Understanding the pathogenesis of the restless legs syndrome at the level of the dopamine receptor. Are we about to identify the neurochemical deficiency causing schizophrenia?
According to a recent hypothesis, the restless legs syndrome is thought to be due to a caffeine-like substance produced by the human body (1). Some researchers have reported a case of familial restless legs that had high concentration of free dopamine in the cerebrospinal fluid (2). Other researchers have noticed the beneficial effect of opioids in the treatment of the restless legs syndrome (3). In this article, I am compiling information reconciling the findings of those researchers with the hypothesis that proposes that the restless legs syndrome is due to a caffeine-like substance produced by the human body. Also, I am addressing the pathogenesis of the restless legs syndrome at the level of the dopamine receptors in the central nervous system. Understanding this pathogenesis probably will help in identifying the neurochemical deficiency causing schizophrenia.


Calcium chelation induces a conformational change in recombinant herpes simplex virus-1-expressed rotavirus VP7.
Rotavirus, strain SA11, glycoprotein VP7 that was expressed by a recombinant herpes simplex virus-1 or contained in purified rotavirus particles lost reactivity with the neutralizing monoclonal antibody (mAb) 159, but not with nonneutralizing mAbs, upon chelation of calcium by EGTA. Exposing VP7, but not the neutralizing mAbs, to a transient excess of EGTA over calcium eliminated VP7 neutralizing epitopes. Therefore, a calcium chelation-induced conformational change in VP7, not in the neutralizing mAbs, caused the epitope loss. Addition of excess calcium or strontium, but not magnesium or barium, to EGTA-treated VP7 restored its 159 epitope. These results suggest that VP7 binds calcium in the absence of other rotavirus proteins and that the calcium chelation-induced conformational change in VP7 may mediate uncoating of double-shelled rotavirus particles.


Predictors for anaerobic bacteraemia beyond the source of infection: retrospective, nested, case-control study.
In a retrospective case-control study, adults with anaerobic bacteraemia (ANB) were matched to patients with aerobic bacteraemia based on source of infection (1:3), date and age. We identified diabetes mellitus as a significant risk factor for ANB when the source of the bacteraemia was unknown, OR 2.29 (95% CI 1.22-4.29).


Hydrocarbon chain packing modes in lipids: effect of altered sub-cell dimensions and chain rotation.
The lateral hydrocarbon chain packing modes of lipids have been described in terms of specific hydrocarbon sub-cells as deduced from single crystal structural studies. To understand the changes in hydrocarbon chain packing in lipid bilayers induced by variations in temperature, hydration, ion-binding, etc., we have examined the effect on the calculated X-ray diffraction pattern of (a) systematic variations in the dimensions of the hydrocarbon sub-cell and (b) the effect of chain rotation at fixed lattice sites. For the O perpendicular (orthorhombic) sub-cell, the a and b sub-cell parameters were varied from as = 4.96 to 4.85 A and bs = 7.42 to 8.40 A in six steps and the positions (s = 2 sin theta/lambda) and intensities (Icalc = F2) of the strong sub-cell reflections calculated. In this way, the conversion of the O perpendicular sub-cell (with either fixed chain orientations or simulated chain rotation) to the hexagonal (H) sub-cell (with chain rotation) was followed. Notably, the two strong reflections characteristic of the O perpendicular sub-cell at 4.12 A (110) and 3.71 A (020) show progressive shifts in position and intensity, finally merging to give the strong (O1O) reflection at 4.2 A characteristic of the hexagonal sub-cell. Similar calculations were performed for the orthorhombic (O' perpendicular) and monoclinic (M parallel) sub-cells. This approach can be used to analyze changes in the X-ray diffraction data due to modifications of the hydrocarbon chain packing modes characteristic of simple and complex lipids.


Contribution of the study of anemia in vitamin D deficiency rickets. I. Study of red blood cell survival.
The red blood cell T50 51Cr was determined in 14 infants with deficiency rickets unaccompanied by a myeloproliferative syndrome. There is a relationship between the values of T50 51Cr and the age of the patients, constant low values having been found in children under 14 months. This suggests hemolysis in the youngest rachitic children.


DSDatlas: disorders of sex development atlas for reproductive endocrinology-related gene discovery in integrative omics platforms.
To facilitate the identification of related genes and candidate biomarkers for disorders of sex development (DSD), we present disorders of sex development atlas (http://dsd.geneworks.cn). Disorders of sex development are a spectrum of endocrine diseases with distinct mutations of genes or chromosomes, but several issues regarding their pathogenesis remain elusive. High-throughput methods have allowed genomic and transcriptomic analyses of DSD; however, these data are deposited in various repositories owing to a lack of integrated online resources. A descriptive study of a specialized gene discovery platform designed for DSD. Publicly available DSD omics datasets and self-produced datasets. None. None. The gene ranking result, with detailed information based on DSD terms in a gene-disease association knowledge base, and results of differential gene expression and mutation analyses from omics datasets. The disorders of sex development atlas maintains both a knowledgebase for ranking DSD candidate genes and a database for DSD-related omics data analysis and visualization. We included 4 dominant classes of DSD in the knowledgebase: 15 subclasses and 44 specific disease names. Construction of the knowledgebase was centered upon Phenolyzer, with add-on seed gene databases customized by DSD-related genes collected from MalaCards, GeneCards, and DisGeNET. For the database, 25 experimental datasets related to DSD were integrated, including 24 public datasets from Gene Expression Omnibus and Sequence Read Archive and 1 self-generated dataset. A total of 474 samples from 240 DSD samples were collected for the database. This platform provides a friendly interface that integrates flexible and comprehensive analysis tools for differential expression and gene mutations between the DSD groups and controls.


The Id proteins and angiogenesis.
Since the identification of the Id proteins over a decade ago, a great many cell cycle and cell fate decisions have been shown to be under the control of these proteins as described in other sections of this review issue. Perhaps the most unsuspected activity of this class of proteins has been their essential role in angiogenesis, both in the forebrain during development and during the growth and metastasis of tumors in adults. This section of the review issue will focus on the key observations which have led to these conclusions, speculations about potential mechanisms and the outlook for potential therapeutic interventions.


[Experimental study on the etiology of idiopathic scoliosis--a deviation of lower motor neurons of the spinal muscle detected by the horseradish peroxidase method].
In order to elucidate the etiology of idiopathic scoliosis, studies were carried out by HRP method on the topographical localization and numerical alteration of spinal motor neurons innervating the spinal muscle of the non-scoliotic Japanese quail and the scoliotic one established by S. Hijikata in 1976. The topographical localization of spinal motor neurons innervating the triceps brachii muscle of the both groups, furthermore, was examined by the same method, and the anatomical fiber connection between the spinal motor neurons and the related spinal muscles was studied by central chromatolysis method. In addition the motor end-plate of the spinal muscle, found as an activated precipitate of AchE, was studied. In these studies on the anatomical fiber connection between the spinal motor neurons and the related spinal muscles, the retrograde axonal transport of HRP in the triceps brachii muscle, characterized by the phasic muscle, and the motor end-plate of the spinal muscle, there was no difference was found between the two groups. On the other hand, the retrograde axonal transport of HRP in the spinal muscle, characterized by the tonic muscle, was distinctly reduced in the scoliotic group, but it did not correlate with an angle of scoliotic curvature and the duration of scoliotic deformity. Reduction of the retrograde axonal transport should be regarded as primary neurogenic change, related with causation of idiopathic scoliosis.


The authors reply: Re: Yamamoto R, Sugiura T, Ashida R, Ohgi K, Yamada M, Otsuka S, and Uesaka K. Prognostic value of carbohydrate antigen 19-9 and the surgical margin in extrahepatic Cholangiocarcinoma. Ann Gastroenterol Surg. 2022;6:307-315.
The specific growth rate of the perioperative carbohydrate antigen 19-9 values was not related to the prognosis of extrahepatic cholangiocarcinoma.


Cross-cultural adaptation of the Taiwan Chinese version of the Falls Efficacy Scale-International for community-dwelling elderly individuals.
The Falls Efficacy Scale-International (FES-I) is a commonly used questionnaire to evaluate concerns about falling. We adapted a Taiwan Chinese version (FES-ITC) and evaluated its reliability and validity in community-dwelling elderly individuals. The discriminative validity was tested in relation to several known risk factors for fear of falling (FOF). The questionnaire was adapted through translation, back-translation, and expert review processes. A convenience sample of 135 community-dwelling elderly individuals (at least 60 years old) completed the adapted questionnaire, and 31 of them had a retest within 7-10 days. Cronbach's α and an intraclass correlation coefficient (ICC) were used to evaluate the internal consistency and test-retest reliability. Principal component factor analysis was performed to assess the factor-construct validity. The discriminative validity was tested in relation to demographic features, fall-related history and performances on three functional tests: timed up and go, four-stage balance and 30-s chair stand tests. Effect sizes were computed. Correlation coefficients between physical functional performance and FES-ITC scores were computed. Receiver operating characteristic curves were used to determine the cutoff point for the score to differentiate high and low concern of falling. The FES-ITC questionnaire had high internal consistency (Cronbach's α = 0.94) and excellent test-retest reliability (ICC = 0.94). Principal component factor analysis yielded a two-factor model, with several items requiring high demand on postural control loading on factor 2. FES-ITC scores discriminated individuals with different ages, reporting FOF, reporting falls in the past year and using walking aids. However, FES-ITC scores did not differ between the participants who were at risk of falling and those who were not at risk based on functional test performance and there was no correlation found between them. The FES-ITC was highly reliable and had adequate construct and discriminative validity. The lack of correlation between FES-ITC scores and functional test performance implied the presence of FOF even in individuals with good functional performance. Further follow up studies are warranted to verify the predictive validity of the FES-ITC.


Accuracy of the spontaneous breathing trial using a combined CPAP + PSV model to predict extubation outcomes in very preterm infants.
Very preterm infants often require mechanical ventilation. However, objective criteria to predict the outcomes of extubation in very premature neonates remain lacking. The aim of this study was to investigate the accuracy of the spontaneous breathing trial (SBT) using a combined model of continuous positive airway pressure (CPAP) and low-level pressure support ventilation (PSV) to predict the extubation outcomes of preterm infants with gestational age < 32 weeks. Preterm infants with gestational age < 32 weeks, birth weight < 1500 g and requiring mechanical ventilation were selected for the study. All infants underwent a 10-minute SBT using CPAP combined with low-level PSV prior to the planned extubation. Then, the infants were extubated within 1 h after SBT. The outcomes of extubation were considered successful if the neonates did not require reintubation 72 h after extubation. A total of 119 eligible preterm infants were enrolled in the study, with a median gestational age of 28.9 (27.1-30.3) weeks and a median birth weight of 1100 (900-1350) g. In total, 101 of all infants had successful extubation, 18 of whom failed and eventually had to be reintubated. Of the 102 infants who achieved SBT, 99 were successfully extubated, and 15 of the 17 infants who did not pass SBT had failed extubation. Finally, the diagnostic value for SBT could be assessed with a sensitivity of 98%, a specificity of 83.3%, a positive predictive value of 97.1% and a negative predictive value of 88.2%. SBT using a combined CPAP + low-level PSV model can predict the outcomes of extubation in very preterm infants with high sensitivity and specificity.


A photovoice documentation of the role of neighborhood physical and social environments in older adults' physical activity in two metropolitan areas in North America.
A substantial body of evidence indicates that regular engagement in moderate-intensity physical activity on most days of the week is sufficient for older adults to achieve positive health outcomes. Although there is a growing body of literature that examines the affect of neighborhood environment on physical activity in older adults, the research tends to overlook social aspects that potentially shape the relationship between physical environment and physical activity. This article presents qualitative themes related to the role of the physical and social environments in influencing physical activity among older adults as identified through the photovoice method with sixty-six older adults in eight neighborhoods in metropolitan Vancouver, British Columbia, Canada and Greater Portland, Oregon, USA. The photovoice data generated seven themes: being safe and feeling secure, getting there, comfort in movement, diversity of destinations, community-based programs, peer support and intergenerational/volunteer activities. Although the majority of these themes have explicit or implicit physical and social aspects, certain themes are primarily based on physical environmental aspects (e.g., safe and feeling secure, comfort in movement), while a few themes are more oriented to social context (e.g., peer support, intergenerational activity/volunteering). The themes are discussed with a focus on how the neighborhood physical and social environmental aspects interplay to foster or hinder older adults in staying active in both everyday activities and intentional physical activities. Policy implications of the findings are discussed.


Long-latency auditory event related potentials in migraine.
The pathophysiology of migraine and its associated perceptual symptoms remains controversial. We recorded long-latency auditory event related potentials (AEPs) in 30 unmedicated patients with common migraine, and compared them to 20 controls. 1,000 and 3,000 Hz tones were presented in an 80:20 ratio at 75 dB SL. 200 responses were recorded and replicated from Cz-A1 + A2, with filter band-pass of 1-100 Hz, analysis time of 1,000 ms., and interstimulus interval of 1.1 second. N100, P200, and N200 ERP components did not differ in latency or amplitude between migraine patients and controls. P300 was longer in latency among those with common migraine, and P300 amplitude was significantly reduced (P greater than 0.05). These findings suggest that migraine may have a central mechanism, and that migraineurs may have a difference in task involvement or perception which may influence their clinical course and response to therapy.


Prevalence of diarrheagenic Escherichia coli and impact on child health in Cap-Haitien, Haiti.
Diarrheagenic Escherichia coli (DEC) are common pathogens infecting children during their growth and development. Determining the epidemiology and the impact of DEC on child anthropometric measures informs prioritization of prevention efforts. These relationships were evaluated in a novel setting, Cap-Haitien, Haiti. We performed pre-specified secondary analysis of a case-control study of community-dwelling children, 6-36 months of age, enrolled 96 cases with diarrhea and 99 asymptomatic controls. Assessments were performed at enrollment and one month later at follow-up. Established endpoint PCR methodologies targeted DEC gDNA isolated from fecal swabs. The association between DEC and anthropometric z-scores at enrollment was determined using multivariate linear regression. Lastly, we assessed the association between specific biomarkers, choline and docosahexaenoic acid (DHA) and diarrheal burden. Enterotoxigenic Escherichia coli (ETEC) was identified in 21.9% of cases vs. 16.1% of controls with heat-stable producing ETEC significantly associated with symptomatic disease. Enteroaggregative E. coli (EAEC) was found in 30.2% of cases vs. 27.3% of controls, and typical enteropathogenic E. coli in 6.3% vs. 4.0% of cases and controls, respectively. Multivariate linear regression, controlled for case or control status, demonstrated ETEC and EAEC were significantly associated with reduced weight-age z-score (WAZ) and height-age z-score (HAZ) after adjusting for confounders. An interaction between ETEC and EAEC was observed. Choline and DHA were not associated with diarrheal burden. DEC are prevalent in north Haitian children. ETEC, EAEC, household environment, and diet are associated with unfavorable anthropometric measures, with possible synergistic interactions between ETEC and EAEC. Further studies with longer follow up may quantify the contribution of individual pathogens to adverse health outcomes.


Evaluation of Sensitivity and Cost-Effectiveness of Molecular Methods for the Co-detection of Waterborne Pathogens in India.
Waterborne microbial diseases are regarded as a major public health concern, particularly in nations with poor sanitation, a lack of social awareness, and problems linked with low socioeconomic status. Waterborne pathogen identification using traditional culture methods is time-consuming and labor-intensive. As a result, there is a growing demand for quick pathogen detection technologies. High sensitivity, specificity, and rapidity are all advantages of using molecular techniques like polymerase chain reaction (PCR) in such instances. In this study, we designed multiplex PCR and quantitative real-time PCR (qPCR) assays for the co-detection and enumeration of waterborne pathogens such as Aeromonas hydrophila, Pseudomonas aeruginosa, Salmonella enterica, Yersinia enterocolitica, Escherichia coli, Vibrio cholerae, and Shigella spp. Specific primers were selected against the virulence and species-specific genes of the seven target pathogens. For all seven target organisms, the detection limits for conventional culture methods were in the range of 103-104 cells/ml. While employing multiplex PCR method in this study, Pseudomonas aeruginosa and Shigella spp. have a detection sensitivity of 101 cells/ml, Vibrio cholerae and Aeromonas hydrophila have a detection sensitivity of 102 cells/ml, whereas Salmonella enterica, E. coli, and Yersinia enterocolitica have a detection sensitivity of only 103 cells/ml. According to our cost-benefit analysis, these molecular technologies are less expensive, with unit analysis costs of ₹52 and ₹173 for qPCR and multiplex PCR, respectively. Furthermore, all of the target genes had a detection limit of 1 cell/ml in qPCR. Because of their speed, sensitivity, specificity, and cost-effectiveness, these multiplex and qPCR assays could be employed for successful co-detection of aquatic pathogens.


Low reduction of prostate volume is a significant predictor of prostate cancer at subsequent biopsy in patients with dutasteride: A retrospective study.
Appropriate decision of prostate biopsy in men with 5α-reductase inhibitor (5AR inhibitor) is still unclear to avoid unnecessary biopsy. We retrospectively investigated patients with initial PSA 4.0 ng/ml or more and underwent subsequent prostate biopsy following dutasteride treatment. From September 2009 to August 2018, 399 cases of benign prostate hyperplasia (BPH) were treated with dutasteride in our department. Of the total, 36 cases with elevated pre-treatment PSA (4.0 ng/ml or more) and underwent subsequent prostate biopsy were included into this study. We evaluated PSA kinetics and changing prostate volumes (PV), and detection of prostate cancer. Overall, average PSA reduced by half at 6 months from dosing. Pre-treatment biopsy was performed in 17 of 36 cases, and all were diagnosed as having no malignancy. After treatment, prostate cancer was detected in 15 cases by subsequent biopsy. Fourteen of 15 cases were clinically significant cancer (Gleason score 7 or more). Logistic regression analysis detected a nominal association between prostate cancer detection and three variants, PSAD, PV reduction (1-Before/After PV) and abnormal MRI findings. In addition to abnormal MRI findings and pre-treatment of high PSAD, the case with low reduction of PV after treatment should consider performing prostate biopsy.


Etiology of neural tube defect in man--Do teratogens play any part? Evidence from sex ratios.
Neural tube defect (NTD) is more common among spontaneously aborted fetuses than in infants born in the third trimester, but there is no direct evidence that NTD-affected conceptuses, presenting at these two different gestational ages, are components of a single disease process. Evidence for homology is here presented in an analysis of the sex ratios of spontaneously and therapeutically aborted NTD-affected fetuses, and of sex ratios differing with variations in prevalence of NTD-affected infants. If it could be shown conclusively that NTD is a single disease process, with an inverse relationship between components expressed early and late in gestation, there would be implications for the ascertainment of families at risk for NTD, and for the search for environmental factors potentially involved in the causation of NTD.


Usefulness of breast-conserving surgery using the round block technique or modified round block technique in Japanese females.
The round block technique (RBT) is an oncoplastic technique in which only the perimamillary scars remain visible. We have performed RBT in cases that require resection of the breast tissue under the nipple-areola complex (NAC) and a modified round block technique (MRBT) in peripheral cases in which performing resection of the breast tissue under the NAC is unnecessary. We herein report the usefulness of these techniques. The study participants consisted of 18 patients who underwent breast-conserving surgery (BCS) using MRBT or RBT between July 2010 and July 2011. In the cases using RBT, de-epithelialization between the outer and inner incision lines was performed and the dermis was cut at the side of the tumor location. For MRBT cases, the dermis was cut in all parts of the inner and outer circles, and the skin between the inner and outer incision lines was resected. Cosmetic results were found to be excellent in three cases, good in eight cases, fair in five cases, and poor in two cases. In this study, the cosmetic results were unacceptable (fair and poor) in patients who underwent ≥25% resection or in whom the resected area was part of the lower portion of the breast. These techniques are useful for performing BCS in the upper portion of the breast. However, if the excision volume is >20% or excision of part of the lower portion of the breast is required, other procedures should be considered.


Role of JNK and Involvement of p53 in Stimulation of Growth Potential Realization of Mesenchymal Precursor Cells by Alkaloid Songorine.
The role of JNK-mediated signal pathway and participation of p53 transcription factor in stimulation of realization of the growth potential of the mesenchymal precursor cells by alkaloid songorine were examined in vitro. Specific inhibitors of JNK and p53 enhanced stimulation of fibroblast colony/cluster formation and proliferative activity of mesenchymal precursor cells. Under these conditions, more pronounced effects were observed with early precursors of fibroblast CFU and in both cases were accompanied by a decrease in differentiation index of progenitor elements.


Genome-Wide Genomic and Functional Association Study for Workability and Calving Traits in Holstein Cattle.
The goal of our study was to identify the SNPs, metabolic pathways (KEGG), and gene ontology (GO) terms significantly associated with calving and workability traits in dairy cattle. We analysed direct (DCE) and maternal (MCE) calving ease, direct (DSB) and maternal (MSB) stillbirth, milking speed (MSP), and temperament (TEM) based on a Holstein-Friesian dairy cattle population consisting of 35,203 individuals. The number of animals, depending on the trait, ranged from 22,301 bulls for TEM to 30,603 for DCE. We estimated the SNP effects (based on 46,216 polymorphisms from Illumina BovineSNP50 BeadChip Version 2) using a multi-SNP mixed model. The SNP positions were mapped to genes and the GO terms/KEGG pathways of the corresponding genes were assigned. The estimation of the GO term/KEGG pathway effects was based on a mixed model using the SNP effects as dependent variables. The number of significant SNPs comprised 59 for DCE, 25 for DSB and MSP, 17 for MCE and MSB, and 7 for TEM. Significant KEGG pathways were found for MSB (2), TEM (2), and MSP (1) and 11 GO terms were significant for MSP, 10 for DCE, 8 for DSB and TEM, 5 for MCE, and 3 for MSB. From the perspective of a better understanding of the genomic background of the phenotypes, traits with low heritabilities suggest that the focus should be moved from single genes to the metabolic pathways or gene ontologies significant for the phenotype.


Analysis and perspective: comparison of insulin diluent leakage post-injection using two different needle lengths and injection volumes in obese patients with type 1 or type 2 diabetes mellitus.
The effects of needle gauge and length on the efficacy and tolerability of insulin injection therapy are becoming better understood. This analysis discusses some of these effects and comments on a new study by Ignaut and Fu in this issue of Journal of Diabetes Science and Technology on the effects of needle length on insulin diluent leakage from injection sites.


Self assembly driven by hydrophobic interactions at alkanethiol monolayers: mechanisms of formation of hybrid bilayer membranes.
The mechanism for the formation of biomimetic model cell membranes consisting of bilayers composed of alkanethiols and phospholipids was probed with a kinetic study using surface plasmon resonance. The kinetics of formation of a monolayer of phospholipid from vesicles in solution onto a hydrophobic alkanethiol monolayer is described by a model that takes into account the lipid concentration, diffusion, and a surface reorganization rate constant. Monomer phospholipid apparently does not play a direct role in determining the kinetics of bilayer formation. Expressions for the limiting cases of this model describe the behavior of two distinct vesicle concentration conditions. At high concentrations of lipid vesicles the formation of the bilayer appears to be limited by the diffusion of vesicles to the surface; at lower concentrations of vesicles, the rate-limiting step is apparently the surface reorganization of lipid. This kinetic model can also be used to describe the formation of a biomimetic bilayer from an alkanethiol monolayer and cell membranes.


An analysis of 3599 midfacial and 1141 orbital blowout fractures among 4426 United States Army Soldiers, 1980-2000.
We sought to present the epidemiology associated with 3599 midfacial and 1141 orbital blowout fractures. We conducted a multicenter, 20-year retrospective analysis of hospitalization data on U.S. Army active duty soldiers. Men composed 96% of the patients, with men aged 20 to 29 years the most affected. Of midfacial and blowout fractures, 54.8% and 70.2% occurred with concomitant injury, with 36.2% and 50.9% sustaining other facial fractures, respectively. Three hundred forty orbital blowout fractures (29.8%) had an associated eye injury. Common mechanisms included fighting and motor vehicle accidents. Young men comprised the most susceptible population, and assault was the predominant mechanism. A high incidence of concomitant injury in midfacial and orbital blowout fractures, particularly ocular and intracranial injury, emphasizes the importance of a thorough physical examination. We report the results from one of the largest series of midfacial and orbital floor blowout fractures from a population that crosses urban, rural, and foreign boundaries.


Impact of tumor contact surface area on collecting system entry in robot-assisted partial nephrectomy: a retrospective analysis.
Collecting system entry in robot-assisted partial nephrectomy may occur even in cases showing a low N factor in the R.E.N.A.L nephrometry score. Therefore, in this study, we focused on the tumor contact surface area with the adjacent renal parenchyma and attempted to construct a novel predictive model for collecting system entry. Among 190 patients who underwent robot-assisted partial nephrectomy at our institution from 2015 to 2021, 94 patients with a low N factor (1-2) were analyzed. Contact surface was measured with three-dimensional imaging software and defined as the C factor, classified as C1, < 10 cm [2]; C2, ≥ 10 and < 15 cm [2]; and C3: ≥ 15 cm [2]. Additionally, a modified R factor (mR) was classified as mR1, < 20 mm; mR2, ≥ 20 and < 40 mm; and mR3, ≥ 40 mm. We discussed the factors influencing collecting system entry, including the C factor, and created a novel collecting system entry predictive model. Collecting system entry was observed in 32 patients with a low N factor (34%). The C factor was the only independent predictive factor for collecting system entry in multivariate regression analysis (odds ratio: 4.195, 95% CI: 2.160-8.146, p < 0.0001). Models including the C factor showed better discriminative power than the models without the C factor. The new predictive model, including the C factor in N1-2 cases, may be beneficial, considering its indication for preoperative ureteral catheter placement in patients undergoing robot-assisted partial nephrectomy.


The biodistribution and pharmacokinetics of meta-iodobenzylguanidine in childhood neuroblastoma.
MIBG is generating considerable interest for the treatment of neuroblastoma. This study has investigated the biological variation in handling of the compound in children with neuroblastoma. The biodistribution of the compound has been characterised in children undergoing tracer administrations of 123I and 131I-mIBG. Estimates of hepatic and whole body radiation dose delivery have been made. The results indicate substantial interpatient variation in hepatic dose delivery. This organ may be critical in some patients undergoing targeted radiotherapy with mIBG.


Pb3+ radiation defects in Ca9Pb(PO4)6(OH)2 hydroxyapatite nanoparticles studied by high-field (W-band) EPR and ENDOR.
W-band pulsed EPR and ENDOR investigations of X-ray irradiated nanoparticles of synthetic hydroxyapatite Ca(9)Pb(PO(4))(6)(OH)(2) are performed. It is shown that in the investigated species lead ions probably replace the Ca(1) position in the hydroxyapatite structure.


Perspective on AHFTC Specialty by Women in Heart Transplant and MCS (WiTMCS).
The advanced heart failure (HF) and transplant cardiology specialty has seen a decrease in applicants seeking training in the field. Data are needed to identify principal reform areas to generate and maintain interest in the field for sustainability. Women in Transplant and Mechanical Circulatory support conducted a survey across their membership group investigating the barriers to attracting new talent and areas that need reform to improve the status of the specialty. A Likert scale was used to assess various perceived barriers to attracting new trainees and reform needed to improve the specialty. A total of 131 women physicians in transplant and mechanical circulatory support responded to the survey. Five principal areas in need of reform were identified: need for practice model variety (86.9%), inadequate compensation for non-revenue value unit activities and total compensation (86.4% and 79.1%, respectively), challenging work-life balance (78.5%), need for curriculum reform and specialized pathways (73.1% and 65.4%, respectively), and exposure during general cardiology fellowship (65.1%). Given the increasing number of patients with HF and the increased demand for more HF specialists, reform is needed to restructure the 5 areas identified in our survey to increase interest in the field of advanced HF and transplant cardiology and maintain the current talent.


Galectin-3 captures interferon-gamma in the tumor matrix reducing chemokine gradient production and T-cell tumor infiltration.
The presence of T cells in tumors predicts overall survival for cancer patients. However, why most tumors are poorly infiltrated by T cells is barely understood. T-cell recruitment towards the tumor requires a chemokine gradient of the critical IFNγ-induced chemokines CXCL9/10/11. Here, we describe how tumors can abolish IFNγ-induced chemokines, thereby reducing T-cell attraction. This mechanism requires extracellular galectin-3, a lectin secreted by tumors. Galectins bind the glycans of glycoproteins and form lattices by oligomerization. We demonstrate that galectin-3 binds the glycans of the extracellular matrix and those decorating IFNγ. In mice bearing human tumors, galectin-3 reduces IFNγ diffusion through the tumor matrix. Galectin antagonists increase intratumoral IFNγ diffusion, CXCL9 gradient and tumor recruitment of adoptively transferred human CD8+ T cells specific for a tumor antigen. Transfer of T cells reduces tumor growth only if galectin antagonists are injected. Considering that most human cytokines are glycosylated, galectin secretion could be a general strategy for tumor immune evasion.Most tumours are poorly infiltrated by T cells. Here the authors show that galectin-3 secreted by tumours binds both glycosylated IFNγ and glycoproteins of the tumour extracellular matrix, thus avoiding IFNγ diffusion and the formation of an IFNγ-induced chemokine gradient required for T cell infiltration.


Oropharyngeal candidiasis caused by non-albicans yeast in patients receiving external beam radiotherapy for head-and-neck cancer.
To characterize non-albicans Candida oral infections in patients with head-and-neck cancer receiving external beam radiotherapy (EBRT) with or without concurrent chemotherapy. Thirty-seven patients with head-and-neck cancer received EBRT in 2.0-Gy daily fractions to a median dose of 60.4 Gy (range 38-82.8, mean 64.6). They were followed for oropharyngeal candidiasis (OPC) confirmed by positive examination, positive KOH smear, and/or positive swab or swish culture. Samples were identified and plated on chromogenic media to identify non-albicans yeasts. Colonies were plated on Sabouraud dextrose slants for microdilution antifungal susceptibility testing to fluconazole. DNA typing, including karyotyping, restriction fragment length polymorphism analysis, and Southern blot hybridization with the moderately repetitive Ca3 probe, was performed on selected isolates to confirm individual species. Of the 37 patients, 10 (27%) developed OPC, and 26 (70.3%) displayed Candida carriage state. The median EBRT dose at time of positive culture was 22.5 Gy and at time of OPC was 28.6 Gy. Of the 6 patients receiving chemotherapy and EBRT, 4 (66%) developed OPC at median dose of 27.6 Gy. Three (8%) of 37 patients were infected with non-albicans Candida, and 3 (30%) of all 10 infections were caused by these organisms. Non-albicans Candida is emerging as a relatively common cause of OPC in head-and-neck cancer patients. Chromogenic media are helpful to screen these infections. Our data also suggest a greater likelihood of developing OPC in patients receiving concomitant chemotherapy and EBRT.


Effect of ethyleneoxide groups of anionic surfactants on lipase activity.
The use of enzymes in laundry and dish detergent products is growing. Such tendency implies dedicated studies to understand surfactant-enzyme interactions. The interactions between surfactants and enzymes and their impact on the catalytic efficiency represent a central problem and were here evaluated using circular dichroism, dynamic light scattering, and enzyme activity determinations. This work focuses on this key issue by evaluating the role of the ethyleneoxide (EO) groups of anionic surfactants on the structure and activity of a commercial lipase, and by focusing on the protein/surfactant interactions at a molecular level. The conformational changes and enzymatic activity of the protein were evaluated in the presence of sodium dodecyl sulfate (SDS also denoted as SLE0 S) and of sodium lauryl ether sulfate with two EO units (SLE2 S). The results strongly suggest that the presence of EO units in the surfactant polar headgroup determines the stability and the activity of the enzyme. While SDS promotes enzyme denaturation and consequent loss of activity, SLE2 S preserves the enzyme structure and activity. The data further highlights that the electrostatic interactions among the protein groups are changed by the presence of the adsorbed anionic surfactants being such absorption mainly driven by hydrophobic interactions. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 32:1276-1282, 2016.


Changes in renal function during acute spinal cord injury: implications for pharmacotherapy.
Laboratory investigation in rats submitted to experimental spinal cord injury (SCI). To characterize changes in renal function during acute SCI. Sprague Dawley rats were subjected to severe spinal cord contusion at T8 level or to laminectomy as control. Twenty-four hours after spine surgery, clearance assessments of a single dose of iohexol (120 mg kg(-1)) or of p-aminohippuric acid (PAH, 100 mg kg(-1)) were used to evaluate glomerular filtration rate (GFR) and tubular secretion (TS), respectively. Blood sampling was used to determine concentrations of both compounds by high-performance liquid chromatography for pharmacokinetic measurements. Iohexol clearance decreased significantly after injury, which resulted in increased concentrations and half-life of iohexol in blood; PAH clearance remained unchanged. GFR but not TS is altered during spinal shock. These observations should be of interest to professionals caring for early cord-injured patients, in order to prevent toxicity and therapeutic failure when administering drugs eliminated by the kidney.


Effect of water velocity and temperature on energy use, behaviour and mortality of pallid sturgeon Scaphirhynchus albus larvae.
Natural reproduction of pallid sturgeon Scaphirhynchus albus has been limited for decades and a recruitment bottleneck is hypothesized to occur during the larval stage of development. In this study, we evaluated the effects of water velocity and temperature on the swimming activity, energy use, settling behaviour and mortality of endogenously feeding larvae. The swimming activity of drifting sturgeon larvae (i.e., fish exhibiting negative rheotaxis) increased at low water velocity. In subsequent experiments, we observed greater energy depletion and resultant mortality of larvae in no-flow environments (0 cm s-1 ) compared to tanks with water velocity ranging from 3.5 to 8.3 cm s-1 . The growth rate of drifting larvae was positively related to water temperature (18.7-23.3°C), but reduced growth rate at low water temperature (18.7°C) resulted in protracted development that extended average drift duration by ~4 days compared to larvae reared at 23.3°C. This study provides evidence that cooler summer water temperatures, characteristic of present-day conditions in the upper Missouri River, can reduce larval development and extend both the drift duration and distance requirements of S. albus. Moreover, if dispersed into low velocity environments, such as in reservoir headwaters, larvae may experience increased mortality owing to a mismatch between early life stage drift requirements and habitat conditions in the river. Manipulation of water releases to increase seasonal water temperature below dams may aid survival of S. albus larvae by shortening the time and distance spent drifting.


Evaluation of emergency department nursing services and patient satisfaction of services.
To identify nursing services and assess patient satisfaction in patients who present to the emergency department. Emergency nursing care is a significant determinant of patient satisfaction. Patient satisfaction is often regarded as a reliable indicator of the quality of services provided in the emergency department. This is a descriptive study. Eighty-four patients who presented to the university emergency department were included in the study. The study data were collected by the Patient Information Form and the Satisfaction Level Form. Emergency nursing services, including history taking, assessing vital signs, preparing the patient for an emergency intervention, oxygen therapy, drug delivery and blood-serum infusion were shown to be more commonly provided compared with other services such as counselling the patients and the relatives about their care or delivering educational and psychosocial services. However, 78·6% of the patients were satisfied with their nursing services. The highest satisfaction rates were observed in the following sub-dimensions of the Satisfaction Level Form: availability of the nurse (82·1%), behaviour of the nurse towards the patient (78·6%) and the frequency of nursing rounds (77·4%). The most common practices performed by nurses in the emergency department were physical nursing services. Patient satisfaction was mostly associated with the availability of nurses when they were needed. Our results suggest that in addition to the physical care, patients should also receive education and psychosocial care in the emergency department. We believe that this study will contribute to the awareness and understanding of principles and concepts of emergency nursing, extend the limits of nursing knowledge and abilities, and improve and maintain the quality of clinical nursing education and practice to train specialist nurses with high levels of understanding in ethical, intellectual, administrative, investigative and professional issues.


Significant decrease in plasma midregional proadrenomedullin level in patients with end-stage renal disease after living kidney transplantation.
Impaired renal function has been suggested to significantly impact plasma midregional proADM (MR-proADM) level. The aim of this study was to assess whether improvement of renal function after living kidney transplantation has an impact on plasma MR-proADM-like immunoreactive substance (IS) level. Eleven patients with end-stage renal disease (ESRD) who were scheduled to undergo the first living kidney allograft transplantation were enrolled. Plasma MR-proADM-IS levels were measured before and 3, 7, 10, 14, 21, 30, 60 and 90 days after kidney transplantation. Plasma MR-proADM-IS level decreased significantly from day 3 after kidney transplantation compared to before kidney transplantation. A significant negative correlation was observed between creatinine clearance and plasma MR-proADM-IS level from before to 90 days after kidney transplantation (rs=-0.70, p<0.0001). These results suggest that recovery of kidney function after kidney transplantation may lead to decrease in plasma MR-proADM level in patients with ESRD, and that plasma MR-proADM level may depend largely on renal function.


Calcium-induced fusion of didodecylphosphate vesicles: the lamellar to hexagonal II (HII) phase transition.
Electron microscopic techniques have been employed to investigate the ability of didodecylphosphate vesicles (diameter approx. 900 A) to fuse in the presence of Ca2+. As revealed by negative staining, Ca2+ induces extensive fusion and large vesicles with diameters up to 7000 A are formed. In a process secondary to fusion, the fused vesicles display a tendency to flatten and are subsequently transformed into extended tubular structures. Freeze-fracture electron microscopy, in conjunction with 31P NMR and selected area electron diffraction measurements indicate that the tubes are packed in a hexagonal (HII) array and that the amphiphiles are converted from the lamellar to the hexagonal HII phase. The relationship between membrane fusion and the lamellar-to-hexagonal phase transition is discussed in terms of formation and abundance of transiently stable inverted micellar intermediates at contact regions between two interacting membranes. A model for the conversion of the (vesicular) lamellar into the (tubular) hexagonal HII phase is presented, taking into account the molecular shape of the amphiphile. The relevance of using simple synthetic amphiphiles as models for phospholipid bilayers and complex biomembrane behavior is briefly discussed.


[Radiotherapy for non-small-cell bronchial cancers: definitions of volumes, patient selection. Recommendations of the International Association for the Study of Lung Cancer (IASLC)].
Chemoradiation is the standard treatment of unresectable, locally advanced non-small cell lung cancer, with a mean dose of 60-66 Gy, excluding escalation dose schemes. The standard treated volume includes primary tumor, ipsilateral hilar and mediastinal nodes, supraclavicular and contralateral nodes as well, regardless of the node status. This work tries to answer the question of the optimal volume to be treated. Drainage routes analysis is in favor of large volumes, while toxicity analysis favors small volumes. Combined modality treatment may increase the observed toxicity. The optimal volume definition is difficult, and requires available conformal therapy tools. Patients selection is another important issue. A volume definition is then attempted, based on the IASLC (International Association for the Study of Lung Cancer) Annecy workshop experience, highlighting the interobservers discrepancies, and suggests basic recommendations to harmonize volume definition.


Sleep Disorder Kleine-Levin Syndrome (KLS) Joins the List of Polygenic Brain Disorders Associated with Obstetric Complications.
Kleine-Levin Syndrome is a rare neurological disorder with onset typically during adolescence that is characterized by recurrent episodes of hypersomnia, behavioral changes, and cognitive abnormalities, in the absence of structural changes in neuroimaging. As for many functional brain disorders, the exact disease mechanism in Kleine-Levin Syndrome is presently unknown, preventing the development of specific treatment approaches or protective measures. Here we review the pathophysiology and genetics of this functional brain disorder and then present a specific working hypothesis. A neurodevelopmental mechanism has been suspected based on associations with obstetric complications. Recent studies have focused on genetic factors whereby the first genome-wide association study (GWAS) in Kleine-Levin Syndrome has defined a linkage at the TRANK1 locus. A Gene x Environment interaction model involving obstetric complications was proposed based on concepts developed for other functional brain disorders. To stimulate future research, we here performed annotations of the genes under consideration for Kleine-Levin Syndrome in relation to factors expected to be associated with obstetric complications. Annotations used data-mining of gene/protein lists related to for hypoxia, ischemia, and vascular factors and targeted literature searches. Tentative links for TRANK1, four additional genes in the TRANK1 locus, and LMOD3-LMO2 are described. Protein interaction data for TRANK1 indicate links to CBX2, CBX4, and KDM3A, that in turn can be tied to hypoxia. Taken together, the neurological sleep disorder, Kleine-Levin Syndrome, shows genetic and mechanistic overlap with well analyzed brain disorders such as schizophrenia, autism spectrum disorder and ADHD in which polygenic predisposition interacts with external events during brain development, including obstetric complications.


Lovastatin dose-dependently potentiates the pro-inflammatory activity of lipopolysaccharide both in vitro and in vivo.
Since contradictory findings have been reported on potential effects of statins in modulating the inflammatory response, we have analysed the biological activity of lovastatin both in vitro using the Raw 264.7 murine macrophagic cell line and in vivo using BALB/c mice. When added to Raw 264.7 cells in combination with lipopolysaccharide, lovastatin significantly potentiated the release of interleukin-1β, interleukin-6 and interleukin-12 with respect to lipopolysaccharide alone and showed an additive effect on the release of nitric oxide. Similarly, when lovastatin was intraperitoneally administrated to BALB/c mice, it did not induce any pro-inflammatory effect when used alone, but it significantly potentiated the pro-inflammatory activity of lipopolysaccharide, in terms of number of intraperitoneal cells and serum levels of serum amyloid A, interleukin-1β, interleukin-6 and interleukin-12. A potential clinical implication of our study is that lovastatin might exert a pro-inflammatory activity in subjects affected by inflammatory processes, with clinically evident or subclinical infections.


Efficiency of serum copper/zinc ratio for differential diagnosis of patients with and without lung cancer.
We examined serum copper (Cu), serum zinc (Zn), and the serum copper/zinc ratio (Cu/Zn) in 162 patients. All of them were seen to have an abnormal shadow in the chest X-ray films, that is, 109 patients with lung cancer (LC) and 53 patients with no lung cancer (NLC). The mean Cu and Cu/Zn in LC patients were significantly higher than those in NLC patients (p < 0.05). In LC patients, Cu and Cu/Zn were higher and Zn was lower in advanced tumors than early ones. There was a significantly clear relation between Cu or Cu/Zn and the tumor (T) stages. When the relative risk (RR) of LC was estimated, it was seen that the higher Cu and Cu/Zn became, the higher RR became. Furthermore, we showed the sensitivity of the receiver operator characteristic of the test (ROC) curve for Cu, Cu/Zn, and carcinoembryonic antigen (CEA) to diagnose LC, as explained in a paragraph of methods. The determinations of Cu, Zn, and Cu/Zn are simple and inexpensive. They also appear to have a great diagnostic value in determining the local invasion of LC and as a screening test in the high-risk patients for LC.


[Tranverse acro-osteolysis: A rare cause of nail dystrophy].
Acro-osteolysis (AO) involves partial or total destruction of the distal phalanges of the fingers or toes. The range of forms of AO is extremely wide. A distinction is generally made between the acquired forms and the genetic and idiopathic forms. Herein we report a case of idiopathic transverse single-finger AO associated with onychopathy. A 48-year-old woman consulted for a nail lesion involving brachyonychia in the right index finger alone (pseudo-clubbing appearance of the finger). The remainder of the clinical examination was normal, particularly in terms of neurological and dermatological investigations. Standard x-rays revealed transverse osteolysis of the middle third of the distal phalanx, occurring solely in the right index finger. While certainty regarding diagnosis of AO depends upon radiological findings, the radiological appearance is not specific. Two subgroups suggesting aetiological diagnosis may be distinguished: transverse AO with banding and longitudinal AO. With transverse AO, the diaphysis of the distal phalanx presents osteolysis with banding, but with sparing of the base of the band (pseudo-fracture appearance); this appearance is suggestive of toxic causes, congenital familial conditions or repetitive micro-trauma. Upon x-ray examination, the longitudinal forms exhibit concentric resorption of the band and these forms are more often seen in a setting of neurological, vascular or metabolic disorders. The associated nail involvement frequently present helps clarify the diagnosis, with nail plate shape being dependent on the integrity of the underlying bone. Herein we report the first case of transverse AO in a single finger associated with brachyonychia, and with no discernible cause.


Grapheme-color synesthetes show peculiarities in their emotional brain: cortical and subcortical evidence from VBM analysis of 3D-T1 and DTI data.
Grapheme-color synesthesia is a neurological phenomenon in which viewing achromatic letters/numbers leads to automatic and involuntary color experiences. In this study, voxel-based morphometry analyses were performed on T1 images and fractional anisotropy measures to examine the whole brain in associator grapheme-color synesthetes. These analyses provide new evidence of variations in emotional areas (both at the cortical and subcortical levels), findings that help understand the emotional component as a relevant aspect of the synesthetic experience. Additionally, this study replicates previous findings in the left intraparietal sulcus and, for the first time, reports the existence of anatomical differences in subcortical gray nuclei of developmental grapheme-color synesthetes, providing a link between acquired and developmental synesthesia. This empirical evidence, which goes beyond modality-specific areas, could lead to a better understanding of grapheme-color synesthesia as well as of other modalities of the phenomenon.


Lipid--lipoprotein composition in hypercholesterolemic children and their parents.
In 13 hypercholesterolemic children, re-screened for serum cholesterol after a 1-year interval, hypercholesterolemia was confirmed in only 61.5% of the cases. A tentative explanation seems to be the statistical principle of regression towards the mean. The lipid--lipoprotein analysis showed that serum and LDL cholesterol concentrations in the 13 hypercholesterolemic children and their parents were significantly higher compared to controls (children and parents). At re-screening, hyper-LDL cholesterolemia was present in only 8 of the 13 children (61.5%); 4 cases exhibited hyper-HDL cholesterolemia (30.7%). The high prevalence of the parents repeating the lipoprotein abnormality and the electrophoretic pattern found in the propositi (children) confirms the familial aggregation of the hypercholesterolemic states (hyper-LDL and hyper-HDL cholesterolemia). In conclusion the results of our study stress the importance of determining the lipid--lipoprotein composition, rather then merely evaluating total serum cholesterol in order to make a correct diagnosis of the hypercholesterolemic state. It should also be emphasized that the lipoprotein disturbances and their familial aggregation may be detected early in childhood, suggesting that the familial screening for risk factors of atherosclerosis should be done at pediatric age.


Leptomeric fibrils and T-tubule desmosomes in the Z-band region of the mouse heart papillary muscle.
The papillary muscle of the heart of adult white mice is investigated. Intrafibrillary located leptomeric fibrils, frequently encountered in the Z-band region of the myofibrils. The leptomeric fibrils are always running in a transverse direction and often in close proximity to the transverse tubules (which are also located at this level). There seems to be a close connection between the dense striae of the leptofibrils and the Z-bands of ordinary myofibrils. The leptomeric fibrils are spindle-shaped and have a length varying between 0.6 and 1.2 microgrometer. The banding periodicity of the fibrils is approximately 0.16 micrometer. Occasionally desmosomes are observed in the T-tubule system.


Peginterferon beta-1a for the treatment of relapsing multiple sclerosis: A case series.
Interferon beta therapies have been effective in the treatment of relapsing forms of multiple sclerosis for over 2 decades. These therapies have varying routes and schedules of administration but broadly similar clinical and radiologic efficacy. The most commonly reported adverse effects are flu-like symptoms and injection site reactions. The most recent addition to the class is peginterferon beta-1a, which is administered subcutaneously every 2 weeks. Although clinically stable patients with multiple sclerosis may switch between platform therapies (such as interferons) based on tolerability or personal preference, few studies have explored the outcomes of switching. Herein I present 3 cases of patients who either initiated therapy with peginterferon beta-1a or switched from another interferon and had positive outcomes. With appropriate patient education and expectation setting regarding potential flu-like symptoms and injection-site reactions, peginterferon beta-1a may be a beneficial alternative for patients who prefer less frequent injections.


Modifications of [3H]imipramine binding sites in platelets of chronic pain patients treated with mianserin.
Tritiated imipramine binding to whole platelets was measured in 16 chronic pain patients who were free from major depression, and in a control group. The maximum binding was significantly lower in chronic pain patients than in the control group, whereas the binding affinity was not significantly different. Twelve patients were treated with mianserin for 21 days; this produced a significant improvement in the mean scores for pain (evaluated with the McGill Questionnaire) and depressive symptoms (assessed with the Zung Self-Rating Scale). The improvement in both types of symptom was accompanied by a significant mean increase in the density of the [3H]imipramine binding sites without modifications in the values of the constant of affinity. All the patients who responded well to treatment (N = 8) had a family history of depressive spectrum disorders (DSD), while none of those who failed to respond had a first degree relative with DSD.


Host range control of cauliflower mosaic virus.
Studies with recombinant genomes of cauliflower mosaic virus (CaMV) strains D4, CM1841, and Cabb-B have shown that a host range determinant of CaMV is encoded within the first half of region VI, a gene which codes for P62, an inclusion body protein. In order to further study the host specificity of CaMV, a fourth CaMV strain, W260, was chosen that has a host range that is intermediate between D4 and CM1841. To determine which portion of the W260 genome controls systemic spread, recombinant viruses made between this strain and CM1841 and D4 were tested for their ability to systemically infect several solanaceous plants (Datura stramonium, Nicotiana edwardsonii, and Nicotiana bigelovii). The first half of gene VI specified the type of local lesions and systemic spread of recombinant strains in D. stramonium. In N. edwardsonii, it was found that the first half of gene VI controlled the type of local lesion formed but systemic spread was dependent on the whole of gene VI. In N. bigelovii the number of genes that determined systemic spread of CaMV varied with the strain of CaMV. Systemic spread of D4 in N. bigelovii was dependent on the first half of gene VI. In contrast, systemic spread of W260 in the same host was dependent on the whole of gene VI and another locus which mapped within genes I-V. Consequently, it appears that other viral proteins may interact with P62 or that P62 may function well in some hosts only in compatible forms of other viral proteins.


The first contribution of capillary electrophoresis to the study of abiotic origins of homochirality: investigation of the enantioselective adsorption of 3-carboxy adipic acid on minerals.
CE with UV detection was used for the first time to determine the enantioselective adsorption of the short-chain tricarboxylic acid, 3-carboxy adipic acid, on minerals as a mean of investigating plausible mechanisms for the origin of biochemical homochirality on Earth. The use of vancomycine as chiral selector in the separation buffer using the partial filling technique enabled the separation of the two enantiomers of this organic acid in about 12 min. Taking into account that this compound has a low absorption of the UV light, and in order to achieve the sensitivity needed to determine the enantiomeric excess of samples of 3-carboxy adipic acid adsorbed on minerals, we applied a strategy consisting of a field-amplified sample stacking together with the use of a bubble capillary and detection at low wavelength (192 nm). This combination enabled an LOD of about 10(-7) M and the determination of the enantiomeric excess of 3-carboxy adipic acid adsorbed on calcite and feldspar mineral samples at subnanomol levels of this acid. Results showed that an enantioselective adsorption of the enantiomers of 3-carboxy adipic acid on minerals took place.


Quantification of gastroesophageal regurgitation in brachycephalic dogs.
Gastroesophageal reflux and regurgitation occurs in brachycephalic dogs, but objective assessment is lacking. Quantify reflux in brachycephalic dogs using an esophageal pH probe and determine the association with scored clinical observations. Fifty-one brachycephalic dogs. Case review study. Signs of respiratory and gastrointestinal disease severity were graded based on owner assessment. An esophageal pH probe with 2 pH sensors was placed for 18-24 hours in brachycephalic dogs that presented for upper airway assessment. Proximal and distal reflux were indicated by detection of fluid with a pH ≤4. The median reflux per hour, percentage time pH ≤4, number of refluxes ≥5 minutes and longest reflux event for distal and proximal sensors were recorded. Association of preoperative respiratory and gastrointestinal grade, laryngeal collapse grade, and previous airway surgery with the distal percentage time pH ≤4 was examined using 1-way ANOVA. A total of 43 of 51 dogs (84%; 95% confidence interval 72-92) displayed abnormal reflux with a median (range) distal percentage time pH ≤4 of 6.4 (2.5-36.1). There was no significant association between the distal percentage time pH ≤4 and respiratory grade, gastrointestinal grade, laryngeal collapse grade, or previous upper airway surgery. The occurrence of reflux is not associated with owner-assessed preoperative respiratory and gastrointestinal grade, laryngeal collapse grade, and previous airway surgery. Esophageal pH measurement provides an objective assessment tool before and after surgery.


Hypodipsic hypernatremia associated with absence of septum lucidum and olfactory dysfunction.
A case of hypodipsic hypernatremia in a 16-month-old Japanese boy is reported. Partial antidiuretic hormone deficiency was present. Computed tomography of the brain revealed absence of septum lucidum. No ophthalmological abnormality could be found. He had hyposmia, which has not been reported previously in association with hypernatremia due to hypodipsia. Forced fluid administration and nasal 1-deamino-8-d-arginine vasopressin treatment could maintain serum electrolyte levels within normal ranges. However, episodes of hypernatremia could not be completely avoided while he was treated with 1-deamino-8-d-arginine vasopressin and ad libitum oral fluid.


Forecasting on Covid-19 infection waves using a rough set filter driven moving average models.
The pandemic outbreak of severe acute respiratory syndrome caused by the Coronavirus 2 disease in 2019, also known as SARS-COV-2 and COVID-19, has claimed over 5.6 million lives till now. The highly infectious nature of the Covid-19 virus has resulted into multiple massive upsurges in counts of new infections termed as 'waves.' These waves consist of numerous rising and falling counts of Covid-19 infection cases with changing dates that confuse analysts and researchers. Due to this confusion, the detection of emergence or drop of Covid waves is currently a subject of intensive research. Hence, we propose an algorithmic framework to forecast the upcoming details of Covid-19 infection waves for a region. The framework consists of a displaced double moving average ( δ DMA) algorithm for forecasting the start, rise, fall, and end of a Covid-19 wave. The forecast is generated by detection of potential dates with specific counts called 'markers.' This detection of markers is guided by decision rules generated through rough set theory. We also propose a novel 'corrected moving average' ( χ SMA) technique to forecast the upcoming count of new infections in a region. We implement our proposed framework on a database of Covid-19 infection specifics fetched from 12 countries, namely: Argentina, Colombia, New Zealand, Australia, Cuba, Jamaica, Belgium, Croatia, Libya, Kenya, Iran, and Myanmar. The database consists of day-wise time series of new and total infection counts from the date of first case till 31st January 2022 in each of the countries mentioned above. The δ DMA algorithm outperforms other baseline techniques in forecasting the rise and fall of Covid-19 waves with a forecast precision of 94.08%. The χ SMA algorithm also surpasses its counterparts in predicting the counts of new Covid-19 infections for the next day with the least mean absolute percentage error (MAPE) of 36.65%. Our proposed framework can be deployed to forecast the upcoming trends and counts of new Covid-19 infection cases under a minimum observation window of 7 days with high accuracy. With no perceptible impact of countermeasures on the pandemic until now, these forecasts will prove supportive to the administration and medical bodies in scaling and allotment of medical infrastructure and healthcare facilities.


Sarcopenia and type 2 diabetes: Pathophysiology and potential therapeutic lifestyle interventions.
Sarcopenia generally refers to the age-related reduction in muscle strength, functional ability, and muscle mass. Sarcopenia is a multifactorial condition associated with poor glucose disposal, insulin resistance, and subsequently type 2 diabetes (T2D). The pathophysiological connection between sarcopenia and T2D is complex but likely involves glycemic control, inflammation, oxidative stress, and adiposity. Resistance exercise and aerobic training are two lifestyle interventions that may improve glycemic control in older adults with T2D and counteract sarcopenia. Further, there is evidence that dietary protein, Omega-3 fatty acids, creatine monohydrate, and Vitamin D hold potential to augment some of these benefits from exercise. The purpose of this narrative review is: (1) discuss the pathophysiological link between age-related sarcopenia and T2D, and (2) discuss lifestyle interventions involving physical activity and nutrition that may counteract sarcopenia and T2D.


Pedicle subtraction osteotomy in the cervical spine.
Description of surgical technique with review of literature. To describe the surgical management of cervical spine deformity, using pedicle subtraction osteotomy. Previous articles have primarily described Smith-Petersen osteotomies and Simmons' modifications to correct fixed cervical deformity. Those were typically performed with the patient awake and sedated in a seated position and without the use of spinal instrumentation. Description of a single surgeon's technique for performing pedicle subtraction osteotomy to treat fixed cervical deformity. The use of pedicle subtraction osteotomy in the cervical spine is a safe and effective procedure when performed by experienced surgeons and can result in a satisfying outcome for both the patient and the surgeon.


Cochlear protein biomarkers as potential sites for targeted inner ear drug delivery.
The delivery of therapies to the cochlea is notoriously challenging. It is an organ protected by a number of barriers that need to be overcome in the drug delivery process. Additionally, there are multiple sites of possible damage within the cochlea. Despite the many potential sites of damage, acquired otologic insults preferentially damage a single location. While progress has been made in techniques for inner ear drug delivery, the current techniques remain non-specific and our ability to deliver therapies in a cell-specific manner are limited. Fortunately, there are proteins specific to various cell-types within the cochlea (e.g., hair cells, spiral ganglion cells, stria vascularis) that function as biomarkers of site-specific damage. These protein biomarkers have potential to serve as targets for cell-specific inner ear drug delivery. In this manuscript, we review the concept of biomarkers and targeted- inner ear drug delivery and the well-characterized protein biomarkers within each of the locations of interest within the cochlea. Our review will focus on targeted drug delivery in the setting of acquired otologic insults (e.g., ototoxicity, noise-induce hearing loss). The goal is not to discuss therapies to treat acquired otologic insults, rather, to establish potential concepts of how to deliver therapies in a targeted, cell-specific manner. Based on our review, it is clear that future of inner ear drug delivery is a discipline filled with potential that will require collaborative efforts among clinicians and scientists to optimize treatment of otologic insults. Graphical Abstract.


Age-dependent interaction between atopy and eosinophils in asthma cases: results from NHANES 2005-2006.
Atopy is an established risk factor for asthma, and an elevated eosinophil level is a hallmark of atopic and non-atopic asthma. Whether atopy and eosinophils act independently or interact to influence asthma has clinical and public health implications. To investigate the relationship between atopy and eosinophils in asthma. Data on current asthma, atopy (IgE positive to ≥ 1 allergen), and blood eosinophil percent (dichotomized at the median) were obtained for persons aged ≥ 6 years from the National Health and Nutrition Examination Survey 2005-2006. Interaction on an additive scale was evaluated by estimating the prevalences of asthma for combinations of atopy (yes or no) and eosinophil percent (high or low) and calculating the excess prevalence due to interaction. For all ages combined, the adjusted prevalences of asthma were 4.6%, 7.6%, 6.9% and 17.2% for persons with neither factor, atopy alone, a high eosinophil percent alone and both factors respectively. The excess prevalence of asthma due to interaction was 7.2%, indicating synergism. The excess prevalence was greatest in children aged 6-17 years (15.3%), and it decreased with each older age category until it was absent in adults aged ≥ 55 years (-0.2%). In children, 94% of asthma cases attributable to the 2 factors were attributable to the interaction, whereas in the oldest adults, no cases were attributable to the interaction. Interaction between atopy and an elevated eosinophil level in asthma cases was very strong in children but absent in the oldest adults, which suggests different mechanistic pathways for these factors by age and supports the notion that asthma is a heterogeneous disease. In addition, the age-dependent interaction between the factors has potential implications for the selection of asthma patients for treatments that would target either IgE or a high eosinophil level.


Long-term results of 32-mm alumina-on-alumina THA for avascular necrosis of the femoral head.
Ceramic bearings in total hip arthroplasty (THA) have been introduced in clinical practice to minimize the problem of polyethylene particle-induced osteolysis. The aim of the study is to report the results of 68 consecutive alumina-on-alumina THAs done in 61 patients for avascular necrosis (AVN) of the femoral head. In all implants a press-fit cup was used; it was combined with a 32-mm alumina head and with titanium-alloy stems. The mean age at surgery was 50 years. At an average follow-up of 13 years two hips have been revised, one for periprosthetic infection and one for excessive abduction of the cup. No revision for aseptic loosening is recorded; one anatomical cementless femoral stem had radiological evidence of definite aseptic loosening. No dislocations occurred, and no osteolysis was observed. The results support the application of alumina-alumina THA for long-lasting replacements.


Signaling filopodia in vertebrate embryonic development.
Next to classical diffusion-based models, filopodia-like cellular protrusions have been proposed to mediate long range signaling events and morphogen gradient formation during communication between distant cells. An increasing wealth of data indicates that in spite of variable characteristics of signaling filopodia in different biological contexts, they represent a paradigm of intercellular crosstalk which is presently being unraveled in a growing literature. Here, we summarize recent advances in investigating the morphology, cellular basis and function of signaling filopodia, with focus on their role during embryonic development in vertebrates.


Morphological specificity analysis of an image-based 3D model of airway filling in a difficult airway.
The purpose of this study was to analyze position-specific morphological changes of the upper airway and to further assess the impact of these changes in difficult airway during intubation. This observational comparative study included two groups (n = 20 patients/group): Group A had normal airway and Group B had difficult airway. Data obtained from two-dimensional magnetic resonance imaging were imported to Mimics V20.0 software for processing. We then reconstructed three-dimensional models of upper airway filling in patients in the supine and maximum extension position based on the imaging data. Those models were projected on coronal, sagittal, and horizontal planes to investigate multiple morphological features. We measured the surface area, radial length, and corner angle of the projected areas. Group A had larger upper airway filling volumes compared to Group B The volumes for the supine position were 6,323.83 ± 156.06 mm3 for Group A and 5,336.22 ± 316.13 mm3 for Group B (p = 0.003). The volumes the maximum extension position were 9,186.58 ± 512.61 mm3 for Group A and 6,735.46 ± 794.63 mm3 for Group B (p = 0.003). Airway volume increased in the upper airway filling model as the body position varied from the supine to maximum extension position (Group A: volume increase 2,953.75 ± 524.6 mm3, rate of change 31%; Group B: volume increase 1,632.89 ± 662.66 mm3, rate of change 25%; p = 0.052). The three-dimensional reconstruction model developed in this study was used to digitally quantify morphological features of a difficult airway and could be used as a novel airway management assessment tool.


Efficacy and safety of gatifloxacin for urinary tract infection in nonspecialized Korean urologic practice.
To investigate the efficacy and safety of gatifloxacin (400mg/day) on chronic prostatitis or cystitis, 453 patients with prostatitis (NIH category II or IIIa) (N=149, mean 45.8+/-13.3 years) and cystitis (N=304, mean 53.8+/-14.3 years) were enrolled. Total NIH CPSI score and symptom score for cystitis decreased from 20.3 to 9.9 (response rate 86.7%, 95% CI 80.2-93.2%) and from 6.2 to 1.8 (response rate 83.2%, 95% CI 78.7-87.7%), respectively. In the overall clinical efficacy, 71.2% and 88.4% of the patients with prostatitis and cystitis were responders, respectively. Of the patients, 15.7% reported insignificant adverse events. These results suggest that gatifloxacin was well tolerated and improved the clinical outcomes in patients with chronic prostatitis or cystitis.


Combined Breast Implant Explantation and Multilevel Mastopexy Technique.
Patients dissatisfied with their breast implants are faced with 2 options: secondary augmentation or removal of the implants. Simple removal of breast implants often leads to wide, deflated, and laterally displaced breasts which are notoriously difficult to reconstruct. We present a surgical technique that was specifically developed to recreate the breast mound using the wide laterally displaced breast tissue left after breast implant removal.


P53 and bcl-2 immunoexpression in patients with oral lichen planus and oral squamous cell carcinoma.
The aim of this study was to determine by immunohistochemistry the presence and significance of p53 and bcl-2 proteins in oral lichen planus (OLP) and oral squamous cell carcinoma (OSCC). We used 21 cases diagnosed as OLP 16 diagnosed as OSCC and four normal gingival biopsies taken from healthy patients were used as controls. Slides were processed for immunohistochemistry using anti-p53 and anti-bcl-2 monoclonal antibodies. We found p53 immunoexpression in 71.4% OLP cases and 68.7% OSCC cases, with no immunoexpression in control cases. Bcl-2 was negative for all OLP and OSCC cases, and mild positivity was observed in normal tissue. We found significant correlation among p53 expression and OSCC malignancy. Our results suggest that TP53 system mainly promotes a hyperproliferative state by cell cycle arrest of the OLP epithelial cells for repairing damaged DNA nor apoptosis and that anti-apoptotic action of bcl-2 is not important in this disease.


"Ryanopathies" and RyR2 dysfunctions: can we further decipher them using in vitro human disease models?
The regulation of intracellular calcium (Ca2+) homeostasis is fundamental to maintain normal functions in many cell types. The ryanodine receptor (RyR), the largest intracellular calcium release channel located on the sarco/endoplasmic reticulum (SR/ER), plays a key role in the intracellular Ca2+ handling. Abnormal type 2 ryanodine receptor (RyR2) function, associated to mutations (ryanopathies) or pathological remodeling, has been reported, not only in cardiac diseases, but also in neuronal and pancreatic disorders. While animal models and in vitro studies provided valuable contributions to our knowledge on RyR2 dysfunctions, the human cell models derived from patients' cells offer new hope for improving our understanding of human clinical diseases and enrich the development of great medical advances. We here discuss the current knowledge on RyR2 dysfunctions associated with mutations and post-translational remodeling. We then reviewed the novel human cellular technologies allowing the correlation of patient's genome with their cellular environment and providing approaches for personalized RyR-targeted therapeutics.


Rapid totally diverting loop sigmoid colostomy with noncontaminating rectal irrigation.
Loop sigmoid colostomy employing a stapling device and catheter irrigation of the distal segment is less time-consuming and has lest potential for contamination than the standard double-barrel colostomy. Unlike the standard loop colostomy, it is totally diverting.


Health assessment instruments for people with intellectual disabilities-A systematic review.
People with intellectual disabilities (ID) experience health disparities and are less likely to undergo recommended age- and gender-specific screening and health promotion. New diagnoses are frequently missed. Assessments with the aid of health assessment instruments are a way to address these problems. The aim of this review is to find the available health assessment instruments for people with ID used in primary care and evaluate their quality. We conducted an electronic literature search of papers published between January 2000 and May 2016. After a two-phase selection process (kappa: 0.81 and 0.77) we collected data from the 29 included peer-reviewed articles on the following four domains; development, clinimetric properties (i.e. validity, reliability, feasibility, acceptability), content (i.e. ID-related health problems, prevention and health promotion topics) and effectiveness of the instruments. We distinguished 20 different health assessment instruments. Limited information was found on the development of the instruments as well as on their clinimetric properties. The content of the instruments was rather diverse. The included papers agreed that health assessment instruments are effective. However, only three instruments evaluated effectiveness in a randomised controlled trial. Patients with ID, carers and general practitioners (GPs) generally appreciated the health assessment instruments. Two instruments, "Stay well and healthy -Health risk appraisal (SWH-HRA)"and the "Comprehensive Health Assessment Programme (CHAP)", appeared to have the highest quality. These instruments can be used to construct a health assessment instrument for people with ID that meets scientific standards.


Can we cure oligometastatic disease? A practical point of view.
To critically analyze the available evidence on oligometastatic breast cancer and to suggest therapeutic approaches for optimal management of these patients. Unlike metastatic breast cancer, which remains incurable, patients with a limited number and extent of metastatic lesions, that is, oligometastatic disease, might achieve disease control and long-term survival when radical therapy of the primary tumor, if present, and metastatic disease is added to standard systemic therapy. However, the lack of a clear definition, variety of presentations, and the absence of biomarkers makes oligometastatic breast cancer a poorly understood clinical entity for which there is no standard treatment. Improvements in systemic therapies along with radical treatment of the primary tumor and metastatic lesions, together with optimization in the use of imaging tools, may help to increase the percentage of patients with metastatic breast cancer who achieve no-evidence-of-disease status or, at least, chronification of the disease. However, the fundamental question remains: which patients may benefit the most from a radical therapeutic approach? In this article, we propose strategies for the appropriate selection and comprehensive management of these patients.


A comparison of the actions of cromakalim and nifedipine on rabbit isolated mesenteric artery.
This study shows that cromakalim (0.4-10 microM) can concentration-dependently hyperpolarize the smooth muscle cell membrane and increase 86Rb efflux from rabbit mesenteric small arteries at concentrations which inhibit noradrenaline-induced increases in perfusion pressure in this preparation. Hyperpolarisation of the cell membrane by cromakalim was inhibited by prior exposure of the tissue to glibenclamide (1 microM). Noradrenaline (greater than 1 microM) depolarized the smooth muscle cell membrane and this effect was reduced in the presence of cromakalim. Experiments involving repetitive stimulation of the perivascular nerves in this tissue showed that cromakalim (2-10 microM) reduced excitatory junction potential amplitude and fall time without affecting the facilitation process. The results of this study suggest that in rabbit small mesenteric arteries the vasodilator action of cromakalim is a consequence of the opening of 86Rb-permeable potassium channels. It is unlikely that any component of the vasorelaxant effects of cromakalim is due to a direct effect on voltage-operated calcium channels or a prejunctional effect on neuroeffector transmission.


Pediatric migraine and episodic syndromes that may be associated with migraine.
Migraine is a common disorder and a frequent cause of medical consultation in children. Many childhood episodic syndromes have been described as common precursors of migraine. To review current knowledge on migraine and childhood episodic syndromes, and to discuss future directions for research and clinical practice. For most children it is difficult to describe a headache and fully verbalize symptoms such as photophobia and phonophobia that must be inferred from behaviour. Classical migraine features are rare before the age of 6 years, but some migraine-related syndromes have been described. Benign paroxysmal torticollis of infancy, benign paroxysmal vertigo of childhood, cyclic vomiting syndrome and abdominal migraine are currently classified as childhood episodic syndromes, and therefore common precursors of migraine. A strong association between infantile colic and migraine has recently been reported. There are similarities between children with episodic syndromes and children with migraine, regarding social and demographic factors, precipitating and relieving factors, and accompanying gastrointestinal, neurologic, and vasomotor features. The real pathophysiological mechanisms of migraine are not fully understood. Current data obtained through molecular and functional studies provide a complex model in which vascular and neurologic events cooperate in the pathogenesis of migraine attacks. Genetic factors causing disturbances in neuronal ion channels, make a migraineur more sensitive to multiple trigger factors that activate the nociception cascade. The expanding knowledge on migraine genetics and pathophysiology may be applicable to childhood episodic syndromes. Migraine preventive strategies are particularly important in children, and could be beneficial in childhood episodic syndromes. Nonspecific analgesics like ibuprofen and acetaminophen are widely used in pediatrics to control pain and have been found to be effective also in the treatment of acute migraine attacks. Triptans are the specific fist-line drugs for acute migraine treatment. Migraine phenotype differs somewhat in the developing brain, and childhood episodic syndromes may arise before typical migraine headache. Diagnosing pediatric migraine may be difficult because of children's language and cognitive abilities. The risk of underestimating migraine in pediatric age is high. An adequate diagnosis is important to maintain a good quality of life and to avoid inappropriate therapy.


Pattern of Cerebral Aneurysms in a Kenyan Population as Seen at an Urban Hospital.
Intracranial aneurysms constitute a significant part of the caseload for any neurosurgical service. Despite the occurrence of intracranial aneurysms and the availability of advanced diagnostic tools and management options, there is a paucity of published data concerning aneurysm patterns in Kenya. This was a combined retrospective and prospective quantitative descriptive study. Following ethical approval, all patients with cerebral aneurysms seen on computed tomography angiography who presented at Nairobi Hospital between May 2010 and June 2014 were included. A standardized questionnaire was used to collect data on patient characteristics, indications for imaging, and radiologic findings. Analysis was carried out SPSS for Windows version 15.0. The study included 121 patients with a female (71.9%) predominance; most (30.58%) of the patients were aged 50-59 years. There were 151 aneurysms observed, with 85.95% of patients having solitary aneurysms and 14.05% having multiple aneurysms; 82.1% of the aneurysms were located in the anterior circulation. Mean aneurysm size was 6.92 mm, mean neck diameter was 2.79 mm, and the range of diameter/neck ratio was 1-11.88 (mean 1.16). The rate of subarachnoid bleeding displayed an exponential increase with aneurysms 3 mm in size and appeared to plateau thereafter despite increasing aneurysm size. Most (78.8%) of the observed anterior communicating artery aneurysms were ruptured. Most patients were postmenopausal women, who had a higher rate of aneurysms with an elevated risk of rupture for small aneurysms; this suggests that clinicians need to be more vigilant and have a higher index of suspicion in such patients with subtle clinical signs. This study revealed a pattern of aneurysms in accord with previous reports and is expected to serve as a basis for further research on aneurysm management, outcome, and prognostic indicators in the Kenyan population.


A collaborative working environment for small group meetings in Second Life.
This paper presents the SLMeetingRoom, a virtual reality online environment to support group meetings of geographically dispersed participants. A prototype was developed to demonstrate the feasibility of the approach using the Second Life platform. Ten additional components had to be added to Second Life environment to support group work essential activities such as participants' communication, tasks' and participants' coordination, participants' collaboration and work evolution's perception. Empirical studies, both pilot and experiment, were developed comparing four different meeting settings: face-to-face, videoconference, stand Second Life and SLMeetingRoom. The study involved graduate students enrolled in the Interface and Multimedia discipline at the Fluminense Federal University (UFF) in Brazil. Results indicated that groups working within SLMeetingRoom environment presented similar results as face-to-face meeting as far as sense of presence is concerned and with low cognitive effort. Task completion and degree of participation were not affected by the meeting set up. It was concluded that Second Life, in conjunction with the SLMeetingRoom components, is a good tool for holding synchronous remote meetings and coexists with other electronic meeting technologies.


Preformulation and Vaginal Film Formulation Development of Microbicide Drug Candidate CSIC for HIV prevention.
5-chloro-3-[phenylsulfonyl] indole-2-carboxamide (CSIC) is a highly potent non-nucleoside reverse transcriptase inhibitor (NNRTI) of HIV-1 which has been shown to have a more desirable resistance profile than other NNRTIs in development as HIV prevention strategies. This work involves generation of preformulation data for CSIC and systematic development of a cosolvent system to effectively solubilize this hydrophobic drug candidate. This system was then applied to produce a polymeric thin film solid dosage form for vaginal administration of CSIC for use in prevention of sexual acquisition of HIV. Extensive preformulation, formulation development, and film characterization studies were conducted. An HPLC method was developed for CSIC quantification. Preformulation tests included solubility, crystal properties, stability, and drug-excipient compatibility. Cytotoxicity was evaluated using both human epithelial and mouse macrophage cell lines. Ternary phase diagram methodology was used to identify a cosolvent system for CSIC solubility enhancement. Following preformulation evaluation, a CSIC film formulation was developed and manufactured using solvent casting technique. The developed film product was assessed for physicochemical properties, anti-HIV bioactivity, and Lactobacillus biocompatibility during 12-month stability testing period. Preformulation studies showed CSIC to be very stable. Due to its hydrophobicity, a cosolvent system consisting of polyethylene glycol 400, propylene glycol, and glycerin (5:2:1, w/w/w) was developed, which provided a uniform dispersion of CSIC in the film formulation. The final film product met target specifications established for vaginal microbicide application. The hydrophobic drug candidate CSIC was successfully formulated with high loading capacity in a vaginal film by means of a cosolvent system. The developed cosolvent strategy is applicable for incorporation of other hydrophobic drug candidates in the film platform.


Use of phenolic glycolipid 1 for serodiagnosis of leprosy in a high prevalence village in Papua New Guinea.
This study reports on the usefulness of an IgM phenolic glycolipid 1 (PGL-1) ELISA for serodiagnosis of leprosy in the first year of a prospective longitudinal community survey in a high (8.8%) prevalence village in Papua New Guinea. The IgM PGL-1 ELISA had limited value as a screening method for detection of new cases. Many normal persons, particularly children, had elevated IgM anti-PGL-1 antibodies, presumably a consequence of early subclinical infection.


Investigations of ticks for the presence of Borrelia in Czechoslovakia.
More than 570 ticks from different parts of the country were studied microscopically. In 45 cases (8%) Borreliae were found. The infectivity rate of ticks in different foci varied from 3-11%, in some instances nearly 20%. Only Ixodes ricinus, male and female ticks were positive in this study.


Distinct gene expression signatures in lynch syndrome and familial colorectal cancer type x.
Heredity is estimated to cause at least 20% of colorectal cancer. The hereditary nonpolyposis colorectal cancer subset is divided into Lynch syndrome and familial colorectal cancer type X (FCCTX) based on presence of mismatch repair (MMR) gene defects. We addressed the gene expression signatures in colorectal cancer linked to Lynch syndrome and FCCTX with the aim to identify candidate genes and to map signaling pathways relevant in hereditary colorectal carcinogenesis. The 18 k whole-genome c-DNA-mediated annealing, selection, extension, and ligation (WG-DASL) assay was applied to 123 colorectal cancers, including 39 Lynch syndrome tumors and 37 FCCTX tumors. Target genes were technically validated using real-time quantitative RT-PCR (qRT-PCR) and the expression signature was validated in independent datasets. Colorectal cancers linked to Lynch syndrome and FCCTX showed distinct gene expression profiles, which by significance analysis of microarrays (SAM) differed by 2188 genes. Functional pathways involved were related to G-protein coupled receptor signaling, oxidative phosphorylation, and cell cycle function and mitosis. qRT-PCR verified altered expression of the selected genes NDUFA9, AXIN2, MYC, DNA2 and H2AFZ. Application of the 2188-gene signature to independent datasets showed strong correlation to MMR status. Distinct genetic profiles and deregulation of different canonical pathways apply to Lynch syndrome and FCCTX and key targets herein may be relevant to pursue for refined diagnostic and therapeutic strategies in hereditary colorectal cancer.


The iatrogenic leukaemias induced by radio- and/or chemotherapy.
A short review, limited to recently published series of data, has been compiled on the 'therapy-induced' secondary malignancies. Their frequency, peak of incidence, haematological and clinical criteria, the influence of age, treated primary disease, choice of drug(s) and modality of prescription and the role of genetic and environmental factors are analyzed. The risk varies between 0.6 and 20.5% after different treatment forms. Some suggestions for the choice of treatment of chronic malignant disorders, and for the design of future epidemiological studies are given.


Synergistic bactericidal effect of clove oil and encapsulated atmospheric pressure plasma against Escherichia coli O157:H7 and Staphylococcus aureus and its mechanism of action.
We investigated the bactericidal effect of clove oil and encapsulated atmospheric pressure plasma (EAP), individually or in combination, against Escherichia coli O157:H7 and Staphylococcus aureus. The bactericidal effect of the combined treatment was also investigated in inoculated beef jerky. For both pathogens, clove oil and EAP single treatments resulted in less than 3.0-log reductions, whereas the combined treatment resulted in more than 7.5-log reductions. The disc-diffusion assay and gas chromatography-mass spectrometry showed no changes in both the clear zone diameter and chemical composition of clove oil before and after the EAP treatment. Significant changes in cell membrane permeability and cell morphology resulting from the combined treatment of clove oil and EAP were evidenced by increased in UV absorption of cell supernatants, increased cell staining with propidium iodide, and changes in cell structure revealed by transmission electron microscopy. The synergistic bactericidal effects of clove oil and EAP against both pathogens were also observed in inoculated beef jerky, but the treatments were less effective against S. aureus, presumably due to thicker peptidoglycan layer. Experiments also demonstrated that the synergistic bactericidal effects between clove oil and EAP are due to clove oil increasing the susceptibility of the bacteria to subsequent EAP treatment, and does not involve alteration of the antibacterial activity of clove oil by EAP.


Comparison of Two Minimally Invasive Techniques with Endoscopy and Microscopy for Extraforaminal Disc Herniations.
Extraforaminal disc herniations are extraordinary herniations because they are located outside the foraminal bony borders and compress the root exiting at the corresponding level, whereas in median or paramedian herniations, the root 1 level below is compressed. Percutaneous endoscopic discectomy (PED) and microscopic extraforaminal discectomy (MEFD) are 2 popular contemporary techniques that have been performed extensively for these herniations since the 1970s. In this study, we retrospectively analyzed 118 patients who underwent either PED (66 patients) or MEFD (52 patients). All the patients were clinically evaluated for neurologic examination findings, visual analog scale (VAS) scores for leg pain and Oswestry Disability Index (ODI) preoperatively and on the seventh postoperative day as well as 6 and 12 months after surgery. The complication rates and types of both techniques were discussed. The preoperative VAS score and ODI were all comparable. Improvements in VAS scores 6 months postoperatively and improvements in ODI at all follow-up periods were statistically significant in favor of PED. However, there was great discrepancy regarding the postsurgical complications in favor of MEFD. PED is more prone to complications because this technique is strictly dependent on the tubular system and the ideal anatomy of the Kambin triangle. Variations in or degeneration of the Kambin triangle can lead to devastating complications in the PED technique, but normal anatomic conditions are feasible in only approximately 20% of patients. The most important feature of this study was that both techniques were performed by the same experienced team, who developed their own concept.