The importance of catch-up growth after early malnutrition for the programming of obesity in male rat.
To investigate whether catch-up growth after maternal malnutrition would favor the development of obesity in adulthood. Pregnant rats were submitted to protein or calorie restriction during the course of gestation. During lactation, pups were protein-restricted, normally fed, or overfed [reduced litter size, control (C) diet]. At weaning, rats were transferred to chow or to a hypercaloric diet (HCD) known to induce obesity. Body weight, food intake, blood parameters, glucose tolerance, adipocyte cellularity, and adipose factors contributing to cardiovascular disease development were measured. Protein and calorie restriction during gestation led to growth retardation at birth. If malnutrition was prolonged throughout lactation, adult body weight was permanently reduced. However, growth-retarded offspring overfed during the suckling period underwent a rapid catch-up growth and became heavier than the normally fed Cs. Offspring of calorie-restricted rats gained more weight than those of dams fed protein-restricted diet. Feeding an HCD postnatally amplified the effect of calorie restriction, and offspring that underwent catch-up growth became more obese than Cs. The HCD was associated with hyperphagia, hyperglycemia, hyperinsulinemia, glucose intolerance, insulin resistance, and adipocyte hypertrophy. The magnitude of effects varied depending on the type and the timing of early malnutrition. The expression of genes encoding factors implicated in cardiovascular disease was also modulated differently by early malnutrition and adult obesity. Catch-up growth immediately after early malnutrition should be a key point for the programming of obesity.


Comparison of Donor Cornea Endothelial Cell Density Determined by Eye Banks and by a Central Reading Center in the Cornea Preservation Time Study.
To evaluate agreement between eye banks (EBs) and a reading center on endothelial cell density (ECD) determinations in the Cornea Preservation Time Study. The Cornea Image Analysis Reading Center (CIARC) performed variable frame image analysis on EB-obtained-preoperative central endothelial images (after lamellar dissection for Descemet stripping automated endothelial keratoplasty by the EBs or before shipping, if surgeon prepared) to determine ECD. The EBs performed their usual method of ECD determination. The CIARC and EBs also provided ECD determinations from screening central endothelial images taken by the EBs during donor evaluation. Two independent masked CIARC readers determined ECD with measurements averaged. The mean preoperative ECD was 15 cells/mm greater by the EBs than by CIARC (N = 1286, P < 0.001) with 95% limits of agreement of (-644, 675 cells/mm). The limits of agreement in preoperative ECD were wider in the After-Lamellar-Dissection Group (-687, 683 cells/mm) than in the Before Shipping Group [(-505, 633 cells/mm); P = 0.03]. The EBs-determined preoperative ECD was within 10% of the CIARC-determined ECD for 886 (69%) image sets, with 236 (18%) higher by >10% and 164 (13%) lower by >10%. Excellent agreement appeared between the EBs and CIARC when 100-300 cells could be analyzed in contrast to <100 cells (SD = 308 cells/mm vs. SD = 603 cells/mm; P < 0.001). The mean ECD by the EBs and CIARC were similar, but there was considerable variability between determinations for individual corneas. Agreement improved between the 2 measurements when more than 100 cells were able to be analyzed.


Pediatric rosacea.
Rosacea is a condition most commonly associated with adults; however, various forms exist in the pediatric population and need to be considered when a child presents with a facial rash. Acne rosacea, steroid rosacea, granulomatous periorificial dermatitis, and other variants of rosacea are presented here and are distinguished from their numerous mimickers. Various topical and systemic therapeutic options exist for the treatment of rosacea with several adjustments and considerations that must be taken into account when treating a child.


[Studies on chemical constituents of Lilium brownii].
Lilium brownii F. E. Brown var. viridulum Baker is a well-known and very important traditional Chinese medicine. It has been used as sedative, antitussive, anti-inflammatory or as a nutrient. Five compounds were isolated from the bulbs of Lilium brownii. On the basis of spectroscopic analysis (IR, FAB-MS, 1HNMR, 13CNMR, DEPT, HMQC, HMBC) and their physicochemical properties, they were identified as beta-sitosterol (I), daucosterol (II), n-butyl-beta-D-fructopyranoside (III), 26-O-beta-D-glucopyranosyl-3 beta, 26-dihydroxy-5-cholesten-16, 22-dioxo-3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranoside (IV), 26-O-beta-D-glucopyranosyl-3beta, 26-dihydroxy cholestan-16, 22-dioxo-3-O-alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranoside(V). Among them, I, II and III were isolated from this plant for the first time, IV and V are new compounds.


Why Do Some Consumers Still Prefer In-Store Shopping? An Exploration of Online Shopping Cart Abandonment Behavior.
Shopping cart abandonment remains a challenge for many e-retailers despite the continued growth of the e-commerce industry worldwide. However, the issue of online shopping cart abandonment (OSCA) has not been explored extensively in the literature. Grounded by the stimulus-organism-response (S-O-R) model, this study explores a sequential mediation model comprising consumers' wait for lower prices as an antecedent, hesitation at checkout and OSCA as mediators, perceived transaction inconvenience as a moderator, and decision to buy from a land-based retailer (DBLR) as an outcome. An online questionnaire was designed and distributed to 883 online consumers in Mainland China. Partial least squares-structural equation modeling (PLS-SEM) was employed to analyze the survey data. The results show that waiting for lower prices positively influences hesitation at checkout, and subsequently, impacts both OSCA and DBLR. Hesitation at checkout and OSCA play sequential mediating roles in the framework path. In addition, perceived transaction inconvenience strengthens the relationship between waiting for lower prices and hesitation at checkout. Overall, this study contributes to theory and serves as a guideline for e-retailers in reducing the OSCA rate.


Mucosal immunization with recombinant adenovirus encoding soluble globular head of hemagglutinin protects mice against lethal influenza virus infection.
Influenza virus is one of the major sources of respiratory tract infection. Due to antigenic drift in surface glycoproteins the virus causes annual epidemics with severe morbidity and mortality. Although hemagglutinin (HA) is one of the highly variable surface glycoproteins of the influenza virus, it remains the most attractive target for vaccine development against seasonal influenza infection because antibodies generated against HA provide virus neutralization and subsequent protection against the virus infection. Combination of recombinant adenovirus (rAd) vector-based vaccine and mucosal administration is a promising regimen for safe and effective vaccination against influenza. In this study, we constructed rAd encoding the globular head region of HA from A/Puerto Rico/8/34 virus as vaccine candidate. The rAd vaccine was engineered to express high level of the protein in secreted form. Intranasal or sublingual immunization of mice with the rAd-based vaccine candidates induced significant levels of sustained HA-specific mucosal IgA and IgG. When challenged with lethal dose of homologous virus, the vaccinated mice were completely protected from the infection. The results demonstrate that intranasal or sublingual vaccination with HA-encoding rAd elicits protective immunity against infection with homologous influenza virus. This finding underlines the potential of our recombinant adenovirus-based influenza vaccine candidate for both efficacy and rapid production.


NON-STEROIDAL ANTI-INFLAMMATORY DRUGS'S ANTINOCICEPTION MEDIATED BY THE OPIOID MECHANISM IN THE NUCLEUS RAPHE MAGNUS.
It has been established that the midbrain periaqueductal gray matter (PAG) and rostral ventro-medial medulla (RVM) are involved in the descending pain control system. The latter involves the midline nucleus raphe magnus (NRM) and adjacent reticular formation. These brain structures are is one of important parts of CNS circuit that controls nociceptive transmission at the level of spinal cord. Here we report that microinjection of commonly used non-steroidal anti-inflammatory drugs (NSAIDs), diclofenac, ketorolac, metamizol, and xefocam into the NRM produces strong antinociception which is mediated by the opioid mechanism. The experiments were carried out on experimental and control (saline) white albino male rats. Animals were implanted with a guide cannula in the NRM and tested for antinociception following microinjection of NSAIDs into the NRM in the tail flick (TF) and hot plate (HP) tests. The analysis of variance (ANOVA) with post-hoc Tukey-Kramer multiple comparison tests were used for statistical evaluation. The obtained data show that microinjection of these NSAIDs into the NRM produced antinociception as revealed by a latency increase in the tail-flick (TF) and hot plate (HP) latencies compared to the saline control microinjected into the same nucleus. Furthermore, we definitely showed that pre-treatment with opioid antagonist naloxone in the NRM diminishes NSAID-induced antinociception expressing in significant decrease in TF and HP latencies (P<0.001). The present findings support the concept that antinociceptive effects of NSAIDs are mediated via an endogenous opioid system possibly involving the descending pain modulatory circuit.


Scalable and Robust Tensor Decomposition of Spontaneous Stereotactic EEG Data.
Identification of networks from resting brain signals is an important step in understanding the dynamics of spontaneous brain activity. We approach this problem using a tensor-based model. We develop a rank-recursive scalable and robust sequential canonical polyadic decomposition (SRSCPD) framework to decompose a tensor into several rank-1 components. Robustness and scalability are achieved using a warm start for each rank based on the results from the previous rank. In simulations we show that SRSCPD consistently outperforms the multi-start alternating least square (ALS) algorithm over a range of ranks and signal-to-noise ratios (SNRs), with lower computation cost. When applying SRSCPD to resting in-vivo stereotactic EEG (SEEG) data from two subjects with epilepsy, we found components corresponding to default mode and motor networks in both subjects. These components were also highly consistent within subject between two sessions recorded several hours apart. Similar components were not obtained using the conventional ALS algorithm. Consistent brain networks and their dynamic behaviors were identified from resting SEEG data using SRSCPD. SRSCPD is scalable to large datasets and therefore a promising tool for identification of brain networks in long recordings from single subjects.


Cancer Communication and Family Caregiver Quality of Life.
Family caregivers have enormous communication responsibilities tied to caregiving, such as sharing the patient's medical history with providers, relaying diagnosis and prognosis to other family members, and making decisions about care with the patient. While caregiver stress and burden has been widely documented in the caregiving literature, little is known about how communication burden, real or perceived communication challenges, impacts caregiver quality of life. In family caregiving, the City of Hope (COH) Quality of Life model proposes that the caregiving experience is reciprocal to the patient experience, impacting physical, social, psychological, and spiritual quality of life. We used data from a pilot study testing a communication coaching call intervention with family caregivers of lung cancer patients to analyze caregiver reported communication burden and quality of life. We found variances in each quality of life domain, suggesting that caregiver interventions should range from self-care skill building for physical care to psycho-educational interventions that support caregiver coping and communication skill building. These findings demonstrate the importance of caregiver assessment and attention to communication burden in quality cancer care.


Transaxillary breast augmentation.
This article will discuss the preoperative, intraoperative, and postoperative nursing interventions specifically related to the patient undergoing transaxillary breast augmentation. Being able to explain the procedure through each of these phases will help to ease a patient's anxiety and, in turn, increase compliance to follow instructions to achieve the best possible result.


Reactions of Th(+) + H2, D2, and HD Studied by Guided Ion Beam Tandem Mass Spectrometry and Quantum Chemical Calculations.
Kinetic energy dependent reactions of Th(+) with H2, D2, and HD were studied using a guided ion beam tandem mass spectrometer. Formation of ThH(+) and ThD(+) is endothermic in all cases with similar thresholds. Branching ratio results for the reaction with HD indicate that Th(+) reacts via a statistical mechanism, similar to Hf(+). The kinetic energy dependent cross sections for formation of ThH(+) and ThD(+) were evaluated to determine a 0 K bond dissociation energy (BDE) of D0(Th(+)-H) = 2.45 ± 0.07 eV. This value is in good agreement with a previous result obtained from analysis of the Th(+) + CH4 reaction. D0(Th(+)-H) is observed to be larger than its transition metal congeners, TiH(+), ZrH(+), and HfH(+), believed to be a result of lanthanide contraction. The reactions with H2 were also explored using quantum chemical calculations that include a semiempirical estimation and explicit calculation of spin-orbit contributions. These calculations agree nicely and indicate that ThH(+) most likely has a (3)Δ1 ground level with a low-lying (1)Σ(+) excited state. Theory also provides the reaction potential energy surfaces and BDEs that are in reasonable agreement with experiment.


The Sda antigen in the human kidney and colon.
The range of concentration of the Sda blood group antigen has been determined in the human adult kidney and colon. No Sda antigen was found in 2% of kidneys. Immunofluorescent studies of the kidney showed that Sda is present in the distal convoluted tubules and collecting ducts and occurs in the same location as Tamm-Horsfall protein. No Sda antigen was detected in about 2% of colons. In an additional 6%, no antigen was detected in saline extracts but was present in an insoluble form. In the colon, Sda is sited on the brush borders of the epithelial cells and in the goblet cells. No Tamm-Horsfall protein was identified in the colon.


Introducing Artificial Solid Electrolyte Interphase onto the Anode of Aqueous Lithium Energy Storage Systems.
Aqueous lithium energy storage systems (ALESSs) offer several advantages over the commercially available nonaqueous systems, and the most noteworthy is that ALESSs have higher ionic conductivity, can be used safely, and are environmental-friendly in nature. The ALESS, however, exhibits faster capacity fading than their nonaqueous counterparts after repeated cycles of charge and discharge, thus limiting their wide-range applications. Excessive corrosion of metallic anodes in the aqueous electrolyte and accelerated growth of dendrites during the charge-discharge process are found to be the main reasons that severely impact the life span of ALESSs. Here, we introduce ultrathin graphene films as an artificial solid electrolyte interface (G-SEI) on the surface of a zinc anode to improve the cycling stability of an aqueous lithium battery system. The G-SEI is fabricated at different thicknesses and areas ranging from ∼1 to 100 nm and ∼1 to 10 cm2, respectively, via a Langmuir-Blodgett trough method and deposited onto the surface of the zinc anode. Electrochemical characterizations show a significant reduction in corrosion current density (0.033 mA cm-2 vs 1.046 mA cm-2 for the control), suppression of dendritic growth (∼50%), and reduction in charge-transfer resistance (222 Ω vs 563 Ω for the control) when the G-SEI is utilized. The aqueous battery system with the G-SEI (100 nm thickness) on the anode exhibits ∼17% improvement in cycling stability (82% capacity retention after 300 cycles) compared to the control system. Comprehensive microscopy and spectroscopy characterizations reveal that the G-SEI not only controls the ion transport between the electrolyte and the anode surface (lower corrosion) but also promotes a uniform deposition (less dendritic growth) of zinc on the anode.


Left atrial appendage aneurysm: correlation of noninvasive with clinical and surgical findings: report of a case.
Congenital left atrial appendage aneurysm is rarely diagnosed on the basis of an abnormal cardiac silhouette. Patients with a left atrial appendage aneurysm often present with symptoms of systemic emboli or supraventricular arrhythmias. A patient with left atrial appendage aneurysm was diagnosed by correlation of two noninvasive techniques echocardiography and radionuclide scintiscanning. Angiography was confirmatory and aneurysmectomy was successfully performed.


A probabilistic model of 3' end formation in Caenorhabditis elegans.
The 3' ends of mRNAs terminate with a poly(A) tail. This post-transcriptional modification is directed by sequence features present in the 3'-untranslated region (3'-UTR). We have undertaken a computational analysis of 3' end formation in Caenorhabditis elegans. By aligning cDNAs that diverge from genomic sequence at the poly(A) tract, we accurately identified a large set of true cleavage sites. When there are many transcripts aligned to a particular locus, local variation of the cleavage site over a span of a few bases is frequently observed. We find that in addition to the well-known AAUAAA motif there are several regions with distinct nucleotide compositional biases. We propose a generalized hidden Markov model that describes sequence features in C.elegans 3'-UTRs. We find that a computer program employing this model accurately predicts experimentally observed 3' ends even when there are multiple AAUAAA motifs and multiple cleavage sites. We have made available a complete set of polyadenylation site predictions for the C.elegans genome, including a subset of 6570 supported by aligned transcripts.


New reagents on the horizon for immune tolerance.
Recent advances in immunology and a growing arsenal of new drugs are bringing the focus of tolerance research from animal models into the clinical setting. The conceptual framework for therapeutic tolerance induction has shifted from a "sledgehammer" approach that relies solely on cellular depletion and cytokine targeting, to a strategy directed toward restoring a functional balance across the immune system, namely the different populations of naive cells, effector and memory cells, and regulatory cells. Unlocking the key to tolerance induction in the future will likely depend on our ability to harness the functions of T regulatory cells. Also, dendritic cells are strategically positioned at the interface between innate and adaptive immunity and may be subject to deliberate medical intervention in a way that can control a chronic inflammatory response. Many reagents with tolerance-inducing potential are currently undergoing clinical testing in transplantation, autoimmune diseases, and allergic diseases, and even more that are on the horizon promise to offer enormous benefits to human health.


Cochlear implants and quality of life: a prospective study.
To evaluate changes in quality of life, anxiety, and depression after cochlear implantation in adults. Twenty-seven postlingually deafened adults who had received a MED-EL Combi 40+ implant were investigated. One generic Health-Related Quality of Life measure, the SF-36, two disease-specific measures, the Patient Quality of Life Form (PQLF) and the Index Relative Questionnaire Form (IRQF) completed by a near relative to the patient, in addition to a domain specific measure, the Hopkins Symptom Check List 25 items (HSCL-25), were used in a prospective study. The subjects were investigated before surgery and 12 to 15 months after surgery. The scores were significantly better after surgery in four of six categories of the PQLF. In the IRQF, where a family member of the cochlear implant recipient was studied, the scores were significantly better in four of five categories. There was a significant improvement in the HSCL-25 scores after surgery. In the SF-36, only one of eight scales showed significant improvement. Cochlear implants were associated with statistically significant improvement in quality of life in postlingually deafened adults. The improvements were largest in the categories concerning communication, feelings of being a burden, isolation, and relations to friends and family. The implants also improved the relatives' daily lives. There was a statistically significant reduction in degree of depression and anxiety. Reduction in anxiety and depression was associated with gain in quality of life.


The skin in psoriasis: assessment and challenges.
The coexistence of psoriasis arthritis (PsA) and psoriasis vulgaris in about 20% of patients with psoriasis leads to a need for rheumatologic-dermatologic team work. We summarise the role of dermatologists in assessment of the skin in psoriasis. Chronic plaque psoriasis must be differentiated from other subtypes such as generalised pustular psoriasis (GPP) or palmoplantar pustulosis (PPP). Therapeutic management is based on the evaluation of the disease severity. Quantitative scoring of skin severity includes calculation of the Psoriasis Area and Severity Index (PASI), body surface area (BSA) as well as the Dermatology Life Quality Index (DLQI). These scoring systems do not replace the traditional dermatologic medical history and physical examination of the patient. The skin should be examined for additional skin diseases; moreover, patients should be monitored for comorbidity, most importantly PsA and cardiovascular comorbidity.


Serum leucine aminopeptidase in head and neck cancer.
Serum leucine aminopeptidase (LAP) activity was assayed in patients with head and neck cancer. The levels were found to be significantly higher than the controls. However, the rise in serum LAP was nearly the same in all patients studied, irrespective of the character or histopathology of the lesion but varied with respect to the site involved, i.e. from about 40 per cent in cancer of the hypopharynx to more than 100 per cent in cancer of the nasopharynx. Serum LAP activity was found to increase with the extent of the lymph node spread. After treatment the levels were found to be reduced.


Plasmodium falciparum pigment induces monocytes to release high levels of tumor necrosis factor-alpha and interleukin-1 beta.
We show that high levels of tumor necrosis factor-alpha (TNF-alpha) activity were consistently detected when monocytes were cocultured with Plasmodium falciparum schizont stage-parasitized erythrocytes that subsequently ruptured. Isolated pigment recovered from ruptured schizonts was found to specifically induce monocyte release of high levels of TNF-alpha and interleukin-1 beta (IL-1 beta). Particulate free-culture supernatant that contained various soluble parasite macromolecules induced relatively low levels of TNF-alpha and IL-1 beta. When isolated pigment was treated with protease, the monokine inducing-activity was abolished. Isolated pigment prepared from different natural isolates of P. falciparum stimulated variable levels of monokine production. We propose that in vivo, malaria pigment from parasites sequestered in the host microvasculature is a physiologically relevant moiety that interacts with monocytes and stimulates the release of TNF-alpha and IL-1 beta. These observations suggest that malaria pigment may be a virulence factor in the monokine-mediated induction of organ-specific and systemic pathophysiology in falciparum malaria.


Brimonidine related acute follicular conjunctivitis: Onset time and clinical presentations, a long-term follow-up.
To evaluate the duration of topical brimonidine therapy before the onset of brimonidine-related allergic conjunctivitis and the clinical characteristics associated with the development of brimonidine allergy.We retrospectively enrolled patients who presented brimonidine allergy from December 1, 2008 to November 30, 2020. The duration of brimonidine treatment, concomitant medications, benzalkonium chloride (BAK) exposure, change in IOP, and season of onset were evaluated.292 patients were included, among which 147 were female and 145 were male. The mean age was 58.3 ± 13.6 years old. The mean (median) duration of brimonidine therapy was 266.6 (196) days, with a peak at 60-120 days. The duration was similar whether the patients received brimonidine monotreatment or in combination with other glaucoma drugs, with or without BAK. The IOP increased by 5.6% after brimonidine allergy (P < .001), which was even higher in the brimonidine monotherapy group (9.2%, P < .001). There was no significant IOP elevation in patients treated with multiple glaucoma medications.Around half of brimonidine allergy occurred within 6 months, with a peak in 2 to 4 months. The duration did not differ in patients receiving brimonidine monotherapy or multiple glaucoma medications. The presence of BAK did not affect the duration either. When brimonidine allergy occurred, there was a loss of IOP control, especially in patients receiving brimonidine monotherapy. It is recommended to switch to other types of glaucoma medications for better IOP control.


Fanconi anemia patient with bilaterally hypoplastic scapula and unilateral winging associated with scoliosis and rib abnormality.
Fanconi anemia is an autosomal recessive disease characterized by bone marrow failure, variable congenital physical abnormalities, and predisposition to hematologic malignancy and several solid tumors. The most frequently associated congenital malformations are those of the skeletal system, mainly radius and thumb. Herein, we report bilaterally hypoplastic scapula with unilateral winging associated with scoliosis and rib abnormality, a previously unreported skeletal abnormality in Fanconi anemia patients.


Minimally invasive versus conventional extracorporeal circulation in minimally invasive cardiac valve surgery.
Minimally invasive extracorporeal circulation (MECC) technology was applied predominantly in coronary surgery. Data regarding the application of MECC in minimally invasive valve surgery are missing largely. Patients undergoing isolated minimally invasive mitral or aortic valve procedures were allocated either to conventional extracorporeal circulation (CECC) group (n = 63) or MECC group (n = 105), and their prospectively generated data were analyzed. Demographic data were comparable between the groups regarding age (CECC vs. MECC: 71.0 ± 7.5 vs. 66.2 ± 10.1 years, p = 0.091) and logistic EuroSCORE I (6.2 ± 2.5 vs. 5.4 ± 3.0, p = 0.707). Hospital mortality was one patient in each group (1.6 vs. 1.0%, p = 0.688). The levels of leukocytes were lower in the MECC group (11.6 ± 3.2 vs. 9.4 ± 4.3 109/L, p = 0.040). Levels of platelets (137.2 ± 45.5 vs. 152.4 ± 50.3 109/L, p = 0.015) and hemoglobin (103.3 ± 11.3 vs. 107.3 ± 14.7 g/L, p = 0.017) were higher in the MECC group. Renal function was better preserved (creatinine: 1.1 ± 0.4 vs. 0.9 ± 0.2 mg/dL, p = 0.019). We were able to validate shorter time of postoperative ventilation (9.5 ± 15.1 vs. 6.3 ± 3.4 h, p = 0.054) as well as significantly shorter intensive care unit (ICU) stay (1.8 ± 1.3 vs. 1.2 ± 1.0 d, p = 0.005) for MECC patients. The course of C-reactive protein did not differ between the groups. We were able to prove the feasibility of MECC even in minimally invasive performed mitral and aortic valve procedures. In addition, the use of MECC provides decreased platelet consumption and less hemodilution. The use of MECC in these selected patients lead to a shorter ventilation time and ICU stay.


Outcomes, Resource Use, and Financial Costs of Unplanned Extubations in Preterm Infants.
Unplanned extubations (UEs) in adult and pediatric populations are associated with poor clinical outcomes and increased costs. In-hospital outcomes and costs of UE in the NICU are not reported. Our objective was to determine the association of UE with clinical outcomes and costs in very-low-birth-weight infants. We performed a retrospective matched cohort study in our level 4 NICU from 2014 to 2016. Very-low-birth-weight infants without congenital anomalies admitted by 72 hours of age, who received mechanical ventilation (MV), were included. Cases (+UE) were matched 1:1 with controls (-UE) on the basis of having an equivalent MV duration at the time of UE in the case, gestational age, and Clinical Risk Index for Babies score. We compared MV days after UE in cases or the equivalent date in controls (postmatching MV), in-hospital morbidities, and hospital costs between the matched pairs using raw and adjusted analyses. Of 345 infants who met inclusion criteria, 58 had ≥1 UE, and 56 out of 58 (97%) were matched with appropriate controls. Postmatching MV was longer in cases than controls (median: 12.5 days; interquartile range [IQR]: 7 to 25.8 vs median 6 days; IQR: 2 to 12.3; adjusted odds ratio: 4.3; 95% confidence interval: 1.9-9.5). Inflation-adjusted total hospital costs were higher in cases (median difference: $49 587; IQR: -15 063 to 119 826; adjusted odds ratio: 3.8; 95% confidence interval: 1.6-8.9). UEs in preterm infants are associated with worse outcomes and increased hospital costs. Improvements in UE rates in NICUs may improve clinical outcomes and lower hospital costs.


The importance of Escherichia coli ribosomal proteins L1, L11 and L16 for the association of ribosomal subunits and the formation of the 70-S initiation complex.
50-S subunits were washed with LiCl solutions of different concentrations. After washing with 1 M LiCl solution the particles lost their ability to attach either to 30-S subunits or to the AUG - 30-S subunit - fMet-tRNAfMet complex or to a poly(U) - 30-S subunit - Phe-tRNAPhe complex. Those proteins which were removed by LiCl were fractionated on a Sephadex G-100 column. Of the fractionated proteins only the combinations L1 and L11 or L1 and L16 were essential for the association of 50-S 1.0 cores (particles prepared by washing 50-S subunits in 1.0 M LiCl) with 30-S subunits. These three proteins were also required for the formation of a stable complex between 50-S 1.0 cores, mRNA, 30-S subunits and aminoacyl-tRNA.


Is the adoption of more efficient strategies of organ procurement the answer to persistent organ shortage in transplantation?
[I]s persistent organ shortage the major obstacle to the performance of more procedures as often popularly portrayed? Does the answer therefore lie in the adoption of more efficient strategies of organ procurement? While the measures taken to improve the efficiency of organ procurement may be inspired by the laudable motive of saving lives, they may ultimately prove to be myopic if the larger ethical issues raised by organ transplant programs for the allocation of national and organ resources are not given their due consideration. For any society that desires to include organ transplantation in its health delivery system, it must consider the social and ethical issues that transplant programs raise for the macroallocation of available national resources and the manner by which organ resources are procured, and distributed. The failure to resolve these issues in an ethically acceptable manner at any of these levels would render any transplant program ethically indefensible. This essay therefore argues that before a society decides on its policy of organ procurement it ought to make prior assessments of: a) its social priorities; b) the policies for ensuring fair access to organ resources; and c) the extent to which it is willing to support transplants.


On being the right size: food-limited feedback on optimal body size.
An insular population of white-tailed deer Odocoileus virginianus introduced in 1896 to predator-free Anticosti Island, Quebec, has caused long-term changes in the plant community. Food quality declined as did body weight. Although different parameters of reproduction changed, overall reproductive rates remained similar, thus maintaining deer density and promoting further change in habitat. These results show (i) long-term feedbacks on carrying capacity, (ii) the mechanism for reduction of body mass, and (iii) the lack of strong reduction in reproductive rates to regulate the population at high density, a feature of Eutherians. They are relevant to mechanisms determining the evolution of vertebrate body sizes.


Crystallization of the AAA domain of the ATP-dependent protease FtsH of Escherichia coli.
FtsH is a membrane-anchored ATP-dependent protease that degrades misfolded or misassembled membrane proteins as well as a subset of cytoplasmic regulatory proteins. It belongs to the family of AAA(+) ATPases with roles in diverse cellular processes. The ATPase domain of FtsH from Escherichia coli has been crystallized from ammonium sulfate solutions and crystals diffracting to 1.5 A resolution have been obtained.


Developing and Implementing a Father-Friendly Neonatal Intensive Care Unit Improved Nurses' Self-Efficacy.
The need for paternal support is rarely addressed in neonatal intensive care units (NICUs). Neonatal nurses often primarily focus on the needs of the mother and infant and may not be trained in support of fathers. To investigate nurses' self-efficacy (SE) in guiding and supporting fathers after implementing a father-friendly NICU. Nurses from the intervention NICU and 13 control NICUs were included in a before-and-after intervention study. Questionnaires measuring nurses' SE regarding support of fathers and mothers were obtained when starting the development process, before and 18 months after the implementation. The primary outcome was the difference between nurses' SE scores for father and mother questions in the intervention group compared with the control group. In total, 294, 330, and 288 nurses responded to the first, second, and third questionnaires, respectively. From the first to third questionnaires, the intervention group showed a significantly higher increase in SE scores for father questions compared with the control group (0.53 vs 0.20, P = .005) and a nonsignificantly higher increase for mother questions (0.30 vs 0.09, P = .13). In the third questionnaire, the intervention group showed a higher SE score for father questions compared with the control group (9.02 vs 8.45, P = .002) and the first questionnaire (9.02 vs 8.49, P = .02). By implementing a father-friendly NICU, nurses' SE for providing support to fathers increased significantly. Training in a father-friendly approach increases nurses' ability to support both parents.


2,3,4- or 2,3,5-trisubstituted furans: catalyst-controlled highly regioselective ring-opening cycloisomerization reaction of cyclopropenyl ketones.
2,3,4- or 2,3,5-trisubstituted furans were highly regioselectively formed from the cycloisomerization reaction of the same starting cyclopropenes 1 via the subtle choice of the transition metal halides. Under the catalysis of 5 mol % PdCl2(CH3CN)2, 2,3,5-trisubstituted furans 2 were given in 50-88% yields with 95-99% regioselectivities, while 2,3,4-trisubstituted furans 3 were formed in 78-96% yields with 99% regioselectivities under the catalysis of 5 mol % CuI.


Open-label safety assessment of bilastine in elderly patients with allergic rhinoconjunctivitis and/or urticaria.
Bilastine is an H1-antihistamine approved for symptomatic treatment of patients with allergic rhinoconjunctivitis or urticaria. The safety profile of bilastine in clinical trials of allergic rhinoconjunctivitis or urticaria, assessed by type and frequency of adverse events (AE), was similar to that of placebo. As part of the risk management plan for bilastine, the safety profile of bilastine in the elderly was assessed. A prospective, multicenter, observational, open-label, 3-month follow-up study was performed to assess the safety profile of bilastine 20 mg in patients aged ≥65 years with allergic rhinoconjunctivitis and/or urticaria. A total of 74 of 146 patients (50.7%) reported 129 treatment-emergent AEs (TEAE) during the study period. The incidence of TEAEs was low, with monthly and quarterly rates of 0.29 (95% confidence intervals [CI], 0.229-0.367) and 0.88 (95% CI, 0.688-1.100), respectively. Monthly and quarterly incidence rates were 0.04 (95% CI, 0.016-0.082) and 0.12 (95% CI, 0.048-0.246), respectively, for related TEAEs (eight TEAEs in seven patients) and were 0.02 (95% CI, 0.003-0.048) and 0.05 (95% CI, 0.010-0.143), respectively, for serious TEAEs (five TEAES in three patients). All serious TEAEs were considered to be unrelated to bilastine. Bilastine 20 mg showed a favorable safety profile with a low incidence of TEAEs in patients aged ≥65 years. The results were in accordance with the known safety profile of bilastine 20 mg and incidence of AEs reported in previous studies and described in the approved summary of product characteristics.


Evaluation of the value of Preoperative Sialic Acid Levels in Diagnosis and Localization of Urothelial Tumors.
Objective: To explore SA levels in the serum of urothelial tumor patients and their correlation with clinical pathological features and localization. Materials and Methods: Our research retrospectively collected data from 591 patients with urothelial tumors between July 2014 and April 2018. The SA levels in the serum of urothelial tumor patients and their correlation with clinical pathological features and localization were investigated. Univariate and multivariate logistic regression analyses were further performed to identify independent associations. Results: The levels of SA were significantly associated with the malignant degree (tumor grade and infiltration) of bladder cancer and tumor localization (all p < 0.05). The multivariate logistic regression model showed that SA levels were independently associated with the presence of high-grade urothelial carcinoma (BUC: HR = 1.941, UTUC: HR = 3.820, all p <0.05) and upper urinary tract urothelial carcinoma (HR = 2.047, p < 0.05). Finally, we validated the diagnosis and localization value of SA in an independent cohort from another institutions. Conclusions: Elevated serum SA levels are an independent predictor of high-grade urothelial carcinoma and upper urinary tract urothelial carcinoma, indicating that SA levels may be a potential biomarker for the diagnosis, prognosis and localization of urothelial tumors.


Effect of nasal airway positive pressure on upper airway size and configuration.
The effect of nasal airway positive pressure (NAPP) on upper airway size and configuration during wakefulness was studied by computerized tomography in 12 obese subjects with obstructive sleep apnea (OSA), seven weight- and age-matched subjects without OSA, and 12 normal subjects. NAPP of 10 to 12 cm H2O was associated with a significant increase in airway area throughout the upper airway in all three groups. The change in airway area per cm H2O NAPP increased from nasopharynx to hypopharynx. The change in airway area per cm H2O NAPP was significantly smaller in the OSA than in the normal subjects in the region of the soft palate. Electromyographic recordings of the genioglossus and alae nasi muscles with and without NAPP during wakefulness in five of the OSA and five of the normal subjects showed either a decrease or no change in phasic and tonic activity with NAPP. In a separate series of experiments in an additional five OSA and five normal subjects, NAPP of zero, 5, 10, and 15 cm H2O was associated with a linear increase in airway area at a given airway level. These results indicate that (1) the increase in pharyngeal cross-sectional area with application of NAPP during wakefulness is smaller in OSA than in normal subjects in the region of the soft palate and (2) changes in upper airway muscle activity may accompany changes in upper airway size and configuration.


Focused review on management of the difficult paediatric airway.
Management of the difficult paediatric airway management may be associated with a high rate of complications. It is important that clinicians understand the patient profiles associated with difficult airway management, and the equipment and techniques available to effectively manage these children. The goal of this focused review is to highlight key airway management concepts when managing the paediatric difficult airway. This includes understanding the advantages and limitations of various airway equipment designed for children and reviewing the difficult airway algorithm with its unique considerations for the paediatric patient. Early recognition of known risk factors and thorough preparation may be helpful in reducing the risk of complications during difficult airway management in children.


Is parental body weight related with their children's overweight and obesity in Gao Hang Town, Shanghai?
This study aimed to evaluate the relationship between parental body weight and their children's overweight and obesity in school students in Gao Hang Town, Shanghai. A cross-sectional study was performed in five primary schools in Gao Hang Town, Shanghai. Overall, 2,025 sets of parents and their children (7-13 years, 981 boys/1044 girls) were enrolled. Body mass index (BMI) and waist circumference for each child were measured. Age, gender, birth weight, and breastfeeding history was recorded for each child and the BMI of their parents was obtained by a self-completion questionnaire. Overweight (including obesity) was defined as a BMI of >=24.0 kg/m2 in parents and a BMI >=P85 in children according to age- and gender-specific percentiles. Re-sults: The total prevalence of overweight was higher in boys than in girls (35.5% vs 19.5%), while it was the same in fathers compared with mothers (50.6% vs 18.9%). The prevalence of overweight in boys showed a trend with increasing age, but remained stable versus age in girls. Parents were further divided into four subgroups as follows: I) both father and mother had a normal BMI; II) father overweight, mother normal weight; III) father normal weight, mother overweight; IV) both father and mother are overweight. The odds ratio of overweight was 2.26 for group II, 2.71 for group III, and 4.36 for group IV, respectively, compared with group I. Gender, paternal BMI, and maternal BMI were chosen as risk factors for children overweight. Parental BMI affects their offspring overweight and obesity in Chinese school students.


[The distribution of HLA alleles class I and class II among patientes with psoriatic arthritis in Croatia].
The aim of the present study was to analyze the distribution of HLA-A, -B, -Cw, and -DRB1 alleles among patients with psoriatic arthritis (PsA) in Croatia. DNA was isolated from peripheral blood of 58 PsA patients (28 male and 30 female) and tested by PCR-SSP (Polymerase Chain Reaction - Sequence Specific Primers) method for polymorphism of the above mentioned HLA loci. The strongest association between psoriatic arthritis and HLA in the Croatian population was observed for alleles at HLA-B locus (B*39 and B*57), while the association of B*27 and B* 13 alleles with PsA reached significance only before correction of p value with the number of tested alleles. Higher frequency of Cw*02 and DRB1*16 alleles is a result of linkage disequilibrium between these alleles and HLA-B alleles associated with PsA in Croatia. We also observed lower frequency of B*0702, B*18 and B*38 alleles in our group of patients.


Expression of cell wall related genes in basal and ear internodes of silking brown-midrib-3, caffeic acid O-methyltransferase (COMT) down-regulated, and normal maize plants.
Silage maize is a major forage and energy resource for cattle feeding, and several studies have shown that lignin content and structure are the determining factors in forage maize feeding value. In maize, four natural brown-midrib mutants have modified lignin content, lignin structure and cell wall digestibility. The greatest lignin reduction and the highest cell wall digestibility were observed in the brown-midrib-3 (bm3) mutant, which is disrupted in the caffeic acid O-methyltransferase (COMT) gene. Expression of cell wall related genes was investigated in basal and ear internodes of normal, COMT antisens (AS225), and bm3 maize plants of the INRA F2 line. A cell wall macro-array was developed with 651 gene specific tags of genes specifically involved in cell wall biogenesis. When comparing basal (older lignifying) and ear (younger lignifying) internodes of the normal line, all genes known to be involved in constitutive monolignol biosynthesis had a higher expression in younger ear internodes. The expression of the COMT gene was heavily reduced, especially in the younger lignifying tissues of the ear internode. Despite the fact that AS225 transgene expression was driven only in sclerenchyma tissues, COMT expression was also heavily reduced in AS225 ear and basal internodes. COMT disruption or down-regulation led to differential expressions of a few lignin pathway genes, which were all over-expressed, except for a phenylalanine ammonia-lyase gene. More unexpectedly, several transcription factor genes, cell signaling genes, transport and detoxification genes, genes involved in cell wall carbohydrate metabolism and genes encoding cell wall proteins, were differentially expressed, and mostly over-expressed, in COMT-deficient plants. Differential gene expressions in COMT-deficient plants highlighted a probable disturbance in cell wall assembly. In addition, the gene expressions suggested modified chronology of the different events leading to cell expansion and lignification with consequences far beyond the phenylpropanoid metabolism. The reduced availability of monolignols and S units in bm3 or AS225 plants led to plants also differing in cell wall carbohydrate, and probably protein, composition. Thus, the deficiency in a key-enzyme of the lignin pathway had correlative effects on the whole cell wall metabolism. Furthermore, the observed differential expression between bm3 and normal plants indicated the possible involvement in the maize lignin pathway of genes which up until now have not been considered to play this role.


Measuring outcomes in adult spinal deformity surgery: a systematic review to identify current strengths, weaknesses and gaps in patient-reported outcome measures.
Adult spinal deformity (ASD) causes severe disability, reduces overall quality of life, and results in a substantial societal burden of disease. As healthcare is becoming more value based, and to facilitate global benchmarking, it is critical to identify and standardize patient-reported outcome measures (PROMs). This study aims to identify the current strengths, weaknesses, and gaps in PROMs used for ASD. Studies were included following a systematic search in multiple bibliographic databases between 2000 and 2015. PROMs were extracted and linked to the outcome domains of WHO's International Classification of Functioning and Health (ICF) framework. Subsequently, the clinimetric quality of identified PROMs was evaluated. The literature search identified 144 papers that met the inclusion criteria, and nine frequently used PROMs were identified. These covered 29 ICF outcome domains, which could be grouped into three of the four main ICF chapters: body function (n = 7), activity and participation (n = 19), environmental factors (n = 3), and body structure (n = 0). A low quantity (n = 3) of papers was identified that studied the clinimetric quality of PROMs. The Scoliosis Research Society (SRS)-22 has the highest level of clinimetric quality for ASD. Outcome domains related to mobility and pain were well represented. We identified a gap in current outcome measures regarding neurological and pulmonary function. In addition, no outcome domains were measured in the ICF chapter body structure. These results will serve as a foundation for the process of seeking international consensus on a standard set of outcome domains, accompanied PROMs and contributing factors to be used in future clinical trials and spine registries.


Physiologically Based Pharmacokinetic Modeling To Guide Management of Drug Interactions between Elexacaftor-Tezacaftor-Ivacaftor and Antibiotics for the Treatment of Nontuberculous Mycobacteria.
Nontuberculous mycobacteria (NTM) are the pathogens of concern in people with cystic fibrosis (pwCF) due to their association with deterioration of lung function. Treatment requires the use of a multidrug combination regimen, creating the potential for drug-drug interactions (DDIs) with cystic fibrosis transmembrane conductance regulator (CFTR)-modulating therapies, including elexacaftor, tezacaftor, and ivacaftor (ETI), which are eliminated mainly through cytochrome P450 (CYP) 3A-mediated metabolism. An assessment of the DDI risk for ETI coadministered with NTM treatments, including rifabutin, clofazimine, and clarithromycin, is needed to provide appropriate guidance on dosing. The CYP3A-mediated DDIs between ETI and the NTM therapies rifabutin, clarithromycin, and clofazimine were evaluated using physiologically based pharmacokinetic (PBPK) modeling by incorporating demographic and physiological "system" data with drug physicochemical and in vitro parameters. Models were verified and then applied to predict untested scenarios to guide continuation of ETI during antibiotic treatment, using ivacaftor as the most sensitive CYP3A4 substrate. The predicted area under the concentration-time curve (AUC) ratios of ivacaftor when coadministered with rifabutin, clofazimine, or clarithromycin were 0.31, 2.98, and 9.64, respectively, suggesting moderate and strong interactions. The simulation predicted adjusted dosing regimens of ETI administered concomitantly with NTM treatments, which required delayed resumption of the standard dose of ETI once the NTM treatments were completed. The dosing transitions were determined based on the characteristics of the perpetrator drugs, including the mechanism of CYP3A modulation and their elimination half-lives. This study suggests increased doses of elexacaftor/tezacaftor/ivacaftor 200/100/450 mg in the morning and 100/50/375 mg in the evening when ETI is coadministered with rifabutin and reduced doses of elexacaftor/tezacaftor 200/100 mg every 48 h (q48h) and ivacaftor 150 mg daily or a dose of elexacaftor/tezacaftor/ivacaftor 200/100/150 mg q72h when coadministered with clofazimine or clarithromycin, respectively. Importantly, the PBPK simulations provide evidence in support of the use of treatments for NTM in pwCF receiving concomitant dose-adjusted ETI therapy.


Differential effects of chronic amphetamine and baclofen administration on cAMP levels and phosphorylation of CREB in distinct brain regions of wild type and monoamine oxidase B-deficient mice.
Roles of GABA(B) transmission were explored in the action of amphetamine (Amph) on the brain. Adult male wild type (WT) and monoamine oxidase B-knocked out (MAOBKO) mice received i.p. injections of saline, d-Amph (5 mg/kg), plus baclofen (GABA(B) receptor agonist, 10 mg/kg), or baclofen and Amph, twice daily for 3 days and single treatments on day 4, followed by immuno-cyclic-AMP (cAMP) and immunoblotting assays on the brain tissue. The WT mice responded with higher levels of behavioral responses than the KO to the daily Amph injection; however, baclofen blocked the Amph-induced behavioral hyperactivity of both WT and KO mice. After the last treatment, levels of cAMP and phosphorylated (p) cyclic-AMP response element binding protein (CREB) were up-regulated in the striatum and somatosensory cortex of Amph-treated WT mice, while similar to the saline-controls in the baclofen+Amph-treated group, indicating the blockade by baclofen to Amph. Baclofen similarly suppressed the Amph-induced increases in pCREB levels of WT hippocampus and amygdala, and decreases of olfactory bulb and thalamus. For MAOBKO mice, baclofen hindered the Amph-generated increases in motor cortical cAMP and pCREB, and amygdaloid pCREB, and the decrease in olfactory bulb pCREB, whereas did not affect the Amph-raised hippocampal pCREB. Furthermore, the levels of CREB were variably modified in distinct regions by the drug exposures. The data reveal that the GABA(B)-mediated intracellular signaling differentially participates in mechanisms underlying Amph perturbation to various regions, and may thereby contribute explanations to the behavioral consequences. Moreover, MAOB is region-dependently involved in responses of the brain to Amph and baclofen, supporting interactions between GABA and monoamines.


ABCG1 as a potential oncogene in lung cancer.
ATP-binding cassette transporter G1 (ABCG1) is a member of the ABC transporter family and regulates cellular cholesterol homeostasis. It has important roles in cholesterol homeostasis and tumor immunity, which has, however, not been reported in lung cancer. The present study showed that ABCG1 protein is upregulated in lung cancer compared with adjacent normal tissues and furthermore, aberrant ABCG1 expression was detected in lung cancer cell lines. ABCG1 was shown to promote the proliferation of HKULC4 lung cancer cells. Moreover, ABCG1 was found to regulate proliferation-, apoptosis- and cancer stem cell-associated markers in HKULC4 cells, implying that ABCG1 has important roles not only in the regulation of proliferation but also of apoptosis and cancer stem cells. A microRNA microarray analysis showed that ABCG1 significantly downregulated miR-29a, -b and -c expression in HKULC4 cells. Finally, it was demonstrated that ABCG1 promoted the migration and invasion in HKULC4 cells. Thus, ABCG1 may be a novel therapeutic target to improve the treatment of non-small cell lung cancer.


Molecular and cellular regulation of thermogenic fat.
Thermogenic fat, consisting of brown and beige adipocytes, dissipates energy in the form of heat, in contrast to the characteristics of white adipocytes that store energy. Increasing energy expenditure by activating brown adipocytes or inducing beige adipocytes is a potential therapeutic strategy for treating obesity and type 2 diabetes. Thus, a better understanding of the underlying mechanisms of thermogenesis provides novel therapeutic interventions for metabolic diseases. In this review, we summarize the recent advances in the molecular regulation of thermogenesis, focusing on transcription factors, epigenetic regulators, metabolites, and non-coding RNAs. We further discuss the intercellular and inter-organ crosstalk that regulate thermogenesis, considering the heterogeneity and complex tissue microenvironment of thermogenic fat.


Isolation of Novel Bacteria Including Rarely Cultivated Phyla, Acidobacteria and Verrucomicrobia, from the Roots of Emergent Plants by Simple Culturing Method.
A number of novel bacteria including members of rarely cultivated phyla, Acidobacteria and Verrucomicrobia, were successfully isolated from the roots of two emergent plants, Iris pseudacorus and Scirpus juncoides, by a simple culturing method. A total of 47.1% (66 strains) for I. pseudacorus and 42.1% (59 strains) for S. juncoides of all isolates (140 strains from each sample) were phylogenetically novel. Furthermore, Acidobacteria and Verrucomicrobia occupied 10.7% (15 strains) and 2.9% (4 strains) of I. pseudacorus isolates, and 2.1% (3 strains) and 3.6% (5 strains) of S. juncoides isolates, respectively, indicating that plant roots are attractive sources for isolating rarely cultivated microbes.


Functional characterization of rs2229094 (T>C) polymorphism in the tumor necrosis factor locus and lymphotoxin alpha expression in human retina: the Retina 4 project.
The objective of this study is to determine the expression and localization of lymphotoxin alpha (LTA) in human retinas and the functionality of one of its polymorphisms rs2229094 (C13R) (T>C), previously associated with proliferative vitreoretinopathy (PVR) development. Total RNA from three healthy human retinas were extracted and subjected to reverse transcription-polymerase chain reaction (RT-PCR) analysis, using flanking primers of LTA cDNA. In addition, three human eyes with retinal detachment (RD) and three healthy control eyes were subjected to immunohistochemistry (IHC) with a specific antibody against LTA. The functionality of T and C alleles was assessed by using pCEFL-Flag expression vector and transient transfection assays in COS-1 cell line. In addition, expression analysis by RT-PCR, Western blot and subcellular localization of both alleles and by immunofluorescence assay was performed. RT-PCR analysis revealed no significant levels of messenger RNA (mRNA) LTA in healthy human retinas. Sequential IHC staining showed differences between healthy human and RD retinas. No differences in mRNA and protein expression levels and in subcellular localization between both alleles were found. Both alleles were located in the cytoplasm of COS-1 cells. Although results suggest lack of functionality, the differences found in IHC study and its strong association with PVR and its relationship with tumor necrosis factor locus, warrant further studies and could justify the use of this polymorphism as a valid biomarker to identify high-risk patients to develop PVR after RD.


[The free-radical processes and antioxidant therapy in brain ischemia].
A role of the free-radical processes and disturbances of oxidative-restorative blood homeostasis and nervous tissue in the pathogenesis of brain ischemic pathology and other diseases are reviewed. Attention is focused on the search for optimal ways of pharmacological correction of oxidative stress in the schemes of complex treatment of chronic blood circulation insufficiency and on the necessity of combined application of several antioxidants with different mechanisms of action which reciprocally potentiate each other. Experimental and clinical suppositions of the use of a-lipoic acid as one of the most studied antioxidant in the treatment of brain ischemia as well as the results of own studies on the preparation berlition which contains a-lipoic acid used in the neuroprotective therapy of chronic brain ischemia for correction of free-radical processes are discussed.


Successful treatment of Placenta Percreta through a combinatorial treatment involving a Bakri Balloon and Methotrexate--a case report.
Placental percreta is a complication involving an abnormally deep placental attachment to the myometrium, resulting in obstetric hemorrhage and peripartum hysterectomy A 38-year-old pregnant woman, with a history of 2 Cesarean births, myomectomy 9 pregnancies, and 6 spontaneous abortions, was admitted after experiencing intrauterine fetal death, which occurred at 19 weeks gestation. The patient was referred to our institution after 8 days of unsuccessful medical treatment. Doppler ultrasonography and vacuum curettage revealed possible signs of abnormal placentation. Because of the unsuccessful separation of the placenta and massive bleeding, we used a Bakri Balloon to treat excessive bleeding during the acute phase, followed by the conservative administration of parenteral methotrexate to treat the spontaneous involution of the placenta at 7 weeks of conservative therapy Bakri Balloon and methotrexate application to treat bleeding after curettage is a useful choice in placenta percreta and hemorrhage after abortion.


Magnetic resonance imaging: Review of imaging techniques and overview of liver imaging.
Magnetic resonance imaging (MRI) of the liver is slowly transitioning from a problem solving imaging modality to a first line imaging modality for many diseases of the liver. The well established advantages of MRI over other cross sectional imaging modalities may be the basis for this transition. Technological advancements in MRI that focus on producing high quality images and fast imaging, increasing diagnostic accuracy and developing newer function-specific contrast agents are essential in ensuring that MRI succeeds as a first line imaging modality. Newer imaging techniques, such as parallel imaging, are widely utilized to shorten scanning time. Diffusion weighted echo planar imaging, an adaptation from neuroimaging, is fast becoming a routine part of the MRI liver protocol to improve lesion detection and characterization of focal liver lesions. Contrast enhanced dynamic T1 weighted imaging is crucial in complete evaluation of diseases and the merit of this dynamic imaging relies heavily on the appropriate timing of the contrast injection. Newer techniques that include fluoro-triggered contrast enhanced MRI, an adaptation from 3D MRA imaging, are utilized to achieve good bolus timing that will allow for optimum scanning. For accurate interpretation of liver diseases, good understanding of the newer imaging techniques and familiarity with typical imaging features of liver diseases are essential. In this review, MR sequences for a time efficient liver MRI protocol utilizing newer imaging techniques are discussed and an overview of imaging features of selected common focal and diffuse liver diseases are presented.


11C-hydroxy-ephedrine-PET/CT in the Diagnosis of Pheochromocytoma and Paraganglioma.
Pheochromocytomas (PCC) and paragangliomas (PGL) may be difficult to diagnose because of vague and uncharacteristic symptoms and equivocal biochemical and radiological findings. This was a retrospective cohort study in 102 patients undergoing 11C-hydroxy-ephedrine (11C-HED)-PET/CT because of symptoms and/or biochemistry suspicious for PCC/PGL and/or with radiologically equivocal adrenal incidentalomas. Correlations utilized CT/MRI, clinical, biochemical, surgical, histopathological and follow-up data. 11C-HED-PET/CT correctly identified 19 patients with PCC and six with PGL, missed one PCC, attained one false positive result (nodular hyperplasia) and correctly excluded PCC/PGL in 75 patients. Sensitivity, specificity, positive and negative predictive values of 11C-HED-PET/CT for PCC/PGL diagnosis was 96%, 99%, 96% and 99%, respectively. In 41 patients who underwent surgical resection and for whom correlation to histopathology was available, the corresponding figures were 96%, 93%, 96% and 93%, respectively. Tumor 11C-HED-uptake measurements (standardized uptake value, tumor-to-normal-adrenal ratio) were unrelated to symptoms of catecholamine excess (p > 0.05) and to systolic blood pressure (p > 0.05). In PCC/PGL patients, norepinephrine and systolic blood pressure increased in parallel (R2 = 0.22, p = 0.016). 11C-HED-PET/CT was found to be an accurate tool to diagnose and rule out PCC/PGL in complex clinical scenarios and for the characterization of equivocal adrenal incidentalomas. PET measurements of tumor 11C-HED uptake were not helpful for tumor characterization.


The membrane form of tumor necrosis factor is sufficient to mediate partial innate immunity to Francisella tularensis live vaccine strain.
Here we characterize Francisella tularensis live vaccine strain (LVS) infection in total tumor necrosis factor (TNF) knockout (KO) mice and in transgenic mice expressing only the membrane form of TNF (memTNF). MemTNF mice, but not TNF KO mice, survived low-dose, sublethal LVS infections. Splenic nitric oxide production was impaired in infected memTNF mice and was absent in infected TNF KO mice. Spleen cell production of interferon-gamma, RANTES, and monocyte chemotactic protein-1 was elevated in TNF KO mice, compared with that in WT mice, by days 4-5 after infection, along with transiently increased numbers of CCR2(+) cells, whereas memTNF mice had an intermediate phenotype. By day 6 after infection, TNF KO mice, but not memTNF mice, exhibited massive apoptosis in spleens and livers, which shortly preceded their death. Thus, memTNF partially functions to regulate chemokine expression, cell recruitment, and nitric oxide production during primary LVS infection and protects against the induction of apoptosis observed in TNF KO mice.


Time to Amyloid Positivity and Preclinical Changes in Brain Metabolism, Atrophy, and Cognition: Evidence for Emerging Amyloid Pathology in Alzheimer's Disease.
Background: Aβ pathology is associated with longitudinal changes of brain metabolism, atrophy, and cognition, in cognitively healthy elders. However, Aβ information is usually measured cross-sectionally and dichotomized to classify subjects as Aβ-positive or Aβ-negative, making it difficult to evaluate when brain and cognitive changes occur with respect to emerging Aβ pathology. In this study, we use longitudinal Aβ information to combine the level and rate of change of Aβ to estimate the time to Aβ-positivity for each subject and test this temporal proximity to significant Aβ pathology for associations with brain structure, metabolism, and cognition. Methods: In 89 cognitively healthy elders with up to 10 years of follow-up, we estimated the points at which rates of fluorodeoxyglucose (FDG) PET, MRI, and cognitive and functional decline begin to accelerate with respect to the time to Aβ-positivity. Points of initial acceleration in rates of decline were estimated using mixed-effects models with penalized regression splines. Results: Acceleration of rates of FDG PET were observed to occur 20+ years before the conventional threshold for Aβ-positivity. Subtle signs of cognitive dysfunction were observed 10+ years before Aβ-positivity. Conclusions: Aβ may have subtle associations with other hallmarks of Alzheimer's disease before Aβ biomarkers reach conventional thresholds for Aβ-positivity. Therefore, we propose that emerging Aβ pathology occurs many years before cognitively healthy elders reach the current threshold for Aβ positivity (preclinical AD). To allow prevention in the earliest disease stages, AD clinical trials may be designed to also include subjects with Aβ biomarkers in the sub-threshold range.


Toward optical spectroscopy-guided lung biopsy: Demonstration of tissue-type classification.
The diagnostic yield of standard tissue-sampling modalities of suspected lung cancers, whether by bronchoscopy or interventional radiology, can be nonoptimal, varying with the size and location of lesions. What is needed is an insitu sensor, integrated in the biopsy tool, to objectively distinguish among tissue types in real time, not to replace biopsy with an optical diagnostic, but to verify that the sampling tool is properly located within the target lesion. We investigated the feasibility of elastic scattering spectroscopy (ESS), coupled with machine learning, to distinguish lung lesions from the various nearby tissue types, in a study with freshly-excised lung tissues from surgical resections. Optical spectra were recorded with an ESS fiberoptic probe in different areas of the resected pulmonary tissues, including benign-margin tissue sites as well as the periphery and core of the lesion. An artificial-intelligence model was used to analyze, retrospectively, 2032 measurements from excised tissues of 35 patients. With high accuracy, ESS was able to distinguish alveolar tissue from bronchi, alveolar tissue from lesions, and bronchi from lesions. This ex vivo study indicates promise for ESS fiberoptic probes to be integrated with surgical intervention tools, to improve reliability of pulmonary lesion targeting.


Isometric contraction induces rapid myocyte remodeling in cultured rat right ventricular papillary muscles.
The hypothesis that elevated systolic stress induces myocyte thickening has been difficult to test directly. We tested this hypothesis in working rat right ventricular papillary muscles using a recently developed technique for long-term muscle culture. Muscles were cultured for 36 h either isometrically at different levels of systolic stress or at physiological amounts and rates of shortening. Isometric contraction induced rapid increases in myocyte diameter regardless of the level of systolic stress, whereas control myocyte dimensions were maintained if physiological amounts and rates of systolic shortening were imposed. Myocyte thickening was accompanied by a significant decrease in cell length and number of sarcomeres in series along the long axis of the myocyte, suggesting that thickening may have occurred in part by rearrangement of existing sarcomeres. We conclude that the pattern of systolic shortening and/or diastolic lengthening regulates myocyte shape in working rat right ventricular papillary muscles, whereas systolic stress plays little or no role.


Sweat gland carcinoma with regional lymph node metastasis.
Description of a 63-year-old man with a sweat gland carcinoma low in the left axilla, and an axillary lymph node metastasis. A five-year survival was obtained. The histological picture of a sweat gland carcinoma may be highly variable. The best treatment seems to be local excision. If the primary tumour is situated close to a regional lymph gland station, regional lymph node extirpation should be seriously considered.


Anxiety and Its Association With Depression Among Institutionalized Elderly.
The authors assessed anxiety and depression among nursing home and congregate housing residents at yearly intervals. At baseline, modified DSM-III-R criteria yielded a 3.5% prevalence rate for anxiety or panic disorders. Another 13.2% reported milder symptoms not meeting diagnostic criteria. Anxiety was strongly associated with depression and with physical health, functional disability, and cognitive status. Follow-up data yielded an overall incidence rate of 2.3% for possible anxiety disorders; the majority of these cases were among those with mild anxiety at baseline. Change in anxiety was strongly associated with depression and, less consistently, with functional disability and cognitive status. Results are interpreted as indicating the indistinguishability of anxiety from depression in this frail elderly population.


Hemoglobin Evanston (alpha 14 Trp----Arg). An unstable alpha-chain variant expressed as alpha-thalassemia.
A new hematologic syndrome with phenotypic features of mild Hb H disease was identified in three children from two unrelated black American families. Erythrocytes from each of these children contained Hb H (beta 4) and Hb Barts (gamma 4), as well as a slowly migrating hemoglobin fraction that made up 7-10% of the total hemoglobin. The parents of the affected children all showed mild thalassemia-like changes, with one of the parents in each family also expressing the variant hemoglobin; in the latter individuals the mutant alpha-chains made up less than 2% of the total, and were present mainly or exclusively in combination with delta-chains in the form of a slowly migrating Hb A2. Purified Hb Evanston showed an increased oxygen affinity, but its Bohr effect, cooperativity, and 2,3-diphosphoglycerate effect were normal. The mutant hemoglobin appeared to have normal stability to heat and to isopropanol, and the stability of its alpha-chain in an extended time course synthesis study also appeared to be similar to that of alpha A. However, the results from short-term globin synthesis studies, and from mRNA translation in vitro, suggest that the two types of alpha-chains were synthesized at relatively equal rates, with a major fraction of the newly synthesized variant alpha-chains undergoing rapid catabolism. The hematologic data taken in combination with DNA hybridization and globin synthesis findings indicate that the proposita in each of these families has the genotype--, alpha A/--, alpha Ev. These observations suggest that two separate mechanisms are contributing to the alpha-thalassemia-like expression of Hb Evanston : the newly synthesized alpha EV-chains are unstable and are subject to early proteolytic destruction; and the mutant alpha-allele is linked to an alpha-globin gene deletion.


A Systematic Review of Community Engagement in the US Environmental Protection Agency's Extramural Research Solicitations: Implications for Research Funders.
We systematically reviewed the Environmental Protection Agency, National Center for Environmental Research's (NCER's) requests for applications (RFAs) and identified strategies that NCER and other funders can take to bolster community engagement. We queried NCER's publically available online archive of funding opportunities from fiscal years 1997 to 2013. From an initial list of 211 RFAs that met our inclusion criteria, 33 discussed or incorporated elements of community engagement. We examined these RFAs along 6 dimensions and the degree of alignments between them. We found changes over time in the number of RFAs that included community engagement, variations in how community engagement is defined and expected, inconsistencies between application requirements and peer review criteria, and the inclusion of mechanisms supporting community engagement in research. The results inform a systematic approach to developing RFAs that support community engagement in research.


Uniform Lithium Deposition Induced by Polyacrylonitrile Submicron Fiber Array for Stable Lithium Metal Anode.
The lithium dendrite growth and low Coulombic efficiency (CE) during lithium plating/striping cycles are the main obstacles for practical applications of lithium metal anode. Herein, we demonstrate that polyacrylonitrile (PAN) submicron fiber array could guide the lithium ions to uniformly disperse and deposit onto current collector. The PAN submicron fiber array nearly does not increase the volume of electrode with ultralow mass. By this simple design, we achieved stable cycling of lithium metal anode with an average CE of ∼97.4% for 250 cycles at a current density of 1 mA cm-2 with total Li capacity of 1 mAh cm-2.


Effective dimensionality for principal component analysis of time series expression data.
Large-scale expression data are today measured for thousands of genes simultaneously. This development has been followed by an exploration of theoretical tools to get as much information out of these data as possible. Several groups have used principal component analysis (PCA) for this task. However, since this approach is data-driven, care must be taken in order not to analyze the noise instead of the data. As a strong warning towards uncritical use of the output from a PCA, we employ a newly developed procedure to judge the effective dimensionality of a specific data set. Although this data set is obtained during the development of rat central nervous system, our finding is a general property of noisy time series data. Based on knowledge of the noise-level for the data, we find that the effective number of dimensions that are meaningful to use in a PCA is much lower than what could be expected from the number of measurements. We attribute this fact both to effects of noise and the lack of independence of the expression levels. Finally, we explore the possibility to increase the dimensionality by performing more measurements within one time series, and conclude that this is not a fruitful approach.


Endothelin-1 induces a glycolytic switch in pulmonary arterial endothelial cells via the mitochondrial translocation of endothelial nitric oxide synthase.
Recent studies have indicated that, during the development of pulmonary hypertension (PH), there is a switch from oxidative phosphorylation to glycolysis in the pulmonary endothelium. However, the mechanisms underlying this phenomenon have not been elucidated. Endothelin (ET)-1, an endothelial-derived vasoconstrictor peptide, is increased in PH, and has been shown to play an important role in the oxidative stress associated with PH. Thus, in this study, we investigated whether there was a potential link between increases in ET-1 and mitochondrial remodeling. Our data indicate that ET-1 induces the redistribution of endothelial nitric oxide synthase (eNOS) from the plasma membrane to the mitochondria in pulmonary arterial endothelial cells, and that this was dependent on eNOS uncoupling. We also found that ET-1 disturbed carnitine metabolism, resulting in the attenuation of mitochondrial bioenergetics. However, ATP levels were unchanged due to a compensatory increase in glycolysis. Further mechanistic investigations demonstrated that ET-1 mediated the redistribution of eNOS via the phosphorylation of eNOS at Thr495 by protein kinase C δ. In addition, the glycolytic switch appeared to be dependent on mitochondrial-derived reactive oxygen species that led to the activation of hypoxia-inducible factor signaling. Finally, the cell culture data were confirmed in vivo using the monocrotaline rat model of PH. Thus, we conclude that ET-1 induces a glycolytic switch in pulmonary arterial endothelial cells via the redistribution of uncoupled eNOS to the mitochondria, and that preventing this event may be an approach for the treatment of PH.


The prodromal phase of leucine-rich repeat kinase 2-associated Parkinson disease: Clinical and imaging Studies.
Asymptomatic, nonmanifesting carriers of leucine-rich repeat kinase 2 mutations are at increased risk of developing PD. Clinical and neuroimaging features may be associated with gene carriage and/or may demarcate individuals at greater risk for phenoconversion to PD. To investigate clinical and dopamine transporter single-photon emission computed tomography imaging characteristics of leucine-rich repeat kinase 2 asymptomatic carriers. A total of 342 carriers' and 259 noncarriers' relatives of G2019S leucine-rich repeat kinase 2/PD patients and 39 carriers' and 31 noncarriers' relatives of R1441G leucine-rich repeat kinase 2/PD patients were evaluated. Motor and nonmotor symptoms were assessed using specific scales and questionnaires. Neuroimaging quantitative data were obtained in 81 carriers and compared with 41 noncarriers. G2019S carriers scored higher in motor scores and had lower radioligand uptake compared to noncarriers, but no differences in nonmotor symptoms scores were observed. R1441G carriers scored higher in motor scores, had lower radioligand uptake, and had higher scores in depression, dysautonomia, and Rapid Eye Movements Sleep Behavior Disorder Screening Questionnaire scores, but had better cognition scores than noncarriers. Among G2019S carriers, a group with "mild motor signs" was identified, and was significantly older, with worse olfaction and lower radioligand uptake. G2019S and R1441G carriers differ from their noncarriers' relatives in higher motor scores and slightly lower radioligand uptake. Nonmotor symptoms were mild, and different nonmotor profiles were observed in G2019S carriers compared to R1441G carriers. A group of G2019S carriers with known prodromal features was identified. Longitudinal studies are required to determine whether such individuals are at short-term risk of developing overt parkinsonism. © 2017 International Parkinson and Movement Disorder Society.


Genotyping of Mycobacterium leprae strains from a region of high endemic leprosy prevalence in India.
Leprosy is still a major health problem in India which has the highest number of cases. Multiple locus variable number of tandem repeat analysis (MLVA) and single nucleotide polymorphism (SNP) have been proposed as tools of strain typing for tracking the transmission of leprosy. However, empirical data for a defined population from scale and duration were lacking for studying the transmission chain of leprosy. Seventy slit skin scrapings were collected from Purulia (West Bengal), Miraj (Maharashtra), Shahdara (Delhi), and Naini (UP) hospitals of The Leprosy Mission (TLM). SNP subtyping and MLVA on 10 VNTR loci were applied for the strain typing of Mycobacterium leprae. Along with the strain typing conventional epidemiological investigation was also performed to trace the transmission chain. In addition, phylogenetic analysis was done on variable number of tandem repeat (VNTR) data sets using sequence type analysis and recombinational tests (START) software. START software performs analyses to aid in the investigation of bacterial population structure using multilocus sequence data. These analyses include data summary, lineage assignment, and tests for recombination and selection. Diversity was observed in the cross-sectional survey of isolates obtained from 70 patients. Similarity in fingerprinting profiles observed in specimens of cases from the same family or neighborhood locations indicated a possible common source of infection. The data suggest that these VNTRs including subtyping of SNPs can be used to study the sources and transmission chain in leprosy, which could be very important in monitoring of the disease dynamics in high endemic foci. The present study strongly indicates that multi-case families might constitute epidemic foci and the main source of M. leprae in villages, causing the predominant strain or cluster infection leading to the spread of leprosy in the community.


CHANGES IN THE HERITABILITY OF FIVE MORPHOLOGICAL TRAITS UNDER COMBINED ENVIRONMENTAL STRESSES IN DROSOPHILA MELANOGASTER.
Heritabilities and evolvabilities for morphological traits were compared between two environments in Drosophila melanogaster using parent-offspring comparisons. One of the environments was favorable. The other stressful environment involved a combination of repeated cold shocks, poor nutrition, and ethanol added to the medium, which markedly decreased viability. For wing traits, heritabilities were relatively lower in the stressful environment, while heritabilities for bristle traits were not influenced by conditions. Heritability changes were largely due to an increase in the environmental variance under stress, whereas levels of additive genetic variance were relatively constant. Evolvabilities were similar between environments except for crossvein length.


A Brief Narrative Review of the Underlying Mechanisms Whereby Omega-3 Fatty Acids May Influence Skeletal Muscle: From Cell Culture to Human Interventions.
Skeletal muscle is essential for human locomotion as well as maintaining metabolic homeostasis. Age-related reduction in skeletal muscle mass, strength, and function (i.e., sarcopenia) is a result of pathophysiological processes that include inflammation, alteration of molecular signaling for muscle protein synthesis and degradation, changes in insulin sensitivity, as well as altered skeletal muscle satellite cell activity. Finding strategies to mitigate skeletal muscle loss with age is deemed paramount as the percentage of the population continues to shift towards having more older adults with sarcopenia. Recent research indicates omega-3 fatty acid supplementation can influence anabolic or catabolic pathways in skeletal muscle. Our brief review will provide a synopsis of some underlying mechanisms that may be attributed to omega-3 fatty acid supplementation's effects on skeletal muscle. We will approach this review by focusing on cell culture, animal (pre-clinical models), and human studies evaluating omega-3 fatty acid supplementation, with suggestions for future research. In older adults, omega-3 fatty acids may possess some potential to modify pathophysiological pathways associated with sarcopenia; however, it is highly likely that omega-3 fatty acids need to be combined with other anabolic interventions to effectively ameliorate sarcopenia.


GluN2B-containing NMDA receptors promote glutamate synapse development in hippocampal interneurons.
In postnatal development, GluN2B-containing NMDARs are critical for the functional maturation of glutamatergic synapses. GluN2B-containing NMDARs prevail until the second postnatal week when GluN2A subunits are progressively added, conferring mature properties to NMDARs. In cortical principal neurons, deletion of GluN2B results in an increase in functional AMPAR synapses, suggesting that GluN2B-containing NMDARs set a brake on glutamate synapse maturation. The function of GluN2B in the maturation of glutamatergic inputs to cortical interneurons is not known. To examine the function of GluN2B in interneurons, we generated mutant mice with conditional deletion of GluN2B in interneurons (GluN2B(ΔGAD67)). In GluN2B(ΔGAD67) mice interneurons distributed normally in cortical brain regions. After the second postnatal week, GluN2B(ΔGAD67) mice developed hippocampal seizures and died shortly thereafter. Before the onset of seizures, GluN2B-deficient hippocampal interneurons received fewer glutamatergic synaptic inputs than littermate controls, indicating that GluN2B-containing NMDARs positively regulate the maturation of glutamatergic input synapses in interneurons. These findings suggest that GluN2B-containing NMDARs keep the circuit activity under control by promoting the maturation of excitatory synapses in interneurons.


CRISPR/Cas9-mediated modification of the extreme C-terminus impairs PDGF-stimulated activity of Duox2.
Duox2 belongs to the large family of NADPH-oxidase enzymes that are implicated in immune response, vasoregulation, hormone synthesis, cell growth and differentiation via the regulated synthesis of H2O2 and reactive oxygen species. We and others have shown that Duox2 and H2O2 are involved in platelet-derived growth factor (PDGF) induced migration of fibroblasts. Now, using the CRISPR/Cas9-mediated genome editing we demonstrate that the extreme C-terminal region of Duox2 is required for PDGF-stimulated activity of Duox2 and H2O2 production. We generated the fibroblast cells that stably co-express the wild-type or C-terminally modified Duox2 and fluorescent H2O2 probe Hyper. We found that nonsense substitution of the last 23 amino acids in Duox2 results in complete loss of PDGF stimulation of intracellular H2O2 and fibroblast migration, yet these mutations have no effects on the expression of Duox2 and other NADPH-oxidases in cells. These findings illustrate for the first time that the extreme C-terminus of Duox2 is required for the functional activity of the enzyme. Furthermore, the conservative nature of the C-terminus suggests its role for activity in other NADPH-oxidases.


Energy intake and resting metabolic rate in preschool Jamaican children with homozygous sickle cell disease.
A relative energy deficiency consequent to a high resting metabolic rate (RMR) may contribute to growth impairment in persons with homozygous (SS genotype) sickle cell disease (SCD). The growth deficit in SCD emerges at an early age, but few studies have addressed the adequacy of energy intake relative to RMR in young children. Our objective was to test the hypothesis that energy intake relative to RMR is lower in children with SCD than in control subjects. The dietary intake of 41 children with SCD and 31 control subjects with a normal hemoglobin genotype (AA) aged 3-6 y was assessed by weighing all food consumed during 3 d. RMR was determined with the use of indirect calorimetry. The RMR in the children with SCD ( +/- SD: 5.47 +/- 0.93 MJ/d) was higher than that in the control subjects (5.19 +/- 1.3 MJ/d) after adjustment for sex and weight (P = 0.04). Energy intake did not differ significantly between the 2 genotype groups. The ratio of energy intake to RMR was lower in the children with SCD ( +/- SD: 1.13 +/- 0.33) than in the control subjects (1.35 +/- 0.38) after adjustment for sex and weight (P = 0.005). Prepubertal children with SCD fail to compensate for their higher RMR by increasing their energy intake. This observation is consistent with a hypothesis of a relative energy deficiency in SCD.


Genetics and hormones in testicular descent.
Testicular descent is an essential part of normal male sexual development. Any anomaly that disrupts normal testicular descent will be clinically evident as cryptorchidism. Several factors, such as Hoxa-10, epidermal growth factor (EGF), calcitonin gene-related peptide (CGRP), and hormones, especially androgens and insulin-like factor 3 (INSL-3), have been suggested as being regulators of testicular descent. Testicular descent from the lower pole of the kidney into the extra-abdominal scrotal sac is a two-stage process of transabdominal and inguino-scrotal migration. The transabdominal phase is androgen independent, whereas the inguino-scrotal phase depends on androgen action. Disruption of androgen action eg. by environmental anti-androgens are suspected as contributing to cryptorchidism. Estrogens can down-regulate INSL-3 production and thereby disturb testicular descent. Familial occurrence in some cases suggests a possible genetic background for cryptorchidism.


Material-Device-Circuit Co-optimization of 2D Material based FETs for Ultra-Scaled Technology Nodes.
Two-dimensional (2D) material based FETs are being considered for future technology nodes and high performance logic applications. However, a comprehensive assessment of 2D material based FETs has been lacking for high performance logic applications considering appropriate system level figure-of-merits (FOMs) e.g. delay, and energy-delay product. In this paper, we present guidelines for 2D material based FETs to meet sub-10 nm high performance logic requirements focusing on material requirement, device design, energy-delay optimization for the first time. We show the need for 2D materials with smaller effective mass in the transport direction and anisotropicity to meet the performance requirement for future technology nodes. We present novel device designs with one such 2D material (monolayer black-phosphorus) to keep Moore's alive for the HP logic in sub-5 nm gate length regime. With these device proposals we show that below 5 nm gate lengths 2D electrostatistics arising from gate stack design becomes more of a challenge than direct source-to-drain tunneling for 2D material-based FETs. Therefore, it is challenging to meet both delay and energy-delay requirement in sub-5 nm gate length regime without scaling both supply voltage (V DD ) and effective-oxide-thickness (EOT) below 0.5 V and 0.5 nm respectively.


Examining the mechanisms underlying contextual preference reversal: Comment on Trueblood, Brown, and Heathcote (2014).
Trueblood, Brown, and Heathcote (2014) provide a new model of multiattribute choice, which accounts for 3 contextual reversal effects (similarity, attraction and compromise). We review the details of the model and highlight some novel predictions. First, we show that the model works by setting a "fine balance" between 2 opposing factors that influence choice. As a result, small changes in the attributes of choice alternatives can disturb this balance. Second, we show that the model gives a partial account of the compromise effect. We describe a number of experiments that could distinguish the MLBA from other models of multiattribute choice.


Maternal and foetal vitamin B12 concentration at parturition among Nigerians.
Serum vitamin B12 concentrations were determined immediately after delivery among fifty healthy mothers and in cord blood of their newly delivered babies. The serum vitamin B12 concentrations of the infants were higher than those of their mothers and the ratio was approximately 2:1. The maternal serum vitamin B12 concentration was significantly higher than other maternal serum vitamin B12 concentration reported previously and the infant serum vitamin B12 level was also significantly higher than other infants studied in similar projects. These results suggest that the high serum vitamin B12 concentration reported among Nigerians is most probably due to both genetical and environmental factors coupled with some microbial synthesis in the gastro-intestinal tract after resuming a full adult diet.


Laparoscopic Retroperitoneal Nephron-Sparing Surgery Without Renal Artery Clamping with Preoperative Selective Arterial Embolization for Management of Right Renal Angiomyolipoma of Diameter 10 cm: A Case Report.
A 38-year-old female without the tuberous sclerosis complex was diagnosed with right renal angiomyolipoma of 10 cm in diameter. She underwent laparoscopic retroperitoneal nephron-sparing surgery without renal artery clamping with preoperative selective arterial embolization to avoid a significant risk of hemorrhage and the damage of the renal function during nephron-sparing surgery. The tumor was resected completely. The time taken to complete the procedure was 4 hours 11 minutes and blood loss was 780 mL. She was transfused 400 mL of autologous blood.


Properties of quantum systems via diagonalization of transition amplitudes. II. Systematic improvements of short-time propagation.
In this paper, building on a previous analysis [I. Vidanović, A. Bogojević, and A. Belić, preceding paper, Phys. Rev. E 80, 066705 (2009)] of exact diagonalization of the space-discretized evolution operator for the study of properties of nonrelativistic quantum systems, we present a substantial improvement to this method. We apply recently introduced effective action approach for obtaining short-time expansion of the propagator up to very high orders to calculate matrix elements of space-discretized evolution operator. This improves by many orders of magnitude previously used approximations for discretized matrix elements and allows us to numerically obtain large numbers of accurate energy eigenvalues and eigenstates using numerical diagonalization. We illustrate this approach on several one- and two-dimensional models. The quality of numerically calculated higher-order eigenstates is assessed by comparison with semiclassical cumulative density of states.


Validation of tissue microarray technology in vulvar cancer.
The aim of the study was to validate tissue microarray (TMA) for vulvar cancer by comparing immunohistochemical staining results of triplicate core biopsies on TMA with the results of full section analysis. The study material consisted of slides and selected tissue blocks from 40 patients with vulvar cancer. A TMA was constructed with 3 cores/case. Both the TMA and the slides were stained with the same antibodies against COX-2, Caspase-3, epidermal growth factor receptor, p16INK4, Cyclin D1, and Ki67. For COX-2, 2 different scoring systems were applied. Agreement in the readings between TMA and slides was expressed in total agreement and kappa. Expression patterns of antibodies can be reproduced on TMA with good reliability (kappa 0.68 to 0.75) for Ki-67, p16INK4, COX-2, Cyclin D1, and epidermal growth factor receptor in comparison with whole slides. For Caspase-3 agreement is only slight with a kappa of 0.40. The majority of discordant cases for COX-2 and Ki67 were negative on slide and positive on TMA. For epidermal growth factor receptor and Caspase-3 an opposite pattern was found. For COX-2, the use of an alternative scoring system resulted in a decrease of kappa from 0.68 to 0.21. Agreement between results on TMA and slides depends on the distribution of the protein in the cancer tissue and on the scoring system used.


Synthesis of biindolizines through highly regioselective palladium-catalyzed C-H functionalization.
Biindolizines were synthesized under mild conditions with excellent regioselectivity in high yields through palladium-catalyzed C-H functionalization of indolizines. Synthesis of a macrocyclic compound was also achieved via intramolecular double C-H functionalization.


Solitary percutaneous transhepatic biliary drainage tract metastasis after curative resection of perihilar cholangiocarcinoma: report of a case.
Percutaneous transhepatic biliary drainage (PTBD) has been widely used, but it has a potential risk of tumor spread along the catheter tract. We herein present a case of solitary PTBD tract metastasis after curative resection of perihilar cholangiocarcinoma. Initially, endoscopic nasobiliary drainage was done on a 65 year-old female patient, but the cholangitis did not resolve. Thus a PTBD catheter was inserted into the right posterior duct. Right portal vein embolization was also performed. Curative surgery including right hepatectomy and bile duct resection was performed 16 days after PTBD. After 12 months, serum CA19-9 had increased gradually without any symptoms. Finally, a small right pleural metastasis was found through strict tumor surveillance for 6 months. Chemoradiation therapy was performed, but there was no response to treatment. As the tumor progressed, she complained of severe dyspnea and finally died from tumor dissemination to the chest and bones 18 months after the first detection of PTBD tract recurrence and 36 months after surgery. No intra-abdominal recurrence was found until the terminal stage. This PTBD tract recurrence was attributed to the PTBD even though it was in place for only 16 days. Although such recurrence is rare, its risk should be taken into account during follow-up of patients who have received PTBD before.


Understanding attributional biases, emotions and self-esteem in 'poor me' paranoia: findings from an early psychosis sample.
Trower and Chadwick's (1995) theory of two types of paranoia ('poor me' and 'bad me') provides a framework for understanding the seemingly contradictory evidence on persecutory delusions. Paranoia has been argued to defend against low self-esteem, but people with persecutory delusions report high levels of emotional distress and, in some instances, low self-worth. The current study investigates attributions and emotions in a sample of people with early psychosis who have persecutory delusions. 'Poor me' paranoia has been found to be more frequent than 'bad me' paranoia in the early stages of psychosis. Anger and a tendency to blame other people are hypothesized to characterize 'poor me' paranoia. The study had a cross-sectional design. Twenty individuals with early psychosis, 21 clinical controls with depression and 32 healthy volunteers completed a thorough assessment of emotions and attributions. The 'poor me' paranoia group showed higher levels of anger, anxiety and depression than the non-clinical control group. Self-esteem and guilt were however preserved. A tendency to blame others but not themselves was characteristic of the 'poor me' paranoia group whereas people in the clinical control group tended to self-blame for failures. Anger, but not self-esteem, was associated with an attributional bias characterized by blaming other people instead of oneself. In conclusion, anger, a previously overlooked emotion in the study of persecutory delusions, warrants further attention. The other-directed nature of this emotion highlights the potential role of interpersonal schemas in understanding paranoia.