Health related quality of life impact from rotavirus diarrhea on children and their family caregivers in Thailand.
Rotavirus diarrhea is a major health problem among young children worldwide with potential negative impacts on health-related quality of life (HRQoL). This study assessed the impact of rotavirus diarrhea on HRQoL of children and their caregivers. We performed a cross-sectional study among 460 hospitalized children with diarrhea aged under 5 years and their family caregivers at three hospitals in Phetchabun province, Thailand during May 2013 and February 2014. The severity of diarrhea was assessed using the Vesikari severity scoring system while the HRQoL was assessed using the EQ-5D-3L. The mean EQ-5D utility of children with all-causes diarrhea was 0.604. The utility of the rotavirus diarrhea group was significantly lower than that of the non-rotavirus diarrhea group (0.593 vs. 0.612; p-value = 0.040). The family caregiver's utility was 0.964 at baseline and significantly decreased to 0.620 (p-value = 0.041) when their children were hospitalized with diarrhea. In multiple regression analyses, severity but not rotavirus infection had significant negative impacts on the utility of both the children and their caregivers. Diarrhea, either caused by rotavirus or non-rotavirus infection, resulted in substantial negative impacts on the quality of life of both the children and their caregivers.


Differences in the immune-inflammatory profiles of unipolar and bipolar depression.
Major depressive disorder (MDD) and bipolar depression (BD) both share increased immune-inflammatory activation. However, there are unclear patterns of differences in peripheral immune profiles between them. We examined such differences in 245 MDD and 59 BD patients, recruited in the same center, who were in an acute depressive episode of moderate severity. Hierarchical binary logistic regression analyses and generalized linear models were used to compare levels of plasma biomarkers between groups and to predict dichotomous classification. Interleukin (IL)-1β, tumor necrosis factor (TNF)-α, soluble TNF receptor (sTNFR)1, IL-12 and IL-10 were significantly higher in MDD than in BD, whereas IL-6, sTNFR2, IL-18, IL-33, ST2 (IL1R Like 1) and KLOTHO were significantly higher in BD than in MDD. Moreover, logistic regression analyses correctly classified BD and MDD patients with 98.1% accuracy, using a combination of IL-6, IL-8, ST2, sTNFR2 (directly associated with BD) and IL-12 and TNF-α (directly associated with MDD). Patients with MDD with melancholic features showed higher IL-1β levels than those without melancholia. The sTNFR1 / sTNFR2 ratio significantly predicted MDD and state and trait anxiety and negative affect. Results remained significant after covariate adjustment, including drug use. Cross-sectional study. Lack of control comparison group. Differences in exposure to medications among participants. Differences in immune profiles between BD and MDD patients exist, especially for the compensatory immune-regulatory system (CIRS): increased IL-10 is the primary immune-regulatory mechanism in MDD, while increased sTNFR2 and KLOTHO are the primary regulatory mechanisms in BD.


A conserved interaction between beta1 integrin/PAT-3 and Nck-interacting kinase/MIG-15 that mediates commissural axon navigation in C. elegans.
Integrins are heterodimeric (alphabeta) transmembrane receptors for extracellular matrix (ECM) ligands. Through interactions with molecular partners at cell junctions, they provide a connection between the ECM and the cytoskeleton and regulate many aspects of cell behavior. A number of integrin-associated molecules have been identified; however, in many cases, their function and role in the animal remain to be clarified. We have identified the Nck-interacting kinase (NIK), a member of the STE20/germinal center kinase (GCK) family, as a partner for the beta1A integrin cytoplasmic domain. We find that NIK is expressed in the nervous system and other tissues in mouse embryos and colocalizes with actin and beta1 integrin in cellular protrusions in transfected cells. To demonstrate the functional significance of this interaction, we used Caenorhabditis elegans, since it has only one beta (PAT-3) integrin chain, two alpha (INA-1 and PAT-2) integrin chains, and a well-conserved NIK ortholog (MIG-15). Using three methods, we show that reducing mig-15 activity results in premature branching of commissures. A significant aggravation of this defect is observed when mig-15 activity is compromised in a weak ina-1 background. Neuronal-specific RNA interference against mig-15 or pat-3 leads to similar axonal defects, thus showing that both mig-15 and pat-3 act cell autonomously in neurons. Finally, we show a genetic interaction between mig-15, ina-1, and genes that encode Rac GTPases. Using several models, we provide the first evidence that the kinase NIK and integrins interact in vitro and in vivo. This interaction is required for proper axonal navigation in C. elegans.


Intracellular calcium mobilization induces period genes via MAP kinase pathways in NIH3T3 cells.
Mammalian period genes have a pivotal role in generating circadian rhythms and are rapidly induced by several stimuli in mammalian cells. In the present study, we revealed that treatment with thapsigargin significantly induced transcripts of mouse period 1 and 2 (mPer1 and mPer2) but not mPer3 among circadian related genes in NIH3T3 cells. Thapsigargin-induced mPer1 and mPer2 mRNA expressions took distinct signaling pathways from protein kinase C and cAMP, but were partially inhibited by inhibitors of MEK1 and p38 mitogen-activated protein kinase, respectively. Thus, the present study suggested that intracellular calcium is one of multiple signaling stimuli triggering mPer gene expression in NIH3T3 cells.


Clinical efficacy of deep brain stimulation for the treatment of medically refractory epilepsy.
Epilepsy affects 50 million people worldwide and about 30% of these patients will not be adequately controlled with antiepileptic drugs (AEDs) alone. For patients where resective surgery is not indicated, deep brain stimulation (DBS) may be an effective alternative. The majority of available literature targets the thalamic nuclei (anterior; centromedian), subthalamic nucleus, hippocampus, and cerebellum. Here, we review patient outcomes and adverse events related to DBS to these various targets. Data show DBS may be a safe and effective treatment option for refractory epilepsy.


Rapid tolerance to the hypotensive effects of glyceryl trinitrate in the rat: prevention by N-acetyl-L- but not N-acetyl-D-cysteine.
1. A new model of tolerance to the hypotensive effect of organic nitrates has been developed in the rat. 2. The fall in mean arterial pressure (MAP) in response to bolus doses of sodium nitroprusside (NP) (4 micrograms kg-1) and glyceryl trinitrate (GTN) (10 micrograms kg-1) was recorded both before and after a 60 min infusion of either 0.9% saline, NP (20 micrograms kg-1 min-1) or GTN (40 micrograms kg-1 min-1). 3. The hypotensive effects of NP or GTN were unchanged following saline infusion, but were reduced in both cases by approximately 40% following the infusion of NP. 4. Infusion of GTN for 60 min virtually abolished the hypotensive effect of a GTN bolus (i.e. nitrate tolerance), whilst the effect of a NP bolus was reduced only to a similar extent (30%) as after an infusion of NP. This latter effect is attributed to a degree of non-specific cross-tolerance between GTN and NP. 5. Co-treatment of a group of rats with N-acetyl-L-cysteine (L-NAC) prevented the development of nitrate tolerance, confirming the role of thiols in this phenomenon, whereas N-acetyl-D-cysteine (D-NAC) did not. 6. The stereospecificity in the effect of NAC in preventing this specific tolerance to GTN suggests that the interaction between GTN and NAC and/or cysteine involves an enzyme-dependent step. 7. NAC was unable to prevent the non-specific cross-tolerance to NP which followed infusion of GTN, suggesting that the mechanism does not directly involve NAC and/or cysteine.


Neural Abnormalities in Nonallergic Rhinitis.
Sensory nerve endings within the airway epithelial cells and the solitary chemoreceptor cells, synapsing with sensory nerves, respond to airborne irritants. Transient receptor potential (TRP) channels (A1 and V1 subtypes, specifically) on these nerve endings initiate local antidromic reflexes resulting in the release of neuropeptides such as substance P and calcitonin G-related peptides. These neuropeptides dilate epithelial submucosal blood vessels and may therefore increase transudation across these vessels resulting in submucosal edema, congestion, and rhinitis. Altered expression or activity of these TRP channels can therefore influence responsiveness to irritants. Besides these pathogenic mechanisms, additional mechanisms such as dysautonomia resulting in diminished sympathetic activity and comparative parasympathetic overactivity have also been suggested as a probable mechanism. Therapeutic effectiveness for this condition has been demonstrated through desensitization of TRPV1 channels with typical agonists such as capsaicin. Other agents effective in treating nonallergic rhinitis (NAR) such as azelastine have been demonstrated to exhibit TRPV1 channel activity through the modulation of Ca(2+) signaling on sensory neurons and in nasal epithelial cells. Roles of antimuscarinic agents such as tiotropium in NAR have been suggested by associations of muscarinic cholinergic receptors with TRPV1. The associations between these channels have also been suggested as mechanisms of airway hyperreactivity in asthma. The concept of the united airway disease hypothesis suggests a significant association between rhinitis and asthma. This concept is supported by the development of late-onset asthma in about 10-40 % of NAR patients who also exhibit a greater severity in their asthma. The factors and mechanisms associating NAR with nonallergic asthma are currently unknown. Nonetheless, free immunoglobulin light chains and microRNA alteration as mediators of these inflammatory conditions may play key roles in this association.


Sustainability in the dairy industry: a systematic literature review.
The dairy industry can contribute to global food security in a sustainable way by efficiently converting milk into dairy ingredients and products, even though they are polluting on a large scale. In this context, this study aimed to conduct a systematic literature review on sustainable indicators and dairy industries. The methodology used has a qualitative and quantitative approach and its technical procedure was the systematic literature review. The bases of journals consulted, using the keywords "sustainability indicator" and "dairy industry" which resulted in 130 valid scientific articles. The main results show that the sustainability indicators in the dairy industry are emerging and lacking research; being found seven papers, that highlight 12 indicators of the environmental, 11 of the social and eight economic dimensions, that may be considered fragile and initial. The studied problems are related to wastewater treatment methods, electric power consumption, efficiency of the industrial plant, among others, and the benefits on the theme are related to solutions to the difficulties, such as electricity reduction, sustainable practices. Among others, it is concluded that the dairy industries address the sustainability theme since 2011, with an ambiguous trend, being found evidence of the fragility of the sustainability indicators was found, mainly in the initial stage of their conception, when considering holistic approach (triple bottom line).


The h-index outperforms other bibliometrics in the assessment of research performance in general surgery: a province-wide study.
The h-index is used as an objective measure of research impact. Its validity, however, is not known in the context of general surgery and comparisons with other bibliometric indices are lacking. We sought to evaluate the h-index as a reliable and valid measure of research performance in general surgery across 6 universities in the province of Ontario, Canada. Bibliometric indices for 219 faculty members in general surgery were calculated using the Scopus and Web of Science online databases. We investigated agreement between the databases. A 2-way analysis of variance was used to compare the h-index of surgeons grouped by institutional affiliation and academic rank and to identify the relative impact of these factors on different bibliometric indices. The agreement on h-indices between the Scopus and Web of Science was problematic. The h-index was associated more strongly with academic rank (academic rank accounted for 33.3% of researcher's h-index) than of the number of publications (12.5%) or the number of citations per author (10.2%). The number of citations per paper was not associated with academic rank. The institutional affiliation affected bibliometric indices to a similar degree to academic rank. Our data suggest better construct validity for the h-index than for other bibliometrics, although the agreement of h-index values between databases can be problematic for some researchers. The use of the h-index as a criterion-based assessment across different universities is problematic and that it should be used as a normative assessment tool, with comparisons with a specified population of interest.


Mapping of angiotensin AT1 receptors in the rat limbic system.
The AT1 receptor is one of the two receptor subtypes able to bind angiotensin II. In the present study, immunohistochemical examination of the distribution of the AT1 receptor in several limbic structures of female rats has been done, revealing new aspects of the distribution of AT1-positive cells. The presence of AT1 receptor expressing cells in the hippocampus and the amygdala is described, but their distribution in these regions has not been examined in a detailed way. We found some notable differences in the distribution of these cells: in female rats, we detected high amounts of labeled cells in the hippocampus, the entorhinal cortex and piriform cortex. In somewhat lower amounts, stained cells could be found in several nuclei of the amygdala (in the basomedial, basolateral, lateral, central and medial nucleus of the amygdala, in the amygdalopiriform transition area and in the amygdalohippocampal transition area as well as in the bed nucleus of the stria terminalis).


The Impact of Spironolactone on Markers of Myocardial Oxidative Status, Inflammation and Remodeling in Hyperthyroid Rats.
Hyperthyroidism promotes the development and progression of cardiovascular diseases (CVD). Aldosterone, a key mediator of myocardial inflammation, oxidative stress and fibrosis, may be activated in hyperthyroidism. To assess the impact of hyperthyroidism on aldosterone levels and myocardial oxidative status, inflammatory and fibrotic markers in hyperthyroid rats, and to test if the use of spironolactone (an aldosterone antagonist) attenuates these changes. Adult Wistar rats were randomly distributed into 4 groups; controls, spironolactone treated rats (Spir, 50mg/kg/day), hyperthyroid rats (Hyper, daily intraperitoneal levothyroxine 0.3mg/kg/day), and spironolactone treated hyperthyroid rats (Hyper+Spir) for 4 weeks. Blood pressure (Bp), and levels of serum and myocardial aldosterone, oxidants/antioxidants, inflammatory and fibrotic markers were measured. Levothyroxine increased serum thyroid hormones and increased Bp, heart rate and heart to bodyweight ratio. Relative to control, serum aldosterone levels were increased in Hyper and Hyper+ Spir groups. In parallel, cardiac lipid peroxides and serum endothelin-1 were increased whereas cardiac superoxide dismutase, catalase, glutathione, and matrix metalloproteinase -2 were reduced in the Hyper group. Spironolactone decreased serum thyroid hormones and improved cardiac lipid peroxides and metalloproteinase -2 levels. The use of spironolactone decreased serum nitrite levels and increased cardiac SOD and glutathione. Cardiac levels of aldosterone, endothelin-1, transforming growth factor-beta and nitrite were similar among all groups. Hyperthyroid status was associated with an increase in aldosterone and oxidant/ inflammatory biomarkers. The use of spironolactone enhanced antioxidant defenses. Aldosterone antagonists may serve as potential drugs to attenuate the development of cardiac disease in hyperthyroidism.


Pheromonal and kairomonal activities can be separated: synthesis and bioactivity studies of pine bast scale sex pheromones and their analogues.
New syntheses were achieved to secure matsuone (1), the pheromone of the pine scale Matsucoccus matsumurae, that of M. feytaudi (2), and that of M. josephi (3). Five analogues (4-8) of 1, 2, and 3 were synthesized and their bioactivities studied. The pheromone analogue 7 showed relatively strong pheromonal activity toward M. josephi, while it was inactive as a kairomone toward the predator Elatophilus hebraicus. Similarly, analogue 8 acted as a pheromone for M. feytaudi, but it did not attract any of its local predators. The M. feytaudi pheromone 2 exhibited strong kairomonal activity toward E. hebraicus, but was not active as a pheromone mimic to attract M. josephi.


Ecosystem service potential, flow, demand and their spatial associations: a comparison of the nutrient retention service between a human- and a nature-dominated watershed.
Nutrient regulation is an important ecosystem regulating service in watersheds. However, systematic investigations of the spatial associations between the potential, flow, and demand of the nutrient regulation service are still lacking. Therefore, we performed a case study comparing the total phosphorus (TP) retention in the Dianchi Lake (DL) watershed (human-dominated) with that in the Lower Reach of the Zi River (LRZR) watershed (nature-dominated). We used four indicators-TP retention potential, TP retention, TP load, and TP export-to represent the potential, flow, demand, and flow-demand budget of the TP retention service, respectively. We estimated the TP retention and export using the InVEST tool, mapped the four TP indicators and calculated their correlations, and estimated the contributions of different ecosystem types and terrain ranges to TP retention and export. We determined the following: (1) the incongruity between the spatial distribution of the TP retention potential and the other three TP indicators was smaller in the LRZR watershed than in the DL watershed; (2) the TP retention potentials generally increased-while the other three TP indicators decreased-with increases in the elevation gradient in the DL watershed and the slope gradients in both study areas; and (3) paddy fields exhibited the highest TP retention intensity and residential areas exhibited the highest TP export intensity among the major ecosystem types in both study areas. Moreover, the TP retention intensities of dryland crops and residential areas in the DL watershed were much higher than they were in the LRZR watershed. Our findings imply that the flow of the nutrient retention service is influenced more by the service demand than by the service potential and that it is influenced by both landscape composition and pattern. Because of the limitations and uncertainties in the modeling outputs, our results should be carefully used in other studies or in decision-making.


Impact of small-scale irrigation on the livelihood and resilience of smallholder farmers against climate change stresses: Evidence from Kersa district, eastern Oromia, Ethiopia.
This study mainly aimed to evaluate the impact of small-scale irrigation on the livelihood and resilience of farmers toward climate change in Kersa district of the eastern Oromia region of Ethiopia. A sample of 288 randomly selected households (158 non-adopters and 130 adopters) was used to gather the data. The data were analyzed using the resilience capacity index and propensity score matching methods. The resilience capacity index was utilized to summarize all the resilience indicators into a single value, and propensity score matching was used to evaluate the impact. The results of the average treatment effect on the treated analysis revealed that adopters were better-off in crop yields by 84.72 quintals per hectare, 55641.60 birr in total income, and by 2.02 resilience capacity index compared to non-adopters. The results of the study indicate that small-scale irrigation significantly improves farm households' livelihoods and mitigates the effects of climate change by enhancing their ability to respond to erratic weather events, which builds their resilience. Therefore, policymakers should prioritize small-scale irrigation practices to improve rural households' livelihoods and farmers' resilience in areas with irregular rainfall and a high risk of drought.


A novel type II collagen gene mutation in a family with spondyloepiphyseal dysplasia and extensive intrafamilial phenotypic diversity.
The purpose of this study was to describe a family with spondyloepiphyseal dysplasia caused by a novel type II collagen gene (COL2A1) mutation and the family's phenotypic diversity. Clinical and radiographic examinations of skeletal dysplasia were conducted on seven affected family members across two generations. The entire coding region of COL2A1, including the flanking intron regions, was analyzed with PCR and direct sequencing. The stature of the subjects ranged from extremely short to within normal height range. Hip deformity and advanced osteoarthritis were noted in all the subjects, ranging from severe coxa plana to mild acetabular dysplasia. Atlantoaxial subluxation combined with a hypoplastic odontoid process was found in three of the subjects. Various degrees of platyspondyly were confirmed in all subjects. Genetically, a novel COL2A1 mutation (c.1349G>C, p.Gly450Ala) was identified in all the affected family members; however, it was not present in the one unaffected family member tested. We described a family with spondyloepiphyseal dysplasia and a novel COL2A1 mutation (c.1349G>C, p.Gly450Ala). Phenotypes were diverse even among individuals with the same mutation and within the same family.


The influence of configuration changes in tuftsin peptide chain on its folding properties.
IR spectra of ten tuftsin structural analogues containing D-amino acid residues were investigated in solid state, and in chloroform and carbon tetrachloride solutions. The effect of configurational changes on folding ability of the peptide and on formation of beta-bend structure seems to depend on the position of the altered residue.


Apolipoprotein E is not related to memory abilities at 70 years of age.
APOE e4-related memory deficits were reported in a normal population aged between 50 and 60 when controlling for general cognitive ability in early adulthood. This extended findings of APOE e4 effects on cognitive ability in 60-80-year-olds to a younger group and confirmed that this effect relates to changes in memory ability with age. The present study tests the association of APOE e4 variation with verbal and spatial memory in a sample of 70-year-olds both adjusted and non-adjusted for childhood and adult general cognitive ability. The 1,013 participants comprise surviving members of the 1947 Scottish Mental Survey resident in the Lothian area of Scotland. They were tested on general cognitive ability at age 11 years and followed up at about age 70 with tests of verbal (immediate and delayed) and spatial memory. General linear models were used to test the association between variation in the APOE polymorphism (e4 presence vs. absence) and memory measures. Of the eight measures tested, Spatial span forward was significantly associated with APOE e4 variation (P = 0.04) when adjusting for IQ, whereas Logical memory immediate was associated with APOE e4 variation (P = 0.04) in the analysis not controlling for IQ. Neither of these tests was significant when a correction for multiple testing was applied. APOE e4 does not influence memory abilities in a normal population of 70-year-olds.


Engineered topographical structure to control spatial cell density using cell migration.
Control of the spatial distribution of various cell types is required to construct functional tissues. Here, we report a simple topographical structure changed the spatial cell density. A concave curved boundary was designed, which allowed the spatial descent moving of cells and the change in spatial distributions of co-cultured cells. We utilized the difference in cell motility between myoblast cells (C2C12) and neuronal cells (PC12) to demonstrate the feasibility of spontaneous change in spatial cell density. Without the curved boundaries, high motility cells (C2C12) did not migrate to the adjacent area, which resulted in a slight temporal change (< 15%) in the spatial cell distribution. In contrast, with the curved boundaries, the cell density of the high motility cells in the groove to those cells on the ridge showed an increase exceeding 45%. On the other hand, the temporal change in the spatial cell distribution of low motility cells (PC12) was below 15% with or without the curved boundaries. In addition, as groove width increased, both cells displayed more initially gathering in groove. Importantly, these cell-type dependent results were also maintained under co-culture conditions. Our results suggest that designing topographical interfaces changes spatial cell density without any manipulation and is useful for multi-cellular constructs.


Multiple hydration layers in cubic insulin crystals.
Cubic insulin crystals contain approximately 30-A-diameter channels filled with aqueous solvent, providing a useful system in which to analyze hydration structure at a variety of distances from protein surfaces. Beginning with an atomic model for the protein and ordered water molecules, the density distribution in the solvent volume of the phasing model was iteratively refined to improve the fit of calculated structure factors with x-ray diffraction data. The free R value, which compares calculated structure factors with a subset of observed structure factors deliberately omitted from the refinement, was used to provide an objective confirmation of the effectiveness of the refinement procedure. Electron density maps of the solvent, computed using the solvent-refined phases and complete low-resolution diffraction data, reveal multiple hydration layers around the protein.


Synthesis, structural and spectroscopic studies of 2-oxoacenaphthylen-1(2H)-ylidene nicotinohydrazide.
The synthesis of a new hydrazone, 2-oxoacenaphthylen-1(2H)-ylidene nicotinohydrazide, and its structural and spectroscopic characterization is reported. The obtained powder was recrystallized from DMSO and ethanol that afforded small crystals used for single-crystal X-ray diffraction studies. The compound was found to crystallize in two polymorphs, depending on the crystallization conditions. One of the polymorphs (form I) crystallizes in the centrosymmetric P21/c monoclinic space group, the other (form II) crystallizes in the non-centrosymmetric, but achiral, orthorhombic space group P212121. Conformation of the molecules is similar in both polymorphs, but the network of weak intermolecular interactions determining the crystal packing is different. In form II an additional C-H⋯O bond connects molecules related by the screw-axis running parallel to the a-axis. Crystals of both polymorphs were also screened by FT-IR and Raman microscopy; a detailed analysis of the spectra and comparison with those of the isolated molecule calculated by ab-initio HF/MP2 and DFT/B3LYP methods using a correlation consistent cc-pVDZ basis set is presented. In addition, UV-vis and NMR studies were performed in solution.


Evaluation of patients for the need of thrombolytic therapy in the prehospital setting.
Maximum benefit from thrombolytic therapy in acute myocardial infarction is obtained with early therapy. The earliest possible time to treat is during the initial evaluation of the patient in the home or ambulance, which requires accurate diagnosis of acute myocardial infarction in the prehospital setting. In our study, paramedics evaluated patients who had chest pain with a 12-lead ECG transmitted by cellular telephone and a checklist for inclusion and exclusion criteria for thrombolytic therapy. This information was transmitted to a hospital-based telemetry physician who diagnosed or excluded acute myocardial infarction and made a mock decision to withhold or administer a thrombolytic agent. Forty-eight patients with chest pain were evaluated. Six were diagnosed as having overt acute myocardial infarction by the hospital-based telemetry physician. All six patients had the diagnosis substantiated by both ECG and enzyme studies on hospital admission. Based on the data supplied by paramedics, two of these six patients were considered eligible for thrombolytic therapy by the physician. Hospital evaluation confirmed the prehospital decision to treat with a thrombolytic agent. In addition, all other patients were appropriately diagnosed as ineligible. Prehospital ECG diagnosis resulted in two patients going directly to the catheterization lab, thereby bypassing the emergency department. Overt acute myocardial infarction can be accurately identified by a prehospital-acquired 12-lead ECG transmitted to a hospital-based physician. Our study demonstrates that in conjunction with specially trained paramedics, the hospital physician can decide whether to administer thrombolytic therapy to such patients in the prehospital setting.


alpha-Hydroxylation of fatty acids in brain. Substrate specificity and deuterium isotope effect.
The alpha-hydroxylation of fatty acids with various chain length by a rat brain postnuclear preparation was investigated. The maximum velocity of the alpha-hydroxylation were higher for lignoceric (tetracosanoic), tricosanoic, docosanoic, and heneicosanoic acids and lower for hexacosanoic, pentacosanoic, eicosanoic, and nonadecanoic acids. Stearic palmitic, and phytanic (3,7,11,15-tetramethylpalmitic) acids were not hydroxylated by this preparation. Apparent Km values were lower for fatty acids with the higher Vmax and higher for those with the lower Vmax values. The relative order of alpha-hydroxylation strongly resembles the relative distribution of these fatty acids in brain cerebrosides, and we suggest that alpha-hydroxylation plays an important role in determining this distribution. An improved synthesis of [U-14C]phytanic acid is described. The rate of alpha-hydroxylation with [2-2H2]lignoceric acid was one-fifth of nondeuterated lignoceric acid and one-third of [3-2H2]lignoceric acid, while apparent Km values for these acids were similar. The reduced rate with [2-2H2]lignoceric acid indicates that the cleavage of the C-H bond is the rate-limiting step of the alpha-hydroxylation.


Efficacy and Safety of an Antioxidant-Enriched Medical Device for Topical Use in Adults with Eczematous Dermatitis.
Emollients reduce the severity of dermatitis-associated symptoms. Antioxidant supplementation may be helpful to control inflammatory processes and consequential skin damage. The clinical performance and safety of an emollient medical device for topical treatment enriched with antioxidant ingredients in adults with mild-to-moderate dermatitis is presented in this manuscript. We performed a monocenter, open-label, uncontrolled clinical trial. Participants applied the product twice a day for 28 days. No other medication or moisturizer was allowed. Changes in dermatitis severity were assessed at days 14 and 28 by study investigators. Subjects self-assessed pruritus, Dermatology Life Quality Index, and product satisfaction. At the end of the study, a global evaluation of the product was done both by patient-reported outcomes and investigators' evaluations. Forty subjects were enrolled in the study (mean age 35 years). Treatment success was achieved in 87.5% of subjects (p < 0.0001) after 28 days. Mean Investigator's Global Assessment (IGA) and Eczema Area and Severity Index (EASI) scores decreased at days 14 and 28 (p < 0.0001). Subjects reported a reduction in pruritus severity and improvement of quality of life (p < 0.0001), along with satisfaction with the product. At the end of the study, skin condition improved in more than 90% of subjects. No safety issues were identified. The medical device studied for topical use in this clinical trial is considered safe and reduces pruritus in adults with atopic and contact dermatitis.


Midwives experiences of interventions to improve breast expression following preterm birth: A qualitative study.
Preterm birth impacts approximately 10% of women globally. Midwives are often the first point of care after the birth of a preterm infant providing mothers with information and support for breast expression. However, despite guidelines that suggest expression within the first hour of birth, most first expressions occur much later. This study aimed to seek an understanding of midwives' experiences with the first expression for mothers of preterm infants, including the barriers and facilitators that midwives may face. A qualitative design using semi-structured interviews via focus groups. Thematic analysis was used to identify relevant themes and sub-themes. Participants included midwives providing care to women in preterm labour and birth at a tertiary maternity hospital in Australia (N=12). All participating midwives cared for mothers of preterm infants between 28 and 35 weeks' gestation up to six hours following birth. Two major themes resulted from the data, including the changing expectations of infant feeding and the responsibility versus expectation to support a woman to express in the first hour of birth with other competing clinical and organisational tasks. Whilst individual philosophies on the benefits of human milk were positive, expressing in the birth suite was dictated by essential clinical tasks and by the institutions value placed on expressing in the first hour. Clear objectives to undertake expressing within the first hour or within the birth suite stay, need to be included in policy and supported by management and team leaders, to increase early expressing rates.


Commentary on "applicability of robot-assisted laparoscopic radical prostatectomy in renal allograft recipients." Wagener N, Nyarangi-Dix JN, Teber D, Zeier M, Hohenfellner M, Department of Urology, University of Heidelberg, Heidelberg, Germany: Transplant Proc 2012; 44(5):1287-92.
To evaluate the general applicability of robotic-assisted laparoscopic radical prostatectomy (RALP) in renal transplant recipients and potential surgical modifications due to the position of the transplanted kidney in the iliac fossa, as RALP has proven to be an effective and safe treatment option for prostate cancer (PCa) removal. A 71-year-old patient who had undergone renal transplantation was diagnosed with biopsy-proven localized Gleason 7a PCa. The prostate-specific antigen value was 12.4ng/mL. RALP was performed by a transperitoneal approach using six ports. By partial mobilization of the bladder, the working space for the radical prostatectomy was created, while leaving the renal transplant and ureter untouched. Lymph node dissection was performed only on the contralateral side of the transplanted kidney. The procedure concluded after 220 minutes and the estimated blood loss was 300mL. The perioperative clinical course was uneventful. The kidney function remained normal with a creatinine value of 1.2mg/dL. A complete extirpation of the prostate with negative surgical margins was achieved. After catheter removal, the patient was completely continent. RALP in renal transplant recipients is feasible and can be achieved with favorable oncological and functional outcome. No modifications to the standard RALP technique are required in these patients, except from a partial dissection of the bladder from the abdominal wall and a one-sided lymph node dissection.


Aging and scotopic sensitivity.
Scotopic sensitivity was compared in young and older adults in good eye health after individualized correction for age-related changes in lens density and control of pupil diameter. Unlike earlier studies on this topic, fundus photography and a grading scale were used to characterize macular health in the older sample. Twenty-four young adults (mean age 27) and 25 older adults (mean age 70 years) underwent scotopic sensitivity testing after 30 min of dark adaptation. Light sensitivity for a 450 nm target was measured at 4, 7, 32, and 38 degrees both nasally and temporally along the horizontal meridian. Lens density was estimated using Sample's method. On average, older adults exhibited a 0.5 log unit decrease in sensitivity even with lens density taken into account, which did not vary with target eccentricity or nasal/temporal hemifield. Although 60% of older subjects exhibited fundoscopic signs of early age-related maculopathy (ARM), even those free from these signs demonstrated a half log unit sensitivity loss, suggesting that this impairment may represent a biological aging process. We found no psychophysical evidence that scotopic sensitivity loss in older adults with relatively good retinal health is accentuated in the peri-macula, even though anatomical studies on donor retinas from older adults have indicated that this area has heightened rod loss.


Calcium-mediated aponecrosis plays a central role in the pathogenesis of estrogenic chemical-induced neurotoxicity.
Estrogen is traditionally associated with females but is also present in males, and influences aspects of brain chemistry and brain morphology in males, females and also during prenatal development. Humans as well as animals are additionally exposed to environmental products that mimic estrogen activity, also known as endocrine disrupters (EDCs). This hypothesis article investigates the role of estrogen (and also EDCs) in the brain and how it influences the Ca2+ pathway. Ca2+ and its movement in and out of the cell is an extremely important ion controlling normal cell physiology. Any dysfunction in the movement from outside to inside the cell or between organelles may have fundamentally negative effects and the disturbance may even lead to apoptosis and/or necrosis. Therefore we consider whether estrogen and EDCs may alter the Ca2+ physiology and whether these changes may be one of the main causes of interference in physiology that is seen when humans and animals are exposed to EDCs. We come to the conclusion that on a molecular level Ca2+ and Ca2+ fluxes ([Ca2+]i, endocrine disrupting chemicals, redox modulation, mitochondria and cytochrome c followed by apoptosis, necrosis or most likely aponecrosis may contribute to chemical-mediated developmental toxicity. Similarly, we hypothesize that calcium-mediated aponecrosis do not only play a central role in the pathophysiology of estrogenic chemical-induced neurotoxicity, but can contribute to chemical-mediated developmental toxicity in general, thereby affecting almost all cells and organs of the living organism.


Effect of Intravenous Thrombolytic Dose of Alteplase on Long-Term Prognosis in Patients with Acute Ischemic Stroke.
This study aimed to investigate the long-term prognostic effects of different alteplase doses on patients with acute ischemic stroke (AIS). In this cohort study, we enrolled 501 patients with AIS treated with intravenous thrombolysis with alteplase, with the primary endpoint event of recurrence of ischemic stroke and the secondary endpoint event of death. The effects of different doses of alteplase on recurrence of ischemic stroke and death were analyzed using a Cox proportional risk model. Among 501 patients with AIS treated with thrombolysis, 295 patients (58.9%) and 206 patients (41.1%) were treated with low-dose and standard-dose alteplase, respectively. During the study period, 61 patients (12.2%) had a confirmed recurrence of ischemic stroke. Multivariate Cox proportional risk analysis showed that standard-dose alteplase thrombolysis (HR 0.511, 95% CI 0.288-0.905, P = 0.021) was significantly associated with a reduced risk of long-term recurrence of AIS, whereas atrial fibrillation was associated with an increased risk of long-term recurrence of AIS. Thirty-nine (7.8%) patients died during the study period. Multivariate Cox proportional risk analysis showed that age, baseline National Institutes of Health Stroke Scale (NIHSS) score, and symptomatic steno-occlusion were associated with an increased long-term risk of death from AIS. The alteplase dose was not associated with the risk of death from AIS. Standard-dose alteplase treatment reduced the risk of long-term recurrence of AIS after hospital discharge and the alteplase dose was not associated with the long-term risk of death from AIS.


Long-term follow-up of postcardiotomy patients with profound cardiogenic shock treated with ventricular assist devices.
Success of ventricular assist devices in patients with postcardiotomy shock has provided enough survivors to allow evaluation of the length and quality of life. Fifteen survivors from 28 to 68 years (mean 53) old from four centers were followed for 6 to 77 months (mean 35) after discharge from the hospital. Four patients suffered perioperative myocardial infarctions. In three patients, ventricular function was normal before surgery and remained so afterward. Of 12 patients with moderate or severely impaired ventricular function, five improved, five were unchanged, and two were worse. One patient died 6 months after surgery of cardiomyopathy. Seven patients are employed full-time and one works part-time. Five patients are retired but active and one is moderately disabled. NYHA functional class improved in the patients as a group: 13 were in classes III and IV before surgery and 13 were in classes I and II after surgery. Two patients had noncardiac partial disability. Survivors of ventricular assist device support for postcardiotomy shock have an excellent chance for high-quality life and the risk of crippling cardiac disability is small.


Factors influencing people's ability to maintain their activity levels during treatment for soft tissue sarcoma - A qualitative study.
Soft tissue sarcoma (STS) is a rare connective tissue cancer treated with chemotherapy in the advanced stages. Emerging evidence suggests that physical activity (PA) improves symptom management and quality of life for people undergoing chemotherapy for advanced cancer. However, little research reports their perspective. Method: Semi-structured interviews were used within a phenomenological approach to explore factors that affect people's ability to be physically active while undergoing treatment. Six participants were recruited with purposive sampling. Thematic analysis was used to analyze the data. Results: Three themes identified that PA was seen as an indicator of a persons' own sense of normality; a feeling of loss and uncertainty for the future had impacts on peoples' ability to be physically active, and finally, participants found it challenging to recognize their support needs as their activity levels reduced. Motivation to remain active was individual, and numerous barriers affected participants' ability to remain active as their disease advanced; this included a lack of specific guidance while undergoing chemotherapy. Participants expressed uncertainty generally in identifying and expressing their support needs as they faced multiple complex issues. Conclusion: Health professionals should be proactive in exploring possibilities for PA to mitigate the expected physical decline, and support symptom management while undergoing palliative chemotherapy.


Depression and academic achievement among Indochinese refugee unaccompanied minors in ethnic and nonethnic placements.
Unaccompanied Indochinese refugee adolescents resettled in the United States with ethnic foster families were significantly less depressed and had higher grade-point averages than those in foster care with Caucasian families or in group homes. The ongoing presence of an adult of similar ethnicity to the adolescent appeared to mitigate against the stress of adaptation to a new country.


Identifying physician-perceived barriers to a pragmatic treatment trial in rheumatoid arthritis.
The aim of this qualitative research was to identify physician-perceived patient and clinic barriers to patient recruitment in a rheumatoid arthritis (RA) pragmatic trial of anti-tumor necrosis factor (TNF) biologic versus non-TNF biologic/Janus-Kinase inhibitor initiation after an inadequate response to methotrexate. Semistructured telephone interviews were conducted with 26 rheumatologists in March 2019. An exploratory thematic analysis approach was used to analyze the interview data. Physician perceived patient barriers to the implementation of an RA pragmatic trial. This theme covers three subthemes: (1) patients' personal barriers, (2) patients' treatment-related factors, and (3) trial-related factors (eg, patient recruitment, side effects, mode of use, etc). Physicians perceived clinic barriers interfered with the pragmatic trial enrollment from the clinic or the healthcare system perspective. This theme covered four subthemes: (1) clinic-related factors, (2) patient-related factors, (3) research personnel, and (4) facilitators (positive factors of the clinic). Our results from the inductive thematic analysis will help researchers understand the key patient and clinic/system factors/barriers that may influence pragmatic RA trial implementation. The themes suggest there are factors that can be modified (eg, coordinator effort needed, effective patient recruitment during clinic visits, provider engagement) and challenges to overcome (patient insurance status, busy clinic flow, and space issues including limited number of patient rooms). In summary, these themes provide a basis for our and other research teams to develop clinic-centered and patientcentered strategies to implement a pragmatic RA trial.


Orthogonal Supramolecular Assembly Triggered by Inclusion and Exclusion Interactions with Cucurbit[7]uril for Photocatalytic H2 Evolution.
The fabrication of efficient and convenient photocatalytic H2 evolution systems is a fascinating research topic in the field of solar energy conversion. A ternary self-assembled photocatalytic H2 evolution system was fabricated through supramolecular host-guest chemistry. The system consisted of the H2 evolution catalyst [Co(dmgH)2 (4-ppy)2 ]NO3 (1; dmgH2 =dimethylglyoxime, 4-ppy=4-phenylpyridine) and the photosensitizer Eosin Y (EY) assembled with the macrocyclic compound cucurbit[7]uril (CB[7]) to form the 1@CB[7]/EY complex through inclusion and exclusion interactions, respectively. The synchronous self-assembly drives an orthogonal arrangement of the 1@CB[7]/EY system. The inclusion complex 1@CB[7] was successfully characterized by 1 H NMR spectroscopy and single-crystal XRD. The exclusion process of CB[7] with EY was identified by NMR titration and the optimized geometry of the exclusion structure was determined by DFT calculations. The use of CB[7] resulted in a 6-fold increase in turnover number, a 3-fold increase in turnover frequency, and a 3-fold extension of lifetime for photocatalytic H2 evolution as compared with the system in the absence of CB[7]. The improvement of the light-driven H2 evolution activity was ascribed to the ability of CB[7] to link the photosensitizer and catalyst.


Bathing in Terminal Care of Cancer Patients and Its Relation to Perceptions of a "Good Death": A Nationwide Bereavement Survey in Japan.
Bathing in a tub is integral to Japanese culture. It improves palliative care patients' symptoms and may improve quality of life. This study aimed to determine the prevalence and impressions of bathing for terminally ill cancer patients and its relations to the evaluations of perceived end-of-life care and achievement of a good death. This was a cross-sectional, anonymous, self-report questionnaire survey. The questionnaire for this study was sent to bereaved family members who had lost loved ones in 14 general hospitals and 187 palliative care wards in Japan. The bereaved family members of the patients who had actually bathed were asked about their impression of bathing. The short version of the Good Death Inventory (GDI) and the Care Evaluation Scale were used to evaluate "achievement of a good death." In total, 1819 surveys were sent between July and September 2018 to bereaved family members of patients who had died between February 2014 and January 2018 in 14 general hospitals and 187 palliative care wards in Japan. Overall 885 questionnaires (valid response rate 48%) returned by bereaved family members were analyzed. Overall, 85% of bereaved family members of patients who bathed evaluated the experience positively, 86% reported that the patient's face seemed to become calm after the bath, and 28% of bereaved family members whose loved one had not bathed reported regretting it. The total GDI score for the bereaved family's desired death was 82.7 ± 13.0 for the bathing group and 75.4 ± 15.7 for the no bathing group, a significant difference (effect size = 0.52, p < 0.01). Bathing before death was evaluated positively and was associated with the achievement of a good death.


Antiretroviral chemotherapy against human immunodeficiency virus (hiv) infection: perspective for therapy of hepatitis B virus infection.
It has been shown that the replication of human immunodeficiency virus (HIV) can be suppressed in the clinical setting by drugs based on the selective in vitro antiretroviral activity. We now know that such antiretroviral chemotherapy can confer prolonged survival and improved quality of life in patients with advanced HIV infection. Hepatitis B virus (HBV) resembles retroviruses, including HIV, in several respects. In particular, both viruses contain reverse transcriptase and replicate through an RNA intermediate. Thus, emerging knowledge of the replicative cycle of HIV may provide a perspective for antiviral therapy of diseases caused by HBV.


Earthworm coelomocytes in vitro.
Contamination and low viability of earthworm coelemocytes in tissue culture have delayed in vitro studies. Using penicillin, streptomycin, tetracycline and Amphotericin B, Lumbricus terrestis coelomocytes were maintained viable and uncontaminated for 10 days at 15degreesC in medium L-15 supplemented with 5 to 10% fetal bovine serum. The coelomocytes survived for at least 10 days with 85% viability as assessed by trypan blue exclusion assays and phagocytosis of heat-killed yeast. Studies on the thymidine uptake, however, were negative. With the involvement of coelomocytes in tissue graft rejection, in vitro techniques can now be applied to study their capacity in the immune response.


Uterine torsion and metabolic abnormalities in a cat with a pyometra.
A 6-year-old, intact female, Russian Blue cat was presented with abdominal distention, vaginal discharge, and a firm tubular structure palpable in the mid-abdomen. Serum biochemical abnormalities included hyperkalemia, hyponatremia, and azotemia. Exploratory laparotomy revealed a pyometra with uterine torsion; an ovariohysterectomy was performed.


Bradykinin B2 type receptor activation regulates fluid and electrolyte transport in the rabbit kidney.
Bradykinin is an important autacoid produced in the kidney, regulating both renal function and blood pressure. In vivo studies in anesthetized rabbits, revealed that BK induced diuresis (UV), natriuresis (U(Na)V) and was not associated with renal hemodynamic changes. These diuretic and natriuretic effects were blocked by the BK-B2 antagonist HOE-140. BK also inhibits vasopressin (AVP)-stimulated water flow (L(p)) in microperfused rabbit cortical collecting ducts (rCCD), in a concentration-dependent fashion, consistent with its in vivo diuretic effects. BK-B1 antagonist Leu8-des-Arg9-BK did not alter the effect of BK on Lp, but HOE-140 completely blocked the inhibitory effects of BK on Lp. While BK did not increase [Ca2+]i in fura-2 loaded freshly microdissected rCCD, BK increased [Ca2+]i in immortalized cultured rCCD cells demonstrating different signaling mechanisms are activated by BK in microdissected versus cultured rCCD. In microperfused rCCD, neither the protein kinase C inhibitor staurosporine nor the phospholipase C (PLC) inhibitor U-73,122 attenuated the BK response arguing against activation of PLC/PKC by BK in rCCD. We conclude: (1) BK induces UV and U(Na)V by a BK-B(2) receptor; (2) BK inhibits AVP-stimulated Lp by a BK-B2 receptor suggesting that its effects on Lp are not via a PLC/PKC; (3) finally, BK raises [Ca2+]i in rCCD cells by a BK-B2 receptor mechanism.


Design, Preparation, and Evaluation of a Novel Elastomer with Bio-Based Diethyl Itaconate Aiming at High-Temperature Oil Resistance.
A novel elastomer poly(diethyl itaconate-co-butyl acrylate-co-ethyl acrylate-co-glycidyl methacrylate) (PDEBEG) was designed and synthesized by redox emulsion polymerization based on bio-based diethyl itaconate, butyl acrylate, ethyl acrylate, and glycidyl methacrylate. The PDEBEG has a number average molecular weight of more than 200,000 and the yield is up to 96%. It is easy to control the glass transition temperature of the PDEBEG, which is ranged from -25.2 to -0.8 °C, by adjusting the monomer ratio. We prepared PDEBEG/CB composites by mixing PDEBEG with carbon black N330 and studied the oil resistance of the composites. The results show that the tensile strength and the elongation at break of the composites with 10 wt% diethyl itaconate can reach up to 14.5 MPa and 305%, respectively. The mechanical properties and high-temperature oil resistance of the composites are superior to that of the commercially available acrylate rubber AR72LS.


Rapid reformation of the thick chromosome fiber upon completion of RNA synthesis at the Balbiani ring genes in Chironomus tentans.
We have studied the ultrastructure of the Balbiani ring genes in Chironomus tentans during treatment with the RNA synthesis inhibitor DRB (5,6-dichloro-1-beta-D-ribofuranosyl-benzimidazole). This nucleoside analogue blocks transcription at or near the initiation site but does not interfere with the elongation and termination processes. In the ordinary active state the Balbiani ring genes display a 5 nm chromosome fiber, carrying densely distributed, growing ribonucleoprotein particles (Andersson et al., 1980). When the transcriptional activity declines, a 10 nm fiber can be observed between sparsely distributed RNA polymerases. Furthermore, after passage of the last RNA polymerase the 10 nm fiber can be seen as well as its gradual packing into a 25 nm thick fiber. Thus, the active chromosome fiber is rapidly packed into higher order structures when the fiber is not directly involved in transcription. The formation of the thick fiber does not require that the gene along its entire length is devoid of active RNA polymerases. The thick fiber can again be mobilized for transcription, since in reversion experiments the BR genes appear as ordinary active genes with an extended nucleofilament and densely packed nascent transcription products. The dynamic behaviour of the chromosome fiber during transcription is discussed as well as the packing and unpacking of a gene into higher order structures.


MEA Recordings and Cell-Substrate Investigations with Plasmonic and Transparent, Tunable Holey Gold.
Microelectrode arrays are widely used in different fields such as neurobiology or biomedicine to read out electrical signals from cells or biomolecules. One way to improve microelectrode applications is the development of novel electrode materials with enhanced or additional functionality. In this study, we fabricated macroelectrodes and microelectrode arrays containing gold penetrated by nanohole arrays as a conductive layer. We used this holey gold to optically excite surface plasmon polaritons, which lead to a strong increase in transparency, an effect that is further enhanced by the plasmon's interaction with cell culture medium. By varying the nanohole diameter in finite-difference time domain simulations, we demonstrate that the transmission can be increased to above 70% with its peak at a wavelength depending on the holey gold's lattice constant. Further, we demonstrate that the novel transparent microelectrode arrays are as suitable for recording cellular electrical activity as standard devices. Moreover, we prove using spectral measurements and finite-difference time domain simulations that plasmonically induced transmission peaks of holey gold red-shift upon sensing medium or cells in close vicinity (<30 nm) to the substrate. Thus, we establish plasmonic and transparent holey gold as a tunable material suitable for cellular electrical recordings and biosensing applications.


Establishing a multivariate clinical laboratory data base.
A regional or hospital-based "reference" value study is well within the range of every clinical laboratory. A program is described that samples one to two "health" subjects each working day under tightly controlled conditions. Sixty-seven variables are tested simultaneously to provide univariate age and sex ranges, and variance/covariance matrices from which associated correlation coefficients are obtained. This ongoing "reference" value program offers essential information for both univariate and multivariate interpretations along with validation and quality control for certain methods within the clinical laboratory.


Studies on the sorption behavior and plant uptake of pesticides in Japanese soils.
To estimate pesticide residue levels in succeeding crops based on those in soils, the relationship between pesticide concentrations in komatsuna (Brassica rapa var. perviridis) and the concentrations extracted sequentially from soils using water and acetone was investigated. The concentrations of many pesticides in komatsuna shoots showed higher positive correlation with water-extractable concentrations (C W) than total-extractable concentrations in soils, so that the C W was available for evaluating the phytoavailability of pesticides in the soil. As a result of examining the dissipation behavior of the C W, the dissipation of the C W was able to be predicted by considering time-dependent soil sorption, which could be estimated using the sorption coefficients (K d) measured by a standard batch method. Furthermore, the present study showed that the properties of soil organic carbon such as black carbon content and the molecular structure of pesticides were important for estimating the K d values more accurately.


Stage-Dependent Expression of Protein Gene Product 9.5 in Donkey Testes.
Molecular markers can be used to identify and isolate specific developmental stages of germ cells and Leydig cells. Protein gene product (PGP)9.5 expression in spermatogonia and Leydig cells has been reported in several species. The stages of spermatogonia and Leydig cells expressing PGP9.5 vary depending on the species and reproductive stages. Thus, the objectives of this study were (1) to identify the localization of PGP9.5 in donkey testicular cells, and (2) to compare the expression patterns of PGP9.5 in donkey testicular cells between pre- and post-pubertal stages. Testes samples were collected following the routine field castration of six donkeys. Western blotting was performed to verify the cross-reactivity of the rabbit anti-human PGP9.5 antibody to donkey testes. Immunofluorescence was performed to investigate the expression pattern of PGP9.5 in testicular tissues at different reproductive stages. In Western blotting, the protein band of the PGP9.5 antibody appeared at approximately 27 kDa, whereas the band was not observed in the negative control treated with normal mouse IgG. In the pre-pubertal stage, the expression of deleted in azoospermia-like (DAZL) was found in some spermatogonia in pre-pubertal testicular tissues. However, the immunolabeling of PGP9.5 in testicular tissue was not observed in the seminiferous tubules. In stages 1 and 2, spermatogonia were immunolabeled with either PGP9.5 or DAZL. In contrast, PGP9.5 and DAZL were co-immunolabeled in some of the spermatogonia in stages 3 to 8. Interestingly, some Leydig cells were immunolabeled with PGP9.5 in both pre- and post-pubertal stages. In conclusion, the PGP9.5 antibody can be used as a tool to identify and isolate spermatogonia from seminiferous tubules.


Four years' results of a prospective, randomized clinical trial comparing polytetrafluoroethylene and modified human umbilical vein for below-knee femoropopliteal bypass.
Polytetrafluoroethylene (PTFE) (Gore-Tex) and human umbilical vein (Biograft) arterial grafts were compared for below-knee femoropopliteal bypass grafting in a prospective randomized clinical trial. One hundred five patients (105 limbs) entered the trial. Seventy-six percent suffered from rest pain, ulceration, or gangrene. The median postoperative ankle-arm blood pressure index was 0.36. Twenty-three limbs had three patent tibial arteries, 46 limbs had two tibial arteries, 31 limbs had one patent artery, and five limbs had isolated popliteal segments. Thirty-four percent were repeat operations. Fifty-five patients were allocated to receive PTFE grafts and 50 to receive human umbilical vein grafts. The two groups were comparable as to preoperative risk factors and operative and postoperative treatment. During the first 4 years (maximum 1609 days) 40 PTFE grafts and 24 umbilical veins occluded. At 1 year the PTFE patency rate was 53% and at 4 years was 22%. For umbilical vein the corresponding figures were 74% and 42% (p = 0.005, Gehan test). During follow-up the incidence of PTFE failure was on the average 2.1 times higher than that of umbilical vein failure (95% confidence limits 1.2 to 3.4).


Computer-aided identification of novel protein targets of bisphenol A.
The xenoestrogen bisphenol A (2,2-bis-(p-hydroxyphenyl)-2-propane, BPA) is a known endocrine-disrupting chemical used in the fabrication of plastics, resins and flame retardants, that can be found throughout the environment and in numerous every day products. Human exposure to this chemical is extensive and generally occurs via oral route because it leaches from the food and beverage containers that contain it. Although most of the effects related to BPA exposure have been linked to the activation of the estrogen receptor (ER), the mechanisms of the interaction of BPA with protein targets different from ER are still unknown. Therefore, the objective of this work was to use a bioinformatics approach to identify possible new targets for BPA. Docking studies were performed between the optimized structure of BPA and 271 proteins related to different biochemical processes, as selected by text-mining. Refinement docking experiments and conformational analyses were carried out using LigandScout 3.0 for the proteins selected through the affinity ranking (lower than -8.0kcal/mol). Several proteins including ERR gamma (-9.9kcal/mol), and dual specificity protein kinases CLK-4 (-9.5kcal/mol), CLK-1 (-9.1kcal/mol) and CLK-2 (-9.0kcal/mol) presented great in silico binding affinities for BPA. The interactions between those proteins and BPA were mostly hydrophobic with the presence of some hydrogen bonds formed by leucine and asparagine residues. Therefore, this study suggests that this endocrine disruptor may have other targets different from the ER.


Dystrophic chick brain lacks a particular neurotrophic factor.
Extracts from normal embryonic chick brain act as "trophic" agents in the newt blastemata assay where they stimulate the incorporation of amino acids into protein. Equivalent extracts prepared from the brains of dystrophic (am/am) chick embryos are apparently devoid of any equivalent activity.


Development of food variety in children.
Eating a variety of foods is essential to achieve adequate coverage of macro- and micronutrient needs. We expose here how eating habits for a variety of foods develop in childhood, from early infancy on. Preferences for specific flavours might develop early, through milk-related flavour exposures. Breastfeeding favours the acquisition of a taste for a variety of foods. At introduction of solid foods, food preferences develop thanks to repeated exposures to a variety of foods. The persistence of these early influences is still unknown. During the third year of life, most children enter a neophobic phase during which previously liked foods are no longer accepted and introduction of new foods becomes difficult. However, habits of eating a variety of foods acquired before the neophobic phase track further on into childhood, adolescence and early adulthood. This underlines the importance of promoting the access to a variety of foods in early childhood. However, beyond the nutritional advantage of eating a varied diet, could this present any drawbacks? Providing a variety of foods generally stimulates food intake and thereby might favour obesity. More research is needed to understand the link between variety and obesity, which might be food-group dependant.


Improved purification of native meningococcal porin PorB and studies on its structure/function.
The outer membrane protein PorB of Neisseria meningitidis is a pore-forming protein which has various effects on eukaryotic cells. It has been shown to (1) up-regulate the surface expression of the co-stimulatory molecule CD86 and of MHC class II (which are TLR2/MyD88 dependent and related to the porin's immune-potentiating ability), (2) be involved in prevention of apoptosis by modulating the mitochondrial membrane potential, and (3) form pores in eukaryotic cells. As an outer membrane protein, its native trimeric form isolation is complicated by its insoluble nature, requiring the presence of detergent throughout the whole procedure, and by its tight association with other outer membrane components, such as neisserial LOS or lipoproteins. In this study, an improved chromatographic purification method to obtain an homogeneous product free of endotoxin and lipoprotein is described, without loss of any of the above-mentioned properties of the porin. Furthermore, we have investigated the requirement of the native trimeric structure for the porin's activity. Inactivation of functional PorB trimers into non-functional monomers was achieved by incubation on ice. Thus, routine long- and medium-term storage at low temperature may be a cause of porin inactivation.


Anatomic and reverse shoulder arthroplasty in patients 70 years of age and older: a comparison cohort at early to midterm follow-up.
Reverse shoulder arthroplasty (RSA) has gained popularity in elderly patients because of its limited reliance on rotator cuff function and high survivorship rates. However, although there are theoretical advantages of RSA over anatomic total shoulder arthroplasty (TSA) in elderly patients, there is little data to guide surgeons on implant selection in this population. Patients were identified from our prospectively collected shoulder arthroplasty registry. We included patients between the age of 50 and 89 years who underwent primary TSA for osteoarthritis with intact rotator cuff or primary RSA for cuff tear arthropathy. The minimum and mean clinical follow-up was 2 and 3.1±1.3 years, respectively. Four patient groups were formed for analysis: (1) TSA age 50-69 years (n=274), (2) TSA age 70-89 years (n=208), (3) RSA age 50-69 years (n=81), and (4) RSA age 70-89 years (n=104). We evaluated age group differences in pain, Constant score, American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) score, patient satisfaction, complications, and revisions. All groups showed significant improvements from preoperative to final follow-up for all outcome measures (P < .001). Visual analog scale for pain average score decreased from 5.8 preoperatively to 1.1, with no significant differences between groups (TSA P = .180; RSA P = .103). Final ASES scores and improvement from preoperative ASES score between the age groups were not significantly different (TSA P = .520; RSA P = .065). There were no significant differences in outcomes between TSA in patients older than 70 years vs. patients younger than 70 years (all P > .05); however, older RSA patients reported better function during activities of daily living (P = .020) than their younger counterparts. Patients undergoing TSA had a lower revision rate of 3.9% compared with 8.1% in the RSA group (P = .043). TSA and RSA are reliable procedures for patients older than 70 years, and have comparable results to their respective patient cohorts younger than 70 years. Although some surgeons anecdotally advocate for RSA in patients older than 70 years with primary osteoarthritis and an intact rotator cuff, we found no difference in outcomes for TSA based on our age cutoff. Given satisfactory results following TSA in patients 70 years of age and older, we do not routinely perform RSA for primary osteoarthritis with an intact rotator cuff solely based on age. Further studies and longer follow-up are needed to determine the optimal implant selection for elderly patients with primary osteoarthritis.


Complications after esophagogastrectomy using stapling instruments.
We studied 195 patients undergoing esophageal resection using stapling instruments during a period of over 8.5 years. Of these, 178 (91.2%) underwent operation for malignant disease. Operative death occurred in 19 patients (9.7%). Nine (4.6%) postoperative complications, excluding stricture formation, were related to the use of stapling instruments, including two operative deaths (1.0%). Anastomotic leaks and gastrotomy staple line leaks were the most common complications (four each). In 7 patients (3.6%) the circular stapler tore the esophagus; anastomotic leaks subsequently developed in 43% of these patients. After we began oversewing gastrotomy staple lines in 1984, we experienced only one gastrotomy leak due to a technical error. Postoperative stricture formation occurred soon after resection and responded well to one or two dilations. It is better to err on the side of choosing too small a stapling head when performing an esophageal anastomosis because this may reduce the incidence of leaks, and further strictures are easily dealt with.


Nurse Practitioners' Comfort in Treating Work-Related Injuries in Adolescents.
This study examined nurse practitioners' (NPs) previous experiences and comfort levels in treating adolescents with work-related injuries in two states where NPs have statutory authority to treat work-related injuries. The authors surveyed all actively licensed NPs in Washington and Oregon (N = 4,849). Factors associated with NPs' previous experiences and comfort in treating adolescents with work-related injuries were identified using modified Poisson regression. Less than a quarter of respondents (21.1%, n = 225) reported having ever treated an adolescent for a work-related injury. Nearly half (43.6%) of respondents reported being uncomfortable or very uncomfortable in treating adolescents with work-related injuries. Previous experience and male gender were associated with greater likelihood of feeling comfortable (p < .01). Nurse practitioners serve as primary care providers for adolescents who may experience work-related injuries. This study documents the need for developing educational and outreach efforts to better prepare NPs to treat adolescents' work-related injuries.


Narrow diameter implants for mandibular denture retention.
Narrow diameter implants are a lower cost alternative to conventional implants and are used to retain mandibular dentures. The experiences at a dental school predoctoral clinic are reviewed. The cumulative success rate for 626 fixtures placed in a six-year period is 92.6 percent with high patient satisfaction. Narrow diameter implants are a useful adjunct in the long-term management of edentulous patients.


Blockade of the high-affinity noradrenaline transporter (NET) by the selective 5-HT reuptake inhibitor escitalopram: an in vivo microdialysis study in mice.
Escitalopram, the S(+)-enantiomer of citalopram is the most selective 5-HT reuptake inhibitor approved. Although all 5-HT selective reuptake inhibitors (SSRIs) increase extracellular levels of 5-HT ([5-HT](ext)). some also enhance, to a lesser extent, extracellular levels of noradrenaline ([NA](ext)). However, the mechanisms by which SSRIs activate noradrenergic transmission in the brain remain to be determined. This study examined the effects of escitalopram, on both [5-HT](ext) and [NA](ext) in the frontal cortex (FCx) of freely moving wild-type (WT) and mutant mice lacking the 5-HT transporter (SERT(-/-)) by using intracerebral microdialysis. We explored the possibilities that escitalopram enhances [NA](ext), either by a direct mechanism involving the inhibition of the low- or high-affinity noradrenaline transporters, or by an indirect mechanism promoted by [5-HT](ext) elevation. The forced swim test (FST) was used to investigate whether enhancing cortical [5-HT](ext) and/or [NA](ext) affected the antidepressant-like activity of escitalopram. In WT mice, a single systemic administration of escitalopram produced a significant increase in cortical [5-HT](ext) and [NA](ext). As expected, escitalopram failed to increase cortical [5-HT](ext) in SERT(-/-) mice, whereas its neurochemical effects on [NA](ext) persisted in these mutants. In WT mice subjected to the FST, escitalopram increased swimming parameters without affecting climbing behaviour. Finally, escitalopram, at relevant concentrations, failed to inhibit cortical noradrenaline and 5-HT uptake mediated by low-affinity monoamine transporters. These experiments suggest that escitalopram enhances, although moderately, cortical [NA](ext) in vivo by a direct mechanism involving the inhibition of the high-affinity noradrenaline transporter (NET).


Discovery, optimization and evaluation of 1-(indolin-1-yl)ethan-1-ones as novel selective TRIM24/BRPF1 bromodomain inhibitors.
TRIM24 (tripartite motif-containing protein 24) and BRPF1 (bromodomain and PHD finger containing protein 1) are epigenetics "readers" and potential therapeutic targets for cancer and other diseases. Here we describe the structure-guided design of 1-(indolin-1-yl)ethan-1-ones as novel TRIM24/BRPF1 bromodomain inhibitors. The representative compound 20l (Y08624) is a new TRIM24/BRPF1 dual inhibitor, with IC50 values of 0.98 and 1.16 μM, respectively. Cellular activity of 20l was validated by viability assay in prostate cancer (PC) cell lines. In PC xenograft models, 20l suppressed tumor growth (50 mg/kg/day, TGI = 53%) without exhibiting noticeable toxicity. Compound 20l represents a versatile starting point for the development of more potent TRIM24/BRPF1 inhibitors.


Regulation of pea mitochondrial pyruvate dehydrogenase complex activity: inhibition of ATP-dependent inactivation.
In contrast to the pyruvate dehydrogenase complex (PDC) from animal mitochondria, our in situ and in vitro studies indicate that the ATP:ADP ratio has little or no effect in regulating the mitochondrial pyruvate dehydrogenase complex from green pea seedlings. Pyruvate was a competitive inhibitor of ATP-dependent inactivation (Ki = 59 microM), while the PDC had a Km for pyruvate of microM. Thiamine pyrophosphate, the coenzyme for the pyruvate dehydrogenase (PDH) component of the complex, did not inhibit ATP-dependent inactivation when used alone but it enhanced inhibition by pyruvate. As such, thiamine pyrophosphate was a competitive inhibitor (Ki = 130 nM) of ATP-dependent inactivation. A model is proposed for the pyruvate plus thiamine pyrophosphate inhibition of ATP-dependent inactivation of the pyruvate dehydrogenase complex in which pyruvate exerts its inhibition of inactivation by altering or protecting the protein substrate from phosphorylation and not by directly inhibiting PDH kinase.


Easily Applicable Predictive Score for Differential Diagnosis of Prefibrotic Primary Myelofibrosis from Essential Thrombocythemia.
Essential thrombocythemia (ET) and prefibrotic primary myelofibrosis (prePMF) initially have a similar phenotypic presentation with thrombocytosis. The aim of our study was to determine significant clinical-laboratory parameters at presentation to differentiate prePMF from ET as well as to develop and validate a predictive diagnostic prePMF model. This retrospective study included 464 patients divided into ET (289 pts) and prePMF (175 pts) groups. The model was built using data from a development cohort (229 pts; 143 ET, 86 prePMF), which was then tested in an internal validation cohort (235 pts; 146 ET, 89 prePMF). The most important prePMF predictors in the multivariate logistic model were age ≥ 60 years (RR = 2.2), splenomegaly (RR = 13.2), and increased lactat-dehidrogenase (RR = 2.8). Risk scores were assigned according to derived relative risk (RR) for age ≥ 60 years (1 point), splenomegaly (2 points), and increased lactat-dehidrogenase (1 point). Positive predictive value (PPV) for pre-PMF diagnosis with a score of ≥points was 69.8%, while for a score of ≥3 it was 88.2%. Diagnostic performance had similar values in the validation cohort. In MPN patients with thrombocytosis at presentation, the application of the new model enables differentiation of pre-PMF from ET, which is clinically relevant considering that these diseases have different prognoses and treatments.


Urea transport in kidney brush-border membrane vesicles from an elasmobranch, Raja erinacea.
Marine elasmobranch fishes maintain high urea concentrations and therefore must minimize urea loss to the environment in order to reduce the energetic costs of urea production. Previous studies have identified a facilitated urea transporter in the kidney of the dogfish. We examined mechanisms of urea transport in the kidney of the little skate Raja erinacea using an isolated brush-border membrane vesicle preparation. Urea uptake by brush-border membrane vesicles is by a phloretin-sensitive, non-saturable uniporter in the dorsal section and a phloretin-sensitive, sodium-linked urea transporter (Km = 0.70 mmol l(-1), Vmax = 1.18 micromol h(-1) mg(-1) protein) in the ventral section of the kidney. This provides evidence for two separate urea transporters in the dorsal versus ventral sections of the kidney. We propose that these two mechanisms of urea transport are critical for renal urea reabsorption in the little skate.


A randomized study of single agent vs combination chemotherapy in FIGO stages IIB, III and IV ovarian adenocarcinoma.
From 1977 until 1980, 179 patients with newly diagnosed FIGO stages IIB, III or IV ovarian adenocarcinoma were randomized in a two-armed clinical trial: dihydroxybusulfan (B) 600 mg/m2 p.o. for 4-6 weeks q 12 weeks or cyclophosphamide (C) 150 mg/m2 p.o. for 7 days q 4 weeks vs a combination of cyclophosphamide 400 mg/m2 i.v., doxorubicin 30 mg/m2 and 5-fluorouracil 400 mg/m2 i.v., days 1 and 8 q 4 weeks (CAF). In addition, stage IIB patients were randomised to +/- pelvic irradiation. The patients were stratified according to anatomic stage. The treatment groups were comparable with respect to performance status, age and histology. Twenty-three patients were excluded because of protocol violation, leaving 156 patients evaluable for survival with an observation period of 3-6 yr. Twenty patients were in stage IIB, while the remaining 136 patients were classified as stages III and IV. No statistically significant difference was found in survival or response between the two single agents. The overall median response rate (single drug: 27%; CAF: 47%) and the median response duration (single drug: 5 months; CAF: 10 months) were significantly superior for the CAF group compared to the single agent group. No statistical difference in median survival was observed between single-drug treatment (12 months) and CAF (14 months), despite the fact that responders lived significantly longer than nonresponders (17 vs 10 months). In stage IIB patients receiving chemotherapy no benefit of pelvic irradiation was found. Thirty patients (19%) underwent second-look laparotomy, with 15 (50%) being completely free of disease. So far only one patient (7%) has relapsed. Two additional patients, who had microscopic disease removed at second-look laparotomy, seem to have been rescued by this procedure.


Behavioral and biochemical changes induced by lithium and L-tryptophan in muricidal rats.
Lithium (0.5--12 meq/kg) and L-tryptophan (100--800 mg/kg) inhibited the muricidal (mouse killing) response in isolated, male, Long Evans rats and did so both in an acute (single dose) and on an longer-term intraperitoneal treatment basis. The response was dose-dependent. There was no concomitant motor impairment at doses effective in inhibiting the muricidal response. Plasma lithium levels were positively correlated with the percentage inhibition of muricidal behavior. When lithium and L-tryptophan were administered in combination in their smallest effective doses, the behavioral interaction was synergistic in the acute and addictive in the longer-term treatment. The effects of pharmacological treatment on the inhibition of muricidal behavior were: lithium and L-tryptophan greater than L-tryptophan greater than - lithium. The results of biochemical assays showed that these compounds fore- and hindbrain serotonin turnover. The biochemical action of lithium and L-tryptophan in combination on brain serotonergic pathways was again clearly more potent than that which occurred after treatment with either lithium or L-tryptophan alone. The magnitude of the biochemical changes paralleled those of psychopharmacological changes. These data show an interaction between lithium and L-tryptophan both in the repression of aggressive behavior in rats and in the alteration of centrally acting serotonergic function. These data further elucidate a mechanism of action through central serotonergic function for a psychotherapeutic agent, lithium, and for aggressive behavior, muricide.


Treatment of endophthalmitis with and without pars plana vitrectomy.
Two series of patients with endophthalmitis were compared. In the group treated with antibiotics or fungistatics, only 1 eye (4.3%) could be salvaged, whereas in the group with pars plana vitrectomy and antibiotics or fungistatics, 7 eyes (33%) had adequate visual acuity afterwards.


Role of ultrasonography in detection of renal artery pseudoaneurysm caused by retroperitoneal malignant peripheral nerve sheath tumor in a patient with neurofibromatosis type 1.
Malignant peripheral nerve sheath tumors (MPNSTs) are extremely uncommon neoplasms, predominantly seen within the deep soft tissues of the extremities, in close proximity to the nerve trunks. Retroperitoneal MPNSTs are exceedingly rare, usually seen in association with neurofibromatosis type 1 (NF-1), and often result from malignant degeneration of a plexiform neurofibroma. These tumors are highly malignant and the prognosis is worsened if they occur in association with NF-1. Metastasis is not uncommon, but local invasion by these tumors is rarely reported. Renal artery pseudoaneurysms are mostly iatrogenic and rarely result from invasion by retroperitoneal neoplasms. Ultrasonography is a valuable tool in early diagnosis of these neoplasms and vascular complications, particularly in emergency cases requiring immediate operative intervention. To the best of our knowledge, no case of renal artery pseudoaneurysm caused by retroperitoneal MPNST has been reported to date. We present a case of a middle-aged female with Von Recklinghausen disease, complaining of sudden onset of severe abdominal pain, where ultrasound accurately diagnosed renal artery pseudoaneurysm caused by a large retroperitoneal MPNST, and who was later treated by radical excision of the tumor and nephrectomy.


Inhibition of cigarette smoke-induced oedema in the nasal mucosa by capsaicin pretreatment and a substance P antagonist.
The effect of cigarette smoke on vascular permeability in the rat nasal mucosa was studied using the Evans blue extravasation method. Exposure to smoke from cigarettes induced a significant extravasation of Evans blue in the nasal mucosa of normal rats, suggesting an increased vascular permeability to plasma proteins. The oedema response was correlated to tar, nicotine and vapour phase components in the smoke. The smoke-induced permeability effect was abolished in rats pretreated neonatally with capsaicin. Also, systemic or local pretreatment with [D-Arg, D-Pro, D-Trp, Leu]Substance P, a substance P antagonist, inhibited the permeability response to cigarette smoke. Insertion of a glass-fibre filter, which removes the particulate phase of the smoke (including nicotine), did not significantly reduce the permeability response. The present findings suggest that the smoke-induced oedema in the rat nasal mucosa is not caused by nicotine but by vapour-phase irritants, which activate capsaicin-sensitive C-fibre afferents. These neurons then release agents such as substance P or a related tachykinin which increase permeability to plasma proteins.


A Super-resolution Guided Network for Improving Automated Thyroid Nodule Segmentation.
A thyroid nodule is an abnormal lump that grows in the thyroid gland, which is the early symptom of thyroid cancer. In order to diagnose and treat thyroid cancer at the earliest stage, it is desired to characterize the nodule accurately. Ultrasound thyroid nodules segmentation is a challenging task due to the speckle noise, intensity heterogeneity, low contrast and low resolution. In this paper, we propose a novel framework to improve the accuracy of thyroid nodules segmentation. Different from previous work, a super-resolution reconstruction network is firstly constructed to upscale the resolution of the input ultrasound image. After that, our proposed N-shape network is utilized to perform the segmentation task. The guidance of super-resolution reconstruction network can make the high-frequency information of the input thyroid ultrasound image richer and more comprehensive than the original image. Our N-shape network consists of several atrous spatial pyramid pooling blocks, a multi-scale input layer, a U-shape convolutional network with attention blocks and a proposed parallel atrous convolution(PAC) module. These modules are conducive to capture context information at multiple scales so that semantic features can be fully utilized for lesion segmentation. Especially, our proposed PAC module is beneficial to further improve the segmentation by extracting high-level semantic features from different receptive fields. We use the UTNI-2021 dataset for model training, validating and testing. The experimental results show that our proposed method achieve a Dice value of 91.9%, a mIoU value of 87.0%, a Precision value of 88.0%, a Recall value 83.7% and a F1-score value of 84.3%, which outperforms most state-of-the-art methods. Our method achieves the best performance on the UTNI-2021 dataset and provides a new way of ultrasound image segmentation. We believe that our method can provide doctors with reliable auxiliary diagnosis information in clinical practice.


Mapping of deoxydi- and trinucleotides liberated by the action of endonucleases from the silkworm and Aspergillis oryzae.
Both silkworm nuclease and nuclease O of Aspergillus oryzae mycelia hydrolyse DNA endolytically to di- and trinucleotides terminating in 5'-phosphate. These oligonucleotides were fractionated first be DEAE-cellulose chromatography with 7 M urea into the respective isoplithic groups and then analysed for the composition and isomerism: each group was labeled 5'-terminally by the [gamma-32P]ATP-polynucleotide kinase reaction and then electrophoresed monodimensionally for the dinucleotides and two-dimensionally for the di- and trinucleotides mixtures, respectively, followed by elution and digestion with snake venom exonuclease. Both nucleases gave rather similar simple maps in which all sixteen dinucleotides and almost all the possible trinucleotides were identified, indicating their random mode of actions.


Tumour-stroma ratio and 5-year mortality in gastric adenocarcinoma: a systematic review and meta-analysis.
Tumour-stroma ratio (TSR) is a novel potential prognostic factor in cancers and based on the proportions of stroma and tumour area. The prognostic value of TSR in gastric cancer is incompletely known. The aim of this study was to estimate prognostic significance of TSR in gastric adenocarcinoma. A search of PubMed (MEDLINE), Web of Science, EMBASE, Cochrane and Scopus databases was performed. A meta-analysis was conducted on five-year survival in gastric cancer patients using inverse variance random-effects methods. The literature search yielded 5329 potential titles, of which a total of seven studies were eligible. Results of six studies including a total of 1779 patients were pooled in the meta-analysis. Only 23 (1.3%) of the patients received neoadjuvant therapy. All six studies had a cut-off of 50% for the proportion of stroma when dividing the patients into low- and high stroma groups. Low TSR (high amount of stroma) was strongly associated with increased five-year mortality (hazard ratio 2.19, 95% CI 1.69-2.85). In conclusion, TSR is a strong prognostic factor in gastric cancer. It could be used to estimate prognosis of gastric cancer patients not receiving neoadjuvant chemotherapy. Further studies including patients receiving neoadjuvant therapy are recommended.


Somatic CNV Detection by Single-Cell Whole-Genome Sequencing in Postmortem Human Brain.
The evidence for a role of somatic mutations, including copy-number variants (CNVs), in neurodegeneration has increased in the last decade. However, the understanding of the types and origins of these mutations, and their exact contributions to disease onset and progression, is still in its infancy. The use of single-cell (or nuclear) whole-genome sequencing (scWGS) has emerged as a powerful tool to answer these questions. In the present chapter, we provide laboratory and bioinformatic protocols used successfully in our lab to detect megabase-scale CNVs in single cells from multiple system atrophy (MSA) human postmortem brains, using immunolabeling prior to selection of nuclei for whole-genome amplification (WGA). We also present an unpublished comparison of scWGS generated from the same control substantia nigra (SN) sample, using the latest versions of popular WGA chemistries, MDA and PicoPLEX. We have used this protocol to focus on brain cell types most relevant to synucleinopathies (dopaminergic [DA] neurons in Parkinson's disease [PD] and oligodendrocytes in MSA), but it can be applied to any tissue and/or cell type with appropriate markers.


The Effect of HER2-Low Status on Pathological Complete Response and Survival in Triple-Negative Breast Cancer: A Systemic Review and Meta-Analysis.
This meta-analysis conducted a comprehensive analysis of research investigating the correlation between HER2 expression levels and treatment outcomes in early-stage triple-negative breast cancer (TNBC) patients. We systematically searched major databases for studies published up to January 01, 2023. The data from various studies examined the relationship between HER2-zero and HER2-low tumors in terms of pathological complete response (pCR) rates, disease-free survival (DFS), and overall survival (OS) outcomes. The odds ratio (OR) and 95% confidence interval (CI) by the number of events were calculated using the Mantel-Haenszel method to analyze pCR. The hazard ratio and 95% CI were calculated using the inverse variance method for DFS and OS. In all comparisons, I2 was 0% and no heterogeneity was detected. A total of 12 retrospective studies involving 4094 patients were included. Thirty-six percent of the patients were in the HER2-low group. All 12 studies were included in the pooled analysis for pCR, and there was no difference between HER2-zero and HER2-low (40% vs. 38%, respectively; pooled OR:1.01 95% CI 0.88-1.16; I2: 0%). Four studies were included in the pooled analysis for DFS and 3 in the OS analysis. DFS and OS were significantly better in the HER2-low group (pooled hazard ratio: 0.67 for DFS, 0.64 for OS). There was no difference between HER2-low and HER2-zero in terms of pCR in early-stage TNBC. However, HER2-low was found to be associated with prolonged DFS and OS. PROSPERO REGISTRATION NUMBER: CRD42023391002.


The homeless mentally ill and the need for a total care environment.
The dual conditions of homelessness and Serious mental illness are examined in a group of 132 former patients of a state hospital. A naturalistic approach was used in a six-month longitudinal Study that focused on the uniqueness and distinctiveness of a homeless existence. A more total care environment that recognizes a continuous service approach is necessary to meet the challenges presented by this population.


Simplified method for the discrimination of acute myelogenous and non-myelogenous leukemias.
Rapid discrimination of acute myelogenous and non-myelogenous leukemias is of great importance when chemotherapy is urgently needed in severely ill patients. For decades the most reliable cytochemical method for this classification is the demonstration of myeloperoxidase in blast cells [1-4, 6, 7]. We combined the simplified myeloperoxidase stain as described by Kaplow with a brief stain similar to Pappenheim's procedure or with commercially available Hemacolor rapid blood smear: this proved to be a simple staining method that permits good morphological judgment of the cells as well as reliable demonstration of peroxidase activity. This procedure takes less than 10 min using Hemacolor and can easily be done with prepared solutions without technical assistance.


Drug-likeness analysis of traditional Chinese medicines: 2. Characterization of scaffold architectures for drug-like compounds, non-drug-like compounds, and natural compounds from traditional Chinese medicines.
In order to better understand the structural features of natural compounds from traditional Chinese medicines, the scaffold architectures of drug-like compounds in MACCS-II Drug Data Report (MDDR), non-drug-like compounds in Available Chemical Directory (ACD), and natural compounds in Traditional Chinese Medicine Compound Database (TCMCD) were explored and compared. First, the different scaffolds were extracted from ACD, MDDR and TCMCD by using three scaffold representations, including Murcko frameworks, Scaffold Tree, and ring systems with different complexity and side chains. Then, by examining the accumulative frequency of the scaffolds in each dataset, we observed that the Level 1 scaffolds of the Scaffold Tree offer advantages over the other scaffold architectures to represent the scaffold diversity of the compound libraries. By comparing the similarity of the scaffold architectures presented in MDDR, ACD and TCMCD, structural overlaps were observed not only between MDDR and TCMCD but also between MDDR and ACD. Finally, Tree Maps were used to cluster the Level 1 scaffolds of the Scaffold Tree and visualize the scaffold space of the three datasets. The analysis of the scaffold architectures of MDDR, ACD and TCMCD shows that, on average, drug-like molecules in MDDR have the highest diversity while natural compounds in TCMCD have the highest complexity. According to the Tree Maps, it can be observed that the Level 1 scaffolds present in MDDR have higher diversity than those presented in TCMCD and ACD. However, some representative scaffolds in MDDR with high frequency show structural similarities to those in TCMCD and ACD, suggesting that some scaffolds in TCMCD and ACD may be potentially drug-like fragments for fragment-based and de novo drug design.


Evolution of post-traumatic cervical syringomyelia: case report.
A patient with complete post-traumatic paraplegia below T6 developed urinary problems and late secondary syringolmyelia. The concordance between the appearance of micturition difficulties and the first sensory symptoms leads us to discuss the rôle of important and repeated efforts to obtain reflex micturition, during the development of post-traumatic syringomyelia.


Microglia subtypes in acute, subacute, and chronic multiple sclerosis.
The study was designed to examine microglia morphology in early and late forms of multiple sclerosis (MS). Archival paraffin embedded tissue samples from 25 cases were examined immunohistochemically. Pío del Río Hortega reported that phagocytes in acute focal destructive CNS lesions develop from microglia with no early contribution from infiltrating monocytes. In this study, we were unable to identify the changes cited by del Río Hortega in support of his theory. Instead, myelin phagocytes in MS appear to originate chiefly from infiltrating monocytes. In 4 cases, walls composed of MHC class II antigen-positive "wall microglia" were observed at plaque margins separating demyelinated and bordering myelinated tissue. Wall microglia in 2 plaques were accompanied by AQP4-positive fiber-forming astrocytes. In chronic but not early disease MS cases, microglia were seen to interact with infiltrating monocytes to form microglial nodules of several types. Also, MHC II-positive "activated" microglia in bordering intact tissue were exceptionally prominent where there was little evidence of ongoing myelin loss. It is concluded that myelin phagocytes in MS derive entirely from infiltrating MRP14-positive monocytes and not from resident microglia and that Río Hortega's microglia play an anti-inflammatory role in MS and not the destructive role favored by the current literature.