c-Jun N-terminal kinase 3 deficiency protects axotomized retinal ganglion cells via affecting mitochondria involved apoptosis pathway.
To illustrate the isoform-specific role and mechanism of c-Jun N-terminal kinases (JNKs) in mouse optic nerve axotomy induced neurotrauma. We firstly investigated the expression of JNK1, JNK2, and JNK3 in the retinal ganglion cells (RGCs) by double-immunofluorescent staining. Then we created optic nerve axotomy model in wild type as well as JNK1, JNK2, JNK3, isoform specific gene deficiency mice. With that, we checked the protein expression profile of JNKs and its active form, and quantified the survival RGCs number by immunofluorescence staining. We further explored the molecules underlying isoform specific protective effect by real-time polymerase chain reaction (PCR) and Western blotting assay. We found that all the three isoforms of JNKs were expressed in the RGCs. Deficiency of JNK3, but not JNK1 or JNK2, significantly alleviated optic nerve axotomy induced RGCs apoptosis. We further established that expression of Noxa, a pro-apoptotic member of BH3 family, was significantly suppressed only in JNK3 gene deficiency mice. But tumor necrosis factor receptor 1 (TNFR1) and Fas, two key modulators of death receptor mediated apoptosis pathway, did not display obvious change in the expression. It is suggested that mitochondria mediated apoptosis, but not death receptor mediated apoptosis got involved in the JNK3 gene deficiency induced RGCs protection. Our study provides a novel insight into the isoform-specific role of JNKs in neurotrauma and indicates some cues for its therapeutics.


Idiopathic central precocious puberty in girls: presentation factors.
It is sometimes difficult to distinguish between premature thelarche and precocious puberty in girls who develop breasts before the age of 8 years. We evaluated the frequencies of the signs associated with breast development and the factors influencing the presentation of girls with idiopathic central precocious puberty (CPP). 353 girls monitored 0.9 +/- 0.7 year after the onset of CPP. The age at CPP was < 3 years in 2%, 3-7 years in 38% and 7-8 years in 60% of cases. Pubic hair was present in 67%, growth rate greater than 2 SDS in 46% and bone age advance greater than 2 years in 33% of cases. Breast development was clinically isolated in 70 (20%) cases. However, only 31 of these (8.8% of the population) had a prepubertal length uterus and gonadotropin responses to gonadotropin releasing hormone and plasma estradiol. The clinical picture of CPP became complete during the year following the initial evaluation.25% of cases were obese. The increase in weight during the previous year (3.7 +/- 1.4 kg) and body mass index were positively correlated with the statural growth and bone age advance (P < 0.0001). There was no relationship between the clinical-biological presentation and the age at puberty, the interval between the onset of puberty and evaluation, or the presence of familial CPP. The variation in presentation of girls with CPP does not depend on their age, interval between the onset and evaluation, or familial factors. This suggests that there are degrees of hypothalamic-pituitary-ovarian activation that are not explained by these factors.


Centralized on-line hemodiafiltration system utilizing purified dialysate as substitution fluid.
We followed the guidelines of the Kyushu Society for Hemodiafiltration (HDF) Therapy on the purification of dialysate used as substitution fluid and clinically applied HDF using only 20 L or 15 L of substitution fluid in the pre- or postdilution mode, respectively. We used a centralized on-line HDF system consisting of a novel multi-patient dialysate delivery system applying 3 endotoxin (ET) removal filters in series, maintaining the ET level within the criteria limit below 1.0 IU/L (measured at the first filter outlet to be 0.1 IU/L and after the third filter to be below the sensitivity limit) irrespective of the fluctuation in the ET level of the tap water. Low molecular weight proteins (beta2-microglobulin, prolactin, alpha1-microglobulin, and alpha1-acid glycoprotein) were more effectively removed in this HDF system than in conventional hemodialysis (HD) using the same dialyzer as that in the HDF system, and the removal of these proteins in the HDF system was enhanced as their molecular weights increased. The clinical effect of the HDF system was demonstrated by a decrease in joint pain accompanied by improvement in joint motion in 6 dialysis patients followed over the long term (100 weeks).


The influence of pore geometry in cp Ti-implants--a cell culture investigation.
Biocompatibility testing of differently structured titanium implants was performed using an in vitro test system of a newly established human fetal osteoblastic cell line (hFOB 1.19). Cell adhesion of osteoblastic cells on the different porous geometries and the suitability of a copper vapor laser system for surface structuring was tested with the following parameters: cell-number, cell viability, alkaline phosphatase expression. The analysis of the cell culture results demonstrated that 25 microm and 200 microm porous geometries showed similar or even better results than the negative control of polystyrene; there was no sign of toxic effects. However, the 100 microm porous geometry showed an impressive negative influence on the calculated parameters. The reason for this effect is unclear. The series with 50 microm, 300 microm, 400 microm and 500 microm showed a comparable, intermediate effect on the cell culture with respect to the different parameters. However, the results were worse than with the 25 and 200 microm porous geometry. In conclusion, the 25 microm and 200 microm porous geometry seems to have the most positive effect on the human osteoblastic cell line hFOB 1.19.


A natural adaptive syndrome as a model for the origins of cereal agriculture.
A novel explanation of the origin of cereal agriculture is proposed, based on the ecology and adaptive morphology of wild cereals ancestral to our founder cereals (einkorn, emmer and barley). Wild cereals are unusually large-seeded. A natural evolutionary-ecological syndrome relates large seed, awns and monodominance (LAM). Awns bury attached seeds in the soil, protecting seed from fire; buried seed needs to be large to emerge on germination; large seeds, growing without competition from small-seeded plants, will produce monodominant vegetation. Climatic and edaphic instability at the Pleistocene-Holocene boundary would have provided an impetus for the spread of annual ruderal grasses. LAM grassland provided an obvious natural model for the origins of cereal agriculture. Subsequent field management would mimic the natural niche (MNN). The fact that monodominance is a long-standing character of the natural LAM syndrome validates cereal monocultures (now producing most of our food). An alternative explanation of crop domestication, by auditioning a great range of species for a human-constructed niche (NCT), is rejected.


Q fever following bone marrow transplantation.
We describe a patient who developed an acute febrile illness 85 days after receiving an allogeneic bone marrow transplant for acute myeloid leukaemia. Serological investigation indicated the cause to be Q fever. The patient was receiving concurrent immunosuppressive therapy for graft-versus-host disease (GVHD). Coxiella burnetii should be added to the list of organisms which may complicate bone marrow transplantation. This case also provides further evidence to support an association between immunocompromised conditions and the development of Q fever.


Kinetics of four limb joints during kick-start motion in competitive swimming.
The kick-start technique in competitive swimming generates a force acting on the starting platform owing to gravity, muscle contraction and resulting joint torque. To understand optimal body movement on the starting platform for maximising take-off velocity, it is necessary to investigate the joint torque in relation to the joint's rotation effects. Joint torques were calculated by inverse dynamics using kinetic and kinematic data. A one-way ANOVA showed significantly greater extensional torque for shoulders than for elbows or wrists, and for hips than for knees or ankles. The results indicated that the force of the hands was mainly influenced by extension torque at the shoulder joint. Hip joint extension torque on the front side lower limb (FSLL) was mainly used for supporting the body weight until hands off. After hands off, the front-foot force originated mainly by increases in ankle joint plantar flexion and knee joint extension torque on the FSLL. Rear side lower limb torque increases in the hip, knee and ankle joints provided the rear-foot force. This investigation clarified the magnitudes and functions of each joint torque acting on the extremities during the kick-start, providing practical information for improving starting performance.


Socioeconomic correlates of overweight and obesity among ever-married urban women in Bangladesh.
The escalating prevalence of overweight and obesity globally is reflected amongst urban women in many low-to-middle income countries. Evidence also shows that overweight and obesity is an increasing trend in Bangladesh. The present study assessed the prevalence and socioeconomic determinants of overweight and obesity among urban women in Bangladesh. Data were extracted from Bangladesh Demographic and Health Survey (BDHS) 2014. A two-stage stratified sampling technique has been used for data collection in this cross-sectional survey. A sample of 1701 ever-married non-pregnant urban women aged 15-49 years was selected for statistical analysis. Descriptive analysis, multiple binomial logistic regression analysis were executed in this study. The prevalence of overweight and obesity was 34% (95% CI, 0.30-0.38) among urban Bangladeshi women. The probability of being overweight and obese increased with increasing age and wealth index. The likelihood of being overweight and obese among the oldest women surveyed (40-49 years) was 4.3 times (OR = 4.3, 95% CI: 2.1-8.8) higher relative to the youngest women (15-19 years). The wealthiest women had 4.1 times (OR = 4.1, 95% CI: 2.5-6.7) higher likelihood of being overweight and obese compared to the reference group of poorest women. Women having higher education (OR = 1.7, 95% CI: 1.0-2.6) were more likely to be overweight and obese. However, women who were no longer living with their husband or separated from their husband were (OR = 0.4, 95% CI: 0.2-0.8) less likely to be overweight and obese. This study provides evidence that a large number of urban women were overweight and obese in Bangladesh. Women having higher levels of education, being older and belonging in both poorer and richest wealth quintile were at risk of being overweight and obese. Appropriate health promoting interventions based on these factors should be envisaged to reduce this problem.


Antibiotic Potential of the Ambigol Cyanobacterial Natural Product Class and Simplified Synthetic Analogs.
The ambigols are cyanobacterial natural products characterized by three polychlorinated aromatic building blocks connected by biaryl and biaryl ether bridges. All ambigols known to date possess promising biological activities. Most significantly, ambigol A was reported to have antibacterial activity against Gram-positive bacteria, such as Bacillus megaterium and B. subtilis. We established a diverse compound library for in-depth biological evaluation building on our previous bio- and total synthetic research on this natural product family. To explore the antimicrobial potential in detail and to determine initial structure-activity relationships of this product class, a large set of dimeric and trimeric compounds were screened against selected bacterial and Candida target strains. Our results reveal exceptional antibiotic activity of the ambigols, especially against challenging clinical isolates.


[Cryptococcal Encephalitis Complicating Anti-N-methyl-D-aspartate Receptor Encephalitis in an Immunosuppressed Patient].
Cryptococcal encephalitis is a fatal central nervous system infectious disease,whereas anti-N-methyl-D-aspartate(NMDA)receptor encephalitis(NMDARE)is an autoimmune syndrome associated with psychological symptoms,behavioural abnormalities,seizures,and dyskinesias.Despite their distinct pathologies and pathogenic mechanisms,both of them can lead to cognitive dysfunction and abnormal behaviors,although anti-NMDARE can also have mood and mental disorders as its core manifestations.A patient with nephrotic syndrome accompanied by both cryptococcal encephalitis and anti-NMDARE was treated in our center,which for the first confirmed that these two conditions could coexist in one patient.The underlying mechanism may be similar to that of anti-NMDARE after other infections.


Nonpharmacological amelioration of age-related learning deficits: the impact of hippocampal theta-triggered training.
Age-related learning deficits are often attributed to deterioration of hippocampal function. Conversely, a well studied index of hippocampal activity, the rhythm, is known to enhance hippocampal plasticity and accelerate learning rate in young subjects, suggesting that manipulations of activity might be used as a means to counteract impairments related to the aging process. Here, young and older rabbits were given eyeblink conditioning trials either when exhibiting hippocampal (+) or regardless of hippocampal activity (yoked control). Although, as expected, older-yoked control animals showed a learning deficit, the older + group learned as fast as young controls, demonstrating that aging deficits, at least in eyeblink classical conditioning, can be overcome by giving trials during episodes of hippocampal activity. The use of several learning criteria showed that the benefits of hippocampal occur in multiple phases of learning that may depend on different cognitive or motor processes. Whereas there was a benefit of -triggered training in both age groups during the early phase of acquisition, the enhancement persisted in older animals, peaking during later performance. These findings have implications for theories of age-related memory deficits and may contribute to the development of beneficial treatments.


[Value of amniotic gamma-glutamyl-transpeptidase assay in the diagnosis of fetal digestive stenosis after 24 weeks of amenorrhea].
In 18 women compared with 1,181 controls, foetal digestive tract stenoses were discriminated, independently of the gestational age, by a more than 50 IU/l level of gamma-glutamyl transpeptidase in the amniotic fluid. This test had a specificity of 99% and a sensitivity of 85% which was accounted for by the inclusion in the study of distal stenoses and oesophageal atresias, all conditions where the gamma-glutamyl transpeptidase level is normal. In cases with ultrasonically detected abdominal wall abnormalities, this test is also useful in the diagnosis of subjacent digestive tract stenosis.


Hyperdense basilar artery. An early computed tomography sign of thrombosis.
Noncontrast computed tomographic scans (CT scans) may show a hyperdense basilar artery before a brainstem infarct is visualized. This early sign should assist clinicians in confirming the diagnosis of basilar artery thrombosis. In a review of admission records of 750 patients with acute cerebrovascular disease from July 1991 to June 1993, at Saint Louis University Hospital, 20 patients were identified with clinical signs of nonlacunar, vertebrobasilar distribution infarction. Eight of these had pontomesencephalic ischemia. Their neuroimaging studies and medical records were evaluated. Four patients with acute clinical signs of pontomesencephalic infarction were found to have a hyperdense basilar artery on CT scans. The scans of 2 patients were excluded because of dolichoectasia; in the other 2 patients, the basilar artery appeared normal on the CT scan. The hyperdense basilar artery was detected within the early hours of neurological symptoms and often was the only detectable abnormality on the scan. In 3 patients extensive brainstem infarcts subsequently developed and they died. Basilar artery thrombosis was confirmed by pathological study in all these patients. In the fourth patient basilar artery occlusion and a large pontine infarct were evident by magnetic resonance imaging and angiography. A hyperdense basilar artery is a common feature on CT scans of patients presenting with an early clinical diagnosis of thrombosis. Untreated, the hyperintense basilar artery often portends a poor prognosis. Its ready recognition should guide further interventional studies and treatment.


Postprandial Effects of Blueberry (Vaccinium angustifolium) Consumption on Glucose Metabolism, Gastrointestinal Hormone Response, and Perceived Appetite in Healthy Adults: A Randomized, Placebo-Controlled Crossover Trial.
The consumption of blueberries, as well as the phenolic compounds they contain, may alter metabolic processes related to type 2 diabetes. The study investigated the effects of adding 140 g of blueberries to a higher-carbohydrate breakfast meal on postprandial glucose metabolism, gastrointestinal hormone response, and perceived appetite. As part of a randomized crossover design study, 17 healthy adults consumed a standardized higher-carbohydrate breakfast along with 2 treatments: (1) 140 g (1 cup) of whole blueberries and (2) a placebo gel (matched for calories, sugars, and fiber of the whole blueberries). Each subject participated in two 2-h meal tests on separate visits ≥8 days apart. Venous blood samples and perceived appetite ratings using visual analog scales were obtained prior to and at 30, 60, 90, and 120 min after consuming the breakfast meals. Results show that glucose metabolism, several gastrointestinal hormones, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), peptide YY (PYY) concentrations and perceived appetite did not change significantly with blueberry consumption. However, pancreatic polypeptide (PP) concentrations were statistically significantly higher (p = 0.0367), and the concentrations were higher during 30, 60, 90, and 120 min after consumption of the blueberry breakfast meal than the placebo breakfast meal. Additional research is needed to determine whether blueberries and other flavonoid-rich foods reduce type 2 diabetes risk by modifying gastrointestinal hormones and perceived appetite.


Noncoordinate regulation of ENaC: paradigm lost?
The epithelial sodium channel (ENaC) is composed of the three homologous subunits alpha, beta, and gamma. The basic oligomerization process inferred from all studies in heterologous systems is preferential assembly of the three subunits into a single oligomeric form. However, there is also considerable evidence that channels composed of only alpha-, alphabeta-, or alphagamma-subunits can form under some circumstances and that individual subunits expressed in heterologous systems can traffic to the cell membrane. In cells that express endogenous ENaC, the three subunits are often synthesized in a differential fashion, with one or two subunits expressed constitutively while the other(s) are induced by different physiological stimuli in parallel with increased ENaC activity. This phenomenon, which we term noncoordinate regulation, has been observed for both whole cell and apical membrane ENaC subunit expression. Several other heteromeric membrane proteins have also been observed to have differential rates of either turnover or trafficking of individual subunits after biosynthesis and membrane localization. Here, we examine the possibility that noncoordinate regulation of ENaC subunits may represent another mechanism in the arsenal of physiological responses to diverse stimuli.


[Epidemiology of envenomation in French Guiana].
Incidence of snake bites, scorpion and venomous fish stings are established in French Guiana (a South American French territory). About 75 snake bites per 100,000 population, 90 scorpion stings and 125 fish stings are recorded in a year by official sanitary services. Authors give geographical and ecological variations, and risks, of venomous animal accidents. Severity of snake bites and medical cost are emphasized. Necrosis and/or bleedings follow 5% of cases and hospital lethality reaches 2.2%.


The Versatile Modiolus Perforator Flap.
Perforator flaps are well established, and their usefulness as freestyle island flaps is recognized. The whereabouts of vascular perforators and classification of perforator flaps in the face are a debated subject, despite several anatomical studies showing similar consistency. In our experience using freestyle facial perforator flaps, we have located areas where perforators are consistently found. This study is focused on a particular perforator lateral to the angle of the mouth; the modiolus and the versatile modiolus perforator flap. A cohort case series of 14 modiolus perforator flap reconstructions in 14 patients and a color Doppler ultrasonography localization of the modiolus perforator in 10 volunteers. All 14 flaps were successfully used to reconstruct the defects involved, and the location of the perforator was at the level of the modiolus as predicted. The color Doppler ultrasonography study detected a sizeable perforator at the level of the modiolus lateral to the angle of the mouth within a radius of 1 cm. This confirms the anatomical findings of previous authors and indicates that the modiolus perforator is a consistent anatomical finding, and flaps based on it can be recommended for several indications from the reconstruction of defects in the perioral area, cheek and nose. The modiolus is a well-described anatomical area containing a sizeable perforator that is consistently present and readily visualized using color Doppler ultrasonography. We have used the modiolus perforator flap successfully for several indications, and it is our first choice for perioral reconstruction.


Differential expression of the estrogen receptors alpha and beta in the rat corpus luteum of pregnancy: regulation by prolactin and placental lactogens.
Estradiol, together with PRL and placental lactogens, regulates steroidogenesis and cell hypertrophy in the rat corpus luteum of pregnancy. Although binding experiments have demonstrated the presence of estrogen-binding sites, no evidence exists as to whether the rat corpus luteum of pregnancy expresses the estrogen receptor (ER) genes. In this investigation, we have analyzed the expression of the two ER genes (ER alpha and ER beta) (by RT-PCR and in situ hybridization) in the rat corpus luteum, studied their developmental changes throughout pregnancy, and investigated the regulation of ER alpha and ER beta messenger RNA (mRNA) expression by PRL and placental lactogens. The RT-PCR studies showed that both ER mRNA species (ER alpha and ER beta) are coexpressed in the rat corpus luteum during pregnancy. Whereas ER alpha mRNA increased from early pregnancy, reached a maximum at midpregnancy, and had a remarkable decline before parturition; ER beta mRNA remained constant throughout pregnancy, with a significant decline at parturition. Examination of ER alpha and ER beta mRNA expression at the cellular level, by in situ hybridization, showed ER alpha expressed in both follicles and corpus luteum, with maximal expression at midpregnancy. In parallel with the RT-PCR studies, ER beta mRNA was similarly expressed throughout pregnancy in the corpus luteum, but it was less abundant when compared with small and growing follicles. Western blot analysis revealed two ER immunoreactive proteins in the nuclear fraction obtained from pregnant rat corpus luteum: a 67-kDa moiety, highly expressed at midpregnancy but barely detectable in early and late gestation; and a 61-kDa form that remained developmentally unchanged. Hypophysectomy, performed early in pregnancy, induced a sharp decline in ER alpha mRNA expression but a less-marked reduction in ER beta mRNA levels. PRL treatment reverted the inhibition induced by hypophysectomy in both receptor subtypes. When primary luteinized cells were used to test the effect of PRL, rat placental lactogen I, and rat placental lactogen II on the expression of ER alpha and ER beta mRNA, all these lactogenic hormones stimulated both ER mRNA species in a dose-dependent manner. The regulation of ER mRNA expression was further evaluated in a luteal cell line, termed GG-CL, which apparently expresses only the ER beta mRNA species. Culture of the GG-CL cells, in the presence of PRL, resulted in a dose-related up-regulation of ER beta mRNA expression. In addition, PRL treatment enhanced the binding activity of GG-CL cell nuclear proteins to a classical estrogen response element. Furthermore, in these cells, estradiol treatment induced a dose-dependent up-regulation of the mRNA encoding protein kinase C delta isoform, a well-known estrogen target gene in the corpus luteum of the pregnant rat.


Evaluation of Low-dose Buprenorphine Initiation With Buprenorphine Buccal Films in Hospitalized Patients: A Retrospective Cohort Study.
Low-dose buprenorphine initiation (LDBI) strategies to transition patients from full opioid agonists to buprenorphine have previously been described using sublingual films, intravenous solution, transdermal patches, and, more recently, buccal films. The objective of this study was to describe the effectiveness of LDBI using novel titration schedules with buccal films. This is a retrospective cohort study of hospitalized patients with opioid use disorder (OUD) or physiologic dependence to opioids who underwent LDBI with buprenorphine buccal films at NYU Langone Health. Two LDBI protocols were evaluated, including a short titration schedule over 4 days and a long schedule over 7 days. The primary outcomes of interest included LDBI completion rates and incidence of opioid withdrawal. Forty-two patients underwent 46 LDBIs at NYU Langone Health between October 2020 and April 2022. The cohort comprised patients with OUD (57%), chronic pain with OUD (33%), and chronic pain without OUD (10%). Indications for LDBI most commonly included co-occurring pain precluding discontinuation of full opioid agonists (72%), prior history of precipitated withdrawal (30%), and methadone use (23%). The overall completion rate of LDBI was 78%. Withdrawal was encountered in 33% of patients; however, only 2 patients required LDBI discontinuation as a result. On multivariate analysis, a diagnosis of OUD was independently associated with withdrawal during LDBI. Buprenorphine buccal films can successfully be used off-label to facilitate LDBI in the hospital setting. We present 4- and 7-day titration protocols, which were well-tolerated, and provide practical considerations for use.


Whole-body imaging with single-cell resolution by tissue decolorization.
The development of whole-body imaging at single-cell resolution enables system-level approaches to studying cellular circuits in organisms. Previous clearing methods focused on homogenizing mismatched refractive indices of individual tissues, enabling reductions in opacity but falling short of achieving transparency. Here, we show that an aminoalcohol decolorizes blood by efficiently eluting the heme chromophore from hemoglobin. Direct transcardial perfusion of an aminoalcohol-containing cocktail that we previously termed CUBIC coupled with a 10 day to 2 week clearing protocol decolorized and rendered nearly transparent almost all organs of adult mice as well as the entire body of infant and adult mice. This CUBIC-perfusion protocol enables rapid whole-body and whole-organ imaging at single-cell resolution by using light-sheet fluorescent microscopy. The CUBIC protocol is also applicable to 3D pathology, anatomy, and immunohistochemistry of various organs. These results suggest that whole-body imaging of colorless tissues at high resolution will contribute to organism-level systems biology.


Protease Hydrolysates of Filefish (Thamnaconus modestus) Byproducts Effectively Inhibit Foodborne Pathogens.
In this study, novel antimicrobial peptides had been derived by enzymatic hydrolysis of filefish (Thamnaconus modestus) byproduct (HFBP). Different proteases, (papain [P], trypsin [T], neutrase [N], pepsin [PE], and the mixture I [PN] and mixture II [PT]) and different hydrolysis time (60, 120, 180, and 240 min), have been used to generate peptides with different lengths and amino acid sequences. The antimicrobial properties of HFBPs were tested, against Gram-positive and Gram-negative strains, using disc diffusion method. HFBP prepared after 120 min of the enzymatic hydrolysis by trypsin (HFBP-T) exhibited greatest antibacterial activities. Bacillus cereus 10451 (BC) and Salmonella enteritidis 10982 (SE) strains were most sensitive to HFBP-T with an inhibitory zone of 24.68 and 29.67 mm diameter and minimum inhibitory concentration of 1.25 and 2.5 mg/mL, respectively. Moreover, the antimicrobial activities of tested HFBPs increased significantly at low pH and temperature. The amino acid analysis showed that HFBP-T protein hydrolysate is high in an amino acid of proline, which probably contributes to the antimicrobial activity. The results obtained from scanning electron microscopy suggested that HFBPs might kill bacteria by acting on the cell wall of bacteria. Conclusively, the HFBP derived from filefish byproduct with biological activates is an interesting alternative to the use of waste from the fishing industry as natural antimicrobials in food stuff.


Genome-Wide Analysis of Carboxylesterases (COEs) in the Whitefly, Bemisia tabaci (Gennadius).
The whitefly (Bemisia tabaci), an important invasive pest that causes severe damage to crops worldwide, has developed resistance to a variety of insecticides. Carboxylesterases (COEs) are important multifunctional enzymes involved in the growth, development, and xenobiotic metabolism of insects. However, systematic studies on the COEs of B. tabaci are scarce. Here, 42 putative COEs in different functional categories were identified in the Mediterranean species of B. tabaci (B. tabaci MED) based on a genome database and neighbor-joining phylogeny. The expression patterns of the COEs were affected by the development of B. tabaci. The expression levels of six COEs were positively correlated with the concentration of imidacloprid to which B. tabaci adults were exposed. The mortality of B. tabaci MED adults fed dsBTbe5 (67.5%) and dsBTjhe2 (58.4%) was significantly higher than the adults fed dsEGFP (41.1%) when treated with imidacloprid. Our results provide a basis for functional research on COEs in B. tabaci and provide new insight into the imidacloprid resistance of B. tabaci.


The Auxiliary Calcium Channel Subunit α2δ4 Is Required for Axonal Elaboration, Synaptic Transmission, and Wiring of Rod Photoreceptors.
Neural circuit wiring relies on selective synapse formation whereby a presynaptic release apparatus is matched with its cognate postsynaptic machinery. At metabotropic synapses, the molecular mechanisms underlying this process are poorly understood. In the mammalian retina, rod photoreceptors form selective contacts with rod ON-bipolar cells by aligning the presynaptic voltage-gated Ca2+ channel directing glutamate release (CaV1.4) with postsynaptic mGluR6 receptors. We show this coordination requires an extracellular protein, α2δ4, which complexes with CaV1.4 and the rod synaptogenic mediator, ELFN1, for trans-synaptic alignment with mGluR6. Eliminating α2δ4 in mice abolishes rod synaptogenesis and synaptic transmission to rod ON-bipolar cells, and disrupts postsynaptic mGluR6 clustering. We further find that in rods, α2δ4 is crucial for organizing synaptic ribbons and setting CaV1.4 voltage sensitivity. In cones, α2δ4 is essential for CaV1.4 function, but is not required for ribbon organization, synaptogenesis, or synaptic transmission. These findings offer insights into retinal pathologies associated with α2δ4 dysfunction.


Attention and information processing in schizophrenia.
The performance of 20 acute schizophrenics and 10 depressives, matched for age, verbal intelligence, and pre-morbid functioning, was assessed on a choice reaction-time card-sorting task. Stimulus and response uncertainty were varied independently, and there were two main conditions, distraction and no distraction. The schizophrenics were slower than the depressives over all the functions examined in the study. Schizophrenics were significantly more affected by increases in response uncertainty than the depressives. Although there was a tendency for the schizophrenic group to be more affected by distraction and by increasing stimulus uncertainty, these differences were not significant. There was no significant interaction between the effects of stimulus and response uncertainty, nor between the effects of distraction and stimulus uncertainty. The effects of distraction increased with increasing response uncertainty. The results are discussed in relation to two models of information processing, suggested by Broadbent (1971) and by Sternberg (1969). Such models allow a more detailed examination of the cognitive abnormalities found in schizophrenia.


Preoperative diagnostic algorithm of primary thyroid lymphoma using ultrasound, aspiration cytology, and flow cytometry.
The aims of this report were to clarify the diagnostic significance of ultrasound (US), fine needle aspiration cytology (FNAC), and flow cytometry for primary thyroid lymphoma, and to establish a preoperative diagnostic algorithm of primary thyroid lymphoma. We retrospectively examined US, FNAC, and flow cytometry in 43 patients with benign lymphoproliferative lesions and 32 patients with primary thyroid lymphoma, who underwent US, FNAC, and flow cytometry at Kuma Hospital between May 2012 and December 2015. Primary thyroid lymphomas included 27 mucosa-associated lymphoid tissue lymphomas, 4 diffuse large B-cell lymphomas, and 1 follicular lymphoma. Flow cytometry had the highest specificity (88.4%) and sensitivity (75.0%). The specificity of US was the lowest (32.6%). Both the positive predictive value (90.5%) and negative predictive value (94.7%) were the highest for FNAC. A scoring system was defined as follows: US, low suspicion 0, intermediate suspicion 1, and high suspicion 2; FNAC, benign 0, undetermined 1, malignant 2; and flow cytometry, 0.33< κ/λ ratio <3 0, κ/λ ratio ≤0.33 2, and κ/λ ratio ≥3 2. We propose that a score ≥4 indicates the need for thyroid resection for diagnosing primary thyroid lymphoma. In such a situation, the case of diffuse large B-cell lymphoma, which was aggressive, was not excluded. Approximately one-fifth of mucosa-associated lymphoid tissue lymphomas may be overlooked, but the patients could be followed up with because of an indolent course.


[Optimization of the method for isolating and culturing rat mesenchymal stem cells].
To optimize the protocols for isolation and culture of mesenchymal stem cells from rat bone marrow (BMSCs). BMSCs were isolated by adherence to plastic with frequent medium change and reduced trypsinization time. The cell growth curves were drawn and the surface markers of BMSCs were detected by flow cytometry. The cells were induced to differentiate into osteogenic, adipogenic, hepatic and cholic lineages. The cells isolated using this method were positive for CD29, CD44, and CD90 and negative for the hematopoietic surface markers CD45. The osteogenic and adipogenic differentiation of the BMSCs was verified by alkaline phosphatase staining, Alizarin red staining and Oil red staining. The cell subcultures up to passage 10 maintained capacities of differentiation into osteogenic and adipogenic lineages. The BMSCs induced with sequential addition of growth factors, cytokines and hormones differentiated into cells expressing hepatocyte- and cholangiocyte-specific markers. The optimized method allows efficient isolation of homogenous populations of MSCs from rat bone marrow, which can be induced into multiple cell lineages.


Catalysis by metal nanoparticles embedded on metal-organic frameworks.
The present review describes the use of metal-organic frameworks (MOFs) as porous matrices to embed metal nanoparticles (MNPs) and occasionally metal oxide clusters, which are subsequently used as heterogeneous catalysts. The review is organized according to the embedded metal including Pd, Au, Ru, Cu, Pt, Ni and Ag. Emphasis is also given in the various methodologies reported for the formation of the NPs and the characterization techniques. The reactions described with this type of solid catalysts include condensation, hydrogenations, carbon-carbon coupling, alcohol oxidations and methanol synthesis among others. Remaining issues in this field have also been indicated.


Endotracheal tube cuff pressure assessment maneuver induces drop of expired tidal volume in the postoperative of coronary artery bypass grafting.
Previous investigations reported that the cuff pressure (CP) can decrease secondary to the CP evaluation itself. However is not established in literature if this loss of CP is able to generate alterations on expired tidal volume (ETV). Therefore, the aim of this study was to evaluate the potential consequences of the endotracheal CP assessment maneuver on CP levels and ETV in the early postoperative of coronary artery bypass grafting (CABG). A total of 488 patients were analyzed. After the operation, the lungs were ventilated in pressure-assist-control mode and the same ventilatory settings were adjusted for all patients. After intensive care unit arrival, the cuff was fully deflated and then progressively inflated by air injection, to promote a minimal volume to occlude the trachea. To assist the cuff inflation and the air leakage identification, the graphical monitoring of the volume-time curve was adopted. After 20 minutes a first cuff pressure evaluation was performed (P1) and a second measurement (P2) was taken after 20 minutes with an analog manometer. ETV was obtained always pre and post P1 measurement. The CP assessment maneuver promoted a significant drop of P2 in relation to P1 when the manometer was attached to the pilot balloon (p < 0.0001). When compared the moments, pre-P1 versus post-P1, a significant drop of the ETV was also observed (p < 0.0001). The CP assessment maneuver promoted a significant decrease in CP values and occurrence of air leakage with reduction of ETV in the early postoperative of CABG.


Affective temperaments in alcohol and opiate addictions.
Temperament is considered as a biological disposition reflected by relatively stable features related to mood and reactivity to external and internal stimuli, including variability in emotional reactions. The aim of the present study is to test the hypothesis that affective temperaments might differ according to co-occurring mood disorders among patients with alcohol and/or opiate dependence; to explore the relationship between temperaments and dual substance use disorders (SUDs, alcohol and other drugs). Ninety-two patients attending an alcohol addiction treatment facility and 47 patients in an opiate addiction treatment facility were assessed for SUDs, mood disorders and affective temperaments using the Temperament Evaluation of Memphis, Pisa, Paris and San Diego 39-item auto-questionnaire. Comparison of patients with bipolar disorder, depressive unipolar disorder and no (or substance-induced) mood disorder revealed significant differences for the cyclothymic subscale, with highest scores among patients with bipolar disorder. No difference was observed for the depressive, irritable, hyperthymic and anxious subscales. After adjustment for age, gender and bipolar disorder, irritable temperament was a significant risk factor for past or present history of drug use disorders in patients treated for alcohol addiction (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.05-1.93). Anxious temperament was a significant risk factor for history of alcohol use disorders in patients treated for opiate addiction (OR 3.30, 95% CI 1.36-7.99), whereas the hyperthymic subscale appeared as a significant protective factor (OR 0.65, 95% CI 0.42-0.99). The results highlight the need to consider temperamental aspects in further research to improve the long-term outcome of patient with addictive disorders, who often present complex comorbidity patterns.


Long-term neurodevelopmental outcome of children from euploid pregnancies with increased nuchal translucency in the first trimester screening.
To assess the long-term neurodevelopmental outcome of children born from singleton euploid pregnancies with increased fetal nuchal translucency (NT) in the first trimester ultrasound screening and without structural anomalies in the second trimester ultrasound screening. This is a register-based retrospective cohort study carried out at a tertiary referral centre from 2002 to 2007. Children were followed up until 2012. All fetuses had increased NT (>95th percentile) at the first trimester ultrasound screening and normal findings in the second trimester ultrasound screening. Data about the neurodevelopmental outcome was retrieved from the hospital databases, The National Institute for Health and Welfare, and the Finnish Causes of Death Statistics Database. Information about received disability allowances was gathered from the Social Insurance Institute of Finland. The study population consists of 691 children. The mean follow-up time was 6.5 years. Neurodevelopmental disorders occurred in 29 children (4.2%). Twelve of these 29 children (1.7%) had severe neurodevelopmental impairment. The long-term neurodevelopmental outcome of children after increased fetal NT is reassuring. This information should be added to the parental counselling of such cases. © 2014 John Wiley & Sons, Ltd.


[Clinical significance of cyclin Dl expression in non-small cell lung cancer].
Lung cancer remains interdisciplinary problem. The genetic alterations in non-small cell lung cancer (NSCLC) are related to tumor suppressor genes and proto-oncogenes. CCND1 gene, coding cyclin DI, in correlation with pRb is involved in regulation of cell cycle arrest in G1 phase. Amplification of CCND1 gene and cyclin D1 over-expression was found in several cancers including head and neck cancers or colorectal cancer, where these alterations were correlated with worse prognosis. The literature addressing the clinical significance of CCND1 gene amplification/expression in NSCLC remains poor and prognostic value of these alterations in that cancer is still controversial.


Iconography of Beans and Related Legumes Following the Columbian Exchange.
Common bean (Phaseolus vulgaris L.), maize, and squash were described by explorers as early as 1492. The illustration of common bean recognized as the first in Europe is in Fuchs' Di Historias Stirpium, published in 1542 and a half-century after beans were observed in the Caribbean. Besides herbals and herbarium specimens, the sources of information on the introduction of New World crops are paintings and illustrations. Two early sources of images of maize and squash are the Grandes Heures d'Anne de Bretagne and the Loggia di Amore e Psiche in the Villa Farnesina, Rome. The former was illustrated between 1507 and 1508 and has an image identified as the common bean. The Villa Farnesina Loggia was decorated in 1515-1518, with festoons containing three instances of bean pods. Our first objective was to evaluate these images to determine whether they represented depictions of common bean earlier than the illustration by Fuchs. Neither image appears to be a common bean based on a combination of botanical characters and size. Folio 194 of the Grandes Heures d'Anne de Bretagne is most likely a Vigna species in the Ceratotropis subgenus. In the Loggia, one set of pods appears to be a species in the Mimosoideae subfamily and the second and third sets of pods most closely resemble Canavalia gladiata. Neither image likely represents common beans and are probably Old-World species. Secondly, illustrations of common beans from ten early herbals were analyzed for traits that are characteristic of the centers of domestication and races of common beans. Our objective was to characterize the diversity observed among herbals and determine whether beans from both centers of domestication were present. We potentially identified both Middle American, race Mesoamerica and Andean, race Nueva Granada types. We posit that both Middle American and Andean types were in the Caribbean at the time of the Columbian exchange and that beans from both centers were informally introduced into Europe early on. This review of 16th-century manuscripts and illustrations has provided some answers to the questions of what and when common beans reached Europe and provide new hypotheses for researchers studying the origins, diversity, and distribution of this crop.


From shape-shifting embryonic cells to oncology: The fascinating history of epithelial mesenchymal transition.
Epithelial-to-mesenchymal transition or transformation (EMT) is a cell shape-changing process that is utilized repeatedly throughout embryogenesis and is critical to the attainment of a precise body plan. In the adult, EMT is observed under both normal and pathological conditions, such as during normal wounding healing, during development of certain fibrotic states and vascular anomalies, as well as in some cancers when malignant cells progress to become more aggressive, invasive, and metastatic. Epithelia derived from any of the three embryonic germ layers can undergo EMT, including those derived from mesoderm, such as endothelial cells (sometimes termed Endo-MT) and those derived from endoderm such as fetal liver stroma. At the cellular level, EMT is defined as the transformation of epithelial cells towards a mesenchymal phenotype and is marked by attenuation of expression of epithelial markers and de novo expression of mesenchymal markers. This process is induced by extracellular factors and can be reversible, resulting in mesenchymal-to-epithelial transformation (MET). It is now clear that a cell can simultaneously express properties of both epithelia and mesenchyme, and that such transitional cell-types drive tumor cell heterogeneity, an important aspect of cancer progression, development of a stem-like cell state, and drug resistance. Here we review some of the earliest studies demonstrating the existence of EMT during embryogenesis and discuss the discovery of the extracellular factors and intracellular signaling pathways that contribute to this process, with components of the TGFβ signaling superfamily playing a prominent role. We mention early controversies surrounding in vivo EMT during embryonic development and in adult diseased states, and the maturation of the field to a stage wherein targeting EMT to control disease states is an aspirational goal.


Understanding heterogeneity in borderline personality disorder: differences in affective reactivity explained by the traits of dependency and self-criticism.
This study examined whether the personality traits of self-criticism and dependency respectively moderated the effects of perceived inferiority and emotional insecurity on negative affect during interpersonal interactions in individuals with borderline personality disorder (BPD). A sample of 38 patients with BPD and matched community comparison participants completed event-contingent record forms after each significant interaction for a 20-day period. Multilevel models showed that, controlling for baseline levels of depressive symptoms and neuroticism, as well as lagged negative affect, event-level elevations in perceived inferiority and emotional insecurity were related to more negative affect in both groups. Event-level perceived inferiority was more strongly associated with negative affect in patients with BPD who reported higher levels of self-criticism, while event-level perceived emotional insecurity was more strongly associated with negative affect in patients with BPD who reported higher levels of dependency. No significant interactions emerged for the comparison group. These findings further our understanding of differences among patients with BPD and support the application of personality-vulnerability or diathesis-stress models in predicting negative affect in BPD. Results have implications for the design of therapies for patients with BPD.


Diagnosis and Treatment of Right Heart Failure in Pulmonary Vascular Diseases: A National Heart, Lung, and Blood Institute Workshop.
Right ventricular dysfunction is a hallmark of advanced pulmonary vascular, lung parenchymal, and left heart disease, yet the underlying mechanisms that govern (mal)adaptation remain incompletely characterized. Owing to the knowledge gaps in our understanding of the right ventricle (RV) in health and disease, the National Heart, Lung, and Blood Institute (NHLBI) commissioned a working group to identify current challenges in the field. These included a need to define and standardize normal RV structure and function in populations; access to RV tissue for research purposes and the development of complex experimental platforms that recapitulate the in vivo environment; and the advancement of imaging and invasive methodologies to study the RV within basic, translational, and clinical research programs. Specific recommendations were provided, including a call to incorporate precision medicine and innovations in prognosis, diagnosis, and novel RV therapeutics for patients with pulmonary vascular disease.


[Gender-specific influences on the results of vascular surgery].
This overview comments on gender-specific differences in prevalence, treatment and outcome in patients with peripheral arterial disease (PAD), carotid stenosis, and abdominal aortic aneurysm (AAA). For the literature review, the Medline database (PubMed) was searched under the key words "peripheral arterial disease AND gender", "carotid stenosis AND gender" and "abdominal aortic aneurysm AND gender". 1.) Women (preferably black women) with PAD experience rather than men bypass failure or amputation. Nevertheless, gender should not constitute a selection criterion for revascularisation therapy. Despite an older age and more advanced stages of disease in women, infrainguinal arterial reconstructions could achieve, in published series, patency and limb salvage rates which did not differ from those of men. 2.) The benefit of carotid endarterectomy (CEA) for asymptomatic carotid artery stenosis is less for women compared with men. However, registries exhibited at best for symptomatic women an increased perioperative risk of CEA compared with men, with CEA especially in women better than carotid artery stenting. The treatment of AAA shows significant gender differences. The risk of rupture for small aneurysms is significantly greater in women compared with men, and they have higher in-hospital mortality rates for both open and endovascular repair of ruptured and intact AAA. Yet women also benefit from endovascular repair of AAA compared to open repair, although their eligibility for endovascular repair is less than that of men due to anatomic conditions. As a rule, for the mentioned diseases less favourable results were reported in women. This may reflect biological disparities, or the differences are based on the fact that women develop arteriosclerotic changes later in life, requiring treatment in older age, with more advanced disease, and with higher comorbidity than men. In addition gender-related differences in the use of secondary medical prevention of PAD have been described. Future studies on the potential impact of gender on the results of vascular surgery are needed.


Genome Sequencing and Analysis of the Hypocrellin-Producing Fungus Shiraia bambusicola S4201.
Shiraia bambusicola has long been used as a traditional Chinese medicine and its major medicinal active metabolite is hypocrellin, which exhibits outstanding antiviral and antitumor properties. Here we report the 32 Mb draft genome sequence of S. bambusicola S4201, encoding 11,332 predicted genes. The genome of S. bambusicola is enriched in carbohydrate-active enzymes (CAZy) and pathogenesis-related genes. The phylogenetic tree of S. bambusicola S4201 and nine other sequenced species was constructed and its taxonomic status was supported (Pleosporales, Dothideomycetes). The genome contains a rich set of secondary metabolite biosynthetic gene clusters, suggesting that strain S4201 has a remarkable capacity to produce secondary metabolites. Overexpression of the zinc finger transcription factor zftf, which is involved in hypocrellin A (HA) biosynthesis, increases HA production when compared with wild type. In addition, a new putative HA biosynthetic pathway is proposed. These results provide a framework to study the mechanisms of infection in bamboo and to understand the phylogenetic relationships of S. bambusicola S4201. At the same time, knowledge of the genome sequence may potentially solve the puzzle of HA biosynthesis and lead to the discovery of novel genes and secondary metabolites of importance in medicine and agriculture.


The Open Triradiate Cartilage: How Young Is Too Young for Total Hip Arthroplasty?
There is, to our knowledge, no published literature regarding primary total hip arthroplasty (THA) in pediatric patients with an open triradiate cartilage. The purpose of this study was to report the outcomes following primary THA in pediatric patients with open triradiate cartilage at a single intuition. Using a single institution's Total Joint Registry, 12 patients (13 hips) were identified as having undergone primary THA with open triradiate cartilage between the years of 2000 and 2019. The mean age and body mass index of this group were 13.1 years and 25.5 kg/m2, respectively. The cohort was composed of 10 males, and the mean follow up was 5.5 years. Indications for surgery, functional outcomes, and radiographic signs of stable fixation were analyzed. The most common indication for surgery was avascular necrosis secondary to corticosteroid use (31%), followed by avascular necrosis after operative management of slipped capital femoral epiphysis (23%). The proportion of patients able to achieve independent, gait-aid free, ambulation improved from 23% to 100%. Mean postoperative Harris Hip Score was 92.3. All constructs were cementless, and bearing surfaces included ceramic-on-ceramic in 62% and ceramic on highly crosslinked polyethylene bearings in the remainder. Radiographic review at final follow up demonstrated osseointegration in 12 of 13 (92%) acetabular components. Although 1 patient experienced both acetabular component loosening and instability, on separate occasions, there were no incidences of infection, wound dehiscence, thromboembolic events, or failure secondary to wear. In this study, THA in patients with an open triradiate cartilage yielded significant clinical improvement, low complication rates and good initial implant survivorship at early follow up. Awaiting closure of the triradiate cartilage for concerns of decreased fixation and implant survivorship may be unnecessary. Level IV-case series.


Navigation of a magnetic micro-robot through a cerebral aneurysm phantom with magnetic particle imaging.
Cerebral aneurysms are potentially life threatening and nowadays treated by a catheter-guided coiling or by a neurosurgical clipping intervention. Here, we propose a helically shaped magnetic micro-robot, which can be steered by magnetic fields in an untethered manner and could be applied for a novel coiling procedure. This is shown by navigating the micro-robot through an additively manufactured phantom of a human cerebral aneurysm. The magnetic fields are applied with a magnetic particle imaging (MPI) scanner, which allows for the navigation and tomographic visualization by the same machine. With MPI the actuation process can be visualized with a localization accuracy of 0.68 mm and an angiogram can be acquired both without any radiation exposure. First in-vitro phantom experiments are presented, showing an idea of a robot conducted treatment of cerebral aneurysms.


Highly efficient evaluation of a gas mixer using a hollow waveguide based laser spectral sensor.
This paper aims to provide a fast, sensitive, and accurate characterization of a Mass Flow Controller (MFC) based gas mixer. The gas mixer was evaluated by using a hollow waveguide based laser spectral sensor with high efficiency. Benefiting from the sensor's fast response, high sensitivity and continuous operation, multiple key parameters of the mixer, including mixing uncertainty, linearity, and response time, were acquired by a one-round test. The test results show that the mixer can blend multi-compound gases quite efficiently with an uncertainty of 1.44% occurring at a flow rate of 500 ml/min, with the linearity of 0.998 43 and the response time of 92.6 s. The results' reliability was confirmed by the relative measurement of gas concentration, in which the isolation of the sensor's uncertainty was conducted. The measured uncertainty has shown well coincidence with the theoretical uncertainties of the mixer, which proves the method to be a reliable characterization. Consequently, this sort of laser based characterization's wide appliance on gas analyzer's evaluations is demonstrated.


Prevalence and determinants of hypertension among older adults: A comparative analysis of the 6th and 8th national health surveys of Bangladesh.
Hypertension is a major public health concern in low-and middle-income countries. A nationwide Health, Population, and Nutrition Sector Development Program in Bangladesh has been shown to be effective in resource-poor settings. This article aims to investigate whether the prevalence and determinants of adult hypertension changed from 2011 to 2018. The determinants of adult hypertension were assessed in 2011 and 2018 data of Bangladesh Demographic and Health surveys. These two surveys included both men and women over the age of 34 years and measured their blood pressure, weight, height, and other covariates. For both surveys, we estimated the age-standard prevalence of hypertension and relative, attributable and mediated risk of determinants of hypertension using hierarchical mixed-effects sequential Poisson regression models. The prevalence of adult hypertension increased by 10.9% from 29.5% in 2011 to 40.4% in 2018. The nationwide awareness program on the Health, Population and Nutrition Sector changed the risks associated with hypertension determinants over the years. During 2011, Socio-economic status (SES) was a major distal determinant of adult hypertension, explaining 21% of population-attributable risk (ART). However, other factors accounted for 90% of risk, mainly by excessive body weight (51%) and awareness of hypertension (39%). In contrast, SES only explained 16% of ART risk, with 97% of the risk mediated by excessive body weight (55%) and awareness of hypertension (41%). The study results highlight that hypertension among older adult was significantly increased over the six-year period. Specially, the socio-economic status, awareness of hypertension and excessive body weight were the significant determinants. Being awareness of hypertension and excessive body weight changed the causal pathways of socio-economic status. The results also highlight the value of studying the effect of non-communicable disease awareness programs to enhance our comprehension of factors influencing health.


Statin therapy lowers muscle sympathetic nerve activity and oxidative stress in patients with heart failure.
Despite standard drug therapy, sympathetic nerve activity (SNA) remains high in heart failure (HF) patients making the sympathetic nervous system a primary drug target in the treatment of HF. Studies in rabbits with pacing-induced HF have demonstrated that statins reduce resting SNA, in part, due to reductions in reactive oxygen species (ROS). Whether these findings can be extended to the clinical setting of human HF remains unclear. We first performed a study in seven statin-naïve HF patients (56 ± 2 yr; ejection fraction: 31 ± 4%) to determine if 1 mo of simvastatin (40 mg/day) reduces muscle SNA (MSNA). Next, to control for possible placebo effects and determine the effect of simvastatin on ROS, a double-blinded, placebo-controlled crossover design study was performed in six additional HF patients (51 ± 3 yr; ejection fraction: 22 ± 4%), and MSNA, ROS, and superoxide were measured. We tested the hypothesis that statin therapy decreases resting MSNA in HF patients and this would be associated with reductions in ROS. In study 1, simvastatin reduced resting MSNA (75 ± 5 baseline vs. 65 ± 5 statin bursts/100 heartbeats; P < 0.05). Likewise, in study 2, simvastatin also decreased resting MSNA (59 ± 5 placebo vs. 45 ± 6 statin bursts/100 heartbeats; P < 0.05). In addition, statin therapy significantly reduced total ROS and superoxide. As expected, cholesterol was reduced after simvastatin. Collectively, these findings indicate that short-term statin therapy concomitantly reduces resting MSNA and total ROS and superoxide in HF patients. Thus, in addition to lowering cholesterol, statins may also be beneficial in reducing sympathetic overactivity and oxidative stress in HF patients.


Formula Feeding as a Risk Factor for Attention-Deficit/Hyperactivity Disorder: Is Bisphenol A Exposure a Smoking Gun?
Breastfeeding during infancy is associated with a lower risk of attention-deficit/hyperactivity disorder (ADHD). Although this is presumably due to breast milk's nutritional advantages, formula-fed infants have, until recently, also been exposed to bisphenol A (BPA), a neurotoxic chemical previously used to manufacture baby bottles and formula cans. Our goal was to examine the association between formula feeding and preschool ADHD in 2 comparable, serial cohorts of preschool children who differ in BPA exposure during infancy. Cross-sectional analysis of the 2007 and 2011/12 National Survey of Children's Health (NSCH). Logistic regression was used to model preschool ADHD diagnoses as a function of breastfeeding, adjusting for 12 possible confounding variables using a propensity score. In the 2007 data set (weighted n = 9,644,405), formula-fed subjects had a 5-fold increased odds of ADHD compared with breastfed subjects (adjusted odds ratio [aOR]: 5.58, 95% confidence interval [CI], 2.16-14.41). In the 2011/12 data set (n = 9,732,865), there was no significant association between formula feeding and later ADHD (aOR: 1.05, 95% CI, 0.42-2.64). This is despite an increase in the prevalence of preschool ADHD in 2011 (0.88%) compared with 2007 (0.40%) (Rao-Scott χ, p < .0075). Compared with breastfed infants, ADHD was more common among formula-fed infants in the 2007 but not the 2011/12 sample, where exposure to BPA was markedly reduced. These findings suggest that the reduced prevalence of ADHD among breastfed infants may not be due to the nutritional benefits of breast milk, but rather early exposure to BPA, a neurotoxic chemical previously found in infant formula.


Pharmacokinetic principles in the inner ear: Influence of drug properties on intratympanic applications.
Local drug delivery to the ear has gained wide clinical acceptance, with the choice of drug and application protocol in humans largely empirically-derived. Here, we review the pharmacokinetics underlying local therapy of the ear using the drugs commonly used in clinical practice as examples. Based on molecular properties and perilymph measurements interpreted through computer simulations we now better understand the principles underlying entry and distribution of these and other drugs in the ear. From our analysis, we have determined that dexamethasone-phosphate, a pro-drug widely-used clinically, has molecular and pharmacokinetic properties that make it ill-suited for use as a local therapy for hearing disorders. This polar form of dexamethasone, used as a more soluble agent in intravenous preparations, passes less readily through lipid membranes, such as those of the epithelia restricting entry at the round window membrane and stapes. Once within the inner ear, dexamethasone-phosphate is cleaved to the active form, dexamethasone, which is less polar, passes more readily through lipid membranes of the blood-perilymph barrier and is rapidly eliminated from perilymph without distributing to apical cochlear regions. Dexamethasone-phosphate therefore provides only a brief exposure of the basal regions of the cochlea to active drug. Other steroids, such as triamcinolone-acetonide, exhibit pharmacokinetic properties more appropriate to the ear and merit more detailed consideration.


Engineering and women's health: a slow start, but gaining momentum.
While biomedical engineers have participated in research studies that focus on understanding aspects particular to women's health since the 1950s, the depth and breadth of the research have increased significantly in the last 15-20 years. It has been increasingly clear that engineers can lend important knowledge and analysis to address questions that are key to understanding physiology and pathophysiology related to women's health. This historical survey identifies some of the earliest contributions of engineers to exploring aspects of women's health, from the behaviour of key tissues, to issues of reproduction and breast cancer. In addition, some of the more recent work in each area is identified and areas deserving additional attention are described. The interdisciplinary nature of this area of engineering, along with the growing interest within the field of biomedical engineering, promise to bring exciting new discoveries and expand knowledge that will positively impact women's health in the near future.


Effect of tubal sterilization on ovarian follicular reserve and function.
Tubal ligation may reduce the ovarian blood flow and lead to tissue damage to the ovary. If so, this may also result in a significant decrease of the total follicular pool. We performed a long-term evaluation of ovarian reserve and function after tubal sterilization in a longitudinal prospective comparison cohort. In an university tertiary-care center, 26 women undergoing laparoscopic tubal sterilization with the use of bipolar coagulation, and 26 matched control subjects underwent measurement of follicle-stimulating hormone, luteinizing hormone, 17beta-estradiol, and inhibin on menstrual cycle day 3 before (baseline) and at 6, 12, 18, 24, and 60 months after the sterilization for ovarian reserve evaluation. At baseline and 12 and 24 months after tubal ligation, women who underwent sterilization were sampled every other day across an entire menstrual cycle for follicle-stimulating hormone, luteinizing hormone, 17beta-estradiol, inhibin, and progesterone determination to evaluate ovarian function. No significant changes were observed either within or between groups for any parameter, despite the fact that a 45% and 30% increase in follicle-stimulating hormone concentration from baseline to the 60-month control was detected in tubal sterilization and control groups of women, respectively. No significant changes were observed in the mean area under the curve of follicle-stimulating hormone, luteinizing hormone, estradiol, inhibin, and progesterone per menstrual cycle at baseline and 12 and 24 months after sterilization. This 5-year follow-up study suggests that there is neither an accelerated decline of ovarian follicular reserve nor ovarian dysfunction after tubal sterilization by electrocoagulation.


Postural control impairments in individuals with autism spectrum disorder: a critical review of current literature.
Motor impairments in individuals with autism spectrum disorder (ASD) have been frequently reported. In this review, we narrow our focus on postural control impairments to summarize current literature for patterns, underlying mechanisms, and determinants of posture in this population. A literature search was conducted through Medline, ISI web of Knowledge, Scopus and Google Scholar to include studies between 1992 and February 2013. Individuals with ASD have problems in maintaining postural control in infancy that well persists into later years. However, the patterns and underlying mechanisms are still unclear. Examining postural control as an endophenotype or early diagnostic marker of autism is a conceptual premise which should be considered in future investigations. At the end of the review, methodological recommendations on the assessment of postural control have also been provided.


Description of four new species of Ochlerini from South America (Hemiptera: Pentatomidae: Discocephalinae).
The tribe Ochlerini Rolston was proposed in 1981 to house 23 genera of Neotropical pentatomids, most of them containing few species and poorly represented in entomological collections. After a quarter century of accumulated taxonomic knowledge the tribe totals 36 genera and 133 species, but a number of taxa still require revision or remain undescribed. Here we describe and illustrate four new species from South America, Cromata flavida sp. nov., Lincus curvatus sp. nov., Ocellatocoris longirostris sp. nov., and Xynocoris ecuadorensis sp. nov. The specimens of L. curvatus and X. ecuadorensis were collected on oil palms (OxG hybrids, Elaeis oleifera x Elaeis guineensis) affected by the lethal wilt (marchitez sorpresiva) disease.


Association between oral fluoroquinolone use and the development of retinal detachment: a systematic review and meta-analysis of observational studies.
Several observational studies have been published investigating the association between oral fluoroquinolone use and the development of retinal detachment; however, the findings are not concordant. This study is a meta-analysis of the existing literature and estimates the overall absolute risk of such an event. Electronic databases were searched for observational studies on the association between oral fluoroquinolone and retinal detachment up to August 2014. Studies that did not meet the criteria for meta-analysis were narratively reviewed. Cases of retinal detachment during current fluoroquinolone use were also extracted for absolute risk calculation. Seven observational studies were included. Three (case-control and self-controlled case series studies) were eligible for meta-analysis and four (cohort studies) were narratively reviewed. The rate ratio of the case-control studies was 1.82 (95% CI 0.67-4.93), I(2) =96% and the incidence rate ratio of the self-controlled case series was 1.03 (95% CI 0.84-1.27), I(2) =36%. Three of the four cohort studies found no significant association between oral fluoroquinolone use and the development of retinal detachment. The pooled absolute risk of retinal detachment whilst on current oral fluoroquinolone treatment is estimated to be 4.85 per 1000000 prescriptions (95% CI 0.78-8.91). The findings of this systematic review and meta-analysis do not support an association between oral fluoroquinolone use and the development of retinal detachment. Given the low absolute risk, such an event would be rare if there were an association. The current prescribing practice for fluoroquinolones should not be altered because of a previously suggested potential risk of retinal detachment.


Influence of trunk muscle co-contraction on spinal curvature during sitting for desk work.
Nowadays, a lot of office workers are forced to sit at a desk for many hours while doing their jobs. While sitting, the pelvis rotates backwardly, and lumbar lordosis is flattened. At the same time, the load on the intervertebral discs and spine increases. Sitting in a slumped position is known to increase disc pressure even more, and to aggravate chronic low back pain (CLBP). Therefore, it is very important to teach workers about the correct sitting posture. In addition, it has been recognized that co-contraction of the deep spine-stabilizing muscles enhances lumbar segmental stability and the sacro-iliac joint. However, little is known about the influence of co-contraction of the trunk deep muscles on spinal curvature during sitting for while doing desk work. The purpose of this study was to compare EMG (electromyographic) activity of the trunk muscles during slump sitting with that during co-contraction of the trunk muscles and to investigate how this co-contraction influences spinal curvature. Ten healthy male volunteers (21.7 +/- 2.5 years old) without CLBP participated in the study. Bipolar surface electrodes were attached to the rectus abdominis, the obliquus externus abdominis, the obliquus internus abdominis, the lower back extensor muscles (L3) and the multifidus on the right side. EMG signals were continuously recorded during slump sitting and co-contraction of the trunk muscles, simulating a desk work sitting posture; i.e., slightly inclined forward. They were amplified, band-pass filtered, digitized and stored by a data acquisition system. The average muscle activity values over the five-second sample for each sitting posture were normalized to maximal voluntary contractions (%MVC). While the subjects performed both sitting postures, the curvature of the spine was measured using a new skin-surface and hand-held device, the "Spinal Mouse". More significant activities of the trunk muscles, with the exception of the rectus abdominis, were observed during co-contraction of the trunk muscles than during slump sitting The co-contraction of the trunk muscles resulted in significantly less lumbar curvature and more sacral angle than during slump sitting. The thoracic curvature showed no significant change during either sitting posture. The results of this study indicated that co-contraction of the trunk muscles during sitting while doing desk work could bring about the correct lumbar curvature, and effectively stabilize the lumbopelvic region, and decrease focal stress on passive structures.


Blood biomarkers for personalized treatment and patient management decisions in community-acquired pneumonia.
In patients with community-acquired pneumonia (CAP), blood biomarkers can help to substantially improve individual decisions involving initiation, (de-)intensification, and cessation of antibiotics, and initial risk stratification, site-of-care assignment (outpatient versus ward versus ICU), and discharge. To illustrate these processes, this review summarizes recent findings from trials investigating the use of two hormokines, procalcitonin (PCT) or proadrenomedullin (ProADM), in personalized treatment and management decisions in CAP patients. Many biomarkers from distinct pathophysiological pathways have been evaluated in observational studies. However, only few analytes have been tested for efficacy and safety in numerous, large observational studies or in prospective, randomized, interventional trials. Among the latter, PCT has been demonstrated to be well tolerated and highly effective for monitoring and de-escalating antibiotic therapy. ProADM has shown higher accuracy for short-term and long-term adverse outcome prediction and improves prognostic accuracy when combined with current clinical risk scores, that is, Pneumonia Severity Index, the CURB65 (confusion, uremia, respiratory rate, blood pressure, age at least 65 years) score, and Risk of Early Admission to ICU, compared to applying the respective score alone. ProADM use has - in a pilot interventional study - improved site-of-care decisions and tended to shorten length hospitalization. Inclusion of biomarker data in clinical algorithms improves individual decision-making in CAP patients. Interventional trials should be conducted to determine these markers' ultimate utility in patient management.


A new direction for cognitive development in nursing to prepare the practitioners of the future.
The quest to improve metacognitive control of critical thinking abilities has gained increasing importance throughout the world during the past thirty years. Self-regulated learning, a concept within the construct of critical thinking, is currently receiving much attention from educational theorists. A self-regulated individual requires a dependable experiential knowledge base, uses cognitive critical thinking strategies in a reflective manner, and is affected by social and cultural influences. One purpose of this article is to review the significant legacy of cognitive research in nursing. The research is categorized according to the concepts of the self-regulation learning model; metacognitive self-regulation (critical thinking, information processing), behavioral self-regulation (reflective practice) and environmental self-regulation (social interaction, clinical context). Another purpose of the article is to explore some self-regulated learning techniques that could be used to improve metacognitive control of critical thinking abilities in practice situations. Nursing leaders in service and education should consider a new approach for cognitive development in practice, since the result could be outcomes that are more closely aligned with mandates of governing bodies, growth of the discipline and patient welfare.


Prospective, randomized comparison of 3-dimensional computed tomography guidance versus TEE data for left atrial appendage occlusion (PRO3DLAAO).
Preliminary data comparing 3-dimensional computed tomography (3D-CT) to transesophageal echocardiography (TEE) for left atrial appendage occlusion (LAAO) indicates that 3D-CT provides more accurate measurements and improves case planning. Therefore, we conducted a pilot study comparing 3D-CT to TEE in occluder selection accuracy and procedural efficiency. From May 2016 to February 2017, 24 patients were prospectively randomized to undergo LAAO using either TEE or 3D-CT. The primary endpoint was device accuracy while the secondary endpoints included # devices per case, # guide catheters used per case, # fluoroscopy angles used, procedure time, fluoroscopy time, radiation dose, and major adverse events (stroke, MI, device embolization, perforation, death). Procedure success was 100% and 92% for the 3D-CT and 2D-TEE cohorts respectively. Accuracy for 1st device selection 92% and 27% (P = .01) for 3D-CT and 2D-TEE respectively but with intra-procedural upsizing in the 2D-TEE cohort, the 2D-TEE cohort accuracy increased to 64% while the 3D-CT groups 92% was accurate (P = .33). Case planning using 3D-CT was significantly more efficient with respect to device utilization (CT 1.33 ± 0.7 vs. 2D-TEE 2.5 ± 1.2 P = .01), guide catheters (CT 1 vs. 2D-TEE 1.7 ± 0.8 P = .01) and procedure time (3D-CT 55 ± 17 min vs. 2D-TEE 73 ± 24 min P < .05). One major adverse event, a stroke occurred in the 2D-TEE group. In this single-center pilot study, CT guided LAAO case planning was associated with improved device selection accuracy and procedural efficiency. This study data supports the notion that comprehensive 3D assessment significantly simplifies LAAO, minimizing the time and number of steps needed.


Using implementation mapping to develop strategies for preventing non-communicable diseases in Japanese small- and medium-sized enterprises.
Workplace programs to prevent non-communicable diseases (NCDs) in the workplace can help prevent the incidence of chronic diseases among employees, provide health benefits, and reduce the risk of financial loss. Nevertheless, these programs are not fully implemented, particularly in small- and medium-sized enterprises (SMEs). The purpose of this study was to develop implementation strategies for health promotion activities to prevent NCDs in Japanese SMEs using Implementation Mapping (IM) to present the process in a systematic, transparent, and replicable manner. Qualitative methods using interviews and focus group discussions with 15 SMEs and 20 public health nurses were conducted in a previous study. This study applied the Consolidated Framework for Implementation Research and IM to analyze this dataset to develop implementation strategies suitable for SMEs in Japan. In task 2 of the IM, we identified performance objectives, determinants, and change objectives for each implementation stage: adoption, implementation, and maintenance; to identify the required actors and actions necessary to enhance implementation effectiveness. Twenty-two performance objectives were identified in each implementation stage. In task 3 of the IM, the planning group matched behavioral change methods (e.g., modeling and setting of graded tasks, framing, self-re-evaluation, and environmental re-evaluation) with determinants to address the performance objectives. We used a consolidated framework for implementation research to select the optimal behavioral change technique for performance objectives and determinants and designed a practical application. The planning team agreed on the inclusion of sixteen strategies from the final strategies list compiled and presented to it for consensus, for the overall implementation plan design. This paper provides the implementation strategies for NCDs prevention for SMEs in Japan following an IM protocol. Although the identified implementation strategies might not be generalizable to all SMEs planning implementation of health promotion activities, because they were tailored to contextual factors identified in a formative research. However, identified performance objectives and implementation strategies can help direct the next steps in launching preventive programs against NCDs in SMEs.


A genome-wide siRNA screen for regulators of tumor suppressor p53 activity in human non-small cell lung cancer cells identifies components of the RNA splicing machinery as targets for anticancer treatment.
Reinstating wild-type tumor suppressor p53 activity could be a valuable option for the treatment of cancer. To contribute to development of new treatment options for non-small cell lung cancer (NSCLC), we performed genome-wide siRNA screens for determinants of p53 activity in NSCLC cells. We identified many genes not previously known to be involved in regulating p53 activity. Silencing p53 pathway inhibitor genes was associated with loss of cell viability. The largest functional gene cluster influencing p53 activity was mRNA splicing. Prominent p53 activation was observed upon silencing of specific spliceosome components, rather than by general inhibition of the spliceosome. Ten genes were validated as inhibitors of p53 activity in multiple NSCLC cell lines: genes encoding the Ras pathway activator SOS1, the zinc finger protein TSHZ3, the mitochondrial membrane protein COX16, and the spliceosome components SNRPD3, SF3A3, SF3B1, SF3B6, XAB2, CWC22, and HNRNPL. Silencing these genes generally increased p53 levels, with distinct effects on CDKN1A expression, induction of cell cycle arrest and cell death. Silencing spliceosome components was associated with alternative splicing of MDM4 mRNA, which could contribute to activation of p53. In addition, silencing splice factors was particularly effective in killing NSCLC cells, albeit in a p53-independent manner. Interestingly, silencing SNRPD3 and SF3A3 exerted much stronger cytotoxicity to NSCLC cells than to lung fibroblasts, suggesting that these genes could represent useful therapeutic targets.


A facile route to nano-sized nickel sulfide via thermolysis of nickel alkanethiolate.
Nano-sized nickel sulfides were synthesized by the thermolysis of nickel alkanethiolates in the presence of coordinating ligands. Nickel alkanethiolates were synthesized by the reaction of the square planar nickel 1-dimethylamino-2-methyl-2-propanolate [Ni(dmamp)2] with various n-alkanethiols. The effect of ligands in the reaction system has been investigated to control the size and shape of nano-sized nickel sulfides. TEM images show that the products are nano-sized nickel sulfides in rod and plate shapes. Nickel alkanethiolates and nano-sized nickel sulfides have been characterized by means of X-ray diffraction and transmission electron microscopy.


Dose-dependent stimulatory and inhibitory effects of luminal and serosal n-butyric acid on epithelial cell proliferation of pig distal colonic mucosa.
Large bowel bacteria convert various carbohydrates into short-chain fatty acids (SCFA). SCFA stimulate epithelial cell proliferation of the large intestine in vivo and inhibit that of various cells in vitro. Supposing that too high concentration of SCFA on the serosal side is responsible for their inhibitory effect in vitro, we studied effects of luminal and serosal n-butyric acid (0, 0.1, 1, or 10 mmol/L, adjusted to neutral pH) on the epithelial cell proliferation rate of pig colonic mucosa in organ culture taking crypt cell production rate (CCPR) as the measure of proliferative activity. With 0 or 0.1 mmol/L n-butyric acid on the serosal side, luminal n-butyric acid increased CCPR at 1.0 mmol/L, and decreased CCPR at 10 mmol/L when compared to the luminal 0 mmol/L control. With 1.0 or 10 mmol/L serosal n-butyric acid, luminal n-butyric acid depressed CCPR dose-dependently. The above results indicated that n-butyric acid stimulated colonic epithelial cell proliferation at low concentration and inhibit it at high concentration with interaction effect to enhance the inhibitory action. The stimulatory effect of a low dose of serosal n-butyric acid may be responsible for the distant trophic effect of SCFA.


Effects of Reiki on Pain and Anxiety in Women Hospitalized for Obstetrical- and Gynecological-Related Conditions.
Purpose: To determine the effect of Reiki on pain and anxiety in women in antepartum, intrapartum, postpartum, gynecology, and gyn/oncology, settings. Method: This exploratory, comparative study used a Likert-type scale of 0 to 10 to measure pain and anxiety, and a survey asking about lingering effects of treatment. Results: Mean pain scores after Reiki significantly decreased from 3.24 to 1.52 (n = 203; z = -11.67, p < .001). Mean anxiety scores after Reiki significantly decreased from 3.56 to 1.28 (n = 195; z = -11.42, p < .001). Women were asked if the effects lingered for any length of time post-Reiki treatment, and 91 of 101 responded affirmatively that decreased pain and/or anxiety continued. Conclusion: Findings from this study confirm the positive and lingering effects of Reiki in women hospitalized for obstetrical and gynecological conditions.


Operating characteristics of the factor flow networks in rural areas: A case study of a typical industrial town in China.
The networks of factor flows in rural areas are the main support for rural revitalization, which has become one of the research trends in rural geography. Taking a typical industrial town in China as an example, the study explored the operating characteristics of rural factor flow networks and the relations of multi-factor flows based on the social survey method and fine-grained flows data. Results showed that population flows, capital flows and policy flows increased significantly in rural areas. Thereinto, population flows, especially labor flows, mainly ran into the townships and industrial cluster villages, so did capital inflows and outflows, while policy flows ran around the township. The villages with dense population and capital flows formed the "central villages", which had exceeded the township in the two flow networks. Policy flows and capital flows played a guiding role in population flows, so did the policy flows on the capital flows. Meanwhile, the population flows and the capital flows could reinforce each other. In conclusion, a multi-center structure network with the separation of economic center and administrative center had been formed in rural areas. And there was a close interaction between these factor flows. Furthermore, the theoretical model of town-village symbiotic network was constructed.


[Surgical treatment for clinical stage II and III small cell lung cancer patients].
To evaluate a surgical resection in multidisciplinary treatment for clinical stage (c-stage) II and III small cell lung cancer (SCLC) patients, we examined the postoperative prognosis concerning in 18 patients who underwent complete surgical resection. Five-year survival rate of 8 c-stage II and 10 c-stage III patients showed 62.5% and 46.7%, respectively. Of these, 7 patients underwent preoperative induction chemotherapy resulting in down-staging to c-stage 0-I, and their survival rate at 5 years after sugery was as good as 68.6%. However, in 4 (57.1%) of 7 patients, tumor cells proved to be alive by pathological assessment of lymph nodes. As a consequence, it was suggested that surgery for c-stage II and III SCLC patients is a meaningful treatment considering their prognoses. In particular, even though the patients show a favorable response of preoperative chemotherapy, to completely eliminate remnant tumor cells, a surgical resection may be necessary.


Control of shunt infection. Report of 150 consecutive cases.
The author analyzes 150 consecutive ventriculovenous, ventriculoperitoneal, and lumboperitoneal shunt procedures with particular attention to shunt colonization by Staphylococcus epidermidis. There was one primary infection with Staphylococcus epidermidis early in the series, and in two other cases, the organism was felt to be a secondary invader. In those procedures involving either primary placement or revision of a ventriculovenous shunt, there was not a single infection. The operative protocol that has virtually eliminated Staphylococcus epidermidis is outlined.


Protective effect of caffeine against high sugar-induced transcription of microRNAs and consequent gene silencing: a study using lenses of galactosemic mice.
Previous studies have shown that caffeine prevents the formation of cataracts induced by a high-galactose diet and consequent oxidative stress. The objective of this study was to investigate if this protective effect is reflected in the attenuation of the transcription of microRNAs (miRNAs) known to induce apoptosis and cell death by gene silencing. Young CD-1 mice were fed either a normal laboratory diet or a diet containing 25% galactose with or without 1% caffeine. One week later, the animals were euthanized, and the lenses isolated and promptly processed for RNA isolation and subsequent preparation of cDNAs by reverse transcriptase reaction. Mature miRNA (miR)-specific cDNAs were then quantified with PCR in a 96-well microRNA-specific cassette using an ABI7900HT PCR machine. As expected from previous studies, the lenses were positive for all 84 miRs corresponding to the miRNA probes present in the cassette wells. However, the levels of at least 19 miRs were significantly elevated in galactosemic lenses compared to those in the normal lenses. The majority are proapoptotic. Such elevation was inhibited by caffeine. This has been demonstrated for the first time. Since aberrant elevation of miRNAs silences various genes and consequently deactivates protein translation, and since caffeine downregulates such aberration, the beneficial effect of caffeine could be attributed to its ability to suppress elevation of toxic miRs and consequent gene silencing.


Immunogenotyping in Hodgkin's disease.
This review presents and discusses the immunogenotypic findings in 112 cases of Hodgkin's disease (HD) and eight Hodgkin's cell lines. Clonal rearrangements of the T cell receptor gamma and beta chain, as well as immunoglobulin heavy and light chain genes, are detected in the majority of nodular sclerosis and lymphocytic depletion subtypes. Together with the recent immunophenotypic data, these findings are in favour of the view that HD is a disease of activated lymphoid cells. Further investigations will be necessary to characterize the morphology and immunophenotype of the clonally rearranged cell population which seems not to be confined to the Sternberg-Reed and Hodgkin cell in every case. Prospective clinical studies including the genotype of HD cases have to be done in order to address the question of whether or not distinctive immunogenotypic profiles correlate with the clinical course of this lymphoproliferative disorder.


[Diagnostic errors in angiomas].
A comparison of clinical statements and histologic findings reveals a lower diagnostic success in angiomas, compared with other benign tumours. Cavernous forms of angiomas are very often not discerned. Capillary angiomas are misdiagnosed as cavernous ones, and teleangiectatic nevi as angiomas. Mistakes and their incidences are pointing not at real difficulties of differentialdiagnosis, but at wrong information of physicians as to the cause of errors. According to this supposition, a great part of textbooks in different medical disciplines offer no correct representation of this object. Our results reveal problems concerning the representation of some aspects of skin diseases outside of Dermatology. The diagnosis of angiomas, with special regard to the therapeutic consequences of the fundamental distinction of angiomas from angiectatic nevi by proliferation of endothelial cells, and of cavernous from capillary angiomas by vascular structure imitating arteries or veins, demands more attention in medical education.


Load knowledge reduces rapid force production and muscle activation during maximal-effort concentric lifts.
Rapid force development is a key factor influencing performance and injury risk in movements where little time is available for force production; thus there is a need to develop interventions that enhance this ability. In the present study, the influence of load knowledge on mechanical output [rate of force development; (RFD) and power] and muscle activation [electromyographic (EMG) responses] in the concentric-only bench press throw exercise was studied. Fifteen strength-trained individuals performed 6 sets of 6 maximal explosive repetitions in a single test session after extensive familiarization. In three of these sets the subjects were given knowledge about the load before each repetition (known condition; KC), whereas in the other three sets they were given no information (unknown condition; UC). In both conditions the loads were 30, 50 and 70 % of maximum, but condition and load orders were randomized. RFD (24-50 %) and power output (20-39 %) were significantly higher in UC in the early time intervals from movement onset (<150 ms). In addition, UC elicited greater EMG amplitudes in anterior deltoid both prior to movement onset (pre50-0 ms) and in the early time intervals (<100 ms) after movement onset, and in pectoralis major after movement onset (<100 ms). UC resulted in a greater initial activation of the muscles and both a higher RFD and mechanical power output in the early phase of the movement under all loading conditions (30-70 % of maximum). UC appears to offer a novel neuromuscular stimulus, and further research on the effects of continued exposure is warranted.


Transfemoral Valve-In-Valve in a Degenerated Small Aortic Bioprosthesis: Five-Year Follow Up.
A small-sized bioprosthesis can limit transcatheter valve-in-valve (V-in-V) implantations. The case is reported of a 91-year-old woman who had successfully undergone a V-in-V procedure with a 26 mm CoreValve in a previously implanted Mitroflow 19 mm valve. At the five-year follow up the prosthesis showed good echocardiographic function and the patient was alive and free from major symptoms. The patient died three months after the follow up examination at the age of 96 years. This case demonstrates the feasibility, with acceptable longterm functioning, of a V-in-V procedure involving a small bioprosthesis. To the authors' knowledge, the present report is the longest follow up of a patient who underwent V-in-V transcatheter aortic valve implantation in a 19 mm bioprosthesis (15.4 mm internal diameter). Video 1: Preoperative aortography showing moderate-to-severe aortic regurgitation. Video 2: Pre-implantation aortic balloon valvuloplasty. Video 3: Post-deployment aortography showing moderate-to-severe aortic regurgitation. Video 4: The final result. After post-dilation of the under-expanded 26 mm CoreValve, the aortic regurgitation is slightly reduced.


[Effect of laparoscopic radical operation on systemic immunity in patients with colorectal cancer].
To compare the effect of laparoscopic radical operation and open operation on systemic immunity in patients with colorectal cancer. Sixty patients with colorectal cancer were randomly divided into laparoscopic and open operation groups from March 2004 to December 2004, each group had 30 cases. CRP, IgA, IgM, IgG, CD3 (+) cells, CD4 (+) cells, CD8 (+) cells, NK cells, CD4 (+) CD5RA (+) cells, CD4 (+) CD45RO (+) cells and lymphocytes in peripheral blood were counted and compared on the 1st day before operation, 3rd and 7th day after operation. The two groups were comparable as for age, tumor location and stages. In open operation group, lymphocyte counts were (1.09+/- 0.29) x 10(9)/L, CD4 (+) cell (0.54 +/- 0.14) x 10(9)/L, CD8 (+) cell (0.31 +/- 0.08) x 10(9)/L, CD4 (+) CD45RO (+) (61.1+/- 8.9)%, and IgM level (136.9+/- 52.8) IU/ml, IgG (115.2 +/- 45.7) IU/ml on the 3rd day after operation, CD8 (+) cell counts were (0.32 +/- 0.09) x 10 (9)/L, CD4 (+) CD45RO (+) cell (63.2 +/- 9.1)% on the 7th day after operation, were all significantly lower than those on the 1st day before operation respectively(P< 0.05, P< 0.01). In laparoscopic operation group, the decreases of such parameters except CD4 (+) CD45RO (+) cell (62.7 +/- 12.5)% were not obvious on the 3rd day after operation. There were significant difference in lymphocyte counts (1.29 +/- 0.37) x 10( 9 )/L, IgM (164.5 +/- 48.2) IU/ml and CD8 (+) cell counts (0.38 +/- 0.09) x 10 (9) /L on the 3rd day after operation between two groups (P< 0.05). Compared with open radical operation, laparoscopic radical operation has predominance in protecting systemic immunity to treat colorectal carcinoma.