Clitoromegaly and abdominal tumour as leading signs of a mediastinal non-Hodgkin lymphoma.
A 2-year-old girl was admitted with clitoromegaly, mediastinal tumour and enlarged kidneys. A seventh cranial nerve palsy was associated with an increased cell count in cerebrospinal fluid. The diagnosis of a lymphoblastic lymphoma was confirmed by a cervical lymph-node biopsy. Six years after diagnosis and treatment according to the BFM protocol the girl remains in first complete remission.


Responsible health insurance revisited: pouring liberal wine into a conservative bottle.
In 1991, an article appeared proposing a plan for "Responsible National Health Insurance" (RHI) that contained three crucial elements supported by economists affiliated with two conservative policy institutions (the American Enterprise Institute and the Heritage Foundation). The central purpose of this article is to revisit RHI in light of developments over the past decade, and to make the case that liberals, rather than reject RHI, now should support it, provided conservatives agree to sufficient funding. In this article, I recommend "pouring liberal wine into this conservative bottle."


Minimal Clinically Important Differences in Functional Independence After a Knowledge Translation Intervention in Stroke Rehabilitation.
To examine the odds of persons with stroke achieving minimal clinically important difference (MCID) in functional independence during inpatient rehabilitation relative to cognitive impairment (CI) severity, site, and rehabilitation teams' exposure to a Cognitive Orientation to daily Occupational Performance (CO-OP) knowledge translation (KT) intervention. A pre-post observational study was conducted using data from a centralized referral system. Our research team implemented a CO-OP KT intervention as part of a larger study aimed at training teams to use the CO-OP approach. Five inpatient rehabilitation units. Cases extracted from a centralized referral system from the 5 participating units. Not applicable. The FIM instrument data from 12 months preintervention and 6 months postintervention were analyzed. A logistic regression was performed to determine the odds ratios (ORs) for achieving MCID based on sample cohort (historical control not exposed to CO-OP KT vs post-CO-OP KT intervention), controlling for site and severity of CI. A model that considered the intervention, admission score, CI severity, and site was the best fit for the cases analyzed. Those with severe CI were less likely to achieve FIM total MCID compared to those with no CI (P=<.001; OR=.18; 95% confidence interval, .09-.39). Taking site and CI into account, cases post CO-OP KT intervention were significantly more likely to achieve MCID on FIM motor (P=.048; OR=1.4; 95% confidence interval, 1.00-1.98) than historical controls. The CO-OP KT intervention is associated with increased odds of achieving MCID in the FIM motor subscale in inpatient stroke rehabilitation.


A Walkthrough of Nonlinear Capacitance Measurement of Outer Hair Cells.
Nonlinear capacitance (NLC) measures are often used as surrogate measures of outer hair cell (OHC) electromotility (eM), since the two are commonly thought to share many biophysical features. The measurement of NLC is simpler than direct measurements of eM and, therefore, many investigators have adopted it. A standard patch-clamp hardware configuration is sufficient for recording NLC, given the proper software interface. Thus, the approach is cost effective. We use the software jClamp since it is tailored to capacitance measurement. Here we detail steps that we use to measure NLC. The walk through includes isolation of guinea pig OHCs, building voltage commands, recording, and analysis.


Isolation and structure of lamprey (Petromyzon marinus) insulin.
Insulin has been purified to homogeneity from the caudal and cranial pancreas of the adult sea lamprey (Petromyzon marinus). The final yield was 18.6 nmol/g (127.8 micrograms/g). The structures of both A- and B-chains have been determined using amino acid analyses, gas-phase sequence analyses, and proteolytic mapping by fast atom bombardment-mass spectrometry. The sequence of the A-chain was found to be GIVEQCCHRKCSIYDMENYCN. The sequence of the B-chain, extended at the amino terminus, was determined to be SALT-GAGGTHLCGSHLVEALYVVCGDRGFFYTPSKT. Lamprey insulin retains the common features of vertebrate insulins. Sea lamprey insulin has no more homology to hagfish (Myxine glutinosa) insulin than it has to the teleost fish or to mammalian insulins.


Clinical Problem Solving and Using New Paths in the Laboratory: Learning from Case Studies.
Three selected casuistic studies of individual patient problems from my long-standing professional experience are presented. I intend to highlight the potential contribution of case studies, including new approaches of laboratory investigation, for the advancement of pathophysiological knowledge and would encourage to "rehabilitate" the low academic profile generally attributed to "case reports."


Influence of glucose on polysensory properties of neurons of the ventromedial nucleus of the hypothalamus.
Using the method of intracellular pickup of neuronal activity, a high degree of convergence of impulses of various modalities onto the cells of the ventromedial nucleus of the hypothalamus was established in cats immobilized by means of diplacin dichloride. Great similarity was identified in the patterns of responses to somatic, visceral, light, and sound stimuli. With intravenous administration of glucose, 32% of the neurons studied increased their convergent capacity, 19% of the cells increased the frequency of spikes, and 23% changed the phase of the reaction. The excitatory type of reaction predominated in the responses of the cells investigated.


High incidence of PI3K pathway gene mutations in South Indian cervical cancers.
Cervical cancer is the second most common cancer in India. The phosphatidylinositol-3 kinase (PI3K) signaling is one of the most commonly activated pathways in cancer and comprises key molecules commonly targeted in cancer therapy. This study analyzed six PI3K pathway gene mutations. We carried out targeted next-generation sequencing of six PI3K pathway genes (PIK3CA, PIK3R1, PTEN, AKT1, TSC2, and mTOR) in a total of 93 South Indian cervical cancer samples and confirmed them by sanger sequencing. The PI3K pathway gene mutations were observed in 54.8% (51/93) of the tumors and PIK3CA was the most mutated (34.4%, 32/93), followed by TSC2 (18.3%, 17/93), and PIK3R1 (14%, 13/93). The PIK3CA hotspot mutations E542K and E545K observed in this study were likely to disrupt the p110α-p85α interaction that could result in the PI3K pathway activation. We also found a few novel mutations in PIK3R1, PTEN, AKT1, TSC2, and mTOR genes while some of the tumors harbored multiple mutations in the genes of the PI3K pathway. The majority of the tumors were positive for high-risk HPV16/18 (60.7%). The high incidence of the PI3K pathway gene mutations observed in this study could be exploited for the therapeutic management of cervical cancers.


RICTULARIA JIYEONI N. SP. (NEMATODA: RICTULARIIDAE) FROM THE STRIPED FIELD MOUSE, APODEMUS AGRARIUS, IN KOREA.
Rictularia jiyeoni n. sp. from the small intestine of the striped field mouse, Apodemus agrarius, in Korea, is described and illustrated. Specimens were studied using light and scanning electron microscopies. This rictulariid nematode is closest to the Rictularia species that have a reduced number of combs and spines. However, the new species can be differentiated from the other species of Rictularia by having 36-58 perioral denticles, a buccal capsule with a single esophageal tooth, and 37-44 pairs of combs and spines of which 32-37 are prevulvar and 5-11 are postvulvar.


Electronic Health Data Predict Outcomes After Aneurysmal Subarachnoid Hemorrhage.
Using electronic health data, we sought to identify clinical and physiological parameters that in combination predict neurologic outcomes after aneurysmal subarachnoid hemorrhage (aSAH). We conducted a single-center retrospective cohort study of patients admitted with aSAH between 2011 and 2016. A set of 473 predictor variables was evaluated. Our outcome measure was discharge Glasgow Outcome Scale (GOS). For laboratory and physiological data, we computed the minimum, maximum, median, and variance for the first three admission days. We created a penalized logistic regression model to determine predictors of outcome and a multivariate multilevel prediction model to predict poor (GOS 1-2), intermediate (GOS 3), or good (GOS 4-5) outcomes. One hundred and fifty-three patients met inclusion criteria; most were discharged with a GOS of 3. Multivariate analysis predictors of mortality (AUC 0.9198) included APACHE II score, Glasgow Come Scale (GCS), white blood cell (WBC) count, mean arterial pressure, variance of serum glucose, intracranial pressure (ICP), and serum sodium. Predictors of death/dependence versus independence (GOS 4-5)(AUC 0.9456) were levetiracetam, mechanical ventilation, WBC count, heart rate, ICP variance, GCS, APACHE II, and epileptiform discharges. The multiclass prediction model selected GCS, admission APACHE II, periodic discharges, lacosamide, and rebleeding as significant predictors; model performance exceeded 80% accuracy in predicting poor or good outcome and exceeded 70% accuracy for predicting intermediate outcome. Variance in early physiologic data can impact patient outcomes and may serve as targets for early goal-directed therapy. Electronically retrievable features such as ICP, glucose levels, and electroencephalography patterns should be considered in disease severity and risk stratification scores.


Mixed micellar properties of cationic trimeric-type quaternary ammonium salts and anionic sodium n-octyl sulfate surfactants.
The properties of quaternary ammonium salt-type cationic trimeric surfactants (m-2-m-2-m, m represents the carbon atom number in alkyl chain lengths of 8, 10, and 12) and oppositely charged anionic monomeric surfactant, sodium n-octyl sulfate (SOS), were characterized by employing several techniques such as static surface tension, fluorescence spectroscopy, and dynamic light-scattering measurements. The critical micelle concentrations (cmc) of m-2-m-2-m were much lower than those of the corresponding dimeric and monomeric surfactants, and decreased with increasing chain length. The addition of SOS to m-2-m-2-m solutions resulted in a further decrease of the cmc. The mixed surfactants showed higher efficiencies in lowering the surface tension than the individual surfactants. The fluorescence measurements suggested the formation of mixed micelles with a hydrophobic environment in the solutions even at lower concentrations. The dynamic light-scattering study indicated the presence of two different kinds of aggregates with different hydrodynamic diameters. The larger one was attributed to the mixed micelle of m-2-m-2-m and SOS. These results indicated a decline of the electrostatic repulsion between cationic head groups through the incorporation of anionic surfactant into the mixed surfactants.


Computed tomography in syringomyelia and the associated Arnold-Chiari type I malformation.
A total of 20 patients with an Arnold-Chiari Type I malformation, i.e. without skeletal abnormality and associated with a syringomyelic syndrome, were studied using the EMI Whole Body Scanner CT5000. Two groups were considered: (i) a retrospective series of 12 patients without intrathecal water soluble contrast media and (ii) a prospective series of eight patients after the introduction of intrathecal Metrizamide. In the first group tonsillar herniation could not be conclusively identified on CT and cord visualisation was possible in only two cases. In the second group, tonsillar herniation and cord expansion were consistently demonstrated. Cord cavitation has also been detected. In both groups it was possible to assess the size and position of the ventricular system. The results of this study indicate that evaluation of the upper cervical cord cerebellar tonsillar herniation, may be achieved, but only following opacification of the CSF. The precise extent of cerebellar tonsillar herniation may be difficult to evaluate. The reasons for these findings are discussed.


Long-term outcome of the first 150 liver transplant recipients: a single-center experience.
Liver transplantation modifies the natural history of end-stage liver diseases and stabilizes the course of familial amyloidotic polyneuropathy. An evaluation of its long-term results allows insight and awareness of factors that impact survival. We included 150 consecutive patients who underwent liver transplantation between October 1992 and January 1998. The impact of disease, cold ischemic time, ABO compatibility, acute and chronic rejection episodes, and vascular, biliary and infectious complications on survival were compared. We included 65 patients (43.3%) with familial amyloidotic polyneuropathy, 41 (27.3%) with cirrhosis, 12 (8%) with hepatocellular carcinoma, and 11 (7.3%) with acute hepatic failure. The mean age was 39 years. The mean cold ischemic time was 493 ± 161 minutes. There were 115 (77.2%) ABO-identical transplants; 25 (16.8%) were ABO compatible, and 9 (6%) were ABO incompatible. Acute cellular rejection occurred in 88 recipients (58.7%); chronic rejection was diagnosed in 9 (6%). Complications included vascular (16.7% patients; n = 25) and biliary (38.7%; n = 58). Infections were bacterial in 92 (61.3%), fungal in 35 (23.3%), and cytomegalovirus in 9 (6%). The survival rates were 78% at 1 year, 68.7% at 5 years, and 58% at 10 years. Of the 150 patients, 82 survived until November 2011. Follow-up ranged from 13 to 19 years. In this study, only bacterial infections had a negative influence on patients' survival (P = .014). The high frequency of biliary and vascular complications was associated with increased morbidity but not mortality. Bacterial infections were related to an ominous outcome, being responsible for short- and long-term mortality.


A pore-occluding phenylalanine gate prevents ion slippage through plant ammonium transporters.
Throughout all kingdoms of life, highly conserved transport proteins mediate the passage of ammonium across membranes. These transporters share a high homology and a common pore structure. Whether NH3, NH4+ or NH3 + H+ is the molecularly transported substrate, still remains unclear for distinct proteins. High-resolution protein structures of several ammonium transporters suggested two conserved pore domains, an external NH4+ recruitment site and a pore-occluding twin phenylalanine gate, to take over a crucial role in substrate determination and selectivity. Here, we show that while the external recruitment site seems essential for AtAMT1;2 function, single mutants of the double phenylalanine gate were not reduced in their ammonium transport capacity. Despite an unchanged ammonium transport rate, a single mutant of the inner phenylalanine showed reduced N-isotope selection that was proposed to be associated with ammonium deprotonation during transport. Even though ammonium might pass the mutant AMT pore in the ionic form, the transporter still excluded potassium ions from being transported. Our results, highlight the importance of the twin phenylalanine gate in blocking uncontrolled ammonium ion flux.


Gastrointestinal problems in runners.
This article reviews the literature regarding gastrointestinal disturbances specifically in runners. Upper gastrointestinal problems such as reflux, nausea, vomiting, and gastritis are reviewed. Exercise has been found to alter esophageal motility. These symptoms worsen with increased exertion as well. H(2) blockers have been found helpful for reflux and nausea. The lower intestinal problems of motility and blood loss are discussed. These problems are generally more common and more directly related to running. Also reviewed are endotoxin involvement and transient abdominal pain. Much of the literature deals with marathon and ultramarathon running, showing the extreme effects of running and exertional stress on the body; however, recreational runners may not be so afflicted as these study participants.


Effects of rhamnolipids on the removal of 2,4,2,4-tetrabrominated biphenyl ether (BDE-47) by Phanerochaete chrysosporium analyzed with a combined approach of experiments and molecular docking.
Effects of rhamnolipids on the removal of 2,4,2,4-tetrabrominated biphenyl ether (BDE-47) by Phanerochaete chrysosporium (P. chrysosporium) had been investigated, as well as the influence of carbon source (i.e. glucose). The results showed that the removal efficiency was over 90% in all treatments in 7 d. Rhamnolipids at low concentrations (0.05 and 0.1 CMC (critical micelle concentration)) could promote the removal of BDE-47, however, the inhibition effects occurred at high concentrations (0.5 and 1.0 CMC). The further study indicated that rhamnolipids at low concentrations not only promote the growth of mycelium, but also had obvious promotion on ligninolytic enzymes activity (i.e. manganese peroxidase (MnP), lignin peroxidase (LiP) and laccase (Lac)), especially for MnP and Lac. However, the opposite effect was generated at high rhamnolipids concentrations. Meanwhile, glucose played an active role for BDE-47 removal. For better understanding the degradation mechanism, the degradation product analysis and molecular docking had been introduced to this study. The degradation product analysis indicated that OH-PBDEs were the major degradation products and hydroxylation should be the important degradation pathway. The docking results showed that the ideal binding conformation occurred between ligninolytic enzymes and BDE-47, and hydrophobic interactions were the main interaction. Moreover, hydrogen bonds and hydrophobic interactions both existed in ligninolytic enzymes and rhamnolipids interaction. That might be the reason that rhamnolipids affected enzymes activity. These results indicated that P. chrysosporium might be a type of ideal microorganisms in the removal of BDE-47 pollution, and rhamnolipids could be a type of additives for better removal efficiency.


Immediate Reconstruction of Failed Implants in the Esthetic Zone Using a Flapless Technique and Autogenous Composite Tuberosity Graft.
We describe a technique for immediate reconstruction of bone after removal of failed dental implants in the esthetic region to optimize the esthetic outcome of retreatment. We conducted a study of 16 consecutive patients in whom the bony defect resulting from implant removal was immediately reconstructed with a combined autogenous bone and soft tissue graft harvested from the maxillary tuberosity. After a healing period of 3 months, implants were inserted. At 1 year after placement of the definitive restoration, no implants had been lost, the peri-implant tissues were healthy, the aesthetics scored with the pink esthetic score were favorable, and the patients were satisfied. With this technique, it appears that immediate reconstruction of the hard and soft tissue components with a combined bone-soft tissue graft after removal of an implant is a feasible treatment option, from the perspective of both patients and professionals. It expedites rehabilitation, reduces morbidity, and results in a favorable esthetic outcome.


One shoot, three birds: Targeting NEK2 orchestrates chemoradiotherapy, targeted therapy, and immunotherapy in cancer treatment.
Combinational therapy has improved the cancer therapeutic landscape but is associated with a concomitant increase in adverse side reactions. Emerging evidence proposes that targeting one core target with multiple critical roles in tumors can achieve combined anti-tumor effects. This review focuses on NEK2, a member of serine/threonine kinases, with broad sequence identity to the mitotic regulator NIMA of the filamentous fungus Aspergillus nidulans. Elevated expression of NEK2 was initially found to promote tumorigeneses through abnormal regulation of the cell cycle. Subsequent studies report that NEK2 is overexpressed in a broad spectrum of tumor types and is associated with tumor progression and therapeutic resistance. Intriguingly, NEK2 has recently been revealed to mediate tumor immune escape by stabilizing the expression of PD-L1. Targeting NEK2 is thus becoming a promising approach for cancer treatment by orchestrating chemoradiotherapy, targeted therapy, and immunotherapy. It represents a novel strategy for inducing combined anti-cancer effects using a mono-agent.


Is surgical smoke harmful to theater staff? a systematic review.
Smoke is generated by energy-based surgical instruments. The airborne byproducts may have potential health implications. This study aimed to evaluate the properties of surgical smoke and the evidence for the harmful effects to the theater staff. Cochrane Database, MEDLINE, PubMed, Embase classic and Embase, and the metaRegister of Controlled Trials were searched for studies reporting the constituents found in the smoke plume created during surgical procedures, the methods used to analyze the smoke, the implications of exposure, and the type of surgical instrument that generated the smoke. Studies were excluded if they were animal based, preclinical experimental work, or opinion-based reports. The common end points were particle size and characteristics, infection risk, malignant spread, and mutagenesis. The inclusion criteria were fulfilled by 20 studies. In terms of particle size, 5 (25%) of the 20 studies showed that diathermy and laser can produce ultrafine particles (UFP) that are respirable in size. With regard to particle characterization, 7 (35%) of the 20 studies demonstrated that a variety of volatile hydrocarbons are present in diathermy-, ultrasonic-, and laser-derived surgical smoke. These are potentially carcinogenic, but no evidence exists to support a cause-effect relationship for those exposed. In terms of infection risk, 6 (30%) of the 20 studies assessed surgical smoke for the presence of viruses, with only 1 study (5%) positively identifying viral DNA in laser-derived smoke. One study (5%) demonstrated bacterial cell culture (Staphylococcus aureus) from a laser plume after surgery. Regarding mutagenesis and malignant spread, one study (5%) reported the mutagenic effect of smoke, and one study (5%) showed the presence of malignant cells in the smoke of a patient undergoing procedures for carcinomatosis. The potentially carcinogenic components of surgical smoke are sufficiently small to be respirable. Infective and malignant cells are found in the smoke plume, but the full risk of this to the theater staff is unproven. Future work could focus on the long-term consequences of smoke exposure.


Quantification of transmission of foot-and-mouth disease virus caused by an environment contaminated with secretions and excretions from infected calves.
Foot-and-mouth disease virus (FMDV) infected animals can contaminate the environment with their secretions and excretions. To quantify the contribution of a contaminated environment to the transmission of FMDV, this study used calves that were not vaccinated and calves that were vaccinated 1 week prior to inoculation with the virus in direct and indirect contact experiments. In direct contact experiments, contact calves were exposed to inoculated calves in the same room. In indirect contact experiments, contact calves were housed in rooms that previously had held inoculated calves for three days (either from 0 to 3 or from 3 to 6 days post inoculation). Secretions and excretions from all calves were tested for the presence of FMDV by virus isolation; the results were used to quantify FMDV transmission. This was done using a generalized linear model based on a 2 route (2R, i.e. direct contact and environment) SIR model that included information on FMDV survival in the environment. The study shows that roughly 44% of transmission occurs via the environment, as indicated by the reproduction ratio R0(2R)environment that equalled 2.0, whereas the sum of R0(2R)contact and R0(2R)environment equalled 4.6. Because vaccination 1 week prior to inoculation of the calves conferred protective immunity against FMDV infection, no transmission rate parameters could be estimated from the experiments with vaccinated calves. We conclude that a contaminated environment contributes considerably to the transmission of FMDV therefore that hygiene measures can play a crucial role in FMD control.


Semantic congruency but not temporal synchrony enhances long-term memory performance for audio-visual scenes.
Human long-term memory for visual objects and scenes is tremendous. Here, we test how auditory information contributes to long-term memory performance for realistic scenes. In a total of six experiments, we manipulated the presentation modality (auditory, visual, audio-visual) as well as semantic congruency and temporal synchrony between auditory and visual information of brief filmic clips. Our results show that audio-visual clips generally elicit more accurate memory performance than unimodal clips. This advantage even increases with congruent visual and auditory information. However, violations of audio-visual synchrony hardly have any influence on memory performance. Memory performance remained intact even with a sequential presentation of auditory and visual information, but finally declined when the matching tracks of one scene were presented separately with intervening tracks during learning. With respect to memory performance, our results therefore show that audio-visual integration is sensitive to semantic congruency but remarkably robust against asymmetries between different modalities.


Effects of dietary supplementation with marine fish oil on leukocyte lipid mediator generation and function in rheumatoid arthritis.
Twelve patients with active rheumatoid arthritis supplemented their usual diet with 20 gm of Max-EPA fish oil, daily, for 6 weeks. Following this supplementation, the ratio of arachidonic acid to eicosapentaenoic acid in the patients' neutrophil cellular lipids decreased from 81:1 to 2.7:1, and the mean generation of leukotriene B4 (with calcium ionophore stimulation) significantly declined by 33%. The mean neutrophil chemotaxis to both leukotriene B4 and FMLP significantly increased toward the normal range at week 6. The generation of 5-lipoxygenase products by calcium ionophore-stimulated monocytes was not significantly suppressed, but a significant decline (37%) in platelet-activating factor generation was noted at week 6. The modulation of these measures of leukocyte inflammatory potential suggests that fish oil supplementation may have an antiinflammatory effect.


Circulating concentrations of free triiodothyronine are associated with central adiposity and cardiometabolic risk factors in young euthyroid adults.
Thyroid dysfunction is associated with classic cardiometabolic risk factors in humans. However, this relationship remains unclear in young euthyroid adults. The present work examines the associations of circulating thyroid hormones (THs) and thyroid-stimulating hormone (TSH) concentrations with body composition and cardiometabolic risk factors in young euthyroid adults. A total of 106 sedentary, euthyroid adults (72 women; 22 ± 2 years old) participated in this cross-sectional study. THs and TSH serum concentrations were determined in fasting conditions (6 h). Body composition (fat mass (FM), lean mass (LM), and visceral adipose tissue (VAT)) was determined by dual-energy X-ray absorptiometry, anthropometric parameters (weight, height, and waist circumference) were measured, and neck adipose tissue mass was quantified through computed tomography (CT) scanning. Cardiometabolic risk factors including fasting glucose and lipid metabolism markers, hepatic phosphatase and transaminases, and blood pressure were also assessed. Free triiodothyronine (FT3) concentration was positively associated with body mass index, LM, VAT, and waist circumference (all P ≤ 0.038). FT3 was also associated with glucose, insulin, HOMA-IR, fatty liver index, and blood pressure (all P < 0.024). All the associations were attenuated when adjusting for sex. In contrast, we found no associations of TSH or free thyroxine with any body composition parameter or cardiometabolic risk factors. In conclusion, FT3 is associated with central adiposity and cardiometabolic risk factors including insulin resistance, fatty liver index, and mean, systolic and diastolic blood pressure in young euthyroid adults. ClinicalTrials.gov identifier: NCT02365129.


[Immunomorphological aspects of post-traumatic subatrophy of the eyeball].
The study attempts to characterize immunomorphological disorders at different degrees of post-traumatic subatrophy of the eyeball. The study included 123 patients with blind and unpromising eyes, eyeball subatrophy of various degrees, who were divided into three groups (1, 2 and 3) depending on the degree of eyeball subatrophy. The greatest risk of autoimmune inflammation was observed in patients with degree I subatrophy. Contusion injury of the eye was proven to not exclude the course of post-traumatic autoimmune uveitis. The development of post-traumatic subatrophic process is associated with activation of systemic organ-specific immunity, shift of balance in main regulatory subpopulations. The study showed that the most severe clinical course of chronic post-traumatic uveitis is observed in patients as a result of penetrating trauma to the eyeball. The contusion nature of such ocular injury does not exclude the development of autoimmune inflammation.


A content validity study of signs, symptoms and diseases/health problems expressed in LIBRAS.
To validate the content of signs, symptoms and diseases/health problems expressed in LIBRAS for people with deafness. Method: Methodological development study, which involved 36 people with deafness and three LIBRAS specialists. The study was conducted in three stages: investigation of the signs, symptoms and diseases/health problems, referred to by people with deafness, reported in a questionnaire; video recordings of how people with deafness express, through LIBRA, the signs, symptoms and diseases/health problems; and validation of the contents of the recordings of the expressions by LIBRAS specialists. Data were processed in a spreadsheet and analyzed using univariate tables, with absolute frequencies and percentages. The validation results were analyzed using the Content Validity Index (CVI). 33 expressions in LIBRAS, of signs, symptoms and diseases/health problems were evaluated, and 28 expressions obtained a satisfactory CVI (1.00). The signs, symptoms and diseases/health problems expressed in LIBRAS presented validity, in the study region, for health professionals, especially nurses, for use in the clinical anamnesis of the nursing consultation for people with deafness.


Participation of limbic-hypothalamic structures in circadian rhythm of slow wave sleep and paradoxical sleep in the rat.
The effect of brain lesion or surgical isolation of the neural circuit on SWS and PS circadian rhythm have been studied in female rats under a 14/10 light-dark schedule. Cortical EEG'S AND DORSAL NECK EMG were used to monitor SWS, PS and alertness in female rats. Intact and operated controls showed regular 4-5-day vaginal cycles and nocturnal sleep rhythm, but the night PS value on proestrus was lower than in other cycles. Following septal lesion, MPO roof cut, vaginal cycles and SWS rhythm were regularly maintained; however, the PS appearance at night, except during proestrus, increased (night PS peak). These results were similar to those for pinealectomized or ovariectomized female rats. A frontal cut of the MBH produced persistent estrus and disturbed both SWS and PS circadian rhythm. The suprachiasmatic-lesioned rats showed persistent estrus and disrupted SWS rhythm, but regularly maintained the circadian PS rhythm. The vaginal cycles and SWS rhythm in the fornical-transected rats were regularly maintained, but the PS rhythm was disturbed during diestrus and showed ultradian rhythm. From these results, it is suggested that the pineal hormone and the gonadal feedback mechanisms may be involved in the night PS peak and this mechanism may involve the septal- and amygdaloid-hypothalamic systems. A different neural mechanism exist for SWS and PS circadian rhythm; SWS rhythm involves the suprachiasmatic-basal hypothalamic system and PS circadian rhythm is related, in part, to the hippocampal-hypothalamic system.


Autism Spectrum Disorders: Challenges and Opportunities for Transition to Adulthood.
Improved outcomes for individuals with autism spectrum disorder (ASD) have opened a range of potential pathways during the transition to adulthood. These include attending college, entering the labor force, and achieving a degree of independent living. Less cognitively able individuals may be eligible for state benefits and may enter supported employment programs. Those attending college require careful support and planning. Practitioners need to be familiar with the unique needs of young adults with ASD. Further research should attempt to define the priorities of individuals and families with ASD making this transition and clarify the value of existing supports and interventions.


Interleukin-31 expression and relation to disease severity in human asthma.
Interleukin 31 (IL-31) is a novel T helper type 2 effector cytokine that plays an important role in the pathogenesis of allergic diseases. However, its role in human asthma remains unclear. The aim of this study was to measure IL-31 levels in the serum, bronchoalveolar lavage fluid (BALF) and bronchial tissue of asthmatics and healthy subjects, and identify its possible correlation to disease severity. We quantified IL-31 levels in the serum of patients with asthma (n = 44), as well as in controls (n = 22). Of these subjects, 9 asthmatics and five controls underwent bronchoscopy with endobronchial biopsy and BALF collection. Our data showed that serum and BALF IL-31 levels were significantly elevated in patients with asthma compared with controls. Expressions of IL-31 and IL-31 receptor (IL-31RA and OSMR) were more prominent in the bronchial tissue in severe compared to mild asthma and controls. Serum IL-31 levels correlated positively with Th2 related cytokines (IL-5, IL-13, and TSLP), asthma severity or total serum immunoglobulin E (IgE), and inversely with asthma control and the forced expiratory volume in 1 second (FEV1). The current data may provide insight into the underlying pathogenesis of asthma, in which IL-31 has an important pathogenic role.


Anti-inflammatory and antibacterial effects of human cathelicidin active fragment KR-12 in the mouse models of colitis: a novel potential therapy of inflammatory bowel diseases.
Inflammatory bowel diseases (IBD) are a group of chronic gastrointestinal tract disorders with complex etiology, with intestinal dysbiosis as the most prominent factor. In this study, we assessed the anti-inflammatory and antibacterial actions of the human cathelicidin LL-37 and its shortest active fragment, KR-12 in the mouse models of colitis. Mouse models of colitis induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) and dextran sulfate sodium (DSS) were used in the study. The extent of inflammation was evaluated based on the macro- and microscopic scores, quantification of myeloperoxidase (MPO) activity and microbiological analysis of stool samples. A preliminary study with LL-37 and KR-12 (1 mg/kg, ip, twice daily) showed a decrease in macroscopic and ulcer scores in the acute TNBS-induced model of colitis. We observed that KR-12 (5 mg/kg, ip, twice daily) reduced microscopic and ulcer scores in the semi-chronic and chronic TNBS-induced models of colitis compared with inflamed mice. Furthermore, qualitative and quantitative changes in colonic microbiota were observed: KR-12 (5 mg/kg, ip, twice daily) decreased the overall number of bacteria, Escherichia coli and coli group bacteria. In the semi-chronic DSS-induced model, KR-12 attenuated intestinal inflammation as demonstrated by a reduction in macroscopic score and colon damage score and MPO activity. We demonstrated that KR-12 alleviates inflammation in four different mouse models of colitis what suggests KR-12 and cathelicidins as a whole are worth being considered as a potential therapeutic option in the treatment of IBD.


Effect of In Ovo Trace Element Supplementation on Immune-Related Cells of the Small Intestine of Post-hatched Broiler Chicken.
Pathological conditions and harmful drugs cause many gastrointestinal diseases in broiler chicken. The current study was conducted to investigate the effect of trace elements zinc (Zn) and selenium (Se) supplementation on histomorphology, immunological role, and functional activity of goblet cells (GCs) of the small intestine. The Alcian blue-periodic acid-Schiff (AB-PAS) was performed to assess the histomorphological changes in GCs, which revealed the regular dispersion with high electron density of GCs throughout the mucosal surface in the supplemented group. However, irregular dispersion with low electron density of GCs was present in the control group. The immunological functional role of GCs within the small intestine was examined by mucicarmine staining, immunohistochemistry, and immunofluorescence. The results showed a high mucin glycol protein secretion in the supplemented group, whereas limited mucin glycol protein secretion in the control group. Furthermore, the biological significance showed a high and low immunoreactivity of Muc2 and Muc13 in the supplemented and control groups, respectively. Immunofluorescence was used to confirm the immunosignaling of Muc2. Results revealed high immunosignaling of Muc2 at the apical part of the small intestine in the supplementation group, while low immunosignaling of Muc2 in the control group. Results suggest that trace element supplementation had significant effect on morphology and immunological role of GCs, which might be essential for immune function and health status of broiler chicken.


Comparison of the Efficacy of Diluted Polyethylene Glycol and Low-Density (0.1% w/v) Barium Sulfate Suspension for CT Enterography.
To compare small bowel distension and side effects between a diluted polyethylene glycol (PEG) solution and a low-density (0.1% w/v) barium sulfate suspension (LDBSS) for CT enterography (CTE) preparation. Total 173 consecutive patients who underwent CTE were enrolled in this study. The LDBSS (1 L) was used in 50 patients, and the diluted iso-osmotic PEG solution (1 L) was used in 123 patients. Two blinded radiologists independently scored jejunal and ileal distensions on a 5-point scale. To compare side effects between the two groups, the patients reported whether they had immediate complications after the administration of the oral contrast media. For ileal and jejunal distension, the diluted PEG solution showed no difference from the LDBSS for either reader (ileum: reader 1, median, 4; 4, interquartile range, 3-4; 3-4, p = 0.997; reader 2, median, 4; 4, interquartile range, 3.3-4.0; 3-4, p = 0.064; jejunum: reader 1, median, 2; 2, interquartile range, 2-3; 2-3, p = 0.560; reader 2, median, 3; 2, interquartile range, 2-3; 2-3, p = 0.192). None of the patients complained of immediate complications following administration of either of the oral contrast media. The diluted PEG solution showed comparable bowel distension compared to LDBSS and no immediate side effects; thus, it can be a useful alternative.


Temperature-responsive polymeric carriers incorporating hydrophobic monomers for effective transfection in small doses.
A series of thermoresponsive ternary random copolymers, poly[N-isopropylacrylamide (PIPAAm)-co-(dimethylamino)ethylmethacrylate (DMAEMA)-co-butylmethacrylate (BMA)], was synthesized and their in vitro gene transfection efficiency in cell culture was evaluated. A control copolymer containing 20 mol% DMAEMA units, IP-20D (mole ratio of IPAAm/DMAEMA/BMA=80/20/0 in feed, no BMA units) was inert in transfection. In contrast, copolymer IP-20D-10B (IPAAm/DMAEMA/BMA=70/20/10 in feed) effectively transfected plasmid DNA into COS-1 cell cultures even under small dosing conditions of 0.1 microg of plasmid DNA per well in a 96-well plate, suggesting that incorporation of the appropriate amount of hydrophobic unit is crucial to transfection efficiency. Gene expression was much more significant when transfected by the IP-20D-10B carrier in comparison with control homopolymer poly-DMAEMA, and almost equal to that of the highly competent lipid carrier, LipofectAMINE PLUS trade mark. Furthermore, the transfection efficiency of IP-20D-10B is altered in a thermally responsive manner. By temporarily lowering the cell culture incubation temperature to 20 degrees C in the posttransfection period, gene expression doubled over that for incubation temperature at 37 degrees C. The DNA EtBr intercalation assay suggested that DNA affinity for IP-20D-10B is decreased by lowering incubation temperature, implying that the thermally regulated gene expression could provide more efficient DNA release from the polymeric carrier.


Community pharmacy and primary health care - Types of integration and their applicability: A narrative review.
There is an urgent need for health care systems to be more efficient and efficacious. An approach to integrate public and private provider organizations such as community pharmacies and public primary health care (PHC) merits consideration. The objective of this review was to identify the types of integration in health care settings and discuss their applicability to the potential integration of community pharmacy and PHC. A narrative review using Medline, Scopus and SciELO databases was performed in which terms related to health were combined with terms related to integration. Levels and Types of integration: 14 types of integration were identified (two in breadth, seven as enablers and five in system levels). A model was created which classifies and assigns the types of integration to the different levels of the health system and to the breadth, intensity, and enablers of the integration process. Due to the nature of community pharmacy and PHC system, a horizontal integration at the micro level, supported by meso and macro levels policy, is suggested. The different elements of intensity and enablers can significantly influence the process. The application of principles, concepts and types of integration suggest that it might be feasible and practical to integrate community pharmacies and PHC. However, the conflictive historical context would need to be overcome with appropriate policy and incentives.


Cryopreservation of freshly isolated synaptosomes prepared from the cerebral cortex of rats.
In the present study, we established a cryopreservation method for freshly isolated synaptosomes prepared from the cerebral cortex of rats. Freshly prepared synaptosomes were either shock-frozen or frozen under temperature-controlled conditions using a programmable temperature controller. Each group was resuspended in iso-osmotic or hyperosmotic sucrose buffer prior to freezing, resulting in 4 different preservation protocols. The viability of the frozen synaptosomes was estimated by the recovery of basal and stimulated respiration after short-term storage (1 h) in liquid nitrogen. With regard to basal, FCCP- and veratridine-induced respiration, best recovery revealed controlled-frozen synaptosomes resuspended in iso-osmotic sucrose buffer (con/iso group). Basal respiration of this group recovered completely, whereas veratridine- and FCCP-induced oxygen uptake was decreased to 87.7% and 82.4% of control, respectively. Further investigations performed with the con/iso group revealed complete recovery of anaerobic and aerobic lactate synthesis, and unaffected synaptosomal integrity, as judged by the amount of released L-lactate dehydrogenase before and after the cryopreservation procedure. Long-term storage of the con/iso group in liquid nitrogen up to 88 days did not have any influence on synaptosomal viability, as evaluated by the recovery of anaerobic lactate production and synaptosomal respiration. Therefore, based on the results of respiration, synaptosomal integrity, and lactate synthesis, metabolically active synaptosomes could be obtained after cryopreservation and storage in liquid nitrogen for at least 88 days.


Intrauterine infusion of platelet-rich plasma is a treatment method for patients with intrauterine adhesions after hysteroscopy.
To evaluate the efficacy of an intrauterine infusion of platelet-rich plasma (PRP) in patients with intrauterine adhesions (IUAs). A retrospective study was conducted from April 2018 to December 2019 to compare the efficacy of intrauterine infusion of PRP with balloon for patients with IUAs. All patients had moderate or severe IUAs, including 28 patients with intrauterine infusion of PRP (group A), 22 patients with intrauterine balloon (group B), and 20 patients with both intrauterine infusion of PRP and balloon in the first operative hysteroscopy. American Fertility Society (AFS) score and rates of chemical pregnancy were compared. The AFS score decreased with an average of 5.18 ± 3.93, 4.91 ± 4.39, and 5.15 ± 3.17 comparing the third hysteroscopy with the first operative hysteroscopy in group A, group B, and group C, respectively. No significant differences were found among these groups (P=0.734). The rates of chemical pregnancy were 40.0% in group A, 38.9% in group B, and 33.3% in group C without significant differences (P=0.944). There were no significant differences between intrauterine infusion of PRP and balloon. PRP is a treatment method for IUAs.


A study of the effects of sodium halides on the performance of air-jet and vibrating-mesh nebulizers.
The influence of sodium halide electrolytes on aerosols generated from the Aeroneb Pro vibrating mesh nebulizer and the Sidestream air-jet nebulizer has been evaluated. Fluids with a range of concentrations of Na halides (i.e. NaF, NaCl, NaBr and NaI) were used as nebulizer solutions and their effect on aerosol properties such as total aerosol output, fine particle fraction (FPF), volume median diameter (VMD) and predicted regional airway deposition were investigated. For both nebulizers, the inclusion of electrolyte significantly enhanced the aerosol properties compared with HPLC grade (deionized) water. Aerosol output, FPF and aerosol fraction less than 2.15 μm were directly proportional to electrolyte concentration. Furthermore, the proportion of aerosols that are likely to deposit in the oropharyngeal region, and the VMD of the droplets were inversely related to the electrolyte concentration for both nebulizers. In general, the inclusion of electrolytes had a greater impact on the aerosol properties of the vibrating-mesh nebulizer. In the Aeroneb Pro, NaI 2.0% (w/v) was the optimum solution as it generated the highest aerosol output, FPF and output fraction below 2.15 μm with the lowest VMD and minimal predicted oropharyngeal deposition. This was attributed to the polarizing ability of iodide ions present in the largest quantity at the air-water interface. This study has shown that the Aeroneb Pro vibrating-mesh device demonstrated greatly enhanced aerosol properties when halides were included in the nebulizer solutions.


Clinical feasibility of a commercially available MRI-only method for radiotherapy treatment planning of the brain.
Advancements in deep-learning based synthetic computed tomography (sCT) image conversion methods have enabled the development of magnetic resonance imaging (MRI)-only based radiotherapy treatment planning (RTP) of the brain. This study evaluates the clinical feasibility of a commercial, deep-learning based MRI-only RTP method with respect to dose calculation and patient positioning verification performance in RTP of the brain. Clinical validation of dose calculation accuracy was performed by a retrospective evaluation for 25 glioma and 25 brain metastasis patients. Dosimetric and image quality of the studied MRI-only RTP method was evaluated by a direct comparison of the sCT-based and computed tomography (CT)-based external beam radiation therapy (EBRT) images and treatment plans. Patient positioning verification accuracy of sCT images was evaluated retrospectively for 10 glioma and 10 brain metastasis patients based on clinical cone-beam computed tomography (CBCT) imaging. An average mean dose difference of Dmean = 0.1% for planning target volume (PTV) and 0.6% for normal tissue (NT) structures were obtained for glioma patients. Respective results for brain metastasis patients were Dmean = 0.5% for PTVs and Dmean =1.0% for NTs. Global three-dimensional (3D) gamma pass rates using 2%/2 mm dose difference and distance-to-agreement (DTA) criterion were 98.0% for the glioma subgroup, and 95.2% for the brain metastasis subgroup using 1%/1 mm criterion. Mean distance differences of <1.0 mm were observed in all Cartesian directions between CT-based and sCT-based CBCT patient positioning in both subgroups. In terms of dose calculation and patient positioning accuracy, the studied MRI-only method demonstrated its clinical feasibility for RTP of the brain. The results encourage the use of the studied method as part of a routine clinical workflow.


The effect of calmodulin antagonists on amylase release from the rat parotid gland in vitro.
The effect of several calmodulin antagonists on the release of alpha-amylase (EC 22.214.171.124) from rat parotid gland minces was investigated as an approach to determine whether calmodulin has a role in the stimulus-secretion coupling mechanism in this tissue. The phenothiazines, trifluoperazine, chlorpromazine, and thioridazine, failed to inhibit amylase release induced by N6,O2'-dibutyryl adenosine 3':5'-cyclic monophosphate. All three phenothiazines increased basal amylase release at high concentrations. This release was independent of cellular energy, indicating that the release was probably due to the membrane perturbing properties of these compounds rather than their ability to antagonize calmodulin. R24571, a more potent calmodulin antagonist, also failed to inhibit amylase release induced by N6,O2'-dibutyryl adenosine 3':5'-cyclic monophosphate but increased basal amylase release. A different calmodulin antagonist, N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide, partially inhibited release while 8-(N,N-diethylamino)-octyl 3,4,5-trimethoxybenzoate hydrochloride (TMB-8) completely blocked the amylase release induced by the cyclic AMP derivative. However, concentrations of TMB-8 inhibiting amylase release drastically reduced the ATP concentration of rat parotid minces, suggesting that the inhibition of secretion was due to toxic effects of TMB-8 on parotid cells rather than the ability of the compound to antagonize calmodulin. The use of calmodulin antagonists has therefore failed to implicate calmodulin as an intermediate in the stimulus-secretion coupling mechanism of the rat parotid gland.


Ecosystem focused therapy in poststroke depression: a preliminary study.
Poststroke depression (PSD) occurs in the context of abrupt, often catastrophic disability that finds the patient and his or her family unprepared. We developed the ecosystem focused therapy (EFT), a systematic intervention aimed to increase the PSD patient's and his or her ecosystem's abilities to address the "psychosocial storm" of PSD and utilize available treatments effectively and efficiently. This is a preliminary study of its efficacy. A total of 24 PSD patients were randomly assigned to receive weekly sessions of EFT or a comparison condition consisting of systematic Education on Stroke and Depression and their treatment for 12 weeks. Ecosystem Focused Therapy may be more efficacious than Education on Stroke and Depression in reducing depressive symptoms and signs, in leading to a higher remission rate, and in ameliorating disability in PSD. Reduction of disability in the early part of the trial mediated later improvement in depressive symptomatology. Similarly, reduction in depressive symptoms and signs early on mediated later improvement in disability. These encouraging findings require replication. Beyond its potential direct benefits in PSD, EFT may provide an appropriate context for efficient and timely administration of pharmacotherapy and of physical, speech, and occupational therapy thus maximizing their efficacy.


Transcriptional response of Medicago truncatula sulphate transporters to arbuscular mycorrhizal symbiosis with and without sulphur stress.
Sulphur is an essential macronutrient for plant growth, development and response to various abiotic and biotic stresses due to its key role in the biosynthesis of many S-containing compounds. Sulphate represents a very small portion of soil S pull and it is the only form that plant roots can uptake and mobilize through H(+)-dependent co-transport processes implying sulphate transporters. Unlike the other organically bound forms of S, sulphate is normally leached from soils due to its solubility in water, thus reducing its availability to plants. Although our knowledge of plant sulphate transporters has been growing significantly in the past decades, little is still known about the effect of the arbuscular mycorrhiza interaction on sulphur uptake. Carbon, nitrogen and sulphur measurements in plant parts and expression analysis of genes encoding putative Medicago sulphate transporters (MtSULTRs) were performed to better understand the beneficial effects of mycorrhizal interaction on Medicago truncatula plants colonized by Glomus intraradices at different sulphate concentrations. Mycorrhization significantly promoted plant growth and sulphur content, suggesting increased sulphate absorption. In silico analyses allowed identifying eight putative MtSULTRs phylogenetically distributed over the four sulphate transporter groups. Some putative MtSULTRs were transcribed differentially in roots and leaves and affected by sulphate concentration, while others were more constitutively transcribed. Mycorrhizal-inducible and -repressed MtSULTRs transcripts were identified allowing to shed light on the role of mycorrhizal interaction in sulphate uptake.


Primary biliary cirrhosis and scleroderma. The possibility of a common pathogenetic mechanism.
A woman with clinical manifestations of progressive systemic sclerosis had liver disease with histologic and immunologic features of primary biliary cirrhosis. Biopsy specimens of salivary gland showed necrosis and lymphocytic infiltrates in and around ducts similar to those observed in hepatic ducts, whereas neither of these tissues exhibited immunoglobulin or complement deposition. The ultrastructural and immunohistochemical studies suggest a common cell-mediated immunologic mechanism for the two disorders.


Operative Effect Comparison of Flexible Drill Guiding vs. Traditional Drill Guiding Template for Lower Cervical Pedicle Screw Insertion: A Retrospective Analysis.
Accurately inserting pedicle screws is the key point of posterior pedicle screw fixation for lower cervical spine (C3-C7) instability. 3D printing technology can improve the accuracy of screw placement. This study compared the safety of 3D-printed flexible drill guiding template vs. traditional rigid drill guiding template for lower cervical pedicle screw insertion. This was a retrospective study. A total of 34 patients who underwent lower cervical pedicle screw fixation from March 2018 to May 2021 were enrolled in this study, and they were divided into the flexible drill flexible drill group and the traditional drill group. A total of 18 patients in the flexible drill flexible drill group underwent pedicle screw fixation assisted by 3D printed flexible drill guiding templates for the lower cervix, and 16 patients in the traditional drill group underwent pedicle screw fixation assisted by 3D printed regular drill guiding templates for the lower cervix. The length of the incision and intraoperative blood loss during surgery were recorded and compared for the two groups. The grade, deviation of the screw entry point, deviation of the screw medial angle and screw length were measured and compared after surgery for the two groups by independent-sample tests. There was a significant difference in the length of the incision and blood loss between the two groups (P < 0.05). There was a significant difference between the two groups for grade (P = 0.016). The deviation of the screw entry point was 0.65 ± 0.50 mm in the flexible drill group and 0.78 ± 0.83 mm in the traditional drill group. The deviation of the screw medial angle was 2.14 ± 1.78 in the flexible drill group and 4.23 ± 2.51 in the traditional drill group, with a significant difference between the two groups (P < 0.05). Compared with regular guiding techniques, lower cervical pedicle screw placement assisted by multistep navigation templates and flexible K-wires results in less trauma and better safety.


Imaging neurovascular, endothelial and structural integrity in preparation to treat small vessel diseases. The INVESTIGATE-SVDs study protocol. Part of the SVDs@Target project.
Sporadic cerebral small vessel disease (SVD) and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) share clinical and neuroimaging features and possibly vascular dysfunction(s). However few studies have included both conditions, assessed more than one vascular dysfunction simultaneously, or included more than one centre. The INVESTIGATE-SVDs study will assess several cerebrovascular dysfunctions with MRI in participants with sporadic SVD or CADASIL at three European centres. We will recruit participants with sporadic SVDs (ischaemic stroke or vascular cognitive impairment) and CADASIL in Edinburgh, Maastricht and Munich. We will perform detailed clinical and neuropsychological phenotyping of the participants, and neuroimaging including structural MRI, cerebrovascular reactivity MRI (CVR: using carbon dioxide challenge), phase contrast MRI (arterial, venous and CSF flow and pulsatility), dynamic contrast-enhanced MRI (blood brain barrier (BBB) leakage) and multishell diffusion imaging. Participants will measure their blood pressure (BP) and its variability over seven days using a telemetric device. INVESTIGATE-SVDs will assess the relationships of BBB integrity, CVR, pulsatility and CSF flow in sporadic SVD and CADASIL using a multisite, multimodal MRI protocol. We aim to establish associations between these measures of vascular function, risk factors particularly BP and its variability, and brain parenchymal lesions in these two SVD phenotypes. Additionally we will test feasibility of complex multisite MRI, provide reliable intermediary outcome measures and sample size estimates for future trials.


Genetic variability in the group of patients with congenital hip dislocation.
Our study of genetic homozygosity degree includes an analysis of the presence, distribution and individual combination of 20 selected genetically controlled morpho-physiological traits in the group of patients (N = 93) with congenital hip dislocation (CDH) and in control sample consisting of school children from Belgrade (N = 200). Assuming that CDH is genetically controlled disease, we made a hypothesis that an increased homozygosity level, as well as the changed variability among the patients, could be population-genetic parameter for the prediction of the illness. Taking into consideration our experience, as well as the experience of numerous scientists who studied the nature of the inheritance of mono- and oligo-genically controlled qualitative traits, we applied a methodology to estimate the proportion of such homozygously recessive characters (HRC-TEST). This population-genetic study did not only show statistically significant difference of the middle values of genetic homozygosity (CDH-7.1+/-0.2; control - 5.2+/-0.1), but of the differences in the type of distribution too, as well as the differences in the presence of certain individual combinations of such traits. The described methodology can be used in further analyses, with hope that it can be applied as an early prognosis for decreased resistance to different diseases. The frequencies of ABO blood types in the sample of CDH patients were similar to the average value of Serbian population, while the percentage of blood group A is slightly increased. Comparing frequencies of Rh blood groups, there is no difference between tested samples.


Increase in suicide by hanging/suffocation in the U.S., 2000-2010.
Recently, suicide exceeded motor vehicle crashes as the leading cause of injury death in the U.S. However, details of this change in suicide methods and the relationship to individual demographics, such as age and societal influences, have not been reported. To determine the characteristics of the changes in suicide rates between 2000 and 2010. Data came from CDC's Web-Based Injury Statistics Query and Reporting System (WISQARS™). Line charts were plotted to reveal changes in suicide rates by firearm, poisoning, and hanging/suffocation (ICD-10 codes: X72-X74, X60-X69, and X70). The measure of change used is the percentage change in suicide rate between 2000 and 2010. The overall suicide rate increased from 10.4 to 12.1 per 100,000 population between 2000 and 2010, a 16% increase. The majority of the increase was attributable to suicide by hanging/suffocation (52%) and by poisoning (19%). Subgroup analysis showed: (1) suicide by hanging/suffocation increased by 104% among those aged 45-59 years and rose steadily in all age groups except those aged ≥70 years; (2) the largest increase in suicide by poisoning (85%) occurred among those aged 60-69 years; and (3) suicide by firearm decreased by 24% among those aged 15-24 years but increased by 22% among those aged 45-59 years. The case fatality rates for suicide by hanging/suffocation during 2000-2010 ranged from 69% to 84%, close to those for suicide by firearm. Analyses were conducted in 2012. Substantial increases in suicide by hanging/suffocation and poisoning merit attention from policymakers and call for innovations and changes in suicide prevention approaches.


Evidence and potential in vivo functions for biofluid miRNAs: From expression profiling to functional testing: Potential roles of extracellular miRNAs as indicators of physiological change and as agents of intercellular information exchange.
A controversial hypothesis in RNA biology is that extracellular microRNAs (miRNAs), including those in biofluids, have non-cell-autonomous activities. Several studies have characterized biofluid miRNA profiles in healthy or diseased individuals but generally have failed to identify distinct disease signatures. It remains unclear whether alterations in fluid miRNA levels are simply indicators of physiological change or whether miRNAs are taken up by new cells at concentrations sufficient to affect gene expression. There are limitations to biofluid miRNA studies performed to date: methodology for isolating and quantifying biofluid miRNAs is not standardized across studies; mechanistic details of miRNA release and uptake are incomplete; and efforts to assess non-cell-autonomous effects of extracellular miRNAs have employed predominantly in vitro strategies. We describe controversies and questions that need to be addressed to test possible in vivo roles of extracellular miRNAs and propose model organisms with rich genetic toolkits for carrying out in vivo functional analyses.


Evaluation of the effects of aldehydes on association colloid properties and oxidative stability in bulk oils.
The effects of amphiphilic aldehydes, including propanal, hexanal, and nonanal, on the critical micelle concentration (CMC) of phospholipids, moisture content, and oxidative stability in soybean oil were evaluated. The selected aldehydes are typical secondary oxidation products from unsaturated fatty acids. Moisture content increased as aldehydes were added to soybean oil during thermal oxidation at a storage temperature of 50 or 100 °C. The CMC of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) increased as propanal and hexanal were added, whereas nonanal decreased the CMC of DOPC, which implies that aldehydes participate in forming association colloids in bulk oils. The addition of aldehydes increased the rates of lipid oxidation significantly in both 50 and 100 °C treatments (p < 0.05), with the effect being more evident in oils treated at 50 °C than at 100 °C. Therefore, aldehydes formed from lipid oxidation affected the association colloidal structures and oxidative stability in a bulk oil matrix.


Life skills programmes for chronic mental illnesses.
Most people with schizophrenia have a cyclical pattern of illness characterised by remission and relapses. The illness can reduce the ability of self-care and functioning and can lead to the illness becoming disabling. Life skills programmes, emphasising the needs associated with independent functioning, are often a part of the rehabilitation process. These programmes have been developed to enhance independent living and quality of life for people with schizophrenia. To review the effects of life skills programmes compared with standard care or other comparable therapies for people with chronic mental health problems. We searched the Cochrane Schizophrenia Group Trials Register (June 2010). We supplemented this process with handsearching and scrutiny of references. We inspected references of all included studies for further trials. We included all relevant randomised or quasi-randomised controlled trials for life skills programmes versus other comparable therapies or standard care involving people with serious mental illnesses. We extracted data independently. For dichotomous data we calculated relative risks (RR) and their 95% confidence intervals (CI) on an intention-to-treat basis, based on a random-effects model. For continuous data, we calculated mean differences (MD), again based on a random-effects model. We included seven randomised controlled trials with a total of 483 participants. These evaluated life skills programmes versus standard care, or support group. We found no significant difference in life skills performance between people given life skills training and standard care (1 RCT, n = 32, MD -1.10; 95% CI -7.82 to 5.62). Life skills training did not improve or worsen study retention (5 RCTs, n = 345, RR 1.16; 95% CI 0.40 to 3.36). We found no significant difference in PANSS positive, negative or total scores between life skills intervention and standard care. We found quality of life scores to be equivocal between participants given life skills training (1 RCT, n = 32, MD -0.02; 95% CI -0.07 to 0.03) and standard care. Life skills compared with support groups also did not reveal any significant differences in PANSS scores, quality of life, or social performance skills (1 RCT, n = 158, MD -0.90; 95% CI -3.39 to 1.59). Currently there is no good evidence to suggest life skills programmes are effective for people with chronic mental illnesses. More robust data are needed from studies that are adequately powered to determine whether life skills training is beneficial for people with chronic mental health problems.


Exploration of a live-together-group-together paradigm with incarcerated drug offenders.
Prisoners who both participated in biweekly, biracial therapy groups and lived together in large cubicles were compared with prisoners who grouped but did not live together. Results suggested: (1) greater group cohesion among inmates who lived and grouped together, (2) greater acceptance of Blacks by Whites exposed to the cubicle system, and (3) that the structure of measures used in studies of this nature may affect results appreciably. Implications for correctional treatment and future research are discussed.


Ultrasonographic assessment of gestational age with the distal femoral and proximal tibial ossification centers in the third trimester.
A prospective sonographic evaluation of the distal femoral and proximal tibial epiphyseal ossification centers in 228 normal pregnant women was carried out from 28 to 40 weeks' gestation. The mean gestational age at which the distal femoral epiphysis and proximal tibial epiphysis were imaged was 34 and 38 weeks, respectively. The distal femoral epiphysis was not identifiable before 28 weeks but was observed in 72% of fetuses at 33 weeks and in 94% of fetuses at 34 weeks' gestation. The presence of a distal femoral epiphysis measuring 1 or 2 mm was associated with a gestational age of greater than 33 weeks in 87.0% of fetuses, whereas a distal femoral epiphysis measuring greater than or equal to 3 mm was associated with a gestational age greater than 37 weeks in 85% of fetuses. The proximal tibial epiphysis, which was absent before 34 weeks' gestation, was observed in 56% of fetuses at 36 weeks, in 80% of fetuses at 37 weeks, and in 100% of fetuses at 39 weeks of gestation. The presence of a proximal tibial epiphysis of 1 or 2 mm was associated with a gestational age of greater than 36 weeks in 88% of fetuses, whereas a proximal tibial epiphysis greater than or equal to 3 mm was associated with a gestational age of greater than 38 weeks in 94% of fetuses. The sonographic evaluation of distal femoral epiphysis/proximal tibial epiphysis can be used as independent markers for estimation of gestational age during the third trimester, a period in which standard fetal biometric estimates of gestational age are least accurate.


Per-nucleus crossover covariation is regulated by chromosome organization.
Meiotic crossover (CO) recombination between homologous chromosomes regulates chromosome segregation and promotes genetic diversity. Human females have different CO patterns than males, and some of these features contribute to the high frequency of chromosome segregation errors. In this study, we show that CO covariation is transmitted to progenies without detectable selection in both human males and females. Further investigations show that chromosome pairs with longer axes tend to have stronger axis length covariation and a stronger correlation between axis length and CO number, and the consequence of these two effects would be the stronger CO covariation as observed in females. These findings reveal a previously unsuspected feature for chromosome organization: long chromosome axes are more coordinately regulated than short ones. Additionally, the stronger CO covariation may work with human female-specific CO maturation inefficiency to confer female germlines the ability to adapt to changing environments on evolution.


Differences in the regulation by poly(ADP-ribose) of repair of DNA damage from alkylating agents and ultraviolet light according to cell type.
Inhibition of poly(ADP-ribose) synthesis by 3-aminobenzamide in various human and hamster cells influenced the responses to DNA damage from methyl methanesulfonate, but not from ultraviolet light. After exposure to methyl methanesulfonate, 3-aminobenzamide increased the strand break frequency in all cell types studied, but only stimulated repair replication in lymphoid and HeLa cells, suggesting these are independent effects. 3-Aminobenzamide also inhibited the pathway for de novo synthesis of DNA purines, suggesting that some of its effects may be due to disturbance of precursor pathways and irrelevant to the role of poly(ADP-ribose) in repair. Previous claims that 3-aminobenzamide stimulates repair synthesis after exposure to UV light are probably artifacts, because the stimulations are only observed in lymphocytes in the presence of a high concentration of hydroxyurea that itself inhibits repair. The initial inhibition of semiconservative DNA synthesis and the excision of the major alkylation products and pyrimidine dimers were unaffected by 3-aminobenzamide. In general poly(ADP-ribose) synthesis appears to be uniquely involved in regulating the ligation stage of repair of alkylation damage but not ultraviolet damage. By regulating the ligation efficiency, poly(ADP-ribosylation) modulates the dynamic balance between incision and ligation, so as to minimize the frequency of DNA breaks. The ligation stage of repair of UV damage appears different and is not regulated by poly(ADP-ribosylation).


Laser light scattering and isothermal titration calorimetric studies of poly(ethylene oxide) aqueous solution in presence of sodium dodecyl sulfate.
The aqueous solution of poly(ethylene oxide) (PEO) in the presence of different concentrations of sodium dodecyl sulfate (SDS) was examined by laser light scattering and isothermal titration calorimetric techniques. A small fraction of PEO aggregates were found to coexist with unimeric PEO chains in dilute solution. The presence of monovalent salt does not alter the hydrodynamic properties of PEO in aqueous solution. Addition of a monovalent anionic surfactant, such as SDS, induces cooperative binding of surfactant monomers to PEO backbones at SDS concentrations ranging from 4.0 mM (critical aggregation concentration) to 16.5 mM (saturation concentration). The hydrodynamic radius of PEO unimers decreases initially and then increases with SDS concentration, resulting from the structural reorganization of the PEO/SDS complex. Beyond the saturation concentration, the hydrodynamic radii of PEO/SDS complex are independent of SDS concentration.


Pathophysiology of lipid transport disorders.
Over the past decade considerable insight into the mechanisms involved in normal and abnormal transport as well as the mode of action of hypolipidaemic drugs has been achieved. This progress has made the approach to the hyperlipidaemic patient increasingly more precise and effective.


Geographic disparities in lung transplantation in the United States before and after the November 2017 allocation change.
The primary lung allocation unit was expanded from the donation service area to a 250-mile radius in 2017. Prior to the change, geographic disparities in donor lung availability impacted waitlist outcomes. We sought to determine if the new allocation system improved these disparities. We conducted a retrospective cohort study comparing the 2-year period before and after the change. Donor lung availability was defined as the ratio of donor lungs to waitlist candidates in the primary allocation unit. Transplant centers were divided into quartiles by donor lung availability. Multivariable competing risk models were used to determine the association between lung availability and waitlist outcomes. Multivariable Cox proportional hazards models compared post-transplant survival. Prior to the allocation change, the unadjusted transplant rate at centers in the lowest and highest quartiles was 132 and 607 transplants per 100 waitlist years. Candidates in the lowest quartile of donor lung availability had a 61% adjusted lower transplantation rate compared to candidates in highest quartile (sub-hazard ratio [sHR]: 0.39, 95% confidence interval [CI]: 0.34-0.44). After the allocation change, the disparity decreased resulting in an unadjusted transplant rate of 141 and 309 among centers in the lowest and highest quartiles. Candidates in the lowest quartile had a 38% adjusted lower transplantation rate compared to those in the highest (sHR: 0.62, 95% CI: 0.57-0.68). There was no significant difference in 1-year post-transplant survival. Although the expansion of the primary allocation unit improved disparities in waitlist outcomes without any change in post-transplant survival, there still remain significant differences due to geography.


A review of new approaches to assessing hepatic function in animals.
Although a multitude of effective liver function tests are available for use in animals, a variety of modifications of currently used tests have been recently reported. In addition, newer procedures now used in human medicine may also provide unique insights into assessing and detecting acquired hepatic disorders in animals. Examples of new procedures are: assessing microsomal mixed function oxidase activity by plasma caffeine clearance; estimating the extent of active hepatic fibrogenesis through serum procollagen-III peptide levels; determining hepatic blood flow and functional mass by the galactose elimination capacity; detecting primary hepatocellular cancer through serum or urinary ligandin levels; and to estimate the liver's maximal capacity to excrete indocyanine green independent of blood flow. In evaluating drugs as to their hepatotoxicity, function tests should be included in the liver profile which measure specific metabolic alterations unique to the compound under study.


Mechanisms of Inflammation-Associated Depression: Immune Influences on Tryptophan and Phenylalanine Metabolisms.
Metabolic parameters have a direct role in the regulation of immune cell function. Thereby the inflammation-induced metabolism of aromatic amino acids, most importantly of tryptophan and phenylalanine, plays a central role. In addition, neuropsychiatric conditions that go along with disorders that are characterized by acute or chronic inflammation, such as the development of depression, decreased quality of life or cognitive impairments, are connected to disturbed amino acid and subsequent neurotransmitter metabolism.The bioanalytical procedures for the determination of concentrations of tryptophan and phenylalanine and their respective first stable intermediates kynurenine and tyrosine as well as some analytical finesses and potential sources of errors are discussed in this chapter. Monitoring of these immunometabolic parameters throughout therapies in addition to biomarkers of immune response and inflammation such as neopterin can be useful to determine disease progression but also to plan psychiatric interventions timely, thus to establish personalized treatments.


Laser Ablation in Pediatric Epilepsy.
Laser ablation is an emerging, minimally invasive treatment for selected children with intractable focal epilepsy with improved procedural morbidity. Data for children lag similar studies in adults, but the hope is for near-equivalent seizure-control rates and improved neuropsychological outcome when compared with standard open surgical resection. The approach seems particularly beneficial when dealing with deep, focal lesions, such as hypothalamic hamartomas or hippocampal sclerosis.


Effects of different cellulases on the release of phenolic acids from rice straw during saccharification.
Effects of different cellulases on the release of phenolic acids from rice straw during saccharification were investigated in this study. All cellulases tested increased the contents of phenolic acids during saccharification. However, few free phenolic acids were detected, as they were present in conjugated form after saccharification when the cellulases from Trichoderma reesei, Trichoderma viride and Aspergillus niger were used. On the other hand, phenolic acids were present in free form when the Acremonium cellulolyticus cellulase was used. Assays of enzyme activity showed that, besides high cellulase activity, the A. cellulolyticus cellulase exhibited high feruloyl esterase (FAE) activity. A synergistic interaction between FAE and cellulase led to the increase in free phenolic acids, and thus an increase in antioxidative and antiradical activities of the phenolic acids. Moreover, a cost estimation demonstrated the feasibility of phenolic acids as value-added products to reduce the total production cost of ethanol.


Commercially pure titanium (cp-Ti) versus titanium alloy (Ti6Al4V) materials as bone anchored implants - Is one truly better than the other?
Commercially pure titanium (cp-Ti) and titanium alloys (typically Ti6Al4V) display excellent corrosion resistance and biocompatibility. Although the chemical composition and topography are considered important, the mechanical properties of the material and the loading conditions in the host have, conventionally, influenced material selection for different clinical applications: predominantly Ti6Al4V in orthopaedics while cp-Ti in dentistry. This paper attempts to address three important questions: (i) To what extent do the surface properties differ when cp-Ti and Ti6Al4V materials are manufactured with the same processing technique?, (ii) Does bone tissue respond differently to the two materials, and (iii) Do bacteria responsible for causing biomaterial-associated infections respond differently to the two materials? It is concluded that: (i) Machined cp-Ti and Ti6Al4V exhibit similar surface morphology, topography, phase composition and chemistry, (ii) Under experimental conditions, cp-Ti and Ti6Al4V demonstrate similar osseointegration and biomechanical anchorage, and (iii) Experiments in vitro fail to disclose differences between cp-Ti and Ti6Al4V to harbour Staphylococcus epidermidis growth. No clinical comparative studies exist which could determine if long-term, clinical differences exist between the two types of bulk materials. It is debatable whether cp-Ti or Ti6Al4V exhibit superiority over the other, and further comparative studies, particularly in a clinical setting, are required.


Chondroblastoma of extra-craniofacial bones: Clinicopathological analyses of 103 cases.
We elucidated clinicopathological characteristics of chondroblastoma (CB) in Japan, and reliable clinicopathologic parameters predicting local recurrence and/or metastasis. Clinicopathological profiles of 103 CB (80 male, 23 female) in extra-craniofacial bones were retrieved. Numerical scoring of nine pathological and five radiological features was statistically analyzed to determine prognostic significance. Age ranged 8-61 years (average 19.6 years). Frequently involved sites were femur, tibia, calcaneus, patella and humerus. Radiologically, tumors were 2-80 mm (average 31.1 mm) in size. Marginal sclerosis and calcification were common. Histologically, pink cartilage, mitoses, and chicken-wire calcification were often seen. Within a follow-up period [2-260 months (average 53.5 months)], the local recurrence rate was 15.5%. No patient had metastasis. Recurrence was most frequently observed at the femur. By log-rank analysis, only cyst formation in images was significant for predicting recurrence free survival (RFS). By Cox hazard analysis with representative clinico-radiological and pathological features, only age (≥16 years) and cyst formation were significant predictors for RFS. Pathological features were not significant in both uni- and multivariate analyses.


Prevalence of rhinoviruses in young children of an unselected birth cohort from the Netherlands.
Rhinovirus (RV) is a frequent pathogen in young children, eliciting symptoms ranging from common colds to wheezing illnesses and lower respiratory tract infections. The recently identified RV-C seems to be associated with asthma exacerbations and more severe disease, but results vary. We studied the prevalence and severity of infection with RV in an unselected birth cohort. Children with respiratory symptoms entered the symptomatic arm of the cohort and were compared with asymptomatic children. Severity of wheezing and other respiratory symptoms was registered. Respiratory viruses were evaluated using throat and nasopharyngeal swabs on first presentation and after recovery (wheezing children). RV genotyping was performed on RV-PCR positive samples. RV was the most prevalent respiratory virus and was found in 58/140 symptomatic children (41%), 24/96 (25%) control children and 19/74 (26%) wheezing symptomatic children after recovery (p <0.05) and did not differ between wheezing and non-wheezing symptomatic children-respectively, 42% (38/90) and 40% (20/50). RV-A was the most commonly detected species (40/68, 59%), followed by RV-C (22/68, 32%) and RV-B (6/68, 9%). RV-B was more frequently detected in asymptomatic children (5/6, p <0.05). There was no significant difference in the frequency of RV species between wheezing and non-wheezing symptomatic children. Children with RV mono-infection had more severe symptoms, but no association between RV species and severity of disease was seen. In an unselected birth cohort from the Netherlands with mild respiratory disease RV was the most prevalent respiratory virus. RV(-C) infection was not associated with more severe disease or wheezing.


Proposing the Stroke Levity Scale: a valid, reliable, simple, and time-saving measure of stroke severity.
National Institutes of Health Stroke Scale (NIHSS) is long and complex. Our objective was to design a valid, reliable, simple, and time-saving stroke severity scale. About 103 and 100 consecutive stroke patients in Berlin (Germany) and Ibadan (Nigeria), respectively were evaluated using the measures listed below. The Stroke Levity Scale (SLS) was calculated as maximum power (0-5) in the dexterous hand + maximum power in the weaker lower limb + mobility score-1 (if aphasia present). It took less than 2 min to administer the SLS in contrast to 8 min for the NIHSS. The SLS showed significant correlation to the NIHSS (rho = -0.79, P < 0.0001), the modified Rankin Scale (rho = -0.79, P < 0.0001), and the health-related quality of life (QOL) in stroke patient's questionnaire (rho = 0.78, P < 0.0001). It had Cronbach's alpha of 0.75 (Ibadan) and 0.71 (Berlin). The kappa-value for test-retest reliability was 0.77 with P < 0.0001. The SLS is a concise, valid, and reliable stroke impairment scale that can be used routinely to monitor outcome in stroke patients. Because it is brief and simple to apply, non-neurologists can be taught to administer it in addition to QOL and disability scales for stroke survivors without significantly increasing the respondent burden.


Effect of lipid peroxidation upon human spermatic adenosinetriphosphate (ATP). Relationship with motility, velocity and linearity of the spermatozoa.
The aim of the present paper was to study the effect of forced lipid peroxidation upon human spermatozoa and its relation with motility, velocity, linearity and ATP content. Forty-three pools of semen samples were studied one hour after liquefaction. After washing, normal and pathological spermatozoa presented no variations in motility, velocity or linearity with respect to basal values. Forced peroxidation produced a significant decrease of motility, velocity and linearity (p less than 0.02) with respect to control. Spermatic ATP was not significantly different in control vs forced peroxidation groups in normozoospermic samples. In contrast, a significant decrease of ATP between control and peroxidation groups was observed in asthenozoospermia at 120 minutes of incubation (p less than 0.02). In the asthenozoospermic group, a significant LPO-p increase was observed in comparison with the normal group.


Risk assessment of Cd polluted paddy soils in the industrial and township areas in Hunan, Southern China.
Cadmium (Cd) contamination in rice in Youxian, Hunan, China is a major environmental health concern. In order to reveal the Cd contamination in rice and paddy soils and the health risks to the population consuming the local rice grain, field surveys were conducted in eight towns in Youxian, China. The Cd contents of paddy soils averaged 0.228-1.91 mg kg(-1), 90% exceeding the allowable limit of 0.3 mg kg(-1) stipulated by the China Soil Environmental Quality Standards. Low average pH values (for air dried oxidized soils) ranging from 4.98 to 6.02 in paddy soil were also found. More than seventy percent (39 of 53) of the grain samples exceeded the maximum safe concentration of Cd, 0.2 mg kg(-1) on a dry weight basis. Considering the high consumption of local rice (339 g capita(-1) DW d(-1)) and Cd levels measured, dietary ingestion of 78% of the sampled rice grains would have adverse health risks because the intake exposure of Cd was greater than the JECFA recommended exposures, 0.8 µg Cd BW kg(-1) day(-1) or 25 µg Cd BW kg(-1) month(-1).


The lipopeptide antibiotic A54145 biosynthetic gene cluster from Streptomyces fradiae.
Ca(2+)-dependent cyclic lipodepsipeptides are an emerging class of antibiotics for the treatment of infections caused by Gram-positive pathogens. These compounds are synthesized by nonribosomal peptide synthetase (NRPS) complexes encoded by large gene clusters. The gene cluster encoding biosynthetic pathway enzymes for the Streptomyces fradiae A54145 NRP was cloned from a cosmid library and characterized. Four NRPS-encoding genes, responsible for subunits of the synthetase, as well as genes for accessory functions such as acylation, methylation and hydroxylation, were identified by sequence analysis in a 127 kb region of DNA that appears to be located subterminally in the bacterial chromosome. Deduced epimerase domain-encoding sequences within the NRPS genes indicated a D: -stereochemistry for Glu, Lys and Asn residues, as observed for positionally analogous residues in two related compounds, daptomycin, and the calcium-dependent antibiotic (CDA) produced by Streptomyces roseosporus and Streptomyces coelicolor, respectively. A comparison of the structure and the biosynthetic gene cluster of A54145 with those of the related peptides showed many similarities. This information may contribute to the design of experiments to address both fundamental and applied questions in lipopeptide biosynthesis, engineering and drug development.


PD-L1 expression is associated with massive lymphocyte infiltration and histology in gastric cancer.
The mechanism of carcinogenesis of gastric cancer (GC) is still unclear now. This study aimed to explore the correlations among PD-L1, Epstein-Barr virus (EBV) infection, lymphocyte infiltration, HER2 expression, HER2 gene status, histology, and other clinicopathological factors in GC. A total of 44 GC patients with massive lymphocyte infiltration (GC-MLI) and 93 GC patients without massive lymphocyte infiltration were involved in this study. Immunohistochemical analysis was used to test the expression levels of PD-L1 and HER2. Fluorescence in situ hybridization was used on HER2-positive cases with a score of 2+ to test the HER2 gene status. EBV-encoded RNA was used to test for EBV infection. In univariate analysis, PD-L1 expression was significantly associated with GC-MLI (P<.001), lower age (P=.019), EBV infection (P<.001), lower HER2 expression (P=.011), and diffuse/mixed type of histology (P=.022). EBV-encoded RNA-positive cases were significantly associated with GC-MLI (P<.001), lower age (P=.016), diffuse/mixed type of histology (P=.011), and lower HER2 expression (P=.032). In the multivariate logistic regression model, GC-MLI and the diffuse/mixed type histology were identified as 2 independent factors that affected PD-L1 expression (P<.001). Furthermore, PD-L1-positive cases have worse overall survival than do PD-L1-negative cases (P=.011). These results suggest that massive lymphocyte infiltration and the diffuse/mixed type histology of GC should be taken into consideration to select the appropriate patients for PD-L1 inhibitory treatment in the future.


Low-molecular-weight cyclin E deregulates DNA replication and damage repair to promote genomic instability in breast cancer.
Low-molecular-weight cyclin E (LMW-E) is an N-terminus deleted (40 amino acid) form of cyclin E detected in breast cancer, but not in normal cells or tissues. LMW-E overexpression predicts poor survival in breast cancer patients independent of tumor proliferation rate, but the oncogenic mechanism of LMW-E and its unique function(s) independent of full-length cyclin E (FL-cycE) remain unclear. In the current study, we found LMW-E was associated with genomic instability in early-stage breast tumors (n = 725) and promoted genomic instability in human mammary epithelial cells (hMECs). Mechanistically, FL-cycE overexpression inhibited the proliferation of hMECs by replication stress and DNA damage accumulation, but LMW-E facilitated replication stress tolerance by upregulating DNA replication and damage repair. Specifically, LMW-E interacted with chromatin and upregulated the loading of minichromosome maintenance complex proteins (MCMs) in a CDC6 dependent manner and promoted DNA repair in a RAD51- and C17orf53-dependent manner. Targeting the ATR-CHK1-RAD51 pathway with ATR inhibitor (ceralasertib), CHK1 inhibitor (rabusertib), or RAD51 inhibitor (B02) significantly decreased the viability of LMW-E-overexpressing hMECs and breast cancer cells. Collectively, our findings delineate a novel role for LMW-E in tumorigenesis mediated by replication stress tolerance and genomic instability, providing novel therapeutic strategies for LMW-E-overexpressing breast cancers.


Restructuring of a meiobenthic assemblage after sediment contamination with an antibacterial compound: Case study of ciprofloxacin.
A microcosm experiment was conducted to evaluate the impacts of the fluoroquinolone antibiotic ciprofloxacin on meiobenthic taxa abundance, nematode genus structure, and functional trait parameters. Sediment samples were experimentally enriched with four different doses of ciprofloxacin [D1 (50 ppm Dry weight 'DW'), D2 (100 ppm DW), D3 (200 ppm DW), and D4 (500 ppm DW)] and were then compared with non-enriched sediments (controls). After one month of exposure, the data showed that ciprofloxacin had altered the meiofaunal taxa abundance. A change in the structure of nematofaunal genera was observed, particularly with the highest dose (D4), which was characterized by the lowest taxonomic diversity. The SIMPER analysis revealed that the average dissimilarity between nematode communities increased with increasing doses of ciprofloxacin. Two dimensional (2D) non-metric multidimensional scaling (nMDS) plots and relative abundances of functional groups of nematode genus assemblages revealed that all functional trait abundances were affected, particularly with the highest dose. However, only the amphid shape and feeding group functions showed a clear distribution separation between the control and ciprofloxacin treatments. The nMDS second-stage ordination of inter-matrix rank correlations for matrices including genus and functional traits showed that the tail shape was the closest functional trait to the generic distribution. Thus, only the curves of cumulative dominance related to the tail shape mirrored discernibly the sedimentary concentrations in ciprofloxacin.


A consensus to determine the ideal critical care transfer bag.
Familiarity with environment, processes and equipment reduces the risk inherently associated with critical care transfers. Therefore, the North West London Critical Care Network decided to create a standardised ideal transfer bag and contents to improve patient safety. A four-round modified Delphi survey developed a condensed and clinically tested content list. An expert panel then designed an ideal transfer bag based on agreed important principles. Participants completed two rounds of an electronic survey. Round 3 comprised an expert clinical panel review, while round 4 tested the contents over 50 clinical transfers. The prototype bag's design was adjusted after clinical use and feedback. This project has introduced a standardised critical care transfer bag across our network. A similar technique could be used for other healthcare regions. Alternatively, the above critical care transfer bag could be adopted or adapted for regional use by clinicians.


Ultrahigh photoconductivity of bandgap-graded CdSxSe1-x nanowires probed by terahertz spectroscopy.
Superiorly high photoconductivity is desirable in optoelectronic materials and devices for information transmission and processing. Achieving high photoconductivity via bandgap engineering in a bandgap-graded semiconductor nanowire has been proposed as a potential strategy. In this work, we report the ultrahigh photoconductivity of bandgap-graded CdSxSe1-x nanowires and its detailed analysis by means of ultrafast optical-pump terahertz-probe (OPTP) spectroscopy. The recombination rates and carrier mobility are quantitatively obtained via investigation of the transient carrier dynamics in the nanowires. By analysis of the terahertz (THz) spectra, we obtain an insight into the bandgap gradient and band alignment to carrier transport along the nanowires. The demonstration of the ultrahigh photoconductivity makes bandgap-graded CdSxSe1-x nanowires a promising candidate as building blocks for nanoscale electronic and photonic devices.


Progress in on-line, at-line, and in-line coupling of sample treatment with capillary and microchip electrophoresis over the past 10 years: A review.
The review presents an evaluation of the development of on-line, at-line and in-line sample treatment coupled with capillary and microchip electrophoresis over the last 10 years. In the first part, it describes different types of flow-gating interfaces (FGI) such as cross-FGI, coaxial-FGI, sheet-flow-FGI, and air-assisted-FGI and their fabrication using molding into polydimethylsiloxane and commercially available fittings. The second part deals with the coupling of capillary and microchip electrophoresis with microdialysis, solid-phase, liquid-phase, and membrane based extraction techniques. It mainly focuses on modern techniques such as extraction across supported liquid membrane, electroextraction, single drop microextraction, head space microextraction, and microdialysis with high spatial and temporal resolution. Finally, the design of sequential electrophoretic analysers and fabrication of SPE microcartridges with monolithic and molecularly imprinted polymeric sorbents are discussed. Applications include the monitoring of metabolites, neurotransmitters, peptides and proteins in body fluids and tissues to study processes in living organisms, as well as the monitoring of nutrients, minerals and waste compounds in food, natural and wastewater.