Physical characteristics of Dornier extracorporeal shock-wave lithotriptor.
Measurements of the pressure, noise, and radiation dose levels from a Dornier lithotriptor are reported. The distribution of the peak pressure around the treatment focus was investigated, and the highest pressures were found to occur within an elongated volume. Within the treatment room, noise levels of 80-90 dB were produced during each shock wave, rising to 95 dB by the patient's head. Ear protection for the staff and patient is recommended, and careful room design is necessary to minimize the sound disturbance to adjacent quarters. Measurements of the radiation skin dose received by patients from the x-ray localization system were relatively high and ranged from 2-55 cGy (rad), with a mean of 12 cGy. The operator needs to be aware of these high doses and should take precautions to minimize them.


Cell culture-adapted IBDV uses endocytosis for entry in DF-1 chicken embryonic fibroblasts.
Although membrane perforation was suggested as the means of penetration mediated by IBDV, the cellular mechanism being hijacked to facilitate its entry is largely unknown. In this study, the entry pathway of cell culture adapted IBDV (caIBDV) was characterized in DF-1 chicken embryonic fibroblasts. We observed that the entry of caIBDV was inhibited by bafilomycin A1 and CaEGTA which interfere with the function of vacuolar H(+)-ATPase (V-ATPase) and retain endosomal Ca(2+). This result suggests that the intact caIBDV particle was transported to the V-ATPase positive vesicles for uncoating and implicates an essential role of endocytosis during the viral entry. The IBDV-mediated endocytosis was demonstrated to be clathrin-independent. Instead, the entry of caIBDV in DF-1 was reduced under the inhibitions or depletions of lipid raft, c-Src tyrosine kinase, dynamin and actin polymerization. In summary, this study confirmed the role of endocytosis in caIBDV entry and characterized the route of its endocytosis.


Multiple sclerosis in the Arabian Gulf countries: a consensus statement.
The epidemiology of multiple sclerosis (MS) is rapidly changing in many parts of the world. Based on the Kurtzke classification, the Arabian Gulf Region is located in a low-risk zone for MS; however, recent studies suggest a moderate-to-high prevalence nearby (31-55 MS per 10,0000 individuals), with an increase in incidence in recent years. The relapsing-remitting disease course ratio is 2.5:1 versus the primary progressive type. In a geographic area that was previously associated with low prevalence; the recent high prevalence and fast rising incidence of MS in the gulf countries, encouraged the neurologists of this region to meet in a consensus panel, in order to share our latest findings in terms of MS epidemiology and consent on MS management in the Arabian Gulf. Therefore 20 key opinion leader neurologists and MS experts representing various countries of the Arabian Gulf have met in Dubai on the 2 and 3 February 2012, they shared their latest epidemiological findings, discussed recent MS aspects in the region, and consented on MS management relevantly to this geographic area.


Elderly patients with non-Hodgkin's lymphoma: population-based results in The Netherlands.
To compare characteristics, treatment and outcome of patients > or = 70 years with patients < 70 years in a population-based non-Hodgkin's lymphoma (NHL) registry. All new patients with NHL (n = 1168) in a geographically defined region in the western part of The Netherlands were registered during a nearly 10-year period. Patient, tumour and treatment characteristics, response to therapy and survival were analysed for both age groups. An age-adjusted prognostic index was determined for elderly patients with aggressive lymphoma. The elderly comprised 41% of the registered patients. There were significantly more females, a preponderance of intermediate-grade histology (diffuse large B-cell lymphoma) and a lower performance status. Incomplete staging in the elderly was mostly due to the omission of a bone marrow biopsy. With respect to WF grading the complete remission rate (except for patients with low-grade/stage I NHL, patients with extranodal NHL and for patients with intermediate grade/extensive NHL) and overall survival at five years (except for patients with low-grade/stage I NHL and for patients with intermediate-grade/extensive NHL) were significantly inferior in the elderly. With respect to the R.E.A.L. Classification the exceptions were in patients with high grade MALT lymphomas (elderly good) and patients with mantle-cell and peripheral T-cell lymphomas (younger group bad too). However, once complete remission was reached, the disease-free survival did not differ significantly between the two age groups, emphasising the importance of achieving complete remission. Although 65% of the classified elderly patients presented with intermediate-grade NHL, only 26% of the elderly patients treated with chemotherapy received anthracycline-based chemotherapy. In the elderly, lymphoma (treatment-related toxicity included) contributed to death in 70% and concomitant disease (other malignancy included) in 30%, versus 78% and 22%, respectively, for the younger group (P = 0.04). The age-adjusted prognostic index, made up of the factors serum LDH, stage and Karnofsky index, showed a clear distinction between the four risk categories low, low/intermediate, intermediate/high and high, with a median survival time of 43, 20, seven and four months, respectively. For the younger group the respective numbers were 144, 45, 19 and 11 months. In a population-based NHL registry the elderly, predominately female patients, formed a larger proportion of the patient group than the one usually reported in the literature. In this population-based cohort inferior remission and overall survival rates were seen in the elderly. However, obtaining complete remission was beneficial for the prognosis of this disease in the elderly. By the application of the R.E.A.L. Classification important subgroups emerge.


Sclerostin: another bone-related protein related to all-cause mortality in haemodialysis?
Derangements in bone metabolism and vascular calcification (VC) substantially contribute to the accelerated cardiovascular morbidity and mortality in chronic kidney disease (CKD). The Wnt signalling pathway is increasingly recognized to play an important role in bone homeostasis and VC. Circulating levels of the Wnt inhibitor sclerostin are elevated in CKD patients. The present study investigated whether the circulating levels of sclerostin are associated with all-cause mortality in haemodialysis (HD) patients. We performed a post-hoc survival analysis in 100 prevalent HD patients (68 ± 13 years, 40 male) recruited in 2006 who were prospectively followed for median 637 (8-1000, range) days. Parameters of mineral metabolism including bone-specific alkaline phosphatase (bsAP) and serum sclerostin were determined in spare blood samples collected at baseline. Serum concentrations of serum sclerostin amounted to 110 (82-151) [median (iqr)] pmol/L. Patients with sclerostin levels above median were characterized by older age, higher haemoglobin and creatinine level and lower bsAP concentration. During a median follow-up of 637 days, 31 patients died. Higher circulating sclerostin levels were associated with decreased mortality in prevalent HD patients: unadjusted hazard ratio (HR) 0.51 (0.24-1.06) (P = 0.06); HR adjusted for age and gender for serum sclerostin levels above versus below median was 0.33 (0.15-0.73) (P = 0.006). When bsAP was entered in the Cox regression analysis, it replaced sclerostin in the final model. Our data show that high circulating sclerostin levels are associated with improved survival and suggest that a low bsAP activity may be in the causal pathway.


Molecular modeling, molecular dynamics simulation, and essential dynamics analysis of grancalcin: An upregulated biomarker in experimental autoimmune encephalomyelitis mice.
The experimental autoimmune encephalomyelitis mouse model is the most commonly used animal model, and it best represents multiple sclerosis. Grancalcin (GCA) was discovered to be upregulated in EAE mice. GCA comprises 220 amino acids that have been assigned the UniprotKB ID Q8VC88. It is a calcium-binding protein that helps neutrophils adhere to fibronectin and the formation of focal adhesions. However, the protein data bank does not contain the crystal structure of mouse GCA. The current study aims to analyze the structural and physicochemical properties of GCA. Mouse GCA showed a high percentage identity (87%) with the crystal structure of des (1-52) grancalcin with bound calcium (chain A) from Homo sapiens identified by its PDB id 1k94_A. Using the SWISS-MODEL server, we used 1k94_A as a template protein to model the mouse GCA protein. Compared to the template structure 1K94, three potential binding sites for calcium-binding have been proposed, ranging from 13 to 20, 80 to 91, and 109 to 120 amino acids. On an i5 personal computer with 8GB of RAM, GROMACS 2020.1 was utilized to run a 100 ns molecular dynamics (MD) simulation. RMSD, Rg, and RMSF analysis of an MD simulation trajectory indicate a stable and compact state throughout the simulation period of modeled proteins. We found that GCA is primarily alpha helical (Class 1), with eight alpha helices. The essential dynamics analysis captures PCA and SASA, culminating in the biological motions that correspond to the last 1000 frames. These findings will aid the development of potential inhibitors as well as the determination of binding pockets and residues for drug-like molecules.


In situ hybridization at light and electron microscopic levels: identification of human papillomavirus nucleic acids.
A comparison of the sensitivities of biotinylated and 32P-labelled human papillomavirus type 6b DNA probes was made. Slot blot hybridization results showed that the sensitivity of biotinylated probes was consistent with that of 32P-labelled, that is, 0.1 pg of pBR 322 plasmid containing 8 kbp HPV cDNA. In situ hybridization using 35S-labelled probes was applied to tissue from condylomata acuminata. After autoradiography, many silver grains were seen concentrated over the superficial koilocytic nuclei with some grains present in the cytoplasm. Biotinylated probes were visualized by 4 different means, i.e., streptavidin alkaline phosphatase, streptavidin biotinylated horseradish peroxidase, monoclonal anti-biotin antibody with 15 nm colloidal gold and streptavidin 5 nm colloidal gold. Strong reaction products were localized in the superficial nuclei while the cytoplasm of koilocytes showed weak hybridization signal. Pre-embedding methods were carried out for electron microscopic studies in which numerous granular diaminobenzidine (DAB) products were present in the nuclear chromatin while viral particles themselves had much fewer DAB products. This suggested that hybridization occurred more efficiently to yet unassembled viral genomes than to matured virions. Post-embedding methods using 15 nm colloidal gold were performed and showed singly scattered or clustered gold particles in superficial koilocytic nuclei.


Antithrombotic and bleeding effects of a new synthetic direct thrombin inhibitor and of standard heparin in the rabbit.
This study reports on the anticoagulant, antithrombotic and bleeding effects of a new synthetic direct thrombin inhibitor (SDTI) in comparison with standard heparin (SH). The anticoagulant effect was determined with the thrombin clotting time (TCT) and the activated partial thromboplastin time (APTT). SDTI was more potent than SH in prolonging the TCT, but as potent as SH in prolonging the APTT. The antithrombotic effect was determined using a modified Wessler model in the rabbit, either 30 min after a continuous IV infusion of increasing doses or at various times after a single SC injection (20 mg/kg). After continuous IV infusion of 187 micrograms/kg/h of SDTI and of 60 micrograms/kg/h of SH, significant thrombus prevention effects were obtained (59 and 57% respectively). Increasing the dose of SDTI up to 3000 micrograms/kg/h did not significantly improve the antithrombotic effect. After SC injection, a significant antithrombotic effect was observed for 12 h with SDTI but for more than 24 h with SH. The bleeding effect was studied using the rabbit ear model 15 min after a continuous infusion of 7.5 and 15 mg/kg/h: the amounts of blood loss were dose-dependent and comparable for SDTI and SH. These studies also indicated that SDTI possesses a considerable shorter half-life in comparison with SH. Accordingly, the ex vivo concentrations generated after continuous IV infusion or SC injection of the same dose were higher for SH than for the SDTI.


Enantiomer resolution of D- and L-alpha-amino acid derivatives by supercritical fluid chromatography on novel chiral diamide phases with carbon dioxide.
The rapid resolution of racemic N-4-nitrobenzoylamino acid isopropyl esters was accomplished without the loss of enantioselectivity by supercritical fluid chromatography (SFC) on novel chiral valine-diamide phases with carbon dioxide and a polar methanol modifier. In each stationary phase, a chiral moiety was anchored to the silica gel surface by a long decamethylene spacer. The enantioselectivity in SFC was comparable to that in liquid chromatography using 2-propanol-n-hexane. The time required for analysis was less than 5 min, and the range of enantiomer resolution (Rs) was 10.8-1.25. On using 2-propanol in place of methanol the separation was improved, but was accompanied by a decrease in column efficiency. The end-capping effect of the remaining surface silanols on enantiomer resolution is discussed.


[Morbus wilson--progressive fatal course of the hepatic form with apoplexy and abscess of the brain (author's transl)].
The onset with a hemolytic crisis, as often described in the literature, led to the diagnosis of Wilson's disease. Treatment was immediately started in the usual way with diet and d-penicillamin. But the disease had already caused serious liver damage and renal lesions, and the patient died fourteen weeks after diagnosis. Examination of further family members disclosed a cousine with impaired liver and kidney function, also suffering from the hepatic form of homozygous Wilson's disease.


Psychometric properties of a Persian-language version of the Beck Depression Inventory--Second edition: BDI-II-PERSIAN.
The Beck Depression Inventory (BDI) is perhaps the most commonly used screening instrument for depression in the general population. We examined the psychometric properties of a Persian-language version of the second edition of this instrument (BDI-II) [Beck et al., 1996] in an Iranian college-student sample. In a sample of 125 student volunteers from two Iranian universities, we compared mean item scores on the BDI-II-Persian with those on the English-language version administered to North American college students, and assessed internal consistency and test-retest reliability of the BDI-II-Persian and its concurrent validity against a measure of negative automatic thoughts in depression, the Automatic Thoughts Questionnaire [Hollon and Kendall, 1980]. We also examined the factor structure of the BDI-II-Persian through comparing the fit of various proposed models to the data using confirmatory factor analysis. The BDI-II-Persian had high internal consistency (Cronbach's alpha=0.87) and acceptable test-retest reliability (r=0.74). The instrument correlated strongly with the Automatic Thoughts Questionnaire. In factor analysis, models with strongly correlated affective-cognitive and somatic-vegetative factors provided a better fit than models with one global factor. These data support the reliability and concurrent validity of the BDI-II-Persian as a measure of depressive symptoms in nonclinical samples.


Structure-based analysis of Toxoplasma gondii profilin: a parasite-specific motif is required for recognition by Toll-like receptor 11.
Profilins promote actin polymerization by exchanging ADP for ATP on monomeric actin and delivering ATP-actin to growing filament barbed ends. Apicomplexan protozoa such as Toxoplasma gondii invade host cells using an actin-dependent gliding motility. Toll-like receptor (TLR) 11 generates an innate immune response upon sensing T. gondii profilin (TgPRF). The crystal structure of TgPRF reveals a parasite-specific surface motif consisting of an acidic loop, followed by a long β-hairpin. A series of structure-based profilin mutants show that TLR11 recognition of the acidic loop is responsible for most of the interleukin (IL)-12 secretion response to TgPRF in peritoneal macrophages. Deletion of both the acidic loop and the β-hairpin completely abrogates IL-12 secretion. Insertion of the T. gondii acidic loop and β-hairpin into yeast profilin is sufficient to generate TLR11-dependent signaling. Substitution of the acidic loop in TgPRF with the homologous loop from the apicomplexan parasite Cryptosporidium parvum does not affect TLR11-dependent IL-12 secretion, while substitution with the acidic loop from Plasmodium falciparum results in reduced but significant IL-12 secretion. We conclude that the parasite-specific motif in TgPRF is the key molecular pattern recognized by TLR11. Unlike other profilins, TgPRF slows nucleotide exchange on monomeric rabbit actin and binds rabbit actin weakly. The putative TgPRF actin-binding surface includes the β-hairpin and diverges widely from the actin-binding surfaces of vertebrate profilins.


[Subtotal bilateral adrenalectomy preserving adrenocortical function].
This study analyzed the frequency of recurrence and postoperative adrenocortical function in 16 patients who had been operated on by bilateral subtotal adrenalectomy since 1995. Bilateral pheochromocytoma was found in 13 patients, bilateral adrenal metastases in 2 patients, and bilateral micronodular adrenocortical hyperplasia with primary aldosteronism in 1 patient. An endoscopic approach was performed in four patients. The remaining 12 patients were operated on by an open approach. In ten patients, unilateral subtotal adrenalectomy with contralateral total adrenalectomy (synchronous or metachronous) was performed. Six patients underwent bilateral subtotal adrenalectomy. In all patients, a total of residual adrenal tissue of at least 1/3 of a normal adrenal gland was left in situ. 15 patients were successfully weaned from exogenous steroid substitution. During a mean follow-up period of 24 months, no recurrences were observed. Three patients died without local recurrence. The present study provided evidence for the safety and benefit of subtotal bilateral adrenalectomy, which could guarantee sufficient adrenocortical function in adrenal remnant volume of more than one-third of one adrenal gland even after dividing the main adrenal vein. At our institution, particularly in patients with inherited pheochromocytoma, subtotal adrenalectomy has become a common surgical strategy.


Modulation of the mitochondrial cyclosporin A-sensitive permeability transition pore. II. The minimal requirements for pore induction underscore a key role for transmembrane electrical potential, matrix pH, and matrix Ca2+.
This paper reports an investigation on the minimal requirements for induction of the mitochondrial cyclosporin A-sensitive permeability transition pore (MTP). Energized rat liver mitochondria incubated in sucrose medium take up a Ca2+ pulse but do not show activation of the MTP upon addition of fully uncoupling concentrations of carbonyl cyanide-p-trifluoromethoxy-phenyl hydrazone (FCCP). Yet, addition of ruthenium red immediately prior to FCCP or inclusion of acetate or low concentrations of phosphate in the incubation medium restore the ability of FCCP to trigger MTP opening. Since ruthenium red, phosphate, or acetate do not induce the MTP per se, they must act upon some additional factor(s) that counteract the increase of pore "open" probability induced by membrane depolarization (Bernardi, P. (1992) J. Biol. Chem. 267, 8834-8839). We show that two key factors determining the overall probability of pore opening are matrix pH and matrix [Ca2+] when the membrane is depolarized. Indeed, in the absence of ruthenium red, phosphate, or acetate the addition of FCCP is followed by fast Ca2+ efflux on the uniporter mirrored by intense matrix acidification following compensatory H+ influx via FCCP. Ruthenium red prevents both Ca2+ efflux and matrix acidification, acetate mainly prevents matrix acidification, and phosphate both slows down Ca2+ efflux and prevents matrix acidification. Taken together, our data indicate that membrane depolarization is both necessary and sufficient to trigger MTP opening when matrix acidification and rapid Ca2+ efflux are prevented. Thus, the wide variety of MTP "inducing agents" may largely reflect the wide variety of the possible combinatorial effects on the minimal requirements for MTP operation.


Eosinophilia associated with perimyositis and pneumonitis.
We describe a patient who had severe myalgias, bronchial asthma, pulmonary infiltrates, and eosinophilia. The findings on physical examination and the erythrocyte sedimentation rate were normal; there was no elevation of the serum creatine kinase. Muscle biopsy demonstrated an inflammatory exudate that contained eosinophils, localized primarily to the perimysium. Pulmonary and muscle manifestations responded to corticosteroids. Systemic eosinophilic disease associated with perimyositis or myositis has not been reported previously. In addition, we review the spectrum of eosinophilic muscle diseases--eosinophilic perimyositis, eosinophilic polymyositis, and focal eosinophilic myositis.


Trichothiodystrophy and the relationship between DNA repair and cancer.
The identification of cellular deficiencies in the ability to repair damage in DNA in individuals with several cancer-prone genetic disorders, has led to the idea that defective DNA repair results in cancer. In patients with trichothiodystrophy, however, a recently discovered defect in the repair of ultraviolet damage in DNA is not associated with cancer-proneness. Thus our previous ideas about the connections between DNA repair capacity and cancer susceptibility need to be reevaluated.


Two-stage acid saccharification of fractionated Gelidium amansii minimizing the sugar decomposition.
Two-stage acid hydrolysis was conducted on easy reacting cellulose and resistant reacting cellulose of fractionated Gelidium amansii (f-GA). Acid hydrolysis of f-GA was performed at between 170 and 200 °C for a period of 0-5 min, and an acid concentration of 2-5% (w/v, H2SO4) to determine the optimal conditions for acid hydrolysis. In the first stage of the acid hydrolysis, an optimum glucose yield of 33.7% was obtained at a reaction temperature of 190 °C, an acid concentration of 3.0%, and a reaction time of 3 min. In the second stage, a glucose yield of 34.2%, on the basis the amount of residual cellulose from the f-GA, was obtained at a temperature of 190 °C, a sulfuric acid concentration of 4.0%, and a reaction time 3.7 min. Finally, 68.58% of the cellulose derived from f-GA was converted into glucose through two-stage acid saccharification under aforementioned conditions.


Clinical features and prognosis of patients with renal cancer and a second malignancy.
To evaluate the epidemiologic aspects, the clinical features, and the prognosis of patients with renal cancer affected by a second malignancy. Since 1983, at our institution, a database concerning all the patients who underwent surgery for renal neoplasia has been prospectively compiled. In the present study, we compared patients with renal cancer and a second primary malignancy, diagnosed before, at the same time, or after the renal cancer, to those affected only by a renal malignancy. Out of 1,673 patients with renal cancer, 285 (17%) were diagnosed with a second malignancy. The follow-up lasted on average 71 months after the treatment of renal neoplasia. The second neoplasia was antecedent in 115 patients (average latency period 8.5 years), synchronous in 97 patients, and subsequent in 103 patients (average latency period 4.4 years). The sites of associated neoplasia were, in descending order of frequency, prostate, bladder, and bowel for men and breast, gynecologic organs, thyroid, and bladder for women. Compared with the patients not affected by a second neoplasm, those with multiple malignancies generally were older and had a smaller, low-grade, low-stage, and asymptomatic renal tumor. Comparing patients with associated neoplasia with a group without associated neoplasia matched for gender, mode of diagnosis, dimension, grade, stage, and histologic subtype of renal cancer, at survival analysis, no significant differences were noticed in renal cancer-related survival. However, among patients with multiple malignancies, the contemporaneous diagnosis of renal and associated cancer had an independent negative impact on survival. The association between renal cancer and other malignancies is a frequent event with an unremarkable impact on prognosis, and it shall not limit surgical indication to treat renal cancer, even if the negative prognostic impact of synchronous occurrence of multiple neoplasias should be regarded, especially in older or unhealthy patients, since ablative therapies or active surveillance could be considered as viable alternative options.


Conventional vs. formulated foods in school lunches. I. Comparison of students' food and nutrient intakes.
School lunches containing all conventional foods were designed to provide either one-third or one-half the Recommended Dietary Allowances for elementary students. The same nutrient goals were used in planning meals containing some formulated foods. Goals and specified portion sizes for first through third graders were distinct from those for fourth through sixth graders, and data from the two groups were maintained separately. Nutrients in meals and plate waste were analyzed to compare nutrient intake among the treatments. Formulated meals weighed less than control and conventional meals, and students ate higher percentages of both the weight and the nutrients served in formulated meals. Nutrient intake was higher when half the allowances was served, but waste was also higher.


Factors Associated With Improvement in Vision Following Femtosecond Astigmatic Keratotomy in Post-Keratoplasty Keratoconus Patients.
To evaluate factors associated with improvement in vision following femtosecond astigmatic keratotomy (FSAK) in patients with keratoconus post-keratoplasty. Retrospective, interventional case series. The study took place in an institutional setting. This was a retrospective study that included patients with keratoconus who underwent FSAK for astigmatism following penetrating (PKP) or deep anterior lamellar keratoplasty (DALK). Success was defined as improvement in 3 Early Treatment Diabetic Retinopathy Study lines (doubling of the visual angle) of uncorrected distance visual acuity (UDVA) or best spectacle-corrected visual acuity (BSCVA). A total of 56 eyes in 56 patients with keratoconus were included. Following FSAK, there was a significant improvement in UDVA (1.30 ± 0.49 to 0.87 ± 0.58 logarithm of minimal angle of resolution [logMAR]; P < .001), BSCVA (0.40 ± 0.26 to 0.27 ± 0.29 logMAR; P <.001), and corneal astigmatism (8.69 ± 2.72 to 3.92 ± 2.13 diopter [D]; P < .001). Success was achieved in 60.7% (34/56) of cases, and this group had a higher proportion of previous PKP (73.5% vs 45.5%; P = .03), worse preoperative UDVA (1.42 ± 0.47 vs 1.11 ± 0.47 logMAR; P = .03), and a greater preoperative manifest cylinder (7.56 ± 2.26 vs 5.72 ± 2.12 D; P = .01). In multiple regression analysis, PKP (vs DALK) (odds ratio [OR]: 8.52; P = .009), worse preoperative UDVA (OR: 9.08, P = .02), and greater preoperative cylinder (OR: 1.51; P = .04) were independently associated with success, and, when combined, led to a sensitivity and specificity of 84.6% and 93.8%, respectively, in predicting success. The optimal cutoff predicting success with a preoperative cylinder was a cylinder >6.75 D. Approximately 60% of patients with keratoconus post-keratoplasty experience doubling of the visual angle following FSAK. Patients with previous PKP and a greater cylinder are more likely to benefit from this procedure. Separate nomograms for DALK and PKP patients may be warranted.


Pigeon MDA5 inhibits viral replication by triggering antiviral innate immunity.
Pigeons are considered less susceptible, and display few or no clinical signs to infection with avian influenza virus (AIV). Melanoma differentiation-associated gene 5 (MDA5), an important mediator in innate immunity, has been linked to the virus resistance. In this study, the pigeon MDA5 (piMDA5) was cloned. The bioinformatics analysis showed that the C-terminal domain (CTD) of MDA5 is highly conserved among species while the N-terminal caspase recruitment domain (CARD) is variable. Upon infection with Newcastle diseases virus (NDV) and AIV, piMDA5 was upregulated in both pigeons and pigeon embryonic fibroblasts (PEFs). Further study found that overexpression of piMDA5 mediated the activation of interferons (IFNs) and IFN-stimulated genes (ISGs) while inhibiting NDV replication. Conversely, the knockdown of piMDA5 promoted NDV replication. Additionally, CARD was found to be essential for the activation of IFN-β by piMDA5. Furthermore, pigeon MDA5, chicken MDA5, and human MDA5 differ in inhibiting viral replication and inducing ISGs expression. These findings suggest that MDA5 contributes to suppressing viral replication by activating the IFN signal pathway in pigeons. This study provides valuable insight into the role of MDA5 in pigeons and a better understanding of the conserved role of MDA5 in innate immunity during evolution.


Variations of enzyme activities in the haemocytes of scallop Chlamys farreri after infection with the acute virus necrobiotic virus (AVNV).
Acute virus necrobiotic virus (AVNV) is one of the main pathogens for large scale mortality of Chinese scallop Chlamys farreri. In this paper, C. farreri were infected by different dilutions of AVNV supernatant (5(0), 5(-1), 5(-2), 5(-3), 5(-4), 5(-5), 5(-6), 5(-7), respectively), and dead individuals were counted every day for 15 days. Samples from groups of 5(-3) and 5(-5) were taken every day till 15 days and the activities of acid phosphatase (ACP), alkaline phosphatase (ALP), superoxide dismutase (SOD), myeloperoxidase (MPO), phenoloxidase (PO), peroxidase (POD) and catalase (CAT) in haemocytes were measured. The results of virus challenge showed that survival rates of scallops in groups of 5(0) and 5(-1) decreased sharply after the first day and died out completely on the 5th and 4th day, respectively. In other groups (5(-2), 5(-3), 5(-4), 5(-5), 5(-6) and 5(-7)), survival rates decreased gradually till 6 or 7 days, then kept steady till 15 days, and they were dose-dependent, increasing from 12% to 80% as the dose decreased from 5(-2) to 5(-7) viral supernatant. In the control group, survival rate was 88%. Enzyme activities for groups of 5(-3) and 5(-5) illustrated that activities of ACP, SOD, MPO, PO in groups of 5(-3) and 5(-5) were significantly higher than the control group in the first 9 or 10 days, and went back to the control group levels gradually after 10 days. Moreover, their activities in group of 5(-3) varied more than that in the group of 5(-5), especially activities of MPO, PO. Differently, the activities of POD and CAT were reduced or induced by virus infection and showed no regular trends in the experiments. The activity of ALP was not detected.


Soyasaponin Ag inhibits triple-negative breast cancer progression via targeting the DUSP6/MAPK signaling.
Soyasaponins are triterpenoid glycosides discovered in soybean and have anti-cancer properties. Soyasaponin A was reported to repress estrogen-insensitive breast cancer cell proliferation. This study intends to explore the role of one isomer of soyasaponin A, i.e. soyasaponin Ag (Ssa Ag), in triple-negative breast cancer (TNBC) development. Bioinformatic databases were used to predict DUSP6 expression in breast cancer (BC) as well as the correlation between the expression of DUSP6 (or MAPK1, MAPK14) with the prognosis of patients with BC. The expression of DUSP6/MAPK signaling-related genes (DUSP6, MAPK1, and MAPK14) in TNBC cell lines was assessed via Western blot analysis and RT-qPCR. Levels of cell apoptosis proteins (Bax and Bcl-2) in TNBC cells were assessed via Western blot analysis. CCK-8 assay, colony formation assay, and flow cytometry analysis were conducted for the measurement of TNBC cell growth and apoptosis. In vivo xenograft assay was employed for investigating the biological influence of Ssa Ag on tumor growth. The poor prognosis of BC patients was linked to the aberrant expression of DUSP6/MAPK pathway genes. Low expression of DUSP6 or high expression of MAPK1 (or MAPK14) was correlated to poor prognosis. DUSP6 was downregulated while MAPK1 and MAPK14 were upregulated in TNBC cells versus normal cells. Ssa Ag upregulated DUSP6 expression while downregulated MAPK1 and MAPK14 expression, inhibiting the MAPK signaling pathway. Additionally, Ssa Ag promoted in vitro TNBC cell apoptosis and restrained cell growth, and repressed in vivo tumor growth. Ssa Ag inhibited TNBC progression via upregulating DUSP6 and inactivating the MAPK signaling pathway.


ERα and/or ERβ activation ameliorates cognitive impairment, neurogenesis and apoptosis in type 2 diabetes mellitus mice.
Estrogen receptors (ERs) are thought to be associated with the onset and progression of neurodegenerative injuries and diseases, but the relationship and mechanisms underlying between ERs and cognition in type 2 diabetes remain elusive. In the current study, we investigated the effects of ERα and ERβ on the cognition, neurogenesis and apoptosis in high-fat diet and streptozocin-induced diabetic mice. We found that ERα and/or ERβ activation using their agonists (0.5 mg/kg E2, PPT or DPN) ameliorate memory impairment in the Morris water maze and Y-maze tests, increase hippocampal neurogenesis and prevent hippocampal apoptotic responses. Importantly, treatment with the pharmacologic ERs agonists caused significant increases in the membrane ERα and ERβ expression and subsequent PI3K/Akt, CREB and BDNF activation in the hippocampus of type 2 diabetes mellitus mice. Our data indicate that ERα and ERβ are involved in the cognitive impairment in type 2 diabetes, and that activated ERs, such as application of ERs agonists, could be a novel and promising strategy for the treatment of diabetic cognitive impairment.


Chimeric Ca(2+)-ATPase/Na+,K(+)-ATPase molecules. Their phosphoenzyme intermediates and sensitivity to Ca2+ and thapsigargin.
Chimeric molecules consisting of parts from the sarcoplasmic reticulum Ca(2+)-ATPase and the Na+,K(+)-ATPase were expressed in COS-1 cells and analysed functionally. One chimera, in which most of the central cytoplasmic loop was derived from the Na+,K(+)-ATPase, while the transmembrane segments and the minor cytoplasmic loop came from the Ca(2+)-ATPase, was able to occlude Ca2+ and to be phosphorylated from ATP with normal apparent affinity for Ca2+ and ATP. This chimera also displayed normal sensitivity to thapsigargin, but was unable to undergo the transition from ADP-sensitive to ADP-insensitive phosphoenzyme and to transport Ca2+. The other chimera, which consisted of the NH2-terminal two-thirds of Na+,K(+)-ATPase and the COOH-terminal one-third of Ca(2+)-ATPase, was unable to phosphorylate from ATP, but phosphorylated from inorganic phosphate in a Ca(2+)-inhibitable and thapsigargin-insensitive reaction. These results can be explained in terms of a structural model in which the non-conserved residues in the central cytoplasmic domain of the Ca(2+)-ATPase are without major importance for the binding and occlusion of Ca2+, but are involved in the E1P-->E2P conformational changes of the phosphoenzyme, whereas residues in transmembrane segments on both sides of the central cytoplasmic domain are involved in formation of the Ca(2+)-binding sites. The data moreover show that thapsigargin sensitivity is dependent on residues in the NH2-terminal one-third of the Ca(2+)-ATPase molecule.


Compartmentalization of acetylcholinesterase in the chick retina.
Using selective inhibitor treatments, we have studied the distribution of asymmetric (A) and globular (G) forms of acetylcholinesterase (AChE) in the extra- and intracellular compartments of chick retina, a specialized region of chick central nervous system (CNS). Our results show that the chick retinal collagen-tailed AChE (an example of class II asymmetric molecular forms) is essentially an extracellular form of the enzyme; this is the first demonstration of the extracellular localization of asymmetric AChE in the vertebrate CNS. The active site of most of the hydrophobic, membrane-bound G4-form is also exposed to the external environment. In turn, the smaller molecular weight G-forms (G2 and G1) are localized within the cells, where they may represent intermediate components in the assembly or degradation of the more complex enzymatic molecular species. Histoenzymatic ultrastructural techniques show internal AChE in amacrine as well as in ganglion cell bodies, and external enzyme, specifically associated with synapses and axons, in the inner plexiform layer. The probable cooperation of the extracellular A12-forms and the membrane-bound G species (mainly G4) of the enzyme to the hydrolysis of acetylcholine (ACh) released into the external compartment is suggested and discussed.


A mixed methods study using case studies prepared by nursing students as a clinical practice evaluation tool.
To identify the presence of variability in the evaluation of case studies prepared by nursing students during their primary care rotations based on the existing evaluation rubric. To explore the difficulties experienced by link lecturers and students in preparing and evaluating case studies. A mixed methods study. The scores for the rubric items and the final grades for the case studies were collected from a sample of 132 cases. Qualitative information was collected by conducting open-ended interviews with lecturers and a focus group session with students. Statistically significant differences were identified between the lecturers' mean final grades [F(5.136) = 3.984, p = 0.002] and a variety of items in the evaluation rubric (p < 0.05). In addition, effect sizes [η2 (≈0.14)] of considerable magnitude were found. Two themes emerged from the qualitative data: (1). the challenge of preparing the case studies and (2). the variable nature of the evaluations.


Evaluation of the use of a biodegradable ureteral stent after retrograde endopyelotomy in a porcine model.
We evaluated the use of a poly-L-lactide-co-glycolide (PLGA) bioabsorbable ureteral stent after Acucise balloon incision (Applied Medical Resources, Rancho Santa Magarita, California) endopyelotomy in a porcine model. After unilateral Acucise endopyelotomy in 9 female Yucatan minipigs a self-reinforced PLGA stent was placed in 5 (group 1) and a 7Fr double pigtail Percuflex stent (Boston Scientific, Natick, Massachusetts) was placed in 4 (group 2). Preoperatively, and 6 and 12 weeks postoperatively plain x-ray of the kidneys, ureters and bladder, cystography, side specific creatinine clearance and retrograde ureterography were done. The contralateral ureters served as untreated controls. The 7Fr stents were removed at 6 weeks. All animals were sacrificed at 12 weeks after bilateral flow studies. Histological specimens from 4 sites along the urinary tract were graded on a healing score of 0-normal, to 3-severe changes. Side specific creatinine clearance was similar to preoperative values at 6 and 12 weeks. At the 2 time points plain x-ray of the kidneys, ureters and bladder in group 1 showed retroperitoneal stent fragments in 3 of the 5 animals, which was confirmed at autopsy. Retrograde ureterography in group 1 showed mild hydronephrosis in all 5 ureters and saccular diverticula in 4, which was similar in 2 and 3 animals, respectively, in group 2. Cystography demonstrated grades 1 to 2 reflux in 2 animals at 6 weeks but none at 12 weeks in group 1 and no reflux at either time point in group 2. Flow rates and healing scores were statistically similar in the 2 groups but the latter trended toward less favorable healing of ureteral musculature with application of the absorbable stent. In this pilot study the use of self-reinforced PLGA biodegradable ureteral stents was feasible after Acucise endopyelotomy in a porcine model with radiographic and fluid flow results that were relatively similar to those of standard 7Fr stents but with less favorable biocompatibility.


Effect of Chrysanthemum indicum Linné extract on melanogenesis through regulation of TGF-β/JNK signaling pathway.
Although several physiological effects of Chrysanthemum indicum Linné (CL) have been researched, the specific effect and molecular mechanism of CL as a functional food material for skin health remain still unknown. Here, it was observed that the α-MSH and IBMX-initiated B16F10 melanogenesis was suppressed by the CL water extract (CLE) treatment. The CLE treatment also increased the mRNA expression levels of pro-collagen1α2, collagen1α2, and fibronectin via exerting the TGF-β/JNK signaling pathway. Together, the beneficial role of CLE in skin health was demonstrated through the downregulation of melanogenesis and enhancement of skin fibril-related genes. It was also revealed that the function of CLE is mediated with the activation of the TGF-β/JNK signaling pathway. These results may provide evidences for the development of functional foods using CLE for maintaining healthy skin.


Mobilisation processes responsible for iron and manganese contamination of groundwater in Central Adriatic Italy.
Iron and manganese are two of the most common contaminants that exceed the threshold imposed by international and national legislation. When these contamination occurs in groundwater, the use of the water resource is forbidden for any purposes. Several studies investigated these two metals in groundwater, but research focused in the Central Adriatic area are still lacking. Thus, the objective of this study is to identify the origin of Fe and Mn contamination in groundwater and the hydrogeochemical processes that can enrich aquifers with these metals. This work is based on hydrogeochemical and multivariate statistical analysis of analytical results undertaken on soils and groundwater. Fe and Mn contamination are widespread in the alluvial aquifers, and their distribution is regulated by local conditions (i.e. long residence time, presence of peat or organic-rich fine sediments or anthropic pollution) that control redox processes in the aquifers and favour the mobilisation of these two metals in groundwater. The concentration of iron and manganese identified within soil indicates that the latter are a concrete source of the two metals. Anthropic impact on Fe and Mn contamination of groundwater is not related to agricultural activities, but on the contrary, the contribution of hydrocarbons (e.g. spills) is evident.


Association Between the Development of Subclinical Cardiovascular Disease and Human Immunodeficiency Virus (HIV) Reservoir Markers in People With HIV on Suppressive Antiretroviral Therapy.
We report that people with human immunodeficiency virus (HIV) diagnosed with coronary artery atherosclerotic plaques display higher levels of HIV DNA compared with those without atherosclerotic plaques. In a multivariable prediction model that included 27 traditional and HIV-related risk factors, measures of HIV DNA were among the most important predictors of atherosclerotic plaque formation.


Identification of a novel mutation in exon 1 of androgen receptor gene in an azoospermic patient with mild androgen insensitivity syndrome: case report and literature review.
To report a case of an azoospermic subject with mild androgen insensitivity syndrome (MAIS) and review the relevant literature. Case report. Academic research hospital. A 49-year-old man with undermasculinized features and a history of cryptorchidism and azoospermia. Hormonal evaluation and genetic testing of the androgen receptor gene (AR). Hormonal levels and sequence chromatogram of the proband and his mother. We found total T in the normal range and high levels of gonadotropins. Karyotype was 46,XY. Genetic testing identified a novel mutation of exon 1 of AR, which resulted in an alanine to serine substitution in the transactivation domain at codon 240 (A240S). Fourteen other mutations of exon 1 of AR have been associated with MAIS to date. The novel mutation A240S of AR is involved in MAIS, a syndrome associated with azoospermia.


[Giant hamartoma of the lung].
Hamartomas are the most common benign tumors of the lungs and usually present as solitary intraparenchymal lesions a few centimeters in diameter which are detected radiologically as an incidental finding. This article reports on a case of a giant pulmonary hamartochondroma 29 cm in diameter, which impressed preoperatively and intraoperatively as an extrapulmonary neoplasm. The detection of smaller mesenchymal neoplastic lesions in the lungs and pleura is a further special feature of this case.


Histomorphometric and histopathological study of the human cricopharyngeus muscle: in health and in motor neuron disease.
Abnormalities in muscle histology have been reported frequently for the cricopharyngeus muscle of patients with oculopharyngeal muscular dystrophy, motor neuron disease and other neurological disorders in which dysphagia is a common clinical sign. However, there are few detailed reports of the normal structure of this muscle nor quantitative baseline data with which to compare the diseased state. In this study, cricopharyngeus muscles from 21 healthy individuals and four patients with motor neuron disease underwent quantitative histological and histochemical examination. In addition to the extensive connective tissue content (40%), comprising abundant elastic fibres, cricopharyngeus muscles from normal individuals possessed small calibre striated muscle fibres (mean narrow diameter 30 microns) of widely varying size (coefficient of variation 41%). The majority of fibres were histochemically type I (82%) and highly oxidative. All muscles comprised numerous muscle fibres with aberrant histological and histochemical features (internalized nuclei, 'ragged red' crescents, splits, degenerating fibres, 'moth-eaten' fibres, or nemaline rods.) The histomorphometric and histopathological features were similar in males and females and some showed a correlation with age. There were increases in fibre size and roundedness and decreases in the numerical density and percentage of type I and split fibres in the specimens from older individuals. Cricopharyngeus muscles from patients with motor neuron disease were not significantly different from the controls for most parameters. It is therefore suggested that previous descriptions of specific cricopharyngeal pathology accompanying neuromuscular disease or dysphagia be interpreted with caution. The importance of obtaining normal structural, morphometric and histopathological data from muscles other than the usually biopsied limb muscles, is emphasized.


Mangrove soil as a source for novel xylanase and amylase as determined by cultivation-dependent and cultivation-independent methods.
Xylanase and α-amylase enzymes participate in the degradation of organic matter, acting in hemicellulose and starch mineralization, respectively, and are in high demand for industrial use. Mangroves represent a promising source for bioprospecting enzymes due to their unique characteristics, such as fluctuations in oxic/anoxic conditions and salinity. In this context, the present work aimed to bioprospect xylanases from mangrove soil using cultivation-dependent and cultivation-independent methods. Through screening from a metagenomic library, three potentially xylanolytic clones were obtained and sequenced, and reads were assembled into contigs and annotated. The contig MgrBr135 was affiliated with the Planctomycetaceae family and was one of 30 ORFs selected for subcloning that demonstrated only amylase activity. Through the cultivation method, 38 bacterial isolates with xylanolytic activity were isolated. Isolate 11 showed an enzymatic index of 10.9 using the plate assay method. Isolate 39 achieved an enzyme activity of 0.43 U/mL using the colorimetric method with 3,5-dinitrosalicylic acid. Isolate 39 produced xylanase on culture medium with salinity ranging from 1.25 to 5%. Partial 16S rRNA gene sequencing identified isolates in the Bacillus and Paenibacillus genera. The results of this study highlight the importance of mangroves as an enzyme source and show that bacterial groups can be used for starch and hemicellulose degradation.


Asymmetric ground reaction forces and knee kinematics during squat after anterior cruciate ligament (ACL) reconstruction.
This bilateral squat study tests whether people with anterior cruciate ligament (ACL) reconstruction have symmetric three-dimensional ground reaction forces (GRFs) and symmetric anterior-posterior (AP) translation rates of the femur with respect to the tibia when compared with healthy control subjects. We hypothesized that there would be no long-term asymmetry in knee kinematics and kinetics in ACL reconstructed subjects following surgery and rehabilitation. Position and GRF data were collected on eight ACL reconstructed and eight control subjects during bilateral squat. The rate of relative AP translation was determined for each subject. Principal component models were developed for each of the three GRF waveforms. Principal component scores were used to assess symmetry within the ACL reconstructed group and within the control group. ACL reconstructed knees analyzed in early flexion during squat descent displayed a four-fold greater rate of change in anterior translation in the reconstructed knee relative to the contralateral side than did a similar comparison of normal knees. Differences were found between the ACL reconstructed subjects' injured and uninjured limbs for all GRFs. Subjects following ACL reconstruction had asymmetric GRFs and relative rates of AP translation at an average of seven years after ACL reconstructive surgery when compared with control subjects. These alterations in loading may lead to altered load distributions across the knee joint and may put some subjects at risk for future complications such as osteoarthritis.


Diminished arachidonate 5-lipoxygenase perturbs phase separation and transcriptional response of Runx2 to reverse pathological ventricular remodeling.
Arachidonate 5-lipoxygenase (Alox5) belongs to a class of nonheme iron-containing dioxygenases involved in the catalysis of leukotriene biosynthesis. However, the effects of Alox5 itself on pathological cardiac remodeling and heart failure remain elusive. The role of Alox5 in pathological cardiac remodeling was investigated by Alox5 genetic depletion, AAV9-mediated overexpression in cardiomyocytes, and a bone marrow (BM) transplantation approach. Neonatal rat cardiomyocytes were used to explore the effects of Alox5 in vitro. Molecular and signaling pathways were revealed by CUT &Tag, IP-MS, RNA sequencing and bioinformatic analyses. Untargeted metabolomics showed that serum 5-HETE (a primary product of Alox5) levels were little changed in patients with cardiac hypertrophy, while Alox5 expression was significantly upregulated in murine hypertensive cardiac samples and human cardiac samples of hypertrophy, which prompted us to test whether high Alox5 levels under hypertensive stimuli were directly associated with pathologic myocardium in an enzymatic activity-independent manner. Herein, we revealed that Alox5 deficiency significantly ameliorated transverse aortic constriction (TAC)-induced hypertrophy. Cardiomyocyte-specific Alox5 depletion attenuated hypertensive ventricular remodeling. Conversely, cardiac-specifical Alox5 overexpression showed a pro-hypertrophic cardiac phenotype. Ablation of Alox5 in bone marrow-derived cells did not affect pathological cardiac remodeling and heart failure. Mechanically, Runx2 was identified as a target of Alox5. In this regard, Alox5 PEST domain could directly bind to Runx2 PTS domain, promoting nuclear localization of Runx2 in an enzymatic activity-independent manner, simultaneously contributed to liquid-liquid phase separation (LLPS) of Runx2 at specific domain in the nucleus and increased transcription of EGFR in cardiomyocytes. Runx2 depletion alleviated hypertrophy in Ang II-pretreated Alox5-overexpressing cardiomyocytes. Overall, our study demonstrated that targeting Alox5 exerted a protective effect against cardiac remodeling and heart failure under hypertensive stimuli by disturbing LLPS of Runx2 and substantial reduction of EGFR transcription activation in cardiomyocytes. Our findings suggest that negative modulation of Alox5-Runx2 may provide a therapeutic approach against pathological cardiac remodeling and heart failure. National Natural Science Foundation of China.


Nitric oxide in critical respiratory failure of very low birth weight infants.
Inhaled nitric oxide (iNO) is a selective pulmonary vasodilator. In randomised trials, iNO increased gas exchange modestly and had no effect on the outcome (survival, chronic lung disease, CLD) in very low birth-weight (VLBW) infants. NO is an important component of the innate immune system and a lipid- soluble free radical scavenger that interacts with the surfactant system. VLBW infants with pneumonia and therapy-resistant, severe respiratory failure soon after birth were studied. Despite their infection, there was no detectable alveolar inducible NO synthase or nitrotyrosine, which is a toxic oxidation product of NO. These infants do not respond to exogenous surfactant and demonstrate severe pulmonary hypertension. However, they require exogenous surfactant prior to iNO. In most cases the disease is complicated by pneumonia and prolonged rupture of fetal membranes. We have shown evidence that iNO given within a few hours after birth reverses the progressive course of respiratory failure and pulmonary hypertension in VLBW infants.


Partial horizontal supraglottic laryngectomy. A method of reconstruction.
Despite the low occurrence of early laryngeal lesions amenable to Partial Supraglottic Laryngectomy, they form a very interesting and important group of lesions. Timing is important in their recognition, since adequate treatment can then be secured and important functions of the larynx preserved. The draw back in the treatment of these lesions by partial laryngectomy lies in the difficulty in restoring the patient to his preoperative pattern of life. Repeated aspiration pneumonitis becomes a life threatening problem in a good number of such patients. A new method of reconstruction is described here by which the aspiration problem is obviated with the aid of a pedicle flap to line the raw surface of the transected base of the tongue allowing the organ to remain in a position capable of occluding the glottis during deglutition, and at the same time guiding the food along the posterior pharyngeal wall and into the esophagus.


Assessment of Medical and Social Risk Factors Before Arthroplasty in Argentina: A Poll of Argentinian Hip and Knee Association (ACARO) Members.
Assessment of risk factors is crucial for lowering complication rates and costs of hip and knee arthroplasty. The objective of this study was to assess if members of the Argentinian Hip and Knee Association (ACARO) are influenced by such risk factors when planning surgery. In 2022, a survey was distributed as an electronically based questionnaire to 370 members of the ACARO. A descriptive analysis was performed on 166 proper answers (44.9%). There were 68% of the respondents who were specialists in joint arthroplasty and 32% practiced general orthopedics. A large number had large volumes at private hospitals without service/residents and 48.2% had been in practice for more than 15 years. Of the responding surgeons, 99% routinely performed a preoperative reversible risk factors evaluation that considered diabetes, malnutrition, weight, and smoking, and 95% canceled/postponed the surgery for abnormalities. Malnutrition was important for 79% of the polled with blood albumin being used by 69.3%. Fall risk assessment was performed by 60.2% of the surgeons. Only 44% of the surgeons felt free to choose the implant for the arthroplasty, possibly because 69.9% work for a capitated system. Important delays for surgery were reported by 63.9 and 84.3% had waiting lists. 74.7% of the polled noted physical or psychological deterioration during such delays. Socioeconomic factors firmly impact on the accessibility to arthroplasty in Argentina. Despite these barriers, the qualitative analysis of this poll let us demonstrate greater awareness of preoperative risk factors, especially diabetes as the most reported comorbidity.


Canadian Human Specimen Bank: an emerging Great Lakes health effects program.
Plans for establishing a Canadian human specimen bank as part of the Great Lakes Health Effects program initiated by the Environmental Health Directorate, Health and Welfare Canada, have been under consideration since 1990. This presentation delineates the program rationale, our objectives in establishing the bank and the progress we have made to-date in achieving our goal. This paper is intended to be a planning document.


Consensus review of best practice of transanal irrigation in adults.
Review article. To provide a consensus expert review of the treatment modality for transanal irrigation (TAI). A consensus group of specialists from a range of nations and disciplines who have experience in prescribing and monitoring patients using TAI worked together assimilating both the emerging literature and rapidly accruing clinical expertise. Consensus was reached by a round table discussion process, with individual members leading the article write-up in the sections where they had particular expertise. Detailed trouble-shooting tips and an algorithm of care to assist professionals with patient selection, management and follow-up was developed. This expert review provides a practical adjunct to training for the emerging therapeutic area of TAI. Careful patient selection, directly supervised training and sustained follow-up are key to optimise outcomes with the technique. Adopting a tailored, stepped approach to care is important in the heterogeneous patient groups to whom TAI may be applied. The review was financially supported by Coloplast A/S.


Vitamin D Levels in Ethnic Minority Adolescents in Primary Care.
This pilot study examined the distribution of low vitamin D levels among ethnic minority adolescents in primary care to elucidate the clinical needs of this diverse population. A cross-sectional study was conducted using a retrospective patient chart review. Participants were a consecutive sample of 119 ethnically diverse adolescents aged 12-18 years, attending a primary care clinic, who had a wellness examination in 2018 and documented vitamin D levels on the basis of previously collected blood work. Sixty-one percent of adolescents had low vitamin D levels. Vitamin D deficiency increased with age, independently of ethnicity or gender. A significant number of ethnically diverse adolescents presented with low vitamin D levels. A need exists to raise awareness among clinicians regarding social determinants of health and culturally sensitive dietary practices to improve vitamin D levels and prevent long-term complications, focusing on adolescent at-risk ethnic groups.


Development and future deployment of a 5 years allograft survival model for kidney transplantation.
Identifying kidney transplant patients at highest risk for graft loss prior to loss may allow for effective interventions to improve 5 years survival. We performed a 10 years retrospective cohort study of adult kidney transplant recipients (n = 1747). We acquired data from electronic health records, United Network of Organ Sharing, social determinants of health, natural language processing data extraction, and real-time capture of dynamically evolving clinical data obtained within 1 year of transplant; from which we developed a 5 years graft survival model. Total of 1439 met eligibility; 265 (18.4%) of them experienced graft loss by 5 years. Graft loss patients were characterized by: older age, being African-American, diabetic, unemployed, smokers, having marginal donor kidneys and cardiovascular comorbidities. Predictive dynamic variables included: low mean blood pressure, higher pulse pressures, higher heart rate, anaemia, lower estimated glomerular filtration rate peak, increased tacrolimus variability, rejection and readmissions. This Big Data analysis generated a 5 years graft loss model with an 82% predictive capacity, versus 66% using baseline United Network of Organ Sharing data alone. Our analysis yielded a 5 years graft loss model demonstrating superior predictive capacity compared with United Network of Organ Sharing data alone, allowing post-transplant individualized risk-assessed care prior to transitioning back to community care.


Metal leaching along soil profiles after the EDDS application--a field study.
One concern about the chelant-enhanced phytoextraction is the potential metal leaching associated with chelant application. A field study was carried out and the metal leaching along the 60-cm depth soil profiles were evaluated within 36 days after the biodegradable chelant EDDS was applied. Results showed EDDS significantly increased soluble Cu in the top 5 cm soil layer 1 day after the application, and the increase of soluble metals was generally limited in the top 20 cm soil. Metal speciation analysis indicated all Cu and Zn were in forms of Cu-EDDS and Zn-EDDS complexes in soil solution, and Ca was the major competitor with trace metals to EDDS. The soluble metals decreased quickly with time, and no significant difference was observed in the extractable Cu between EDDS treatments and the controls 22 days after the EDDS addition. The potential leaching associated with biodegradable EDDS addition may be controlled under field conditions.


Effects of context on the subjective equation of auditory and visual intensities.
Thirty-six subjects were instructed to equate the loudness of a pure tone with the brightness of an illuminated field. Eighteen of the subjects had been given brief preliminary experience with tones of low intensity; the remaining 18, with tones of high intensity. A significant and substantial effect upon equation was demonstrated.


Retracted: Lidocaine Ameliorates Diabetic Peripheral Neuropathy in Streptozotocin-Induced Diabetic Rats through Modulating the c-Jun Signaling Pathway.
[This retracts the article DOI: 10.1155/2022/1888153.].


Performance evaluation of serological assays to determine the immunoglobulin status in SARS-CoV-2 infected patients.
Serological assays for the determination of the immune status of patients that have tested positive for infection with SARS-CoV-2 by RT-PCR are required for, e.g., contact tracing and epidemiological studies. However, data concerning the performance parameters of commercially available high-throughput ELISA tests are still not available on a large scale. In our study, we have evaluated an in-house developed ELISA for the detection of the immunoglobulin classes A, G and M directed against the full-length spike glycoprotein from SARS-CoV-2. For this analysis, we have included 110 sera from patients presenting with COVID-19 symptoms or blood donors without symptoms collected at the Austrian Red Cross, Blood Transfusion Service for Upper Austria, Linz. In addition, we have selected four commercially available IgG-based ELISAs as well as one IgA/IgG-based ELISA for the detection of SARS-CoV-2 antigens as well as a multiplexed IgG-based micro-ELISA assay developed for rapid Point of Care testing applications. All assays evaluated in the course of this study demonstrated suitable sensitivity and specificity values for the identification of patients that have experienced a past infection with SARS-CoV-2. However, testing for the presence of additional immunoglobulins (IgA and IgM) as well as using combinations of different viral antigens is highly advised to improve the predictive values of serological assays.


Assessment of image quality of contrast-enhanced power doppler imaging in hepatocellular carcinoma with the personal ultrasound imager: Comparison with the conventional machine.
To evaluate the usefulness of contrast-enhanced power Doppler imaging with the personal ultrasound imager in depicting intratumoral vascularity in hepatocellular carcinoma. Contrast-enhanced power Doppler imaging was used to examine 52 hepatocellular carcinoma nodules in 29 patients, using both the personal ultrasound imager and the conventional ultrasound machine in combination with intravenous injection of Levovist(®). Results obtained using dynamic CT were used as the gold standard. The ability of the personal ultrasound imager to detect intratumoral vascularity was compared with that of the conventional ultrasound machine, and the usefulness of the personal ultrasound imager in assessing therapeutic effect after nonsurgical treatment was compared with that of dynamic CT at the same time. The personal ultrasound imager and the conventional ultrasound machine, using the fundamental power Doppler imaging mode (p=0.13) and contrast-enhanced power Doppler imaging mode (p=0.41), did not differ significantly in depicting the vascularity of the 52 hepatocellular carcinomas. The sensitivity, specificity, and accuracy of contrast-enhanced power Doppler imaging on the personal ultrasound imager were 95.5%, 87.5%, and 94.2%, respectively, in close agreement with results obtained using dynamic CT. After the 22 hepatocellular carcinomas were treated, the personal ultrasound imager provided diagnostic accuracy of 90.9% on residual tumors when compared with results obtained by dynamic CT, and results obtained using the conventional ultrasound machine were similar. The highly portable personal ultrasound imager using Levovist(®)-enhanced power Doppler imaging can clearly depict the intratumoral vascularity of hepatocellular carcinoma nodules before and after treatment, achieving results very close to those obtained using the conventional diagnostic ultrasound machine. The personal ultrasound imager is an alternative to the conventional ultrasound machine for depicting tumor vascularity.


Outcome of Descemet stripping automated endothelial keratoplasty in eyes with an Ahmed glaucoma valve.
The purpose was to investigate the survival of Descemet stripping automated endothelial keratoplasty (DSAEK) in eyes with an Ahmed glaucoma valve (AGV). The study had a retrospective case-series of patients with an AGV in the anterior chamber undergoing a DSAEK. Included in the analysis were graft size, number of previous operations, post-operative glaucoma medications, post-operative intraocular pressure (IOP) control, graft size and donor factors (age, endothelial cell density, and post-mortem time). A generalised linear model with binary logistic regression was used to test for an effect on graft survival at 1 year and 1.5 years. Fourteen eyes from 13 patients were included. The survival rate of the first DSAEK at 6, 12, 18, 24 and 30-months was 85%, 71%, 50%, 36% and 30%, respectively. The mean duration to graft failure was 12.9 ± 6.2 months. Five of the seven failed first grafts went on to have a repeat DSAEK. The mean follow-up in this subgroup was 30.7 ± 18.4 months. The survival rate of second DSAEK at 6, 12, 18 and 24 months was 100% (5/5), 100% (5/5), 75% (3/4) and 67% (2/3). Only one second DSAEK failed in the duration of the study and went on to receive a third DSAEK which failed at 18-months. The mean IOP within the first year was significantly lower for grafts that survived at 1 and 1.5 years (17.4 mmHg, 16.9 mmHg) than for grafts that failed (19.4 mmHg, 19.4 mmHg) (p = 0.04, p = 0.009). DSAEK is a viable alternative to PK to restore visual function in eyes with an AGV sited in the anterior chamber. IOP is an important risk factor for graft failure.


Factors contributing to the separation of endodontic files.
Cleaning and shaping of the root canal system is essential for successful endodontic treatment. However, despite improvements in file design and metal alloy, intracanal file separation is still a problematic incident and can occur without any visible signs or permanent deformation. Only a few studies have reported high success rates of fractured file removal using contemporary techniques. Conflicting results have been reported regarding the clinical significance of retaining separated files within root canals. An understanding of the mechanisms of, factors contributing to, file fracture is necessary to reduce the incidence of file separation within root canals. This article reviews the factors that are of utmost importance and in light of these, preventive procedures and measures are suggested.


A survey estimate of academic liver transplant teams' selection practices for alcohol-dependent applicants.
Alcoholism itself is not a contraindication to liver transplantation. However, certain individual alcoholic applicants may pose an unacceptably high psychosocial risk of poor outcome. Transplant psychiatrists or psychologists at 14 academic liver transplant centers were asked to estimate their centers' selection practices with regard to specific problems in the more difficult alcohol-dependent applicant and with regard to hypothetical problem cases. There was impressive variability in estimated selection practice between the centers. However, the centers consistently appeared to prefer to require rehabilitation or observation in difficult situations rather than to reject applicants outright. The results provide an initial estimate of current thinking and practice with regard to the more difficult alcoholic applicant and suggest directions for further study.


Effects of ketanserin on transmembrane sodium transport in erythrocytes.
Ketanserin, an antagonist of 5-HT2-serotonergic and alpha 1-adrenergic receptors, has come into use for the therapy of mild to moderate arterial hypertension. Quite recent observations have shown changes in transmembrane sodium (Na) transport after the acute administration of high doses of this drug to normal subjects. It is well known that some of these transport systems have an altered activity in essential hypertension. We evaluated the effects of long-term (3 months) administration of ketanserin (40-80 mg/day) on Na and potassium (K) intracellular concentrations and transmembrane fluxes in red blood cells (RBCs) from 12 essential hypertensive patients. In addition the present study describes the in vitro effects of two different concentrations of the drug (5 x 10(-8) and 5 x 10(-7) M) on erythrocytes in normal subjects. In the first study, both systolic and diastolic blood pressure were significantly lowered by the treatment with ketanserin (from 165/103 to 143/89; p less than 0.001). Na and K intraerythrocyte concentrations fell markedly during ketanserin administration (both p less than 0.001). A marked decrease in Na,K-pump activity (p less than 0.001) and an increase in Na,lithium(Li)-countertransport function (p less than 0.001) were observed. Na outward cotransport, Na leak, and K leak were not modified by the therapy. Direct correlation was found between the fall in mean blood pressure and in Na and K intraerythrocyte concentration (respectively, p less than 0.01 and p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Reactions of methyl, hydroxyl and peroxyl radicals with the DOTA chelating agent used in medical imaging.
The mechanism of reaction of DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid) with ·CH3, CH3O2· and ·OH radicals were studied. The radicals were formed in situ radiolytically. The methyl radicals react orders of magnitude slower with DOTA and with MIII(DOTA)- than the hydroxyl radicals. The various final products were identified and mechanisms for their formation are proposed. CH3O2· radicals do not react, or react too slowly to be observed, with DOTA and with MIII(DOTA)- as long as the central cation is not oxidized by the peroxyl radical. The results imply that synthesis of the MIII(DOTA)-(MIII = radioisotope) complexes in a water-organic solvent (ethanol or 2-propanol or acetonitrile) mixture is not only kinetically desired but the so formed complex also decreases the radiolytic decomposition of DOTA.


Is AC TightRope fixation better than Bosworth screw fixation for minimally invasive operative treatment of Rockwood III AC joint injury?
Injuries to the acromioclavicular (AC) joint are common in sports participants and may lead to instability or degenerative changes that require surgical intervention. Diagnostics include X-ray projections; MRI could also be a useful method. Surgical treatment of acute Rockwood type III AC dislocation varies on a case-by-case basis and includes coracoclavicular (CC) stabilisation with two techniques of minimal invasive fixation: the Bosworth screw and AC TightRope fixation (Arthrex, US). The aim of this study was to analyse whether there is a difference between these two surgical procedures in the quality of repair of CC ligaments by comparing preoperative and postoperative AC joint radiological and clinical findings. In this study, we evaluated our 5 years' experience of surgical management of Rockwood type III AC dislocation. Radiological analyses included measurement of CC distance at the AC joint, X-ray and MRI evaluation of CC ligament scar tissue continuity; clinical outcome was assessed using the Constant Murley, Oxford Shoulder and DASH scores preoperatively and during 6 months of postoperative follow-up. A total of 68 patients with Rockwood type III AC dislocation were treated surgically with minimally invasive CC fixation using either the AC TightRope implant (34 patients, TR group) or the Bosworth screw (34 patients, BS group) in a prospective, randomised clinical trial. There was no statistically significant difference in radiological X-ray and MRI evaluations of postoperative results between the two groups of patients at the end of follow-up. Patients in the TR group reported significantly less inconvenience with treatment as the patients in the BS group had to undergo a second operation to remove the Bosworth screw. Postoperative recurrence of dislocation was observed in two patients in the TR group (5.88%) and in four patients in the BS group (11.76%) 6 months postoperatively. The difference between the two groups was not statistically significant (p=0.4). MRI could be a useful method to evaluate quality of repair of CC ligaments. The minimally invasive surgical techniques used in this study showed similar radiological and clinical efficacy in the treatment of acute Rockwood type III AC dislocation, but AC TightRope fixation provided patients with significantly more treatment satisfaction and less inconvenience than Bosworth screw fixation.


Does stabilization of the degenerative lumbar spine itself produce multifidus atrophy?
The effect of stabilization of the degenerative segment on changes in the pattern of paraspinal muscle activity was investigated using a previously developed musculoskeletal model. Muscle activity change depending on L4-L5 segment stabilization with and without taking into account the presence of multifidus atrophy according to direct invasion of the back muscle during surgery (MADIBM) was analysed in erect standing and 20° flexed postures. For the stabilization of the degenerative segment, a fusion or non-fusion stabilization with a pedicle-based dynamic stabilization system (PBDS) was applied. During erect standing, fusion generated a 12% reduction in the total multifidus muscle force, while its reduction was 6.6% with PBDS application. The presence of MADIBM produced 23.0% and 22.5% reductions in fusion and with PBDS application, respectively. During 20° flexion, 10.5% and 9.3% reductions were produced for fusion and PBDS application, respectively, and the corresponding values were 23.4% and 23.0%, respectively, in the presence of MADIBM. Increased facet joint contact forces were produced at the non-stabilized levels after stabilization while in erect standing posture. Alterations in muscle activity, which could be regarded as adaptions to altered spinal stability, may generate unexpected secondary problems in the spine.


Paracoccidioidomycosis: an uncommon clinical presentation.
Paracoccidoiomycosis is a systemic mycosis with a higher incidence in males with history of exposure to the rural environment; its classic clinical manifestation is an oro-pulmonary lesion. The authors report a case of a female, urban, 76-year-old patient with atypical clinical-dermatological presentation and diagnostic conclusion after histopathological examination. The clinical response was quick and complete after treatment with itraconazole 400mg/day in the first month, decreased to 200mg/day until the sixth month of treatment.


UV-MALDI mass spectrometry analysis of NBD-glycosphingolipids without an external matrix.
Each day, advances in the instrumentation and operating protocols bring new applications and insights into the molecular processes of ultra violet-matrix assisted laser desorption/ionization-mass spectrometry (UV-MALDI MS), increasing its potential use. We report here an approach in which mass spectrometry analysis of sphingolipids has been performed using a fluorescent tag (nitrobenz-2-oxa-1, 3-diazole, NBD) covalently linked to the sphingoid base as matrix. Thus, different labeled-sphingolipids were analyzed: ceramide, dihydroceramide, acetylceramide, glucosylceramide, galactosylceramide, galactosyldihydroceramide. In addition an extract of glycosphingolipids obtained from epimastigote forms of Trypanosoma cruzi metabolically labeled with NBD-ceramide was analyzed. The goal of this work is to show that no matrix needs to be added for the mass spectrometry analysis as the same tag used to label the lipids may generate efficiently analyte ions to obtain high quality signals.


Pediatric facial injuries: Hitting close to home.
The aims of this study were as follows: To determine the national incidence of facial fractures among infants, toddlers, and children; to evaluate the types of facial fractures; and to analyze common products/activities associated with the fractures. A retrospective review was conducted to explore patterns of facial fractures among infants (<1 year), toddlers (1-3 years), and children (3-5 years), using the National Electronic Injury Surveillance System (NEISS) from the Consumer Product Safety Commission (CPSC). The database was searched for emergency department (ED) visits involving facial fractures sustained by children 1 month through 5 years of age from 2004 through 2016 and analyzed for patient demographics, primary diagnosis and associated products/activities. Subset analyses were performed between age groups to determine the relationship between causes of injury and age using extrapolated national incidences. A total of 1507 ED visits for facial fractures among infants, toddlers, and children were obtained and extrapolated to an estimated total of 39,388 ED visits, averaging 3030 annually. The majority of these ED visits were for facial fractures that occurred at home. Most facial fractures sustained at the age period of 1 month-5 years old were nasal fractures. Facial fractures in infants were caused most commonly by floors or flooring materials, likely due to falls, while household items/furniture-related injuries were the most common cause of facial fractures in both toddlers and children. Facial fractures from playground equipment and riding toys were more common in children than in the other age groups. The reported trends in the incidence by age group and types of fracture can assist physicians by serving as supplement for clinical history and examination when encountering this challenging patient population. Our findings highlight preventative opportunities, particularly in baby care items and beds for reducing facial fractures in infants. Similarly, preventative opportunities are highlighted in household items and furniture for lowering the incidence of facial fractures in toddlers and children. Our study also suggests ensuring safe handling of playground equipment and riding toys for the prevention of facial fractures in children.


Vaccination against Lucilia cuprina: the causative agent of sheep blowfly strike.
The sheep blowfly, Lucilia cuprina, is responsible for over 80% of cases of blowfly strike in Australia and the losses in production and sheep deaths due to flystrike exceed $200 million per annum. Traditional methods of control are becoming less effective because of the blowfly's resistance to insecticides and thus other methods of control are necessary. In general, sheep develop very little immunity to flystrike even after repeated infestation, however vaccination against L. cuprina has shown considerable potential for controlling flystrike. The most successful sources of antigens have been the larvae's secreted proteases and several extracts from gut or peritrophic membrane. Immunization with these antigens results in retardation of larval growth and in some cases larval mortality. On sheep immunized with peritrophic membrane extracts, the growth retardation appears to be caused by a blocking of the peritrophic membrane which results in the larvae being starved of nutrients. The prospects for vaccine development and the remaining barriers to be overcome are discussed.


Contractile reactivity of human myometrium in isolated non-pregnant uteri.
Perfusion of the isolated uterus has been shown to be a feasible experimental system for studies of the human endometrium and myometrium. Utilizing our established experimental perfusion model we perfused 20 uteri for 27 h and investigated the contractile reactivity of the myometrium in response to 17beta-estradiol (E2) and oxytocin (OT). Uteri of group A (n = 4) were stimulated with OT; group B (n = 4) was treated continuously with E2; group C (n = 4) received both E2 and OT for 27 h; group D (n = 4) was perfused for 27 h with E2 with the addition of OT for the last 3 h of the experiment; group E (n = 4) as control group remained without any treatment. The pressure and duration of uterine contractions were recorded during the entire perfusion period using intramural and endoluminal pressure catheters. Compared to the other treatment groups and controls, the most effective myometrial activity was achieved in group D during the OT stimulation period. No relevant myometrial activity was detected in the control group. Continuous E2 treatment, with the addition of OT for the last 3 h of the 27 h perfusion period, led to the most pronounced uterotonic effects in the presented experimental condition.


Effects of the starfish Patiria miniata on the distribution of the sea urchin Lytechinus anamesus in a southern Californian kelp forest.
At two stations in the San Onofre kelp bed near San Clemente, California the abundance of sea urchins, Lytechinus anamesus, and starfish, Patiria miniata, were negatively correlated. At one station, urchins were more abundant outside compared to inside the kelp bed, a pattern which generally occurs in southern California. In contrast, at the other station urchins were more abundant inside the bed. This exception to the general rule indicates that the distributions were not simply determined by something associated with the presence of kelp. Samples of substrates, sea urchins and sea stars suggested that the distribution of Patiria but not Lytechinus was controlled by the availability of suitable substrates. Further experiments showed that: 1) Patiria elicit an escape response from Lytechinus, the strength of which is positively related to the size of the urchins, 2) small urchins, which react less strongly to Patiria, are preyed on more heavily than are larger ones, and 3) escape responses elicited by Patiria cause local reductions of Lytechinus in the field. We conclude from these results that predation by Patiria controls the distribution of Lytechinus at our study sites, and may account for this species distribution in kelp forests throughout southern California. The possible effects of this predator-prey interaction on the structure of kelp forest communities are discussed.


Development of present and future of telepathology in Hungary.
Pathologists in Hungary evaluate several hundred thousand histological specimens yearly, and a second opinion is requested in 5-10 percent of cases. Application of multimedia systems (i.e. telepathology) is convenient and efficient to establish a correct diagnosis in such cases. The first telepathology connection in Hungary has been established between the 1st Department of Pathology and Experimental Cancer Research, Semmelweis University and the Department of Pathology, Central Hospital of the Ministry of the Interior. Further development occurred in the course of various projects, supported by the EU (Inter-path, Re-transplant, Be Pro): new stations were established in three university institutes and six county hospitals. Electronic fixation of the images and their transmission by telephone line (ISDN) is easily available and an important feature of the multimedia system applied in telepathology. The system used by us is suited to evaluate frozen or paraffin-embedded histologic sections, as well as immunohistochemical and cytologic specimens, if necessary supplemented with transmission of macroscopic pictures. Our experience with bilateral consultations has proven the importance of telepathology. The telepathology system established in Hungary is now ready to join the telepathology network of the EU.


Characterising the epidemic spread of influenza A/H3N2 within a city through phylogenetics.
Infecting large portions of the global population, seasonal influenza is a major burden on societies around the globe. While the global source sink dynamics of the different seasonal influenza viruses have been studied intensively, its local spread remains less clear. In order to improve our understanding of how influenza is transmitted on a city scale, we collected an extremely densely sampled set of influenza sequences alongside patient metadata. To do so, we sequenced influenza viruses isolated from patients of two different hospitals, as well as private practitioners in Basel, Switzerland during the 2016/2017 influenza season. The genetic sequences reveal that repeated introductions into the city drove the influenza season. We then reconstruct how the effective reproduction number changed over the course of the season. While we did not find that transmission dynamics in Basel correlate with humidity or school closures, we did find some evidence that it may positively correlated with temperature. Alongside the genetic sequence data that allows us to see how individual cases are connected, we gathered patient information, such as the age or household status. Zooming into the local transmission outbreaks suggests that the elderly were to a large extent infected within their own transmission network. In the remaining transmission network, our analyses suggest that school-aged children likely play a more central role than pre-school aged children. These patterns will be valuable to plan interventions combating the spread of respiratory diseases within cities given that similar patterns are observed for other influenza seasons and cities.


Quantification of resistant alleles in the β-tubulin gene of field strains of gastrointestinal nematodes and their relation with the faecal egg count reduction test.
Benzimidazole (BZ) resistance in gastrointestinal nematodes is associated with a single nucleotide polymorphism (SNP) at codons 167, 198 and 200 in the isotype 1 of beta-tubulin gene although in some species these SNPs have also been associated with resistance to macrocyclic lactones. In the present study we compared the levels of resistance in Teladorsagia circumcincta and Trichostrongylus colubriformis by means of the faecal egg reduction test (FECRT) and the percentage of resistant alleles obtained after pyrosequencing. The study was conducted in 10 naturally infected sheep flocks. Each flock was divided into three groups: i) group treated with albendazole (ABZ); ii) group treated with ivermectin (IVM); iii) untreated group. The number of eggs excreted per gram of faeces was estimated at day 0 and 14 post-treatment. Resistance to ABZ was observed in 12.5% (1/8) of the flocks and to IVM in 44.4% (4/9) of them. One flock was resistant to both drugs according to FECRT. Coprocultures were performed at the same dates to collect L3 for DNA extraction from pooled larvae and to determine the resistant allele frequencies by pyrosequencing analysis. In T. circumcincta, SNPs were not found at any of the three codons before treatment; after the administration of ABZ, SNPs were present only in two different flocks, one of them with a frequency of 23.8% at SNP 167, and the other 13.2% % at SNP 198. In relation to T. colubriformis, we found the SNP200 before treatment in 33.3% (3/9) of the flocks with values between 48.5 and 87.8%. After treatment with ABZ and IVM, the prevalence of this SNP increased to 75 and 100% of the flocks, with a mean frequency of 95.1% and 82.6%, respectively. The frequencies observed for SNP200 in T. colubriformis indicate that the presence of resistance is more common than revealed by the FECRT.


[Neural regulation of glucose, sodium and potassium transport in the kidneys].
When the speed of filtration and plasma circulation are constant, the absolute sodium reabsorption is increased in kidney on the side of stimulation of nervous fibers. The stimulating effect of adrenergic nerves on the tubular transport of sodium and potassium is inhibited with guanethidin. The maximum transport of glucose is increased by the activity of cholinergic fibers of vagus nerves.


Comparable outcomes in fracture reduction and bone properties with RANKL inhibition and alendronate treatment in a mouse model of osteogenesis imperfecta.
We report a direct comparison of receptor activator of nuclear factor kappa B ligand (RANKL) inhibition (RANK-Fc) with bisphosphonate treatment (alendronate, ALN) from infancy through early adulthood in a mouse model of osteogenesis imperfecta. Both ALN and RANK-Fc decreased fracture incidence to the same degree with increases in metaphyseal bone volume via increased number of thinner trabeculae. The potential therapeutic benefit of RANKL inhibitors in osteogenesis imperfecta (OI) is under investigation. We report a direct comparison of RANKL inhibition (RANK-Fc) with bisphosphonate treatment (ALN) from infancy through early adulthood in a model of OI, the oim/oim mouse. Two-week-old oim/oim, oim/+, and wildtype (+/+) mice were treated with RANK-Fc 1.5 mg/kg twice per week, ALN 0.21 mg/kg/week or saline (n = 12-20 per group) for 12 weeks. ALN and RANK-Fc both decreased fracture incidence (9.0 ± 3.0 saline 4.4 ± 2.7 ALN, 4.3 ± 3.0 RANK-Fc fractures per mouse). Serum TRACP-5b activity decreased to 65% after 1 month in all treated mice, but increased sacrifice with RANK-Fc to 130-200% at sacrifice. Metaphyseal density was significantly increased with ALN in +/+ and oim/oim mice (p < 0.05) and tended to increase with RANK-Fc in +/+ mice. No changes in oim/oim femur biomechanical parameters occurred with treatment. Both ALN and RANK-Fc significantly increased trabecular number (3.73 ± 0.77 1/mm for oim/oim saline vs 7.93 ± 0.67 ALN and 7.34 ± 1.38 RANK-Fc) and decreased trabecular thickness (0.045 mm ± 0.003 for oim/oim saline vs 0.034 ± 0.003 ALN and 0.032 ± 0.002 RANK-Fc) and separation in all genotypes (0.28 ± 0.08 mm for oim/oim saline vs 0.12 ± 0.010 ALN and 13 ± 0.03 RANK-Fc)., with significant increase in bone volume fraction (BVF) with ALN, and a trend towards increased BVF in RANK-Fc. Treatment of oim/oim mice with either a bisphosphonate or a RANK-Fc causes similar decreases in fracture incidence with increases in metaphyseal bone volume via increased number of thinner trabeculae.


Antiobesity effects of melanin-concentrating hormone receptor 1 (MCH-R1) antagonists.
Despite remarkable progress in the elucidation of energy balance and regulation, the development of new antiobesity drugs is still at the stage of infancy. This review describes the MCH and MCH receptor system with regard to its involvement in energy homeostasis and summarizes the pharmacological profiles of selected small molecule MCH-R1 antagonists that are relevant for their development as antiobesity drugs. Although their clinical value still has to be demonstrated, and challenges with regard to unwanted side effects remain to be resolved, MCH-R1 antagonists may provide an effective pharmacotherapy for the treatment of obesity in the near future.


Cumulative evidence for the relationship between body mass index and the risk of esophageal cancer: An updated meta-analysis with evidence from 25 observational studies.
A large number of papers reporting the relationships between body mass index (BMI) and esophageal cancer (EC) risk have been published in the past few decades; however, these results are inconsistent. Therefore, we carried out meta-analyses to explore the relationships between BMI and the risk of EC (including esophageal squamous cell carcinoma [ESCC] and esophageal adenocarcinoma [EADC]). We used the Web of Science, PubMed, and Embase to identify all published/online articles before December 30, 2018, which yielded 25 articles eligible for data extraction (including 16,561 cases and 11,954,161 controls), and then pooled the relative risks (RRs) and corresponding 95% confidence intervals (CIs) using random-effects model. Our study presented that underweight had statistically significant association with the risk of EC (RR = 1.78, 95% CI = 1.48, 2.14, P < 0.001) and ESCC (RR = 1.57, 95% CI = 1.20, 2.06, P = 0.001) when compared with normal weight. Interestingly, both overweight and obesity could increase the risk of EADC (RR = 1.56, 95% CI = 1.42, 1.71, P < 0.001; RR = 2.34, 95% CI = 2.02, 2.70, P < 0.001) while decrease the risk of ESCC (RR = 0.71, 95% CI = 0.60, 0.84, P < 0.001; RR = 0.63, 95% CI = 0.60, 0.84, P = 0.002). Additionally, obesity could increase the risk of EC (RR = 1.51, 95% CI = 1.21, 1.89, P < 0.001). These meta-analyses provide a comprehensive and updated epidemiological evidence to confirm the associations between BMI and EC risk. These findings have public health implications with respect to better control bodyweight and then reduce the occurrence of EC (including ESCC and EADC).


Endogenous fibrinolysis in neonatal cerebrospinal fluid.
Although many infants with intraventricular haemorrhage (IVH) recover without hydrocephalus, little is known about how blood is cleared from the CSF pathways. Fibrinolytic activity was measured by the fibrin plate method in CSF from 11 normal infants and 17 infants with IVH. Normal CSF showed no fibrinolytic activity. All the samples taken less than 17 days from diagnosis of IVH failed to show fibrinolytic activity. All but 1 of the CSF samples taken between 17 and 60 days of IVH showed fibrinolytic activity. In 1 infant where 14 serial samples were taken, there was no detectable fibrinolysis up to 16 days after IVH but from 19 to 52 days there was definite fibrinolytic activity. Delayed endogenous fibrinolysis in the CSF is common after IVH but may, in some cases, be insufficient to prevent hydrocephalus.


Bensulide-induced oxidative stress causes developmental defects of cardiovascular system and liver in zebrafish (Danio rerio).
Bensulide is an organophosphate herbicide commonly used in agricultural crops; however, no studies have reported on its toxic effects in the embryonic development of vertebrates, particularly gene expression level and cellular response. Therefore, to identify developmental toxicity, zebrafish eggs 8 h post-fertilization (hpf) were exposed to bensulide concentrations of up to 3 mg/L. The results indicated that exposure to 3 mg/L bensulide inhibited the hatching of all eggs and decreased the size of the body, eyes, and inner ear. There were demonstrated effects observed in the cardiovascular system and liver caused by bensulide in fli1:eGFP and L-fabp:dsRed transgenic zebrafish models, respectively. Following exposure to 3 mg/L bensulide, normal heart development, including cardiac looping, was disrupted and the heart rate of 96 hpf zebrafish larvae decreased to 16.37%. Development of the liver, the main detoxification organ, was also inhibited by bensulide, and after exposure to 3 mg/L bensulide its size reduced to 41.98%. Additionally, exposure to bensulide resulted in inhibition of antioxidant enzyme expression and an increase in ROS levels by up to 238.29%. Collectively, we identified various biological responses associated with the toxicity of bensulide, which led to various organ malformations and cytotoxic effects in zebrafish.