Aging or comorbid conditions - what is the main cause of kidney damage?
Chronic kidney disease (CKD) is widespread in the general population. It is generally accepted that worsening renal function is common with aging. However, the question still remains whether it is caused by the natural process of aging or whether coexisting chronic diseases and comorbid conditions contribute to deteriorating renal function. The frequency of albuminuria-the marker of early kidney damage-was evaluated according to different coexisting conditions in younger (18/64 years old, n=2,074) and elderly (=65 years old, n=395) participants of the Polish study PolNef on early detection of CKD. Multivariate logistic regression was performed to identify associations between elevated levels of albuminuria, age and coexisting conditions. 12% of the younger group demonstrated albuminuria compared to 18% of the elderly. Independent predictors of detecting an elevated level of albuminuria for the whole examined population were male gender (2.48, 1.59-3.88), hypertension ineffectively treated (1.8, 1.34-2.4), diabetes (1.67, 1.11-2.49), and age (1.56, 0.97-2.52) at border levels of significance. Moreover, elevated levels of albuminuria occurred more frequently in the obese elderly group (1.89, 0.98-3.63, p=0.058). The following predictors were found based on gender: for men, hypertension regardless of efficacy of treatment, diabetes, smoking, and age at border level of significance, in contrast to women who had the sole predictor of ineffectively treated hypertension. The influence of aging alone on kidney damage is not evident. Moreover, it is different in males and females. Hypertension is the only coexisting comorbid condition contributing to kidney damage in both males and females. Advanced age together with comorbid conditions is more harmful to the kidney in males.


Exposure-enhanced cognitive behavioral therapy for adolescents with binge eating: An initial case series.
Binge eating (BE) often develops during adolescence and is associated with deleterious psychological and physical consequences. Current treatments for adolescents achieve suboptimal results, likely due to failure to adequately address fear of weight gain (FOWG) which maintains BE. Thus, exposure treatment (the most powerful intervention for fear) may be a promising approach. However, exposure treatment has only minimally tested in adults with BE and never tested in adolescents. Thus, the current study is the first to evaluate a 4-session exposure module within a 12-session standard cognitive behavioral therapy for adolescents with BE. We recruited adolescents with BE (N = 5) and examined treatment feasibility, acceptability, and preliminary effects on FOWG and eating pathology. Overall, the 4-session exposure module was feasible and acceptable and showed preliminary evidence that it could reduce FOWG. However, several participants did not endorse significant fears of weight gain; rather, these participants reported that fears of deprivation or social judgment were more related to their BE. Future research should test higher doses of exposure and further examine the role of fear of deprivation/social judgment. Finally, future iterations of this treatment could include more parent involvement or test exposure in combination with treatments other than cognitive behavioral therapy, such as family-based treatment.


Primary and revision total hip arthroplasty in osteogenesis imperfecta.
Due to an increasing lifespan, patients with osteogenesis imperfecta have a high incidence of hip osteoarthritis. The presence of recurrent fractures and deformities make primary and particularly revision total hip arthroplasty challenging. We present a series of patients with osteogenesis imperfecta undergoing total hip arthroplasty at a tertiary referral centre with a median follow-up of 7.6 years (4 to 35 years). There were four primary total hip arthroplasties and eight revision total hip arthroplasties performed in four patients. Three femoral components were custom computer assisted design computer assisted manufactured. The survival rate of the primary total hip arthroplasty was 16% and there were ten complications: five intraoperative fractures, one case of septic loosening and four cases of aseptic loosening. Patients with pre-operative acetabular protrusio were significantly more likely to require revision surgery (p = 0.02). At latest follow-up, the median Oxford hip score was 41 (37 to 46). As the largest series of primary and revision total hip arthroplasty performed in patients with osteogenesis imperfecta, we report good medium to long-term outcomes. Preoperative planning and consideration of custom made prostheses have an important role in these complex cases.


The esophageal coin: is it a penny?
Because of their high zinc content modern U.S. pennies that become lodged in the esophagus may react with stomach acid thereby damaging the esophageal mucosa. Management of esophageal pennies may therefore differ from that of other esophageal coins making differentiation of pennies from other coins important. We reviewed the records of 111 children who underwent endoscopic esophageal coin removal over a 19-year period to determine the ability of history and size of esophageal coin images on posterior-anterior and lateral chest radiographs alone and in combination to differentiate esophageal pennies from other esophageal coins. History alone accurately identified 83 per cent of esophageal coins. Ranges of two standard deviations around mean image sizes were determined for each coin denominations. We determined the probability of an esophageal coin being a penny based on combinations of historical data and whether or not image sizes fell within the calculated range for a penny. When all data agree that a coin is or is not a penny they are nearly always correct. When there is disagreement among historical and image size data the probability that is a coin is a penny is strongly influenced by the size of the radiographic images.


How water layers on graphene affect folding and adsorption of TrpZip2.
We present a computational study of the folding of the Trp-rich β-hairpin TrpZip2 near graphene, a surface of interest as a platform for biosensors. The protein adsorbs to the surface, populating a new bound, folded state, coexisting with extended, adsorbed conformations. Adsorption and folding are modulated by direct interactions between the indole rings of TrpZip2 and the rings on the graphene surface, as well as by indirect water-mediated interactions. In particular, we observe strong layering of water near graphene, ice-like water configurations, and the formation of short lived hydrogen-bonds between water and protein. In order to study the effect of this layering in more detail, we modified the interactions between graphene and water to obtain two extreme cases: (1) enhanced layering of water that prevents the peptide from penetrating the water layer thereby enabling it to fold to a bulk-like structure, and (2) disruption of the water layer leading to adsorption and unfolding of the protein on the surface. These studies illuminate the roles of direct and solvent mediated interactions in modulating adsorption and folding of proteins on surfaces.


Hepatitis, cirrhosis, and hepatoma.
Virus hepatitis and liver cirrhosis are found at high incidence in Asia, and they require not only biochemical examination of blood but also subsequent imaging, because they are often complicated by hepatocellular carcinoma (HCC). It is, therefore, very important to know the specific appearances of hepatitis, liver cirrhosis, and HCC when we diagnose these diffuse liver diseases. Liver necrosis due to severe hepatitis is seen as high intensity on T2-weighted spin echo images. Regeneration is seen as low intensity on T2-weighted images. Morphologic and pathologic changes of cirrhotic liver are well demonstrated by MR imaging techniques. Fibrotic septum with inflammatory cell infiltration or rich pseudo bile duct show high intensity on T2-weighted images, and regenerating nodules shows low intensity. Gradient echo images show regenerating nodules with iron deposition as low-intensity nodules due to susceptibility artifact. MRI also has the potential to evaluate function of diffuse liver disease, cirrhosis, and hepatitis. MRI can visualize and diagnose HCC objectively. Dynamic MRI is very useful for diagnosing HCC. It is also applied for evaluation of effect after transcatheter arterial chemoembolization, because it shows enhancement only in the viable region at an arterial phase. MRI is less invasive and is thus an extremely important form of liver imaging.


Palpebral twitching in a depressed adolescent on citalopram.
Current estimates suggest that between 0.4% and 8.3% of children and adolescents are affected by major depression. We report a favorable response to treatment with citalopram by a 15-year-old boy with major depression who exhibited palpebral twitching during his first 2 weeks of treatment. This may have been a side effect of citalopram as it remitted with redistribution of doses.


The effects of lornoxicam on brain edema and blood brain barrier following diffuse traumatic brain injury in rats.
In this experiment, the effects of lornoxicam on brain edema and the blood brain barrier (BBB) following diffuse traumatic brain injury (TBI) were studied. Twenty adult male Wistar albino rats were anesthetized, and experimental closed head trauma was induced by the Marmarou method. After head injury, the rats were randomly divided into two groups: Group I was the control group, to which 2 ml saline was administered intraperitoneally, and Group II was the lornoxicam group, to which 2 ml 1.3 mg kg-1 lornoxicam was administered intraperitoneally. Twenty-four hours after head trauma, 99 mTc pentetate (DTPA) was injected at a dose of 37 MBq, and posterior planar images of each rat were obtained using an Infinia gamma camera. After imaging of BBB permeability, brain tissues were dissected from the cranium. The brain water content (BWC) of each sample was calculated using the wet-dry method. The lesion/background (L/b) ratio of Group I was 3.76±0.46 and 3.02±0.66 for early (5th min) and late (60th min) imaging, respectively. In Group II, the L/b ratios were 3.52±0.96 and 2.63±0.63 for early and late imaging, respectively (p>0.05). BWC was 79.6±2.5% and 77.5±1.1% for Groups I and II, respectively (p<0.05). In this rat model of TBI, lornoxicam reduced brain edema but did not affect BBB permeability.


EMAT phased array: A feasibility study of surface crack detection.
Electromagnetic-acoustic transducers (EMATs) consist of a magnet and a coil. They are advantageous in some non-destructive evaluation (NDE) applications because no direct contact with the specimen is needed to send and receive ultrasonic waves. However, EMATs commonly require excitation peak powers greater than 1kW and therefore the driving electronics and the EMAT coils have to be bulky. This has hindered the development of EMAT phased arrays with characteristics similar to those of conventional piezoelectric phased arrays. Phased arrays are widely used in NDE because they offer superior defect characterization in comparison to single-element transducers. In this paper, we report a series of novel techniques and design elements that make it possible to construct an EMAT phased array that performs similarly to conventional piezoelectric arrays used in NDE. One of the key enabling features is the use of coded excitation to reduce the excitation peak power to less than 4.8W (24 Vpp and 200mA) so that racetrack coils with dimensions 3.2×18mm2 can be employed. Moreover, these racetrack coils are laid out along their shortest dimension so that 1/3 of their area is overlapped. This helps to reduce the crosstalk between the coils, i.e., the array elements, to less than -15dB. We show that an 8-element EMAT phased array operating at a central frequency of 1MHz can be used to detect defects which have a width and a depth of 0.2 and 0.8mm respectively and are located on the surface opposite to the array.


Acquired external auditory canal stenosis: assessment and management.
Although uncommon, acquired external auditory canal stenosis is an entity that is encountered by many otolaryngologists. This paper reviews the causes, pathogenesis, assessment, and management options for external auditory canal stenosis. Initially, acquired external auditory canal stenosis was described as resulting from a number of different causes. Since then, histology and imaging studies of this disease have shown that a common cascade of inflammatory changes resulting from these different causes is the primary pathogenesis leading to medial canal fibrosis. Once there is complete obstruction of the external auditory canal, surgery is the primary treatment. Understanding the strong role of inflammation in the pathogenesis of external auditory canal stenosis may lead to new preventative medical therapies. Although acquired external auditory canal was described several years ago, its underlying pathophysiology is now better understood. From this knowledge, improved medical as well as surgical approaches can be developed.


Cytoplasmic tubular structures in the diagnosis of oral discoid lupus erythematosus.
Biopsies from oral lesions of 5 patients with discoid lupus erythematosus (DLE), 5 with lichen planus (LP), 5 with leukoplakia (LEUK) and 3 patients with uncertain diagnoses termed DLE?, LP? were examined in the electron microscope for presence of cytoplasmic tubular structures (CTS) in vascular endothelium. Five vessels were examined in each of two randomly selected sections from each biopsy, without knowledge of the clinical diagnosis. All five DLE biopsies showed presence of CTS in 4-9 out of 10 vessels, as compared with none of 10 vessels in biopsies from LP or LEUK, the difference being significant. Further, CTS occurred in 4 out of 10 vessels in one DLE?, LP? biopsy from a patient with serologic signs of systemic lupus erythematosus. As CTS seem to be absent in oral lesions of LP and LEUK, which are the most important differential diagnoses for oral DLE, the identification of CTS in vascular endothelium sing electron microscopy may be an auxiliary diagnostic procedure in oral DLE.


Joint 1994 Wolff Award Presentation. Peripheral and central trigeminovascular activation in cat is blocked by the serotonin (5HT)-1D receptor agonist 311C90.
Migraine headache involves the activation of trigeminal afferents that are predominantly found in the first or ophthalmic division of the nerve. The headache is often pounding and the connections of the trigeminal nerve, the trigeminovascular system, have therefore been implicated in the pathophysiology of migraine and studied extensively. Considerable attention has been given to the peripheral ramifications of the system as a possible locus of action for anti-migraine drugs while little attention has been focused upon possible central sites of action. It has been shown that certain peptides can act as markers for the trigeminal system, in particular calcitonin gene-related peptide (CGRP), and that CGRP is elevated in migraine. We have employed an animal model for activation of the trigeminovascular system to evaluate a new antimigraine compound, 311C90, that may have central and as well as peripheral trigeminal actions. Cats were anesthetized by halothane induction and alpha-chloralose maintenance (60 mg/kg, intraperitoneal), intubated, paralyzed and ventilated. Biparietal craniotomies were carried out to measure cerebral blood flow using laser Doppler flowmetry (CBFLDF). The external jugular vein was cannulated and blood drawn, centrifuged and frozen until processing. Stimulation of the trigeminal ganglion resulted in a mean maximum increase in CBFLDF of 39 +/- 5% at 20/s. The 5HT1 agonist 311C90 was administered intravenously in two doses (30 and 100 micrograms/kg) to cover the range of doses likely to be effective clinically. At each dose the CBFLDF effect of trigeminal ganglion stimulation was inhibited.(ABSTRACT TRUNCATED AT 250 WORDS)


Application of the Multi-Facet Rasch Model to Evaluate the Chief Resident Selection Survey: A Two-Year Study.
Introduction The Chief Resident (CR) selection process is described by many residency programs as a collective effort from the residency program leadership, key faculty members, and resident peers. Unfortunately, the literature does not show any established guidelines, methods, or psychometric sound instruments to aid this process. The purpose of this study was to evaluate the properties of the newly developed CRs selection survey across two years using the Multi-Facet Rasch Model (MFRM). Methods This study used the MFRM to analyze two-year data from the newly developed CRs selection survey. After the first implementation of the tool in 2015, this instrument had its second-round evaluation process for the CRs selection in 2016. We applied a three-facet Rasch model (candidates, questions, and raters). We used Facets v. 3.66 and SAS 9.4 (SAS Institute Inc., Cary, NC) for data analysis. Results In 2015, 40 out of100 residents completed the survey to select three of the four candidates for the 2017-2018 CRs positions. The mean rating for each candidate showed that Candidate 1 received the highest rating of 5.56 while Candidates 2 and 4 received the exact same ratings. The majority of survey items performed very well based on the results from the MFRM while leaving room for improvement for a few items. In 2016, 55 out of 100 residents completed the revised survey to select three of the six candidates for the 2018-2019 CR positions. The mean rating showed that Candidate 3 received the highest mean rating of 5.81 while Candidate 2 received the lowest mean rating of 5.12. The item reliability was improved from 0.70 to 0.88 based on the results from the revised survey. The results were used to help inform decisions regarding the selection of chief residents. Conclusions The CR selection process requires a fair and collective effort from program leadership, relevant faculty members, and input from the resident group. Our study demonstrated that the survey tool we developed is appropriate to select CR candidates and MFRM is a promising technique in survey development and the evaluation of survey items.


Dynamics of stock prices.
We show that the dynamics of stock prices can be accurately described as a continuous time random walk with a time dependent diffusion coefficient. The time evolution of the diffusion coefficient can be derived from tick by tick databases provided the stock price is characterized in terms of a couple of values describing the best ask and the best bid. We are then led to a finding and, namely, that the transition rate of the random walk process is different from the frequency of transactions. Our results allow us to obtain a fast and reliable determination of the diffusion coefficient and precisely confirm that fat tails in the distribution of price variations are due to volatility fluctuations.


Cellular Morphology-Mediated Proliferation and Drug Sensitivity of Breast Cancer Cells.
The interpretation of the local microenvironment of the extracellular matrix for malignant tumor cells is in intimate relation with metastatic spread of cancer cells involving the associated issues of cellular proliferation and drug responsiveness. This study was aimed to assess the combination of both surface topographies (fiber alignments) and different stiffness of the polymeric substrates (poly(l-lactic acid) and poly(ε-caprolactone), PLLA and PCL, respectively) as well as collagen substrates (coat and gel) to elucidate the effect of the cellular morphology on cellular proliferation and drug sensitivities of two different types of breast cancer cells (MDA-MB-231 and MCF-7). The morphological spreading parameter (nucleus/cytoplasm area ratio) induced by the anthropogenic substrates has correlated intimately with the cellular proliferation and the drug sensitivity the half maximal inhibitory concentration (IC50) of cancer cells. This study demonstrated the promising results of the parameter for the evaluation of cancer cell malignancy.


Meningococcal disease--probable transmission during an international flight.
Two cases of meningococcal disease were identified in passengers who travelled on the same international flight. Both cases were serogroup B with the same allelic profile. The public health action involved chemoprophylaxis for persons seated adjacent to, and in the rows in front and behind, each case. The most likely scenario is that transmission of N. meningitidis occurred on board a long distance flight, either from one case to the other or from an asymptomatic carrier to both cases. This scenario and the absence of reports of similar cases in the literature, indicate the risk to other passengers in this setting is low. This investigation reinforces the need for, and the distribution of, good national and international surveillance information to better inform public health decision making.


Complications of planned home births in the Czech Republic.
This study evaluated complications that can occur during planned home births that require transfer to the hospital. These factors were assessed to improve the current status of deliveries performed outside health care facilities in the Czech Republic. This prospective cohort study included data on 105 cases of complicated home births during 2017 to 2021 using an online form accessible to all hospital maternity wards in the Czech Republic. Planned home births were complicated by fetal/neonatal causes, maternal causes, and combined fetomaternal complications in 28 (26.7%), 20 (19%), and 2 (1.9%) cases, respectively. The need for transfer was most often realized after the birth of the fetus (86; 81.9%); however, it was realized during birth in 19 (18.1%) cases. The following complications were noted most often: postpartum hemorrhage (23; 21.9%); neonatal asphyxia (17; 16.2); placental retention (14; 13.3%); birth injury (12; 11.4%); neonatal hypothermia (5; 4.8%); and placental birth (5; 4.8%). Indications for transfer during labor were as follows: labor obstruction (10; 9.5%); fetal hypoxia (5; 4.8%); bleeding during labor (2; 1.9%); preeclampsia (1; 0.9%); and fetal malformation (1; 0.9%). Perinatal death occurred in 8 (7.6%) cases. Permanent neonatal morbidity occurred in 4 (3.8%) cases. Patients with home birth complications were transferred to the hospital most often after the birth of the fetus. The low proportion of transfers during childbirth is caused by the unprofessional management of planned home births, resulting in a high number of perinatal deaths and high rate of permanent neonatal morbidity.


Effect of TiO2 nanoparticles on UASB biomass activity and dewatered sludge.
The accumulation of the nanowastes in the wastewater treatment plants has raised several concerns; therefore, it is an utmost priority to study the nanoparticle (NP) toxicity in such systems. In this work, the effect of TiO2 NPs on up-flow anaerobic sludge blanket (UASB) microflora and their photocatalytic effect on dewatered sludge were studied. We observed 99.98% removal of TiO2 NPs by sludge biomass within 24 h, though negligible toxicity was found up to 100 mg/L TiO2 concentration on extracellular polymeric substances (EPS), volatile fatty acid and biogas generation. The low toxicity corresponds to the agglomeration of TiO2 NPs in UASB sludge. Alterations in dewatered sludge biochemical composition and increase in cell damage were observed upon exposure to sunlight as evidenced by FTIR and fluorescent microscopy, respectively. Results suggest the negligible toxicity of TiO2 NPs on UASB biomass activity; however, once exposed to open environment and sunlight, they may exert detrimental effects.


Fatigue, pain interference, and psychiatric morbidity in multiple sclerosis: The role of childhood stress.
Multiple sclerosis (MS) is a progressive, autoimmune disease of the central nervous system that affects nearly one million Americans. Despite the existence of immunomodulatory therapies to slow physical and cognitive disability progression, interventions to ameliorate common symptoms of MS, including fatigue and pain, remain limited. Poor understanding of risk factors for these symptoms may contribute to treatment challenges. In recent years, childhood stress has been investigated as a risk factor for chronic autoimmune conditions including MS; yet remarkably few studies have investigated the relationship between childhood stressors and chronic MS symptoms. Our aim was to examine clusters of stressors and three key features of MS: fatigue, pain interference, and psychiatric morbidity. Cross-sectional data were collected from a sample of People with MS (PwMS) via a national web-based survey that assessed the presence and type of childhood stressors and MS clinical features. Hierarchical block regression was used to assess associations among emotional, physical, and environmental childhood stressors and three clinical features commonly experienced by PwMS. N = 719 adults with MS (aged 21-85) completed the survey. Childhood emotional and physical stressors were significantly associated with overall presence of fatigue (p = 0.02; p<0.03) and pain interference (p<0.001; p<0.001) in adulthood, as well as the magnitude of both outcomes. Environmental stressors (p<0.001), in addition to emotional (p<0.001) and physical (p<0.001) stressors were significantly associated with psychiatric morbidity in PwMS. Childhood stress may predict fatigue, psychiatric morbidity, and pain in adults with MS. Further research is needed to show cause and effect; however, if an association exists, strategies to mitigate the impact of childhood stress could offer new pathways to reduce the severity of these symptoms. Broadly, this work adds to the body of evidence supporting upstream preventive measures to help address the stress on children and families.


Histopathologic Findings of Patients With Biopsy-Negative Giant Cell Arteritis Compared to Those Without Arteritis: A Population-Based Study.
To evaluate whether there are histopathologic features of negative temporal artery biopsy (TAB) that allow differentiation between patients with giant cell arteritis (GCA) and those without. All consecutive patients with negative TAB seen between January 2009 and December 2012 were selected retrospectively. Demographic, clinical, and laboratory data at presentation and at each followup visit were collected. A pathologist with expertise in vasculitis and blinded to clinical data and final diagnosis reviewed all negative TABs. Histopathologic features evaluated were the presence of a focal mediointimal scar, medial attenuation, intimal hyperplasia, fragmentation of inner elastic lamina, calcification, adventitial fibrosis, and neoangiogenesis. After a median (interquartile range [IQR]) followup period of, respectively, 19 months (9.2-31.2) and 26.3 months (4.9-36.7) (P = 0.041), 38 (55%) of 69 patients had a final diagnosis of TAB-negative GCA, while in the remaining 31 (45%) of 69 patients GCA was excluded. The American College of Rheumatology classification criteria for GCA were satisfied by 31 (81.6%) of 38 patients and 2 (6.5%) of 31 patients (P < 0.0001). Compared to non-GCA patients, those with TAB-negative GCA had more frequent cranial manifestations and higher erythrocyte sedimentation rates and C-reactive protein levels. The frequency of patients receiving prednisone, the mean dose, and the duration of prednisone treatment at TAB were similar in the 2 groups. There were no significant differences between TAB-negative GCA and non-GCA patients in the frequencies of all the histologic features evaluated. The histologic features of negative TABs evaluated in this study do not allow for the differentiation between GCA and non-GCA patients. In the absence of an inflammatory infiltrate, other histologic changes of the temporal artery wall are not specific for GCA.


THE ECOLOGICAL GENETICS OF INTRODUCED POPULATIONS OF THE GIANT TOAD, BUFO MARINUS. III. GEOGRAPHICAL PATTERNS OF VARIATION.
The allele frequencies at ten polymorphic loci are described from 31 Bufo marinus populations in the Moreton Bay region in southeastern Queensland, Australia and the variation of these is found to be non-random in all cases. The pattern of non-randomness varies among loci, being clinal in two instances. The allele frequencies at the same ten loci are also described for 12 populations sampled from throughout B. marinus' Australian range. The frequency variation on this larger geographical scale is non-random at all but two loci (Mpi and Hbdh) and also varies among loci, in this case being clinal in four instances. In both cases, the patterns of variation are most reasonably explained as having resulted from genetic drift occurring during the recent range expansion which B. marinus is known to have experienced in Australia. It seems that natural selection has played little, if any, role in generating the observed gene frequency patterns. These results emphasize the need for caution in interpreting geographical patterns of variation. They show that even when clinal patterns exist at some loci but not at others, one cannot conclude that the patterns result from natural selection, unless the demographic histories of the studied populations are known and are inconsistent with the alternative hypothesis that the patterns result from genetic drift.


Contribution of genetic factors to platinum-based chemotherapy sensitivity and prognosis of non-small cell lung cancer.
Although platinum-based chemotherapy remains the standard treatment for advanced NSCLC patients, clinical outcomes are poor and most patients develop high-grade toxicities. Genetic factors, such as single nucleotide polymorphisms (SNPs) involved in platinum pharmacodynamics, metabolism and mechanism of action, may account for inter-individual differences shown in effectiveness and toxicity. Polymorphisms in genes involved in DNA repair and others such as PI3K/PTEN/AKT and TGF-β pathways have been demonstrated to be associated with response, survival and toxicity in advanced NSCLC patients treated with platinum-based chemotherapy. Other cellular processes, like DNA methylation and proliferation have been connected with clinical outcome for platinum-based chemotherapy regimens through folate metabolism and cytokine signaling. The influence of gene polymorphisms in the NER pathway on clinical outcome has been extensively investigated in advanced NSCLC patients treated with platinum-based chemotherapy but contradictory results have been reported. The most recent and thorough meta-analyses have failed to show an association between ERCC1 C118T/C8092A and ERCC5 rs1047768 polymorphisms and response to platinum based chemotherapy. However, other polymorphisms in ERCC2 (Lys751Gln and Asp312Asn) and ERCC5 (rs2094258 and rs2296147) and have been related with overall survival (OS) and progression-free survival (PFS), respectively. The Arg194Trp and Gln399Arg polymorphisms in XRCC1, have also been extensively investigated. Their effects seem to be dependent on ethnicity, and recent meta-analyses have confirmed an association with response in Asian but not in Caucasian patients. The influence on overall response rate (ORR) of the rs861539 polymorphism in XRCC3, part of (DSB) repair pathway, has also been confirmed in a meta-analysis. Finally, SNPs in genes coding proteins of the p53, PI3K, TGF-β, membrane transporters, gluthatione metabolism enzymes and cytokine pathways have been less extensively investigated. Some polymorphisms have been reported to be associated with toxicity or clinical outcome, but data generally come from a limited number of studies and need to be confirmed.


Electronic transitions in cis- and trans-dichloroethylenes and tetrachloroethylene.
Electronic structures of trans- and cis-dichloroethylenes and tetrachloroethylene were studied using symmetry-adapted cluster configuration interaction theory. Basis sets up to the aug-cc-pVTZ of Dunning, Jr., augmented with appropriate Rydberg functions were used for the calculations. The results derived in the present study show good agreement with the available experimental values. In all cases, the main bright excitation was the pi-->pi( *) transition. The other vertical excitations, pi-->sigma( *), n-->sigma( *), and n-->pi( *), which have not been studied before, were also investigated. First Rydberg series involving transitions from the pi orbitals to one 3s, three 3p, and five 3d orbitals were identified clearly. Several new assignments and reassignments of features in the experimental spectra were suggested. Contrary to earlier prediction, two n-sigma( *) states, along with a pi-sigma( *) state in the dichloroethylenes, were calculated to be located above the main pi-pi( *) state. Accordingly, crossing between both the n-sigma( *) states with the bright pi-pi( *) state is highly likely, unlike conclusions made in the earlier studies. This indicates that the photodissociation mechanism proposed by the earlier calculations warrants revision. Several low-lying triplet excited states were also studied. Electronic spectra of trans-1-chloro-2-fluoroethylene and cis-1-chloro-2-fluoroethylene were also calculated. The pi-->pi( *) transitions of these haloethylenes are compared and interpreted in terms of the inductive and resonance effects.


The path of mRNA through the bacterial ribosome: a site-directed crosslinking study using new photoreactive derivatives of guanosine and uridine.
Two new photoreactive nucleotide derivatives have been applied in site-directed crosslinking studies with mRNA analogues. 6-Thioguanosine triphosphate or 5-methyleneaminouridine triphosphate was incorporated into mRNA analogues by T7 transcription; after transcription, the 5-methyleneaminouridine residues were converted to a diazirine derivative. mRNA analogues carrying either 6-thioguanosine or the diazirine derivative were bound to Escherichia coli ribosomes in the presence of tRNA(f)(Met), and photo-crosslinking was induced by irradiation at 350 nm. With 6-thioguanosine, specific crosslinks were observed from downstream positions +8 or +9 of the mRNA to nt 1196 in helix 34 of the 16S rRNA, and from position +12 to nt 530 in helix 18. With the diazirine derivative, a crosslink from position +2 (within the AUG codon) to nt 926 in helix 28 was found. Taken together with previous data obtained from downstream sites in mRNA analogues carrying 4-thiouridine residues, specific crosslinks have now been identified from downstream mRNA positions +2, +4, +6, +7, +8, +9, +11, and +12. The data confirm that the three 16S rRNA regions involved-helices 18, 28, and 34-are in the direct neighborhood of the decoding area of the 30S subunit.


The Influence of Chelating Agent on the Structural and Magnetic Properties of CoFe2O4, Nanoparticles.
We have studied the influence of chelating agents (glycerin and sucrose) on the structural and magnetic properties of cobalt ferrite (CoFe2O4) nanoparticles synthesized via co-precipitation method. The Rietveld refinements from X-ray diffraction patterns confirm that all samples are single phase identified in a cubic crystalline system belonging to the space group Fd-3m. Besides, we have verified that the addition of chelating agents produces a decreasing in the particles average size from 14(2) to 5(1) nm. Magnetization measurements as a function of temperature show a decrease in the blocking temperature (T(B)) to sample obtained with addition of sucrose. A superparamagnetic behavior at room temperature was observed by magnetic measurements as function of field in the sample with 0.020 mol/L of sucrose. The results show that character chelating of sucrose reduces the coalescence effect and magnetic interaction in the CoFe2O4 nanoparticles. These results suggest that sucrose could be an alternative to control the structural and magnetic properties of other oxides nanoparticles.


Resolution of Students t-tests, ANOVA and analysis of variance components from intermediary data.
Significance testing in comparisons is based on Student's t-tests for pairs and analysis of variance (ANOVA) for simultaneous comparison of several procedures. Access to the average, standard deviation and number of observations is sufficient for calculating the significance of differences using the Student's tests and the ANOVA. Once an ANOVA has been calculated, analysis of variance components from summary data becomes possible. Simple calculations based on summary data provide inference on significance testing. Examples are given from laboratory management and method comparisons. It is emphasized that the usual criteria of the underlying distribution of the raw data must be fulfilled.


Hidradenitis suppurativa: Epidemiology and scope of the problem.
Hidradenitis suppurativa (HS) is a chronic inflammatory disease involving painful, deep abscesses and chronic, draining sinus tracts. Because of the variable signs and symptoms displayed by patients, it remains widely unrecognized and difficult to treat, resulting in significant diagnostic delay and inconsistent treatment process. No medical specialty has successfully designated a criterion standard of treatment, resulting in variable care and unmet patient needs. Widespread causes and effects of HS are difficult to determine because the prevalence is dependent on a variety of things, including how and where data are collected, resulting in significant bias. Therefore, the task must be to assess existing studies to produce a best estimate of prevalence. In addition, the 3 types of studies available for HS (ie, self-report, registry-based, and group examination studies) must be evaluated because each offers important insights into who is impacted by this disease. The exact prevalence of HS remains unknown because of the difficulty in collecting and extrapolating data and the usefulness of studies; however, high comorbidity and disease severity is observed, resulting in increased hospital visits for patients with HS--nearly double that of other diseases. Finally, comparisons between HS and psoriasis are worth mentioning because the similarities are clear, but the severity of HS appears to be more debilitating in many aspects of life. This article will address the epidemiology of HS through current available research.


[Epidemiology of thyroid cancer in Poland].
The aim of the paper is to analyse the epidemiological situation of thyroid cancer in Cracow region from 1986 to 1999 and to review regional thyroid cancer registers in Poland (including 43.7% of the Polish population) in 1999. The standardized register was based upon assumptions: 100% of histopathological verification according to ICD-10, the register ascertainment in at least 80%, the demographic area not smaller than 100,000 inhabitants, the incidence rate (IR) calculated as the newly diagnosed cases number per 100,000 inhabitants in a calendar year. Since 1990 a statistically significant rise of the thyroid cancer incidence affecting mainly women > 40 years of age have been observed. From 1998-1999 the cancer morbidity was reduced. Within the last 5 years in the Cracow area the follicular carcinoma incidence has decreased significantly, which has been associated with effective iodine prophylaxis. The highest incidence values have been observed in Cracow and Olsztyn, showing a territorial relationship with the highest thyroid irradiation doses after Chernobyl accident. The mean IR value has been 3.86 (1.48 men, 6.08 women), which corresponds to about 1500 newly diagnosed cases in Poland in 1999. The follicular to papillary carcinoma ratio has been 5.32. The major etiological factors have been iodine deficiency and ionising radiation. The present data have indicated that iodine prophylaxis should be continued and that the population should be protected against ionising radiation.


Cytotoxicity of methanol extracts of 10 Cameroonian medicinal plants towards multi-factorial drug-resistant cancer cell lines.
Cancer chemotherapy is still hampered by clinical failures due to multi-drug resistance (MDR) of tumor cells. In the present study, we have investigated the cytotoxicity of 20 methanol extracts from 10 medicinal plants against the sensitive leukemia CCRF-CEM cells. The most cytotoxic extracts were then further tested on a panel of 8 human cancer cell lines, including various MDR phenotypes. The cytotoxicity of the 20 methanol extracts from 10 Cameroonian medicinal plants was determined using a resazurin reduction assay. Meanwhile, flow cytometry was used to measure cell cycle, apoptosis, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS). In the preliminary assay using CCRF-CEM cells, 12 extracts from five plants displayed IC50 values below 80 μg/mL, namely Albizia adianthifolia, Alchornea cordifolia, Alchornea laxiflora, Pennisetum purpureum, and Spathodea campanulata. the four best extracts were from two plants: Albizia adianthifolia roots (AAR) and bark (AAB) as well as Alchornea cordifolia leaves (ACL) and bark (ACB) had respective IC50 values of 0.98 μg/mL, 1.45 μg/mL, 8.02 μg/mL and 12.57 μg/mL in CCRF-CEM cells. They were further tested in 8 other cell lines as well as in normal AML12 hepatocytes. IC50 values ranging from 2.71 μg/mL (towards glioblastoma U87MG.ΔEGFR cells) to 10.30 μg/mL (towards breast adenocarcinoma MDA-MB-231-BCRP cells) for AAB, from 3.43 μg/mL (towards U87MG cells) to 10.77 μg/mL (towards colon carcinoma HCT116 (p53 (-/-) ) cells) for AAR and from 0.11 μg/mL (towards CCRF-CEM cells) to 108 μg/mL (towards leukemia CEM/ADR5000 cells) for doxorubicin (as control drug) were obtained. ACL and ACB extracts displayed selective activities. AAR and ACL extracts induced apoptosis in CCRF-CEM cells, through caspases activation and loss of MMP, while apoptotic cell death was mediated by MMP diruption and increase ROS production for ACL. Some of the tested plants namely Albizia adianthifolia, Alchornea cordifolia, Alchornea laxiflora, Pennisetum purpureum, Spathodea campanulata represent a potential source of novel anticancer drugs. Especially, Albizia adianthifolia and Alchornea cordifolia revealed considerable cytotoxic activities that could be exploited to develop phytomedicines to fight cancers including MDR phenotypes.


Investigation of the major cytochrome P450 1A2 genetic variant in a healthy Tibetan population in China.
The cytochrome P450 (CYP) 1A2 gene is involved in the metabolism of several carcinogens and clinically important drugs, generating a high potential for pharmacokinetic interactions. Since no data are available for Tibetan aborigines, the present study aimed to investigate the distribution of variant CYP1A2 alleles in a population living in Tibetan region of China. Genotyping analyses of CYP1A2 were conducted in 96 unrelated, healthy volunteers of Tibetan ancestry using direct sequencing assays. A total of 14 different CYP1A2 polymorphisms, including two novel variants (1690G>A and 2896C>T) in the intron region and a novel non‑synonymous one (795G>C, Gln265His) were detected. CYP1A2*1A (6.77%), CYP1A2*1B (58.33%) and CYP1A2*1F (14.58%) were the most frequent defective alleles identified in the sample. The frequencies of the prevalent genotypes CYP1A2*1A/*1B, *1B/*1B, *1B/*1F were 13.54%, 16.67% and 29.17%, respectively. In addition, the novel non‑synonymous variant 795G>C (Gln265His) was predicted to be benign by PolyPhen‑2 and SIFT tools. The present study provides useful information on the pattern of CYP1A2 polymorphisms in Chinese Tibetan population. The current results may have potential benefits for the development of personalized medicine in the Tibetan population.


Stem cells rejuvenate radiation-impaired vasculogenesis in murine distraction osteogenesis.
Radiotherapy is known to be detrimental to bone and soft-tissue repair. Bone marrow stromal cells have been shown to enhance bone regeneration during distraction osteogenesis following radiation therapy. The authors posit that transplanted bone marrow stromal cells will significantly augment the mandibular vascularity devastated by radiation therapy. Nineteen male Lewis rats were split randomly into three groups: distraction osteogenesis only (n = 5), radiation therapy plus distraction osteogenesis (n = 7), and radiation therapy plus distraction osteogenesis with intraoperative placement of 2 million bone marrow stromal cells (n = 7). A mandibular osteotomy was performed, and an external fixator device was installed. From postoperative days 4 through 12, rats underwent a gradual 5.1-mm distraction followed by a 28-day consolidation period. On postoperative day 40, Microfil was perfused into the vasculature and imaging commenced. Vascular radiomorphometric values were calculated for regions of interest. An analysis of variance with post hoc Tukey or Games-Howell tests was used, dependent on data homogeneity. Stereologic analysis indicated significant remediation in vasculature in the bone marrow stromal cell group compared with the radiation therapy/distraction osteogenesis group. Each of five metrics idicated significant improvements from radiation therapy/distraction osteogenesis to the bone marrow stromal cell group, with no difference between the bone marrow stromal cell group and the distraction osteogenesis group. Bone marrow stromal cells used together with distraction osteogenesis can rejuvenate radiation-impaired vasculogenesis in the mandible, reversing radiation therapy-induced isotropy and creating a robust vascular network. Bone marrow stromal cells may offer clinicians an alternative reconstructive modality that could improve the lifestyle of patients with hypovascular bone.


Dermal wound healing potency of single alkaloid (betaine) versus standardized crude alkaloid enriched-ointment of Evolvulus alsinoides.
Evolvulus alsinoides Linn. (Convolvulaceae), well known as shankhpushpi in Ayurvedic text, is traditionally used for several healing purposes. A comparative evaluation of dermal wound healing potential of acidic and basic alkaloid enriched-ointment (AAO and BAO) of aerial parts of E. alsinoides versus pure alkaloid, betaine (BEO), was undertaken. The effect of topical application (50 mg/animal/day) of AAO-1%, AAO-2%, BAO-1%, BAO-2%, BEO-0.5% and BEO-1% was assessed through excision (14 days) and incision (10 days) models on rats. The percentage wound contraction, total protein content, and breaking strengths were determined followed by histopathological studies. The total alkaloid in acidic and basic alkaloid enriched fractions was found to be 0.1114 and 0.1134 μg/mL, respectively. Thus, 0.1528, 0.3056, 0.1380 and 0.2459 μg of total alkaloid were estimated to be present in AAO-1%, AAO-2%, BAO-1% and BAO-2%, respectively. AAO and BAO promoted wound healing activity significantly in both the models. Higher rate of wound contraction (p < 0.001) with significant increase in protein content in the treatment groups (from 2.32 to 2.55) demonstrated stimulation of cellular proliferation and epithelization, which was further supported by histopathological reports. High skin breaking strength (mean value 393 in control was increased to the range of 535-572 in treated groups) proved a significant (p < 0.001) wound healing potential of E. alsinoides. Early dermal and epidermal regeneration in drug-treated groups also confirmed the positive effect. Observation of higher healing power of alkaloid enriched-ointment compared with single alkaloid ointment corroborated the synergy mechanism.


Contrast media reactions: experimental evidence against the allergy theory.
In order to clarify whether adverse reactions to radiographic contrast media may be allergic in nature, it is essential to show that contrast media can act as haptens and induce antibody formation in vivo. Experiments in Hooded Lister rats have been carried out using techniques specifically designed to produce favourable conditions for the production of antibodies. No evidence of any antibody formation was found in any of the experiments. These experiments suggest that radiographic contrast media in their native form do not act as haptens, contrary to previously published data, and it therefore seems unlikely that the majority of adverse reactions to radiographic contrast media are allergic in nature.


Early origins of mental disorder - risk factors in the perinatal and infant period.
There is increasing understanding of the significance of early neurodevelopment in establishing risk for the range of mental disorders. Models of the early aetiology of mental disorders are complex with a range of potential factors from genetic and epigenetic to environmental influencing neurological and psychological development. Whilst the mechanisms are not fully understood, this paper provides an overview of potential biological and neurobiological factors that might be involved. An aetiological model is presented and discussed. The discussion includes a range of risk factors for mental disorder. Maternal anxiety disorder is presented and reviewed as an example of the interaction of placental, epigenetic and early parenting factors elevating risk of poor neonatal outcome. Available evidence points to the importance of in-utero influences as well as the role of early attachment and emotional care. Transgenerational mechanisms such as the impact of maternal mental disorder on foetal development are important models for examination of early risk. Maternal anxiety, as an example, is a significant risk factor for compromised mental health. Development of models for understanding the early origins of mental disorder is an important step in elaborating risk reduction strategies. Comprehensive early identification of risk raises the possibility of preventive interventions.


Cationic and Anionic Impact on the Electronic Structure of Liquid Water.
Hydration shells around ions are crucial for many fundamental biological and chemical processes. Their local physicochemical properties are quite different from those of bulk water and hard to probe experimentally. We address this problem by combining soft X-ray spectroscopy using a liquid jet and molecular dynamics (MD) simulations together with ab initio electronic structure calculations to elucidate the water-ion interaction in a MgCl2 solution at the molecular level. Our results reveal that salt ions mainly affect the electronic properties of water molecules in close vicinity and that the oxygen K-edge X-ray emission spectrum of water molecules in the first solvation shell differs significantly from that of bulk water. Ion-specific effects are identified by fingerprint features in the water X-ray emission spectra. While Mg2+ ions cause a bathochromic shift of the water lone pair orbital, the 3p orbital of the Cl- ions causes an additional peak in the water emission spectrum at around 528 eV.


[Aortocoronary bypass. Intermittent clamping of the aorta versus cardioplegia].
Cardioplegia is the standard method of myocardial protection during aorto-coronary bypass surgery. However, there are other alternatives which the authors intend to test. Forty consecutive, non-selected cases of coronary artery bypass surgery done with intermittent aortic crossclamping (Group A) are compared with the 40 preceding consecutive cases where cardioplegia was used (Group B). The mean age of the patients of group A was 57.5 years (range 42-69 years) and that of group B was 57.1 years (range 39-76 years). Patients of group A had an incidence of previous myocardial infarct of 42.5% against 65.0% in group B. Chronic angina led to surgery in 33 cases of group A and in 32 of group B. The remainder (18.8%) had unstable angina. The mean number of grafts per patient was 2.9 in group A and 3.2 in group B. Internal mammary arteries were used in most patients of both groups, with 61 anastomoses in group A (1.5/patient) and 57 in group B (1.4/patient). The mean ischaemic time per graft was 7.4 min (range 5.5-11 min) in group A and 15.6 min (8.5-22 min) for group B. Serial analysis of myocardium-specific serum enzymes and the CPK-MB/total CPK ratio has not evidenced perioperative infarction in any patient of either group. Although enzyme levels were slightly higher in group A, the difference has not reached statistical significance. However, the electrocardiograms have shown one perioperative infarct in each group. Vasodilators were generally used in the 2 groups, for a mean of 16.8 hours, while inotropic drugs were required in only 4 cases of group A and 3 of group B. There has been no hospital mortality in either group. These results, in a series of non selected patients, demonstrate that intermittent crossclamping may be an acceptable alternative method of myocardial protection during aorto-coronary bypass surgery thus made simple, quick and secure.


Direct determination of pregabalin in human urine by nonaqueous CE-TOF-MS.
Determination of pregabalin in urine samples was carried out by nonaqueous CE with TOF-MS via ESI, with a mixture of 10 mM ammonium formate and 0.05% acetic acid in methanol. By using TOF-MS, accurate mass information was obtained, thus causing a great improvement in qualitative ability. In order to avoid ionic suppression, urine samples dilution 1:10 was used. This was the only treatment to urine samples before the injection. Despite this dilution, the detection limit was as low as 0.03 μg/mL for pregabalin. The method was validated with respect to accuracy, precision, and linearity, LOD, and LOQ. This method was applied to the analysis of urine samples from seven different cancer patients undergoing treatment with pregabalin. The developed method may find wide application for the routine determination of pregabalin in biological samples in order to establish a more efficient and safe dosage.


Cardiac reprogramming factor Gata4 reduces postinfarct cardiac fibrosis through direct repression of the profibrotic mediator snail.
The administration of a variety of reprogramming factor cocktails has now been shown to reprogram cardiac fibroblasts into induced cardiomyocyte-like cells. However, reductions in ventricular fibrosis observed after reprogramming factor administration seem to far exceed the extent of induced cardiomyocyte-like cell generation in vivo. We investigated whether reprogramming factor administration might primarily play a role in activating antifibrotic molecular pathways. Adult rat cardiac fibroblasts were infected with lentivirus encoding the transcription factors Gata4, Mef2c, or Tbx5, all 3 vectors, or a green fluorescent protein control vector. Gene and protein expression assays were performed to identify relevant antifibrotic targets of these factors. The antifibrotic effects of these factors were then investigated in a rat coronary ligation model. Gata4, Mef2c, or Tbx5 administration to rat cardiac fibroblasts in vitro significantly downregulated expression of Snail and the profibrotic factors connective tissue growth factor, collagen1a1, and fibronectin. Of these factors, Gata4 was shown to be the one responsible for the downregulation of the profibrotic factors and Snail (mRNA expression fold change relative to green fluorescent protein for Snail, Gata4: 0.5 ± 0.3, Mef2c: 1.3 ± 1.0, Tbx5: 0.9 ± 0.5, Gata4, Mef2c, or Tbx5: 0.6 ± 0.2, P < .05). Chromatin immunoprecipitation quantitative polymerase chain reaction identified Gata4 binding sites in the Snail promoter. In a rat coronary ligation model, only Gata4 administration alone improved postinfarct ventricular function and reduced the extent of postinfarct fibrosis. Gata4 administration reduces postinfarct ventricular fibrosis and improves ventricular function in a rat coronary ligation model, potentially as a result of Gata4-mediated downregulation of the profibrotic mediator Snail.


Three-dimensional visualisation of the feto-placental vasculature in humans and rodents.
Adequate development of the feto-placental circulation is critical for placental exchange function and healthy fetal growth. Understanding the structure of this circulation and how it informs fetal outcomes is important both in the human placenta, and the rodent, a purported comparative experimental model. Vascular casting and micro-CT imaging approaches enable detailed quantification of the complex vascular relationships in the feto-circulation, and provide detailed data to parameterise in silico models. Here, to assist researchers to apply these technically challenging methods we provide detailed approaches to cast and image; 1) human placentas at the cotyledon-level, and 2) whole rodent placentas.


Unusual presentation of a metastatic esophageal carcinoma.
Esophageal cancer most commonly presents with upper digestive symptoms such as dysphagia. Lymph nodes are among the most common metastatic sites of this type of cancer. We report the case of a 53-year-old man presenting with unusual sole presenting features of esophageal cancer. The patient sought medical attention for abdominal pain without dysphagia, which was first investigated with an abdominal computed tomography scan. A large abdominal mass was discovered on imaging. Biopsies of this mass were in keeping with esophageal squamous cell cancer. With this finding, gastroscopy was performed, confirming the presence of primary esophageal cancer. This is a rare presentation of esophageal cancer without upper gastrointestinal symptoms. This case reinforces the value of biopsy for any neoplastic mass, especially in a context of unusual symptoms.


[Cleido-cranial dysplasia. Contribution to study of this disease on the basis of four cases (author's transl)].
First described in 1898 under the name of cleido-cranial dysostosis by Pierre Marie and Sainton, this hereditary disease is highly polymorphous and progressive, hence the multiplicity of its manifestations. These involve not only the skull and clavicle, but also the hands, the spine and the teeth. In fact, it is disturbance of growth rather than a dysostosis in the strict sense of the term. Its mode of transmission is dominant. Its pathogenesis is totally unknown.


Leukocyte recruitment to airways by cigarette smoke and particle phase in contrast to cytotoxicity of vapor.
After hamsters had breathed fresh cigarette smoke in a miniature chamber, airways of the lung showed recruitment of polymorphonuclear leukocytes. Exposure to particles alone by removal of the vapor phase with charcoal did not change the leukocyte response. However, exposure to cigarette smoke vapor after removal of particles with Cambridge filters did not recruit leukocytes but produced nuclear and cytoplasmic vacuoles, double nuclei, and exfoliation of cells.


Determining antigenic relationships on the basis of MLC testing. I. A matrix approach for listing all possible antigenic assignments.
We present an approach for determining all possible antigenic relationships among a group of individuals, on the basis of MLC results. We assume that the researcher or tissue typer has a criterion for classifying responses into positives and negatives, and that this classification has already been done for the data set being considered. Given any set of positive and negative MLC responses, our technique produces all antigenic assignments consistent with the assumption that a response occurs if and only if the stimulator has antigen(s) foreign to the responder. No genetic assumptions are made.


Ethylammonium and diethylammonium salts of chloranilic acid.
In the crystals of two title salts of chloranilic acid (2,5-dichloro-3,6-dihydroxy-p-benzoquinone), namely ethylammonium chloranilate, C(2)H(8)N(+).C(6)HCl(2)O(4)(-), (I), and diethylammonium chloranilate, C(4)H(12)N(+).C(6)HCl(2)O(4)(-), (II), the chloranilate ions are present as a hydrogen-bonded dimer which has an inversion center. The ethylammonium and diethylammonium ions link the dimers through N-H.O hydrogen bonds, forming a three-dimensional hydrogen-bond network in (I) and a one-dimensional chain in (II).


Effects of previous episodes of influenza and vaccination in preventing laboratory-confirmed influenza in Navarre, Spain, 2013/14 season.
We estimated whether previous episodes of influenza and trivalent influenza vaccination prevented laboratory-confirmed influenza in Navarre, Spain, in season 2013/14. Patients with medically-attended influenza-like illness (MA-ILI) in hospitals (n = 645) and primary healthcare (n = 525) were included. We compared 589 influenza cases and 581 negative controls. MA-ILI related to a specific virus subtype in the previous five seasons was defined as a laboratory-confirmed influenza infection with the same virus subtype or MA-ILI during weeks when more than 25% of swabs were positive for this subtype. Persons with previous MA-ILI had 30% (95% confidence interval (CI): -7 to 54) lower risk of MA-ILI, and those with previous MA-ILI related to A(H1N1)pdm09 or A(H3N2) virus, had a, respectively, 63% (95% CI: 16-84) and 65% (95% CI: 13-86) lower risk of new laboratory-confirmed influenza by the same subtype. Overall adjusted vaccine effectiveness in preventing laboratory-confirmed influenza was 31% (95% CI: 5-50): 45% (95% CI: 12-65) for A(H1N1)pdm09 and 20% (95% CI: -16 to 44) for A(H3N2). While a previous influenza episode induced high protection only against the same virus subtype, influenza vaccination provided low to moderate protection against all circulating subtypes. Influenza vaccine remains the main preventive option for high-risk populations.


Rapidly progressive human herpesvirus 8-associated solid anaplastic lymphoma in a patient with AIDS--associated Kaposi sarcoma.
We report a case of rapidly progressive solid lymphoma with anaplastic large cell morphology, followed by systemic Kaposi sarcoma in an adult patient with AIDS. The lymphoma cells expressed human herpesvirus 8 (HHV-8)-encoded latent and lytic proteins and Epstein-Barr virus-encoded small RNA, suggesting that this case could be categorized into HHV-8-associated solid lymphoma, a recently identified disease entity.


COVID-19 Vaccine Clinic Real-Time Throughput Analysis: Development and Implementation of an Innovative Data Collection Tool.
The novel coronavirus disease 2019 (COVID-19) pandemic has presented the healthcare system with a plethora of challenges, including implementation of an efficient vaccination strategy. Mass vaccinations have been used during previous pandemics; however, the associated data have largely been limited to theoretical simulations and post hoc analysis. An innovative data collection tool was created to deliver real-time data analysis during a drive-through mass vaccination. Patients were assigned unique identification numbers at the clinic entrance. Using these identification numbers, and the web-based spreadsheet, patients were tracked throughout the vaccination process. Static timestamps corresponding to the entry and exit at each checkpoint were recorded in real time. Data were collected on a total of 3,744 vehicles over five clinic days. Total time was collected, from entry to exit, on 2,860 vehicles. Registration and vaccination times were collected on 3,111 vehicles. Of the vehicles sampled, 1,588 (42%) had data points associated with all checkpoints. This open-source, innovative data collection tool was successfully implemented in our mass vaccination clinic for tracking patients in real time providing actionable data on overall throughput efficiency. This cost-effective tool can be used on a variety of healthcare-related projects to provide data-driven evaluation on the efficiency of care.


Design, synthesis, and biological evaluation of unconventional aminopyrimidine, aminopurine, and amino-1,3,5-triazine methyloxynucleosides.
Herein we describe a class of unconventional nucleosides (methyloxynucleosides) that combine unconventional nucleobases such as substituted aminopyrimidines, aminopurines, or aminotriazines with unusual sugars in their structures. The allitollyl or altritollyl derivatives were pursued as ribonucleoside mimics, whereas the tetrahydrofuran analogues were pursued as their dideoxynucleoside analogues. The compounds showed poor, if any, activity against a broad range of RNA and DNA viruses, including human immunodeficiency virus (HIV). This inactivity may be due to lack of an efficient metabolic conversion into their corresponding 5'-triphosphates and poor affinity for their target enzymes (DNA/RNA polymerases). Several compounds showed cytostatic activity against proliferating human CD4(+) T-lymphocyte CEM cells and against several other tumor cell lines, including murine leukemia L1210 and human prostate PC3, kidney CAKI-1, and cervical carcinoma HeLa cells. A few compounds were inhibitory to Moloney murine sarcoma virus (MSV) in C3H/3T3 cell cultures, with the 2,6-diaminotri-O-benzyl-D-allitolyl- and -D-altritolyl pyrimidine analogues being the most potent among them. This series of unconventional nucleosides may represent a novel family of potential antiproliferative agents.


Effect of interleukins on UGT2B15 and UGT2B17 steroid uridine diphosphate-glucuronosyltransferase expression and activity in the LNCaP cell line.
Cytokines are known to modulate the level of both phase 1 and phase 2 drug-metabolizing enzymes in hepatocytes. Although the effects of cytokines on cytochrome P450 (CYP450) enzymes are well understood, there is limited knowledge on how cytokines may affect steroid UDP-glucuronosyltransferase (UGT) phase 2 enzyme activity and expression in different cell types, including hepatocytes and steroid target cells. LNCaP cells, which is a human prostate cancer cell line, is a good model to study the effect of cytokines in steroid target cells because it is known to express steroidogenic enzymes, including UGT2B15 and UGT2B17, which are widely expressed steroid UGT enzymes known to conjugate androgens. In this study, we examined the possible interaction among interleukin-1alpha (IL-1alpha), IL-4, IL-6, and steroid UGT enzymes (UGT2B15 and UGT2B17). Treatment of LNCaP cells with IL-1alpha led to a dose-dependent inhibition of dihydrotestosterone (DHT) glucuronidation. IL-1alpha decreased both UGT activity and LNCaP cell proliferation in the absence and presence of DHT (0.5 nM); a maximal inhibition of 70% was observed. IL-6 inhibited LNCaP cell proliferation as well as the DHT-induced proliferation of these cells. However, neither IL-4 nor IL-6 significantly affected the formation of DHT glucuronide. Ribonuclease protection and Western blot analyses demonstrated a specific reduction of UGT2B17 transcript and protein levels in IL-1alpha-treated LNCaP cells. The level of UGT2B15 was not affected by cytokine treatments, indicating a differential regulation between these two UGT enzymes. Transfection experiments performed with the UGT2B17 gene promoter region indicates that the regulation occurs at the transcription level via putative cis-acting elements. This study indicates that cell proliferation and UGT expression in steroid-responsive cancer cells are differentially regulated depending on the cytokines present in the cell microenvironment.


Multi-center study: the biochemical efficacy, safety and tolerability of a new alpha1-proteinase inhibitor, Zemaira.
Augmentation therapy with a plasma derived alpha l-Proteinase Inhibitor (alpha1 -PI) has been demonstrated to be effective in restoring serum Alpha1 -antitrypsin (AAT)* levels in individuals with AAT Deficiency (note: alpha1 PI and AAT are synonymous). The objective of this study was to demonstrate that the steady-state trough serum alphal-PI levels, achieved by a new plasma derived alpha,-PI (Zemaira, study drug, ZLB Behring LLC, King of Prussia, Pennsylvania, USA), were bioequivalent to those achieved by the currently available alpha-PI therapy, Prolastin (control drug, Bayer Corporation, Berkeley, California, USA), and maintained weekly trough serum antigenic alpha1-PI levels above the protective threshold of 11 microM. This multi-center, controlled study randomized a total of 44 subjects to receive either study or control drug for a 10-week double-blind phase. The control group was then crossed over to receive the study drug for the remainder of the study (14 weeks). The difference in mean trough serum antigenic alpha1-PI level between the treatment groups was 1.45 microM (90% CI-2.77, -0.13), signifying bioequivalence. The mean trough serum antigenic alpha1-PI level in the study drug group was greater than the therapeutic threshold of 11 microM, achieving a level of 17.7 microM during the steady-state period. Treatment-related adverse events (AEs) were seen in 7% and 21% of study and control drug treated subjects, respectively. No documented viral transmission occurred. These results demonstrate that the new plasma derived alpha1-PI (Zemaira) is bioequivalent to the currently available product Prolastin, is well tolerated, and safe with respect to the risk of viral transmission.


Cervicovaginal DNA Virome Alterations Are Associated with Genital Inflammation and Microbiota Composition.
While the link between the cervicovaginal bacterial microbiome, human papillomavirus (HPV) infection, and cervical cancer is recognized (P. Łaniewski, D. Barnes, A. Goulder, H. Cui, et al., Sci. Rep. 8:7593, 2018, http://dx.doi.org/10.1038/s41598-018-25879-7; A. Mitra, D. A. MacIntyre, Y. S. Lee, A. Smith, et al., Sci. Rep. 5:16865, 2015, http://dx.doi.org/10.1038/srep16865; A. Mitra, D. A. MacIntyre, J. R. Marchesi, Y. S. Lee, et al., Microbiome 4:58, 2016, http://dx.doi.org/10.1186/s40168-016-0203-0; J. Norenhag, J. Du, M. Olovsson, H. Verstraelen, et al., BJOG, 127:171-180, 2020, http://dx.doi.org/10.1111/1471-0528.15854; E. O. Dareng, B. Ma, A. O. Famooto, S. N. Adebamowo, et al., Epidemiol. Infect. 144:123-137, 2016, http://dx.doi.org/10.1017/S0950268815000965; A. Audirac-Chalifour, K. Torres-Poveda, M. Bahena-Roman, J. Tellez-Sosa et al., PLoS One 11:e0153274, 2016, http://dx.doi.org/10.1371/journal.pone.0153274; M. Di Paola, C. Sani, A. M. Clemente, A. Iossa, et al., Sci. Rep. 7:10200, 2017, http://dx.doi.org/10.1038/s41598-017-09842-6), the role of the cervicovaginal virome remains poorly understood. In this pilot study, we conducted metagenomic next-generation sequencing of cervicovaginal lavage specimens to investigate the relationship between the cervicovaginal DNA virome, bacterial microbiome, genital inflammation, and HPV infection. Specific virome alterations were associated with features of the local microenvironment related to HPV persistence and progression to cervical cancer. Cervicovaginal viromes clustered distinctly by genital inflammation state. Genital inflammation was associated with decreased virome richness and alpha diversity and an increased abundance of Anelloviridae species from the genus Alphatorquevirus. Lactobacillus bacteriophages were closely associated with increased Lactobacillus abundance, consistent with phage-host relationships. Interestingly, bacteria-bacteriophage transkingdom interactions were linked to genital inflammation and showed specific interactions with bacterial vaginosis-associated bacteria, including Gardnerella, Prevotella, and Sneathia. Taken together, our results reveal prominent virome interactions with features of the cervicovaginal microenvironment that are associated with HPV and cervical cancer. These findings expand our understanding of the cervicovaginal host-microbiome interactions in women's health. IMPORTANCE HPV infection is an established risk factor for cervical cancer. However, more broadly, the role of the cervicovaginal virome in cervical cancer progression is not well understood. Here, we identified cervicovaginal DNA virome alterations associated with local microenvironment factors (vaginal microbiota and genital inflammation) that influence HPV persistence and progression to cervical cancer. These findings indicate that the cervicovaginal virome plays an important role in women's health.


Study of Bone Mineral Density (BMD) in Patients with Rheumatoid Arthritis and its Co-relation with Severity of the Disease.
Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown etiology marked by a symmetric, peripheral polyarthritis.1-3 People with rheumatoid arthritis are at increased risk of osteoporosis. Hence this article intends to highlight the importance of BMD measurement in patients with RA as a tool for assessment of disease activity and severity. To evaluate Bone Mineral Density in patients of Rheumatoid Arthritis and Co-relate it with severity of disease. Hand bone density was measured on the plain radiographs of the right hand using digital x-ray radiogrammetry (Pronosco Xposure System 2.0). This BMD was correlated with markers of disease activity using DAS 28 Scoring system.4. In our study there were 200 patients with equal number of controls. 70 patients in study group and 131 patients in control group were <45 years old and had normal Z-score while in age group >45 years 26 and 20 cases in study and control groups respectively had their Z-score within normal range. There were total 21 and 2 cases of study and control groups respectively (age <45 years) who had osteoporosis while in age group >45 years 12 and 10 cases in study and control groups respectively had osteopenia. Patients with RA are more susceptible for bone loss in comparison to normal age and gender related subjects. Patients with longer duration and higher disease activity are more susceptible for developing osteopenia and osteoporosis. Occurrence of joint deformities increases with longer disease duration. Limitation of physical activity impairs the bone mineral density. Patient taking anti-rheumatic therapy (steroids and Disease-modifying antirheumatic drugs) are at increased risk of bone loss. All these factors contribute to bone loss independent of each other.


High physiological function for corals with thermally tolerant, host-adapted symbionts.
The flexibility to associate with more than one symbiont may considerably expand a host's niche breadth. Coral animals and dinoflagellate micro-algae represent one of the most functionally integrated and widespread mutualisms between two eukaryotic partners. Symbiont identity greatly affects a coral's ability to cope with extremes in temperature and light. Over its broad distribution across the Eastern Pacific, the ecologically dominant branching coral, Pocillopora grandis, depends on mutualisms with the dinoflagellates Durusdinium glynnii and Cladocopium latusorum. Measurements of skeletal growth, calcification rates, total mass increase, calyx dimensions, reproductive output and response to thermal stress were used to assess the functional performance of these partner combinations. The results show both host-symbiont combinations displayed similar phenotypes; however, significant functional differences emerged when exposed to increased temperatures. Negligible physiological differences in colonies hosting the more thermally tolerant D. glynnii refute the prevailing view that these mutualisms have considerable growth tradeoffs. Well beyond the Eastern Pacific, pocilloporid colonies with D. glynnii are found across the Pacific in warm, environmentally variable, near shore lagoonal habitats. While rising ocean temperatures threaten the persistence of contemporary coral reefs, lessons from the Eastern Pacific indicate that co-evolved thermally tolerant host-symbiont combinations are likely to expand ecologically and spread geographically to dominate reef ecosystems in the future.


Organic carbon stock and composition in 3.5-m core mangrove soils (Trat, Thailand).
Mangroves are increasingly recognized as an important component of regional and global carbon cycles especially for their high carbon storage capacity. Global estimation of mangrove soil organic carbon (SOC) storage requires detailed regional studies, but estimates of SOC data in deep soils are currently missing in many countries. Furthermore, little is explored on the molecular composition of mangrove SOC. Here, we assessed the SOC stock in a Trat mangrove forest (Thailand) by collecting deep soils (3.5 m) and analyzed the SOC composition for better understanding its potential sources and influencing factors. The Trat mangrove forest had four times higher SOC stock than has been considered for Thai mangrove forests, with the per-area SOC stock of nearly 1000 Mg C ha-1 which rivals that of Indo-Pacific mangrove forests. The SOC composition analyzed by C/N ratios and spectroscopic techniques differed by tree species and depth. Compositional data principal component analysis revealed that a biological factor (root abundance) had stronger influences than the soil texture (sand versus clay) on the abundance and composition of mangrove SOC. Although surface soil (~1 m) C density was largely controlled by the recent vegetation, deep soil C density reflected other historical processes. This study contributed to a refined estimate of Thailand mangrove SOC stock and revealed that factors influencing SOC abundance and composition differ by tree species and depth.


Social problem solving as a mediator of the stress-pain relationship among individuals with noncardiac chest pain.
The present study tested the hypothesis that social problem solving (SPS) served to mediate the relationship between preceived stress and noncardiac chest pain (NCCP). Adults undergoing stress myocardial perfusion imaging (MPI) to determine the presence of underlying cardiovascular disease related to the experience of chest pain were recruited prior to stress testing to complete a series of self-report inventories. MPI results were used to identify individuals with NCCP (N = 166; 91 men, 75 women; mean age = 53.92 years, SD = 11.98). Measures included perceived stress, SPS, and chest pain frequency and intensity. In direct tests of the mediational effects of SPS, it was found that two problem-solving dimensions, negative problem orientation and rational problem solving, each served as significant mediators of the effects of stress on both NCCP intensity and frequency. These results support a mediational analysis of NCCP that includes stress and SPS. As such, it identifies SPS as a potentially important clinical target to consider when developing future psychosocial-based therapy protocols for treating individuals with NCCP.


Structural Analogue of Thioflavin T, DMASEBT, as a Tool for Amyloid Fibrils Study.
Fluorescent dye trans-2-[4-(dimethylamino)styryl]-3-ethyl-1,3-benzothiazolium perchlorate (DMASEBT) is a relatively recently synthesized probe for detection of amyloid fibrils accumulating in the organs and tissues of patients with a wide range of serious incurable diseases. DMASEBT was developed as an alternative of its widely used analogue thioflavin T (ThT), which is the "gold standard" for the amyloid fibrils study. Our results show the similarity of both dyes binding to amyloid fibrils and allow one to propose a mechanism of such probes interaction with some types of the fibrils. At the same time, DMASEBT has a significant advantage, namely, improved photophysical properties compared with ThT, which allows for the detection of DMASEBT-stained amyloid fibrils in the spectral region of the "transparency window of biological tissues". The ability of the dye to penetrate into the cells was shown to open the prospect of this dye's use for amyloid fibrils bioimaging and biosensing in vivo. Furthermore, it was proven that DMASEBT can be used not only as a test for amyloid fibrils formation but also for the comparative study of the fibrils structure (both their fibers and bunches), which in turn may underlie the variability of amyloidosis and affect the cytotoxicity of these protein aggregates.


Zirconium-Porphyrin-Based Metal-Organic Framework Hollow Nanotubes for Immobilization of Noble-Metal Single Atoms.
Single atoms immobilized on metal-organic frameworks (MOFs) with unique nanostructures have drawn tremendous attention in the application of catalysis but remain a great challenge. Various single noble-metal atoms have now been successfully anchored on the well-defined anchoring sites of the zirconium porphyrin MOF hollow nanotubes, which are probed by aberration-corrected scanning transmission electron microscopy and synchrotron-radiation-based X-ray absorption fine-structure spectroscopy. Owing to the hollow structure and excellent photoelectrochemical performance, the HNTM-Ir/Pt exhibits outstanding catalytic activity in the visible-light photocatalytic H2 evolution via water splitting. The single atom immobilized on MOFs with hollow structures are expected to pave the way to expand the potential applications of MOFs.


Epidemiology and spatial distribution of Echinococcus granulosus in sheep and goats slaughtered in a hyperendemic European Mediterranean area.
Cystic echinococcosis (CE) is a worldwide parasitic zoonosis caused by the larval stage of Echinococcus granulosus sensu lato affecting livestock, particularly sheep and goats. However, often this parasitosis is underestimated. For this reason, this study aimed to evaluate the epidemiological features and spatial distribution of CE in sheep and goats slaughtered in a hyperendemic Mediterranean area. A survey was conducted in the Basilicata region (southern Italy) from 2014 to 2019. A total of 1454 animals (1265 sheep and 189 goats) from 824 farms were examined for hydatid cyst detection by visual inspection, palpation and incision of target organs. All the CE cysts were counted and classified into five morphostructural types (unilocular, multiseptate, calcified, caseous and hyperlaminated). Molecular analysis was performed on 353 cysts. For spatial analysis, a kriging interpolation method was used to create risk maps, while clustering was assessed by Moran's I test. CE prevalence of 72.2% (595/824) and 58.4% (849/1454) was observed at the farm and animal levels, respectively, with higher values in sheep (62.9%) than goats (28.0%). The liver and lungs were the most frequently infected organs in both sheep and goats. Most of recovered cysts were of the calcified and multiseptate morphotypes. All the isolates were identified as E. granulosus sensu stricto (genotypes G1-G3). Spatial distribution showed a moderate clustering of positive animals. The findings of this study can be used to better understand the eco-epidemiology of echinococcosis and to improve CE surveillance and prevention programs in regions highly endemic for CE.


Topical non-occlusive polymers in hand-foot syndrome.
Many cytotoxic and biological drugs are cause of severe dermatological side effects, such as hand-foot syndrome (HFS) and hand-foot skin reaction (HFSR). Oncologic patients with HFS or HFSR presents relevant symptoms that interferes with daily activities and with adherence to anticancer treatment. The HFRS control and treatment are important goals to enhance the quality of life of oncologic patients. The aim of this study was to assess the efficacy and tolerability of a b.i.d. (bis in die) topical administration of an anhydric ointment based on topical non-occlusive polymers (TNOP) in patients with HFS on current anticancer drug regiments. A prospective, open, multicenter clinical study was conducted in oncologic patients with HFS attended two hospital-based Italian dermatological unit. A global-non-instrumental evaluation, based on different standardized tools (i.e., Sum Score System Index [SRRC] Score, Dermatology Life Qualiy Index [DLQI] and global efficacy) was conducted using measurements at baseline, at 4 and 8 weeks. Non-parametric test for two correlate samples, was used to assess changes in means of the different scores. The protocol was approved by ethical committee of both dermatology service pariticipating to the study. Twenty-one oncologic patients were enrolled. Thirteen (61.9%) of participants were female. The median age was 63 years (range: 37-73). Seventeen (80.9%) patients presenting a HFS associated to capecitabine, and four patients (19.1%) associated to docetaxel. At the enrollment, 33.3% (7/21) of patients showed at level of the hands a HFS of grade 2 and 9.5% (2/21) of grade 3. At level of the feet, 28.6% (6/21) showed a HFS of grade 2, and 17.4% (4/21) of grade 3. The SRRC scores were significantly decreased after 8 weeks of treatment compared to baseline, for both sites. In particular, SRRC score decreased from 4.38 to 1.67 (Z=-3.60, P=0.00) and from 4.48 to 1.43 (Z=-3.87, P=0.00) for hands and feet, respectively. A consistent significant improvement in the perceived QoL of patients was also observed. From baseline to visit 3, the total mean score of DLQI decreased from 10.62 to 4.57 (Δ=-57%, Z=-4.020, P=0.000). In a sample of oncologic patients with HFS, the b.i.d. administration of TNOP for eight weeks, induced a progressive and significant decrease of the SRRC Score and a relevant improvement in the perceived quality of life.


Estradiol replacement enhances working memory in middle-aged rats when initiated immediately after ovariectomy but not after a long-term period of ovarian hormone deprivation.
The goal of the present study was to explore the effects of long-term hormone deprivation on the ability of subsequent estrogen replacement to affect cognition. Female rats, 12 months of age, underwent ovariectomies (n = 30) or sham surgeries (n = 10). Intact rats and 20 ovariectomized rats received cholesterol implants. Ten ovariectomized rats received implants containing 25% estradiol. Five months later, implants were replaced. Half of the ovariectomized rats with cholesterol implants received estradiol implants and half received new cholesterol implants. Rats with estradiol implants received new estradiol implants. Intact rats were ovariectomized and given estradiol implants. Beginning 1 wk later, working memory performance was assessed in an eight-arm radial maze across 24 d of acquisition and during eight additional trials in which a 2.5-h delay was imposed between the fourth and fifth arm choices. Estradiol replacement initiated immediately after ovariectomy at either 12 or 17 months of age significantly improved performance during acquisition and delay trials, compared with control treatment. When estradiol replacement was initiated at 17 months of age, 5 months after ovariectomy, no enhancements were evident. Uteri of rats that experienced delayed estradiol replacement weighed significantly more than uteri of ovariectomized controls but significantly less than uteri of rats that received immediate estradiol replacement. Uterine weight negatively correlated with mean errors during acquisition. These results indicate that whereas chronic estradiol replacement regimens positively affect working memory in middle-aged animals when initiated immediately after ovariectomy, estradiol replacement is not effective when initiated after long-term hormone deprivation.


Template-directed growth of copolymers.
The theory of multistate template-directed reversible copolymerization is developed by extending the method based on iterated function systems to matrices, taking into account the possibility of multiple activation states instead of a single one for the growth process. In this extended theory, the mean growth velocity is obtained with an iterated matrix function system and the probabilities of copolymer sequences are given by matrix products defined along the template. The theory allows us to understand the effects of template heterogeneity, which include a fractal distribution of local growth velocities far enough from equilibrium, and a regime of sublinear growth in time close to equilibrium.


[Antibiotic treatment of diarrhea in dogs and cats].
The most important reason for diarrhea in dogs and cats are dietary errors. In addition there is a multitude of other influences which may lead to diarrhea. Bacteria play a minor role in diarrhea-associated disease. The so-called primary bacterial intestinal infections occur rarely as it is shown in the examinations presented. Except for the situation in which a specific bacterial activator is the cause of continuous diarrhea in general the administration of antibiotics is ineffective. The treatment of diarrhea should rather consist of food deprivation, oral or parenteral rehydration, use of antisecretory medicaments and of adsorbents, diet and, in case of spasms, administration of anti-cholinergics.


Semi-Supervised Pixel Contrastive Learning Framework for Tissue Segmentation in Histopathological Image.
Accurate tissue segmentation in histopathological images is essential for promoting the development of precision pathology. However, the size of the digital pathological image is great, which needs to be tiled into small patches containing limited semantic information. To imitate the pathologist's diagnosis process and model the semantic relation of the whole slide image, We propose a semi-supervised pixel contrastive learning framework (SSPCL) which mainly includes an uncertainty-guided mutual dual consistency learning module (UMDC) and a cross image pixel-contrastive learning module (CIPC). The UMDC module enables efficient learning from unlabeled data through mutual dual-consistency and consensus-based uncertainty. The CIPC module aims at capturing the cross-patch semantic relationship by optimizing a contrastive loss between pixel embeddings. We also propose several novel domain-related sampling methods by utilizing the continuous spatial structure of adjacent image patches, which can avoid the problem of false sampling and improve the training efficiency. In this way, SSPCL significantly reduces the labeling cost on histopathological images and realizes the accurate quantitation of tissues. Extensive experiments on three tissue segmentation datasets demonstrate the effectiveness of SSPCL, which outperforms state-of-the-art up to 5.0% in mDice.


Dental caries and Cariostat test in preschool children.
The aim of this study was to investigate the caries status and susceptibility of children in preschool age. Sixty one children ages between 3 to 5 years (mean age 4.38 +/- 0.71) participated in this study. Caries status was assessed according to WHO criteria, and caries susceptibility by using the Cariostat test. The mean df-t was found to be 2.28 +/- 0.71 (df-s 6.26 +/- 11.92) and 31 children were caries-free. Cariostat scores were 1.75, 2.00, 2.16 in the 3, 4, and 5 year age groups respectively. There were no significant differences in caries status or Cariostat scores between boys and girls. The df-t for the 5 year age group was significantly higher than that for the 3 year age groups (p < 0.05). The test found 77% of the children to have a high caries risk (Cariostat score > 2.0).


Measurement of changes in cerebrospinal fluid pulsation after traumatic brain injury using echo-planar imaging-based functional MRI.
Traumatic brain injury (TBI) is a major public health concern worldwide, with a high incidence and a significant impact on morbidity and mortality. The alteration of cerebrospinal fluid (CSF) dynamics after TBI is a well-known phenomenon; however, the underlying mechanisms and their implications for cognitive function are not fully understood. In this study, we propose a new approach to studying the alteration of CSF dynamics in TBI patients. Our approach involves using conventional echo-planar imaging-based functional MRI with no additional scan, allowing for simultaneous assessment of functional CSF dynamics and blood oxygen level-dependent-based functional brain activities. We utilized two previously suggested indices of (i) CSFpulse, and (ii) correlation between global brain activity and CSF inflow. Using CSFpulse, we demonstrated a significant decrease in CSF pulsation following TBI (p < 0.05), which was consistent with previous studies. Furthermore, we confirmed that the decrease in CSF pulsation was most prominent in the early months after TBI, which could be explained by ependymal ciliary loss, intracranial pressure increment, or aquaporin-4 dysregulation. We also observed a decreasing trend in the correlation between global brain activity and CSF inflow in TBI patients (p < 0.05). Our findings suggest that the decreased CSF pulsation after TBI could lead to the accumulation of toxic substances in the brain and an adverse effect on brain function. Further longitudinal studies with larger sample sizes, TBI biomarker data, and various demographic information are needed to investigate the association between cognitive decline and CSF dynamics after TBI. Overall, this study sheds light on the potential role of altered CSF dynamics in TBI-induced neurologic symptoms and may contribute to the development of novel therapeutic interventions.


Effects of a Bulking Agent on the Protein:Carbohydrate Ratio, Bioconversion, and Cost-effectiveness of a Larval Diet for Anastrepha ludens (Diptera: Tephritidae).
Although the bulking agent is categorized as 'inert', it could modify protein bioavailability and nutritional quality. In this study, the main goal was to determine if the bulking agent modified the protein:carbohydrate (P:C) ratio and bioconversion from diet biomass to larval biomass of Anastrepha ludens. The diet was altered only by modifying the type of bulking agent (corncob powder, coconut fiber, carrot fiber, oatmeal) added without changing the composition and concentration of the other components in the formulation. This allowed reclassification of the food matrices according to P:C ratios of 1:30, 1:35, 1:64, and 1:93. A food matrix with a high P:C ratio promoted a high protein and carbohydrate content in the larval hemolymph and immediately influenced the life-history traits of the larva or delayed them in the adult. The present study indicated a positive relationship between the P:G+T (glucose+trehalose) ratio in the larval hemolymph and the P:C ratio in the larval diet. Our results highlight the importance of including the optimum and real P:C ratio in whole fresh larval diets, since considering only the theoretical concentration of the formulation is not enough to understand the variation in key life-history traits. In addition, the bioconversion index should be included as an indicator of the efficacy of larval diets for mass rearing insects. A diet with high cost-effectiveness should be evaluated by taking into account flying flies as the end product of the mass rearing process to enhance operational SIT programs.


Gastric Ectopic Pyloric Opening with Gastric Ulcer: A Rare Case.
The stomach temporarily stores food and secretes gastric juices to break down and digest food. The normal process is the movement of food digested from the stomach to the duodenum, with the pylorus as a passageway. This paper reports the case of a patient with an ectopic gastric pylorus who presented with gastrointestinal bleeding. A 62-year-old man complained of melena with mild dizziness and nausea. An endoscopic examination revealed a gastric ulcer, approximately 1 cm in diameter, and exposed blood vessels on the posterior wall of the upper body. No normal pyloric structure was observed in the distal antrum, and an opening leading to the duodenum was noted in the posterior wall of the upper body adjacent to the ulcer. This case presents a congenital pyloric ectopic opening in the upper body of the stomach, not in the distal antrum, suggesting a rare gastric morphological variation.


Nitroprusside treatment of erythromelalgia in an adolescent female.
To report a case of erythromelalgia in an adolescent patient successfully treated with nitroprusside. A 15-year-old girl with erythromelalgia resistant to aspirin therapy received an infusion of nitroprusside. The response of the erythromelalgia to nitroprusside was dramatic, with complete pain resolution within 17 hours after the start of therapy. No relapse of erythromelalgia was seen when nitroprusside was discontinued and the patient remained well after 6 months. This case adds to existing literature substantiating the benefit of nitroprusside for the treatment of erythromelalgia in pediatric patients. Erythromelalgia in children may represent a different disease entity than that seen in adults, which is commonly responsive to aspirin therapy. The pathogenesis of erythromelalgia is unclear and precludes formulating a proposed mechanism by which nitroprusside has benefit in children. Nitroprusside is valuable for erythromelalgia resistant to aspirin therapy in pediatric patients. Because of unanswered questions regarding the disease, aspirin remains the agent of first choice in all patients with this rare disease.


Identification of the chemotypes of Ocimum forskolei and Ocimum basilicum by NMR spectroscopy.
The chemotypes of Ocimum forskolei Benth and Ocimum basilicum L. growing wild in Oman have been established by (13)C-NMR analyses of the vegetative and floral oils of the plants. The chemotypes, estragole for O. forskolei and linalool for O. basilicum, suggested by (13)C-NMR fingerprinting were also confirmed by GC-FID and GC/MS analyses. The oil of O. forskolei demonstrated better activities against bacteria and dermatophytes. The significance of the presence of estragole and linalool in the volatile oils of plants whose fragrances are traditionally inhaled, added to food, or rubbed on the skin are discussed.


A Bi-Gradient Dielectric Polymer/High-Κ Nanoparticle/Molecular Semiconductor Ternary Composite for High-Temperature Capacitive Energy Storage.
Attaining compact energy storage under extreme temperature conditions is of paramount importance in the development of advanced dielectric materials. The polymer composite approach has proved effective towards this goal, and addressing the correlation between filler distribution and electrical properties is foremost in designing composite dielectrics, especially in multifiller systems. Here, the design of a bi-gradient polymer composite dielectric using an integrated framework based on the phase field model is reported. This framework can predict the charge-inhibiting behavior of composite dielectrics, which is a key factor impacting the high-temperature capacitive performance but unfortunately is ignored in conventional phase field models. It is found that due to the traps provided by the functional organic fillers, more carriers are trapped near the electrodes and weaken the electric field, thus significantly suppressing the breakdown initialization process. An interpenetrating gradient structure is designed rationally and synthesized experimentally, which exhibits concurrent high energy density (5.51 J cm-3 ) and high charge-discharge efficiency (90%) up to 200 °C. This work provides a strategy to predict the high-temperature energy storage performance of polymer composites containing charge-inhibiting components and helps broaden the scope of data-driven materials design based on phase-field modeling.