Rationality of drug prescriptions in rural health centres in Burkina Faso.
The objective of this study is to investigate the quality of drug prescriptions in nine health centres of three districts in rural Burkina Faso. 313 outpatient consultations were studied by methods of guided observation. Additionally interviews were held with the health care workers involved in the study. A total of 793 drugs prescribed by 15 health care workers during the observation period and 2815 prescribed drugs copied from the patient register were analyzed. An average of 2.3 drugs were prescribed per visit. 88.0% of the prescribed drugs were on the essential drug list. 88.4% were indicated according to the national treatment guidelines. 79.4% had a correct dosage. The study revealed serious deficiencies in drug prescribing that could not be detected by assessing selected quantitative drug-use indicators as recommended by the WHO. In two-thirds of the cases the patients received no information on how long the drug had to be taken. Errors in dosage occurred significantly more often in children under 5 years. The combined analysis of choice and dosage of drugs showed that 59.3% of all the patients received a correct prescription. Seven out of 21 pregnant women received drugs contraindicated in pregnancy. We conclude that assessment of quantitative drug-use indicators alone does not suffice in identifying specific needs for improvement in treatment quality. We recommend that prescribing for children under 5 and for pregnant women should be targeted in future interventions and that the lay-out, content and distribution of treatment guidelines must be improved.


The Proteocephalus species-aggregate (Cestoda) in sticklebacks (Gasterosteidae) of the Nearctic Region, including description of a new species from brook stickleback, Culaea inconstans.
A survey of the species of the Proteocephalus-aggregate from sticklebacks (Actinopterygii: Gasterosteidae) is provided. The occurrence of three species in North America is confirmed: (i) Proteocephalus filicollis (Rudolphi, 1802), which has been reported from the three-spined stickleback, Gasterosteus aculeatus Linnaeus, in the northeastern part of North America (Newfoundland); (ii) Proteocephalus pugetensis Hoff et Hoff, 1929 occurs also in G. aculeatus, but in northwestern North America (British Columbia and Washington); and (iii) Proteocephalus culaeae sp. n., which is described from the brook stickleback, Culaea inconstans (Kirtland), in Manitoba (Canada). Another species, Proteocephalus ambiguus (Dujardin, 1845), a specific parasite of the nine-spined stickleback, Pungitius pungitius (Linnaeus), and type species of the genus, has also been found in North America (Alberta, Canada), but its vouchers are in poor condition and cannot be reliable assigned to this species. Both species reported from three-spined stickleback differ from each other by the shape of the scolex (rounded in P. filicollis versus continuously tapered towards the anterior extremity in P. pugetensis) and the apical sucker (widely oval to subspherical in frontal view in P. filicollis versus flattened in P. pugetensis). Proteocephalus culaeae sp. n. is characterised by a short body composed of a few, continuously widened proglottids, a short scolex narrower than the strobila and devoid of an apical sucker, a short, pyriform cirrus sac, no vaginal sphincter, and few testes. A key to species of the Proteocephalus-aggregate from sticklebacks is provided.


Oviposition responses of gravid Culex quinquefasciatus and Culex tarsalis to bulrush (Schoenoplectus acutus) infusions.
Laboratory bioassays demonstrated that fermented infusions of dried bulrushes (Schoenoplectus acutus) strongly attracted and stimulated oviposition by gravid female Culex quinquefasciatus and Culex tarsalis. The responses of the 2 species varied with the concentration and method of preparation of the infusions, with responses generally increasing with increasing concentration. No major differences were found in the responses of either species to infusions prepared with bulrushes alone, or with bulrushes plus lactalbumin hydrolysate and brewer's yeast. Infusions remained more attractive than distilled water controls to both species for up to 8 wk. Field tests corroborated the results from the laboratory bioassays. Culex quinquefasciatus, Cx. tarsalis, and Cx. stigmatosoma egg rafts were collected from water pan traps baited with bulrush infusions. A few Culiseta incidens eggs also were collected. In multiple-choice tests using gravid female or egg traps, Cx. quinquefasciatus preferred the most concentrated bulrush infusions, whereas Cx. tarsalis preferred intermediate concentrations. Female Cx. stigmatosoma and Culiseta incidens also were attracted. Overall, these results may provide new leads towards developing synthetic chemical baits to attract bloodfed mosquitoes.


Mechanism of intrinsic resistance of lung squamous cell carcinoma to epithelial growth factor receptor-tyrosine kinase inhibitors revealed by high-throughput RNA interference screening.
Although targeted therapy has achieved a great breakthrough in the treatment of lung adenocarcinoma, there are still no effective targeted drugs for lung squamous cell carcinoma (SqCC). In addition, as immunotherapy can only prolong the overall survival (OS) of lung SqCC by ≤5 months, chemotherapy and radiotherapy are still the main types of therapy for advanced SqCC. The expression level of epithelial growth factor receptor (EGFR) in patients with lung SqCC is higher compared with those with adenocarcinoma, but the former group is intrinsically resistant to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). Therefore, if the drug resistance in patients with lung SqCC could be reversed, the majority of patients may benefit from EGFR-TKIs. In the present study, the high-throughput RNA interference technology was used to screen the genes involved in the EGFR-TKI erlotinib resistance of lung SqCCs, and integrin-linked kinase (ILK) was identified to be the most effective. The role of ILK in erlotinib resistance was further studied in cell lines, and the expression of ILK was analyzed in patients with SqCC and adenocarcinoma. Finally, the mechanism of ILK in EGFR-TKIs resistance was analyzed using Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO) and ingenuity pathway analysis (IPA). The results demonstrated that the ILK gene knockdown could overcome erlotinib resistance by inhibiting cell proliferation, inducing apoptosis and blocking the cell cycle at the G2/M phase. The expression of ILK in patients with SqCC was significantly higher compared with those with adenocarcinoma with sensitizing EGFR mutations. In addition, the cell cycle pathway 'G2/M DNA damage and checkpoint regulation' was identified to be significantly inhibited by ILK knockdown in IPA, KEGG and GO analysis. The results of the present study may improve the understanding of EGFR-TKI resistance in lung SqCCs, thus promoting the development of potential targeted therapies for lung SqCCs.


Modeling of transcellular Ca transport in rat duodenum points to coexistence of two mechanisms of apical entry.
Employing realistic parameters, we have demonstrated that a relatively simple mathematical model can reproduce key features of steady-state Ca2+ transport with the assumption of two mechanisms of Ca2+ entry: a channel-like flux and a carrier-mediated transport. At low luminal [Ca2+] (1-5 mM), facilitated entry dominates and saturates with Km = 0.4 mM. At luminal [Ca2+] of tens of millimolar, apical permeability is dominated by the channel flux that in turn is regulated by cytosolic Ca2+. The model reproduces the linear relationship between maximum Ca2+ transport rate and intestinal calbindin D9K (CaBP) content. At luminal [Ca2+] > 50 mM, local sensitivity analysis shows transcellular transport to be most sensitive to variations in CaBP. At low luminal [Ca2+], transport becomes sensitive to apical entry regulation. The simulations have been run within the Virtual Cell modeling environment, yielding the time course of external Ca2+ and spatiotemporal distributions of both intracellular Ca2+ and CaBP. Coexistence of two apical entry mechanisms accords with the properties of the duodenal Ca2+ transport protein CaT1 and the epithelial Ca2+ channel ECaC.


mRNA transfection of CXCR4-GFP fusion--simply generated by PCR-results in efficient migration of primary human mesenchymal stem cells.
We present a general, entirely PCR-based strategy to construct mRNAs coding for green fluorescent protein (GFP) fusion proteins from a cDNA pool. We exemplify our approach for the chemokine receptor CXCR4. mRNA transfection of the PCR-generated fusion of CXCR4-GFP into K562 cells or primary mesenchymal stem cells (MSCs) resulted in excellent viability (> 90%) with more than 90% of target cells expressing easily detectable CXCR4-GFP for > 72 h. The fusion protein was localized in the plasma membrane and was rapidly internalized upon incubation with the CXCR4 ligand stromal cell-derived factor-1 (SDF-1). Transwell migration experiments showed significantly increased migration of CXCR4-GFP mRNA-transfected MSCs toward a gradient of SDF-1, demonstrating that mRNA-mediated chemokine receptor overexpression allows for transient initiation of chemotaxis. The presented strategy to construct a PCR-based fluorescent fusion protein can be generally applied to other genes of interest to study their function by simple overexpression and easy detection in primary cells.


Phenotypic characterization of gamma delta (γδ) T cells in chickens infected with or vaccinated against Marek's disease virus.
Marek's disease (MD) vaccines reduce the incidence of MD but cannot control virus shedding. To develop new vaccines, it is essential to elucidate mechanisms of immunity to Marek's disease virus (MDV) infection. In this regard, gamma delta (γδ) T cells may play a significant role in prevention of viral spread and tumor surveillance. Here we demonstrated that MDV vaccination induced interferon (IFN)-γ+CD8α+ γδ T cells and transforming growth factor (TGF)-β+ γδ T cells in lungs. γδ T cells from MDV-infected chickens exhibited cytotoxic activity. Importantly, γδ T cells from the vaccinated/challenged group exhibited maximum cytotoxic activity following ex vivo stimulation. These results suggest that MDV vaccines activate effector γδ T cells which may be involved in the development of protective immune responses against MD. Further, it was demonstrated that MDV infection increases the frequency of a subpopulation of γδ T cells expressing membrane-bound TGF-β in MDV-infected birds.


Emergence of an invasive clone of nontoxigenic Corynebacterium diphtheriae in the urban poor population of Vancouver, Canada.
Invasive disease due to Corynebacterium diphtheriae is rare in North America. Here we describe the emergence of a predominant clone of a nontoxigenic strain of C. diphtheriae in the impoverished population of Vancouver's downtown core. This clone has caused significant morbidity and contributed to at least two deaths. Over a 5-year period, seven cases of bacteremia due to C. diphtheriae were detected in patients admitted to Vancouver hospitals. Injection drug use, diabetes mellitus, skin colonization/infection with C. diphtheriae, and homelessness all appeared to be related to the development of bacteremia with the organism. Ribotyping of isolates recovered from blood culture revealed a predominant ribotype pattern that has not previously been reported in North America.


VEGFR and EGFR inhibition increases epithelial cellular characteristics and chemotherapy sensitivity in mesenchymal bladder cancer cells.
The present study investigated the effect of VEGFR and EGFR inhibition via vandetanib (Zactima) on epithelial-mesenchymal transition (EMT) in bladder cancer. Markers of EMT (EGFR, VEGR, E-cadherin and vimentin) were interogated by Western blotting at baseline and after treatment with EGF, VEGF, vandetanib, cisplatin, or their combination using representative epithelial- and mesenchymal-type human bladder cancer cells. Morphological changes induced by these treatments were examined by microscopy over various time courses. The effect of these changes on cisplatin chemotherapy sensitivity was assessed by MTT assay. RT4 and HTB3 cells had epithelial features while CRL1749 and J82 cells had mesenchymal features. After treatment with EGF, the epithelial-type cells demonstrated increased intercellular separation and pseudopodia, with these changes blocked by vandetanib. In contrast, the mesenchymal cells did not exhibit any morphological changes with the EGF treatment but adopted a clustered/epithelial appearance after the administration of vandetanib. Western blotting shows that treatment of epithelial cells with vandetanib increased the expression of E-cadherin. In comparison, mesenchymal cells demonstrated decreased vimentin expression with the treatment of vandetanib in the presence of EGF and VEGF. Improved growth inhibition was seen in the epithelial cells but not in mesenchymal cells with the concurrent treatment of vandetanib and cisplatin. Sequential treatment of mesenchymal cells with vandetanib followed by cisplatin demonstrated synergy with improved cisplatin activity. The findings offer a novel role of vandetanib on the EMT in bladder cancer, providing insight into EMT in bladder cancer.


Risk Factors for Community-associated Clostridium difficile-associated Diarrhea in Children.
Clostridium difficile-associated diarrhea (CDAD) is increasingly diagnosed in children in community settings. This study aims to assess recent antibiotic use and other risk factors in children with community-associated (CA-) CDAD compared with children with other diarrheal illnesses in a tertiary care setting. Children with CA-CDAD evaluated at Texas Children's Hospital (Houston, TX) from January 1, 2012 to June 30, 2013 were identified. Two control subjects with community-associated diarrhea who tested negative for C. difficile were matched to case subjects. Data on demographics, medication exposure and outpatient healthcare encounters were collected from medical records. Multivariate logistic regression was performed to identify predictors of pediatric CA-CDAD. Of 69 CA-CDAD cases, most (62.3%) had an underlying chronic medical condition and 40.6% had antibiotic exposure within 30 days of illness. However, no traditional risk factor for CDAD was identified in 23.2% and 15.9% of CA-CDAD cases within 30 and 90 days of illness onset, respectively. Outpatient healthcare encounters within 30 days were more common among CA-CDAD cases than control subjects (66.7% vs. 48.6%; P = 0.01). In the final multivariate model, CA-CDAD was associated with cephalosporin use within 30 days [odds ratio: 3.32; 95% confidence interval: 1.10-10.01] and the presence of a gastrointestinal feeding device (odds ratio: 2.59; 95% confidence interval: 1.07-6.30). Recent use of cephalosporins and the presence of gastrointestinal feeding devices are important risk factors for community- associated CDAD in children. Reduction in the use of outpatient antibiotics may decrease the burden of CA-CDAD in children.


Validity of transcranial Doppler ultrasonography-determined dynamic cerebral autoregulation estimated using transfer function analysis.
Transcranial Doppler ultrasonography (TCD) is used widely to evaluate dynamic cerebral autoregulation (dCA). However, the validity of TCD-determined dCA remains unknown because TCD is only capable of measuring blood velocity and thus only provides an index as opposed to true blood flow. To test the validity of TCD-determined dCA, in nine healthy subjects, dCA was evaluated by transfer function analysis (TFA) using cerebral blood flow (CBF) or TCD-measured cerebral blood velocity during a perturbation that induces reductions in TCD-determined dCA, lower body negative pressure (LBNP) at two different stages: LBNP - 15 mmHg and - 50 mmHg. Internal carotid artery blood flow (ICA Q) was assessed as an index of CBF using duplex Doppler ultrasound. The TFA low frequency (LF) normalized gain (ngain) calculated using ICA Q increased during LBNP at - 50 mmHg (LBNP50) from rest (P = 0.005) and LBNP at - 15 mmHg (LBNP15) (P = 0.015), indicating an impaired dCA. These responses were the same as those obtained using TCD-measured cerebral blood velocity (from rest and LBNP15; P = 0.001 and P = 0.015). In addition, the ICA Q-determined TFA LF ngain from rest to LBNP50 was significantly correlated with TCD-determined TFA LF ngain (r = 0.460, P = 0.016) despite a low intraclass correlation coefficient. Moreover, in the Bland-Altman analysis, the difference in the TFA LF ngains determined by blood flow and velocity was within the margin of error, indicating that the two measurement methods can be interpreted as equivalent. These findings suggest that TCD-determined dCA can be representative of actual dCA evaluated with CBF.


[Effect of chronic intermittent hypoxia on the expression of fractalkine in rat liver].
To investigate the effect of chronic intermittent hypoxia (CIH) on liver injury and the expression of fractalkine in rats and explore its possible mechanism. A CIH murine model was established to mimic the pathophysiology of obstructive sleep apnea-hypopnea syndrome (OSAHS) in humans. Thirty healthy male Spraque-Dawley rats were randomly assigned to 3 groups: a 5% CIH group, a 5% CIH+RH (removal of hypoxia) group and a control group ( 10 rats in each group). The 5% CIH and 5% CIH+RH groups were exposed to CIH for 3 weeks, 8 h/d, and the frequency of hypoxia was 20 times/h. The 5% CIH+RH group was then exposed to normal gaseous environment for another 3 weeks. After the experiment, liver sections were stained with hematoxylin-eosin (HE) and the liver pathology was observed. The expression of fractalkine in the liver tissues was detected by immunohistochemical method. 1) Compared with the control group, the hepatic steatosis and inflammatory activities in the 5% CIH and 5% CIH+RH groups were more severe (all P<0.01 ); compared with the 5% CIH group, the hepatic steatosis and inflammatory activity in the 5% CIH+RH group were dramatically reduced (P<0.01 ). 2) Compared with the control group, the fractalkine expression in the 5% CIH and 5% CIH+RH groups was increased (both P<0.01). The fractalkine expression in the 5% CIH+RH group was dramatically downregulated compared with that in the 5% CIH group (P<0.01). CIH can induce liver injury and high fractalkine expression in rat liver tissues.


A large conjugative Acinetobacter baumannii plasmid carrying the sul2 sulphonamide and strAB streptomycin resistance genes.
Acinetobacter baumannii is an important nosocomial pathogen that often complicates treatment because of its high level of resistance to antibiotics. Though plasmids can potentially introduce various genes into bacterial strains, compared to other Gram-negative bacteria, information about the unique A. baumannii plasmid repertoire is limited. Here, whole genome sequence data was used to determine the plasmid content of strain A297 (RUH875), the reference strain for the globally disseminated multiply resistant A. baumannii clone, global clone 1(GC1). A297 contains three plasmids. Two known plasmids were present; one, pA297-1 (pRAY*), carries the aadB gentamicin, kanamycin and tobramycin resistance gene and another is an 8.7kb cryptic plasmid often found in GC1 isolates. The third plasmid, pA297-3, is 200kb and carries the sul2 sulphonamide resistance gene and strAB streptomycin resistance gene within Tn6172 and a mer mercuric ion resistance module elsewhere. pA297-3 transferred sulphonamide, streptomycin and mercuric ion resistance at high frequency to a susceptible A. baumannii recipient, and contains several genes potentially involved in conjugative transfer. However, a relaxase gene was not found. It also includes several genes encoding proteins involved in DNA metabolism such as partitioning. However, a gene encoding a replication initiation protein could not be found. pA297-3 includes two copies of a Miniature Inverted-Repeat Transposable Element (MITE), named MITE-297, bracketing a 77.5kb fragment, which contains several IS and the mer module. Several plasmids related to but smaller than pA297-3 were found in the GenBank nucleotide database. They were found in different A. baumannii clones and are wide spread. They all contain either Tn6172 or a variant in the same position in the backbone as Tn6172 in pA297-3. Some related plasmids have lost the segment between the MITE-297 copies and retain only one MITE-297. Others have segments of various lengths between two MITE-297 copies, and these can be derived from the region in pA297-3 via a deletion adjacent to IS related to IS26 such as IS1007 or IS1007-like. pA297-3 and its relatives represent a third type of conjugative Acinetobacter plasmid that contributes to the dissemination of antibiotic resistance in this species.


Clinical analysis and significance of cholangiography for biliary cast/stone after orthotopic liver transplantation.
Cholangiography is an important method for the diagnosis of biliary complications after orthotopic liver transplantation. The cholangiography after orthotopic liver transplantation presents special challenges, especially in patients with biliary cast/stone and biliary stenosis. We described the T-tube cholangiography combined therapeutic fibro-choledochoscopy for the diagnosis and treatment of biliary cast following after orthotopic liver transplantation. Fourteen patients who developed biliary cast/stone after liver transplantation were analyzed retrospectively. The complications were divided into three temporal stages, early, medium, and late. Hepatic functions and the characteristics of the bile duct were observed by T-tube cholangiography and endoscopy. The biliary cast after liver transplantation was divided into three categories: Solitary, multiple, and columnar. Three months after liver transplantation, bile ducts appeared fuzzy by T-tube cholangiography, but no evidence of biliary cast was found. The bile duct was feculent with flocculation during the middle stage 3-6 months after liver transplantation. At six months after transplantation, bile ducts (especially intrahepatic bile ducts) were distended; cholangiectasis was obvious with biliary cast. The intrahepatic bile duct stricture was observed on occasion by T-tube cholangiography and the intrahepatic bile duct could be thin and distended, and resembled withered branches or strings of beads. The intrahepatic bile ducts even disappeared at this stage; hepatic functions were usually unacceptable and the icterus gradually aggravated. Four cases were diagnosed earlier according to the categories of stone and stage. Curative therapy was performed promptly and the clinical outcome was acceptable. Biliary tracts of the transplanted livers could be observed by T-tube channels and biliary complications were treated effectively by therapeutic fibro-choledochoscopy. It is necessary to combine T-tube cholangiography with fibro-choledochoscopy for the diagnosis and treatment of biliary complications after orthotopic liver transplantation.


Early Results of Irrigating Goniectomy With TrabEx+: A Novel Device for the Treatment of Open-angle Glaucoma.
Irrigating goniectomy with the TrabEx+ device can lower intraocular pressure (IOP) in patients with glaucoma, as a standalone procedure or combined with cataract surgery. The aim was to describe the efficacy and safety of irrigating goniectomy performed using the TrabEx+ device, either as a standalone procedure or combined with cataract surgery, in eyes with medically treated open-angle glaucoma. A retrospective case series of eyes treated by a single surgeon at a single UK teaching hospital. Data was collected at follow-up visits at 1 week, 3, 6, 12, 18, and 24 months postoperatively. Primary outcomes included IOP and glaucoma medication reduction after surgery. Proportion of eyes achieving >20% IOP reduction, IOP <21 mm Hg, and no reoperation were classified as surgical success. Seventy-three consecutive eyes of 64 patients (mean age 68.4±13.7 y) were enrolled. 62% were treated as combined procedures with cataract surgery. Overall, mean IOP decreased from 31.3±7.3 to 20.9±10.4 mm Hg at the latest follow-up (34% reduction) (P<0.001) at the latest follow-up (16.1±10.3 mo) with mean preoperative medications decreased from 2.9±1.2 to 1.9±1.3 (P<0.001). 73% met the definition of success at latest follow-up. Postoperative complications were recorded including hyphaema (17%), uveitis (3%), hypotony (1%), and persistent vitreous hemorrhage (1%). Eighteen percent required reoperation because of treatment failure. TrabEx+ appears to be effective in lowering IOP and medication with or without cataract surgery. However, long-term safety and efficacy will be better understood in a prospective study with longer follow-up.


Roles for 53BP1 in the repair of radiation-induced DNA double strand breaks.
In mammalian cells, the mediator protein, 53BP1, exerts distinct impacts on the repair of DNA double strand breaks (DSBs) depending on the setting, for example whether the DSBs arise at telomeres or during replication or class switch recombination. Here, we focus on two roles of 53BP1 in response to ionising radiation (IR)-induced DSBs (IR-DSBs). Canonical DNA non-homologous end-joining (c-NHEJ) is the major DSB repair pathway with homologous recombination (HR) contributing to DSB repair in S/G2 phase. ATM signalling promotes histone modifications and protein assembly in the DSB vicinity, which can be visualised as irradiation induced foci (IRIF). 53BP1 assembles at DSBs in a complex manner involving the formation of nano-domains. In G1 and G2 phase, X- or gamma-ray induced DSBs are repaired with biphasic kinetics. 70-80 % of DSBs are repaired with fast kinetics in both cell cycle phases by c-NHEJ; the remaining DSBs are repaired with slower kinetics in G2 phase via HR and in G1 by a specialised form of c-NHEJ termed Artemis and resection-dependent c-NHEJ, due to a specific requirement for the nuclease, Artemis and resection factors. 53BP1 is essential for the repair of DSBs rejoined with slow kinetics in G1 and G2 phase. This 53BP1 function requires its tandem BRCT domain and interaction with NBS1. As a distinct function, 53BP1 suppresses resection during both HR and Artemis and resection-dependent c-NHEJ. This latter role requires RIF1 and is counteracted by BRCA1. 53BP1 appears to be dispensable for the rejoining of the fast c-NHEJ repair process.


Endothelin-1 and endothelin-3 stimulate ovarian steroidogenesis.
The possible direct involvement of endothelin (ET) in preovulatory follicular steroidogenesis was investigated in vitro. Follicular development in immature rats was induced by pregnant mare's serum gonadotropin (PMS). Twenty-four and 48 h after PMS injection, ovarian follicles were incubated in vitro with or without 4 x 10(-11) to 4 x 10(-5) M endothelin-1 (ET-1) or endothelin-3 (ET-3) for 2 h, or perifused in vitro with 4 x 10(-7) M of ET-1 or ET-3 for 3 h. In the incubation study, ET-1 and ET-3 significantly stimulated progesterone, testosterone, and 17 beta-estradiol production by follicles 24 and 48 h after PMS injection. Progesterone, testosterone, and 17 beta-estradiol were increased in a dose-dependent manner by 4 x 10(-11) to 4 x 10(-6) M ET-1 or ET-3; in the case of ET-3, this increase occurred only at 24 h after PMS injection. In addition, ET-1 stimulated ovarian steroid production more effectively than ET-3. In addition to their effects on ovarian steroidogenesis, both ET-1 and ET-3 increased tissue cyclic adenosine-3',5'-monophosphate (cyclic AMP) production. The steroidogenic effect of ET-1 or ET-3 was most pronounced by follicles 48 h after PMS injection. In the perifusion experiment, ET-1 and ET-3 also stimulated progesterone, testosterone, and 17 beta-estradiol secretion. These indicate the involvement of ET-1 or ET-3 in the regulation of ovarian differentiation by stimulating steroidogenesis, at least partially through the mediation of cyclic AMP.


Validation of the alpine skiing 90 seconds box jump field test and prediction of power output.
The purpose of this study was to validate the alpine ski racing 90 s box jump field-test (BJ90) with the 90 s Wingate test (W90). Fifteen elite alpine ski racers were tested on the BJ90 (0.45 m × 0.75 m × 0.9 m) and the W90 (Ergomedic 894 E Monark; Monark AB, Varberg, Sweden) test in a random order. The number of hits on the BJ90 was written down every 15 s and for the W90 the load (7.5% of body weight) was manually dropped once the subjects reached maximum RPM without resistance. Correlations and partial correlations were calculated with a 2-tailed Pearson correlation analysis. A stepwise forward regression analysis was also performed. Results present significant (P<0.05) correlations and partial correlations adjusted for body weight between the total number of hits on the BJ90 and W90 peak W, peak W/kg, mean W and mean W/kg as well as with the number of hits and W90 Mean W and mean W/kg between each 15 s time slot. A linear regression predictive equation for mean relative power (W/kg) generated from the BJ90 was established: mean relative power (W/kg)=0.055*total hits+1.080 (r=0.79, P<0.001; total hits with mean W/kg). A stepwise forward regression equation for mean absolute power (W) generated from the BJ90 was also established: mean absolute power (W)=2.305*number of hits+5.081*body weight in kg-1 -169.8 (R=0.964, P<0.001, SEE=23.56). Practitioners could use the BJ90 to assess alpine skiers lower body power as previous research showed that both are correlated with performance and are able to discriminate skier level.


Experience with selective external cephalic version at term in Saudi Arabia: a three year review.
Thirty-six patients were selected for external cephalic version at term in an attempt to reduce the number of caesarean sections performed for breech presentation. All had the option of elective caesarean section on account of a big fetus or small maternal pelvis. Our results showed that 20 fetuses out of 24 (83.3%) who had a successful external cephalic version went on to vaginal delivery.


The effect of age on seizure semiology in childhood temporal lobe epilepsy.
Complex partial seizure is the characteristic seizure type observed in epilepsy arising from temporal lobe structures. The seizure evolution in adult patients is quite stereotyped and well characterized, manifesting initially with an aura, behavioral arrest, and oroalimentary and gestural automatism. A greater variability of semiology including motor features with tonic or myoclonic components, as well as a paucity of automatism, has been reported in young children with temporal lobe epilepsy. The aim of our study was to examine in more detail the effects of age on individual ictal features to be able to determine the critical age when lesional temporal lobe seizure semiology undergoes transition from the pediatric to the more adult-type clinical pattern. We performed a video analysis of 83 seizures from 15 children (aged 11-70 months) selected by post-temporal lobectomy seizure-free outcome, looking specifically at the motor and behavioral (nonmotor) manifestations in relation to age of the children. All of the children younger than 42 months had seizures with early and marked motor features, which included tonic and myoclonic components and epileptic spasms. Parallel with age, the frequency of these motor components decreased, and in five of 11 children older than 3 years, motor features were totally absent. Analyzed quantitatively, we saw a linear and inverse correlation of the ratio of motor components with age at monitoring. These findings support the hypothesis that events in brain maturation significantly affect clinical seizure semiology and may override the more typical localizing features seen in adult-type temporal lobe epilepsy. These findings are important to consider in the early diagnosis of childhood temporal lobe epilepsy.


Dynamics of spiral waves under phase feedback control in a Belousov-Zhabotinsky reaction.
Feedback control of spiral waves by the phases of the spiral tip is investigated experimentally in a light-sensitive Belousov-Zhabotinsky reaction. The phases of rotation (Psi(r)) and meandering (Psi(m)) of the spiral tip are obtained in real time during experiments. It is found that, for both meandering and rigid rotating spirals, one can manipulate the spirals to move with any arbitrary paths by the feedback signals derived from Psi(r). Synchronization between meandering and rotation dynamics can be induced when both Psi(m) and Psi(r) are used simultaneously as control signals. Experimental findings are compared well with numerical simulations of the Oregonator model.


Factors Contributing to Attenuation of Cerebral Venous Sinus in Brain Noncontrast Computed Tomography Scan.
Background/Aim In noncontrast computed tomography (NCCT), an apparently hyper-attenuated cerebral venous sinus (CVS) may lead to suspicion of CVS thrombosis. Understanding the factors affecting attenuation of CVS can guide us toward true diagnosis. Hence, the aim of the study was to determine the effect of different factors such as hematocrit, hemoglobin, age, blood urea nitrogen (BUN), creatinine, leukocyte and platelet count, and sex on the attenuation of CVS on brain NCCT. Material and Methods Total 1,680 patients were included in this study, and their demographic and laboratory data and brain NCCT were reviewed. In their brain NCCT, the average attenuation of superior sagittal sinus and both right and left sigmoid sinuses was measured. Data analysis was conducted using the Statistical Package for the Social Sciences version 21.0 software by Kolmogorov-Smirnov, Spearman's correlation coefficient, and multiple linear regression tests. The significance level was considered less than 0.05. Results Hematocrit (B = 0.251, p < 0.001), hemoglobin (B = 0.533, p < 0.001), and creatinine (B = - 0.270, p = 0.048) were determined as predictors of attenuation of superior sagittal sinus. For both sigmoid sinuses, hematocrit ( p < 0.001) and hemoglobin ( p < 0.001) were determined as positive predictors, and creatinine ( p < 0.001) and BUN ( p < 0.002) were determined as negative and positive predictors, respectively. Conclusion Hemoglobin, hematocrit, creatinine, and BUN are the main factors that should be considered in the assessment of CVS density on brain NCCT. As with increasing hematocrit and hemoglobin of the subject, the CVS density in NCCT increases, and with increasing creatinine and in some instance decreasing BUN of the subject, the CVS density in NCCT decreases.


The Impact of COVID-19 on Older Adults' Perceptions of Virtual Care: Qualitative Study.
In response to the COVID-19 pandemic, older adults worldwide have increasingly received health care virtually, and health care organizations and professional bodies have indicated that virtual care is "here to stay." As older adults are the highest users of the health care system, virtual care implementation can have a significant impact on them and may pose a need for additional support. This research aims to understand older adults' perspectives and experiences of virtual care during the pandemic. As part of a larger study on older adults' technology use during the pandemic, we conducted semistructured interviews with 20 diverse older Canadians (mean age 76.9 years, SD 6.5) at 2 points: summer of 2020 and winter/early spring of 2021. Participants were asked about their technology skills, experiences with virtual appointments, and perspectives on this type of care delivery. Interviews were digitally recorded and transcribed. A combination of team-based and framework analyses was used to interpret the data. Participants described their experiences with both in-person and virtual care during the pandemic, including issues with accessing care and long gaps between appointments. Overall, participants were generally satisfied with the virtual care they received during the pandemic. Participants described the benefits of virtual care (eg, increased convenience, efficiency, and safety), the limitations of virtual care (eg, need for physical examination and touch, lack of nonverbal communication, difficulties using technology, and systemic barriers in access), and their perspectives on the future of virtual care. Half of our participants preferred a return to in-person care after the COVID-19 pandemic, while the other half preferred a combination of in-person and virtual services. Many participants who preferred to access in-person services were not opposed to virtual care options, as needed; however, they wanted virtual care as an option alongside in-person care. Participants emphasized a need for training and support to be meaningfully implemented to support both older adults and providers in using virtual care. Overall, our research identified both perceived benefits and perceived limitations of virtual care, and older adult participants emphasized their wish for a hybrid model of virtual care, in which virtual care is viewed as an addendum, not a replacement for in-person care. We recognize the limitations of our sample (small, not representative of all older Canadians, and more likely to use technology); this body of literature would greatly benefit from more research with older adults who do not/cannot use technology to receive care. Findings from this study can be mobilized as part of broader efforts to support older patients and providers engaged in virtual and in-person care, particularly post-COVID-19.


Photodimerisation of a coumarin-dipeptide gelator.
Here we report a coumarin based hydrogelator that can form bulk gels, or homogeneous thin gels via an electrochemical pH drop. The gel can then be strengthened by post-gelation photodimerisation of the coumarin groups by irradiating with UV light.


Microbiome function predicts amphibian chytridiomycosis disease dynamics.
The fungal pathogen Batrachochytrium dendrobatidis (Bd) threatens amphibian biodiversity and ecosystem stability worldwide. Amphibian skin microbial community structure has been linked to the clinical outcome of Bd infections, yet its overall functional importance is poorly understood. Microbiome taxonomic and functional profiles were assessed using high-throughput bacterial 16S rRNA and fungal ITS2 gene sequencing, bacterial shotgun metagenomics and skin mucosal metabolomics. We sampled 56 wild midwife toads (Alytes obstetricans) from montane populations exhibiting Bd epizootic or enzootic disease dynamics. In addition, to assess whether disease-specific microbiome profiles were linked to microbe-mediated protection or Bd-induced perturbation, we performed a laboratory Bd challenge experiment whereby 40 young adult A. obstetricans were exposed to Bd or a control sham infection. We measured temporal changes in the microbiome as well as functional profiles of Bd-exposed and control animals at peak infection. Microbiome community structure and function differed in wild populations based on infection history and in experimental control versus Bd-exposed animals. Bd exposure in the laboratory resulted in dynamic changes in microbiome community structure and functional differences, with infection clearance in all but one infected animal. Sphingobacterium, Stenotrophomonas and an unclassified Commamonadaceae were associated with wild epizootic dynamics and also had reduced abundance in laboratory Bd-exposed animals that cleared infection, indicating a negative association with Bd resistance. This was further supported by microbe-metabolite integration which identified functionally relevant taxa driving disease outcome, of which Sphingobacterium and Bd were most influential in wild epizootic dynamics. The strong correlation between microbial taxonomic community composition and skin metabolome in the laboratory and field is inconsistent with microbial functional redundancy, indicating that differences in microbial taxonomy drive functional variation. Shotgun metagenomic analyses support these findings, with similar disease-associated patterns in beta diversity. Analysis of differentially abundant bacterial genes and pathways indicated that bacterial environmental sensing and Bd resource competition are likely to be important in driving infection outcomes. Bd infection drives altered microbiome taxonomic and functional profiles across laboratory and field environments. Our application of multi-omics analyses in experimental and field settings robustly predicts Bd disease dynamics and identifies novel candidate biomarkers of infection. Video Abstract.


Bilateral sleeve fracture of the inferior poles of the patella in a healthy child: case report and review of the literature.
The initial diagnosis of a sleeve fracture of the patella is key to a successful outcome with poor results well documented in the literature from delayed management. Diagnosis is difficult due to the rarity of this injury and thus the low likelihood the admitting junior doctor would think of this injury in their differential. They are very uncommon in incidence and have features on plain radiography that are difficult to interpret unless the surgeon is familiar with the anatomy of the immature patella. Missing the diagnosis can be disastrous for the patient. In this paper we describe the presentation of bilateral sleeve fractures in a healthy child, our initial investigations and subsequent management. We chose to repair with 5 Ethibond via 3 transosseous tunnels, initially reinforced with a circlage wire. On last review the boy maintains stable, pain-free knees with a full range of motion. The authors hope that this case and literature review will provide a valuable teaching aid and so assist in early, accurate diagnosis and cover the management options to achieve a positive outcome.


Comparison of Volatiles Profile and Contents of Trichothecenes Group B, Ergosterol, and ATP of Bread Wheat, Durum Wheat, and Triticale Grain Naturally Contaminated by Mycobiota.
In natural conditions cereals can be infested by pathogenic fungi. These can reduce the grain yield and quality by contamination with mycotoxins which are harmful for plants, animals, and humans. To date, performed studies of the compounds profile have allowed for the distinction of individual species of fungi. The aim of this study was to determine the profile of volatile compounds and trichothecenes of group B, ergosterol, adenosine triphosphate content carried out on a representative sample of 16 genotypes of related cereals: triticale, bread wheat, and durum wheat. Based on an analysis of volatile compounds by means of gas chromatography mass spectrometry and with the use of an electronic nose, volatile profiles for cereals were determined. Differentiation is presented at four levels through discriminant analysis, heatmaps, principal component analysis (PCA), and electronic nose maps. The statistical model was built by subsequent incorporation of chemical groups such as trichothecenes (GC/MS), fungal biomass indicators ergosterol (HPLC) and ATP (luminometric) and volatiles. The results of the discriminatory analyses showed that the volatile metabolites most markedly differentiated grain samples, among which were mainly: lilial, trichodiene, p-xylene. Electronic nose analysis made it possible to completely separate all the analyzed cereals based only on 100 ions from the 50-150 m/z range. The research carried out using chemometric analysis indicated significant differences in the volatile metabolites present in the grain of bread wheat, durum wheat and triticale. The end result of the performed analyses was a complete discrimination of the examined cereals based on the metabolites present in their grain.


Reductions in the incidence of nitrofen-induced diaphragmatic hernia by vitamin A and retinoic acid.
Congenital diaphragmatic hernia (CDH) is a serious medical condition in which the developing diaphragm forms incompletely, leaving a hole through which the abdominal contents can enter the thoracic space and interfere with lung growth. A perturbation of the retinoid system has been linked to the etiology of CDH. This includes findings that nitrofen, which induces CDH in rodents, inhibits the key enzyme for retinoic acid (RA) production, retinaldehyde dehydrogenase-2 (RALDH2) in vitro. Published studies indicate that antenatal vitamin A administration on gestational day (D) 12 in the nitrofen model of CDH reduced the severity and incidence of right-sided defects and lung hypoplasia. In this study, we administered nitrofen on D8, to include the induction of clinically more prevalent left-sided defects, and examined the efficacy of several vitamin A administration paradigms to gain insights into the developmental stage of susceptibility. Furthermore, we tested the hypothesis that administration of RA, the product of RALDH2 activity, is more potent than administering the substrate, vitamin A, in reducing the incidence of CDH. The incidence of CDH was reduced from approximately 54% (nitrofen alone) to approximately 32% with vitamin A treatment. The efficacy of RA treatment was very marked, with a reduction in the incidence of CDH to approximately 15%. Administration of vitamin A or RA on approximately D10 was most effective. These data lend further support for the potential involvement of retinoid signaling pathways and the etiology of CDH and support data from in vitro studies demonstrating a nitrofen-induced suppression of RALDH2.


Prevalence and characteristics of complementary medicine used by pediatric cancer patients in a mixed western and middle-eastern population.
Complementary alternative medicine (CAM) usage and physicians' attitude was evaluated by interviewing all 100 pediatric cancer patients' parents and adolescents seen in the last half of 2003 at Meyer Children's Hospital in Israel. Sixty-one percent of the patients used CAM, an average of 3 different treatments per patient. CAM use was higher: among parents having previous CAM experience (85% vs. 51%, P=0.001) and higher education (79% vs. 50%, P=0.024), and in nonreligious families (71% vs. 50%). Jews and Arabs had similar CAM use rates as with different types of therapies. Socioeconomic status does not affect the rate of CAM use (P=0.9) but does affect the type of treatments used: patients of the higher socioeconomic level mainly used chemi-biological remedies and homeopathy (24% and 28% of interviewees; P=0.002). Middle or lower socioeconomic patients mostly used traditional Arab treatments (32% and 54%, respectively; P=0.012). Only 36% discussed it with their physicians, and most discussions were initiated by parents (79%). Beneficial effect was reported by 69% of CAM users. Most interviewees were interested in getting CAM information and availability in the hospital. Most pediatric cancer patients, regardless of their ethnic origin, use CAM without informing their physicians. Physicians should be aware and know more about it, to be advisors for better integrated care.


Deer antlers: a zoological curiosity or the key to understanding organ regeneration in mammals?
Many organisms are able to regenerate lost or damaged body parts that are structural and functional replicates of the original. Eventually these become fully integrated into pre-existing tissues. However, with the exception of deer, mammals have lost this ability. Each spring deer shed antlers that were used for fighting and display during the previous mating season. Their loss is triggered by a fall in circulating testosterone levels, a hormonal change that is linked to an increase in day length. A complex 'blastema-like' structure or 'antler-bud' then forms; however, unlike the regenerative process in the newt, most evidence (albeit indirect) suggests that this does not involve reversal of the differentiated state but is stem cell based. The subsequent re-growth of antlers during the spring and summer months is spectacular and represents one of the fastest rates of organogenesis in the animal kingdom. Longitudinal growth involves endochondral ossification in the tip of each antler branch and bone growth around the antler shaft is by intramembranous ossification. As androgen concentrations rise in late summer, longitudinal growth stops, the skin (velvet) covering the antler is lost and antlers are 'polished' in preparation for the mating season. Although the timing of the antler growth cycle is clearly closely linked to circulating testosterone, oestrogen may be a key cellular regulator, as it is in the skeleton of other male mammals. We still know very little about the molecular machinery required for antler regeneration, although there is evidence that developmental signalling pathways with pleiotropic functions are important and that novel 'antler-specific' molecules may not exist. Identifying these pathways and factors, deciphering their interactions and how they are regulated by environmental cues could have an important impact on human health if this knowledge is applied to the engineering of new human tissues and organs.


The role of disodium pamidronate in the management of bone pain due to malignancy.
A number of controlled studies have recently demonstrated the role of disodium pamidronate in the prevention of skeletal complications in patients with metastatic bone disease due to breast cancer and multiple myeloma. They have also shown that it relieves pain and is well tolerated. The aim of this open prospective study was to evaluate the acceptability of a new schedule of pamidronate infusion and to assess pain, analgesic consumption and the Karnofsky Performance Status (KPS) in patients with metastatic bone pain treated with pamidronate in association or not with chemotherapy, radiotherapy, and hormone therapy. Patients with different types of cancer and at least one painful bone metastasis were treated with two cycles of 60 mg intravenous (iv) pamidronate weekly for three consecutive doses, with a 3-week interval between the two cycles (six infusions over 7 weeks), followed by one infusion every 3 weeks for a total of 24 infusions. Two hundred patients were enrolled in the study, of whom 94 received at least the first six infusions; 25 patients received all 24 infusions. Pamidronate was well tolerated in the majority of the patients both during the first six infusions and during the whole study period. In the patients under study, pain intensity decreased compared with T0 after the first two infusions (second week of treatment). The mean equivalent daily dose of oral morphine required ranged from 21.5 to 41.5 mg/day and was low and stable during the study. For the patients who remained in the study, the KPS remained around 70 during the whole treatment period and intrasubject analysis showed a substantial stability of the KPS within each subject. A first fracture occurred within 321 days in 25% of the whole population under study. Pamidronate represents a further valid therapy to add to an already consolidated list of therapies such as radiotherapy, chemotherapy, hormone therapy and orthopaedic intervention in the pain management of patients with bone metastases. Future studies are necessary to evaluate the role of pamidronate and the appropriate schedule in patients with advanced or terminal cancer who are no longer being treated with oncological therapies.


Tolmerus calceatus (Meigen) confirmed as a valid species separate from Tolmerus atricapillus (Fallén) (Diptera: Asilidae).
The status of Tolmerus atricapillus calceatus (Meigen) is discussed. Based on morphological, ecological as well as genetic information it is concluded that Tolmerus calceatus stat. rev. should be treated as a valid species separate from T. atricapillus (Fallén). Characters to separate both are provided as well as a key to all Tolmerus species of northwestern Europe.


Flow cytometric analysis of cerebrospinal fluid samples and its usefulness in routine clinical practice.
Low volume and few cells have hampered the use of flow cytometry for studying cerebrospinal fluid (CSF) in routine clinical practice, although information about the cellular phenotypes present in this type of sample is of great value in many diseases. We developed a novel flow cytometric strategy capable of identifying total CSF T lymphocytes and the CD4+ subset, even in CSF samples with as few as 1 leukocyte per 3 microL of sample. We also showed that identification of CD8+ T cells could be achieved in most samples, while B lymphocytes are detectable only in samples with more than 5 cells per microliter. These findings demonstrate the reliability of this method to improve the diagnostic accuracy of classic cytologic studies in many neurologic disorders.


Hormones and young leaves control development of cotyledonary buds in tomato seedlings.
Hormonal and plant factors regulating the development of the inhibited cotyledonary buds of Lycopersicon esculentum Mill. cv. ;Fireball' seedlings were studied. Excision of the immature plumular leaves of 5- to 20- millimeter length significantly stimulated bud development after 2 to 4 days, but excision of leaves exceeding 20-millimeter length was without effect. Apical application of 20 microliters of 5 millimolar abscisic acid significantly promoted development of the cotyledonary buds after 6 days. A subapical ring of 0.1 millimolar concentration of 2,3,5-triiodobenzoic acid (TIBA) in lanolin significantly promoted cotyledonary bud development after 11 days. Twenty microliters of 0.1 millimolar 6-benzylaminopurine (BAP) applied directly to the cotyledonary bud loci significantly promoted bud development, but 1 micromolar gibberellin A(4/7) was ineffective. Application of 0.1 millimolar BAP in lanolin to the petiole or hypocotyl was ineffective. However, application of 0.1 millimolar TIBA as a ring around the petioles of the cotyledons or 1-centimeter on the hypocotyl below the cotyledons significantly promoted cotyledonary bud development.


Selecting Scenarios for Hearing-Related Laboratory Testing.
For hearing aid users to experience everyday benefit from their hearing aids, research, development, and fitting of hearing aids must be performed using evaluation methods that are indicative of everyday performance. These evaluations can take place both in peoples' ordinary lives and in laboratory settings. For the results of laboratory testing to be ecologically valid, the selected test scenarios must capture the essence of everyday listening. The present article discusses the selection of these laboratory test scenarios in three parts. Part 1 reviews prior research on the selection of everyday listening situations for laboratory testing and discusses realistic test scenarios as important research tools. Part 2 presents findings from an ecological momentary assessments study in which 19 experienced hearing aid users reported real-time auditory reality data, including their current listening activity and their current sound environment. Participants categorized their listening situations according to the common sound scenarios framework and rated how often each situation occurred, how important it was to hear well, and how difficult it was to hear in the situation. These ratings made it possible to filter the data according to three criteria (occurrence, importance, and difficulty). The filtered data could potentially be used for selecting laboratory test scenarios. Part 3 uses the data from Part 2 and data from the studies reviewed in Part 1 to broadly explore the test scenarios that various selection criteria lead to. Further, implementation of test scenarios in the laboratory, and the strengths and limitations of data collection methods for investigating auditory reality are briefly discussed. The article concludes with a summary of the collected study.


Effects of sediment exposure on corals: a systematic review of experimental studies.
Management actions that address local-scale stressors on coral reefs can rapidly improve water quality and reef ecosystem condition. In response to reef managers who need actionable thresholds for coastal runoff and dredging, we conducted a systematic review and meta-analysis of experimental studies that explore the effects of sediment on corals. We identified exposure levels that 'adversely' affect corals while accounting for sediment bearing (deposited vs. suspended), coral life-history stage, and species, thus providing empirically based estimates of stressor thresholds on vulnerable coral reefs. We searched online databases and grey literature to obtain a list of potential studies, assess their eligibility, and critically appraise them for validity and risk of bias. Data were extracted from eligible studies and grouped by sediment bearing and coral response to identify thresholds in terms of the lowest exposure levels that induced an adverse physiological and/or lethal effect. Meta-regression estimated the dose-response relationship between exposure level and the magnitude of a coral's response, with random-effects structures to estimate the proportion of variance explained by factors such as study and coral species. After critical appraisal of over 15,000 records, our systematic review of corals' responses to sediment identified 86 studies to be included in meta-analyses (45 studies for deposited sediment and 42 studies for suspended sediment). The lowest sediment exposure levels that caused adverse effects in corals were well below the levels previously described as 'normal' on reefs: for deposited sediment, adverse effects occurred as low as 1 mg/cm2/day for larvae (limited settlement rates) and 4.9 mg/cm2/day for adults (tissue mortality); for suspended sediment, adverse effects occurred as low as 10 mg/L for juveniles (reduced growth rates) and 3.2 mg/L for adults (bleaching and tissue mortality). Corals take at least 10 times longer to experience tissue mortality from exposure to suspended sediment than to comparable concentrations of deposited sediment, though physiological changes manifest 10 times faster in response to suspended sediment than to deposited sediment. Threshold estimates derived from continuous response variables (magnitude of adverse effect) largely matched the lowest-observed adverse-effect levels from a summary of studies, or otherwise helped us to identify research gaps that should be addressed to better quantify the dose-response relationship between sediment exposure and coral health. We compiled a global dataset that spans three oceans, over 140 coral species, decades of research, and a range of field- and lab-based approaches. Our review and meta-analysis inform the no-observed and lowest-observed adverse-effect levels (NOAEL, LOAEL) that are used in management consultations by U.S. federal agencies. In the absence of more location- or species-specific data to inform decisions, our results provide the best available information to protect vulnerable reef-building corals from sediment stress. Based on gaps and limitations identified by our review, we make recommendations to improve future studies and recommend future synthesis to disentangle the potentially synergistic effects of multiple coral-reef stressors. The online version contains supplementary material available at 10.1186/s13750-022-00256-0.


Correlation between anticurare activity of tetanic stimulation and neostigmine in anesthetized man.
Frequency and dose-dependent changes in neuromuscular transmission were examined in 70 patients undergoing elective surgical procedures requiring the use of muscle relaxants. Anesthesia was induced with sodium thiopental and maintained with N2O-O2 and fractional dose of meperidine or fentanyl. Neuromuscular block was produced and maintained at 80% level with incremental intravenous doses of d-tubocurarine. Neuromuscular function was measured by recording the force of thumb adduction evoked by supramaximal stimulation of the ulnar nerve at the wrist. Single stimuli were applied every 2.5 seconds as square pulses of 0.1-msec duration. In 30 patients tetanic trains of 10-second duration ranging from 10 to 400 Hz were used. In 40 patients neostigmine doses ranging from 0.5 to 5.0 mg were used. Criteria for responses to 10-second tetanic trains during 80% neuromuscular block were determined and compared with responses after neostigmine. At a frequency of 50 Hz a complete tetanic fade was followed by partial posttetanic relief of block. At a frequency of 200 Hz tetanic fade was followed by complete but transient posttetanic decurarization. The original control twitch tension was not exceeded in posttetanic or postdrug responses. It is concluded that the transient after effects of tetanic stimulation are closely related to the anticurare effects of neostigmine.


An N-terminal region of Caenorhabditis elegans RGS proteins EGL-10 and EAT-16 directs inhibition of G(alpha)o versus G(alpha)q signaling.
Regulator of G protein signaling (RGS) proteins contain an RGS domain that inhibits G(alpha) signaling by activating G(alpha) GTPase activity. Certain RGS proteins also contain a Ggamma-like (GGL) domain and a poorly characterized but conserved N-terminal region. We assessed the functions of these subregions in the Caenorhabditis elegans RGS proteins EGL-10 and EAT-16, which selectively inhibit GOA-1 (G(alpha)(o)) and EGL-30 (G(alpha)(q)), respectively. Using transgenes in C. elegans, we expressed EGL-10, EAT-16, their subregions, or EGL-10/EAT-16 chimeras. The chimeras showed that the GGL/RGS region of either protein can act on either GOA-1 or EGL-30 and that a key factor determining G(alpha) target selectivity is the manner in which the N-terminal and GGL/RGS regions are linked. We also found that coexpressing N-terminal and GGL/RGS fragments of EGL-10 gave full EGL-10 activity, whereas either fragment alone gave little activity. Biochemical analysis showed that coexpressing the two fragments caused both to increase in abundance and also caused the GGL/RGS fragment to move to the membrane, where the N-terminal fragment is localized. By coimmunoprecipitation, we found that the N-terminal fragment complexes with the C-terminal fragment and its associated Gbeta subunit, GPB-2. We conclude that the N-terminal region directs inhibition of G(alpha) signaling by forming a complex with the GGL/RGS region and affecting its stability, membrane localization, and G(alpha) target specificity.


Dendritic cells generated in the presence of vitamin D3 and stimulated with lipopolysaccharide secrete IL-8, IL-1β, IL-10 and induce relatively low levels of CD4+CD25hiFoxp3+ T cells.
Vitamin D3 (VD3) has been described as a modulator of immune system cells, including dendritic cells (DC). Previous studies have shown its importance in in vitro generation of tolerogenic DC, which have a similar function and phenotype to that of CD141 dermal DCs that produce IL-10 and induce (LTreg) CD4+ T regulator cells. This paper presents a study that compares the phenotype and cytokines produced by DC generated in presence and absence of VD3, which were matured with lipopolysaccharide (LPS), and their ability to induce LTreg from naïve allogeneic CD4+ T cells. In order to compare them, peripheral blood mononuclear cells were isolated to select monocytes CD14+ T cells and differentiate them in vitro from DC in the presence and absence of VD3, and to mature them with LPS. Phenotype and cytokine levels were also analyzed in the culture supernatants. Dendritic cells were then co-cultured with naïve allogeneic CD4+ T cells and the frequencies of LTreg were determined (naïve-activated). The results showed that unstimulated DC generated with VD3 kept the CD14. When activated with LPS, they expressed lower levels of C83, CD83 and CD86; HLA-DR; higher amounts of IL-1β, IL-8, IL-10, and tended to lessen IL-6, IL-12p70 and TGF-β1, compared to DCs not treated with VD3. The frequency of naïve LTreg was similar, although immature DC generated with VD3 tended to induce activated LTregs. Based on these results, it is possible to conclude that DCs generated with VD3 and treated with LPS presented a 'semi-mature' phenotype, and were able to secrete pro-inflammatory and anti-inflammatory cytokines. Besides, they did not increase their capacity to promote the polarization of naïve allogenic CD4+ T cells towards LTregs.


Isolation of mycobacteria from clinical samples collected in the United States from 2004 to 2011.
Mycobacteria other than M. bovis may interfere with current bovine tuberculosis diagnostic tests resulting in false positive test results. As the prevalence of M. bovis decreases in the United States, interference from other mycobacteria play an increasingly important role in preventing the eradication of M. bovis. To identify mycobacteria other than M. bovis that may be interfering with current diagnostic tests, a retrospective study was performed to identify mycobacteria isolated from clinical tissues at the National Veterinary Services Laboratories between 1 January 2004 and 9 October 2011. During the study period, 2,366 mycobacteria other than M. bovis were isolated from samples submitted for clinical diagnosis of M. bovis. Fifty-five mycobacterial species were isolated during this time period. In cattle, M. avium complex, M. fortuitum/fortuitum complex, M. smegmatis, M. kansasii, and M. terrae complex were the predominate species other than M. bovis isolated from tissues submitted for culture. Mycobacteria other than M. bovis isolated from deer were predominantly M. avium complex, M. terrae/terrae complex, and M. fortuitum/fortuitum complex. These data provide information characterizing the species and relative prevalence of mycobacteria other than M. bovis that may interfere with current diagnostic tests.


Missing metastases as a model to challenge current therapeutic algorithms in colorectal liver metastases.
In oncosurgical approach to colorectal liver metastases, surgery remains considered as the only potentially curative option, while chemotherapy alone represents a strictly palliative treatment. However, missing metastases, defined as metastases disappearing after chemotherapy, represent a unique model to evaluate the curative potential of chemotherapy and to challenge current therapeutic algorithms. We reviewed recent series on missing colorectal liver metastases to evaluate incidence of this phenomenon, predictive factors and rates of cure defined by complete pathologic response in resected missing metastases and sustained clinical response when they were left unresected. According to the progresses in the efficacy of chemotherapeutic regimen, the incidence of missing liver metastases regularly increases these last years. Main predictive factors are small tumor size, low marker level, duration of chemotherapy, and use of intra-arterial chemotherapy. Initial series showed low rates of complete pathologic response in resected missing metastases and high recurrence rates when unresected. However, recent reports describe complete pathologic responses and sustained clinical responses reaching 50%, suggesting that chemotherapy could be curative in some cases. Accordingly, in case of missing colorectal liver metastases, the classical recommendation to resect initial tumor sites might have become partially obsolete. Furthermore, the curative effect of chemotherapy in selected cases could lead to a change of paradigm in patients with unresectable liver-only metastases, using intensive first-line chemotherapy to intentionally induce missing metastases, followed by adjuvant surgery on remnant chemoresistant tumors and close surveillance of initial sites that have been left unresected.


p53: an overview of over two decades of study.
p53 is the most commonly mutated gene in human cancers. It encodes a 53 kilodalton protein with several evolutionarily conserved domains viz sequence-specific DNA binding, tetramerisation, SH3 molecule binding, C-terminal and N-terminal. Existing in the cell at a very low level and in a relatively inactive form, p53 protein is increased and activated during periods of cellular stress. Unlike other proteins, the increase in protein level and its activation result from modification of the protein rather than genetic transcriptional or translational upregulation. Normally, Mdm2 protein interacts with p53 protein and effectively targets it for ubiquitin proteolysis within an autoregulatory feedback loop. Phosphorylation at the N-terminus reduces p53 interaction with Mdm2 with a resultant increase in p53 protein level. Modification at the C and N termini via phosphorylation or acetylation upregulates binding to specific DNA targets increasing transcription of these downstream genes. The net effect of p53 protein increase and activation lies in arrest of the cell in cycle which allows time for repair of the incurred damage or apoptosis or death of the cell. Failure of these normal protective and adaptive mechanisms caused by mutation of the p53 gene with product of an abnormal protein, loss of p53 protein through interaction with and degradation by HPV E6 protein or overexpressed Mdm2 etc. permits DNA-damaged cells to continue replicating. Left unchecked, this frequently contributes to tumourigenesis. Various methods have been devised to screen for mutations of the p53 gene, still the most common source of failed p53 mechanism. These include immunohistochemical detection of mutated proteins or identification of altered electrophoretic mobility of mutated p53 sequences. Sequencing of the gene nonetheless remains the most accurate method for determination of mutation. Major advances have been made in p53 research but the most meaningful probably lies in the promising results achieved in tumour therapy where introduction of wild type p53 gene has resulted in regression of non-small-cell lung cancer (NSCLC). Many other notable developments in this field include description of p53 homologues, "gain of function" mutants, p53 polymorphisms, angiogenesis-inhibiting properties of wild type p53 protein etc.


Does percutaneous transluminal coronary angioplasty accelerate atherosclerotic lesions?
Recent reports have suggested that angioplasty may cause or accelerate coronary arterial stenoses secondary to traumatic injury. Ninety-four coronary angiograms performed in a 1 yr period were reviewed in patients who had successful coronary angioplasty 6 to 30 mo (mean 10.7) prior to restudy. Restenosis was found in 43 of 140 dilated lesions (31%) and in 41 of 94 patients (44%). Thirty-three (35%) patients had new or progressive lesions outside the angioplasty site. New or progressive lesions occurred with similar frequency in the arteries that did not have angioplasty (23/155 = 15%) as in the arteries that did (13/127 = 10%; chi-square n.s.). In the arteries which underwent angioplasty, new or progressive lesions occurred as commonly proximal to the PTCA site (7/14, 50%) as distal (6/13, 46%). New or progressive lesions occurred in 29% of patients with concomitant restenosis, and 40% of those without restenosis (chi-square n.s.). No clinical, angiographic, or procedural factors distinguished patients with new and progressive lesions in target vessels from those without these lesions in target vessels. Patients with progressive lesions anywhere in the coronary tree were more likely to have had a shorter duration of anginal symptoms before angioplasty and a family history of coronary disease when compared with patients without progressive atherosclerosis. In conclusion, new and progressive lesions outside the angioplasty site occur after the procedure but appear unrelated to the restenosis process or traumatic injury by angioplasty instrumentation.


Is surgical excision necessary for focal atypical ductal hyperplasia found at stereotactic vacuum-assisted breast biopsy?
Our goal was to determine the upgrade rate for lesions described as focal atypical ductal hyperplasia (ADH) after 9- or 11-gauge stereotactic vacuum-assisted breast biopsy (VABB) to determine whether surgical excision is indicated in this setting. We retrospectively reviewed the results of 991 consecutive 9- or 11-gauge stereotactic core VABB procedures from February 2001 through June 2006 and identified lesions diagnosed as ADH. On the basis of the descriptions in pathology reports each lesion was placed in one of three categories: (1) focal ADH, (2) ADH suspicious for ductal carcinoma-in-situ, or (3) ADH not otherwise specified. The final diagnosis after surgical excisional biopsy was determined from medical records. The frequencies and upgrade rates to carcinoma were calculated and compared for all lesions and for each ADH category. A total of 141 (14.2%) of 991 lesions yielded ADH at stereotactic core VABB, and 123 (87.2%) of 141 underwent surgical excisional biopsy of the stereotactic core VABB site. A total of 56 (45.5%) of 123 were categorized as focal ADH, and 7 (12.5%) of 56 were upgraded to carcinoma. A total of 49 (39.8%) of 123 were categorized as ADH not otherwise specified, and 11 (22.4%) of 49 were upgraded. Eighteen (14.6%) of 123 were categorized as suspicious for ductal carcinoma-in-situ, and 8 (44.4%) of 18 were upgraded. Neither the frequency of ADH (P = .66) nor the upgrade rates (P = .87) were significantly different between 9- and 11-gauge VABB. Surgical excisional biopsy is indicated to exclude carcinoma in cases of focal ADH discovered at 9- or 11-gauge VABB.


Clinical Study of NeuroRegen Scaffold Combined With Human Mesenchymal Stem Cells for the Repair of Chronic Complete Spinal Cord Injury.
Regeneration of damaged neurons and recovery of sensation and motor function after complete spinal cord injury (SCI) are challenging. We previously developed a collagen scaffold, NeuroRegen, to promote axonal growth along collagen fibers and inhibit glial scar formation after SCI. When functionalized with multiple biomolecules, this scaffold promoted neurological regeneration and functional recovery in animals with SCI. In this study, eight patients with chronic complete SCI were enrolled to examine the safety and efficacy of implanting NeuroRegen scaffold with human umbilical cord mesenchymal stem cells (hUCB-MSCs). Using intraoperative neurophysiological monitoring, we identified and surgically resected scar tissues to eliminate the inhibitory effect of glial scarring on nerve regeneration. We then implanted NeuroRegen scaffold loaded with hUCB-MSCs into the resection sites. No adverse events (infection, fever, headache, allergic reaction, shock, perioperative complications, aggravation of neurological status, or cancer) were observed during 1 year of follow-up. Primary efficacy outcomes, including expansion of sensation level and motor-evoked potential (MEP)-responsive area, increased finger activity, enhanced trunk stability, defecation sensation, and autonomic neural function recovery, were observed in some patients. Our findings suggest that combined application of NeuroRegen scaffold and hUCB-MSCs is safe and feasible for clinical therapy in patients with chronic SCI. Our study suggests that construction of a regenerative microenvironment using a scaffold-based strategy may be a possible future approach to SCI repair.


Lexical access in college students with learning disabilities: an electrophysiological and performance-based investigation.
The purpose of this study was to compare the semantic processing abilities of college students with learning disabilities (LD) to those of their peers without learning disabilities (NLD) who were matched for age, gender, and intelligence. Participants were compared on results from the Test of Adolescent/Adult Word Finding (TAWF) and from event-related potential (N400) sampling to the processing of semantically incongruous sentences. The LD and NLD groups did not significantly differ in accuracy on the TAWF; however, students with LD demonstrated a significantly greater number of delayed responses. The LD group's N400 responses were significantly delayed at the Pz electrode site. Effect size indicators also revealed somewhat reduced amplitudes at Fz and Cz locations. The significant delays of the students with LD on standardized testing and on N400 suggest an inefficiency in the semantic processing of these individuals, in both automatic and attention-based aspects of lexical access.


The osteogenesis performance of titanium modified via plasma-enhanced chemical vapor deposition: in vitro and in vivo studies.
Titanium (Ti) and its alloys are widely used in dental implants due to their favorable mechanical properties and biocompatibility. Surface characteristics, including physical and chemical properties, are crucial factors to enhance the osteogenesis performance of Ti. The aim of this study is to evaluate amino group surface modification to facilitate the osteogenic potential and bone repair of dental implants both in vitro and in vivo. Herein, amino group-modified Ti surfaces were constructed via the plasma-enhanced chemical vapor deposition (PECVD) technique with an allylamine monomer. The adhesion, proliferation, alkaline phosphate activity and osteogenesis-related genetic expression of MG-63 cells on the surfaces were performed in vitro and presented a significant increase in amino group-modified Ti compared with that in Ti. The in vivo study in miniature pigs was evaluated through micro-computed tomography analysis and histological evaluation, which exhibited enhanced new bone formation in amino group-modified Ti compared with that in Ti after implantation for 4, 8 and 12 weeks. Consequently, amino group surface modification with the PECVD technique may provide a promising modification method to enhance the osteogenesis performance of Ti implants.


Synthesis of Monometallic (Au and Pd) and Bimetallic (AuPd) Nanoparticles Using Carbon Nitride (C3N4) Quantum Dots via the Photochemical Route for Nitrophenol Reduction.
In this study, we report the synthesis of monometallic (Au and Pd) and bimetallic (AuPd) nanoparticles (NPs) using graphitic carbon nitride (g-C3N4) quantum dots (QDs) and photochemical routes. Eliminating the necessity of any extra stabilizer or reducing agent, the photochemical reactions have been carried out using a UV light source of 365 nm where C3N4 QD itself functions as a suitable stabilizer as well as a reducing agent. The g-C3N4 QDs are excited upon irradiation with UV light and produce photogenerated electrons, which further facilitate the reduction of metal ions. The successful formation of Au, Pd, and AuPd alloy nanoparticles is evidenced by UV-vis, powder X-ray diffraction, X-ray photon spectroscopy, and energy-dispersive spectroscopy techniques. The morphology and distribution of metal nanoparticles over the C3N4 QD surface has been systematically investigated by high-resolution transmission electron microscopy (HRTEM) and SAED analysis. To explore the catalytic activity of the as-prepared samples, the reduction reaction of 4-nitrophenol with excellent performance is also investigated. It is noteworthy that the synthesis of both monometallic and bimetallic NPs can be accomplished by using a very small amount of g-C3N4, which can be used as a promising photoreducing material as well as a stabilizer for the synthesis of various metal nanoparticles.


Assessing the Role of Inhibition in Stabilizing Neocortical Networks Requires Large-Scale Perturbation of the Inhibitory Population.
Neurons within cortical microcircuits are interconnected with recurrent excitatory synaptic connections that are thought to amplify signals (Douglas and Martin, 2007), form selective subnetworks (Ko et al., 2011), and aid feature discrimination. Strong inhibition (Haider et al., 2013) counterbalances excitation, enabling sensory features to be sharpened and represented by sparse codes (Willmore et al., 2011). This balance between excitation and inhibition makes it difficult to assess the strength, or gain, of recurrent excitatory connections within cortical networks, which is key to understanding their operational regime and the computations that they perform. Networks that combine an unstable high-gain excitatory population with stabilizing inhibitory feedback are known as inhibition-stabilized networks (ISNs) (Tsodyks et al., 1997). Theoretical studies using reduced network models predict that ISNs produce paradoxical responses to perturbation, but experimental perturbations failed to find evidence for ISNs in cortex (Atallah et al., 2012). Here, we reexamined this question by investigating how cortical network models consisting of many neurons behave after perturbations and found that results obtained from reduced network models fail to predict responses to perturbations in more realistic networks. Our models predict that a large proportion of the inhibitory network must be perturbed to reliably detect an ISN regime robustly in cortex. We propose that wide-field optogenetic suppression of inhibition under promoters targeting a large fraction of inhibitory neurons may provide a perturbation of sufficient strength to reveal the operating regime of cortex. Our results suggest that detailed computational models of optogenetic perturbations are necessary to interpret the results of experimental paradigms.SIGNIFICANCE STATEMENT Many useful computational mechanisms proposed for cortex require local excitatory recurrence to be very strong, such that local inhibitory feedback is necessary to avoid epileptiform runaway activity (an "inhibition-stabilized network" or "ISN" regime). However, recent experimental results suggest that this regime may not exist in cortex. We simulated activity perturbations in cortical networks of increasing realism and found that, to detect ISN-like properties in cortex, large proportions of the inhibitory population must be perturbed. Current experimental methods for inhibitory perturbation are unlikely to satisfy this requirement, implying that existing experimental observations are inconclusive about the computational regime of cortex. Our results suggest that new experimental designs targeting a majority of inhibitory neurons may be able to resolve this question.


Additive manufacturing of micrometric crystallization vessels and single crystals.
We present an all-additive manufacturing method that is performed at mild conditions, for the formation of organic single crystals at specific locations, without any photolithography prefabrication process. The method is composed of two steps; inkjet printing of a confinement frame, composed of a water soluble electrolyte. Then, an organic semiconductor solution is printed within the confinement to form a nucleus at a specific location, followed by additional printing, which led to the growth of a single crystal. The specific geometry of the confinement enables control of the specific locations of the single crystals, while separating the nucleation and crystal growth processes. By this method, we printed single crystals of perylene, which are suitable for the formation of OFETs. Moreover, since this method is based on a simple and controllable wet deposition process, it enables formation of arrays of single crystals at specific locations, which is a prerequisite for mass production of active organic elements on flexible substrates.


Mfd and transcriptional derepression cause genetic diversity in Bacillus subtilis.
Scientists have been aware for many years of genetic programs that get activated under stress and produce genetic variants in cells that escape non-proliferating conditions. These programs are well conserved in all organisms and expand our view of evolution. They mediate genome instability, create diversity in antibody formation, expand metabolism and increase fitness of pathogens within host environments. Error-prone DNA replication and repair are genetic variability-causing agents that get stimulated by the onset of cellular stresses. Embedded in these programs is the ability to limit mutagenesis to defined genomic regions and times, ensuring integrity of most of the genome. Recent evidence suggests that factors involved in RNA polymerase (RNAP) processivity or transcriptional derepression contribute to the generation of stress-induced mutations. In Bacillus subtilis, transcription-associated mutagenesis has been shown to be independent of recombination-dependent repair and, in some cases, of the Y DNA polymerases. Central to stationary-phase mutagenesis in B. subtilis is the requirement for Mfd, transcription coupling repair factor, which suggests a novel mechanism from those described in other model systems.


Coxiella burnetii abortion in captive dama gazelle (Gazella Dama) in the United Arab Emirates.
Abstract: Five cases of late-stage abortion in dama gazelle (Gazella dama) occurred in the United Arab Emirates. Histopathologic and molecular diagnostics found the abortions to be associated with Coxiella burnetii infection. Examination of the herd 6 mo later revealed a significant number of serologically positive animals but failed to detect the antigen in genital swabs. There are few reports in the literature of C. burnetii abortion in nondomestic ungulates and no published reports from the United Arab Emirates.


Protease-activated receptor-1 contributes to renal injury and interstitial fibrosis during chronic obstructive nephropathy.
End-stage renal disease, the final stage of all chronic kidney disorders, is associated with renal fibrosis and inevitably leads to renal failure and death. Transition of tubular epithelial cells (TECs) into mesenchymal fibroblasts constitutes a proposed mechanism underlying the progression of renal fibrosis and here we assessed whether protease-activated receptor (PAR)-1, which recently emerged as an inducer of epithelial-to-mesenchymal transition (EMT), aggravates renal fibrosis. We show that PAR-1 activation on TECs reduces the expression of epithelial markers and simultaneously induces mesenchymal marker expression reminiscent of EMT. We next show that kidney damage was reduced in PAR-1-deficient mice during unilateral ureter obstruction (UUO) and that PAR-1-deficient mice develop a diminished fibrotic response. Importantly, however, we did hardly observe any signs of mesenchymal transition in both wild-type and PAR-1-deficient mice suggesting that diminished fibrosis in PAR-1-deficient mice is not due to reduced EMT. Instead, the accumulation of macrophages and fibroblasts was significantly reduced in PAR-1-deficient animals which were accompanied by diminished production of MCP-1 and TGF-β. Overall, we thus show that PAR-1 drives EMT of TECs in vitro and aggravates UUO-induced renal fibrosis although this is likely due to PAR-1-dependent pro-fibrotic cytokine production rather than EMT.


Exploring the apparent absence of psychosis amongst the Borana pastoralist community of Southern Ethiopia. A mixed method follow-up study.
There are few reports of the prevalence of psychotic disorders among isolated population groups. Where present, variations in prevalence estimates raise questions about the validity of methods of case ascertainment in such settings. In a previous population-based survey of the Borana pastoralist community in Ethiopia using the Composite International Diagnostic Interview, no cases of schizophrenia were identified. In order to further explore this finding and investigate how serious mental disorder is conceptualized, we conducted focus group discussions with key members of the Borana pastoralist community. Subsequently, focus group participants were used as key informants to identify cases with possible psychotic disorder, based on their conceptualization. Cases identified by key informants were interviewed by a trained psychiatrist using the Schedules for Clinical Assessment in Neuropsychiatry (SCAN), to confirm presence of disorder. Focus group discussions were subjected to thematic analysis. The incongruity between local and psychiatric concepts lay mainly in the fact that key informants described characteristics of marata ("madness") in terms of overt behavioural symptoms. Following the focus group discussions, participants identified eight individuals with schizophrenia and 13 with a psychotic mood disorder, confirmed through SCAN interview. Studies of psychotic disorders in such communities are likely to benefit from combining structured interviews with the key informant method.


Impact of Climatic Variations on Drug-induced Skin Reactions in Two Different Regions of India.
Around 2-3% of hospitalizations have been reported due to dermatological adverse drug reactions. Recent studies suggest that climatic variations affect the skin barrier function and extreme conditions aggravate skin disorders. The present study was designed to compare the impact of climatic variations on drug-induced skin reactions in the Northern and Eastern regions of India. We performed a one-year retrospective study to evaluate the impact of climatic variations (temperature and humidity) on drug-induced skin reactions in the Eastern (Kalyani, West Bengal) and Northern (Karnal, Haryana) regions. Drug-induced skin reactions were reported month-- wise in both the Eastern and Northern regions. Temperature and humidity levels were also noted month-wise in both regions. The direct correlation between climatic variations and the number of drug reactions were assessed using Pearson's correlation and quadratic regression analysis. Overall, 99 and 81 dermatological adverse drug reactions were reported in tertiary care hospitals in the Northern and Eastern regions, respectively. During the summer season, the humidity level was found to be low in the Northern region as compared to the Eastern region. During this period, drug-induced skin reactions were reported significantly (p<0.05) more in the Northern region as compared to the Eastern region. Furthermore, quadratic regression analysis revealed that climatic variations contributed to drug reaction variability in the Northern region (68.5%) and Eastern region (23.5%). Therefore, the difference in the prevalence of drug-induced skin reactions may be related to the different climatic conditions among these two regions. Further studies in controlled climatic conditions should be performed for definitive correlations and to look into possible solutions.


Socioeconomic status and microalbuminuria in an Asian population.
In studies from developed Western countries, lower socioeconomic status (SES) has been reported to be associated with kidney diseases. However, this hypothesis has not been examined in populations from newly industrialized Asian countries. We evaluated the association between SES and micro/macroalbuminuria in a population-based sample in Singapore. We examined 920 participants of Malay ethnicity aged 40-80 years (49.6% female). SES was defined through education, income and housing type of participants. The main outcome of interest was the presence of micro/macroalbuminuria defined as a urinary albumin-to-creatinine ratio (ACR) >or=17 mg/g for men and >or=25 mg/g for women. Lower categories of SES were associated with micro/macroalbuminuria; compared to the higher categories of SES, the odds ratio (95% confidence interval) of micro/macroalbuminuria was 1.76 (1.23-2.52) for primary/lower education, 1.64 (1.16-2.31) for income <1000 Singapore dollars (SGD)/retired status, 1.44 (1.01-2.06) for small/medium housing type and 2.37 (1.56-3.60) for the coexistence of all three low SES factors (primary/ below education, income <1000 SGD/retired status and small/medium housing type) compared to <or=1 low SES factor. This pattern of association was consistently present in subgroup analyses by gender and age. Lower SES is associated with the presence of micro/macroalbuminuria independent of age, gender, smoking, alcohol intake and body mass index among Malay adults in Singapore.


Surface Activity and Aggregation Behavior of Siloxane-Based Ionic Liquids in Aqueous Solution.
Six novel siloxane-based surface-active ionic liquids (SAILs)--siloxane ammonium carboxylate [Si(n)N(2)-CA(1), (n = 3, 4)]--were designed and synthesized. Their melting points, surface activities, and self-aggregation behavior in aqueous solution were studied. The results showed that because of the bulky hydrophobic siloxane chains at the end of the tail, all six siloxane-based SAILs are room-temperature ionic liquids (RT-SAILs). The introduction of the siloxane group can reduce the melting point of ionic liquids to below room temperature and can promote the micellization and aggregation behavior more efficiently. These siloxane-based SAILs can greatly reduce the surface tension of water, as shown by the critical aggregation concentration (γCAC) values of 20 mN·m(-1); all six siloxane RT-SAILs can form a vesicle spontaneously in aqueous solution, indicating potential uses as model systems for biomembranes and vehicles for drug delivery.


The Southeastern Asian house mouse (Mus musculus castaneus Linn.) as a new passenger host for Cryptococcus neoformans var. grubii molecular type VNI.
We describe Mus musculus castaneus as a new mammalian host for Cryptococcus neoformans var. grubii (VNI). Eighteen apparently healthy adults and pups of the rodent were collected from human dwellings in Varanasi, a city of India. Both clinical and behavioral examinations of the rodents did not reveal any sign of the disease. Among visceral organs, histological examination of only liver exhibited the presence of single celled, encapsulated, Southgate's mucicarmine positive fungal structures consistent with C. neoformans. Nevertheless, culture of tissue homogenates of brain, lungs, liver, and kidneys yielded white colonies on Sabouraud's dextrose agar and brown mucoid colonies of C. neoformans on Staib's and Tobacco agar media. The pathogen was isolated from habitat soil as well as fresh faeces of the animals. All isolates were urease positive, nitrate and canavanine-glycine bromothymol blue negative, exhibited phenoloxidase activity and grew at 37°C. The isolates were identified as C. neoformans var. grubii with ITS primers and unique marker (GACA)4. The pathogen when inoculated in immunosuppressed mice showed low pathogenicity. To our knowledge, we for the first time report case cluster of Mus musculus castaneus as new passenger host for C. neoformans var. grubii (VNI).


[Safety and side effects of inhalant steroid therapy in children with bronchial asthma].
Therapy of asthma with inhaled steroids in children becomes the main standard for treatment of asthmatic airway inflammation. Thus, in most children asthma is controlled by the new galenic formulations of topical inhalative corticosteroids. Dose-dependent side effects must be known and have to be detected by appropriate testing. In childhood the suppression of the hypothalamic-pituitary-adrenocortical axis and of growth is the main concern of steroid therapy. The latter depends on dose and duration of intake as well as the susceptibility of the growth phase during which the child inhales steroids. Today, doses of topical steroid up to about 800 micrograms/day seem to be safe. However, some cases with individual reactions to low doses of inhaled steroids are known: therefore, close clinical control of children on inhaled steroids is extremely important.


The use of strain-gauge plethysmography in the functional assessment of chronic venous disease: five-year experience at a single centre.
Plethysmography can be used in the diagnosis and evaluation of chronic venous disease in the lower extremities. This study aimed to evaluate the applicability and reliability of strain-gauge plethysmography (SDP) in the functional assessment of chronic venous disease. This descriptive study was conducted between 2016 and 2021 at a single centre. Four hundred and thirty-two patients with symptomatic chronic venous disease were included in the study. All participants were diagnosed initially with Doppler ultrasonography. SGP was then performed to evaluate venous outflow capacity, venous reflux and muscle pump function. The average age was 45.16 ± 12.54 years (median age 46 years; range 20-78 years), and 239 (55.3%) women and 193 (44.7%) men were included in the study. The age groups, diagnosis, pathological distribution and risk factors were quantitatively determined according to gender. Localisation and lateralisation statistics of the pathologies are given. SGP measurements, including venous volume (V), venous emptying (VE), expelled volume ratio in four seconds (EV4/V), half refilling time (t½) and refilling volume (RV) of each lower extremity, were done individually to compare the involved extremity with the normal contralateral side. SGP measurements of each affected lower limb were also compared separately by gender, age group and disease onset. The correlation between t½ values and skin discolouration or oedema of the affected limb was examined. Finally, receiver operating characteristic curve analyses of the V, VE, EV4/V, t½ and RV values were done, and the cut-off values of each parameter were defined accordingly. High reliability and consistent results indicate that SGP is a practical and sensitive test for quantitative functional assessment of patients with chronic venous disease. It can be used as an effective method in diagnosing and following up chronic venous disorders. As there are no currently accepted cut-off values, we suggest that ours can be used as new reference values for SGP measurements.


Human disposition, metabolism and excretion of etamicastat, a reversible, peripherally selective dopamine β-hydroxylase inhibitor.
Etamicastat is a reversible dopamine-β-hydroxylase inhibitor that decreases noradrenaline levels in sympathetically innervated tissues and slows down sympathetic nervous system drive. In this study, the disposition, metabolism and excretion of etamicastat were evaluated following [(14)C]-etamicastat dosing. Healthy Caucasian males (n = 4) were enrolled in this single-dose, open-label study. Subjects were administered 600 mg of unlabelled etamicastat and 98 µCi weighing 0.623 mg [(14)C]-etamicastat. Blood samples, urine and faeces were collected to characterize the disposition, excretion and metabolites of etamicastat. Eleven days after administration, 94.0% of the administered radioactivity had been excreted; 33.3 and 58.5% of the administered dose was found in the faeces and urine, respectively. Renal excretion of unchanged etamicastat and its N-acetylated metabolite (BIA 5-961) accounted for 20.0 and 10.7% of the dose, respectively. Etamicastat and BIA 5-961 accounted for most of the circulating radioactivity, with a BIA 5-961/etamicastat ratio that was highly variable both for the maximal plasma concentration (19.68-226.28%) and for the area under the plasma concentration-time curve from time zero to the last sampling time at which the concentration was above the limit of quantification (15.82- 281.71%). Alongside N-acetylation, metabolism of etamicastat also occurs through oxidative deamination of the aminoethyl moiety, alkyl oxidation, desulfation and glucuronidation. Etamicastat is rapidly absorbed, primarily excreted via urine, and its biotransformation occurs mainly via N-acetylation (N-acetyltransferase type 2), although glucuronidation, oxidation, oxidative deamination and desulfation also take place.