP3 with MCC950 significantly reversed cardiac dysfunction, macrophage polarization and pyroptosis aggravated by IL-30 deficiency. Recombinant IL-30 inhibited pro-inflammatory macrophage polarization and pyroptosis in vivo and vitro. Taken together, these results suggest that IL-30 protects against SIMD by inhibiting pro-inflammatory macrophage polarization and pyroptosis.


Immunogold staining procedure for the localisation of regulatory peptides.
The use of protein A- and IgG-conjugated colloidal gold staining methods for the immuno-localisation of peptide hormones and neurotransmitters at light- and electron microscope level are described and discussed. Bright-field and dark-ground illumination modes have been used to visualise the gold-labelled antigenic sites at the light microscope level. Immunogold staining procedures at the ultrastructural level using region-specific antisera have been adopted to localise specific molecular forms of peptides including gastrin (G17 and G34), glucagon and pro-glucagon, insulin and pro-insulin, in normal tissue and in tumours of the gastroenteropancreatic system. Similar methods have been used to demonstrate the heterogeneity of p-type nerves in the enteric nervous system. Vasoactive intestinal polypeptide (VIP) has been localised to granular sites (mean +/- S.D. granule diameter = 98 +/- 19 nm) in nerve terminals of the enteric plexuses and in tumour cells of diarrhoeogenic VIP-producing neoplasias (mean +/- S.D. granule diameter = 126 +/- 37 nm) using immunogold procedures applied to ultraviolet-cured ultrathin sections. Co-localisation of amines and peptides in carotid body type I cells and in chromaffin cells of normal adrenal medulla and phaeochromocytomas has also been demonstrated. Advantages of the immunogold procedures over alternative immunocytochemical techniques are discussed.


Non-invasive assessment of hepatic mitochondrial metabolism by positional isotopomer NMR tracer analysis (PINTA).
Hepatic mitochondria play a central role in the regulation of intermediary metabolism and maintenance of normoglycemia, and there is great interest in assessing rates of hepatic mitochondrial citrate synthase flux (V CS) and pyruvate carboxylase flux (V PC) in vivo. Here, we show that a positional isotopomer NMR tracer analysis (PINTA) method can be used to non-invasively assess rates of V CS and V PC fluxes using a combined NMR/gas chromatography-mass spectrometry analysis of plasma following infusion of [3-13C]lactate and glucose tracer. PINTA measures V CS and V PC fluxes over a wide range of physiological conditions with minimal pyruvate cycling and detects increased hepatic V CS following treatment with a liver-targeted mitochondrial uncoupler. Finally, validation studies in humans demonstrate that the V PC/V CS ratio measured by PINTA is similar to that determined by in vivo NMR spectroscopy. This method will provide investigators with a relatively simple tool to non-invasively examine the role of altered hepatic mitochondrial metabolism.Liver mitochondrial metabolism plays an important role for glucose and lipid homeostasis and its alterations contribute to metabolic disorders, including fatty liver and diabetes. Here Perry et al. develop a method for the measurement of hepatic fluxes by using lactate and glucose tracers in combination with NMR spectroscopy.


Prostacyclin, thromboxane A2, and prostaglandin E2 formation in atherosclerotic human carotid artery.
Prostaglandin (PG) formation in 16 atherosclerotic human carotid endarterectomy specimens was compared systematically with that of normal carotid artery from seven white pigs and six rhesus monkeys. Prostacyclin (PGI2) formation (picomoles 6-keto-PGF1a/2 min/100 micrograms homogenate protein plus 2 mM glutathione [GSH]) of nonatheromatous intima adjacent proximal (276 +/- 32, mean +/- SEM) or distal (271 +/- 14) to carotid plaque was comparable to that of normal carotid artery from white pig (272 +/- 25, NS) and rhesus monkey (219 +/- 41, NS), and was greater than stenotic intima (156 +/- 17, p less than 0.01), subintimal plaque (168 +/- 14, p less than 0.01), and ulceration (65 +/- 16, p less than 0.01). GSH modulated PGI2 synthesis in all carotid specimens except areas of ulceration (p less than 0.05), but did not restore PGI2 formation in atheromatous fractions to basal level. No detectable arterial thromboxane A2 (TXA2) formation or GSH-dependent PGE2 isomerase activity was observed. The decrement in atherosclerotic carotid artery PGI2 formation was focal (confined to the plaque) and may have been related to loss of effective GSH modulation. These conditions could contribute to a localized imbalance between arterial PGI2 and platelet TXA2 with adverse vascular thromboregulatory consequences.


Evoked potential correlates of echolocation in the mustached bat, Pteronotus p. parnellii.
The biosonar signals of the greater mustached bats are characterized by a long constant frequency component that is preceded and terminated by frequency modulated components. It has generally been concluded that the terminal FM (TFM) is important for target ranging while the initial FM (IFM), or beginning of the signal, is relatively insignificant. With the aid of chronically implanted electrodes, acoustically evoked brainstem potentials were recorded from bats during simulated flight on a pendulum and when targets were placed at fixed distances from the bat's head. Distinct pulse- and echo-evoked potentials were recorded in relation to the onset of both the IFM and TFM, or the onset of the CF when no IFM was present. Echo-evoked potentials were often as high in amplitude as pulse-evoked potentials and the timing of the IFM- and TFM-pulse and echo-evoked potentials seemed to accurately reflect target distance. Data indicate that the IFM, or signal onset, must be a significant part of the echo even though it is usually faint, overlaps the intense outgoing CF component, and returns to the ear when the middle ear muscles are contracting.


Preventive resin restorations and sealants in light of current evidence.
Pit and fissure sealant should be treatment option provided to all children, particularly at the age immediately after eruption of the posterior teeth and especially, but not exclusively, the permanent teeth. Preventive resin restoration is minimally invasive procedure that should be the treatment of choice for small carious lesions in the posterior teeth. The Class I amalgam should not be placed as a first-time restorative material to treat incipient or small carious lesions under any circumstances. The amount of tooth structure removal necessary for Class I Black preparation, which requires sufficient depth of amalgam and extension for prevention, is an unacceptable treatment when minimally-invasive options are available.


PM2.5 exposure regulates Th1/Th2/Th17 cytokine production through NF-κB signaling in combined allergic rhinitis and asthma syndrome.
Particulate matter (PM) is a major component of air pollution from emissions from anthropogenic and natural sources and is a serious problem worldwide due to its adverse effects on human health. Increased particulate air pollution increases respiratory disease-related mortality and morbidity. However, the impact of PM with an aerodynamic diameter of ≤ 2.5 μm (PM2.5) on combined allergic rhinitis and asthma syndrome (CARAS) remains to be elucidated. Accordingly, in the present study, we investigated the effect of PM2.5 in an ovalbumin (OVA)-induced CARAS mouse model with a focus on NF-κB signaling. We established an OVA-induced mouse model of CARAS to determine the effects of exposure to PM2.5. BALB/c mice were randomly divided into four groups: (1) naive, (2) PM2.5, (3) CARAS, and (4) CARAS/PM2.5. Mice were systemically sensitized with OVA and challenged with inhalation of ultrasonically nebulized 5% OVA three times by intranasal instillation of OVA in each nostril for 7 consecutive days. Mice in the PM2.5 and CARAS/PM2.5 groups were then exposed to PM2.5 by intranasal instillation of PM2.5 for several days. We then examined the impacts of PM2.5 exposure on histopathology and NF-κB signaling in our OVA-induced CARAS mouse model. PM2.5 increased infiltration of eosinophils in bronchoalveolar lavage fluid (BALF) samples and inflammatory cells in lung tissue. It also increased production of GATA3, RORγ, IL-4, IL-5, IL-13, and IL-17 in nasal lavage fluid (NALF) and BALF samples in the CARAS mouse model, but secretion of IL-12 and IFN-γ was suppressed. Exposure to PM2.5 increased OVA-specific IgE and IgG1 levels in serum, inflammatory cell infiltration in the airways, and fibrosis in lung tissue. It also activated the NF-κB signaling pathway, increasing Th2/Th17 cytokine levels while decreasing Th1 cytokine expression, thereby inducing an inflammatory response and promoting inflammatory cell infiltration in nasal and lung tissue. Our results demonstrate that PM2.5 can aggravate OVA-induced CARAS.


Epigenetic disruption of interferon-gamma response through silencing the tumor suppressor interferon regulatory factor 8 in nasopharyngeal, esophageal and multiple other carcinomas.
16q24 is frequently deleted in multiple tumors including cancers of nasopharynx, esophagus, breast, prostate and liver. By array comparative genomic hybridization (aCGH), we refined a 16q24 hemizygous deletion in nasopharyngeal carcinoma (NPC) cell lines. Semi-quantitative RT-PCR analysis revealed interferon regulatory factor 8 (IRF8) as the only downregulated gene within this deletion. IRF8 belongs to a family of interferon (IFN) regulatory factors that modulate various important physiologic processes including host defense, cell growth and differentiation and immune regulation. In contrast to the broad expression of IRF8 in normal adult and fetal tissues, transcriptional silencing and promoter methylation of IRF8 were frequently detected in multiple carcinoma (except for hepatocellular) cell lines (100% in NPC, 88% in esophageal and 18-78% in other carcinoma cell lines) and in a large collection of primary carcinomas (78% in NPC, 36-71% in other carcinomas). Methylation of the IRF8 promoter led to the disruption of its response to IFN-gamma stimulation. Pharmacological and genetic demethylation could restore IRF8 expression, indicating a direct epigenetic mechanism. Ectopic expression of IRF8 in tumor cells lacking its expression strongly inhibited their clonogenicity, confirming its tumor suppressor function. Thus, IRF8 was identified as a functional tumor suppressor, which is frequently silenced by epigenetic mechanism in multiple carcinomas.


Hb Constant Spring [alpha 142, Term-->Gln (TAA>CAA in alpha2)] in the alpha-thalassemia of anemic patients in Myanmar.
Hb Constant Spring (Hb CS), the gene (alpha(CS)) of which arises from a point mutation in the termination codon of the alpha2-globin gene, is the most prevalent variety of nondeletional alpha-thalassemia (alpha-thal) in Asian populations. It is a major cause of Hb H disease in compound heterozygotes who have Hb CS combined with a duplicated alpha gene deletion (--/alpha(CS)alpha), and it tends to be more severe than Hb H disease which is caused by a triple alpha gene deletion (--/-alpha). Hb CS is often missed by routine electrophoresis but not by polymerase chain reaction (PCR) methods. During alpha-thal screening and genotyping of 235 patients diagnosed by laboratory tests hemoglobin (Hb), MCV, MCH and Hb H inclusion bodies] using the gap-PCR method, 175 patients were diagnosed to be carriers of an alpha-thal gene, genotypes of which were 133 alpha-thal-2, 34 alpha-thal-1 (including one only by laboratory test) and eight with Hb H disease. Detection of the alpha(CS) gene for the carriers of alpha-thal-1 and Hb H disease was done by the mismatched PCR-RFLP (restriction fragment length polymorphism) method and the alpha(CS) gene was found in the homozygous state in an alpha-thal-1 patient and a single gene form in two Hb H disease patients. These genotypes were characterized by the PCR-sequencing method. These patients clinically presented the aspects of Hb H disease and of a homozygote form of alpha-thal-1. The description of the alpha(CS) gene in Myanmar is of great value in the development of an effective procedure for prenatal diagnosis of Hb Bart's hydrops fetalis syndrome.


Bilingualism contributes to reserve and working memory efficiency: Evidence from structural and functional neuroimaging.
This study compared brain and behavioral outcomes for monolingual and bilingual older adults who reported no cognitive or memory problems on three types of memory that typically decline in older age, namely, working memory (measured by n-back), item, and associative recognition. The results showed that bilinguals were faster on the two-back working memory task than monolinguals but used a set of frontostriatal regions less than monolinguals. There was no group difference on an item/associative recognition task. In brain structure, gray matter volume and white matter integrity (fractional anisotropy) were generally lower in bilinguals than in monolinguals, but bilinguals had better white matter integrity than monolinguals in the bilateral superior corona radiata and better gray matter density in the left inferior temporal gyrus. These regions may help preserve bilinguals' executive functions despite generally more significant atrophy throughout the brain than monolinguals in that these structures contribute to efficient communication between executive frontal regions and subcortical motor regions, and perceptual pathways. Reliable negative correlations between brain structure and age were only observed in bilinguals, and to the extent that bilinguals (but not monolinguals) had better brain structure, their performance was enhanced. Collectively, the findings provide evidence for reserve in bilingual older adults.


A Rare Occurrence of Premature Birth and Recurrent Acute Pulmonary Oedema in the Mother due to Cushing's Syndrome: A Case Report.
Presentation of Cushing's syndrome during pregnancy is extremely rare. We report a 21-year-old female with Cushing's syndrome diagnosed at 23 weeks of gestation and had recurrent acute pulmonary oedema during the antepartum and postpartum period. She delivered prematurely via emergency caesarean section at 28 weeks of gestation. This case highlights the rare occurrence of recurrent acute pulmonary oedema during pregnancy and consequential premature birth in a patient with adrenal Cushing's. She was diagnosed with adrenal Cushing's during the postpartum period based on unsuppressed serum cortisol after overnight and low-dose dexamethasone suppression test with a suppressed ACTH. CT scan of the adrenal glands revealed a right adrenal cortical adenoma. The risk of complications in infants and mothers who suffer from Cushing's syndrome needs to be handled carefully. The diagnosis of Cushing's syndrome in pregnant women often overlaps and is difficult to establish in early pregnancy.


Differences in global gene expression in melanoma cell lines with and without homozygous deletion of the CDKN2A locus genes.
We studied differential global gene expression in four melanoma cell lines with three cell lines without homozygous deletion of the CDKN2A locus using HG-U133A microarrays with 22 277 transcripts. None of the cell lines carried mutations in the B-RAF and N-RAS genes. Data analysis using stringent criteria showed specific upregulation of 70 genes and downregulation of 86 genes in cell lines with homozygous deletion of the CDKN2A gene. A comparison with previous expression data showed overlapping of upregulation and downregulation of seven and 23 genes, respectively, in melanoma cell lines with homozygous deletion of the CDKN2A locus or mutations in the B-RAF and N-RAS genes. Microarray data for eight selected genes were validated with an extended number of cell lines using quantitative real-time polymerase chain reaction. The upregulated genes in cell lines with the deletion besides others included MAGE A2 [fold change 128, 95% confidence interval (CI) 82.8-172.2; t-test P=0.004], MAGE A6 (fold change 623, 95% CI 473.4-772.1; t-test P=0.001), MAGE A12 (fold change 90, 95% CI 65.1-115.5; t-test P=0.001) and dopachrome tautomerase (fold change 42, 95% CI 32.5-51.8; t-test P=0.001). Downregulated genes included interleukin 18 (fold change 489, 95% CI 146.4-831.2; t-test P=0.04), ID2 (fold change 3, 95% CI 2.2-4.9; t-test P=0.001), KLF4 (fold change 9, 95% CI 4.3-14.7; P=0.01) and CD24 antigen (fold change 1308, 95% CI 766.0-1850.8; t-test P=0.01). The upregulated genes common to cell lines with homozygous deletion of the CDKN2A gene and mutations in B-RAF and N-RAS gene included those that are involved in RAS/RAF/MEK/ERK pathways. Our results highlight effects of homozygous deletion of the CDKN2A locus on global gene expression.


Results of surgery to the damaged facial nerve.
Neurological surgery of the paralysed face can be rewarding if performed early using appropriate surgical techniques. The results of 32 operations are analyzed. Excellent restoration of facial function is achieved with early surgical intervention but some results are poor. The reasons for failure are analyzed.


Relationship of the ventilatory response to hypoxia with neonatal apnea in preterm infants.
Correlate the ventilatory response of preterm infants to hypoxic exposure with incidence of neonatal apnea. Study design Seventeen stable convalescing premature infants underwent bedside cardiorespiratory monitoring of respiration using respiratory inductance plethysmography, heart rate, and oxygen saturation (SaO(2)) for a 12-hour period. These studies were scored for number of apneas > or =15 and > or =20 seconds. Infants then underwent a 3-minute hypoxic exposure. Minute ventilation (V(E)) was calculated for 30-second epochs from the time inspired oxygen reached 15%. Linear regression analysis was used to correlate the change in V(E) normalized for decrease in SaO(2) (DeltaV(E)/DeltaSaO(2)) during the first and third minutes of hypoxic exposure with the number of apneic episodes during the 12-hour study. The majority of infants exhibited an anticipated biphasic ventilatory response to hypoxia. There was a significant positive correlation between DeltaV(E)/DeltaSaO(2) during the first and third minutes of hypoxic exposure and number of apneic episodes > or =15 and > or =20 seconds during the preceding 12 hours. Preterm infants with a greater number of apneic episodes exhibit an increased ventilatory response to hypoxic exposure, suggesting that apnea of prematurity may be associated with enhanced peripheral chemoreceptor activity.


Intracellular insulin-receptor dissociation and segregation in a rat fibroblast cell line transfected with a human insulin receptor gene.
The cellular processing of insulin and insulin receptors was studied using a rat fibroblast cell line that had been transfected with a normal human insulin receptor gene, expressing approximately 500 times the normal number of native fibroblast insulin receptors. These cells bind and internalize insulin normally. Biochemical assays based on the selective precipitation by polyethylene glycol of intact insulin-receptor complexes but not of free intracellular insulin were developed to study the time course of intracellular insulin-receptor dissociation. Fibroblasts were incubated with radiolabeled insulin at 4 degrees C, and internalization of insulin-receptor complexes was initiated by warming the cells to 37 degrees C. Within 2 min, 90% of the internalized radioactivity was composed of intact insulin-receptor complexes. The total number of complexes reached a maximum by 5 min and decreased rapidly thereafter with a t 1/2 of approximately 10 min. There was a distinct delay in the appearance, rate of rise, and peak of intracellular free and degraded insulin. The dissociation of insulin from internalized insulin-receptor complexes was markedly inhibited by monensin and chloroquine. Furthermore, chloroquine markedly increased the number of cross-linkable intracellular insulin-receptor complexes, as analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis autoradiography. These findings suggest that acidification of intracellular vesicles is responsible for insulin-receptor dissociation. Physical segregation of dissociated intracellular insulin from its receptor was monitored, based on the ability of dissociated insulin to rebind to receptor upon neutralization of acidic intracellular vesicles with monensin. The results are consistent with the view that segregation of insulin and receptor occurs 5-10 min after initiation of dissociation. These studies demonstrate the intracellular itinerary of insulin-receptor complexes, including internalization, dissociation of insulin from the internalized receptor within an acidified compartment, segregation of insulin from the receptor, and subsequent ligand degradation.


The year in cardiovascular medicine 2021: diabetes and metabolic disorders.
In the current paper, we review recently published studies that are helping us to understand how the treatment landscape for glucagon-like peptiide-1 receptor agonists and sodium glucose cotransporter 2 inhibitors is moving forward. We have also included relevant articles related to cardiovascular disease prevention in the setting of obesity, atherogenic dyslipidaemia and chronic kidney disease.


Real-Time t(14;18)(q32;q21) PCR assay combined with high-resolution capillary electrophoresis: a novel and rapid approach that allows accurate quantitation and size determination of bcl-2/JH fusion sequences.
Follicular lymphoma is characterized by the presence of the t(14;18)(q32;q21) chromosomal translocation that juxtaposes the bcl-2 gene at 18q21 with the immunoglobulin heavy chain (IgH) locus at 14q32. We have previously shown that accurate quantitation of t(14;18)-carrying cells in follicular lymphoma patients can be achieved by non-gel-based real-time TaqMan polymerase chain reaction (PCR; Applied Biosystems, Foster City, CA). Since our report, several studies have demonstrated that real-time PCR is highly sensitive and a reliable tool for evaluating treatment effectiveness and for following minimal residual disease in follicular lymphoma patients. Unfortunately, currently available real-time PCR methods do not determine the size of the amplification product, which is useful for excluding contamination and is commonly used as presumptive evidence of clonal identity or disparity when multiple samples from the same patient are analyzed. We describe a modified real-time PCR assay that rapidly allows accurate quantitation and precise determination of the size of the t(14;18) fusion sequence without the need for gel electrophoresis. In this assay, a consensus immunoglobulin heavy chain-joining region gene (JH) primer labeled at its 5' end with the fluorescent dye NED (Applied Biosystems) is included in the real-time PCR assay and thus is incorporated into the bcl-2/JH fusion product. The JH-NED primer did not interfere with the TaqMan probe fluorescent signal or target detection and allowed subsequent amplicon size determination by semiautomated high-resolution capillary electrophoresis.


[Retrocaval ureter].
To improve the diagnosis of retrocaval ureter. 20 cases of retrocaval ureter with an average age of 33.4 years were reported. The diagnosis of this disease depends on urography and retrograde ureterography. Operation was the principal treatment. Ureter orthopedics and reduction were performed in 19 cases of type 1 (low loop) except one case of type II (high loop). After removing 3 - 4 cm retrocaval ureter with pathological changes, we anastomosed the ureter without tension and regained its normal anatomic position. B-ultrasound and excretory urography showed no stenosis and improvement of hydronephrosis. Ureter orthopedics and reduction are ideal for the treatment of retrocaval ureter.


Transmastoid repair of superior semicircular canal dehiscence.
The aim of this study was to describe the successful operative management of a patient with superior semicircular canal dehiscence syndrome, using the transmastoid approach under local anaesthesia. The transmastoid approach was used to plug the superior semicircular canal. Post-operatively, the patient experienced significant improvement in his symptoms of sound- and pressure-induced dysequilibrium, autophony and imbalance. Successful operative management of superior semicircular canal dehiscence can be achieved via the transmastoid approach under local anaesthesia.


A novel strategy for analysis of gene homologues and segmental genome duplications.
Transformation-associated recombination (TAR) cloning allows selective isolation of a desired chromosomal region or gene from complex genomes. The method exploits a high level of recombination between homologous DNA sequences during transformation in the yeast Saccharomyces cerevisiae. We investigated the effect of nonhomology on the efficiency of gene capture and found that up to 15% DNA divergence did not prevent efficient gene isolation. Such tolerance to DNA divergence greatly expands the potential applications of TAR cloning for comparative genomics. In this study, we were able to use the technique to isolate nonidentical chromosomal duplications and gene homologues.


Modulation of absence seizures by the GABA(A) receptor: a critical rolefor metabotropic glutamate receptor 4 (mGluR4).
Experimental absence seizures are associated with perturbations in the presynaptic release of GABA and glutamate within thalamocortical circuitry. The release of both glutamate and GABA is regulated by group III metabotropic glutamate receptors (mGluRs). Therefore, we examined the susceptibility of mice lacking the mGluR4 subtype of mGluR (mGluR4(-/-)) versus their wild-type controls (mGluR4(+/+)) to absence seizures induced either by gamma-hydroxybutyrate (GHB) or the GABA(B) agonist (-) baclofen or by low doses of the GABA(A) receptor (GABA(A)R) antagonists pentylenetetrazole, bicuculline, or picrotoxin. There was no difference between mGluR4(-/-) and mGluR4(+/+) mice in threshold to absence seizures induced by either GHB or (-) baclofen. In contrast, the mGluR4(-/-) mice were markedly resistant to absence seizures induced by low doses of GABA(A)R antagonists. No differences were observed between mGluR4(-/-) and mGluR4(+/+) mice in threshold to clonic or tonic seizures induced by higher doses of GABA(A)R antagonists, strychnine, or electroshock, indicating that seizure resistance in the mGluR4(-/-) mice was restricted solely to absence seizures. The resistance of mGluR4(-/-) mice to absence seizures induced by GABA(A)R antagonists was mimicked by bilateral administration of a mGluR4 antagonist into the nucleus reticularis thalami (nRT) of mGluR4(+/+) mice. Conversely, intra-nRT administration of a mGluR4 agonist in mGluR4(+/+) mice exacerbated GABA(A)R-induced absence seizures. These data indicate that the presence of mGluR4 within nRT is critical to GABAergic modulation of thalamocortical synchronization in normal and pathological states, such as generalized absence epilepsy.


Potential Cardiologic Protective Effects of Acetylcholinesterase Inhibitors in Patients With Mild to Moderate Dementia.
In patients with mild to moderate dementia, acetylcholinesterase inhibitors (AChE-I) are used to improve cognitive functions, but bradycardia, conduction abnormalities, and hypotension are possible side effects because of the peripheral muscarinic M2 receptor stimulation. This study aimed to evaluate the main cardiologic clinical outcomes in patients with dementia who are on AChE-I. In this retrospective, monocentric, observational cohort study, 2 groups were considered: (1) patients with dementia because of the typical and atypical forms of Alzheimer disease treated with AChE-I and (2) cognitively unimpaired, matched control group. The primary end point was a composite of cardiovascular death, nonfatal acute myocardial infarction, myocardial revascularization, occurrence of stroke and/or transient ischemic attacks, and hospitalization for heart failure occurring during a mean of 3.1 years of follow-up. The secondary end points were each individual component of the primary end point, total mortality, noncardiovascular death, and incidence of pacemaker implant. Each group included 221 patients who were homogeneous in terms of age, gender, and main cardiovascular risk factors. Major adverse cardiovascular events occurred in 24 patients with dementia (2.1 per 100 patient-years) compared with 56 in control group (5.0 per 100 patient-years), p = 0.036. Even if not significant, the difference was mainly driven by myocardial revascularization (3.2% vs 6.8%) and hospitalization for heart failure (4.5% vs 14.5%). As expected, noncardiovascular mortality was significantly higher in the treatment group (13.6% vs 2.7% p = 0.006). No significant difference between the groups was observed in terms of other secondary outcomes. In conclusion, in patients with dementia, the use of AChE-I may be protective for cardiovascular outcomes, especially in reducing heart failure hospitalization and myocardial revascularization.


Early amelioration of neurologic deficit by lidoflazine after fifteen minutes of cardiopulmonary arrest in dogs.
A prospective, controlled, blind study was done to test the effect of a calcium entry blocker on the neurologic integrity of dogs after cardiopulmonary arrest. Ten male mongrel dogs were anesthetized, prepared with sterile technique, and instrumented for pulmonary arterial (PA) and systematic arterial pressure monitoring. A left thoracotomy and pericardotomy were performed. Cardiac arrest was produced by injecting KCl (1 mEq/kg) through the PA line, and the respirator was stopped. Full arrest was maintained for 15 minutes. Thereafter, the dogs were resuscitated with ventilation, internal massage, fluids, bicarbonate, epinephrine, and internal defibrillation. All dogs were resuscitated within 6 to 10 minutes. Five control dogs received saline placebo, and five dogs were treated with lidoflazine (1 mg/kg) IV drip immediately post resuscitation. All dogs were scored neurologically every two hours by a deficit grading scale. All treated dogs had spontaneous ventilation, reactive pupils and corneals, voluntary movements, and responses to tactile stimulation at 12 hours post resuscitation. Four of five control dogs had maximum deficit scores without improvement. The difference in neurologic scores between the treated and control groups became increasingly divergent with time, and was statistically significant (P less than .05) by four hours post resuscitation. Thus the calcium antagonist lidoflazine produces improvement in neurologic recovery in the first 12 hours after cardiopulmonary arrest in dogs.


Dementia risk prediction in individuals with mild cognitive impairment: a comparison of Cox regression and machine learning models.
Cox proportional hazards regression models and machine learning models are widely used for predicting the risk of dementia. Existing comparisons of these models have mostly been based on empirical datasets and have yielded mixed results. This study examines the accuracy of various machine learning and of the Cox regression models for predicting time-to-event outcomes using Monte Carlo simulation in people with mild cognitive impairment (MCI). The predictive accuracy of nine time-to-event regression and machine learning models were investigated. These models include Cox regression, penalized Cox regression (with Ridge, LASSO, and elastic net penalties), survival trees, random survival forests, survival support vector machines, artificial neural networks, and extreme gradient boosting. Simulation data were generated using study design and data characteristics of a clinical registry and a large community-based registry of patients with MCI. The predictive performance of these models was evaluated based on three-fold cross-validation via Harrell's concordance index (c-index), integrated calibration index (ICI), and integrated brier score (IBS). Cox regression and machine learning model had comparable predictive accuracy across three different performance metrics and data-analytic conditions. The estimated c-index values for Cox regression, random survival forests, and extreme gradient boosting were 0.70, 0.69 and 0.70, respectively, when the data were generated from a Cox regression model in a large sample-size conditions. In contrast, the estimated c-index values for these models were 0.64, 0.64, and 0.65 when the data were generated from a random survival forest in a large sample size conditions. Both Cox regression and random survival forest had the lowest ICI values (0.12 for a large sample size and 0.18 for a small sample size) among all the investigated models regardless of sample size and data generating model. Cox regression models have comparable, and sometimes better predictive performance, than more complex machine learning models. We recommend that the choice among these models should be guided by important considerations for research hypotheses, model interpretability, and type of data.


WITHDRAWN: Sports and sportsmen as role models - or otherwise - in the COVID-19 era.
This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.


Single-step immunosorbent preparation of F-protein from mouse liver with conservation of the allo-antigenic site, and determination of concentration in liver and serum.
A single-step immunopurification procedure is described for murine protein F, in which the T-cell-defined allo-antigenic site on the protein is fully conserved. The procedure is based on the use of a newly developed monoclonal antibody. The protein is isolated as a 42,500 mol. wt (F.1) and a 43,000 mol. wt (F.2) monomer. The content in liver, as estimated by radioimmune inhibition assay, is 0.083% and the yield is approximately one third. An assay of immunogenic activity in adoptive transfer, which detects the T-cell-defined site, provides a similar estimate of content in liver. The adoptive transfer assay yields concns of F-protein in serum of young mice of 0.5-1.2 X 10(-9)M, the lowest concn of protein known to induce complete immunological tolerance.


Convergence of self-report scales and Rorschach indexes of psychological distress: the moderating role of self-disclosure.
In this study, we addressed the weak associations found in research between self-report measures and the Rorschach test (Exner, 1978, 1991), from the perspective of Bornstein's (2002) "process dissociation framework." Specifically, in the study, we focused on the associations between self-report measures of psychological distress and their corresponding Rorschach indexes while inspecting the moderating role of self-disclosure. A total of 59, nonpatient Israeli adults participated in a 2-session study. In the first session, they completed self-report scales measuring self-disclosure and psychological distress (suicidality, depression, and loneliness). In the second session, the Rorschach test was administered and coded. The participants were divided into high and low self-disclosure groups. A convergence between self-report and Rorschach measures of psychological distress was found only among high self-disclosers. In the discussion, we address the theoretical and clinical implications of these findings.


Determination of the enantiomers of ketamine and norketamine in human plasma by enantioselective liquid chromatography-mass spectrometry.
A sensitive enantioselective liquid chromatographic assay with mass spectrometric detection has been developed and validated for the simultaneous determination of plasma concentrations of (R)- and (S)-ketamine, and (R)- and (S)-norketamine. The compounds were extracted from human plasma using solid-phase extraction and then directly injected into the LC-MS system for detection and quantification. Enantioselective separations were achieved on a liquid chromatographic chiral stationary phase based upon immobilized alpha(1)-acid glycoprotein (the Chiral AGP column). The separations were achieved using a mobile phase composed of 2-propanol-ammonium acetate buffer (10 mM, pH 7.6) (6:94, v/v), a flow-rate of 0.5 ml/min and a temperature of 25 degrees C. Under these conditions, the analysis time was 20 min. Detection of the ketamine, norketamine and bromoketamine (internal standard) enantiomers was achieved using selected ion monitoring at m/z 238.1, 224.1 and 284.0, respectively. Extracted calibration curves were linear from 1 to 125 ng/ml per enantiomer for each analyte with correlation coefficients better than 0.9993 and intra- and inter-day RSDs of less than 8.0%. The method was applied to samples from a clinical study of ketamine in pain management.


Exposure to urban green space may both promote and harm mental health in socially vulnerable neighborhoods: A neighborhood-scale analysis in New York City.
There is growing evidence that exposure to green space can impact mental health, but these effects may be context dependent. We hypothesized that associations between residential green space and mental health can be modified by social vulnerability. We conducted an ecological cross-sectional analysis to evaluate the effects of green space exposure on mental disorder related emergency room (ER) visits in New York City at the level of census tract. To objectively represent green space exposure at the neighborhood scale, we calculated three green space exposure metrics, namely proximity to the nearest park, percentage of green space, and visibility of greenness. Using Bayesian hierarchical spatial Poisson regression models, we evaluated neighborhood social vulnerability as a potential modifier of greenness-mental disorder associations, while accounting for the spatially correlated structures. We found significant associations between green space exposure (involving both proximity and visibility) and total ER visits for mental disorders in neighborhoods with high social vulnerability, but no significant associations in neighborhoods with low social vulnerability. We also identified specific neighborhoods with particularly high ER utilization for mental disorders. Our findings suggest that exposure to green space is associated with ER visits for mental disorders, but that neighborhood social vulnerability can modify this association. Future research is needed to confirm our finding with longitudinal designs at the level of individuals.


Embedding new technology into clinical ultrasound practice: Is role extension for sonographers the key to improving patient pathways?
MicroUS is a new imaging technique that may have potential to reliably monitor prostate disease and therefore release capacity in MRI departments. Firstly, however, it is essential to identify which healthcare staff may be suitable to learn to use this modality. Based on previous evidence, UK sonographers may be well placed to harness this resource. Currently, there is sparse evidence on the performance of MicroUS for monitoring prostate disease but early findings are encouraging. Although its uptake is increasing, it is believed that only two sites in the UK have MicroUS systems and only one of those uses just sonographers to undertake and interpret this new imaging technique. UK sonographers have a history of role extension dating back several decades and have proven repeatedly that they are reliable and accurate when measured against a gold standard. We explore the background of UK sonographer role extension and postulate that sonographers are best placed to adopt and embed new imaging techniques and technology into routine clinical practice. This is of particular importance given the dearth of ultrasound focussed radiologists in the UK. To effectively introduce challenging new work streams, multi-professional collaboration in imaging, alongside sonographer role extension, will ensure precious resources are maximised thus ensuring optimum patient care. UK sonographers have repeatedly demonstrated reliability in many areas of role extension in various clinical settings. Early data indicate that the adoption of MicroUS for use in prostate disease surveillance may be another role suited to sonographers.


Population-based estimate for the correlation of the Oncotype Dx Breast Recurrence Score® result and Ki-67 IHC MIB-1 pharmDx in HR+, HER2-, node-positive early breast cancer.
The United States Food and Drug Administration recently approved a Ki-67 immunohistochemistry (IHC) assay to identify patients with early breast cancer at high disease recurrence risk. The Oncotype Dx Breast Recurrence Score® assay has been validated in hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) invasive breast cancer (IBC) to predict chemotherapy benefit and distant recurrence risk, regardless of nodal status. This study assessed the correlation between Recurrence Score® (RS) results and the Ki-67 IHC MIB-1 pharmDx assay. HR+, HER2-, N1 IBC samples with RS results were examined by Ki-67 IHC; 311 specimens were collected, including 275 without regard to RS ("unselected RS") and 36 more with RS 26-100; 12 were lymph node negative upon pathology report review, and one had no Ki-67 score, leaving 262 unselected RS and 298 total samples. Spearman rank correlation was calculated using the unselected samples and a weighted rank correlation using all samples. A receiver operating characteristic (ROC) curve for predicting high RS (26-100) from Ki-67 was constructed. The Spearman rank correlation between Ki-67 and RS results was moderately positive (unselected RS samples: 0.396; 95% confidence interval [CI] 0.288-0.493; all samples: 0.394; 95% CI 0.294-0.486). While 71% of samples with RS 26-100 had Ki-67 ≥ 20%, 75% with RS 0-25 had Ki-67 < 20%. ROC area under the curve was 0.792 (95% CI 0.725-0.859). The moderately positive correlation is consistent with previous analyses suggesting the Oncotype Dx® assay and Ki-67 IHC MIB-1 assay should not be used interchangeably in clinical practice.


Metabolic-associated fatty liver disease in relation to site-specific and multiple-site subclinical atherosclerosis.
Non-alcoholic fatty liver disease (NAFLD) and the newly proposed metabolic-associated fatty liver disease (MAFLD) were each associated with subclinical atherosclerosis. However, there is limited evidence on risk of atherosclerosis in individuals who meet the criteria for one but not the other. We aimed to investigate the associations of MAFLD or NAFLD status with site-specific and multiple-site atherosclerosis. This is a prospective cohort study involving 4524 adults within the MJ health check-up cohort. Logistic regression model was used to estimate odds ratios (ORs) and confidence intervals (CIs) for subclinical atherosclerosis (elevated carotid intima-media thickness [CIMT], carotid plaque [CP], coronary artery calcification [CAC] and retinal atherosclerosis [RA]) associated with MAFLD or NAFLD status, MAFLD subtypes and fibrosis status. MAFLD was associated with higher risks of elevated CIMT, CP, CAC and RA (OR: 1.41 [95% CI 1.18-1.68], 1.23 [1.02-1.48], 1.60 [1.24-2.08], and 1.79 [1.28-2.52], respectively), whereas NAFLD per se did not increase risk of atherosclerosis except for elevated CIMT. Individuals who met both definitions or the definition for MAFLD but not NAFLD had higher risk of subclinical atherosclerosis. Among MAFLD subtypes, MAFLD with diabetes had the highest risk of subclinical atherosclerosis, but the associations did not differ by fibrosis status. Stronger positive associations were observed of MAFLD with multiple-site than single-site atherosclerosis. In Chinese adults, MAFLD was associated with subclinical atherosclerosis, with stronger associations for multiple-site atherosclerosis. More attention should be paid to MAFLD with diabetes, and MAFLD might be a better predictor for atherosclerotic disease than NAFLD.


[Safety, efficacy and control of the menstrual cycle by a monophasic oral contraceptive containing 75 mcg of gestodene and 30 mcg of ethynyl estradiol].
Al oral monophasic contraceptive formulation containing gestodene (75 mcg) and ethynilestradiol (30 mcg) is evaluated concerning its safety, efficacy and cycle-control. Sixty-seven healthy women were included, allowing a total of 574 evaluable cycles. This formulation showed a high degree of efficacy, with no pregnancies after its utilization. Side affects were similar or lower to other reported with another hormonal contraceptive oral formulations. Hematologic, biochemical or urinary parameters were not altered. An acceptable menstrual pattern was maintained. In conclusion, this formulation constitutes an oral contraceptive with a high efficacy rate, a well degree of acceptability and with a side effects profile similar or lower than those produced by other oral contraceptives.


Flavobacterium nackdongense sp. nov., a cellulose-degrading bacterium isolated from sediment.
A Gram-negative, non-motile, rod-shaped bacterial strain, designated GS13T, was isolated from sediments in a branch of the Nackdong River in Sangju, Korea. Optimal growth occurred at pH 7.0, 20 °C, and 0% NaCl. Phylogenetic analyses using 16S rRNA showed that strain GS13T is a member of the genus Flavobacterium, with highest similarity to Flavobacterium soyangense IMCC26223T (97.0%). The DNA G+C content of strain GS13T was 36.2 mol%. The dominant fatty acids were summed feature 3 (C16:1ω7c and/or C16:1ω6c) and iso-C15:0. The major polar lipids were phosphatidylethanolamine, three unidentified aminolipids, three unidentified lipids, and one unidentified aminophospholipid. The predominant respiratory quinone was MK-6. Our data demonstrate that strain GS13T can be distinguished from closely-related Flavobacterium species. Thus, strain GS13T is a novel Flavobacterium species, and we propose the name Flavobacterium nackdongense sp. nov. The type strain is GS13T (=KCTC 62569T = JCM 32765T).


Using Social Media for Breastfeeding Support.
To explore the variables that lead to sustained, exclusive breastfeeding to 6 months for breastfeeding women of the millennial generation who follow social media breastfeeding support groups (SMBSGs). Repeated-measures, longitudinal, mixed-methods design. Online across 21 countries. Convenience sample of exclusively breastfeeding millennial women (N = 241) who followed at least one of 17 SMBSGs. Participants completed the following: a demographic questionnaire; the Perceived Work Demand Scale; the Perceived Family Demand Scale; the Perceived Health-Related Social Support From Facebook Friends Measure; and the Breastfeeding Confidence, Knowledge, and Attitudes Measure. Using structural equation modeling, I examined relationships among personal factors; competing situational demands; social support; and confidence in, knowledge of, attitude toward, and sustainability of breastfeeding. Age, education, and competing work and family demands were all predictive of social support. Breastfeeding social support had a direct effect on participants' breastfeeding confidence, knowledge, and attitudes (F = 4.96, R2 = .07, p < .002). Furthermore, within SMBSGs, exclusive breastfeeding to 6 months was reported to be three times (66%) greater than the U.S. national average (22%). Interventions aimed at providing women with resources to gain breastfeeding social support, such as SMBSGs, may be vehicles to improve women's confidence, knowledge, and attitudes and, therefore, increase the potential for exclusive breastfeeding to 6 months.


Aphasia and apraxia in dementia: cognitive regression or focal symptoms?
A review is given of the neuropsychological conceptualizations of aphasia and apraxia in SDAT. In the beginning of this century localisationism was prevailing. Later, developmental and cognitive psychology gave an important impetus to reconsider these symptoms in an holistic framework. More recently, since the application of new brain imaging techniques, there is a revival of localizing conceptualizations.


Effect of perampanel on aggression in patients with refractory focal epilepsy: A 6-month longitudinal study.
Clinical trials have demonstrated the efficacy of perampanel for the treatment of epilepsy. However, patients treated with this and other antiepileptic drugs often exhibit aggressive behaviors. We investigated the clinical factors contributing to aggression in patients with refractory focal epilepsy during 6 months of adjunctive perampanel treatment. This was a single-center longitudinal study involving patients treated with perampanel (starting dose, 2 mg/day; maximal dose, 12 mg/day). Patients were assessed with an aggression questionnaire (Korean version of Aggression Questionnaire [AQ-K]) and the hospital anxiety depression scale (HADS) at the beginning of the study and after receiving treatment for 6 months. Paired t-tests were used to compare AQ-K and HADS scores at the beginning of the study with those recorded at the end, and stepwise linear regression models were applied to identify predictive factors. Thirty-two patients (mean age, 42.4 ± 10.3 years) successfully completed the 6-month study. The AQ-K and HADS scores increased after 6 months of adjunctive perampanel treatment (p < .1). The HADS scores related to depression at baseline predicted changes in total AQ-K scores, whereas the change in this HADS score was a predictor of physical and verbal aggression. A perampanel dose of ≥8 mg was a predictive factor for changes in anger and HADS scores related to depression after 6 months. Unexpectedly, concomitant use of topiramate had protective effects on AQ-K scores (including for verbal aggression and anger) in patients receiving perampanel. Depressive symptoms and a high dose of perampanel are potential predictors for aggression, whereas concomitant use of topiramate is protective against aggression in patients receiving perampanel for focal epilepsy.


Correlation between RICTOR overexpression and amplification in advanced solid tumors.
Rapamycin-insensitive companion of mTOR (RICTOR) is a key component of mammalian target of rapamycin (mTOR) complex 2 (mTORC2), and promotes cellular proliferation and survival through the activation of downstream AGC kinase family members. The amplification of RICTOR has been proposed as a therapeutically relevant genomic alteration. However, other than next-generation sequencing, precise diagnostic methods to detect RICTOR amplification in advanced solid cancers have not been fully explored. We performed immunohistochemistry (IHC) analysis on solid tumor tissues from 435 cancer patients. Overexpression of RICTOR was found in 213 cases (49.0 %: 1+, 29.4 %; 2+, 15.2 %; 3+, 4.4 %) consisting of 111 colorectal cancers, 42 gastric cancers, 16 renal cell carcinomas, 8 soft tissue sarcomas, 6 hepatocellular carcinomas, 6 cholangiocarcinomas, 4 lung cancers, and 37 other tumors. RICTOR overexpression was heterogeneous (stained < 50 % of the tumor volume) in 32.4 % (12/37) of IHC-positive cases. We performed fluorescence in situ hybridization (FISH) in 37 RICTOR-overexpressed IHC-positive cases (1+, 12; 2+, 11; 3+, 14) and 13 IHC-negative solid tumors. FISH enabled us to detect RICTOR amplification in 7/12 (58.3 %) IHC 1+, 10/11 (90.9 %) IHC 2+, and 11/14 (78.6 %) IHC 3+ cases. In total, there was amplification in 75.7 % (n = 28) of the RICTOR-overexpressed cases, according to FISH. There was RICTOR amplification in only 7.7 % of the RICTOR IHC-negative cases. RICTOR amplification was significantly more common in IHC-positive cases than in IHC-negative cases (p < 0.0001). The IHC results correlated well with those of FISH (r = 0.60). RICTOR overexpression is more common in solid tumors than previously reported in cases detected by next-generation sequencing. This discrepancy may be caused by intratumoral heterogeneity. In conclusion, heterogeneous RICTOR overexpression is common in solid tumors and RICTOR IHC can be used as a screening tool to detect RICTOR amplification.


Insecticidal activities of Citrus aurantifolia essential oil against Aedes aegypti (Diptera: Culicidae).
In the recent time, global attention for the control of vectors has shifted from chemical insecticides to botanicals. In the present investigation, authors attempted to evaluate the efficacy of peel and leaf essential oil (EO) of Citrus aurantifolia against Aedes aegypti. The results revealed that both the oils possess more ovicidal activity (LC50 value of 5.26 ppm and 17.71 ppm for leaf and peel oil respectively at 72 h) than larvicidal activity. As larvicide, the essential oil from the peel of Citrus aurantifolia showed rapid effect with LC50 value of 128.81 ppm at 24 h which reduced to 106.77 ppm at 72 h while the leaf oil showed slow effect with LC50 value of 188.59 ppm, 107.37 ppm and 104.59 ppm at 24 h, 48 h and 72 h respectively. Again, the two essential oils did not show significant adulticidal activity. GC-MS analysis of both the oils recorded presence of different compounds. As a major constituent compound of the leaf EO of Citrus aurantifolia, citral was tested for their ovicidal, larvicidal and adulticidal activities against Aedes aegypti. The result showed highest ovicidal activities (LC50 value of 4.84 ppm at 72 h) of citral followed by larvicidal (LC50 value of 87.02 ppm at 24 h) and adulticidal (LC50 value of 103.88 ppm at 24 h) activities. From this study, it can be concluded that the essential oil extracted from the leaf and peel of Citrus aurantifolia and one of its major constituent compound citral can be included in the mosquito control programme of Aedes aegypti.


Anthropometry analysis of nutritional indicators in Indonesian adolescents.
Malnutrition is an emerging health problem that has challenged healthcare authorities worldwide. This study aims to determine anthropometric values and the nutritional status of Indonesian school adolescents. In total, 510 students (288 girls and 222 boys) studying at Darul Ihsan Islamic Boarding School Banda Aceh participated in this cross-sectional study. All participants were examined for weight, height, and body mass index (BMI). The BMI category was classified using BMI criteria for the Asia-Pacific population. For data analysis, a descriptive analysis, chi-square (p < 0.05), and independent sample t-test (p < 0.05) were employed. The rate of malnutrition among school adolescents in Banda Aceh was underweight 36.67% (girls = 47.6% and boys = 52.4%) and overweight/obesity 21.96% (girls = 60.66% and boys = 39.33%). There was a significant difference in the number of overweight girls and boys: 127 (60.2%) and 84 (39.8%) p = 0.007, respectively. Obesity I was more common among girls than boys: (31; 66%) versus (16; 34%), p = 0.020. There was a slight difference in the prevalence of being underweight: 89 (47.6%) versus 98 (52.4%), p = 0.520, and no difference in the number of girls and boys with obesity II: 6 (50%) versus 6 (50%), respectively. This study reports multiple malnutrition problems in adolescent schools in Banda Aceh, namely being underweight, overweight, and obesity. This calls for urgent attention by healthcare authorities to initiate public awareness campaigns to curtail malnutrition.


Changing patterns of infectious diseases.
In the 20 years that have passed since I received my medical degree, some of the most evident, striking, and interesting changes in patterns of diseases have occurred among those due to transmissible agents. Among other changes are the recognition of new diseases, new clinical manifestations for old diseases, new ecologic niches for traditional pathogens, and new modes of disease transmission. Implicated causes for these changes include alterations in lifestyle such as sexual behaviour, leisure activity, and dietary trends, along with the impact of immigration and the effects of medical progress. A review of these changing patterns demonstrates the dynamic nature of medicine and suggests lessons for medical education.


Relationship between cold temperature and cardiovascular mortality, with assessment of effect modification by individual characteristics: Ibaraki Prefectural Health Study.
Cold temperature has been reported to contribute to cardiovascular mortality, but it is not clear which people are more susceptible to cold temperature. The relationship between ambient temperature and mortality was examined in 3,593 subjects from the Ibaraki Prefectural Health Study who died of cardiovascular disease during a mean follow-up period of 9.7±4.0 years. Daily values of meteorological variables were obtained from the Japan Meteorological Agency. Time-stratified case cross-over analysis was used. The multivariate odds ratios (ORs; 95% confidence interval) per 1°C decrease in daily maximum temperature over the day of death and the 2 days prior to this day adjusted for relative humidity were 1.018 (1.003-1.034) for all cardiovascular deaths and 1.025 (1.003-1.048) for stroke deaths. Risk-stratified analysis showed that younger subjects aged <80 years and those with hyperglycemia were more susceptible to cold temperature. The OR of all cardiovascular deaths related to cold temperature was 1.034 (1.012-1.056) for subjects aged <80 years, and that of stroke deaths was 1.076 (1.023-1.131) for those with hyperglycemia. Exposure to cold temperature triggers cardiovascular deaths. Additionally, younger age and hyperglycemia could enhance susceptibility to cold temperature.


Stream habitat structure influences macroinvertebrate response to pesticides.
Agricultural pesticides continue to impair surface water ecosystems, although there are few assessments of interactions with other modifications such as fine sediment and physical alteration for flood drainage. We, therefore, surveyed pesticide contamination and macroinvertebrates in 14 streams along a gradient of expected pesticide exposure using a paired-reach approach to differentiate effects between physically modified and less modified sites. Apparent pesticides effects on the relative abundance of SPEcies At Risk (SPEAR) were increased at sites with degraded habitats primarily due to the absence of species with specific preferences for hard substrates. Our findings highlight the importance of physical habitat degradation in the assessment and mitigation of pesticide risk in agricultural streams.


Current state of the treatment of perforating veins.
Perforating veins may play a role in the development of chronic venous insufficiency and ulceration. There is renewed interest in minimally invasive treatments vs historic surgical options. Current indications for treatment, technical success, and evidence for clinical efficacy are summarized. Existing recommendations include perforator closure in Clinical, Etiology, Anatomy, and Pathophysiology class 5 or class 6 disease through percutaneous thermal ablation, subfascial endoscopic perforator surgery, open surgery, or sclerotherapy. Closure rates for percutaneous thermal ablation are reported as 60% to 80% initially. More recanalization and de novo perforator formation have been reported than after thermal saphenous closure. Ultrasound-guided foam sclerotherapy has shown promise in perforator closure and wound healing, but with variable success rates. Regardless of method used, successful closure of perforators appears predictive of wound healing with minimal morbidity. However, the power and design of all studies supporting this are far from robust, and more work is needed.


Effect of vitamin D3 supplementation on blood pressure in adults: An updated meta-analysis.
Previous randomized clinical trials (RCTs) of the effects of vitamin D3 supplementation (VD3S) on blood pressure have generated inconsistent results. We evaluated the effect of VD3S on systolic blood pressure (SBP) and diastolic blood pressure (DBP) in a meta-analysis. Literature searches of PubMed, Scopus, Ovid, and Google scholar for publications in English were conducted up to April 2015. RCTs that assessed the effect of VD3S on SBP and DBP were selected. A total of 30 RCTs with 41 arms including 4744 participants were included. The mean duration of the studies was 5.6 ± 4.0 months, and doses of VD3S varied between 200 and 12,000 IU/day. VD3S had no effect on SBP (-0.68 mmHg, 95%CI: -2.19 to 0.84), and DBP (-0.57 mmHg, 95%CI: -1.36 to 0.22). Subgroup analysis revealed that daily vitamin D3 therapy at a dose of >800 IU/day for <6 months in subjects ≥50 years old reduced both SBP and DBP (p < 0.001). In addition, VD3S showed hypotensive effects in healthy subjects and hypertensive patients, but a hypertensive effect in overweight and obese subjects. However, after excluding overweight and obese subjects, VD3S significantly reduced SBP and DBP. VD3S in combination with calcium supplementation significantly elevated SBP (3.64 mmHg, 95%CI: 3.15-4.13) and DBP (1.71 mmHg, 95%CI: 1.25-2.18). No evidence of publication bias was found. The effects of VD3S on blood pressure depend on dose of supplementation, treatment regimens, trial duration, and population subgroup. Supplementation may be beneficial at daily doses >800 IU/day for <6 months in subjects ≥50 years old.


Patient doses in multi-slice CT and the importance of optimisation.
Substantive surveys of patient doses arising from CT examinations have been conducted in our Hospital. In the first instance doses were measured on a single-slice Siemens Plus 4 scanner. A similar survey was conducted initially following commissioning of a Siemens multi-slice Sensation scanner and subsequently after some effort was made to optimise scanning protocols. Doses are reported in terms of dose-length products (DLPs) and as effective doses. The optimisation process on the multi-slice scanner resulted in a reduction in DLP values by between 14% and 58%. With two exceptions, significantly lower or comparable DLP values were obtained when meaningful comparisons were made with results previously obtained with the single-slice scanner. Specific results for the multi-slice scanner in terms of the median DLP in mGy.cm (and median effective dose in mSv) are: routine brain, 660 (1.5); routine chest, 195 (4.0); chest with portal liver phase, 370 (7.2); routine chest with high resolution component, 250 (5.1); chest/abdomen/pelvis with contrast, 560 (11.0); routine abdomen without contrast, 145 (2.4); routine abdomen with contrast 215 (3.6); routine abdomen/pelvis without contrast, 230 (4.4); routine abdomen/pelvis with contrast, 345 (6.3); abdomen/pelvis triple phase, 715 (13.3); renal scan, 260 (4.6); lumbar spine, 445 (7.2); cerebral angiography, 240 (0.58); pulmonary angiography, 165 (3.4); aortic angiography, 305 (5.7). Based on the survey findings possible values for CT examination local diagnostic reference levels (LDRLs) are suggested.


Endoscopic submucosal tunnel dissection for early esophageal squamous cell carcinoma in patients with cirrhosis: A propensity score analysis.
Although early esophageal squamous cell carcinoma (EESCC) with cirrhosis is a relatively rare clinical phenomenon, the management of EESCC in cirrhotic patients continues to be a challenge. To evaluate the feasibility, safety, efficacy and long-term survival outcomes of endoscopic submucosal tunnel dissection (ESTD) for treating EESCC in patients with cirrhosis. This was a single-center retrospective cohort study. We examined 590 EESCC patients who underwent ESTD between July 14, 2014, and May 26, 2021, from a large-scale tertiary hospital. After excluding 25 patients with unclear lesion areas or pathological results, the remaining 565 patients were matched at a ratio of 1:3 by using propensity score matching. A total of 25 EESCC patients with comorbid liver cirrhosis and 75 matched EESCC patients were ultimately included in the analysis. Parametric and nonparametric statistical methods were used to compare the differences between the two groups. The Kaplan-Meier method was used to create survival curves, and differences in survival curves were compared by the log-rank test. Among 25 patients with liver cirrhosis and 75 matched noncirrhotic patients, there were no significant differences in intraoperative bleeding (P = 0.234), 30-d post-ESTD bleeding (P = 0.099), disease-specific survival (P = 0.075), or recurrence-free survival (P = 0.8196). The mean hospitalization time and costs were significantly longer (P = 0.007) and higher (P = 0.023) in the cirrhosis group than in the noncirrhosis group. The overall survival rate was significantly lower in the cirrhosis group (P = 0.001). ESTD is technically feasible, safe, and effective for patients with EESCC and liver cirrhosis. EESCC patients with Child-Pugh A disease seem to be good candidates for ESTD.


An efficient synthesis of vinylsilanes from acylsilanes and alkyl 1-phenyl-1H-tetrazol-5-yl sulfones. Brook vs Smiles rearrangement.
[reaction: see text] Vinylsilanes are formed in high yields in the reaction of representative acyl(trimethyl)silanes with anions generated from Kocienski's sulfones.


A possible mechanism of choleretic action of 3-(2,4,5-triethoxybenzoyl)-propionic acid (AA-149) in dogs.
The choleretic action of 3-(2,4,5-triethoxybenzoyl)propionic acid (AA-149) was studied in anesthetized dogs. AA-149 produced a dose-dependent increase of the bile flow with both i.v. and intrajejunal administration of doses 1 mg/kg and higher. Biliary clearance of 14C-erythritol showed that AA-149 stimulated canalicular bile formation without enhancement of water secretion and/or inhibition of bile reabsorption in the biliary ductules and ducts. AA-149 did not increase the excretion of bile acids into the bile, but enhanced the excretion of the biliary electrolytes, in particular sodium ion, in proportion to an increase of the bile flow. About 3--4% of AA-149 administered i.v. was excreted into the bile during the first 1 h period, so that biliary AA-149 was insufficient to increase the bile flow via its osmotic effect. These results strongly suggest that the choleretic action of AA-149 is attributable to stimulation of a bile acid-independent bile formation in the canaliculi coupled with an active sodium transport system.