BRCA promoter methylation in sporadic versus BRCA germline mutation-related breast cancers.
In breast cancer, BRCA promoter hypermethylation and BRCA germline mutations are said to occur together rarely, but this property has not yet been translated into a clinical test. Our aim in this study was to investigate the diagnostic value of BRCA1/2 methylation in distinguishing breast carcinomas of BRCA1 and BRCA2 germline mutation carriers from sporadic breast carcinomas using a recently developed BRCA methylation assay based on methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA). MS-MLPAs were performed to assess BRCA1 and BRCA2 methylation in breast carcinoma tissues from 39 BRCA1 and 33 BRCA2 germline mutation carriers, 80 patients with sporadic breast cancer, and normal breast tissues from 5 BRCA1 and 4 BRCA2 mutation carriers and 5 nonmutation carriers. Methylation frequencies varied considerably between CpG sites across the BRCA1 and BRCA2 promoters. Some CpG sites were methylated more frequently in BRCA1/2-related than in sporadic carcinomas, whereas other CpG sites were methylated more frequently in sporadic carcinomas, with large variances in sensitivity and specificity as a consequence. The diagnostic value of BRCA promoter methylation analysis in distinguishing BRCA1/2-related from sporadic breast carcinomas seems to be considerably dependent on the targeted CpG sites. These findings are important for adequate use of BRCA methylation analysis as a prescreening tool for BRCA germline genetic testing or to identify BRCAness patients who may benefit from targeted therapies such as poly(adenosine diphosphate-ribose) polymerase inhibitors.


Vanilloid receptor type 1-immunoreactive nerves in the rat urinary bladder and primary afferent neurones: The effects of age.
The vanilloid receptor (VR1) is a molecular integrator of various painful stimuli, including capsaicin, acid and high temperature. VR1 protein functions both as a receptor for capsaicin and a transducer of noxious thermal stimuli. In addition, VR1 is well characterised at the terminals of sensory nerves involved in the pain pathway. VR1 is also expressed in a capsaicin-sensitive and peptide-containing sub-population of primary sensory nerves. Indirect immunohistochemistry was used to examine the distribution of nerves immunoreactive (ir) for VR1 in the base of the urinary bladder and in the neurones of the lumbosacral dorsal root ganglia (L1-L2 and L6-S1) of young adult (3 months) and aged (24 months) male rats. Semi-quantitative estimations of nerve densities were assessed and quantitative studies were also used to examine the effects of age on the percentage of VR1-ir dorsal root ganglion neurones. The bladder base in young adults showed dense VR1-ir fibres within the urothelium and in the subepithelium and fibres ranging from sparse to moderate in number in the muscle coat. In comparison to the young animals, the aged rats showed sparse to moderate densities of VR1-ir nerves in the subepithelium and sparse fibres in the muscle layers. In the lumbosacral dorsal root ganglia the percentage of VR1-ir neuronal profiles showed a significant reduction from (mean +/- SEM) 17.8 +/- 2% in the young adult to 12 +/- 1.6 in the aged rats. The present findings suggest that the effects of VR1 on bladder function (nociception and reflex micturition) are influenced by age and the reduction with age of VR1-ir neurones in the dorsal root ganglia could also have important implications for the micturition reflex.


Right Ventricular Free Wall Strain and Congestive Hepatopathy in Patients with Acute Worsening of Chronic Heart Failure: A CATSTAT-HF Echo Substudy.
Right ventricular (RV) function is an important predictor of prognosis in patients with heart failure. However, the relationship of the RV free wall longitudinal strain (RV FWS) and the degree of hepatic dysfunction during the acute worsening of heart failure (AWHF) is unknown. We sought to determine associations of RV FWS with laboratory liver function tests and parameters of RV function including tricuspid annular plane systolic excursion (TAPSE), RV fractional area change (RV FAC), maximal tricuspid jet velocity (TR Vmax), RV S' velocity, and estimated RV systolic pressure (RVSP). A total of 42 AWHF patients from the CATSTAT-HF study were stratified in two groups by the RV FWS median (-16.5%). Patients < RV FWS median had significantly prolonged international normalized ratio (INR; p = 0.002), increased total bilirubin (p < 0.001) and alkaline phosphatase (ALP; p = 0.020), and decreased albumin (p = 0.005) and thrombocytes (p = 0.017) compared to patients > RV FWS median. RV FWS independently correlated to total bilirubin (β = 0.457, p = 0.004), ALP (β = 0.556, p = 0.002), INR (β = 0.392, p = 0.022), albumin (β = -0.437, p = 0.013), and thrombocytes (β = -404, p = 0.038). Similarly, TAPSE, RV FAC, and RV S' significantly correlated with RV FWS. In conclusion, RV impairment, reflected in reduced RV FWS, is independently associated with a higher degree of hepatic dysfunction among patients with AWHF (CATSTAT-HF ClinicalTrials gov number, NCT03389386).


Glycomic mapping of pseudomucinous human ovarian cyst glycoproteins: identification of Lewis and sialyl Lewis glycotopes.
Expression of sialyl Lewis x (sLe(x)) and sialyl Lewis a (sLe(a)) on cell-surface glycoproteins endows cells with the ability to adhere to E-, P-, and L-selectins present on endothelia, platelets, or leukocytes. Special arrangements of these glycotopes in cancers are thought to play a key role in metastasis. Previous studies have mostly described membrane-bound sLe(x) and sLe(a) activities. In this report, the major O-glycans of the secreted human ovarian cyst sialoglycoproteins from a Le(a+) nonsecretor individual (human ovarian cyst sample 350) were characterized by MS/MS analyses and immuno-/lectin-chemical assays. The results showed that HOC 350 carries a large number of epitopes for sLe(x), sLe(a), and Le(a) reactive antibodies. Advanced MS/MS sequencing coupled with mild periodate oxidation and exoglycosidase digestions further revealed that the O-glycans from HOC 350 are mostly of core 1 and 2 structures, extended and branched on the 3-arm with both type I and type II chains, complete with variable degrees of terminal sialylation and/or fucosylation to yield the sLe(x) or sLe(a) epitopes. Thus, the underlying core and peripheral backbone structures are similar to that of a previously proposed composite structural model for nonsialylated human ovarian cysts O-glycans, but with some notable distinguishing structural features in addition to sialylation.


First drive-through pharmacy services in Taiwan.
Taiwan has separated drug prescribing and drug dispensing services since 1997. Because of this, patients with chronic illness as well as those with diseases that have a relatively stable status may have their prescriptions refilled in nearby clinic pharmacies without having to go to hospitals. Shuang-Ho Hospital in Taipei, Taiwan, implemented a drive-through pharmacy service as a more convenient refilling system to provide patients in need with a more effective way to refill their prescriptions. To assess the efficacy of this new refilling system, changes in patient drug prescription behavior were compared 6 months before and 6 months after the system was deployed. We found an increase in the overall refilling prescription rate, with an increased use of online reservations (7.9% vs. 4.9%, p < 0.001), an increased proportion of medications picked up (93.0% vs. 88.1%, p < 0.001) after the implementation period, and an elevation in the percentage of patients using drive-through pharmacy services (45.4% vs. 28.9%, p < 0.001; second vs. first quarter, respectively) during the 6 months after the implementation period. Generally, the prescription refilling rate for all population categories at Shuang-Ho Hospital increased significantly after the drive-through service was provided (51.1% vs. 50.2%, p < 0.01). The middle-aged population group (40-65 years of age) was found to utilize the drive-through prescription service more than other age groups. The drive-through pharmacy provides patients with convenient access to pick up refilling prescriptions in a shorter time than ordinary pharmacy service. During a short-term follow-up, an overall increase in the prescription refilling rate was noted after the drive-through service was put into place. Our survey revealed that an upward of 90% of the patients were satisfied with the drive-through service. Future promotion of the service may help patients effectively utilize drive-through pharmacy prescription refilling and enhance disease control.


Large-scale survey of Cryptosporidium spp. in chickens and Pekin ducks (Anas platyrhynchos) in Henan, China: prevalence and molecular characterization.
Few data are available on the molecular characterization of Cryptosporidium spp. in chickens and ducks in China. In this study, 2579 faecal samples from 46 chicken farms and eight Pekin duck farms in 21 prefectures in Henan Province were examined. The overall infection rate of Cryptosporidium was 10.6% (163/1542) in layer chickens (10 out of 17 farms), 3.4% (16/473) in broilers (five out of 29 farms), and 16.3% (92/564) in Pekin ducks (four out of eight farms), respectively. The highest infection rates were observed in 31-day-old to 60-day-old layer chickens (24.6%) and 11-day-old to 30-day-old Pekin ducks (40.3%). The season of highest prevalence in chickens was spring (15.6%) and the lowest was winter (P<0.01). One hundred and eighty-seven Cryptosporidium-positive samples were analysed by polymerase chain reaction (PCR)-restriction fragment length polymorphism analysis of the small subunit rRNA gene, and 55 were further analysed by DNA sequencing of the PCR products. Two Cryptosporidium species were identified: Cryptosporidium baileyi (184/187) on 15 chicken farms and four duck farms, and Cryptosporidium meleagridis (3/187) on three layer chicken farms. C. baileyi was the predominant Cryptosporidium species, found in all age groups of chickens and all Cryptosporidium-positive ducks examined, whereas C. meleagridis was only identified in 31-day-old to 120-day-old layer chickens. Considering the large size of the chicken industry and the close contact between chickens and humans, and that C. meleagridis is the third most common Cryptosporidium parasite in humans, then C. meleagridis could potentially become an emerging zoonosis in some areas in China.


Laparoscopic Duhamel Procedure with Ex-Anal Rectal Transection for Right-Sided Hirschsprung's Disease.
Increased defecation frequency and soiling are common complications of surgery for right-sided Hirschsprung's disease (HD). Though the laparoscopic Duhamel procedure is a favorable option in right-sided HD, the conventional laparoscopic technique is time consuming and has complications that are associated with the reservoir. In this study, we described a modified laparoscopic Duhamel technique with ex-anal rectal transection combined with the Deloyer's procedure for right-sided HD. Between March 2010 and January 2015, 18 right-sided HD underwent this modified laparoscopic Duhamel procedure (MLDP). The main modifications were to mobilize the colon and to dissect the retrorectal space under laparoscopy, pull out, and transect ex-anally by using a linear stapling device through a transverse incision on posterior wall of the rectum. Seven age-matched patients who underwent a conventional laparoscopic Duhamel procedure (CLDP) between March 2008 and December 2010 were included as the control group. Demographics, surgical procedures, operative data, postoperative complications, and clinical outcomes were compared between these two groups. Operative time was significantly shorter in the MLDP group (150 minutes versus 195 minutes; P = .03). There was no significant difference in mean timespan to obtain a normal defecation frequency (3.8 months versus 3.6 months), incidence of soiling (11.1% versus 14.3%; P = .34), and constipation (5.6% versus 14.3%; P = .69). Pouchitis were not found in the MLDP group, whereas 2 patients in the CLDP group (28.6%) presented with pouchitis and intractable diarrhea, requiring spur division. The incidence of postoperative enterocolitis was not significantly different in the two groups (11.1% in MLDP versus 14.3% in CLDP; P = .68). All 22 patients had a normal defecation over 4 years of age. Laparoscopic Duhamel with ex-anal rectal transection is a simple, easy-to-learn, and effective procedure for right-sided HD. It has low postoperative pouchitis because of a short pouch.


A Novel Variant of OCT4 Entitled OCT4B3 is Expressed in Human Bladder Cancer and Astrocytoma Cell Lines.
Alternative splicing is an important mechanism that regulates gene expression and function in human cells. OCT4, a crucial pluripotency marker in embryonic stem/carcinoma cells generates several spliced variants in different cell types and cancers. The expression of OCT4 in cancers has been challenged in many studies. The existence of several OCT4 spliced variants and absence of specific discriminating primers is the main reason of this controversy. Therefore, using specific primers and discriminating OCT4 variants from each other might help to reduce these discrepancies in carcinogenesis and stem cell researches. 17 various human cancer, pluripotent and normal cells were cultured and their RNAs were extracted. Related cDNAs were synthesized and the expression pattern of OCT4 variants was investigated by RT-PCR assay. PCR products were cloned into pTZ57R/T vector and their authenticity was confirmed by DNA sequencing. Expression pattern of OCT4 variants (OCT4A, OCT4B and OCT4B1) was analyzed by RT-PCR assay and the authenticity of PCR products was confirmed by DNA sequencing. A novel spliced variant of OCT4 was discovered and named as OCT4B3. This variant was very similar to OCT4B2 transcript except that 207-nt of exon 1b is lost. Moreover, the expression pattern of OCT4B3 variant was investigated in 17 human cell types, where its expression was only found in astrocytoma and bladder cancer cell types 1321N1 and 5637, respectively. OCT4 variants are differentially expressed in various human cancer cell lines. Moreover, a novel variant of OCT4, OCT4B3, was detected in two human cancer cell lines of bladder carcinoma (5637) and brain astrocytoma (1321N1) for the first time.


An In Vivo Assessment of the Effect of Hexane Extract from Endlicheria paniculata Branches and Its Main Compound, Methyldehydrodieugenol B, on Murine Sponge-Induced Inflammation.
The present study aims to explore the anti-inflammatory potential activity of the hexane extract from branches (HEB) of Endlicheria paniculata (Lauraceae) and its main compound, methyldehydrodieugenol B, in the inflammatory response induced by a murine implant sponge model. HPLC-ESI/MS analysis of HEB led to the identification of six chemically related neolignans, with methyldehydrodieugenol B as the main compound. An in silico analysis of the pharmacokinetic parameters of the identified compounds suggested moderate solubility but good absorption and biodistribution in vivo. Thus, the treatment of mice with HEB using in vivo assays indicated that HEB promoted pro-inflammatory, antiangiogenic, and antifibrogenic effects, whereas treatment with methyldehydrodieugenol B caused anti-inflammatory, antifibrogenic, and antiangiogenic effects. The obtained results shown the therapeutic potential of HEB and methyldehydrodieugenol B in the treatment of pathologies associated with inflammation and angiogenesis, including chronic wounds.


Phospholipase A2 activity of peroxiredoxin 6 promotes invasion and metastasis of lung cancer cells.
Peroxiredoxins (PRDX) are a family of thiol-dependent peroxidases. Among the six mammalian members of this family, PRDX6 is the only protein that additionally exhibits phospholipase A(2) (PLA(2)) activity. The physiologic role of this interesting PRDX6 feature is largely unknown at present. In this study, we show that PRDX6 increases the metastatic potential of lung cancer cells. Functional analyses of the enzymatic activities of PRDX6, using specific pharmacologic inhibitors and mutagenesis studies, reveal that both peroxidase and PLA(2) activities are required for metastasis. Specifically, peroxidase activity facilitates the growth of cancer cells, and PLA(2) activity promotes invasiveness. Further investigation of the latter event discloses that PLA(2) activity promotes accumulation of arachidonic acid, which, in turn, induces the invasive pathway involving p38 kinase, phosphoinositide 3-kinase, Akt, and urokinase-type plasminogen activator. This study is the first to define the functions of the enzymatic activities of PRDX6 in metastasis and to show the involvement of arachidonic acid in PRDX6 action in intact cells. These novel findings provide a significant step toward elucidating the role of PRDX6 in cancer and the mechanism of its action. Mol Cancer Ther; 9(4); 825-32. (c)2010 AACR.


Human papillomavirus E2 down-regulates the human telomerase reverse transcriptase promoter.
The transcriptional regulation of the human telomerase reverse transcriptase (hTERT) gene is a critical step in transformation and differentiation. Human papillomavirus E2 protein inhibits cell growth in HPV-infected cells and triggers apoptosis in HeLa cells. Because E2 induces cell growth suppression and senescence, we hypothesize that the protein may modulate cellular gene expression related to these processes. In this report, we demonstrate that E2 inhibits the hTERT promoter. The mapping of the E2-responsive region of hTERT reveals that Sp1 is important for E2-mediated repression of this promoter in 293T cells. Site-directed mutagenesis data on the hTERT promoter show that E2 does not abolish E-Box-mediated transcription and represses promoter activity via the Sp1 binding site. Furthermore, chromatin immunoprecipitation assays indicate that E2 is actively recruited to the hTERT promoter region. Our findings provide novel insights into the biological function of human papillomavirus E2.


Serum immunoglobulin G subclasses and serum immunoglobulin A in acute bronchiolitis in infants.
Serum IgG subclasses and Serum IgA were studied in 43 infants with acute bronchiolitis and 20 healthy infants. IgG subclasses were determined by a capture ELISA and IgA was quantified by turbidimetry. IgG1 concentrations were significantly lower in infants with bronchiolitis than in normal infants. The other IgG subclasses and IgA did not differ between the groups. The subgroups of infants with bronchiolitis who had previously suffered from otitis media or bronchitis, had significantly lower IgG2 than the other infants with bronchiolitis. The same was found for infants with bronchiolitis who had suffered from three or more lower respiratory tract infections. In infants who had suffered from upper or lower respiratory infections before the acute bronchiolitis, IgA was significantly higher than in infants without previous respiratory infections. Ten infants with bronchiolitis (23%) had IgG1 deficiency, that is values below the lower reference limit calculated in a population of healthy Norwegian infants. No healthy infants had any IgG1 deficiency. No infant with bronchiolitis had IgG2 or IgG3 deficiency. The low IgG1 values found in infants with acute bronchiolitis, may be one cause for infants to be more susceptible to RS virus infections.


Intermittent pneumatic compression in fracture and soft-tissue injuries healing.
Current methods of fracture care use various adjuncts to try and decrease time to fracture union, improve fracture union rates and enhance functional recovery. Intermittent pneumatic compression (IPC), one such modality, is used in the management of both fractures and soft-tissue injuries. A search of PubMed, Medline, CINAHL, DH data and Embase databases was performed using the following keywords 'intermittent pneumatic compression', 'fracture healing' and 'soft tissue healing'. Sixteen studies on the use of IPC in fracture and soft-tissue healing were identified. These studies demonstrated that IPC facilitates both fracture and soft-tissue healing with rapid functional recovery. IPC appears to be an effective modality to enhance fracture and soft-tissue healing. However, the number of subjects in human studies is small, and adequately powered randomized controlled trials in humans are required to produce stronger clinically relevant evidence.


Intraluminal pressures in the seminiferous tubules and in different regions of the epididymis in the rat.
Intraluminal pressures in the seminiferous tubules and in various regions along the epididymis of the rat were measured by micropuncture using a servo-nulling pressure transducer system. The intraluminal hydrostatic pressure in the testis was significantly lower than that in all regions of the epididymis. There was an increasing pressure gradient from the caput to the cauda epididymidis. Spontaneous contractions were observed in all parts of the epididymis but not in the seminiferous tubules. The amplitude of contraction in the epididymis increased from the caput to the proximal cauda. However, an appreciable decrease in the amplitude occurred in the distal cauda, although the frequency of contraction declined from the proximal caput to the distal cauda with substantial reductions in the mid-caput and the proximal cauda.


Reporter-based growth assay for systematic analysis of protein degradation.
Protein degradation by the ubiquitin-proteasome system (UPS) is a major regulatory mechanism for protein homeostasis in all eukaryotes. The standard approach to determining intracellular protein degradation relies on biochemical assays for following the kinetics of protein decline. Such methods are often laborious and time consuming and therefore not amenable to experiments aimed at assessing multiple substrates and degradation conditions. As an alternative, cell growth-based assays have been developed, that are, in their conventional format, end-point assays that cannot quantitatively determine relative changes in protein levels. Here we describe a method that faithfully determines changes in protein degradation rates by coupling them to yeast cell-growth kinetics. The method is based on an established selection system where uracil auxotrophy of URA3-deleted yeast cells is rescued by an exogenously expressed reporter protein, comprised of a fusion between the essential URA3 gene and a degradation determinant (degron). The reporter protein is designed so that its synthesis rate is constant whilst its degradation rate is determined by the degron. As cell growth in uracil-deficient medium is proportional to the relative levels of Ura3, growth kinetics are entirely dependent on the reporter protein degradation. This method accurately measures changes in intracellular protein degradation kinetics. It was applied to: (a) Assessing the relative contribution of known ubiquitin-conjugating factors to proteolysis (b) E2 conjugating enzyme structure-function analyses (c) Identification and characterization of novel degrons. Application of the degron-URA3-based system transcends the protein degradation field, as it can also be adapted to monitoring changes of protein levels associated with functions of other cellular pathways.


Characterization of butyrylcholinesterase antagonism of cocaine-induced hyperactivity.
Although there are several published demonstrations that exogenous butyrylcholinesterase (EC 126.96.36.199) works to antagonize cocaine in vivo, a systematic characterization of the enzyme-drug interaction is lacking as is confirmation of the mechanism of effect. This has been addressed using cocaine-induced locomotor activity in mice as a behavioral endpoint. The enzyme was effective, but the enzyme dose-antagonist effect relationship revealed an asymptotic partial maximum effect. This effect was not due to dose-dependent enzyme pharmacokinetics or to a stimulant effect of the cocaine metabolites but rather to partial metabolism of cocaine. Since neither metabolite of cocaine inhibited enzyme activity as potently as cocaine, partial metabolism is not likely due to end-product inhibition. The enzyme reduced the maximum effect of cocaine on locomotor activity. The mechanistic data are generally consistent: the enzyme was inactive against the nonester dopamine/norepinephrine uptake inhibitor, nomifensine, and a paraoxon-inactivated sample of enzyme was ineffective. However, the enzyme was effective against bupropion, a nonester dopamine uptake inhibitor.


Dynamics of the Ablowitz-Ladik soliton train.
It is shown that dynamics of a train of N weakly interacting Ablowitz-Ladik solitons with (almost) equal velocities and masses is governed by the complex Toda chain model. The integrability of the complex Toda chain model provides the means to describe analytically various dynamical regimes of the N-soliton train and to predict initial soliton parameters responsible for each of the regimes. Numerical simulations corroborate well analytical predictions. A specific feature arising for the discrete soliton train system is the appearance of an additional (with respect to the lattice spacing) spatial scale-intersoliton distance. We comment on interplay between both spatial scales.


Aegilops tauschii Accessions with Geographically Diverse Origin Show Differences in Chromosome Organization and Polymorphism of Molecular Markers Linked to Leaf Rust and Powdery Mildew Resistance Genes.
Aegilops tauschii (2n = 2x = 14) is a diploid wild species which is reported as a donor of the D-genome of cultivated bread wheat. The main goal of this study was to examine the differences and similarities in chromosomes organization among accessions of Ae. tauschii with geographically diversed origin, which is believed as a potential source of genes, especially determining resistance to fungal diseases (i.e., leaf rust and powdery mildew) for breeding of cereals. We established and compared the fluorescence in situ hybridization patterns of 21 accessions of Ae. tauschii using various repetitive sequences mainly from the BAC library of wheat cultivar Chinese Spring. Results obtained for Ae. tauschii chromosomes revealed many similarities between analyzed accessions, however, some hybridization patterns were specific for accessions, which become from cognate regions of the World. The most noticeable differences were observed for accessions from China which were characterized by presence of distinct signals of pTa-535 in the interstitial region of chromosome 3D, less intensity of pTa-86 signals in chromosome 2D, as well as lack of additional signals of pTa-86 in chromosomes 1D, 5D, or 6D. Ae. tauschii of Chinese origin appeared homogeneous and separate from landraces that originated in western Asia. Ae. tauschii chromosomes showed similar hybridization patterns to wheat D-genome chromosomes, but some differences were also observed among both species. What is more, we identified reciprocal translocation between short arm of chromosome 1D and long arm of chromosome 7D in accession with Iranian origin. High polymorphism between analyzed accessions and extensive allelic variation were revealed using molecular markers associated with resistance genes. Majority of the markers localized in chromosomes 1D and 2D showed the diversity of banding patterns between accessions. Obtained results imply, that there is a moderate or high level of polymorphism in the genome of Ae. tauschii determined by a geographical origin, which we proved by cytogenetic and molecular markers analysis. Therefore, selected accessions might constitute an accessible source of variation for improvement of Triticeae species like wheat and triticale.


Inhibiting 5-hydroxytryptamine receptor 3 alleviates pathological changes of a mouse model of Alzheimer's disease.
Extracellular amyloid beta (Aβ) plaques are main pathological feature of Alzheimer's disease. However, the specific type of neurons that produce Aβ peptides in the initial stage of Alzheimer's disease are unknown. In this study, we found that 5-hydroxytryptamin receptor 3A subunit (HTR3A) was highly expressed in the brain tissue of transgenic amyloid precursor protein and presenilin-1 mice (an Alzheimer's disease model) and patients with Alzheimer's disease. To investigate whether HTR3A-positive interneurons are associated with the production of Aβ plaques, we performed double immunostaining and found that HTR3A-positive interneurons were clustered around Aβ plaques in the mouse model. Some amyloid precursor protein-positive or β-site amyloid precursor protein cleaving enzyme-1-positive neurites near Aβ plaques were co-localized with HTR3A interneurons. These results suggest that HTR3A -positive interneurons may partially contribute to the generation of Aβ peptides. We treated 5.0-5.5-month-old model mice with tropisetron, a HTR3 antagonist, for 8 consecutive weeks. We found that the cognitive deficit of mice was partially reversed, Aβ plaques and neuroinflammation were remarkably reduced, the expression of HTR3 was remarkably decreased and the calcineurin/nuclear factor of activated T-cell 4 signaling pathway was inhibited in treated model mice. These findings suggest that HTR3A interneurons partly contribute to generation of Aβ peptide at the initial stage of Alzheimer's disease and inhibiting HTR3 partly reverses the pathological changes of Alzheimer's disease.


Molecular mechanisms of ethanol-induced pathogenesis revealed by RNA-sequencing.
Acinetobacter baumannii is a common pathogen whose recent resistance to drugs has emerged as a major health problem. Ethanol has been found to increase the virulence of A. baumannii in Dictyostelium discoideum and Caenorhabditis elegans models of infection. To better understand the causes of this effect, we examined the transcriptional profile of A. baumannii grown in the presence or absence of ethanol using RNA-Seq. Using the Illumina/Solexa platform, a total of 43,453,960 reads (35 nt) were obtained, of which 3,596,474 mapped uniquely to the genome. Our analysis revealed that ethanol induces the expression of 49 genes that belong to different functional categories. A strong induction was observed for genes encoding metabolic enzymes, indicating that ethanol is efficiently assimilated. In addition, we detected the induction of genes encoding stress proteins, including upsA, hsp90, groEL and lon as well as permeases, efflux pumps and a secreted phospholipase C. In stationary phase, ethanol strongly induced several genes involved with iron assimilation and a high-affinity phosphate transport system, indicating that A. baumannii makes a better use of the iron and phosphate resources in the medium when ethanol is used as a carbon source. To evaluate the role of phospholipase C (Plc1) in virulence, we generated and analyzed a deletion mutant for plc1. This strain exhibits a modest, but reproducible, reduction in the cytotoxic effect caused by A. baumannii on epithelial cells, suggesting that phospholipase C is important for virulence. Overall, our results indicate the power of applying RNA-Seq to identify key modulators of bacterial pathogenesis. We suggest that the effect of ethanol on the virulence of A. baumannii is multifactorial and includes a general stress response and other specific components such as phospholipase C.


Intraarterial 5-FU infusion with or without oral testolactone treatement in irresectable pancreatic cancer.
The results of a prospective study of 19 patients with pancreatic cancer treated with regional intraarterial 5-FU infusion with or without oral tesolactone are reported. No primary mortality was noted. No measurable tumor remission was seen. The median survival time from the state of infusion therapy was 6.5 months. Median time of hospitalization from the start of infusion therapy was 2 months, which corresponds approximately to 30% of remaining survival time. No significant improvement of quality of life was registered during the treatment period. The results indicate that intrrarterial regional 5-FU--neither with nor without testolactone--cannot be recommended for patients with irresectable pancreatic cancer.


Ultra-wideband microwave photonic filter with a high Q-factor using a semiconductor optical amplifier.
An ultra-wideband microwave photonic filter (MPF) with a high quality (Q)-factor based on the birefringence effects in a semiconductor optical amplifier (SOA) is presented, and the theoretical fundamentals of the design are explained. The proposed MPF along orthogonal polarization in an active loop operates at up to a Ku-band and provides a tunable free spectral range from 15.44 to 19.44 GHz by controlling the SOA injection current. A prototype of the equivalent second-order infinite impulse response filter with a Q-factor over 6300 and a rejection ration exceeding 41 dB is experimentally demonstrated.


[Secondary amyloidosis (AA) and renal disease].
Amyloidosis is a disease resulting from extracellular deposition of fibrillar protein in various organs. AA amyloidosis may complicate chronic inflammatory diseases, chronic infections and another chronic diseases. We review 31 patients (13 males and 18 females) with biopsy proven renal or rectal AA amyloidosis, referred to out hospital between january 1999 and november 2002. Renal failure was defined as serum creatinine > or = 1.5 mg/dl. Mean age was 58.4 +/- 15.7 years. The causes of AA amyloidosis were an underlying chronic rheumatologic disease (51.6%), chronic infection (41.9%) and a chronic inflammatory intestinal disorder (6.5%). Renal failure (RF) was detected in 20 patients (61.2%) and proteinuria and hematuria were found in 90.3% and 45.5 respectively. Proteinuria at diagnosis was 5.2 +/- 3.9 g/24 h and mean serum creatinine 3.5 +/- 3.7 mg/dl. Survival of patients without dialysis was 66.8 (51.1% RF, 90.9% non-RF) and 53.4% (38.2 RF, 77.9% non-RF) at 12 and 24 months respectively (p = 0.017). End-stage renal disease developed in 13 patients (41.9%). Ten patients were maintained on hemodialysis and 3 on CAD. Survival in dialysis at 6 and 12 months was 68.3% and 42.7% respectively. Fifteen patients died and the main causes of death were: infections (46.6) haemorrhagic complications (33.3%), cardiovascular events (13.3%) and cachexia (6.6%).


[CYP2C19 genetic polymorphism and monitoring voriconazole plasma concentrations in the treatment and prevention of invasive fungal disease for hematological patients].
Objective: To evaluate the effects of CYP2C19 genetic polymorphism on the plasma concentration of voriconazole in patients with hematological disease and the value of serial monitoring plasma concentrations in the treatment and prevention of invasive fungal disease (IFD). Methods: From January 2016 to December 2016, 65 hematological patients who received voriconazole intravenous administration for the treatment of invasive fungal disease were enrolled in this study. The population CYP2C19 polymorphism of voriconazole were performed using PCR-Pyrosequencing. The trough plasma concentrations of vriconazole (Ctrough) was detected by ultra performance liquid chromatography tandem mass spectrometry. Results: Based on the genotype analysis, 65 subjects were identified as extensive metabolizers' group (30 cases) and poor metabolizers' group (35 cases). The Ctrough of the 65 patients were detected for 169 times totally, and there was a significant difference of Ctrough values between the two groups [0.98(0.38-2.08) mg/L vs 2.19(1.53-4.27) mg/L, z=10.286, P<0.001]. The medium of Ctrough in 65 hematological patients were described. Lack of response to therapy was more frequent in patients with voriconazole levels <1.5 mg/L (50.0%) than in those with voriconazole levels >1.5 mg/L (20.5%) (P=0.052). And the risk of adverse events was more frequent in patients with voriconazole levels >5.5 mg/L (80.0%) than in those with voriconazole levels ≤5.5 mg/L (8.3%) (χ2=11.689, P=0.020). Conclusion: Patients with CYP2C19 wild-type phenotype are extensive metabolizers, their Ctrough of voriconazole are significantly lower than patients with CYP2C19 non-wild-type phenotype (poor metabolizers). Appropriate concentrations of vriconazole can improve the efficacy and safety during treatment.


Causal dissipation for the relativistic dynamics of ideal gases.
We derive a general class of relativistic dissipation tensors by requiring that, combined with the relativistic Euler equations, they form a second-order system of partial differential equations which is symmetric hyperbolic in a second-order sense when written in the natural Godunov variables that make the Euler equations symmetric hyperbolic in the first-order sense. We show that this class contains a unique element representing a causal formulation of relativistic dissipative fluid dynamics which (i) is equivalent to the classical descriptions by Eckart and Landau to first order in the coefficients of viscosity and heat conduction and (ii) has its signal speeds bounded sharply by the speed of light. Based on these properties, we propose this system as a natural candidate for the relativistic counterpart of the classical Navier-Stokes equations.


Bereaved Military Dependent Spouses and Children: Those Left Behind in a Decade of War (2001-2011).
U.S. military service members die from a variety of causes (i.e., accidents, combat, illnesses, homicide, suicide, and terrorism) while on duty and in greater numbers during times of war, leaving behind bereaved dependent family members. Identifying characteristics of these dependent families improves our understanding of their unique needs, helps educate service providers who offer assistance to these surviving family members, and better informs policy addressing their health and well-being. This study describes deceased U.S. military service members (DSMs) who died on active duty between September 11, 2001 and September 11, 2011 and their surviving dependent spouses and children. Characteristics of DSMs (service branch, rank, and cause of death) and characteristics of spouse-with-children and spouse-only families (ages of dependents, time since loss, and distance from a military installation) were examined. 15,938 DSMs died from a variety of causes (e.g., accidents, combat, and illnesses). 55% of DSMs had dependent spouses and 56% of those spouses had children. Most surviving dependent spouses and children were young (mean ages = 32.8, 10.3 years; SD = 9.3, 7.3 years, respectively) at the time of DSM death. Many of these young dependents were related to a DSM who experienced a sudden and violent death. 60% of spouse-with-children families and 58% of spouse-only families lived farther than 60 miles from a military installation. Time since loss (range = 1.3-11.3 years) did not predict distance to installation. Findings characterize surviving spouses and their children, suggest potential risk for problematic grief outcomes, and underscore the importance of educating service providers about how to support military survivor family health and resilience.


Genotype-by-environment interaction in Holstein heifer fertility traits using single-step genomic reaction norm models.
The effect of heat stress on livestock production is a worldwide issue. Animal performance is influenced by exposure to harsh environmental conditions potentially causing genotype-by-environment interactions (G × E), especially in highproducing animals. In this context, the main objectives of this study were to (1) detect the time periods in which heifer fertility traits are more sensitive to the exposure to high environmental temperature and/or humidity, (2) investigate G × E due to heat stress in heifer fertility traits, and, (3) identify genomic regions associated with heifer fertility and heat tolerance in Holstein cattle. Phenotypic records for three heifer fertility traits (i.e., age at first calving, interval from first to last service, and conception rate at the first service) were collected, from 2005 to 2018, for 56,998 Holstein heifers raised in 15 herds in the Beijing area (China). By integrating environmental data, including hourly air temperature and relative humidity, the critical periods in which the heifers are more sensitive to heat stress were located in more than 30 days before the first service for age at first calving and interval from first to last service, or 10 days before and less than 60 days after the first service for conception rate. Using reaction norm models, significant G × E was detected for all three traits regarding both environmental gradients, proportion of days exceeding heat threshold, and minimum temperature-humidity index. Through single-step genome-wide association studies, PLAG1, AMHR2, SP1, KRT8, KRT18, MLH1, and EOMES were suggested as candidate genes for heifer fertility. The genes HCRTR1, AGRP, PC, and GUCY1B1 are strong candidates for association with heat tolerance. The critical periods in which the reproductive performance of heifers is more sensitive to heat stress are trait-dependent. Thus, detailed analysis should be conducted to determine this particular period for other fertility traits. The considerable magnitude of G × E and sire re-ranking indicates the necessity to consider G × E in dairy cattle breeding schemes. This will enable selection of more heat-tolerant animals with high reproductive efficiency under harsh climatic conditions. Lastly, the candidate genes identified to be linked with response to heat stress provide a better understanding of the underlying biological mechanisms of heat tolerance in dairy cattle.


Laparoscopic proctectomy: oncologic considerations.
The role of laparoscopic proctectomy in rectal cancer has not clearly been defined. Publications on long-term outcomes after laparoscopic proctectomy is lacking and there is a wide variation of practice patterns of rectal cancer management. Current data supports the feasibility of laparoscopic proctectomy for rectal cancer but due to surgeon, patient and tumor related factors open technique may be favored. Current series suggest that laparoscopic proctectomy can be performed with similar oncologic adequacy with regards to, circumferential resection margin, distal margin, local recurrence and quality of life. Ongoing trials will provide evidence clarifying the role of laparoscopic proctectomy in rectal cancer. Until then, high-level laparoscopic skills and meticulous preoperative evaluation of both patient and tumor can identify appropriate candidates.


Classification of Southeast Asian mints (Mentha spp.) based on simple sequence repeat markers.
Mentha is a complex genus encompassing many species as a consequence of their interspecific hybridization and polyploidy. Southeast Asian mints have been poorly distinguished though they are widely used for culinary and medical purposes. In this study, we have analyzed Southeast Asian mints and known varieties as well as a related Lamiaceae species (Nepeta sp.) using simple sequence repeat (SSR) markers and leaf morphology. Two types of mints were clearly distinguished based on their venation pattern and leaf shape index. We developed 12 SSR markers that allowed good amplification in the Mentha and another Lamiaceae species. In the SSR-based phylogram, the Mentha lines could be delimited into groups I-VI. The Southeast Asian mints divided into groups I and II, and the phylogram separated most of the available species, with groups I and II containing the known species M. × cordifolia and M. arvensis, respectively. The separation of the two groups was supported by a population structure analysis. The SSR markers developed in this study enabled the simultaneous classification of mints and will help improve our understanding of the genetic composition of known mint varieties and as yet unclassified Southeast Asian mints.


Critical connections: health and academics.
While it is a national priority to support the health and education of students, these sectors must better align, integrate, and collaborate to achieve this priority. This article summarizes the literature on the connection between health and academic achievement using the Whole School, Whole Community, and Whole Child (WSCC) framework as a way to address health-related barriers to learning. A literature review was conducted on the association between student health and academic achievement. Most of the evidence examined the association between student health behaviors and academic achievement, with physical activity having the most published studies and consistent findings. The evidence supports the need for school health services by demonstrating the association between chronic conditions and decreased achievement. Safe and positive school environments were associated with improved health behaviors and achievement. Engaging families and community members in schools also had a positive effect on students' health and achievement. Schools can improve the health and learning of students by supporting opportunities to learn about and practice healthy behaviors, providing school health services, creating safe and positive school environments, and engaging families and community. This evidence supports WSCC as a potential framework for achieving national educational and health goals.


Salt preference: age and sex related variability.
Salt preference was assessed in 60 adults of 18-21 yrs of age (30 males and 30 females) and in 60 children of 7-12 yrs of age (30 boys and 30 girls). Subjects rated the preference on Likert scale for popcorns of five salt concentrations (OM, 1M, 2M, 3M and +3M). Statistical analysis using Two way ANOVA revealed statistically significant effect of age and sex on salt preference (F4,100 = 15.027, P < 0.01) and One Way ANOVA revealed statistically significant sex difference in salt preference of adults (F4,50 = 16.26, P < 0.01) but no statistically significant sex difference in salt preference of children (F4,50 = 4.08, P > 0.05). Dietary experiences during development and more physical activity in children may be responsible for higher salt preference in children while finding no sex variability in children favours the role of sex hormones in salt preference of male and females.


[Evolution of in vivo and in vitro tests during specific immunotherapy against hymenoptera venoms].
In this study, on a population of 26 patients with systemic reactions after hymenoptera stings, different immunobiological tests have been used to confirm the sensitivity to hymenoptera venom. These 26 patients were divided into two groups according to the stage of their immunotherapy: group 1 (n = 8) included all assessments from day 0 (before IT) and group 2 (n = 16) the assessments at 1 and 2 years during IT. In general, there was a good correlation between skin tests, RAST and histamine release. The results show that the IgE level seems to be more informative than histamine release and that measurement of the specific IgE level is more sensitive with Allerbio allergen compared with other allergens. However these preliminary results must be confirmed on a statistically significant number of patients. HL by Agf is less sensitive than that done with Ags.


Cultural competency of a mobile, customized patient education tool for improving potential kidney transplant recipients' knowledge and decision-making.
Patients considering renal transplantation face an increasingly complex array of choices as a result of the revised kidney transplant allocation system. Decision aids have been shown to improve patient decision-making through the provision of detailed, relevant, individualized clinical data. A mobile iOS-based application (app) including animated patient education and individualized risk-adjusted outcomes following kidney transplants with varying donor characteristics and DSA waiting times was piloted in two large US transplant programs with a diverse group of renal transplant candidates (N = 81). The majority (86%) of patients felt that the app improved their knowledge and was culturally appropriate for their race/ethnicity (67%-85%). Patients scored significantly higher on transplant knowledge testing (9.1/20 to 13.8/20, P < .001) after viewing the app, including patients with low health literacy (8.0 to 13.0, P < .001). Overall knowledge of and interest in living and deceased donor kidney transplantation increased. This pilot project confirmed the benefit and cultural acceptability of this educational tool, and further refinement will explore how to better communicate the risks and benefits of nonstandard donors.


Transcriptome analysis reveals temperature-regulated antiviral response in turbot Scophthalmus maximus.
Megalocytivirus is a severe pathogen to turbot (Scophthalmus maximus), a popular aquaculture species in many countries. In this study, we investigated the effect of temperature on the antiviral response of turbot at transcriptome level. We found that when turbot were infected with megalocytivirus RBIV-C1 at low temperatures (14 °C, 16 °C, and 18 °C), viral replication was undetectable or moderate and no fish mortality occurred; in contrast, when turbot were infected with RBIV-C1 at high temperatures (20 °C, 22 °C, and 24 °C), viral replication was robust and 100% host mortality was observed. During the course of viral infection, downward temperature shift curbed viral replication and augmented host survival, whereas upward temperature shift promoted viral replication and reduced host survival. Comparative transcriptome analyses were conducted to examine the whole-genome transcription of turbot infected with RBIV-C1 at 16 °C and 22 °C for 4 days (samples S16-4d and S22-4d, respectively) and 8 days (samples S16-8d and S22-8d, respectively). The results showed that compared to S22-4d and S22-8d, 1600 and 5927 upregulated unigenes of various functional categories were identified in S16-4d and S16-8d, respectively. Of these genes, 22 were immune-related, most of which were detected in S16-8d and exhibited more genetic subtypes in S16-8d than in S16-4d. In addition, upregulated genes associated with cell junctions and cell membrane were also identified. These results indicate that temperature had a profound effect on the global transcription of turbot, which consequently affects the immune as well as physical resistance of the fish against viral infection.


[Use of comet assay for the risk assessment of oil- and chemical-industry workers].
The comet assay is a fluorescent microscopic method that is able to detect DNA strand-breaks even in non-proliferative cells in samples with low cell counts. The aim of the authors was to measure genotoxic DNA damage and assess oxidative DNA damage caused by occupational exposure in groups exposed to benzene, polycyclic aromatic carbohydrates and styrene at the workplace in order to clarify whether the comet assay can be used as an effect marker tool in genotoxicology monitoring. In addition to the basic steps of the comet assay, one sample was treated with formamido-pirimidine-DNA-glycolase restriction-enzyme that measures oxidative DNA damage. An increase was observed in tail moments in each group of untreated and Fpg-treated samples compared to the control. It can be concluded that occupational exposure can be detected with the method. The comet assay may prove to be an excellent effect marker and a supplementary technique for monitoring the presence or absence of genotoxic effects.


The introduction of a phytase gene from Bacillus subtilis improved the growth performance of transgenic tobacco.
Phytate, the main form of phosphorus storage in plant seeds, is well known to be an anti-nutrient and a major source of phosphorus pollution in animal manure. To improve phosphorus bio-availability, we introduced a recently characterized phytase from Bacillus subtilis into the cytoplasm of tobacco cells. Although the introduction of acid fungal phytase from Aspergillus niger in previous studies did not result in any phenotypic changes in tobacco, here we show that a tobacco line transformed with a neutral phytase exhibited phenotypic changes in flowering, seed development, and response to phosphate deficiency. The transgenic line showed an increase in flower and fruit numbers, small seed syndrome, lower seed IP6/IP5 ratio, and enhanced growth under phosphate-starvation conditions compared with the wildtype. The results suggest that the over-expression of Bacillus phytase in the cytoplasm of tobacco cells shifts the equilibrium of the inositol phosphate biosynthesis pathway, thereby making more phosphate available for primary metabolism. The approach presented here can be applied as a strategy for boosting productivity in agriculture and horticulture.


Mounting of biological microsamples on protein coats for TaOTO non-coated scanning electron microscopy.
Gelatin-coated glass cover slips were immersed in a mixture of glutaraldehyde and tannic acid, and rinsed in bovine or human serum. The gelatin-coated cover slips were first placed in a human blood cell suspension, and subsequently placed in a solution of glutaraldehyde or osmium tetroxide. This preliminary mounting of the blood cells eliminated troublesome centrifugations in the tannin-osmium-thiocarbohydrazide-osmium (TaOTO) impregnation. The blood cells seldom detached from the cover slips even when the specimens were dehydrated with ethanol and critical point dried with liquid carbon dioxide. Both the mounting media as well as the mounted cells were intensely stained by the TaOTO method, and exhibited no charging in the scanning electron microscope even at acceleration voltages of 25 kV. The scanning images of the white blood cells with their microvilli were clearly visible with sharp contrast.


Pyomyositis after vaginal delivery.
Pyomyositis is a purulent infection of skeletal muscle that arises from haematogenous spread, usually with abscess formation. It can develop after a transient bacteraemia of any cause. This type of infection has never been reported before in the literature after vaginal delivery. A 34-year-old woman had progressive severe pain in the left buttock and thigh and weakness in the left lower limb day 1 post spontaneous vaginal delivery. MRI showed severe oedema of the left gluteus, iliacus, piriformis and adductor muscles of the left thigh and a small fluid collection at the left hip joint. She was diagnosed with pyomyositis. She had fever of 37.9°C immediately postpartum and her risk factors for bacteraemia were a mild IV cannula-associated cellulitis and labour itself. She required prolonged treatment with antibiotics before significant clinical improvement was noted.


[Impact on serum 5-HT and TH1/TH2 in patients of depressive disorder at acute stage treated with acupuncture and western medication].
To compare the difference in depression relief in the treatment of depressive disorder at the acute stage between the combined therapy of acupuncture and 5-HT (5-hydroxytryptamine) selective serotonini reuptake inhibitors (SSRIs) and the single application of SSRIs and explore the impact on the imbalance of 5-HT and TH1/TH2. Ninety cases of depressive disorder at the acute stage were randomized into a combined therapy group and a medication group, 45 cases in each one. In the medication group, SSRIs were prescribed forl oral administration, once or twice a day, continuously for 4 weeks. In the combined therapy group, on the basis of treatment as the medication group, acupuncture was combined. The main acupoints were Baihui (GV 20), Yintang (GV 29), Shenting (GV 24), Fengchi (GB 20), Dazhui (GV 14) and Sishencong (EX-HN 1), once every two. days, continuously for 4 weeks. Before treatment, and after the 1st, 2nd and 4th weeks of treatment, the Hamilton depression scale (HAMD) was used to evaluate the depression severity. Separately, before and after the 4 weeks of treatment, the levels of serum 5-HT, interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-4 (IL-4) and interleukin-10 (IL-10) were determined and compared with those in 45 cases of the healthy group. HAMD score was reduced in the 1st, 2nd and 4th weeks of treatment as compared with that before treatment in the combined therapy group (all P<0 01). HAMD score was reduced in the 2nd and 4th weeks of treatment as compared with that before treatment in the medication group (all P<0. 01). HAMD scores in the combined therapy group were lower than those in the medication group in the 1st, 2nd and 4th weeks of treatment (all P< 0. 01). Before treatment, in the combined therapy group and the medication group, the levels of serum 5-HT, IL-4 and IL-10 were all lower than those in the healthy group (all P<0. 01); the levels of IL-1β and IL-6 were higher than those in the healthy group (all P<0. 01). In the combined therapy group and the medication group, the levels of 5-HT, IL-4 and IL-10 in 4 weeks of treatment were all increased as compared with those before treatment (all P<0. 01), and the levels of IL-1β and IL-6 were lower than those before treatment (all P<0. 01). In the combined therapy group, the levels of IL-1β and IL-6 in 4 weeks of treatment were lower than those in the medication group, and the levels of 5-HT, IL-4 and IL-10 were higher than those in the medication group (P<0. 01, P< 0. 05). The combined therapy of acupuncture and SSRIs achieves much quicker and more effective re-' sult for relieving depression in the patients of depressive disorder as compared with simple oral administration of' SSRIs, and much more contributes to adjust the imbalance of serum 5-HT and TH1/TH2.


Evaluation of some heavy metals residues in batteries and deep litter rearing systems in Japanese quail meat and offal in Egypt.
The main objectives of this study were for comparing the effect of batteries and deep litter rearing systems of domesticated Japanese quail, Coturnix coturnix japonica, on the concentration levels of cadmium, copper, lead, and zinc from the quail meat and offal in Ismailia, Egypt. A total of 40 quail meat and their offal samples were randomly collected from two main quail rearing systems: Battery (Group I) and deep litter system (Group II) for determination of concentration levels of cadmium, copper, lead, and zinc. In addition, 80 water and feed samples were randomly collected from water and feeders of both systems in the Food Hygiene Laboratory, Faculty of Veterinary Medicine, Suez Canal University for heavy metals determination. The mean concentration levels of cadmium, copper, lead, and zinc in Group I were 0.010, 0.027, 1.137, and 0.516 ppm and for Group II were 0.093, 0.832, 0.601, and 1.651 ppm, respectively. The mean concentration levels of cadmium, copper, lead, and zinc in quail feed in Group I were 1.114, 1.606, 5.822, and 35.11 ppm and for Group II were 3.010, 2.576, 5.852, and 23.616 ppm, respectively. The mean concentration levels of cadmium, copper, lead, and zinc in quail meat for Group I were 0.058, 5.902, 10.244, and 290 ppm and for Group II were 0.086, 6.092, 0.136, and 1.280 ppm, respectively. The mean concentration levels of cadmium, copper, lead, and zinc for liver samples in Group I were 0.15, 8.32, 1.05, and 3.41 ppm and for Group II were 0.13, 8.88, 0.95, and 4.21 ppm, respectively. The mean concentration levels of cadmium, copper, lead, and zinc in kidney samples for the Group I were 0.24, 4.21, 1.96, and 4.03 ppm and for Group II were 0.20, 5.00, 1.56, and 3.78 ppm, respectively. Kidney had the highest concentration levels of heavy metals followed by liver then muscles. The highest concentration levels of copper were observed in liver samples. The order of the levels of these trace elements obtained from the four different quail organs is Ca > Pb > Zn > Cu. Lead and cadmium concentration levels in quail meat samples were exceeded the Egyptian standardization limits and suggesting a health threat from lead and cadmium to the quail consumers. Battery rearing system is more hygienic than deep litter system from the point of heavy metals pollution of water and feeds of quail. Feed samples from battery system had means concentration levels of lead not significantly higher (p>0.05) than those samples from deep litter system. Meanwhile, water samples from battery system had means concentration levels of cadmium, copper, and zinc significantly higher (p>0.05) than those samples from deep litter system. Quail may carry health risks to consumers.


Anxiolytics and sedative/hypnotics dependence.
Anxiolytics and sedative/hypnotics are commonly used drugs. Benzodiazepines have largely replaced barbiturate and non-barbiturate anxiolytics and sedative/hypnotics as they are as effective and safer. Experiments in laboratory animals have shown that chronic administration of benzodiazepines tested to date can induce physical dependence. The severity of the withdrawal syndrome is clearly related to the dose, duration of administration and elimination rate of the drugs. It is now also clear that high doses of barbiturates and benzodiazepines can induce physical dependence in humans. In addition, a withdrawal syndrome after discontinuation of chronic benzodiazepine therapeutic treatment, with and without tolerance, has been well characterized. Symptoms may resemble those of anxiety or 'rebound' phenomena but some are typical of withdrawal. A relationship between benzodiazepine discontinuation and self-administration has been well documented. Negative reinforcement associated with a reduction of withdrawal symptoms may play a role supporting persistent benzodiazepine use.


Repair of UVB-induced DNA damage is reduced in melanoma due to low XPC and global genome repair.
UVB exposure leads to DNA damage, which when unrepaired induces C>T transitions. These mutations are found throughout the melanoma genome, particularly in non-transcribed regions. The global genome repair (GGR) branch of nucleotide excision repair (NER) is responsible for repairing UV-induced DNA damage across non-transcribed and silent regions of the genome. This study aimed to examine the relationship between UVB and GGR in melanoma. DNA repair capacity and relative expression of NER in melanocytes and melanoma cell lines before and after treatment with UVB was quantified. Transcript expression from 196 melanomas was compared to clinical parameters including solar elastosis and whole transcriptome data collected. Melanoma cell lines showed significantly reduced DNA repair when compared to melanocytes, most significantly in the S phase of the cell cycle. Expression of GGR components XPC, DDB1 and DDB2 was significantly lower in melanoma after UVB. In the melanoma tumours, XPC expression correlated with age of diagnosis and low XPC conferred significantly poorer survival. The same trend was seen in the TCGA melanoma dataset. Reduced GGR in melanoma may contribute to the UV mutation spectrum of the melanoma genome and adds further to the growing evidence of the link between UV, NER and melanoma.


Navigating the Pandemic Response Life Cycle: Molecular Diagnostics and Immunoassays in the Context of COVID-19 Management.
Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). To counter COVID-19 spreading, an infrastructure to provide rapid and thorough molecular diagnostics and serology testing is the cornerstone of outbreak and pandemic management. We hereby review the clinical insights with regard to using molecular tests and immunoassays in the context of COVID-19 management life cycle: the preventive phase, the preparedness phase, the response phase and the recovery phase. The spatial and temporal distribution of viral RNA, antigens and antibodies during human infection is summarized to provide a biological foundation for accurate detection of the disease. We shared the lessons learned and the obstacles encountered during real world high-volume screening programs. Clinical needs are discussed to identify existing technology gaps in these tests. Leverage technologies, such as engineered polymerases, isothermal amplification, and direct amplification from complex matrices may improve the productivity of current infrastructure, while emerging technologies like CRISPR diagnostics, visual end point detection, and PCR free methods for nucleic acid sensing may lead to at-home tests. The lessons learned, and innovations spurred from the COVID-19 pandemic could upgrade our global public health infrastructure to better combat potential outbreaks in the future.


Effect of insulin on albumin production and incorporation of 14C-leucine into proteins in isolated parenchymal liver cells from normal rats.
Parenchymal rat liver cells were isolated by a modification of the collagenase method of Quistorff, Bondesen and Grunnet. The cells secreted albumin into the medium and incorporated 14C-leucine both into cell proteins and proteins secreted into the medium. Albumin production measured from the immunologically determined increment in the incubation medium was 1.7 +/- 0.2 mug albumin/min per g liver wet wt. This is about 30% of the rate of production in the perfused liver. Addition of insulin (10(-6)-10(-10) M) enhanced albumin production (50-17%), and incorporation of 14C-leucine both into albumin (50-8%), secreted proteins (40-9%) and cell proteins (20-8%). Insulin does not increase the production of albumin by depleting the cells. The effect of insulin on albumin production is compatible with an effect on the rate of synthesis as the specific activity of albumin is unaffected by addition of insulin.


[Biochemical analysis of the cerebrospinal fluid in multiple sclerosis: study of various formulas].
Multiple sclerosis (MS) is often characterized by a intrathecal synthesis of immunoglobulins (Ig) in cerebrospinal fluid (CSF), which may be evaluated in several ways: ratio methods (IgG index, Schuller's or Tourtelotte's formulae) or demonstration of an oligoclonal distribution, or both. In a retrospective study, 256 CSF analyses were evaluated. The 4 parameters studied were disturbed in about the same proportions in each of the 3 MS subgroups of Mac Alpine's classification. An oligoclonal distribution is more rarely present in pathologies other than MS. None of these tests is specific for the diagnosis of MS. Haptoglobin index variations do not distinguish between the different groups of patients. From a physiopathological point of view, however, they may perhaps reveal an acute local inflammatory reaction, different from the immune reaction giving rise to the Ig synthesis.


[Analgesic and sedative effects of Mongolian medicine Syringa pinnatifolia].
The peeled root,stem or twig of Syringa pinnatifolia is a representative Mongolian folk medicine with the effects of antidepression and pain relief. It has been used for the treatments of heart tingling,heart palpitations,upset,insomnia and other symptoms. Inspired by Mongolian medical theory and clinical practices,this study evaluated the analgesic effect of S. pinnatifolia ethanol extract( T) through three analgesic models including acetic acid writhing test,formalin test,and hot plate test,and the sedative effect of T was evaluated by locomotor activity and synergistic sleeping experiments,and furthermore the effects of T on the GABAergic nervous system were investigated by ELISA,immunohistochemistry,Western blot,and PCR methods. The results showed that T can significantly reduce the number of writhing,the time of paw licking and extend the thermal threshold of mice,suggesting the analgesic effect of T.T also can indicate its sedative effect by reducing the number of activities,decreasing latency of sleeping and extending sleeping time of mice. ELISA results showed that T can increase the content of GABA/Glu in rat cortex,hippocampus,and hypothalamus,and the most significant increase in hypothalamus. The immunohistochemistry and Western blot results showed that T can up-regulate the expression of GAD67 protein in hypothalamus,and the PCR results showed that T can up-regulate the expression of GABAA Rα1,α2,α3,α5,β1-3,γ1-3 genes,suggesting a sedative effect through the GABAergic nervous system. In conclusion,this study shed insight into the theoretical basis and clinical application of S. pinnatifolia,and also provides inspiration for subsequent development and application.


Neglected alkaptonuric patient presented with low back pain and radiculopathy: A case report.
Alkaptonuria (AKU) is a rare hereditary disorder in which excess homogentisic acid (HGA) deposits in connective tissues (ochronosis). Here, we report the unusual presentation of a lumbar disc herniation occurring in a patient with AKU warranting surgical intervention. A 28-year-old male presented with 1 year of low back pain. The lumbar magnetic resonance imaging showed an extruded disc at the L4-L5 level accompanied extensive disc space narrowing and osteophyte formation. At surgery, the interspinous ligaments, facet joints, and disc herniation were black. In addition, the postoperative re-examination revealed a black discoloration of the nasal and ear cartilage. Finally, the diagnosis of AKU was confirmed when the urine specimen was positive for HGA. Rarely, younger patients with AKU who develop excess black deposits of HGA in connective tissues (i.e., ochronosis) may present with lumbar disc herniations and spondylosis.


Topical Management of Pediatric Psoriasis: A Review of New Developments and Existing Therapies.
Psoriasis is a chronic immune-mediated disorder that commonly affects adults and children. In recent years, pediatric psoriasis has increased in prevalence and the disease is often associated with various comorbidities and psychological distress. The conventional topical treatments for psoriasis, such as corticosteroids, calcineurin inhibitors, vitamin D analogs, anthralin, and coal tar, are often limited by their side effects, tolerability, and/or efficacy, particularly for use in children and on sensitive and intertriginous areas. Recently, the US Food and Drug Administration approved two new topical non-steroidal agents for treating psoriasis that target different pathogenic pathways than the conventional treatments. Roflumilast is a phosphodiesterase type 4 inhibitor approved for the treatment of plaque psoriasis in patients aged 12 years and older. Tapinarof is a novel aryl hydrocarbon receptor modulator approved for adult psoriasis and currently undergoing studies for pediatric psoriasis. Ongoing efforts are also being made to optimize conventional treatments, for instance, a new foam formulation of halobetasol propionate was recently approved for pediatric psoriasis. Clinical trials of various new drugs targeting one or multiple pathogenic pathways of psoriasis, such as Janus kinase inhibitors, different formulations of phosphodiesterase type 4 inhibitors, and aryl hydrocarbon receptor modulators have also been explored. The recent emergence of novel topical agents provides promising new options for managing pediatric psoriasis with the potential to improve clinical outcomes and quality of life. In this article, we review the mechanism of action, efficacy, and safety profile of novel topical agents and discuss their potential roles in the management of pediatric psoriasis.


Evaluation of Drug Responses to Human β2AR Using Native Mass Spectrometry.
We aimed to develop a platform to rapidly investigate the responses of agonists and antagonists to G-protein-coupled receptors (GPCRs) using native mass spectrometry (MS). We successfully observed the ligand-bound human β2 adrenergic receptor (hβ2AR); however, it was challenging to quantitatively discuss drug efficacy from MS data alone. Since ligand-bound GPCRs are stabilized by the Gα subunit of G proteins on the membrane, mini-Gs and nanobody80 (Nb80) that can mimic the Gα interface of the GPCR were utilized. Ternary complexes of hβ2AR, ligand, and mini-Gs or Nb80 were prepared and subjected to native MS. We found a strong correlation between the hβ2AR-mini-Gs or -Nb80 complex ratio observed in the mass spectra and agonist/antagonist efficacy obtained using a cell-based assay. This method does not require radioisotope labeling and would be applicable to the analysis of other GPCRs, facilitating the characterization of candidate compounds as GPCR agonists and antagonists.


Probing nuclear motion by frequency modulation of molecular high-order harmonic generation.
Molecular high-order harmonic generation (MHOHG) in a non-Born-Oppenheimer treatment of H(2)(+), D(2)(+), is investigated by numerical simulations of the corresponding time-dependent Schrödinger equations in full dimensions. As opposed to previous studies on amplitude modulation of intracycle dynamics in MHOHG, we demonstrate redshifts as frequency modulation (FM) of intercycle dynamics in MHOHG. The FM is induced by nuclear motion using intense laser pulses. Compared to fixed-nuclei approximations, the intensity of MHOHG is much higher due to the dependence of enhanced ionization on the internuclear distance. The width and symmetry of the spectrum of each harmonic in MHOHG encode rich information on the dissociation process of molecules at the rising and falling parts of the laser pulses, which can be used to retrieve the nuclear dynamics. Isotope effects are studied to confirm the FM mechanism.


[2,5-diaryl-substituted 1,3,4-oxadiazoles: synthesis and preliminary pharmacological investigation].
Seven 2,5-diarylalkyloxysubstituted 1,3,4-oxadiazoles were synthesized. They showed pronounced antiphlogistic action together with central activity (sedative, analgesic) that principally seems to be connected with the presence in the molecule of the 3,4-dioxymethylenephenyl radical.


Electrode surface confinement of self-assembled enzyme aggregates using magnetic nanoparticles and its application in bioelectrocatalysis.
Self-assembled enzyme aggregates, prepared from magnetic iron oxide nanoparticles, avidin, and a biotinylated redox enzyme, were shown particularly useful for the simple, fast, and efficient construction of highly enzyme-loaded electrodes with the help of a magnet. The approach was illustrated in the case of the bioelectrocatalytic oxidation of NADH by a diaphorase oxidoreductase in the presence of a ferrocene mediator. Two different self-assembling procedures were tested, taking advantage of the spontaneous aggregation of the nanoparticles in the presence of avidin and also of the multivalency binding of biotinylated diaphorase toward avidin. Activities of the bound and unbound diaphorase were systematically controlled allowing determination of the number of active biotinylated diaphorase per nanoparticle incorporated within each magnetic enzyme aggregate. An active enzyme loading capacity of up to 2.35 nmol mg-1 was found for the best nanostructured enzyme assembly, which is 200 times better than for commercialized magnetic micrometer-sized beads coated with streptavidin and saturated with diaphorase. With the help of a permanent magnet, the magnetic enzyme aggregates were finally magnetically collected as a film on the surface of a small screen-printed carbon electrode and the catalytic currents recorded by cyclic voltammetry. From the analysis of the steady-state catalytic current responses and the kinetic rate constants of biotinylated diaphorase, it was possible to determine the enzyme concentration within the magnetic films. Owing to the high enzyme loading in the aggregates of nanoparticles (i.e., 130 microM), the catalytic current responses were definitely higher than the ones measured at an electrode coated with a closed-packed monolayer of diaphorase or at an electrode covered with a film of magnetic micrometer-sized streptavidin beads saturated with diaphorase.


Pharmacokinetics of procainamide and N-acetylprocainamide in rats.
The pharmacokinetics of distribution and elimination of procainamide and its major metabolite, N-actylprocainamide, were studied in rats. Eight rats were selected randomly, and each received intravenously 14C-labeled procainamide hydrochloride (75 mg/kg) or 14C-labeled N-acetylprocainamide hydrochloride (86 mg/kg) according to a two-way crossover design. Serial blood samples were withdrawn for 8 hr, and cumulative urine and feces were collected for 48 hr. The plasma concentration-time relationships of procainamide and N-acetylprocainamide were characterized by one- and two-compartment open models, respectively. A pseudo-three-compartment model was necessary to characterize the time course of N-acetylprocainamide in plasma formed after administration of procainamide. The biological half-lives of procainamide and N-acetylprocainamide averaged 0.66 and 2.1 hr, respectively. The urinary excretion profiles of these drugs and the ratio of their biological half-lives in rats were similar to those in humans.


Salt sensitivity in hypertensive type-1 diabetes mellitus.
As sodium retention has been proposed as a causal factor in the development of hypertension in diabetic patients, a high incidence of salt sensitivity has been suggested. To evaluate the influence of dietary sodium intake on blood pressure, casual and 24-h blood pressure was measured in 30 hypertensive type-1 diabetic patients aged 24-67 (mean 46) years while they were on habitual diet, after 6 days of low-sodium diet (50 mmol/day), and after 6 days of high-sodium diet (250 mmol/day). Nine patients (30%) who increased their 24-h mean blood pressure by more than 10% when going from low- to high-sodium intake were classified as salt sensitive; the others as salt resistant. The salt sensitive group had a significantly lower urinary excretion of dopamine at baseline, and a higher diuresis and a more pronounced decrease in 24-h blood pressure during salt depletion (all p < 0.01). Low-sodium diet reduced casual and 24-h blood pressure by 4% in the total study population compared with 9% in the salt sensitive group (p < 0.01). There was no difference in glomerular filtration rate, filtration fraction, proteinuria or urinary sodium excretion between the groups. Sodium restriction more effectively reduces blood pressure in the salt sensitive minority of hypertensive type-1 diabetic patients irrespective of renal function. The incidence of salt sensitivity is not increased in hypertensive type-1 diabetic patients compared with essential hypertensive patients.


Streptococcus mutans Gene Expression and Functional Profile in Root Caries: An RNA-Seq Study.
The literature is still scarce on studies describing Streptococcus mutans global gene expression under clinical conditions such as those found on complex biofilms from sound root surfaces (SRS) and carious root surfaces (RC). This study aimed to investigate the S. mutans gene expression and functional profile within the metatranscriptome of biofilms from SRS and from RC in an attempt to identify enriched functional signatures potentially associated with the healthy-to-disease transitioning process. Total RNA was extracted, and prepared libraries (SRS = 10 and RC = 9) were paired-end sequenced using the Illumina HiSeq2500. A read count assigned to each gene of the S. mutans UA159 strain was obtained. Differentially expressed genes (DEG) between SRS and RC were identified using the DESeq2 R package, and weighted gene co-expression network analysis (WGCNA) was performed to explore and identify functional modules related to SRS and RC. We found seventeen DEG between SRS and RC samples, with three overexpressed in RC and related to membrane protein, alanyl-tRNA synthetase, and GTP-binding protein, with the remaining ones overexpressed in SRS samples and related to hypothetical protein, transposon integrase, histidine kinase, putative transporter, bacteriocin immunity protein, response regulator, 6-phospho-beta-galactosidase, purine metabolism, and transcriptional regulator. Key-functional modules were identified for SRS and RC conditions based on WGCNA, being 139 hub genes found on SRS key-module and 17 genes on RC key-module. Functional analysis of S. mutans within the metatranscriptome of biofilms from sound root and from carious root revealed a similar pattern of gene expression, and only a few genes have been differentially expressed between biofilms from SRS and those from root carious lesions. However, S. mutans presented a greater functional abundance in the carious lesion samples. Some functional patterns related to sugar (starch, sucrose, fructose, mannose, and lactose) and heterofermentative metabolisms, to cell-wall biosynthesis, and to acid tolerance stress seem to be enriched on carious root surfaces, conferring ecological advantages to S. mutans. Altogether, the present data suggest that a functional signature may be associated with carious root lesions.


COVID-19 and Unmet Medical Needs for People With Chronic Diseases: A Cross-Sectional Study.
Gaps between medical needs and health services accessibility are defined as unmet medical needs (UMN). Previous studies assessing UMNs during the coronavirus disease 2019 (COVID-19) pandemic did not account for factors such as the type of medical insurance or chronic disease. Therefore, this study investigated various factors, including medical insurance and chronic diseases, affecting self-reported UMN during the pandemic in Daejeon Metropolitan City, South Korea. This cross-sectional study was conducted using Daejeon Metropolitan City Health Surveys data from 2020. The weighted prevalence of UMN was estimated among participants (n = 1494) aged ≥18 years, while chi-squared and logistic models were used to assess the association between UMN and participant characteristics. The prevalence of UMN was 6.4% (n = 97). Female sex and low education levels were significantly associated with reporting UMN. Medical aid beneficiaries were less likely to report UMN than adults with National Health Programs coverage. Participants with chronic diseases, such as hypertension and arthritis, and those with depression, were more likely to report UMN than adults without these conditions. The findings highlight the need for targeted efforts to decrease UMN in the COVID-19 pandemic, especially for women and individuals with low education levels. The results also indicate that high-risk disease groups should be targeted with additional enabling services to support the management of chronic conditions.


The C4 Model Grass Setaria Is a Short Day Plant with Secondary Long Day Genetic Regulation.
The effect of photoperiod (day:night ratio) on flowering time was investigated in the wild species, Setaria viridis, and in a set of recombinant inbred lines (RILs) derived from a cross between foxtail millet (S. italica) and its wild ancestor green foxtail (S. viridis). Photoperiods totaled 24 h, with three trials of 8:16, 12:12 and 16:8 light:dark hour regimes for the RIL population, and these plus 10:14 and 14:10 for the experiments with S. viridis alone. The response of S. viridis to light intensity as well as photoperiod was assessed by duplicating photoperiods at two light intensities (300 and 600 μmol.m-2.s-1). In general, day lengths longer than 12 h delayed flowering time, although flowering time was also delayed in shorter day-lengths relative to the 12 h trial, even when daily flux in high intensity conditions exceeded that of the low intensity 12 h trial. Cluster analysis showed that the effect of photoperiod on flowering time differed between sets of RILs, with some being almost photoperiod insensitive and others being delayed with respect to the population as a whole in either short (8 or 12 h light) or long (16 h light) photoperiods. QTL results reveal a similar picture, with several major QTL colocalizing between the 8 and 12 h light trials, but with a partially different set of QTL identified in the 16 h trial. Major candidate genes for these QTL include several members of the PEBP protein family that includes Flowering Locus T (FT) homologs such as OsHd3a, OsRFT1, and ZCN8/12. Thus, Setaria is a short day plant (flowering quickest in short day conditions) whose flowering is delayed by long day lengths in a manner consistent with the responses of most other members of the grass family. However, the QTL results suggest that flowering time under long day conditions uses additional genetic pathways to those used under short day conditions.


Assessment of ejection fraction of the right and left ventricles in patients with acute myocardial infarction by magnetic resonance imaging.
Right and left ventricular function in acute myocardial infarction (AMI) was assessed by ECG-gated magnetic resonance imagine (MRI) in 64 patients and 8 volunteers. Five short axis images for intrinsic cardiac long-axis of the left ventricle were obtained at 9 msec and 309 msec after the R wave as end-diastole and end-systole. Right and left ventricular volumes were measured by Simpson's rule. The intraobserver variabilities in right and left ventricular ejection fraction (RVEF: r = 0.94, LVEF: 0.89) were excellent. The interobserver variabilities in RVEF (r = 0.61) and LVEF (r = 0.77) were fair. LVEF, but not RVEF, was significantly reduced in patients with AMI. Among left ventricular dysfunction (LVEF < or = 40%) patients, 50% exhibited right ventricular dysfunction (RVEF < or = 40%). Among patients without left ventricular dysfunction, only 12% exhibited right ventricular dysfunction. In left ventricular and biventricular dysfunction compared with control, the left ventricular end-diastolic volume index increased (65 +/- 10 ml/m2, 68 +/- 12 ml/m2 vs 54 +/- 8 ml/m2), the end-systolic volume index increased (40 +/- 16 ml/m2, 43 +/- 7 ml/m2 vs 18 +/- 1 ml/m2), and the right ventricular end-diastolic volume index decreased (52 +/- 13 ml/m2, 53 +/- 20 ml/m2 vs 65 +/- 8 ml/m2). MRI can thus be used to assess ventricular systolic function. Since patients with left ventricular dysfunction revealed a high incidence of right ventricular dysfunction, an interaction between the left and right ventricles may occur in ventricular dysfunction.


Screening for uveitis in juvenile chronic arthritis.
Three hundred and fifteen patients with anterior uveitis associated with juvenile chronic arthritis (JCA) were studied in order to identify the various risk factors for uveitis. Girls were more susceptible to uveitis than boys by a ratio of 3:1. In 94% of cases the uveitis was diagnosed after the development of arthritis. The risk of uveitis was small after seven or more years had elapsed from the onset of arthritis. Patients with pauciarticular onset JCA had the highest risk of uveitis and systemic onset patients the least risk. The presence of circulating antinuclear antibody was also an important marker for an increased risk of uveitis. A regimen for routine screening of patients is suggested.


Reconstitution of lymphocyte subpopulations after hematopoietic stem cell transplantation: comparison of hematologic malignancies and donor types in event-free patients.
The reconstitution of different immunocyte subsets after hematopoietic stem cell transplantation (HSCT), follows different timelines. We prospectively investigated changes in lymphocyte subsets after HSCT and their associations with primary diagnosis, conditioning regimen, and HSCT type in event-free patients. A total of 95 patients (48 with acute myeloid leukemia, 22 with acute lymphoid leukemia, and 25 with myelodysplastic syndrome) who underwent allogeneic HSCT (34 sibling matched, 37 unrelated matched, and 24 haploidentical HSCT) but did not experience any events such as relapse or death were enrolled in this study. Lymphocyte subpopulations (T cells, helper/inducer T cells, cytotoxic/suppressor T cells, memory T cells, regulatory T cells, natural killer (NK) cells, NK-T cells, and B cells) were quantified by flow cytometry of peripheral blood from recipients 7 days before and 1, 2, 3, 6, and 12 months after HSCT. Leukocyte counts recovered within 1 month after HSCT. However, the number of T and B lymphocytes recovered at 2 months after HSCT. NK cell counts recovered shortly after haploidentical HSCT. However, T lymphocytes and their subpopulations showed delayed recovery after haploidentical HSCT. Lymphocyte subsets showed different sequential patterns according to HSCT type but no differences were seen according to primary diagnosis or conditioning regimen.


[Reliability and validity of the Severe Impairment Battery, short form (SIB-s), in patients with dementia in Spain].
People with progressive dementia evolve into a state where traditional neuropsychological tests are not effective. Severe Impairment Battery (SIB) and short form (SIB-s) were developed for evaluating the cognitive status in patients with severe dementia. To evaluate the psychometric attributes of the SIB-s in patients with severe dementia. 127 institutionalized patients (female: 86.6%; mean age: 82.6 ± 7.5 years-old) with dementia were assessed with the SIB-s, the Global Deterioration Scale (GDS), Mini-Mental State Examination (MMSE), Severe Mini-Mental State Examination (sMMSE), Barthel Index and FAST. SIB-s acceptability, reliability, validity and precision were analyzed. The mean total score for scale was 19.1 ± 15.34 (range: 0-48). Floor effect was 18.1%, only marginally higher than the desirable 15%. Factor analysis identified a single factor explaining 68% of the total variance of the scale. Cronbach's alpha coefficient was 0.96 and the item-total corrected correlation ranged from 0.27 to 0.83. The item homogeneity value was 0.43. Test-retest and inter-rater reliability for the total score was satisfactory (ICC: 0.96 and 0.95, respectively). The SIB-s showed moderate correlation with functional dependency scales (Barthel Index: 0.48, FAST: -0.74). Standard error of measurement was 3.07 for the total score. The SIB-s is a reliable and valid instrument for evaluating patients with severe dementia in the Spanish population of relatively brief instruments.


Lymphedema After Axillary Lymph Node Dissection in Breast Cancer: Prevalence and Risk Factors-A Single-Center Retrospective Study.
Background: Lymphedema may develop when axillary lymph node dissection (ALND) injures and obstructs the lymph ducts in the upper limb. In patients with breast cancer, lymphedema is difficult to treat and can cause arm swelling, heaviness, and restricted movement. We aimed to identify the prevalence and risk factors for lymphedema after ALND in patients with breast cancer. Methods and Results: This retrospective study included 175 patients with breast cancer who underwent ALND in the Nagasaki University Hospital, Japan, between 2005 and 2018. Lymphedema was defined as symptomatic arm swelling with a >2-cm difference in the arm circumference between the affected and contralateral arms. Patients were divided into two groups according to the presence or absence of lymphedema. Surgical and pathological findings were compared between the two groups. Univariate and multivariate analyses were performed, including the chi-square test, Student's t-test, and logistic regression analysis. Lymphedema was prevalent in 20% of the study participants, and the mean time interval from surgery to development of lymphedema was 479 days. In the univariate analysis, a body mass index of >26 kg/m2, smoking, radiotherapy (RT), and dissection of >18 axillary lymph nodes (ALNs) significantly increased the risk of lymphedema. In the multivariate analysis, smoking, RT, and dissection of >18 ALNs significantly increased the risk of lymphedema. Conclusions: The prevalence of lymphedema in our study was 20%. Our findings suggest that smoking, RT, and dissection of >18 ALNs are risk factors for lymphedema. Aggressive and empiric ALND might be associated with axillary lymph duct damage.


High-level aminoglycoside-resistant enterococcus causing endocarditis successfully treated with a combination of ampicillin, imipenem and vancomycin.
We describe a case of bacterial endocarditis caused by Enterococcus faecalis, which was highly resistant to aminoglycosides. The patient was successfully treated with a combination of ampicillin, imipenem and vancomycin. We believe this to be the first case in the literature to be treated successfully with this combination.


Paracellin-1 and the modulation of ion selectivity of tight junctions.
Tight junctions play a key selectivity role in the paracellular conductance of ions. Paracellin-1 is a member of the tight junction claudin protein family and mutations in the paracellin-1 gene cause a human hereditary disease, familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) with severe renal Mg2+ wasting. The mechanism of paracellin-1 function and its role in FHHNC are not known. Here, we report that in LLC-PK1 epithelial cells paracellin-1 modulated the ion selectivity of the tight junction by selectively and significantly increasing the permeability of Na+ (with no effects on Cl-) and generated a high permeability ratio of Na+ to Cl-. Mutagenesis studies identified a locus of amino acids in paracellin-1 critical for this function. Mg2+ flux across cell monolayers showed a far less-pronounced change (compared to monovalent alkali cations) following exogenous protein expression, suggesting that paracellin-1 did not form Mg2+-selective paracellular channels. We hypothesize that in the thick ascending limb of the nephron, paracellin-1 dysfunction, with a concomitant loss of cation selectivity, could contribute to the dissipation of the lumen-positive potential that is the driving force for the reabsorption of Mg2+.


Cantharidin alters the expression of genes associated with the NKG2D-associated immune response in TSGH-8301 human bladder carcinoma cells.
Cantharidin (CTD) is a natural toxin in beetles of the Mylabris genus (blister beetle), which has been revealed to induce cell death in various types of human cancer cells. However, to the best of our knowledge, no previous studies have investigated the effect of CTD on the expression of genes and their associated signaling pathways in human bladder carcinoma cells. In the present study, CTD-induced cell morphological changes and apoptosis were observed using phase-contrast microscopy and the terminal deoxynucleotidyl transferase dUTP nick end labeling assay, respectively, in TSGH-8301 human bladder carcinoma cells. In addition, a complementary DNA microarray analysis demonstrated that CTD treatment led to a >2-fold upregulation of 269 genes. For example, the DNA damage-associated gene DNA-damage-inducible transcript 3 had a 4.75-fold upregulation. Furthermore, another 286 genes were >2-fold downregulated in response to CTD treatment. Matrix-remodeling associated 5, which is associated with cell migration and invasion, was downregulated 7.98-fold.


Ethical issues on the "synthetic" phosphoethanolamine clinical trial.
Notwithstanding its approval by the National Committee for Ethics in Research (Conep) on April 19, 2016, a trial of the so-called "synthetic" phosphoethanolamine (syn-phospho) pill in cancer patients raises ethical concerns. An analysis by a laboratory contracted by the Ministry of Science, Technology and Innovation (MCTI) revealed that syn-phospho contained a great amount of impurities and did not meet standards of pharmaceutical quality required for an investigational drug. Cytotoxicity against human tumor cell lines and in vivo rodent xenograft tumor assays consistently failed to demonstrate a potential anticancer activity of syn-phospho. Preclinical safety studies of syn-phospho were also insufficient to support a trial of this investigational drug in cancer patients. Moreover, the ethical approval decision apparently overlooked two previous findings that suggested a possible enhancement of mammary carcinoma cell proliferation by phosphoethanolamine, and an apparent increase in lung metastases (rat implanted tumor assay) by syn-phospho. The syn-phospho risk-benefit ratio is clearly unfavorable and, thus, this trial in cancer patients does not fulfill a key requirement to make a clinical research ethical. There are also concerns regarding whether the study design is robust enough (scientific validity), and the social value of the trial of syn-phospho in cancer patients is questionable.


An Insight on the Prospect of Quinazoline and Quinazolinone Derivatives as Anti-tubercular Agents.
Multiple potential drugs have been developed based on the heterocyclic molecules for the treatment of different symptoms. Among the existing heterocyclic molecules, quinazoline and quinazolinone derivatives have been found to exhibit extensive pharmacological and biological characteristics. One significant property of these molecules is their potency as anti-tubercular agents. Thus, both quinazoline and quinazolinone derivatives are modified using different functional groups as substituents for investigating their anti-tubercular activities. We present a summary of the reported anti-tubercular drugs, designed using quinazoline and quinazolinone derivatives, in this review.


Case report: biceps tenosynovial rice bodies.
Here we report the first documented case of rice body formation within the biceps tenosynovium in a patient with juvenile rheumatoid arthritis. We discuss the pathophysiology and the clinical and radiographic findings and correlate these to prior case studies. Lastly, we suggest that limited awareness is a barrier in achieving a timely diagnosis and appropriate management.


Sister chromatid resolution: a cohesin releasing network and beyond.
When chromosomes start to assemble in mitotic prophase, duplicated chromatids are not discernible within each chromosome. As condensation proceeds, they gradually show up, culminating in two rod-shaped structures apposed along their entire length within a metaphase chromosome. This process, known as sister chromatid resolution, is thought to be a prerequisite for rapid and synchronous separation of sister chromatids in anaphase. From a mechanistic point of view, the resolution process can be dissected into three distinct steps: (1) release of cohesin from chromosome arms; (2) formation of chromatid axes mediated by condensins; and (3) untanglement of inter-sister catenation catalyzed by topoisomerase II (topo II). In this review article, we summarize recent progress in our understanding the molecular mechanisms of sister chromatid resolution with a major focus on its first step, cohesin release. An emerging idea is that this seemingly simple step is regulated by an intricate network of positive and negative factors, including cohesin-binding proteins and mitotic kinases. Interestingly, some key factors responsible for cohesin release in early mitosis also play important roles in controlling cohesin functions during interphase. Finally, we discuss how the step of cohesin release might mechanistically be coordinated with the actions of condensins and topo II.