Evidence and recommendations for the use of segmental motion testing for patients with LBP - A systematic review.
Assessment of low back pain (LBP) includes segmental motion tests. Although often used in clinical practice, the validity, inter- and intra-rater reliability of such tests in individuals with LBP are not universally accepted, making it difficult to interpret findings in clinical practice. The purposes of this study were to determine the validity and reliability of segmental motion tests for patients with LBP and to give reasoned recommendations for their use in practice. Systematic review. A systematic literature research was conducted of databases PubMed, LIVIVO and Cochrane library. The included studies were appraised for quality by using QUADAS-2 and an adapted version of QAREL tools. Results of studies were appraised to give reasoned recommendations taking quality criteria into account. Thirteen studies were included covering passive accessory intervertebral motion testing (PAIVMs), passive physiological intervertebral motion testing (PPIVMs) and the prone instability test (PIT). The risk of bias of studies ranged from high to low. When used in isolation, specificity of PAIVMS and PPIVMs was generally high and sensitivity poor. Reliability was overwhelming poor for both. Reliability of the PIT was inconsistent. None of these assessments can be strongly recommended when used in isolation. The evidence regarding validity and reliability of segmental motion testing is poor and clinical use of stand-alone tests cannot be recommended. Superiority of the combination of tests as a test battery or with other clinical information needs further investigation.


PD-L1 and HLA Class I Antigen Expression and Clinical Course of the Disease in Intrahepatic Cholangiocarcinoma.
More effective therapy is needed for intrahepatic cholangiocarcinoma (ICC). The encouraging clinical results obtained with checkpoint molecule-specific monoclonal antibodies (mAb) have prompted us to investigate whether this type of immunotherapy may be applicable to ICC. The aims of this study were to determine whether (i) patients mount a T-cell immune response to their ICC, (ii) checkpoint molecules are expressed on both T cells and tumor cells, and (iii) tumor cells are susceptible to recognition by cognate T cells. Twenty-seven ICC tumors were analyzed for (i) lymphocyte infiltrate, (ii) HLA class I and HLA class II expression, and (iii) PD-1 and PD-L1 expression by T cells and ICC cells, respectively. The results of this analysis were correlated with the clinicopathologic characteristics of the patients investigated. Lymphocyte infiltrates were identified in all tumors. PD-L1 expression and HLA class I antigen expression by ICC cells was observed in 8 and 11, respectively, of the 27 tumors analyzed. HLA class I antigen expression correlated with CD8(+) T-cell infiltrate. Furthermore, positive HLA class I antigen expression in combination with negative/rare PD-L1 expression was associated with favorable clinical course of the disease. ICC patients are likely to mount a T-cell immune response against their own tumors. Defects in HLA class I antigen expression in combination with PD-L1 expression by ICC cells provide them with an immune escape mechanism. This mechanism justifies the implementation of immunotherapy with checkpoint molecule-specific mAbs in patients bearing ICC tumors without defects in HLA class I antigen expression.


Key issues in sphincter of Oddi dysfunction.
SOD is a challenging condition that is difficult to diagnose and treat. The high failure rate of endoscopic and surgical treatment reflects the difficulties in establishing accurate diagnosis and the lack of specific objective criteria by which appropriate therapy could be determined. In general, sphincter ablation should be offered for type I patients. An initial trial of medical therapy is appropriate for type II patients with mild-to-moderate symptoms and for all type III patients. SOM is highly recommended for type II patients and is mandatory for all type III patients if sphincter ablation is contemplated. Other causes of abdominal pain such as chronic pancreatitis or functional disorders should be considered in patients not benefiting from sphincter ablation. All procedures on the sphincter should be undertaken with caution after meticulous investigation, and patient selection should be based on strict objective criteria.


Electrochemically induced surface reconstruction of Ni-Co oxide nanosheet arrays for hybrid supercapacitors.
Transition metal oxides (TMOs) are promising materials for supercapacitors (SCs) because of their high theoretical capacity. However, their finite active sites and poor electrical conductivity lead to reluctant electrochemical performance. Herein, we report a facile electrochemical activation (ECA) method to boost the electrochemical activity of Ni-Co oxide nanosheet arrays (NiCoO NSA) for SCs. Specifically, honeycomb-like NiCoO NSA that was made through a solvothermal method followed by air annealing was activated by simply exerting certain cyclic voltammetry scans (the activated sample is named ac-NiCoO NSA). We have found this treatment results in dramatic surface structure change, forming numerous sub-nanostructures (nanoparticles and nano-leaves) on the NiCoO nanosheets. Rich antisite defects and oxygen vacancies in the NiCoO spinel phase were also created by the ECA treatment. Consequently, the ac-NiCoO NSA delivered a maximum capacity of 206.5 mAh g-1 (0.5 A g-1), which is about three times of the NiCoO NSA without treatment. A hybrid SC based on the ac-NiCoO NSA demonstrated excellent energy storage capacity (power density of 17.3 kW kg-1 and energy density of 45.4 Wh kg-1) and outstanding cyclability (>20,000 cycles, 77.4% retention rate). Our method provides a simple strategy for fabricating high performance TMOs for electrical energy storage devices like SCs.


Engineering a Carbonyl Reductase for Scalable Preparation of (S)-3-Cyclopentyl-3-hydroxypropanenitrile, the Key Building Block of Ruxolitinib.
(S)-3-Cyclopentyl-3-hydroxypropanenitrile is the key precursor for the synthesis of ruxolitinib. The bioreduction of 3-cyclopentyl-3-ketopropanenitrile (1 a) offers an attractive method to access this important compound. A carbonyl reductase (PhADH) from Paraburkholderia hospita catalyzed the reduction of 1 a giving the (S)-alcohol (1 b) with 85 % ee. Rational engineering of PhADH resulted in a double mutant H93C/A139L, which enhanced the enantioselectivity from 85 % to >98 %, as well as a 6.3-fold improvement in the specific activity. The bioreduction of 1 a was performed at 200 g/L (1.5 M) substrate concentration, leading to isolation of (S)-1 b in 91 % yield. Similarly, using this mutant enzyme, 3-cyclohexyl-3-ketopropanenitrile (2 a) and 3-phenyl-3-ketopropanenitrile (3 a) were reduced at high concentration affording the corresponding alcohols in >99 % ee, and 90 % and 92 % yield, respectively. The results showed that the variant H93C/A139L was a powerful biocatalyst for reduction of β-substituted-β-ketonitriles.


Surface plasmon resonance imaging biosensor for cathepsin G based on a potent inhibitor: development and applications.
A specific surface plasmon resonance imaging (SPRI) array biosensor for the determination of the enzymatically active cathepsin G (CatG) has been developed. For this purpose, a specific interaction between an inhibitor immobilized onto a chip surface and CatG in an analyzed solution was used. The MARS-115 CatG peptidyl inhibitor containing the 1-aminoalkylphosphonate diaryl ester moiety at the C terminus and N-succinamide with a free carboxylic function was synthesized and covalently immobilized onto the gold chip surface via the thiol group (cysteamine). Atomic force microscopy was used for the observation of surface changes during the subsequent steps of chip manufacture. Optimal detection conditions were chosen. High specificity of synthesized inhibitor to CatG was proved. The precision, as well as the accuracy, was found to be well suited to enzyme determination. The sensor application for the determination of CatG in white blood cells and saliva was shown for potential diagnosis of leukemia and oral cavity diseases during the early stages of those pathological states.


Functional localization of brainstem and cervical spinal cord nuclei in humans with fMRI.
To our knowledge, no published functional map of the human lower brainstem exists. Our purpose was to use 1.5-T functional MR imaging (fMRI) to visualize the location of cranial nerve (CN) nuclei and other pontine, bulbar, and cervical spinal cord nuclei by using specific sensory stimulation or motor performance. We localized nuclei by using cross-correlation analysis of regional blood oxygen level-dependent (BOLD) signal intensity during specific motor and sensory procedures based on known functions of specific nuclei. Statistical parametric mapping (SPM) analysis was used for comparison. Head, cardiac, and respiratory motion artifact correction was applied. Histologic atlases aided localization. We obtained evidence of localization of the following nuclei by using tests, as follows: main trigeminal sensory (CN V), brushing the face; abducens (CN VI), left-right eye movement; facial (CN VII), smiling and lip puckering; hypoglossal (CN XII), pushing the tongue against the hard palate; nucleus ambiguus, swallowing; nucleus tractus solitarii (NTS), tasting a sweet-sour-salty-bitter mixture; nucleus cuneatus, finger tapping; and cervical spinal cord levels C1-C3, tongue movement to activate the strap muscles. Activation of cortical motor and sensory areas and somatosensory thalamus corresponded with the tasks and sites of brainstem activation. Head movement was minimal, typically less than 1 mm in all three axes. With 1.5-T fMRI, the CN nuclei of the pons and medulla, and other nuclei of the lower brainstem and cervical spinal cord, can be localized in awake humans with specific sensory stimulation or motor performance.


Analysis of teleost hemoglobin by Adair and Monod-Wyman-Changeux models. Effects of nucleoside triphosphates and pH on oxygenation of tench hemoglobin.
The allosteric effects of the erythrocytic nucleoside triphosphates (NTP) and of proton concentrations were investigated by precise measurement of Hb-O2 equilibria of tench hemoglobin (including extreme, high and low saturation ranges) and analysed in terms of the MWC two state model and the Adair four step oxygenation theory. At low concentrations (NTP/Hb ratio = 1.0, and pH greater than 7.3) ATP, GTP and protons decrease Hb-O2 affinity by increasing the allosteric constant L and reducing KT, the association constant of the deoxy, tense state of the Hb, without significantly affecting that (KR) of the oxy state, increasing the free energy of cooperativity (delta G). High concentrations of these effectors, however, also reduce KR. The greater sensitivity of the half-saturation O2 tension (P50) of the Hb to GTP than to ATP at the same concentration, correlates with greater effects of GTP on both KT and KR. The pH and NTP dependence of the four Adair association constants and the calculated fractional populations of Hb molecules in different stages of oxygenation show that the autochthonous NTP effectors and protons stabilize the T structure and postpone the T----R transition basic to cooperativity in fish Hb. The possible implications of the findings for aquatic respiration are discussed.


Recent innovations in renal replacement technology and potential applications to transplantation and dialysis patients: a review of current methods.
The current standard of care for patients with end-stage renal disease (ERSD) is a kidney transplant or dialysis when a donor organ isnot available. The growing gap between patients who require a kidney transplant and the availability of donor organs as well as thenegative effects of long-term dialysis, such as infection, limited mobility, and risk of cancer development, drive the impetus to developalternative renal replacement technology. The goal of this review is to assess the potential of two of the most recent innovations inkidney transplant technology-the implantable bioartificial kidney (BAK) and kidney regeneration technology-in addressing the aforementionedproblems related to kidney replacement for patients with ERSD. Both innovations are fully implantable, autologous, personalizedwith patient cells, and can replace all aspects of kidney function. Not only do these new innovations have the potential toimprove the possibility of transplantation for more patients, they also have potential to improve the outcome of transplantation or dialysis-related renal cancer diagnosis. A major limitation of the current technology is that both implantable BAK and kidney regenerationtechnology are still in preclinical stages, and thus their potential effects cannot be comprehensively generalized to human patients.


Protease inhibitor monotherapy: what is its role?
Protease inhibitor monotherapy has been shown to be effective in maintaining long-term viral suppression in a majority of patients. Withdrawal of nucleoside analogues can prevent long-term toxicity related to these drugs. Clinical trials have recently reported preliminary data on the beneficial effect of protease inhibitor monotherapy on body fat distribution and bone metabolism. Some of the uncertainties possibly associated with protease inhibitor monotherapy such as the increased risk of neurological events and a higher level of subclinical inflammation will be discussed in this review.


Urokinase receptor deficiency results in EGFR-mediated failure to transmit signals for cell survival and neurite formation in mouse neuroblastoma cells.
Urokinase-type plasminogen activator uPA and its receptor (uPAR) are the central players in extracellular matrix proteolysis, which facilitates cancer invasion and metastasis. EGFR is one of the important components of uPAR interactome. uPAR/EGFR interaction controls signaling pathways that regulate cell survival, proliferation and migration. We have previously established that uPA binding to uPAR stimulates neurite elongation in neuroblastoma cells, while blocking uPA/uPAR interaction induces neurite branching and new neurite formation. Here we demonstrate that blocking the uPA binding to uPAR with anti-uPAR antibody decreases the level of pEGFR and its downstream pERK1/2, but does increase phosphorylation of Akt, p38 and c-Src Since long-term uPAR blocking results in a severe DNA damage, accompanied by PARP-1 proteolysis and Neuro2a cell death, we surmise that Akt, p38 and c-Src activation transmits a pro-apoptotic signal, rather than a survival. Serum deprivation resulting in enhanced neuritogenesis is accompanied by an upregulated uPAR mRNA expression, while EGFR mRNA remains unchanged. EGFR activation by EGF stimulates neurite growth only in uPAR-overexpressing cells but not in control or uPAR-deficient cells. In addition, AG1478-mediated inhibition of EGFR activity impedes neurite growth in control and uPAR-deficient cells, but not in uPAR-overexpressing cells. Altogether these data implicate uPAR as an important regulator of EGFR and ERK1/2 signaling, representing a novel mechanism which implicates urokinase system in neuroblastoma cell survival and differentiation.


On two new linstowiid cestodes from Australian dasyurid marsupials.
Two new species of the genus Oochoristica Lühe, 1898 from Australian dasyurid marsupials are described and their affinities discussed. The new species are O. antechini sp. nov. from Antechinus macdonnellensis and O. eremophlia sp. nov. from Antechinus rosamondae.


Parasitic infection of the male breast.
Breast lumps are commonly seen in clinical practice, yet deeper exploration of this particular case presented an unusual diagnostic challenge.


DHU-Pred: accurate prediction of dihydrouridine sites using position and composition variant features on diverse classifiers.
Dihydrouridine (D) is a modified transfer RNA post-transcriptional modification (PTM) that occurs abundantly in bacteria, eukaryotes, and archaea. The D modification assists in the stability and conformational flexibility of tRNA. The D modification is also responsible for pulmonary carcinogenesis in humans. For the detection of D sites, mass spectrometry and site-directed mutagenesis have been developed. However, both are labor-intensive and time-consuming methods. The availability of sequence data has provided the opportunity to build computational models for enhancing the identification of D sites. Based on the sequence data, the DHU-Pred model was proposed in this study to find possible D sites. The model was built by employing comprehensive machine learning and feature extraction approaches. It was then validated using in-demand evaluation metrics and rigorous experimentation and testing approaches. The DHU-Pred revealed an accuracy score of 96.9%, which was considerably higher compared to the existing D site predictors. A user-friendly web server for the proposed model was also developed and is freely available for the researchers.


Intrinsically determined turnover underlies broad heterogeneity in plasma-cell lifespan.
Antibodies produced by antibody-secreting plasma cells (ASCs) underlie multiple forms of long-lasting immunity. Here we examined the mechanisms regulating ASC turnover and persistence using a genetic reporter to time-stamp ASCs. This approach revealed ASC lifespans as heterogeneous and falling on a continuum, with only a small fraction surviving for >60 days. ASC longevity past 60 days was independent of isotype but correlated with a phenotype that developed progressively and ultimately associated with an underlying "long-lived" ASC (LL ASC)-enriched transcriptional program. While some of the differences between LL ASCs and other ASCs appeared to be acquired with age, other features were shared with some younger ASCs, such as high CD138 and CD93. Turnover was unaffected by altered ASC production, arguing against competition for niches as a major driver of turnover. Thus, ASC turnover is set by intrinsic lifespan limits, with steady-state population dynamics governed by niche vacancy rather than displacement.


Effective treatment for suppression of acrylamide formation in fried potato chips using L-asparaginase from Bacillus subtilis.
It has been reported that acrylamide, a potential carcinogen, is formed from the reaction of L-asparagine (L-Asn) and reducing sugars contained in foods during heating processes and free asparagine is a limiting factor for acrylamide formation. It has been reported that potato products such as potato chips, which are made through heating processes, contain high levels of acrylamide. To decrease the amount of L-Asn in potatoes using L-asparaginase, effective treatment conditions of sliced potatoes with the enzyme have been investigated. By treating sliced potatoes with Bacillus subtilis L-asparaginase II (BAsnase; 4 U/g potato), appriximately 40 % of L-Asn in the sliced potatoes was converted into L-aspartic acid (L-Asp). To make this enzyme more effective, prior to enzymatic treatment, sliced potatoes were freeze-thawed, dried at 90 °C for 20 min, and vacuum treated for 10 min under decompressed condition, resulting in the hydrolysis of approximately 90 % of L-Asn to L-Asp. The acrylamide content of BAsnase-treated fried potato chips decreased to below 20 % of that of BAsnase-untreated fried potato chips. Treatment conditions examined in this study were found to be effective to suppress the formation of acrylamide in fried potato chips.


The Impact of Worksite Wellness Programs by Size of Business: A 3-Year Longitudinal Study of Participation, Health Benefits, Absenteeism, and Presenteeism.
Worksite wellness programs (WWP) may positively impact employee health, medical expenditures, absenteeism, and presenteeism. However, there has been little research to assess the benefits of WWP in small businesses. The purpose of this study is to prospectively evaluate changes in health, absenteeism, and presenteeism for employees who participated in a WWP. We conducted an observational, 3-year cohort study of 5766 employees from 314 businesses of differing sizes. We followed two cohorts of employees, who completed at least two annual health risk assessments (HRA) between May 2010 and December 2014. Changes from baseline to the first and second follow-up periods were assessed for chronic and non-chronic health conditions, absenteeism, and presenteeism. Small business employees were more likely to participate in the WWP than were employees from large businesses. Changes in chronic and non-chronic health conditions varied by size of business, with small business employees showing improvements in stress, overall health, depression, smoking status, vegetable and fruit consumption, and physical activity, and in their perceptions of job health culture. In contrast, large business employees experienced improvements in stress, vegetable consumption, and alcohol use. No changes in absenteeism or presenteeism were observed. Small businesses achieve higher employee participation rates and more health improvements when compared to employees from large employers. Findings suggest that small businesses may gain the most from a WWP.


Palmo-plantar lesions in paucibacillary leprosy--unusual clinical expressions.
Paucibacillary leprosy of the palmo-plantar skin is regarded as unusual. Three cases of Paucibacillary leprosy with such lesions are discussed and the relevent literature reviewed.


Reconstruction with free jejunal autograft after pharyngolaryngoesophagectomy.
Twenty-four patients with hypopharyngeal or cervical esophageal carcinoma were treated surgically. All had squamous cell carcinoma, and none had intrathoracic lymph node involvement by preoperative computed tomography. Endoscopy in 18 patients confirmed there was no intramural spread into the thoracic esophagus. The patients underwent pharyngolaryngoesophagectomy and bilateral modified radical neck dissection. Reconstruction of the cervical esophagus was performed with transplantation of a free jejunal autograft. Postoperative complications included anastomotic leak in 2 patients (8.3%), wound infection in 3 (12.5%), and intussusception in 4 (16.7%). Reconstruction of the cervical esophagus was successful in 23 (95.8%) of the 24 patients. The operative mortality rate was 4.2%, and the 5-year survival rate was 39.7%. We emphasize that pharyngolaryngoesophagectomy followed by transplantation of a free jejunal graft is suitable for cervical esophageal carcinoma or hypopharyngeal carcinoma when the disease is limited to the cervical region.


A new strikingly-colored species of the genus Galathea Fabricius, 1793 (Crustacea: Decapoda: Anomura: Galatheidae) from the Ryukyu Islands, Japan.
A new shallow-water squat lobster, Galathea ryuguu, is described on the basis of material obtained from a colony of unidentified sea fan of the genus Muricella Verrill, 1868. The new species is most closely allied to G. squamea Baba, 1979, but is distinguished by the ornamentation and armature of the carapace, third maxilliped, and ambulatory legs.


Induction of osteoprogenitor cell differentiation in rat marrow stroma increases mitochondrial retention of rhodamine 123 in stromal cells.
Bone marrow stromal cells contain colony forming cells with the potential to differentiate into osteoprogenitor (OPC) cells. OPC-stimulation medium, containing dexamethasone, ascorbate, and beta-glycerophosphate is widely used to recruit OPCs in culture. Cultures were incubated 24 h with rhodamine 123 (Rho), on different days, to examine the effect of the OPC-stimulation medium on the mitochondrial membrane potential of stromal cells. Cultures grown in both ordinary medium (DMEM with 15% FCS) and OPC-stimulation medium showed 2 Rho retention peaks on days 3-4 and 10-11. Between days 5 and 10 there was a drop in Rho retention/cell. OPC-stimulation medium increased Rho retention by at least twice the amount relative to ordinary medium, and has quadrupled it on day 7. Incubation with Rho concentrations above 5.0 micrograms/ml inhibited the portion of increased Rho retention which was contributed by the OPC-stimulation medium. Prolonged exposure to 0.1, 1.0, and 10.0 micrograms/ml Rho for 12 days only slightly increased day 12 ALP activity/cell, had no effect on day-21 mineralization and only the high dose, 10.0 micrograms/ml, doubled stromal cell proliferation. Under 24 h incubation Rho concentrations of 1.0 microgram/ml and below can serve as a marker for mitochondrial membrane potential in differentiating stromal cells. The results indicate that under both culture conditions stromal cell mitochondria undergo cycles of high and low membrane potential states and that the OPC-stimulation medium constantly maintains an elevated membrane potential relative to ordinary medium.


The effect of narrowband ultraviolet B phototherapy on antinuclear antibody status: A case-control study.
Narrowband ultraviolet B (NB-UVB) phototherapy has become a widely used, standard treatment modality in dermatology. The effect of 8-methoxypsoralen plus ultraviolet A on antinuclear antibody (ANA) formation has been investigated extensively, but there are very scarce data about the potential risk of NB-UVB phototherapy inducing production of ANAs. The aims of this study were evaluation of ANA status before and after NB-UVB treatment and comparison of ANA status with the healthy control group. Phototherapy unit database was used to identify patients who had received whole body NB-UVB treatment. Analyses of ANA were performed twice in the study group that were before initiation of the NB-UVB phototherapy and after cessation of the therapy. Also, ANAs were screened in the control group. A total of 95 patients (50 males and 45 females; mean age: 43.03 ± 13.40) treated with NB-UVB radiation and 90 age- and sex-matched controls were included in the study. Thirteen patients (13.7%) were found to develop ANAs at the end of the treatment. ANA positivity was significantly more common in patients after phototherapy than in patients before phototherapy and than in the control group. None of the patients in the positive ANA group was diagnosed with any connective tissue diseases. This study revealed that ANA positivity increased after NB-UVB phototherapy. However, it did not provide evidence for increased connective tissue disease risk. Therefore, ANA might not need to be routinely checked before treatment unless the patients have signs and symptoms indicating autoimmune diseases.


Intestinal obstruction due to a defect in the omentum.
An unusual cause of instestinal obstruction is described in a 46-year-old woman thought before operation to have Crohn's disease. The right colon and terminal ileum had passed through a defect that had developed spontaneously in the greater omentum and had remained in that position for at least 1 year. The bowel was reduced and the multiple defects in the omentum were repaired.


Managing bronchiolitis obliterans syndrome (BOS) and chronic lung allograft dysfunction (CLAD) in children: what does the future hold?
The success of pediatric lung transplantation continues to be limited by long-term graft dysfunction. Historically this has been characterized as an obstructive spirometric defect in the form of the bronchiolitis obliterans syndrome (BOS). It is recognized, however, that this does not reflect many of the other acknowledged etiologies of chronic lung dysfunction-noting it is the sum of the parts that contribute to respiratory morbidity and mortality after transplant. The term chronic lung allograft dysfunction (CLAD) has been coined to reflect these other entities and, in particular, a group of relatively recently described lung disorders called the restrictive allograft syndrome (RAS). RAS is characterized by a restrictive spirometric defect. Although these entities have not yet been studied in a pediatric setting their association with poor compliance, antibody-mediated rejection (AMR), and post-infectious lung damage (particularly viral) warrants attention by pediatric lung transplant teams. Current therapy for the BOS subset of CLAD is otherwise limited to changing immunosuppressants and avoiding excessive infectious risk by avoiding over-immunosuppression. Long-term macrolide therapy in lung transplantation is not of proven efficacy. Reviewing previous BOS studies to explore restrictive spirometric cases and joint projects via groups like the International Pediatric Lung Transplant Collaborative will be the way forward to solve this pressing problem.


The influence of lapses of attention on working memory capacity.
In three experiments, the influence of lapses of attention on working memory (WM) capacity measures was examined. Participants performed various change detection tasks while also reporting whether they were focused on the current task or whether they were unfocused and mind-wandering. Participants reported that they were mind-wandering roughly 27% of the time, and when participants reported mind-wandering, their performance was worse compared to when they reported being on-task. Low WM capacity individuals reported more mind-wandering and lapses of attention than high WM capacity individuals, and mind-wandering and filtering abilities were shown to make independent contributions to capacity estimates. These results provide direct support for the notion that the ability to focus attention on-task and prevent lapses of attention is an important contributor to performance on measures of WM capacity.


Is lactate lower in septic patients who are prescribed beta blockers? Retrospective cohort study of an intensive care population.
Elevated serum lactate has long been considered an important marker of sepsis severity. Increasing evidence supports catecholamine-stimulated aerobic glycolysis being a major contributor to the hyperlactataemia seen in sepsis. Beta-blockade may blunt such catecholamine mediated rise in lactate analogous to the way it can mask tachycardia. This could impact the way we evaluate sepsis severity and adequacy of initial treatment. The objective of this study is to investigate whether septic patients who were on beta-blocker treatment at presentation have lower serum lactate level. Using a retrospective cohort design we gathered data on patients admitted to our base hospital intensive care unit with APACHE III diagnosis of sepsis and septic shock during the 2017 calendar year. Serum lactate, current medications, presenting vital signs, illness severity scores, laboratory data and mortality outcome were extracted from patients' medical record and the unit's clinical database. Of 189 records analysed, 49 patients were concurrently prescribed beta-blockers. More beta-blocked patients were male, beta-blocked patients were older, and a greater proportion of beta blocked patients had their first lactate measured as an inpatient. After regression to correct for identified significant covariates mean serum lactate was 0.87 (95% confidence interval 0.05-1.69) mmol/L lower in those prescribed beta blockers. In our cohort pre-existing beta blocker treatment was associated with lower serum lactate measurements in patients presenting with sepsis. Pre-existing beta blocker treatment may reduce serum lactate at presentation in patients with sepsis.


"Autoinflammatory psoriasis"-genetics and biology of pustular psoriasis.
Psoriasis is a chronic inflammatory skin condition that has a fairly wide range of clinical presentations. Plaque psoriasis, which is the most common manifestation of psoriasis, is located on one end of the spectrum, dominated by adaptive immune responses, whereas the rarer pustular psoriasis lies on the opposite end, dominated by innate and autoinflammatory immune responses. In recent years, genetic studies have identified six genetic variants that predispose to pustular psoriasis, and these have highlighted the role of IL-36 cytokines as central to pustular psoriasis pathogenesis. In this review, we discuss the presentation and clinical subtypes of pustular psoriasis, contribution of genetic predisposing variants, critical role of the IL-36 family of cytokines in disease pathophysiology, and treatment perspectives for pustular psoriasis. We further outline the application of appropriate mouse models for the study of pustular psoriasis and address the outstanding questions and issues related to our understanding of the mechanisms involved in pustular psoriasis.


Editorial Commentary: Interportal Capsulotomy for Hip Arthroscopy in Patients With Borderline Hip Dysplasia May Result in Inferior Outcomes: Periportal Capsulotomy May Reduce Hip Capsular Damage.
Management of the hip capsule remains an ongoing discussion in the field of hip arthroscopy. Interportal and T-capsulotomies remain the most common approaches to gain access to the hip during surgery, and biomechanical and clinical research supports repair of these types of capsulotomies. Less is known, however, about the quality of the tissue that heals at these repair sites during the postoperative period, particularly in the setting of patients with borderline hip dysplasia. The capsular tissue provides important joint stability to these patients, and disruption to the capsule can result in significant functional impairments. There is also an association between borderline hip dysplasia and joint hypermobility, which increases the risk of insufficient healing after capsular repair. Patients with borderline hip dysplasia show poor capsular healing after arthroscopy followed by interportal hip capsule repair, and incomplete healing results in inferior patient-reported outcomes. Periportal capsulotomy may limit capsular violation and improve outcomes.


Peripheral polyneuropathy in children and young adults with ataxia-telangiectasia.
Ataxia-telangiectasia (A-T) is a rare, autosomal recessive, multisystem disorder that leads to progressive neurodegeneration with cerebellar ataxia and peripheral polyneuropathy. Cerebellar neurodegeneration is well described in A-T. However, peripheral nervous system involvement is an underdiagnosed but important additional target for supportive and systemic therapies. The aim of this study was to conduct neurophysiological measurements to assess peripheral neurodegeneration and the development of age-dependent neuropathy in A-T. In this prospective study, 42 classical A-T patients were assessed. The motor and sensory nerve conduction of the median and tibial nerves was evaluated. Data were compared to published standard values and a healthy age- and gender-matched control group of 23 participants. Ataxia scores (Klockgether, Scale for the Assessment and Rating of Ataxia) were also assessed. In A-T, neurophysiological assessment revealed neuropathic changes as early as the first year of life. Subjective symptomatology of neuropathy is rarely described. In the upper extremities, motor neuropathy was predominantly that of a demyelinating type and sensory neuropathy was predominantly that of a mixed type. In the lower extremities, motor and sensory neuropathy was predominantly that of a mixed type. We found significant correlations between age and the development of motor and sensory polyneuropathy in A-T compared with healthy controls (p < 0.001). In A-T, polyneuropathy occurs mostly subclinically as early as the first year of life. The current study of a large national A-T cohort demonstrates that development of neuropathy in A-T differs in the upper and lower extremities.


Methods for producing experimental complete atrioventricular block in dogs.
This paper reviews methods for producing experimental complete atrioventricular (A-V) block in dogs, with emphasis on those methods that enable chronic A-V block to be obtained. The dog with chronic complete A-V block, particularly when unanesthetized, is a useful experimental model, and the production of complete A-V block is an approach to the clinical treatment of certain supraventricular arrhythmias. Criteria for the choice of method are discussed, and the results obtained to date in the unanesthetized dog with chronic A-V block are briefly described to illustrate the usefulness of this experimental model.


Clinical and Radiological Discrimination of Solitary Pulmonary Lesions in Colorectal Cancer Patients.
The lung is one of the most common organs of metastasis from colorectal cancer (CRC), and we have encountered lung cancer patients with a history of CRC. There have been few studies regarding methods used to discriminate between primary lung cancer (PLC) and pulmonary metastasis from CRC (PM-CRC) based only on preoperative findings. We retrospectively investigated predictive factors discriminating between these lesions in patients with a history of CRC. Between 2006 and 2015, 117 patients with a history of CRC (44 patients with 47 PLC and 73 patients with 102 PM-CRC) underwent subsequent or concurrent resection of pulmonary lesions. We compared the clinical and radiological characteristics of 100 patients with solitary lesions (43 PLC and 57 PM-CRC). Using univariate and multivariate analyses, we examined predictive factors for discrimination of these two lesions. All tumors with findings of ground-glass opacity (GGO) were PLC (n = 19). In a multivariate analysis of 81 radiologically solid tumors, two factors were found to be significant independent predictors of PLC: a history of stage I CRC and presence of pleural indentation. All tumors in 26 patients with either GGO or both a stage I CRC history and pleural indentation were PLC, while most tumors in patients without all three factors were PM-CRC (43/44; 97.7%). The presence or absence of GGO, pathological CRC stage, and pleural indentation could be useful factors to distinguish between PLC and PM-CRC.


Sex differences in glycated hemoglobin in diabetic and non-diabetic C57BL/6 mice.
Pathophysiological implications of gender may be important in a number of disease states. We therefore decided to study the influence of gender on glycation in mice. Plasma glucose and glycated hemoglobin levels were determined by ion exchange (HbA1c) and/or affinity chromatography (GHb) in C57BL/6 ob/ob mice during the onset and subsequent decline of hyperglycemia. In preweanling ob/ob mice, glucose and glycated hemoglobin concentrations were equal to those of lean sex-matched controls. Shortly after weaning, plasma glucose in ob/ob mice increased to reach a maximum between 2 and 3 months of age, then declined over the next several weeks to levels within the range of lean mice. HbA1c values were closely associated with the glycemic changes. Male mice of both phenotypes consistently had higher values of glycated hemoglobin at a given glucose value than did females. Disappearance rates of chromium-labeled erythrocytes were slightly higher in lean female mice than in other subgroups but after correcting for phenotype/sex differences in blood volume, no phenotype or gender differences in RBC lifespan were observed. We conclude that there are gender differences in glycation of hemoglobin in mice and that factors other than RBC turnover are associated with the gender effects in both obese and lean mice.


Self-floating black phosphorous nanosheets as a carry-on solar vapor generator.
Efficient solar vapor generation has provided a feasible way to solve the water shortage in undeveloped and arid areas. However, some photo-thermal materials need additional large-volume support materials being harmful to carry around to obtain float capacity, while suppressing the solar steam generation. Herein, the decrease approach of surface tension was presented for solving the moist-environment degradation behavior of black phosphorus (BP) nanosheets and obtaining the self-floating capacity, thus applying BP nanosheets in solar vapor generation field. With the in situ cross-linking polymerization, trichloro(1H,1H,2H,2H-perfluorooctyl) silane successfully modified BP nanosheets (F-BP). Due to the significantly decreased surface tension, F-BP nanosheets are capable of self-floating easily on water surface and spreading out spontaneously. With assistance of desirable photo-thermal conversion capacity, self-floating BP nanosheets convert the incident photon into local heat, showing excellent vapor generation performance. With simulated sun illumination (1 kW/m2), 238.7 g/m2 BP nanosheets present the evaporation rate of ~0.9437 kg/(m2·h) and efficiency of ~64.63 ± 2.3%. Meanwhile, the super-hydrophobicity successfully imparts BP nanosheets with resistance to the deterioration caused by salt precipitation. The carriable F-BP nanosheets are an ideal photo-thermal convertor to produce drinking water, successfully providing a feasible way to solve water shortage in limited condition.


Neural correlates of turn-taking in the wild: Response planning starts early in free interviews.
Conversation is generally characterized by smooth transitions between turns, with only very short gaps. This entails that responders often begin planning their response before the ongoing turn is finished. However, controversy exists about whether they start planning as early as they can, to make sure they respond on time, or as late as possible, to minimize the overlap between comprehension and production planning. Two earlier EEG studies have found neural correlates of response planning (positive ERP and alpha decrease) as soon as listeners could start planning their response, already midway through the current turn. However, in these studies, the questions asked were highly controlled with respect to the position where planning could start (e.g., very early) and required short and easy responses. The present study measured participants' EEG while an experimenter interviewed them in a spontaneous interaction. Coding the questions in the interviews showed that, under these natural circumstances, listeners can, in principle, start planning a response relatively early, on average after only about one third of the question has passed. Furthermore, ERP results showed a large positivity, interpreted before as an early neural signature of response planning, starting about half a second after the start of the word that allowed listeners to start planning a response. A second neural signature of response planning, an alpha decrease, was not replicated as reliably. In conclusion, listeners appear to start planning their response early during the ongoing turn, also under natural circumstances, presumably in order to keep the gap between turns short and respond on time. These results have several important implications for turn-taking theories, which need to explain how interlocutors deal with the overlap between comprehension and production, how they manage to come in on time, and the sources that lead to variability between conversationalists in the start of planning.


Nitrogen-doped carbon nanospheres derived from cocoon silk as metal-free electrocatalyst for glucose sensing.
Nitrogen-doped carbon materials have attracted tremendous attention because of their high activity in electrocatalysis. In the present work, cocoon silk -- a biomass material is used to prepare porous carbon fibers due to its abundant nitrogen content. The as-prepared carbon microfibers have been activated and disintegrated into carbon nanospheres (CNS) with a diameter of 20--60 nm by a simple nitric acid refluxing process. Considering their excellent electrocatalytic activity towards the reduction of oxygen, the CNS modified electrodes are further applied in the construction of glucose amperometric biosensor using glucose oxidase as a model. The proposed biosensor exhibits fast response, high sensitivity, good stability and selectivity for glucose detection with a wide linear range from 79.7 to 2038.9 μM, and a detection limit of 39.1 μM. The performance is comparable to leading literature results indicating a great potential for electrochemical sensing application.


Liver Transplantation to the Active Smoker: Transplant Provider Opinions and How They Have Changed : Transplantation in Smokers: A Survey.
Awareness of smoking complications in liver transplantation patients is increasing. No study in the past 15 years has addressed attitudes toward offering transplantation to smokers. Our aim was to determine smoking policies nationwide. We conducted a survey of liver transplantation centers. The seven-question survey was sent to medical and surgical directors of liver transplantation. Results were analyzed in R 3.1.1 using two-tailed t testing and ANOVA. Fifty one of 110 centers (46 %) responded. Volume transplanted annually ranged from 10 to 190. Most respondents acknowledged a policy on smoking (38/51, 75 %). Most centers with policies required cessation (32/38, 84 %). All other centers did encourage attempts at cessation (19/19, 100 %). Whether smoking cessation was required differed by region (p = 0.02). Southern programs more commonly required smoking cessation (87.5 vs. 38.4 %, p < 0.001). The highest rates of smoking cessation were noted in the Southwest (90.0 %) and the lowest in the Northeast (26.2 %). There was a trend toward requiring cessation in larger-volume centers. Most respondents had a tobacco policy and tended to require abstinence; however, ultimately centers were divided on requiring cessation. Regional differences were noted, with the South more commonly requiring cessation. Our results indicate lack of consensus among transplantation centers regarding access of smokers to liver transplantation.


Role of metallothionein in lung inflammation induced by ozone exposure in mice.
Metallothionein (MT) is a free radical scavenger induced by inflammatory stimuli; however, its roles in inflammation have not been fully investigated. In the present study, we genetically determined the role of MT in ozone (O(3))-induced lung inflammation using MT-I/II null (-/-) mice. Subacute (65 h) exposure to O(3) (0.3 ppm) induced lung inflammation and enhanced vascular permeability, which was significantly greater in MT(-/-) than in corresponding wild-type mice. Electron microscopically, O(3) exposure induced vacuolar degeneration of pulmonary endothelial and epithelial cells, and interstitial edema with focal loss of the basement membrane, which was more prominent in MT(-/-) than in wild-type mice. O(3) -induced lung expression of interleukin-6 was significantly greater in MT(-/-) than in wild-type mice; however, lung expression of the chemokines examined was comparable in both genotypes of mice in the presence of O(3). Following O(3) exposure, the formation of oxidative stress-related molecules/adducts, such as heme oxidase-1, inducible nitric oxide synthase, 8-hydroxy-2'-deoxyguanosine, and nitrotyrosine, in the lung was significantly greater in MT(-/-) than in wild-type mice. Collectively, MT protects against O(3)-induced lung inflammation, at least partly, via the regulation of pulmonary endothelial and epithelial integrity and its antioxidative property.


Advances in antibody engineering for rheumatic diseases.
The advent of biologic therapies, particularly antibody therapeutics, has revolutionized the pharmacological treatment of many rheumatic diseases. Antibody discovery began with the immunization of mice for the production of rodent immunoglobulins, but advances in protein and genetic engineering have now made it possible to generate fully human antibodies, which are better tolerated by patients. For most clinical applications in rheumatology, antibodies have been used as blocking agents capable of neutralizing the function of pro-inflammatory proteins, such as TNF. The latest strategies involve antibody products armed with effector moieties, such as anti-inflammatory drugs or cytokines, or antibody products that are specific for multiple targets for the selective inhibition of inflammation at sites of disease. Antibodies are some of the best-selling drugs in the world, and with further advances in antibody development, engineering of armed antibodies and bispecific products will have an important role in the treatment of rheumatic diseases.


Transient visually evoked potentials to the pattern reversal and onset of sinusoidal gratings.
Transient visually evoked potentials (VEPs) recorded in response to the contrast reversal and onset of spatially sinusoidal gratings have been investigated. Previous reports of an increase in the latency of the response at higher spatial frequencies have been confirmed but only for spatial frequencies higher than 2 c/deg. At lower spatial frequencies it is suggested that two positive components interact resulting in a departure from a monotonic relationship between latency and spatial frequency. Below 1 c/deg pattern reversal and pattern onset modes of stimulation produced VEPs of similar amplitude and wave form. Above 1 c/deg the amplitude of the pattern onset response peaked at a higher spatial frequency than the response to pattern reversal, and the response was dominated by a negative (N1) rather than a positive component (P1). This distinction has been corroborated by investigating the effect of field size variation. The peak amplitudes shifted to a lower spatial frequency with increase in field size but at all field sizes the N1 component of the pattern onset response peaked at a higher spatial frequency than the other components measured. It is attempted to relate these findings to previous studies of both grating and checkerboard VEPs and to psychophysical studies of contrast sensitivity.


Emergency laparoscopic surgery--the Changi General Hospital experience.
This paper analyses the emergency laparoscopic procedures undertaken by our unit over a 1-year period in an effort to evaluate the diagnostic-therapeutic use of laparoscopy in an emergency situation. This is a retrospective study that analysed 137 emergency laparoscopic procedures that were performed for patients who presented with acute abdominal pain over a 1-year period from 31 December 1999 to 31 December 2000. A definitive diagnosis was made in 91.2% (125). Of the 78 cases that required surgical intervention, 71.8% (56) were performed laparoscopically. The conversion rate (to open surgery) was 16.8% (23) and the morbidity rate was 8% (11); with no mortalities. We conclude that laparoscopic surgery is effective and safe in the non-elective setting and it offers a high potential for diagnosis and therapy in selected patients in whom the diagnoses are equivocal.


RUNX2 Promotes Malignant Progression in Glioma.
Glioblastoma (GBM) is the most aggressive and lethal form of brain tumor. However, therapeutic strategies against malignant gliomas have not been completely established. Runt-related transcription factor 2 (Runx2) is an essential gene for skeletal development but its regulatory role in the malignant progression of glioma remains unclear. Here we investigated expression levels of RUNX2 in glioma tissues and its regulatory effects on aberrant growth of glioma cells. RUNX2 mRNA levels were higher in GBM tissues than that of normal brains or low-grade gliomas. RUNX2 protein was detected in five out of seven human GBM cell lines and its level was positively correlated with proliferative capacity. Stable transduction of dominant-negative Runx2 in rat-derived C6 glioma cells not only inhibited the promoter activity containing Runx2 response element, but also decreased mRNA expression levels of Runx2 target genes, such as Mmp13 and Spp1, as well as the proliferative capacity. Furthermore, transient introduction of Runx2-targeted siRNAs into C6 glioma cells significantly decreased mRNA expression levels of Mmp13 and Spp1 and the proliferative capacity. Furthermore, Runx2 knockdown suppressed both Ccnd1 mRNA expression and activation of the Ccnd1 promoter by forskolin, a PKA-activating reagent, in C6 glioma cells. Our results demonstrate that cross-talk between cAMP/PKA signaling and RUNX2 promotes a malignant phenotype of glioma cells.


Photocatalytic inactivation of viral particles of human norovirus by Cu-doped TiO2 non-woven fabric under UVA-LED wavelengths.
Metal-doped TiO2 photocatalysis are recognized as effective materials for eliminating human norovirus (HuNoVs). In recent years, the airborne transmission of viral particles of HuNoVs has been a cause for concern. In this study, we evaluated the virucidal effects of a Cu/TiO2 non-woven fabric (NWF) on viral particles of HuNoV genogroup II genotype 4 (HuNoV GII.4) under an ultraviolet A light-emitting diode (UVA-LED) source. For the optimized parameters, a multivariate statistical analysis using the Box-Behnken design (BBD) technique combined with the response surface methodology (RSM) was applied. The experimental results showed that the Cu/TiO2-based NWF degraded HuNoV viral particles in the air samples. The BBD-based RSM indicated that the optimum treatment conditions for inactivating the HuNoV GII.4 droplets with the Cu/TiO2 NWF were a 1:7.7 ratio of Cu:TiO2 and the use of a 373-nm UVA-LED source for 48.08 min. The optimal conditions for the photocatalytic efficacy in HuNoV GII.4 of Cu/TiO2 NWF were verified experimentally, giving a value of 2.89 ± 0.11 log10 genomic copies, which was the same as the predicted value (2.91611) within experimental uncertainty. This result adequately validated the predicted model and confirmed that viral particles of HuNoVs could efficiently be disinfected using Cu/TiO2 NWF stimulated by UVA-LED light.


Rapid biomimetic remineralization of the demineralized enamel surface using nano-particles of amorphous calcium phosphate guided by chimaeric peptides.
The objective of this study was to develop a rapid and effective method to remineralize human carious-like enamel using chimaeric peptide-mediated nanocomplexes of carboxymethyl chitosan/amorphous calcium phosphate (CMC/ACP), mimicking the mineralizing pattern of the oriented assembly of ACP guided by amelogenin in the biomineralization of enamel. CMC/ACP nanocomplex solution was first synthesized through the successive addition of carboxymethyl chitosan, calcium chloride, and dipotassium phosphate into distilled water. ACP nanoparticles were degraded by 1% NaClO from CMC/ACP nanocomplexes. The morphology of the particles at different periods was tested by transmission electron microscopy (TEM). The chimaeric peptides were added to guide the arrangement of ACP nanoparticles and to bind ACP nanoparticles to the demineralized enamel surface specifically. X-ray diffraction (XRD)/scanning electron microscope (SEM)/confocal laser scanning microscopy (CLSM)/nano-indentation tests were applied to check the remineralization effects. CMC/ACP nanocomplexes were obtained and could be kept without precipitation for a long time. After the degradation of NaClO and guidance of chimaeric peptides, ACP nanoparticles were arranged into oriented arrays before transforming into crystals, and the enamel-like crystals were tightly bound onto the demineralized surface. The newly formed enamel-like crystals were nearly well-organized and equipped with strong mechanical properties.


Hazardous alcohol use and associated factors in a rural Ethiopian district: a cross-sectional community survey.
Alcohol related health and social problems are on the rise in sub-Saharan Africa. This survey reports the prevalence and associated factors for hazardous drinking in rural Sodo district, southern Ethiopia. The survey was part of a multi-center study, Programme for Improving Mental Health Care (PRIME), which is a consortium of research institutions and ministries of health of five low and middle income countries, namely Ethiopia, India, Nepal, South Africa and Uganda in partnership with UK institutions and World Health Organization (WHO). A cross-sectional community survey was conducted involving 1500 adults, age 18 and above, recruited using multi-stage random sampling. Data on alcohol use was collected using the Fast Alcohol Screening Test (FAST). Standardised instruments were used to measure potential associated factors, including a validated adaptation of the Kessler 10 (psychological distress), the List of Threatening Experiences (number of adverse life events). Exploratory multivariable logistic regression was conducted to examine factors associated with hazardous alcohol use. The overall prevalence of hazardous alcohol use was found to be 21 %; 31 % in males and 10.4 % in females, P < 0.05. Factors independently associated with hazardous alcohol use were being male (adjusted OR = 4.0, 95 % CI = 2.44, 6.67), increasing age, having experienced one or more stressful life events (adjusted OR = 1.71, 95 % CI = 1.18, 2.48, and adjusted OR = 2.12, 95 % CI = 1.36, 3.32 for 1-2 and 3 or more adverse life events, respectively) and severe psychological distress (adjusted OR = 2.96, 95 % CI = 1.49, 5.89). High social support was found to be protective from hazardous alcohol use (adjusted OR = 0.41, 95 % CI = 0.23, 0.72). High level of hazardous alcohol use was detected in this predominantly rural Ethiopian setting. The finding informed the need to integrate services for hazardous alcohol use such as brief intervention at different levels of primary care services in the district. Public health interventions to reduce hazardous alcohol use also need to be launched.


Postural change from lateral to supine is an important mechanism enhancing cephalic spread after injection of intrathecal 0.5% plain bupivacaine for cesarean section.
Spinal anesthesia is widely used for cesarean section, but the factors that affect the spread of the block in pregnant patients are still not fully explained. This study was designed to investigate the effect of postural changes on sensory block level. Thirty patients scheduled for elective cesarean section under combined spinal-epidural anesthesia were randomly allocated into three groups. After intrathecal injection of 0.5% plain bupivacaine 7.5mg, patients in group S were immediately placed in the supine position with left tilt, patients in group L5 were kept lateral for 5 min and then turned to the supine position with left tilt, and patients in group L10 were kept lateral for 10 min and then turned to the supine position with left tilt. At 5 min, median cephalad level of sensory block was lower in groups L5 and L10 compared with group S (corrected P<0.001); at 10 min, median cephalad sensory block level was lower in group L10 compared with group S (corrected P<0.001) and group L5 (corrected P<0.001), and lower in group L5 compared with group S (corrected P=0.033); at 15 min, median cephalad level of sensory block was lower in group L10 compared with group S (corrected P=0.003) and group L5 (corrected P=0.015). In our population, using 0.5% plain bupivacaine 7.5mg, postural change from the lateral position to the supine position is an important mechanism enhancing cephalic spread of spinal anesthesia during late pregnancy.


Methods to quantify the velocity dependence of common gait measurements from automated rodent gait analysis devices.
Walking slowly is a different biomechanical task than walking quickly, thus measures of gait will be different at different velocities, such as pre/post injury. It is necessary to determine if the difference in gait measures are from the experimental changes, or simply from traveling at different speeds. Instead of limiting this effect, we have developed techniques to embrace the velocity dependence of gait measures. By translating the pawprints into a body coordinate frame we are able to measure location of paw placement in addition to the standard gait measures. At higher velocities rats have greater consistency of steps, place their forelimb initial contact more medially and anteriorly, and place their hindlimb toe off more medially and posteriorly. Interlimb phasing also becomes more consistent at higher velocities. Following a cervical spinal cord injury consistency is reduced and the velocity dependent behaviors are significantly different. Translating the coordinate frame improves the ability to measure changes in base of support following spinal cord injury. Employing a treadmill, or limiting analysis to a narrow velocity window does address the effects of velocity. We feel that measuring across all velocities is more appropriate than dictating that the animals match speeds. Quantifying locomotion with automated gait analysis devices is a great way to evaluate the changes that experimental treatments provide. These new methods allow for a more appropriate way to address the confound of many gait measures being velocity dependent.


Review of some causes of stillbirth.
Stillborn fetuses commonly demonstrate three mechanisms of death: hydrops, asphyxia, or shock. For each mechanism, the autopsy can discover any of multiple etiologies. This paper reviews the etiologies and pathogeneses of fetal death from that perspective.


Investigating traffic fatality trends and restraint use among rear-seat passengers in the United States, 2000-2016.
Motor-vehicle crash is one of the leading causes of unintentional injury death in the United States. Previous studies focused on fatalities among drivers and front-seat passengers, with a limited number of studies examining rear-seat passenger fatalities. The objectives of this study were to assess trends in rear-seat passenger motor-vehicle fatalities in the United States from 2000 to 2016 and to identify demographic factors associated with being unrestrained among fatally injured rear-seat passengers. Rear-seat passenger fatality data were obtained from the Fatality Analysis Reporting System (FARS) database. The fatality rate ratios for overall rear-seat passengers and for different age and sex groups were determined by comparing fatality rates in 2000 and 2016 using random effects models. Risk ratios of being unrestrained for age and sex groups were obtained using general estimating equations. Compared to 2000, the overall rear-seat passenger fatality rate in 2016 decreased by 44% (95% confidence interval [CI]: 39-49%). In particular, the fatality rate among rear-seat passengers decreased more in males than females, and passengers aged 14-19 years experienced a larger decline than all other age groups. Fatally injured male rear-seat passengers had a higher risk of being unrestrained (adjusted risk ratio: 1.06, 95% CI: 1.04-1.07) than their female counterparts, and both youngest (≤13 years) and oldest (65-85 years) passengers were less likely to be unrestrained than those aged 20-64 years. Overall, fatality rates among rear-seat passengers have declined, with differential degrees of improvement by age and sex. Practical Applications: Continued restraint use enforcement campaigns targeted at teenagers and males would further preserve them from fatal injuries and improve traffic safety for the overall population.


Regulation of estrogen receptors in primary cultured hepatocytes of the amphibian Xenopus laevis as estrogenic biomarker and its application in environmental monitoring.
The present study aims to introduce the regulation of estrogen receptors (ER) in primary cultured hepatocytes of the amphibian Xenopus laevis as a further potential estrogenic biomarker. Time courses of free ER in cell cultures treated with 17beta-estradiol (E2), nonylphenol (NP), and bisphenol A (BPA) were determined by means of radioreceptorassay (RARA). All compounds led to an immediate drop of free ER followed by a significant increase. The estrogen specific induction of ER-mRNA in vitro during time course was verified by using semiquantitative RT-PCR demonstrating greatest differences after 36 h. Dose-response curves of ER-mRNA for E2, NP, and BPA revealed that E2 possessed highest estrogenicity starting at 10(-9) M, while NP and BPA induced significant increases at 10(-8) and 10(-7) M, respectively. Extracts of the river Alb were subjected to RARA for ER binding to cytosolic liver fraction as well as to primary cultured hepatocytes for assessment of ER-mRNA induction. The results by RARA demonstrated clearly that binding to ER was highest in sewage treatment plant effluents and increased during the course of the river. These findings could be correlated with induction of ER-mRNA levels in vitro indicating that both techniques are suitable for application in monitoring of estrogenic EDC.


Assessment of renal function with dynamic contrast-enhanced MR imaging.
MR imaging is a promising noninvasive modality that can provide a comprehensive picture of renal anatomy and function in a single examination. The advantages of MR imaging are its high contrast and temporal resolution and lack of exposure to ionizing radiation. In the past few years, considerable progress has been made in development of methods of renal functional MR imaging and their applications in various diseases. This article reviews the key factors for acquisition and analysis of dynamic contrast-enhanced renal MR imaging (MR renography) and the most significant developments in this field over the past few years.


Culprit-Only Versus Immediate Multivessel Percutaneous Coronary Intervention in Patients With Acute Myocardial Infarction Complicating Advanced Cardiogenic Shock Requiring Venoarterial-Extracorporeal Membrane Oxygenation.
Background Despite the benefit of culprit-only percutaneous coronary intervention (PCI) in the CULPRIT-SHOCK (Culprit Lesion Only PCI Versus Multi-vessel PCI in Cardiogenic Shock) trial, the optimal revascularization strategy for refractory cardiogenic shock (CS) requiring mechanical circulatory support devices remains controversial. This study aimed to compare clinical outcomes between the culprit-only and immediate multivessel PCI strategies in patients with acute myocardial infarction complicated by CS who underwent venoarterial-extracorporeal membrane oxygenation before revascularization. Methods and Results This study included patient-pooled data from the RESCUE (Retrospective and Prospective Observational Study to Investigate Clinical Outcomes and Efficacy of Left Ventricular Assist Devices for Korean Patients With Cardiogenic Shock) and SMC-ECMO (Samsung Medical Center-Extracorporeal Membrane Oxygenation) registries. A total of 315 patients with acute myocardial infarction with multivessel disease who underwent venoarterial-extracorporeal membrane oxygenation before revascularization attributable to refractory CS were included in this analysis. The study population was classified into culprit-only versus immediate multivessel PCI according to nonculprit lesion treatment strategies. The primary end point was 30-day mortality or renal-replacement therapy, and the key secondary end point was 12-month follow-up mortality. Among the study population, 175 (55.6%) underwent culprit-only PCI and 140 (44.4%) underwent immediate multivessel PCI. Compared with culprit-only PCI, immediate multivessel PCI was associated with significantly lower risks of 30-day mortality or renal-replacement therapy (68.0% versus 54.3%; P=0.018) and all-cause mortality during 12 months of follow-up (59.5% versus 47.5%; hazard ratio [HR], 0.689 [95% CI, 0.506-0.939]; P=0.018) in patients with acute myocardial infarction and CS who underwent venoarterial-extracorporeal membrane oxygenation before revascularization. These results were also consistent in the 99 pairs of propensity score-matched population (60.6% versus 43.6%; HR, 0.622 [95% CI, 0.420-0.922]; P=0.018). Conclusions Among patients with acute myocardial infarction with multivessel disease complicated by advanced CS requiring venoarterial-extracorporeal membrane oxygenation before revascularization, immediate multivessel PCI was associated with lower incidences of 30-day mortality or renal replacement therapy and 12-month follow-up mortality, compared with culprit-only PCI. Registration Information clinicaltrials.gov. Identifier: NCT02985008.


Incarceration of the gravid uterus.
Incarceration of the gravid uterus is a rare but serious complication of pregnancy. Reported is the case of a gravida 2, para 1 26-year-old woman who presented with lower abdominal pain. The patient was 14 weeks pregnant and presented with a one-day history of abdominal pain and vaginal discharge. Examination revealed a retroflexed uterus with the cervical opening pointing toward the anterior abdominal wall. An ultrasound revealed a uterus incarcerated between the sacral promontory and the pubis. Manual reduction was performed successfully in the emergency department.


Effects of prazosin on hemodynamics and sympatho-adrenal activity in hypertensive patients.
We studied peripheral and central hemodynamics and plasma catecholamine levels in 12 previously untreated patients with essential hypertension before and during treatment with the alpha 1-adrenoceptor antagonist prazosin (9.8 +/- 1.1 mg/day for 3-6 weeks following dose titration) as a single drug. Prazosin did not alter intra-arterially recorded blood pressures in the group as a whole, in spite of adequate plasma levels (12.6 +/- 1.2 ng/ml). There were no changes in cardiac output, blood volume, systemic or forearm vascular resistance, or forearm venous tone at rest during treatment. The blood pressure response to prazosin was correlated to pretreatment systemic and forearm vascular resistances. Arterial adrenaline levels were unchanged, but noradrenaline levels increased from 1.30 +/- 0.10 to 1.85 +/- 0.20 nM (p less than 0.05). Both noradrenaline and blood pressure responses to isometric hand-grip exercise were delayed and reduced during treatment. The hemodynamic and plasma catecholamine responses to a cold pressor test and tilting (50% head-up during 10 min) were similar before and during treatment. Our results may be related to development of tolerance to the alpha-adrenoceptor blocking effect of prazosin during long-term treatment. The elevation of arterial noradrenaline levels suggests that increased sympathetic activity also may have opposed the hypotensive response to prazosin.


A modified Rutter children's behaviour questionnaire. Its reliability and validity in screening for behaviour disturbances in part-Aboriginal children.
The Rutter Children's Behaviour Questionnaire was completed by the teachers of 108 Aboriginal pupils at two rural schools in the far west of New South Wales. The questionnaire ratings were compared with a contemporaneous psychiatric study of behaviour disturbance for each child. Some modification of the questionnaire was required because of cultural factors. The modified questionnaire was found to be of acceptable reliability and validity in screening for emotional disturbance in Aboriginal children. It is suggested that it would be a useful case finding instrument for teachers of part-Aboriginal children.


Healthcare-associated infections studies project: an American Journal of Infection Control and National Healthcare Safety Network data quality collaboration-Ventilator-associated event 1, 2013.
This is the second case study published in a series in AJIC since the Centers for Disease Control and Prevention/National Healthcare Safety Network (NHSN) surveillance definition update of 2013. These cases reflect some of the complex patient scenarios Infection Preventionists (IP) have encountered in their daily surveillance of health care-associated infections (HAI) using NHSN definitions. This is the first case utilizing the new NHSN Ventilator-associated Events (VAE) module and criteria.


Luxury uptake of phosphorus by sediment bacteria.
This note reports the results of experiments aimed at confirming the luxury uptake of phosphorus (P) by sediment bacteria as polyphosphate (Poly-P). Aerobic suspensions of sediments from two different sites were spiked with 1 mg P/L as orthophosphate and augmented with acetate (a fermentation product) or glucose. The orthophosphate was rapidly taken up over a period of a few hours. When these aerobic uptake experiments were made anaerobic and additional organic carbon added, only the acetate-amended sediment released a significant amount of the added phosphorus. It was hypothesised that during the aerobic stage, and with the addition of acetate, some of the phosphorus was accumulated as Poly-P by sediment microorganisms, which was released during the subsequent anaerobic stage (provided acetate was still present). Two lines of evidence--transmission electron microscope analysis of sediment bacteria and 31P-NMR analysis of sediment extracts--are presented to support the hypothesis that a portion of the phosphorus taken up during the aerobic experiments was stored as Poly-P.


Intracellular behaviour of Leishmania enriettii within murine macrophages.
Both promastigotes and amastigotes of Leishmania enriettii were readily ingested by mouse peritoneal macrophages (MPM). Promastigotes after their entry within MPM were rapidly immobilized and their multiplication was never observed. Microscopic examination revealed that ingested promastigotes were degraded with MPM. Nonmotile amastigotes of L. enriettii taken up by MPM, on the other hand, multiplied intracellularly and eventually destroyed the infected cells.


Multiple infundibular tumours of the head and neck.
A condition of multiple benign and sometimes self-healing infundibular tumours of the skin is described. It effects the sun-exposed areas of the head and neck in Caucasians. The individual lesions consist of a cluster of thick pockets, representing in many details the supra-sebaceous portions of the follicular unit. Follicular poroma, tumours of the deeper part of the follicular infundibulum, virus warts, inverted follicular keratosis and prurigo nodules do not correspond adequately with the appearance described in the present series of six cases.


Kepler-62: a five-planet system with planets of 1.4 and 1.6 Earth radii in the habitable zone.
We present the detection of five planets--Kepler-62b, c, d, e, and f--of size 1.31, 0.54, 1.95, 1.61 and 1.41 Earth radii (R⊕), orbiting a K2V star at periods of 5.7, 12.4, 18.2, 122.4, and 267.3 days, respectively. The outermost planets, Kepler-62e and -62f, are super-Earth-size (1.25 R⊕ < planet radius ≤ 2.0 R⊕) planets in the habitable zone of their host star, respectively receiving 1.2 ± 0.2 times and 0.41 ± 0.05 times the solar flux at Earth's orbit. Theoretical models of Kepler-62e and -62f for a stellar age of ~7 billion years suggest that both planets could be solid, either with a rocky composition or composed of mostly solid water in their bulk.


The bioconversion of 5-deoxystrigol to sorgomol by the sorghum, Sorghum bicolor (L.) Moench.
Strigolactones, important rhizosphere signalling molecules and a class of phytohormones that control shoot architecture, are apocarotenoids of plant origin. They have a structural core consisting of a tricyclic lactone connected to a butyrolactone group via an enol ether bridge. Deuterium-labelled 5-deoxystrigol stereoisomers were administered to aquacultures of a high sorgomol-producing sorghum cultivar, Sorghum bicolor (L.) Moench, and conversion of these substrates to sorgomol stereoisomers was investigated. Liquid chromatography-mass spectrometry analyses established that 5-deoxystrigol (5-DS) and ent-2'-epi-5-deoxystrigol were absorbed by sorghum roots, converted to sorgomol and ent-2'-epi-sorgomol, respectively, and exuded out of the roots. The conversion was inhibited by uniconazole-P, implying the involvement of cytochrome P450 in the hydroxylation. These results provide experimental evidence for the postulated biogenetic scheme for formation of strigolactones, in which hydroxylation at C-9 of 5-DS can generate sorgomol.


Prophylactic In Vivo Hematopoietic Stem Cell Gene Therapy with an Immune Checkpoint Inhibitor Reverses Tumor Growth in Syngeneic Mouse Tumor Models.
Population-wide testing for cancer-associated mutations has established that more than one-fifth of ovarian and breast carcinomas are associated with inherited risk. Salpingo-oophorectomy and/or mastectomy are currently the only effective options offered to women with high-risk germline mutations. Our goal here is to develop a long-lasting approach that provides immunoprophylaxis for mutation carriers. Our approach leverages the fact that at early stages, tumors recruit hematopoietic stem/progenitor cells (HSPC) from the bone marrow and differentiate them into tumor-supporting cells. We developed a technically simple technology to genetically modify HSPCs in vivo. The technology involves HSPC mobilization and intravenous injection of an integrating HDAd5/35++ vector. In vivo HSPC transduction with a GFP-expressing vector and subsequent implantation of syngeneic tumor cells showed >80% GFP marking in tumor-infiltrating leukocytes. To control expression of transgenes, we developed a miRNA regulation system that is activated only when HSPCs are recruited to and differentiated by the tumor. We tested our approach using the immune checkpoint inhibitor anti-PD-L1-γ1 as an effector gene. In in vivo HSPC-transduced mice with implanted mouse mammary carcinoma (MMC) tumors, after initial tumor growth, tumors regressed and did not recur. Conventional treatment with an anti-PD-L1 mAb had no significant antitumor effect, indicating that early, self-activating expression of anti-PD-L1-γ1 can overcome the immunosuppressive environment in MMC tumors. The efficacy and safety of this approach was further validated in an ovarian cancer model with typical germline mutations (ID8 p53-/- brca2-/-), both in a prophylactic and therapeutic setting. This HSPC gene therapy approach has potential for clinical translation. SIGNIFICANCE: Considering the limited prophylactic options that are currently offered to women with high-risk germ-line mutations, the in vivo HSPC gene therapy approach is a promising strategy that addresses a major medical problem.


Long-term renal denervation normalizes disrupted blood pressure circadian rhythm and ameliorates cardiovascular injury in a rat model of metabolic syndrome.
Although renal denervation significantly reduces blood pressure in patients with resistant hypertension, the role of the renal nerve in hypertension with metabolic syndrome is unknown. We investigated the impact of long-term renal denervation on SHR/NDmcr-cp(+/+) (SHRcp) rats, a useful rat model of metabolic syndrome, to determine the role of the renal nerve in hypertension with metabolic syndrome. SHRcp rats were divided into (1) a renal denervation (RD) group and (2) a sham operation group (control) to examine the effects of long-term RD on blood pressure circadian rhythm, renal sodium retention-related molecules, the renin-angiotensin-aldosterone system, metabolic disorders, and organ injury. RD in SHRcp rats not only significantly reduced blood pressure but also normalized blood pressure circadian rhythm from the nondipper to the dipper type, and this improvement was associated with an increase in urinary sodium excretion and the suppression of renal Na(+)-Cl(-) cotransporter upregulation. RD significantly reduced plasma renin activity. RD significantly prevented cardiovascular remodeling and impairment of vascular endothelial function and attenuated cardiovascular oxidative stress. However, RD failed to ameliorate obesity, metabolic disorders, and renal injury and failed to reduce systemic sympathetic activity in SHRcp rats. By including the upregulation of the Na(+)-Cl(-) cotransporter, the renal sympathetic nerve is involved in the disruption of blood pressure circadian rhythm as well as hypertension in metabolic syndrome. Thus, RD seems to be a useful therapeutic strategy for hypertension with metabolic syndrome.


Association between the 5HT1B receptor gene (HTR1B) and the inattentive subtype of ADHD.
Preclinical and genetic studies have implicated the 5HT1B receptor gene (HTR1B) in attention-deficit/hyperactivity disorder (ADHD). Association with a single nucleotide polymorphism (SNP; G861C) has been observed, but more extensive linkage disequilibrium analyses have not been reported. To examine haplotype structure, we genotyped 21 SNPs in and around the gene in 12 multigenerational CEPH pedigrees. We identified a haplotype block encompassing HTR1B and performed haplotype and single-marker association analyses for the eight SNPs within or flanking this block in 229 families of ADHD probands. In light of previous studies suggesting distinct genetic influences on ADHD subtypes, we also examined association with the inattentive and combined subtypes. We observed nonsignificant overtransmission of the G861 allele to ADHD offspring (one-tailed p = .07). Single-marker and haplotype tests of a haplotype block encompassing HTR1B revealed no other associations with ADHD. However, this haplotype block was associated with the inattentive subtype (global p < .01). Additionally, three SNPs in this block were nominally (p < .05) associated with the inattentive subtype, although these did not remain significant after correction for multiple testing. As reported in previous studies, we found paternal overtransmission of the G861 allele to offspring with ADHD; this appeared to be largely attributable to inattentive cases. These analyses suggest that variation in the HTR1B gene may primarily affect the inattentive subtype of ADHD.


Physical activity in vascular cognitive impairment: Systematic review with meta-analysis.
Vascular cognitive impairment (VCI) is the second most common cause of cognitive impairment worldwide and includes a spectrum from vascular cognitive impairment no dementia (VCIND) to vascular dementia (VaD). There is no specific pharmacological treatment approved for VCI. Physical activity has been indicated to be a promising preventive measure for cognition, with direct as indirectly benefits, while improving several modifiable vascular risk factors, so potentially effective when considering VCI. Our aim was to conduct a systematic review with a meta-analysis approaching the potential preventive role of physical activity on VCI. A systematic search was conducted in 7 databases. A total of 6786 studies were screened and assessed for eligibility, culminating in the inclusion of 9 observational prospective studies assessing physical activity impact irrespectively the type for quality assessment and qualitative and quantitative synthesis. Quantitative synthesis was performed using the reported adjusted HRs. Physical activity was handled as a dichotomous variable, with two groups created (high versus low physical activity). Subgroup analyses were done for risk of bias, VaD and length of follow-up. There was considerable methodological heterogeneity across studies. Only three studies reported significant associations. The overall effect was statistically significant (HR 0.68, 95%CI 0.54-0.86, I2 6.8%), with higher levels of physical activity associated with a smaller risk of VCI overtime, particularly VaD. These findings suggest that physical activity is a potential preventive factor for vascular dementia. Insufficient data is available on VCIND. Randomized studies are desired to confirm these results.


Multiplexed methylation profiles of tumor suppressor genes and clinical outcome in lung cancer.
Changes in DNA methylation of crucial cancer genes including tumor suppressors can occur early in carcinogenesis, being potentially important early indicators of cancer. The objective of this study was to examine a multiplexed approach to assess the methylation of tumor suppressor genes as tumor stratification and clinical outcome prognostic biomarkers for lung cancer. A multicandidate probe panel interrogated DNA for aberrant methylation status in 18 tumor suppressor genes in lung cancer using a methylation-specific multiplex ligation-dependent probe amplification assay (MS-MLPA). Lung cancer cell lines (n = 7), and primary lung tumors (n = 54) were examined using MS-MLPA. Genes frequently methylated in lung cancer cell lines including SCGB3A1, ID4, CCND2 were found among the most commonly methylated in the lung tumors analyzed. HLTF, BNIP3, H2AFX, CACNA1G, TGIF, ID4 and CACNA1A were identified as novel tumor suppressor candidates methylated in lung tumors. The most frequently methylated genes in lung tumors were SCGB3A1 and DLC1 (both 50.0%). Methylation rates for ID4, DCL1, BNIP3, H2AFX, CACNA1G and TIMP3 were significantly different between squamous and adenocarcinomas. Methylation of RUNX3, SCGB3A1, SFRP4, and DLC1 was significantly associated with the extent of the disease when comparing localized versus metastatic tumors. Moreover, methylation of HTLF, SFRP5 and TIMP3 were significantly associated with overall survival. MS-MLPA can be used for classification of certain types of lung tumors and clinical outcome prediction. This latter is clinically relevant by offering an adjunct strategy for the clinical management of lung cancer patients.


Adrenomedullin immunoreactivity in the human carotid body.
We studied by immunocytochemistry the expression of AM in human carotid bodies, sampled at autopsy from 16 adult subjects (mean age+/-S.D.: 44.3+/-3.4 years) and from six fetuses (mean gestational age+/-S.D.: 167+/-11 days). No AM immunoreactivity was visible in the type II cells of both series. The percentage of immunoreactive type I cells was higher in the adult subjects (32.3+/-7.7%) with respect to the fetuses (11.8+/-2.7%, P < 0.001). Dark cells showed a higher percentage of positive immunoreaction with respect to light cells, both in adult subjects (61.7+/-13.4% versus 19.2+/-5.2%) and in fetuses (25.3+/-4.4% versus 6.2+/-2.0%). AM may play a role in the regulation of chemoreceptor discharge through paracrine releasing action and/or vasodilator effect. The low expression of AM in fetuses may be ascribed to the absence of pulmonary respiration with lack of regulatory role of the carotid body during the prenatal period.


Quality of life after children undergo a radical arterial switch operation at an older age.
The goal of the study was to evaluate the quality of life of children after the older corrective arterial switch operation (ASO) by means of the Pediatric Quality of Life Inventory (PedsQL), version 4.0. The records of 86 patients who had complete transposition of the great arteries plus a nonrestrictive ventricular septal defect, or a Taussig-Bing anomaly, and severe pulmonary arterial hypertension, and who underwent a corrective ASO at an older age (>6 months) between May 2000 and October 2008 were reviewed retrospectively. Eighty survivors were followed up, and the health-related quality of life of the survivors was evaluated with the PedsQL, version 4.0. There were 6 hospital deaths. The mean (SD) follow-up interval was 3.5 ± 2.3 years, and the mean age at last visit was 7.0 ± 1.2 years. Two late deaths occurred, and 8 patients were lost to follow-up. Patients who underwent a corrective ASO at an older age showed acceptable scores for all scales, and they were all comparable with those of a healthy population. Our data suggest that the quality of life of children who undergo a corrective ASO at an older age (>6 months) is acceptable, compared with that of healthy children in China.


Impact of the COVID-19 pandemic on Swedish adults aged 77 years and older: Age differences in lifestyle changes.
This study aimed to describe the impact of the COVID-19 pandemic on lifestyle and social activities among older adults in Sweden, with a special focus on differences between the 'younger old' (aged 77-84) and 'older old' (aged 85-109). This study is based on a nationally representative sample of older adults (aged ⩾77 years) in Sweden (SWEOLD). Data were collected between May 2021 and April 2022, when many recommendations were removed but the virus was still classified as a public health disease. We studied occurrences and differences between the two age groups in several lifestyle factors and social activities. The younger old displayed larger changes in lifestyles because of the pandemic than the older old. Most changes were found in social interactions with family. Our results highlight the large heterogeneity within the Swedish population aged ⩾77 years, and that the younger old experienced a bigger lifestyle change than the older old. Previous activity levels might be important to consider in order to understand how regulations may affect the older population. Finally, our findings indicate large age differences in Internet use, which require attention to prevent digital exclusion of an already vulnerable group.


Isolation and characterization of an unusual 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase gene from Enterobacter cloacae UW4.
A genomic library of the 1-aminocyclopropane-1-carboxylic acid (ACC) deaminase-containing plant growth-promoting bacterium Enterobacter cloacae UW4 in pUC19 in Escherichia coli was screened for the ability to utilize ACC as a sole source of nitrogen. One of the clones that was isolated contained a plasmid with an insert of approximately 0.8 kb that conferred ACC deaminase activity. Sequence analysis revealed that this DNA fragment contains an open-reading frame of 696 nucleotides predicted to encode a protein of 232 amino acids, a member of the amidohydrolase protein superfamily, i.e., a deaminase that contains a mononuclear or binuclear metal center as compared to the canonical ACC deaminase which contains pyridoxal phosphate as a co-factor.


Poor sleep quality is responsible for the nondipper pattern in hypertensive but not in normotensive chronic kidney disease patients.
This study was designed to evaluate the relationship between sleep quality and hypertension and to determine if there was an association between nondipper blood pressure (BP) and sleep quality in chronic kidney disease (CKD) patients. A total of 775 pre-dialysis CKD patients (314 normal BP patients, 461 hypertension patients) defined as dippers or nondippers by ambulatory BP monitoring were recruited for this study. Demographics and clinical correlates were collected, including body mass index, estimated glomerular filtration rate (eGFR) and other measures. Sleep quality was measured using the Pittsburgh Sleep Quality Index (PSQI). A total of 185 (58.9%) patients with normal BP and 341 (74.0%) hypertensive patients had a nondipper BP pattern. The hypertension group had a higher prevalence of the nondipper BP pattern, smoking, alcohol intake and diabetes mellitus (DM) and lower eGFR levels and poorer sleep quality than the normal BP group. Patients with the nondipper BP pattern had lower haemoglobin, worse renal function and poorer sleep quality when compared with hypertensive CKD patients with the dipping BP pattern. PSQI scores were significantly associated with the rate of nocturnal BP decline (P < 0.05) in the hypertension group but not in the normal BP group. Poor sleep quality was an independent factor affecting BP pattern in hypertensive CKD patients using multivariate linear and logistic regression analyses. There was no association between sleep quality and hypertension in CKD patients after multivariate logistic regression analyses. Poor sleep quality, which is commonly observed in pre-dialysis CKD patients, is an independent associated factor of the nondipper BP pattern in hypertensive CKD patients. No association was found between poor sleep and nondipper BP in normotensive patients.


Mohs Mapping in the Cloud: An Innovative Method for Mapping Tissue in Mohs Surgery.
Mohs micrographic surgery (MMS) is the most useful surgical method for the treatment of skin cancer. One of the key factors in MMS is the mapping of the excised tissue in relation to its original location. Since the introduction of MMS, mapping has been modified from simple drawing to digital photographic maps. Maps during MMS were taken using Samsung and LG tablets. The maps were saved to the cloud in the operating rooms. A short time after, the maps were downloaded to the laboratory's computer by the Mohs technician and processed to a digital photographic map. When additional stage was needed, the map was uploaded by the technician to the cloud and viewed by the Mohs surgeon on the tablet in the operating room. Mohs mapping on the cloud is a new method of mapping tissue in MMS. It is an easy, fast, and accurate method of mapping and serves the new era of modern web and photographic technologies.


Study of the micellization behavior of different order amino block copolymers with heparin.
The purpose of this study was to prepare and characterize copolymers presenting different pendant amino groups and to study their ability to form polyelectrolyte complexes with heparin. The responsiveness of the complexes to variations in pH and ionic strength was correlated to the nature of the copolymers. Copolymers composed of different aminoethyl methacrylate monomers were synthesized by atom transfer radical polymerization (ATRP) from a poly(ethylene glycol) macroinitiator. Copolymers were characterized by gel permeation chromatography and nuclear magnetic resonance spectroscopy. Micellization properties were assessed by atomic force microscopy, multiangle static light scattering, and dynamic light scattering on complexes formed from the addition of heparin to a solution of polymer. Primary, tertiary, and quaternary amine-based diblock copolymers with molecular weights ranging from 4900 to 7400 and low polydispersity indexes were prepared. The synthesis of a copolymer bearing primary amines was achieved for the first time by ATRP. Micellization was found to be pH- and polymer-dependent. All polymers interacted with heparin at acidic pH to yield monodisperse assemblies of less than 30 nm. Complexes dissociated in response to increases in ionic strength. Electrostatic interactions between the amino copolymers and heparin triggered the formation of small, monodisperse, and stable complexes that present great potential as oral drug delivery systems.


Impulsive and risky decision-making in adolescents with attention-deficit/hyperactivity disorder (ADHD): The need for a developmental perspective.
Impulsive and risky decision-making peaks in adolescence, and is consistently associated with the neurodevelopmental disorder Attention-Deficit/Hyperactivity Disorder (ADHD), regardless of age. In this brief review, we demonstrate the similarity of theoretical models explaining impulsive and risky decision-making that originate in two relatively distinct literatures (i.e., on adolescence and on ADHD). We summarize research thus far and conclude that the presence of ADHD during adolescence further exacerbates the tendency that is already present in adolescents to make impulsive and risky decisions. We also conclude that much is still unknown about the developmental trajectories of individuals with ADHD with regard to impulsive and risky decision making, and we therefore provide several hypotheses that warrant further longitudinal research.


Synthesis of C-ring aromatic taxoids and evaluation of their multi-drug resistance reversing activity.
The C-aromatic taxoids were synthesized to develop effective inhibitors against drug efflux mediated by p-glycoproteins. Among those tested using multi-drug resistant tumor cells (2780AD), the benzoate 11 exhibited significant activity as potent as verapamil, a well-established MDR reversing agent.


Associations of ABCB1, NFKB1, CYP3A, and NR1I2 polymorphisms with cyclosporine trough concentrations in Chinese renal transplant recipients.
Cyclosporine requires close therapeutic drug monitoring because of its narrow therapeutic index and marked inter-individual pharmacokinetic variation. In this study, we investigated the associations of CYP3A4, CYP3A5, ABCB1, NFKB1, and NR1I2 polymorphisms with cyclosporine concentrations in Chinese renal transplant recipients in the early period after renal transplantation. A total of 101 renal transplant recipients receiving cyclosporine were genotyped for CYP3A4(*)1G, CYP3A5(*)3, ABCB1 C1236T, G2677T/A, C3435T, NFKB1 -94 ins/del ATTG, and NR1I2 polymorphisms. Cyclosporine whole blood levels were measured by a fluorescence polarization immunoassay. Trough concentrations of cyclosporine were determined for days 7-18 following transplantation. The dose-adjusted trough concentration (C0) of cyclosporine in ABCB1 2677 TT carriers was significantly higher than that in GG carriers together with GT carriers [90.4±24.5 vs 67.8±26.8 (ng/mL)/(mg/kg), P=0.001]. ABCB1 3435 TT carriers had a significantly higher dose-adjusted C0 of cyclosporine than CC carriers together with CT carriers [92.0±24.0 vs 68.4±26.5 (ng/mL)/(mg/kg), P=0.002]. Carriers of the ABCB1 1236TT-2677TT-3435TT haplotype had a considerably higher CsA C0/D than carriers of other genotypes [97.2±21.8 vs 68.7±26.9 (ng/mL)/(mg/kg), P=0.001]. Among non-carriers of the ABCB1 2677 TT and 3435 TT genotypes, patients with the NFKB1 -94 ATTG ins/ins genotype had a significantly higher dose-adjusted C0 than those with the -94 ATTG del/del genotype [75.9±32.9 vs 55.1±15.1 (ng/mL)/(mg/kg), P=0.026]. These results illustrate that the ABCB1 and NFKB1 genotypes are closely correlated with cyclosporine trough concentrations, suggesting that these SNPs are useful for determining the appropriate dose of cyclosporine.


Polypodium leucotomos inhibits ultraviolet B radiation-induced immunosuppression.
An extract of the tropical fern Polypodium leucotomos (PL) administered orally to mice inhibits ultraviolet B (UVB) radiation-induced skin cancer formation. UVB-induced murine skin cancers occur, in part, because of UVB-induced immunosuppression. Thus, we examined whether PL inhibits UVB-suppression of the induction of contact hypersensitivity (CHS) locally or systemically. C57BL/6 mice received standard drinking water or water-containing PL. In the local model, mice were shaved on the dorsum and exposed to 3500 J/m(2) of UVB radiation daily for 4 days. Control mice were not irradiated. After the last irradiation they were sensitized to oxazolone topically at the irradiated site. To examine the ability of PL to inhibit systemic UVB-induced immunosuppression, mice were given 10,000 J/m(2) of UVB radiation once and immunized at a non-exposed site 3 days later. Six days after immunization (in both models), mice were challenged on the ears with oxazolone and 24/48 h ear swelling assessed. PL in drinking water significantly reduced the inhibition of CHS observed with exposure to UVB radiation in both the local and systemic models. The ability of PL to inhibit UVB radiation-induced immune suppression may explain, in part, its ability to inhibit UVR-induced skin cancer induction in mice.