Individual heterogeneity in vital parameters and demographic stochasticity.
Most population models assume that individuals have equal opportunities for survival and reproduction, although many natural populations consist of individuals with different vital parameters that remain different over time. Individual heterogeneity in vital parameters, which may depend on age or stage, can alter many population characteristics compared with a homogeneous population, affecting both deterministic and stochastic properties of the population process. Demographic variance is an important parameter influenced by heterogeneity. However, whether heterogeneity leads to increased or decreased demographic variance has been an unresolved question, except for special cases. Here, we present a general stochastic matrix model for a heterogeneous population that allows us to examine effects of heterogeneity on population dynamics, even when the degree of heterogeneity depends on age. Using this model, we found that the demographic variance may increase, decrease, or remain unaltered compared with a homogeneous comparison model, depending on the vital parameter values and on how these are distributed among individuals at each time step. Furthermore, if the reproductive value is the same for all individuals, heterogeneity has no effect on the demographic variance. Thus, we provide a general theoretical framework for analyzing how individual heterogeneity caused by different biological mechanisms affects fluctuations of especially small populations.


[Experience with the Bogota bag technique for temporary abdominal closure].
The Bogota bag technique is a reliable method for open abdominal closure. The aim of this study was to describe our experience with this technique. We retrospectively evaluated our experience with the Bogota Bag technique between January 2000 and March 2006. Descriptive statistical techniques were applied and percentages and means were calculated. The Bogota bag technique was applied in 12 patients. The technique was the preferred closure system to prevent abdominal compartment syndrome in 11 patients (91.66%) and was required to treat abdominal compartment syndrome in one patient (8.34%). No complications occurred in relation to placement or withdrawal of the Bogota bag. There were no intestinal fistulas or intra-abdominal abscesses. The mean length of hospital stay was 46.33 days and the mean length of stay in the intensive care unit was 16.58 days. The survival rate was 41.66%. In our experience, the Bogota bag is a useful technique and is the preferred closure system to prevent or treat abdominal compartment syndrome. The high mortality rates described are due to the underlying diseases leading to open abdominal closure and not directly to the Bogota bag technique itself.


Computational analysis and mapping of novel open reading frames in influenza A viruses.
The influenza A virus contains 8 segmented genomic RNAs and was considered to encode 10 viral proteins until investigators identified the 11th viral protein, PB1-F2, which uses an alternative reading frame of the PB1 gene. The recently identified PB1-N40, PA-N155 and PA-N182 influenza A proteins have shown the potential for using a leaking ribosomal scanning mechanism to generate novel open reading frames (ORFs). These novel ORFs provide examples of the manner in which the influenza A virus expands its coding capacity by using overlapping reading frames. In this study, we performed a computational search, based on a ribosome scanning mechanism, on all influenza A coding sequences to identify possible forward-reading ORFs that could be translated into novel viral proteins. We specified that the translated products had a prevalence ≥5% to eliminate sporadic ORFs. A total of 1,982 ORFs were thus identified and presented in terms of their locations, lengths and Kozak sequence strengths. We further provided an abridged list of ORFs by requiring every candidate an upstream start codon (within the upstream third of the primary transcript), a strong Kozak consensus sequence and high prevalence (≥95% and ≥50% for in-frame and alternative-frame ORFs, respectively). The PB1-F2, PB1-N40, PA-N155 and PA-N182 proteins all fulfilled our filtering criteria. Subject to these three stringent settings, we additionally named 16 novel ORFs for all influenza A genomes except for HA and NA, for which 43 HA and 11 NA ORFs from their respective subtypes were also recognized.


Learning causal and predictive clinical practice guidelines from data.
Clinical practice guidelines (CPG) propose preventive, diagnostic and treatment strategies based on the best available evidence. CPG enable practice of evidencebased medicine and bring about standardization of healthcare delivery in a given hospital, region, country or the whole world. This study explores generation of guidelines from data using machine learning, causal discovery methods and the domain of high blood pressure as an example.


[Informed consent forms in medical practice: the results of a knowledge survey].
"Federico II" University of Naples Hospital Management's Staff considered 47 informed consent forms in order to evaluate quality and quantity of the information transmitted to patients. Every form, distinguished by procedure (surgical, pharmacological, anesthesiologic or related to blood transfusions) was evaluated for the accuracy and validity of information related to: diagnosis, prognosis, diagnostic and therapeutic opportunities, expected benefits, adverse-side effects, iatrogenic risks, privacy policy on personal data. The forms were judged by information completeness criteria "conformed" or "not conformed" with standards. Our analysis demonstrate that physicians often are unaware of legal and ethical topics related to constructing informed consent forms. They usually omit crucial information or would use strict technical language. So far, we conclude Hospital Management's Staff definitively has a role in improving informed consent forms by establishing guidelines and promoting ethical issues. Final result could be to deserve stronger patient confidence in medical institutions.


Factors driving changes in freshwater mussel (Bivalvia, Unionida) diversity and distribution in Peninsular Malaysia.
Freshwater mussels (Bivalvia, Unionida) fulfil important ecosystem functions and are one of the most threatened freshwater taxa globally. Knowledge of freshwater mussel diversity, distribution and ecology in Peninsular Malaysia is extremely poor, and the conservation status of half of the species presumed to occur in the region has yet to be assessed. We conducted the first comprehensive assessment of Peninsular Malaysia's freshwater mussels based on species presence/absence and environmental data collected from 155 sites spanning all major river catchments and diverse habitat types. Through an integrative morphological-molecular approach we recognised nine native and one widespread non-native species, i.e. Sinanodonta woodiana. Two species, i.e. Pilsbryoconcha compressa and Pseudodon cambodjensis, had not been previously recorded from Malaysia, which is likely a result of morphological misidentifications of historical records. Due to their restriction to single river catchments and declining distributions, Hyriopsis bialata, possibly endemic to Peninsular Malaysia, Ensidens ingallsianus, possibly already extinct in the peninsula, and Rectidens sumatrensis, particularly require conservation attention. Equally, the Pahang, the Perak and the north-western river catchments are of particular conservation value due to the presence of a globally unique freshwater mussel fauna. Statistical relationships of 15 water quality parameters and mussel presence/absence identified acidification and nutrient pollution (eutrophication) as the most important anthropogenic factors threatening freshwater mussel diversity in Peninsular Malaysia. These factors can be linked to atmospheric pollution, deforestation, oil-palm plantations and a lack of functioning waste water treatment, and could be mitigated by establishing riparian buffers and improving waste water treatment for rivers running through agricultural and residential land.


Corneal hydration control in Fuchs' dystrophy.
Corneal hydration control was tested in 22 patients with Fuchs' dystrophy, and eight subjects of similar age without the disease, by measuring the corneal thickness recovery from swelling induced by hypoxia or following overnight sleep. Measurement precision was enhanced by using a modified optical pachometer and conducting two test procedures which were analyzed by a coupled exponential model. We have identified three parameters of the recovery from corneal swelling which may be used to describe hydration control: percent recovery per hour (PRPH) (mean 25.4% for Fuchs' and 34.2% for normals), time for 95% of corneal thickness recovery (mean 10.2 hr for Fuchs' and 7.1 hr for normals), and the open-eye steady-state thickness (mean 562 microns for Fuchs' and 537 microns for normals.) A PRPH of 17.1%/hr was identified as the minimum below which the cornea could not regain its open-eye steady state during the entire day and approaches decompensation. Our test procedure quantifies the corneal hydration control mechanism and may provide a test of endothelial function which can be used to monitor the progression of Fuchs' disease and guide decisions related to corneal surgery.


Histopathology of the host response to Lewis lung carcinoma: modulation by pyran.
The growth and metastasis of sc transplanted Lewis lung carcinoma were inhibited in C57BL/6J mice by treatment with pyran copolymer. The mean volume of the tumors of pyran-treated animals was 15% that of the saline-treated controls at day 33 post transplantation. Thereafter, the carcinomas gradually increased in volume. Pulmonary metastasis was first observed histologically at day 28 after pyran treatment, compared to day 15 after saline administration. All saline-treated animals died by day 48, whereas 70% of those given pyran remained alive. Tumor necrosis was much more extensive in the lesions of pyran-treated mice. Although neutrophils and monocytes, but few lymphocytes, infiltrated the subcutaneous connective tissue above the neoplasms of animals receiving saline, few leukocytes were present in other connective tissue sites around the tumor. In contrast, treatment with pyran was characterized by a shift at an early interval from a predominance of neutrophils to a predominance of histiocytes and some lymphocytes in the connective tissue above and around the subcutaneous tumor. These cells were often closely associated with degenerate-appearing tumor cells. Additionally, activated macrophages removed from the peritoneal cavity of pyran-treated, tumor-bearing mice exhibited nonspecific cytotoxicity for tumor cells in vitro.


[Molecular-biological properties of blood lymphocytes of Hodgkin's lymphoma patients. Plausible possibility of treatment effect prognosis].
Hodgkin's lymphoma (HL) patients were investigated before and during chemical and radiation therapy. The properties of peripheral blood lymphocytes of the HL patients before treatment have been compared with healthy donors and the patients during the treatment. The genetic damage--frequency of cells with micronuclei (MN), the level of DNA single- and double-strand breaks (SSB and DSB), DNA-protein cross-links (DPC) have been studied. Biochemical and physiological parameters have been compared as well: the concentration of reactive oxygen species (ROS), the ability to the adaptive response induction. The radiosensitivity of lymphocytes in vitro exposed to the 1 Gy irradiation has also been determined (by MN test). It was shown that in Hodgkin's lymphoma patients' lymphocytes (in comparison with healthy donors) the frequency of cells with MN does not change, the level of SSBs and DSBs increases, the amount of DPC does not change, and ROS concentration (on average) significantly increases because of the part of the population that have high ROS content. The ROS concentration decreases to control level, the frequency of cells with MN increases, the level of DSBs does not change but the level of DPCs (which prevents the determination of DSB) increases in the patients during treatment. It was also discovered that lymphocyte radiosensitivity correlates with the MN cells frequency before treatment and the ROS concentration. These results make it possible to suppose that the high MN frequency and high ROS concentration in Hodgkin's lymphoma patient lymphocytes (before treatment) can serve as prognostic factors for the effectiveness of radio and chemical therapy.


Functional expression of system x(c)- is upregulated by asbestos but not crystalline silica in murine macrophages.
Inhalation of asbestos or silica is associated with chronic and progressive diseases, including fibrosis, cancer, and increased risk of systemic autoimmunity. Because there is a need for treatment options for these diseases, a better understanding of their mechanistic etiologies is essential. While oxidative stress in macrophages is an early consequence of these exposures, it may also serve as a signaling mechanism involved in downstream immune dysregulation. The system x(c)(-) exchange protein is induced by oxidative stress, and exchanges equimolor levels of extracellular cystine for intracellular glutamate. Cystine is subsequently reduced to cysteine, the rate-limiting precursor for glutathione synthesis. As the primary transporter responsible for cystine/glutamate exchange on macrophages, system x(c)- was hypothesized to be inducible in response to asbestos and silica, and to increase viability through protection from oxidative stress. When challenged with amphibole asbestos, but not crystalline silica, RAW 264.7 macrophages increased expression of xCT and the rate of cystine/glutamate exchange in sodium-free conditions. This upregulation was prevented with N-acetylcysteine, implicating oxidative stress. Cystine protected the macrophages from asbestos-induced oxidative stress and cell death, supporting the hypothesis that imported cystine was used for synthesis of cellular antioxidants. System x(c)(-) inhibitors, glutamate and S-4-carboxyphenylglycine ((S)-4-CPG), significantly increased oxidative stress and cell death of asbestos-treated macrophages. System x(c)(-) plays a critical role in survival of macrophages exposed to asbestos, but not silica. These data demonstrate a very early difference in the cellular response to these silicates that may have important downstream implications in the pathologic outcome of exposure.


A comparative study of the course-related family and financial problems of mature nursing students in Scotland and Australia.
This study reports a comparative survey of mature students undertaking pre-registration undergraduate nursing education in Australia and Scotland. The study aimed to explore comparisons between the course-related and course-related financial difficulties faced by mature students in two very different educational and funding systems. Financial stress is a predictor of both physical and mental health problems. A similar pattern of course-related problems were reported by both Australian and Scottish students with the exception that Scottish students experienced more problems with childcare and caring for elderly relatives. Course-related problems may be inherent in the nature of undergraduate nursing education although the relatively time-intensive nature of Scottish curricula may explain the childcare and elderly relatives difference. Scottish students reported higher overall financial-related problems but Australian students reported more problems with funding placements. These findings have implications for both curriculum designers and policy makers.


Are third-generation cephalosporins unavoidable for empirical therapy of community-acquired pneumonia in adult patients who require ICU admission? A retrospective study.
Third-generation cephalosporins (3GCs) are recommended for empirical antibiotic therapy of community-acquired pneumonia (CAP) in patients requiring ICU admission. However, their extensive use could promote the emergence of extended-spectrum beta-lactamases-producing Enterobacteriaceae. Our aim was to assess whether the use of 3GCs in patients with CAP requiring ICU admission was justified. We assessed all patients with CAP who required ICU admission during a 7-year period. We recorded empirical and definitive antibiotic therapies and susceptibility of causative pathogens. Amoxicillin, amoxicillin/clavulanate (A/C) susceptibilities as well as amikacin susceptibility of A/C-resistant strains were recorded. From January 2007 to March 2014, 391 patients were included in the study. Empirical 3GCs were used in 215 patients (55%). Among 267 patients with microbiologically documented CAP (68%), 241 received a beta-lactam as definitive therapy, and of those, 3CGs were chosen for 43 patients (18%). Amoxicillin or A/C was active against isolated pathogens in 159 patients (66%), while 39 patients (16%) required a beta-lactam with a broader spectrum than 3GCs. Ninety-four per cent of A/C-resistant strains were amikacin susceptible. In ICU patients with CAP, 3GCs given on an empirical basis are changed, according to microbiological documentation, for another beta-lactam in 82% of cases especially to A/C in the absence of resistance risk factor. In patients evidencing risk factors for A/C-resistant strains infection, 3GCs or antipseudomonal beta-lactams including carbapenem associated with amikacin in the most severe patients seem a relevant empirical antibiotic therapy. This strategy could decrease 3GCs' use.


Acanthamoeba Activates Macrophages Predominantly through Toll-Like Receptor 4- and MyD88-Dependent Mechanisms To Induce Interleukin-12 (IL-12) and IL-6.
Acanthamoeba castellanii is a ubiquitous free-living amoeba with a worldwide distribution that can occasionally infect humans, causing particularly severe infections in immunocompromised individuals. Dissecting the immunology of Acanthamoeba infections has been considered problematic due to the very low incidence of disease, despite the high exposure rates. While macrophages are acknowledged as playing a significant role in Acanthamoeba infections, little is known about how this facultative parasite influences macrophage activity. Therefore, in this study we investigated the effects of Acanthamoeba on the activation of resting macrophages. Consequently, murine bone marrow-derived macrophages were cocultured with trophozoites of either the laboratory Neff strain or a clinical isolate of A. castellaniiIn vitro real-time imaging demonstrated that trophozoites of both strains often established evanescent contact with macrophages. Both Acanthamoeba strains induced a proinflammatory macrophage phenotype characterized by the significant production of interleukin-12 (IL-12) and IL-6. However, macrophages cocultured with the clinical isolate of Acanthamoeba produced significantly less IL-12 and IL-6 than the Neff strain. The utilization of macrophages derived from MyD88-, TRIF-, Toll-like receptor 2 (TLR2)-, TLR4-, and TLR2/4-deficient mice indicated that Acanthamoeba-induced proinflammatory cytokine production was through MyD88-dependent, TRIF-independent, TLR4-induced events. This study shows for the first time the involvement of TLRs expressed on macrophages in the recognition of and response to Acanthamoeba trophozoites.


How can be best explain retrograde amnesia in human memory disorder?
I firstly consider general issues relating to our attempts to understand retrograde amnesia. Three main hypotheses are reviewed that have been proposed to account for retrograde amnesia. A theory is outlined to explain the dense autobiographical amnesia that is a focal phenomenon in some cases of severe head injury. This theory postulates that autobiographical retrieval requires the activation of a distributed network of cognitive operations, and that autobiographical amnesia results from the occurrence of multiple areas of pathology, distributed over both space and time.


m6A RNA Methylation Regulates the Self-Renewal and Tumorigenesis of Glioblastoma Stem Cells.
RNA modifications play critical roles in important biological processes. However, the functions of N6-methyladenosine (m6A) mRNA modification in cancer biology and cancer stem cells remain largely unknown. Here, we show that m6A mRNA modification is critical for glioblastoma stem cell (GSC) self-renewal and tumorigenesis. Knockdown of METTL3 or METTL14, key components of the RNA methyltransferase complex, dramatically promotes human GSC growth, self-renewal, and tumorigenesis. In contrast, overexpression of METTL3 or inhibition of the RNA demethylase FTO suppresses GSC growth and self-renewal. Moreover, inhibition of FTO suppresses tumor progression and prolongs lifespan of GSC-grafted mice substantially. m6A sequencing reveals that knockdown of METTL3 or METTL14 induced changes in mRNA m6A enrichment and altered mRNA expression of genes (e.g., ADAM19) with critical biological functions in GSCs. In summary, this study identifies the m6A mRNA methylation machinery as promising therapeutic targets for glioblastoma.


Neuronal apoptosis and protection: effects of nitric oxide and endoplasmic reticulum-related proteins.
This review presents recent findings with regard to the cellular and molecular mechanisms of neuronal apoptosis induced by cerebral ischemia/hypoxia. The protection of neuronal death by hypoxia-induced proteins in the endoplasmic reticulum (ER) is also reviewed. The excess amount of nitric oxide (NO) generated by inducible NO synthase (iNOS) up-regulated in response to ischemic stress causes neuronal apoptosis through following processes; 1) reduction in mitochondrial membrane potential, 2) release of cytochrome c from mitochondria, and 3) activation of caspase-9 and -3, although low concentrations of NO protect against neuronal death. In contrast, hypoxia induces expression of several proteins such as protein disulfide isomerase (PDI), ubiquilin and HRD1 in the endoplasmic reticulum (ER). PDI and ubiquilin are involved in the protection against neuronal apoptosis probably by interacting with each other and enhancing the effects of PDI as a molecular chaperon. HRD1 is also up-regulated by hypoxia in the ER and induces protection against hypoxia-induced neuronal apoptosis by activating the protein degradation system. The present review hopefully gives pertinent suggestions for further studies on the development of novel prophylactic/therapeutics for neuronal apoptosis-related diseases.


Oral Health Assessment of a Group of Children with Autism Disorder.
The aim of this research was to determine the oral status of a group of children with autism. An observational transversal study was carried out in 96 pediatric patients between the ages of 2 and 16 years old with a diagnosis of autism. The patients were assessed to determine the presence of caries with Index Caries (WHO criteria) and debris and calculus with the Simplified Oral Hygiene Index, as well as the type of diet they followed. It was established that 41.7% of the patients had caries, with the result of an index of DMFT= 0.96 and dmft =2.41. In terms of the periodontal health 59.4% suffered from calculus. The OHI-S was 3.4. Children with autism exhibited a higher caries prevalence in primary teeth than in permanents. They also presented poor hygiene and an extensive presence of calculus.


Novel Zn1-xMnxSe (x = 0.1-0.4) one-dimensional nanostructures: nanowires, zigzagged nanobelts, and toothed nanosaws.
Novel Zn1-xMnxSe one-dimensional nanostructures-straight nanowires (x = 0.1 and 0.3), zigzagged nanobelts (x = 0.4), and toothed nanosaws (x = 0.4)-were synthesized using the chemical vapor deposition method. They all consisted of single-crystalline wurtzite ZnSe crystals, irrespective of the Mn content. In particular, the nanosaws have a unique structure in which double-sided teeth are rooted in the nanowire core and bent so as to align as two parallel rows. The long axis is parallel to the [010] direction, and all of the teeth have the [0001] growth direction. The X-ray diffraction pattern confirms the formation of wurtzite ZnSe crystal and the decrease of the lattice constant owing to Mn doping. The Mn2+ emission at 2.1 eV (appeared below 100 K), originating from the d-d (4T1 --> 6A1) transition, proves the effective substitution of Mn2+ ions at the tetrahedral coordinate sites.


Internet gaming disorder: Inadequate diagnostic criteria wrapped in a constraining conceptual model.
Background and aims The paper "Chaos and confusion in DSM-5 diagnosis of Internet Gaming Disorder: Issues, concerns, and recommendations for clarity in the field" by Kuss, Griffiths, and Pontes (in press) critically examines the DSM-5 diagnostic criteria for Internet gaming disorder (IGD) and addresses the issue of whether IGD should be reconceptualized as gaming disorder, regardless of whether video games are played online or offline. This commentary provides additional critical perspectives on the concept of IGD. Methods The focus of this commentary is on the addiction model on which the concept of IGD is based, the nature of the DSM-5 criteria for IGD, and the inclusion of withdrawal symptoms and tolerance as the diagnostic criteria for IGD. Results The addiction framework on which the DSM-5 concept of IGD is based is not without problems and represents only one of multiple theoretical approaches to problematic gaming. The polythetic, non-hierarchical DSM-5 diagnostic criteria for IGD make the concept of IGD unacceptably heterogeneous. There is no support for maintaining withdrawal symptoms and tolerance as the diagnostic criteria for IGD without their substantial revision. Conclusions The addiction model of IGD is constraining and does not contribute to a better understanding of the various patterns of problematic gaming. The corresponding diagnostic criteria need a thorough overhaul, which should be based on a model of problematic gaming that can accommodate its disparate aspects.


The specificity and reproducibility of general Schallamach pattern on heel part of rubber outsole.
The Schallamach pattern is an acquired characteristic that is sometimes observed in crime scenes. However, the detailed pattern is not always visible, although its general pattern is still recognizable. To determine the discrimination power (DP) of the general Schallamach pattern (GSP), 55 outsoles worn by 33 volunteers were chosen for the experiment. Their prints were lifted after different intervals for six months using magnetic powder and self-adhesive lifters. After the prints were segmented into grids using Photoshop CS6, the presence/absence, angle, and density of the GSP were observed and measured in each grid. There were 18747 pairs of same-source samples among the 1447 dust impressions. An algorithm (weight combination of the presence/absence, angle, and density) was determined when a weight combination of the parameters considered recognized most of the same-source sample pairs. The results showed that the angles of the GSP on the left and right shoes were concentrated in the range [-5.5°, -20.43°] and [8.8°, 24.97°], respectively, and the DP was only 37.5%. With a simply optimized algorithm, the DP reached 54.82%, and the DP of sample pairs lifted within one day reached 79.04%. The study demonstrates that one can distinguish the Schallamach pattern on the heel part of the outsole without information regarding the presence/absence, angle, and density of patterns.


Turnover in humans of beta 2-microglobulin: the constant chain of HLA-antigens.
The turnover of beta 2-microglobulin, the common subunit of the HLA antigens, has been examined in normal subjects and in some patients with kidney disorders, multiple myeloma and rheumatoid arthritis. All patients displayed elevated serum levels of beta 2-microglobulin. The plasma disappearance curve of 125I-beta 2-microglobulin demonstrated that the protein has a rapid turnover (t 1/2 = 2.1 h; range 1.1-2.8 h) in normal persons and in patients with a normal glomerular filtration rate. In patients with kidney disorders the impaired renal filtration prolonged the turnover time and led to elevated serum levels of beta 2-microglobulin. Simultaneous measurements of 125I-beta 2-microglobulin in serum and urine allowed estimations of the beta 2-microglobulin net reabsorption in the renal tubuli. Two patients with renal disease reabsorbed 84% and 89%, respectively, of the beta 2-microglobulin filtered in the glomeruli. In normal persons the net reabsorption is close to 100%. In patients with normal kidney function increased serum levels of beta 2-microglobulin seem to be due to an increased synthetic rate of the protein as the elimination rate is normal. HLA antigen heavy chains in serum are present in smaller amounts than beta 2-microglobulin. The present data, therefore, suggest an imbalanced synthesis of the two chains.


Pathogenesis of subcortical visuo-spatial neglect. A HMPAO SPECT study.
The pathophysiology of neuropsychological disorders due to right deep-seated hemispheric lesions remains a debated point. We undertook this study to check the hypothesis according to which remote cortical dysfunction could be responsible for the occurrence of neglect. Twenty-eight patients presenting with a right-sided subcortical stroke were studied. A neuropsychological battery of tests suitable for assessment of possible visuo-spatial neglect was performed as well as HMPAO SPECT. Neglect was observed in 15 cases out of 28. The lesion's site (at CT and/or MRI) did not allow discrimination between patients without neglect and patients with neglect. The latter however could be distinguished from the former by the presence of a remote decrease in cortical blood flow in the right temporo-parietal region. By suggesting that cortical involvement is necessary for the occurrence of neglect, the results were interpreted according to a network approach in which subcortical neglect is attributed to a cortical deprivation from afferent input in the posterior part of the brain.


Review: The intersection of surfactant homeostasis and innate host defense of the lung: lessons from newborn infants.
The study of pulmonary surfactant, directed towards prevention and treatment of respiratory distress syndrome in preterm infants, led to the identification of novel proteins/genes that determine the synthesis, packaging, secretion, function, and catabolism of alveolar surfactant. The surfactant proteins, SP-A, SP-B, SP-C, and SP-D, and the surfactant lipid associated transporter, ABCA3, play critical roles in surfactant homeostasis. The study of their structure and function provided insight into a system that integrates the biophysical need to reduce surface tension in the alveoli and the innate host defenses required to maintain pulmonary structure and function after birth. Alveolar homeostasis depends on the intrinsic, multifunctional structures of the surfactant-associated proteins and the shared transcriptional regulatory modules that determine both the expression of genes involved in surfactant production as well as those critical for host defense. Identification of the surfactant proteins and the elucidation of the genetic networks regulating alveolar homeostasis have provided the basis for understanding and diagnosing rare and common pulmonary disorders, including respiratory distress syndrome, inherited disorders of surfactant homeostasis, and pulmonary alveolar proteinosis.


[Immobilization of Candida sp. lipase on resin D301].
We immobilized Candida sp. lipase onto seven kinds of industrial adsorption and ion exchange resins. By determining the activity of each immobilized enzyme, the weakly basic anionic exchange resin of D301 showed the best results for the immobilization of Candida sp. lipase. Comparing the scanning electron micrographs of D301 with Novozym 435 (immobilized Candida antarctica lipase B from Novo Nordisk Corp.), we selected D301 as a carrier for the immobilization of Candida sp. lipase. And we pretreated the resin D301 with the bifunctional agent glutaraldehyde and crosslinked it with Candida sp. lipase. The optimal conditions for the immobilization of Candida sp. lipase were as follows: 8 mL of the amount of 5% glutaraldehyde solution, five hours of the time pretreated D301 with glutaraldehyde, 1.0 g/L the concentration of Candida sp. lipase used, pH of the phosphate buffered, 6.0 and 10 hours of time for immobilization, respectively. The activity of immobilized enzyme was over 35 U/mg and the efficiency of immobilization was around 3.5 Ul(mg x h).


MG132 Attenuates the Replication of Classical Swine Fever Virus in vitro.
The 26S proteasome, in charge of intracellular protein degradation, plays significant roles in the modulation of various cellular activities as well as in the interplay between virus and host. However, studies about the relationship between 26S proteasome and classical swine fever virus (CSFV) is limited up to now. MG132 is a proteasome inhibitor and has been extensively used in studies about replication of many viruses. Herein, we investigated the role of MG132 in CSFV replication and results showed that MG132 significantly decreased virus titers and viral RNA copies in CSFV-infected PK-15 cells. Further studies demonstrated that MG132 upregulated the expression of several interferon-stimulated genes (ISGs), in CSFV-infected cells. Since the activation of ISGs is controlled by the JAK-STAT signal pathway, we next examined the effect of MG132 on the expression and localization of key molecular STAT1 in the infected cells using Western blot and confocal laser scanning microscopy, respectively. Results showed that CSFV infection and viral NS4A protein decreased the protein level of STAT1, and MG132 promoted the accumulation of STAT1 in the nucleus of cells adjacent to the CSFV-infected cells. Besides, MG132 did not affect the expressions of IFN-α, STAT1, Mx1, OAS1, and PKR genes in cells without CSFV. In conclusion, we identify that MG132 significantly inhibits CSFV replication in vitro, in which the activation of the JAK-STAT pathway and the subsequent upregulation of expressions of ISGs might play significant roles, providing a potential preventive method for CSF.


Cytochrome P450CAM enzymatic catalysis cycle: a quantum mechanics/molecular mechanics study.
The catalytic pathway of cytochrome P450cam is studied by means of a hybrid quantum mechanics/molecular mechanics method. Our results reveal an active role of the enzyme in the different catalytic steps. The protein initially controls the energy gap between the high- and low-spin states in the substrate binding process, allowing thermodynamic reduction by putidaredoxin reductase and molecular oxygen addition. A second electron reduction activates the delivery of protons to the active site through a selective interaction of Thr252 and the distal oxygen causing the O--O cleavage. Finally, the protein environment catalyzes the substrate hydrogen atom abstraction step with a remarkably low free energy barrier ( approximately 8 kcal/mol). Our results are consistent with the effect of mutations on the enzymatic efficacy and provide a satisfactory explanation for the experimental failure to trap the proposed catalytically competent species, a ferryl Fe(IV) heme.


Maternal Serum Angiogenic Profile and Its Correlations with Ultrasound Parameters and Perinatal Results in Normotensive and Preeclamptic Pregnancies Complicated by Fetal Growth Restriction.
FGR is a complication of pregnancy in which the fetus does not reach its programmed growth potential due to placental reasons and it is the single largest risk factor of stillbirth. Babies with FGR are at increased risk of mortality and morbidity not only in the perinatal period, but also in later life. FGR presents a huge challenge for obstetricians in terms of its detection and further monitoring of pregnancy. The ultrasound is the gold standard here; apart from assessing fetal weight, it is used to measure Doppler flows in maternal and fetal circulation. It seems that additional tests, like biochemical angiogenic factors measurement would be helpful in diagnosing FGR, identifying fetuses at risk and adjusting the surveillance model. The study aimed to assess the potential relationship between the concentration of sEng, sFlt-1, PlGF, and the sFlt-1/PlGF ratio in maternal serum at delivery and maternal and fetal Doppler flow measurements as well as perinatal outcomes in pregnancies complicated by FGR with and without PE, isolated PE cases and normal pregnancies. The use of angiogenic markers is promising not only in PE but also in FGR. Numerous correlations between ultrasound and Doppler studies, perinatal outcomes and disordered angiogenesis marker levels in maternal serum suggest that biochemical parameters have a great potential to be used as a complementary method to diagnose and monitor pregnancies with FGR. The, PlGF in particular, could play an outstanding role in this regard.


Evaluation of health-related quality of life for hypothesized medical states associated with cervical cancer.
When evaluating health-economics for cervical cancer prevention policies in Japan, it is important to use Japanese value settings. This study aimed to obtain preference-based measures (preference measures) for hypothesized health states among healthy Japanese women, and to examine differences between the EuroQol-5D (EQ-5D) and standard gamble (SG) instruments. The investigation was performed among female students at a nursing university. We used written hypothetical scenarios describing three grades of cervical intraepithelial neoplasia (CIN) and eight stages of cervical cancer, both at diagnosis and after medical intervention. Preference measures were evaluated using both EQ-5D and SG. We received responses from 136 women. The mean number of respondents per stage was 24.6 (SD: 2.7). At diagnosis, average EQ-5D scores for CIN1, CIN2, CIN3, IA1, IA2, IB1, IB2, IIA, IIB, III, and IV stages were 0.84 (0.14), 0.78 (0.12), 0.73 (0.10), 0.78 (0.12), 0.72 (0.12), 0.63 (0.13), 0.64 (0.12), 0.68 (0.08), 0.62 (0.13), 0.55 (0.21), and 0.18 (0.24), respectively. Using one-way analysis of variance with the Tukey-Kramer method for multiple comparisons (each stage vs. CIN1), we found significant differences for IB1 and more advanced stages (p<0.05). After medical intervention, corresponding EQ-5D scores were 0.84 (0.12), 0.81 (0.12), 0.84 (0.12), 0.80 (0.15), 0.78 (0.11), 0.64 (0.15), 0.63 (0.15), 0.71 (0.15), 0.50 (0.17), 0.52 (0.17), 0.21 (0.28). The multiple comparisons identified significant differences for IB1 and more advanced stages, excepting IIA (p<0.05). SG evaluations were more variable and relatively higher than EQ-5D evaluations. We obtained preference measures for three grades of CIN1-3 and eight stages of cervical cancer. In combination with appropriate sensitivity analyses, these preference measures will provide a basis for an economic evaluation of cervical cancer prevention in Japan. We suggest that EQ-5D is appropriate for cost-utility analysis of this topic.


Navicula sp. Sulfated Polysaccharide Gels Induced by Fe(III): Rheology and Microstructure.
A sulfated polysaccharide extracted from Navicula sp. presented a yield of 4.4 (% w/w dry biomass basis). Analysis of the polysaccharide using gas chromatography showed that this polysaccharide contained glucose (29%), galactose (21%), rhamnose (10%), xylose (5%) and mannose (4%). This polysaccharide presented an average molecular weight of 107 kDa. Scanning electron microscopy (SEM) micrographs showed that the lyophilized Navicula sp. polysaccharide is an amorphous solid with particles of irregular shapes and sharp angles. The polysaccharide at 1% (w/v) solution in water formed gels in the presence of 0.4% (w/v) FeCl₃, showing elastic and viscous moduli of 1 and 0.7 Pa, respectively. SEM analysis performed on the lyophilized gel showed a compact pore structure, with a pore size of approximately 150 nm. Very few studies on the gelation of sulfated polysaccharides using trivalent ions exist in the literature, and, to the best of our knowledge, this study is the first to describe the gelation of sulfated polysaccharides extracted from Navicula sp.


[Successful treatment of intravenous cyclophosphamide pulse therapy for lupus myelitis with urinary disturbance and acute confusional state].
A 18-year-old female had low grade fever, butterfly rush, proteinuria, leukocytopenia and hypocomplimentemia in 1988, and she was diagnosed as systemic lupus erythematosus (SLE) with lupus nephritis (WHOIIb). Treatments with prednisolone and mizoribine resulted in the remission for three years. In May 2001, she presented neurosis and polakisuria despite of the increase of prednisolone to 20 mg/day. Finally, she admitted in our hospital because of manic and repressive state and disorientaion. A brain MRI revealed high intensity lesions in bilateral basal ganglia in T2 weighted images, and cerebrospinal fluid showed elevated protein and IFN-alpha (421 IU/ml). In addition, she manifested neurogenic bladder, muscle weakness and hyperactive deep tendon reflex of bilateral lower limbs due to both supranuclear disorder and hypesthesia under the Th 10 level. Spinal MRI revealed marked atrophy and high intensity signals at the middle to lower thoracic spinal cord in T2 weighted images, indicating complication of lupus myelitis as well as cerebral involvement. Although the symptoms of CNS lupus did not respond to prednisolone, twelve monthly cyclophosphamide pulse therapy (IV-CY) has resolved urinary disturbance, muscle weakness and sensory loss, along with the improvement of both cerebral and spinal MRI images. Lupus myelitis and neurogenic bladder are the rare, but very refractory manifestation among CNS involvement of SLE. We here propose IV-CY as an invaluable choice for the treatment of not only active lupus myelitis but also neurogenic bladder resisted for steroid.


Establishment and characterization of an immortalized bovine glomerular endothelial cell line.
Bovine subcultures (second passage) of glomerular endothelial cells (GEN) isolated from one-year-old kidney were successfully transfected by recombinant plasmids containing the simian virus (SV)-40 T antigen (Tag) using a lipofectin-mediated procedure. One cell clone was selected, propagated and characterized. This clone can be grown in RPMI 1640 medium supplemented with 10% fetal calf serum. The advantage of this cell line is the cultivation of bovine GEN without the addition of fibroblast growth factor or a coating of fibronectin or gelatin on the culture plate. More than 80 passages were achieved and the doubling time was 32 h. The Tag was easily identified in transfected-GEN by indirect immunofluorescence. These cells weakly expressed factor VIII-related antigen, slightly took up acetylated-low density lipoprotein and secreted a detectable amount of angiotensin-converting enzyme. Immunocytochemical staining for UAE-1 was also positive. Moreover, oncoproteins, such as Ki-67 and p53, were expressed in these cells. Cell cycle analysis by flow cytometry revealed that the percentages of G1, S, and G2/M stages in cycling transfected-GEN culture in RPMI 1640 medium supplemented with 10% fetal calf serum were 34%, 52.9%, and 13.1%, respectively. The conditioned medium from confluent transfected-GEN stimulated [3H]thymidine incorporation into glomerular mesangial cells. This cell line may provide a useful tool for examining modulators of mesangial cell growth. Thus this cell line is the first immortalized bovine GEN that retain the morphologic, phenotypic, and functional characteristics of bovine GEN.


Sperm telomere length in motile sperm selection techniques: A qFISH approach.
Several studies have associated telomere shortening with alterations in reproductive function. The objective of the present study was to determine telomere length (TL) in spermatozoa selected by either density-gradient centrifugation (DGC) or swim-up. The analysis of TL was performed using quantitative fluorescent in situ hybridisation (qFISH) using PNA probes in combination with a chromatin decompaction protocol in sperm cells. Results of TL were 24.64 ± 5.00 Kb and 24.95 ± 4.60 Kb before and after DGC, respectively, and 19.59 ± 8.02 Kb and 20.22 ± 5.18 Kb before and after swim-up respectively. Sperm selected by DGC or swim-up did not show any significant differences in TL as compared to nonselected sperm (p > .05). Negative correlations between TL and sperm motility (r = -.308; p = .049) and concentration (r = -.353; p = .028) were found. Furthermore, exposure of sperm to increasing concentrations of hydrogen peroxide during incubation resulted in a reduction in TL. These data indicate that oxidative stress may be one of the main factors involved in the reduction of TL in sperm. Preliminary clinical results from patients included in this study indicate that TL was shorter in spermatozoa from couples who never achieved a pregnancy compared to couples who did achieve at least one natural pregnancy (p < .05); however, the clinical utility of this biomarker still needs to be confirmed in further studies.


A Campylobacter enteritis outbreak in a military base in Israel.
An outbreak of gastroenteritis due to Campylobacter jejuni occurred during a 2-day period in June 1982 in a military base in Israel. Of 22 patients with acute gastroenteritis examined at the unit's medical clinic, 17 were available for complete clinical evaluation. Stool cultures were taken from them as well as from 23 asymptomatic soldiers including food handlers. In 6 of the 17 patients with enteritis (35%) Campylobacter jejuni serotype 11 was isolated, while the stool cultures of all the asymptomatic soldiers were negative. A temporary food handler was the most probable source of the infection. He had suffered from symptoms of acute gastroenteritis prior to the outbreak but had not reported them, and was found to harbor the same Campylobacter serotype as the other patients.


Deficiency of the Immunoproteasome LMP10 Subunit Attenuates Angiotensin II-Induced Cardiac Hypertrophic Remodeling via Autophagic Degradation of gp130 and IGF1R.
Hypertensive cardiac hypertrophy is the leading cause of cardiac remodeling and heart failure. We recently demonstrated that the immunoproteasome, an inducible form of the constitutive proteasome, plays a critical role in regulating cardiovascular diseases. However, the role of the immunoproteasome LMP10 (β2i) catalytic subunit in the regulation of angiotensin II (Ang II)-induced cardiac hypertrophic remodeling remains unclear. Wild-type (WT) and LMP10 knockout (KO) mice were infused with Ang II 1,000 ng/kg/min for 2 weeks. Blood pressure was measured using a tail-cuff system. Cardiac function and hypertrophic remodeling were examined by echocardiography and histological staining. The expression levels of genes and proteins were examined with quantitative real-time PCR and immunoblotting analysis, respectively. LMP10 mRNA and protein expression was significantly increased in Ang II-stimulated hearts and primary cardiomyocytes. Moreover, Ang II infusion for 2 weeks increased systolic blood pressure, abnormal cardiac function, hypertrophy, fibrosis, and inflammation in WT mice, which were significantly reversed in KO mice. Moreover, a marked reduction in the protein levels of insulin growth factor-1 receptor (IGF1R), glycoprotein 130 (gp130), and phosphorylated AKT, mTOR, STAT3, and ERK1/2 and an increase in the LC3II/I ratio were also observed in LMP10 KO mice compared with WT mice after Ang II infusion. In vitro culture experiments confirmed that LMP10 knockdown activated autophagy and increased IGF1R and gp130 degradation, leading to the inhibition of cardiomyocyte hypertrophy. However, inhibiting autophagy with chloroquine reversed this effect. The results of this study indicate that LMP10 KO attenuates Ang II-induced cardiac hypertrophic remodeling via the autophagy-dependent degradation of IGF1R and gp130, and suggests that LMP10 may be a novel therapeutic target for hypertrophic heart diseases.


Discrepancy between cardiorespiratory system and skeletal muscle in elite cyclists after hypoxic training.
BACKGROUND: The purpose of this study was to determine the effects of hypoxic training on the cardiorespiratory system and skeletal muscle among well-trained endurance athletes in a randomized cross-over design. METHODS: Eight junior national level competitive cyclists were separated into two groups; Group A trained under normoxic condition (21% O2) for 2 hours/day, 3 days/week for 3 weeks while Group B used the same training protocol under hypoxic condition (15% O2). After 3 weeks of each initial training condition, five weeks of self-training under usual field conditions intervened before the training condition was switched from NT to HT in Group A, from HT to NT in Group B. The subjects were tested at sea level before and after each training period. O2 uptake (O2), blood samples, and muscle deoxygenation were measured during bicycle exercise test. RESULTS AND DISCUSSION: No changes in maximal workload, arterial O2 content, O2 at lactate threshold and O2max were observed before or after each training period. In contrast, deoxygenation change during submaximal exercise in the vastus lateralis was significantly higher at HT than NT (p < 0.01). In addition, half time of oxygenation recovery was significantly faster after HT (13.2 PlusMinus; 2.6 sec) than NT (18.8 PlusMinus; 2.7 sec) (p < 0.001). CONCLUSIONS: Three weeks of HT may not give an additional performance benefit at sea level for elite competitive cyclists, even though HT may induce some physiological adaptations on muscle tissue level.


New and known zoonotic nematode larvae within selected fish species from Queensland waters in Australia.
Zoonotic fish-borne nematodes are a significant and growing global health concern. However, in Australia their occurrence and geographical distribution are not well known. Moreton Bay in Queensland, Australia, is a popular tourist destination for domestic and international visitors where seafood is a popular food item. The aim of this study was to determine the occurrence of zoonotic nematodes within four commercially significant teleost fish species from Moreton Bay; Surf Bream, Sea Mullet, Yellow-Fin Tripod fish and Gold-Lined Sea Bream. Overall, 34.03% of fish examined (n = 144) were found to be a host to at least one parasitic nematode. The seasonal dynamics and prevalence of nematode infection was tested by statistical means. Results indicated a significant difference in seasonal infection for Surf Bream (p < 0.005) only. Several potentially zoonotic larval morphotypes were found, including Contracaecum types I and II, and Terranova type II (Family Anisakidae), and Hysterothylacium types VI and XIV and a new Hysterothylacium larval type herein assigned as type XVII (Family Raphidascarididae). ITS sequence data showed that some Contracaecum type II and Hysterothylacium types VI found in the present study are genetically distinct from those previously reported. The new genotypes were assigned to Contracaecum type II Genotype B and Hysterothylacium type VI, Genotypes B and C. This study provides essential information for future research on specific identification and differentiation of infective stages of zoonotic nematoda in edible fish.


Interactive Effects of Temperature and UV Radiation on Photosynthesis of Chlorella Strains from Polar, Temperate and Tropical Environments: Differential Impacts on Damage and Repair.
Global warming and ozone depletion, and the resulting increase of ultraviolet radiation (UVR), have far-reaching impacts on biota, especially affecting the algae that form the basis of the food webs in aquatic ecosystems. The aim of the present study was to investigate the interactive effects of temperature and UVR by comparing the photosynthetic responses of similar taxa of Chlorella from Antarctic (Chlorella UMACC 237), temperate (Chlorella vulgaris UMACC 248) and tropical (Chlorella vulgaris UMACC 001) environments. The cultures were exposed to three different treatments: photosynthetically active radiation (PAR; 400-700 nm), PAR plus ultraviolet-A (320-400 nm) radiation (PAR + UV-A) and PAR plus UV-A and ultraviolet-B (280-320 nm) radiation (PAR + UV-A + UV-B) for one hour in incubators set at different temperatures. The Antarctic Chlorella was exposed to 4, 14 and 20°C. The temperate Chlorella was exposed to 11, 18 and 25°C while the tropical Chlorella was exposed to 24, 28 and 30°C. A pulse-amplitude modulated (PAM) fluorometer was used to assess the photosynthetic response of microalgae. Parameters such as the photoadaptive index (Ek) and light harvesting efficiency (α) were determined from rapid light curves. The damage (k) and repair (r) rates were calculated from the decrease in ΦPSIIeff over time during exposure response curves where cells were exposed to the various combinations of PAR and UVR, and fitting the data to the Kok model. The results showed that UV-A caused much lower inhibition than UV-B in photosynthesis in all Chlorella isolates. The three isolates of Chlorella from different regions showed different trends in their photosynthesis responses under the combined effects of UVR (PAR + UV-A + UV-B) and temperature. In accordance with the noted strain-specific characteristics, we can conclude that the repair (r) mechanisms at higher temperatures were not sufficient to overcome damage caused by UVR in the Antarctic Chlorella strain, suggesting negative effects of global climate change on microalgae inhabiting (circum-) polar regions. For temperate and tropical strains of Chlorella, damage from UVR was independent of temperature but the repair constant increased with increasing temperature, implying an improved ability of these strains to recover from UVR stress under global warming.


Otogenic Meningitis: A Comparison of Diagnostic Performance of Surgery and Radiology.
Development of intracranial complications from middle ear infections might be difficult to diagnose. We compared radiological and surgical findings of 26 patients affected by otogenic meningitis. Results of our analysis showed that surgery is more reliable than imaging in revealing bone defects. Therefore, suggest that surgery be performed for diagnosis and eventual management of all cases of suspected otogenic meningitis.


Chemical Source Searching by Controlling a Wheeled Mobile Robot to Follow an Online Planned Route in Outdoor Field Environments.
In this paper, we present an estimation-based route planning (ERP) method for chemical source searching using a wheeled mobile robot and validate its effectiveness with outdoor field experiments. The ERP method plans a dynamic route for the robot to follow to search for a chemical source according to time-varying wind and an estimated chemical-patch path (C-PP), where C-PP is the historical trajectory of a chemical patch detected by the robot, and normally different from the chemical plume formed by the spatial distribution of all chemical patches previously released from the source. Owing to the limitations of normal gas sensors and actuation capability of ground mobile robots, it is quite hard for a single robot to directly trace the intermittent and rapidly swinging chemical plume resulting from the frequent and random changes of wind speed and direction in outdoor field environments. In these circumstances, tracking the C-PP originating from the chemical source back could help the robot approach the source. The proposed ERP method was tested in two different outdoor fields using a wheeled mobile robot. Experimental results indicate that the robot adapts to the time-varying airflow condition, arriving at the chemical source with an average success rate and approaching effectiveness of about 90% and 0.4~0.6, respectively.


Prelabour Rupture of Membranes among Pregnant Women Visiting a Tertiary Care Centre: A Descriptive Cross-sectional Study.
Prelabour rupture of membranes is a common obstetrics problem associated with maternal and perinatal morbidity and mortality. The exact cause is not known although various factors are found to be related to this condition. Hence, the objective of this study was to find out the prevalence of prelabour rupture of membranes among pregnant women in a tertiary care centre. This was a descriptive cross-sectional study conducted from 1 November 2021 to 30 November 2022. Ethical approval was taken from the Institutional Review Committee (Reference number: 2078/79/49). A structured proforma was filled out after taking a detailed history from each pregnant woman. Convenience sampling method was used. Point estimate and 99% Confidence Interval were calculated. Among 700 pregnant women, the prevalence of prelabour rupture of membranes was 56 (8%) (5.36-10.64, 99% Confidence Interval). Among them, 40 (71.43%) occurred in the term, while preterm (before 37 weeks) occurred in 16 (28.57%) of all pregnancies. Previous miscarriage occurred in 15 (26.78%) followed by gestational diabetes mellitus 8 (14.28%). The prevalence of prelabour rupture of membranes was found to be lower than other studies done in similar settings. miscarriage; oligohydramnios; prevalence.


Preconception Health Risk Factors in Women with and without a History of Military Service.
Given the increasing number of women service members and veterans of childbearing age, it is important to understand the preconception risks in this potentially vulnerable population. This study compared the prevalence of modifiable preconception risk factors among women with and without a history of service. Analyses included data from the 2013 and 2014 Centers for Disease Control and Prevention Behavioral Risk Factor Surveillance System. Preconception risk factors included health behaviors, chronic conditions, and mental health among women of childbearing age. Multivariate logistic regressions were used to compare the adjusted prevalence of each outcome among women with and without a history of service. Interaction terms assessed variation by age and history of service. Compared with women without a history of service, women with a history of service reported higher prevalence of insufficient sleep (49.6% vs. 36.3%; p < .001) and diagnosed depression (26.5% vs. 21.6%; p < .01). Women with a history of service were overall less likely to have obesity (19.8% vs. 26.5%; p < .001). Age-stratified results suggested that, compared with women without a history of service, women with a history of service were more likely to smoke in the 25 to 34 age group and reported comparable levels of obesity in the 35 to 44 age group. Women with a history of service demonstrated a preconception health profile that differs from women without a history of service. It is critical that providers are aware of their patients' military status and potential associated risks.


IPS Empress: a standard of excellence.
For 10 years, clinicians have been able to provide patients with a proven aesthetic and functional restoration that exhibits wear-compatibility, durability, and marginal integrity. This leucite-reinforced, pressed ceramic (IPS Empress, Ivoclar Williams, Amherst, NY) presents to patients and dentists the option of a metal-free alternative which retains the functional advantages of a porcelain-fused-to-metal restoration. This article illustrates the importance of sound laboratory communication in the utilization of this restorative material, focusing upon three aspects: midline and incisal edge inclination, elimination of open gingival embrasures, and incisal edge translucency. Techniques are also presented in order to efficiently communicate details of each case presented to the laboratory.


Frontal small craniostomy and irrigation for treatment of chronic subdural haematoma.
A new surgical method for the treatment of chronic subdural haematoma is presented. A small craniostomy is made on the superior lateral angle of the forehead just beneath the hair line without hair removal using a high-speed drill. Through this aperture, evacuation and irrigation of the haematoma can be carried out safely. No infections occurred in a series of patients treated in this way, and the recurrence rate was 10% (2/20). The surgical wound was negligible. Because of its simplicity, and the lack of a need for hair removal, the procedure appears to be acceptable as an optional therapeutic modality.


Impact of selective reporting of antimicrobial susceptibility testing report on clinicians' prescribing behavior of antibiotics.
Background: Selective reporting has important value in antibiotic management. The purpose of this study was to explore the impact of AST selective reporting on prescribing behavior, so as to provide evidence for the implementation and improvement of selective reporting policies in microbiology laboratories at home and abroad. Methods: A cross-sectional study was conducted in a teaching tertiary hospital in China in July 2021. We designed selective reports and routine reports for urinary tract infections caused by Escherichia coli and lower respiratory tract infections caused by Pseudomonas aeruginosa. Questionnaires were conducted among participants by case vignettes, and 116 valid questionnaires were collected. The appropriateness rate of antibiotic prescription and the prescription rate of drug-resistant antibiotics, cephalosporins, fluoroquinolones, and carbapenems were calculated and compared between the selective reporting group and the routine reporting group in each case. Results: In most cases, we found that AST selective reporting could increase the appropriateness rate of antibiotic prescription (p < 0.05) and reduce the drug-resistant antibiotic prescription rate (p < 0.01), cephalosporin drug prescription rate (p < 0.05) and fluoroquinolone drug prescription rate (p < 0.01). Although the difference in carbapenems prescription rate was not significant, selective reporting could reduce the number of its prescriptions to some extent. Conclusion: AST selective reporting can help promote the appropriate use of antibiotics and reduce the use of broad-spectrum antibiotics. It is suggested to develop scientific and effective selective reporting practices and strengthen the two-way communication between clinicians and microbiology laboratories, thereby enabling microbiology laboratories to play a more important role in clinical antimicrobial management.


Atomistic Chemical Elucidation of the Higher-Rate Reaction Mechanism in Hf-Pyridyl Amido-Catalyzed Copolymerization of Ethene and 1-Octene: Application of Red Moon Simulation with Polymer Propagation Diagrams.
The Hf-pyridyl amido complex ((pyridylamido)Hf(IV)) is a cationic catalyst activated by ion-pairing with auxiliary catalyst B(C6F5)4 to show high activity for α-olefin polymerization. Previously, it was experimentally observed that the consumption rate of 1-octene in the 1-octene/ethene copolymerization is 3-fold compared to the 1-octene homopolymerization in coordinative chain transfer polymerization using the catalyst HfCat+-B(C6F5)4- ion pair (IP) and the chain transfer agent (CTA) ZnEt2. In the present study, we have performed atomistic chemical simulations of the IP-catalyzed homopolymerization of 1-octene and copolymerization of 1-octene and ethene on the basis of the Red Moon (RM) methodology. Using the analysis by polymer propagation diagrams (PPDs), in the 1-octene homopolymerization and the 1-octene/ethene copolymerization with the 1-octene-inserted catalyst (oHfCat), it is theoretically shown that the propagation reactions intermittently pause due to the steric hindrance of two hexyl groups of the oHfCat and the 1-octene inserted adjacent to the Hf atom. On the other hand, in the polymerizations with the ethene-inserted catalyst (eHfCat), it is reasonably recognized that the propagation reactions occur smoothly at a constant rate, and the polymerization continuously proceeds due to the relatively smaller steric hindrance. In conclusion, it was shown, for the first time, that the RM method can be used to reveal the microscopic effects of monomers and substituents in the polymerization reaction processes. Therefore, our current work using PPDs demonstrates the promising potential of the RM methodology in studying catalytic olefin polymerizations and complex chemical reaction systems in general.


Symmetry Breaking in Side Chains Leading to Mixed Orientations and Improved Charge Transport in Isoindigo-alt-Bithiophene Based Polymer Thin Films.
The selection of side chains is important in design of conjugated polymers. It not only affects their intrinsic physical properties, but also has an impact on thin film morphologies. Recent reports suggested that a face-on/edge-on bimodal orientation observed in polymer thin films may be responsible for a three-dimensional (3D) charge transport and leads to dramatically improved mobility in donor-acceptor based conjugated polymers. To achieve a bimodal orientation in thin films has been seldom explored from the aspect of molecular design. Here, we demonstrate a design strategy involving the use of asymmetric side chains that enables an isoindigo-based polymer to adopt a distinct bimodal orientation, confirmed by the grazing incidence X-ray diffraction. As a result, the polymer presents an average high mobility of 3.8 ± 0.7 cm2 V-1 s-1 with a maximum value of 5.1 cm2 V-1 s-1, in comparison with 0.47 and 0.51 cm2 V-1 s-1 obtained from the two reference polymers. This study exemplifies a new strategy to develop the next generation polymers through understanding the property-structure relationship.


Joint Reconstruction Strategy for Structured Illumination Microscopy With Unknown Illuminations.
The blind structured illumination microscopy strategy proposed by Mudry et al. is fully re-founded in this paper, unveiling the central role of the sparsity of the illumination patterns in the mechanism that drives super-resolution in the method. A numerical analysis shows that the resolving power of the method can be further enhanced with optimized one-photon or two-photon speckle illuminations. A much improved numerical implementation is provided for the reconstruction problem under the image positivity constraint. This algorithm rests on a new preconditioned proximal iteration faster than existing solutions, paving the way to 3D and real-time 2D reconstruction.


Cellular protection during myocardial ischemia: the development and characterization of a procedure for the induction of reversible ischemic arrest.
An isolated perfused working rat heart model was used to investigate the extent to which various protective agents, used either singly or in combination, were able to increase the resistance of the heart to periods of transient ischemia. The aim of the studies was to develop a solution which, if infused into the coronary vessels just prior to the onset of ischemia, would rapidly induce arrest and would also counteract several of the deleterious cellular changes known to occur during myocardial ischemia. Agents with induce cardiac arrest, modify cellular ion loss, affect substrate utilization, energy production and energy stores, affect coronary vessel diameter and cell swelling, prevent dysrhythmias, and affect metabolic rate were investigated. The additive effects of these agents were evaluated. An aqueous solution was formulated which contained high concentrations of potassium and magnesium, in combination with adenosine triphosphate, creatine phosphate and procaine. This solution increased the recovery of the ischemic (37 degrees C for 30 min) rat heart from 0% to 93%. The safe period of ischemia could be further increased by the use of hypothermia.


Improved biological performance of magnesium by micro-arc oxidation.
Magnesium and its alloys have recently been used in the development of lightweight, biodegradable implant materials. However, the corrosion properties of magnesium limit its clinical application. The purpose of this study was to comprehensively evaluate the degradation behavior and biomechanical properties of magnesium materials treated with micro-arc oxidation (MAO), which is a new promising surface treatment for developing corrosion resistance in magnesium, and to provide a theoretical basis for its further optimization and clinical application. The degradation behavior of MAO-treated magnesium was studied systematically by immersion and electrochemical tests, and its biomechanical performance when exposed to simulated body fluids was evaluated by tensile tests. In addition, the cell toxicity of MAO-treated magnesium samples during the corrosion process was evaluated, and its biocompatibility was investigated under in vivo conditions. The results of this study showed that the oxide coating layers could elevate the corrosion potential of magnesium and reduce its degradation rate. In addition, the MAO-coated sample showed no cytotoxicity and more new bone was formed around it during in vivo degradation. MAO treatment could effectively enhance the corrosion resistance of the magnesium specimen and help to keep its original mechanical properties. The MAO-coated magnesium material had good cytocompatibility and biocompatibility. This technique has an advantage for developing novel implant materials and may potentially be used for future clinical applications.


Calcineurin, Calcium-Dependent Serine-Threonine Phosphatase Activation by Prion Peptide 106-126 Enhances Nuclear Factor-κB-Linked Proinflammatory Response through Autophagy Pathway.
Prion diseases are mortal neurodegenerative pathologies that are caused by the accumulation of abnormal prion protein (PrPSc) in the brain. Recent advances reveal that calcineurin may play a critical role in regulating nuclear factor kappa B (NF-κB) in the calcium-calmodulin pathway. However, the exact mechanism by calcineurin remains unclear. In the present study, we observed that the prion peptide induces calcineurin and autophagy activation. Also, NF-κB and proinflammatory cytokines like interleukin (IL)-6 and tumor necrosis factor (TNF)-α are upregulated upon exposure to prion peptide in human neuroblastoma. The results show that the prion peptide induces calcineurin activation, leading to the activation of NF-κB transcription factor via autophagy signaling. Expression of TNF-α and IL-6 was increased by calcineurin activation and blocked by calcineurin inhibitor and autophagy inhibitor treatments. Collectively, these findings indicate that calcineurin activation mediated by prion protein induces NF-κB-driven neuroinflammation via autophagy pathway, suggesting that calcineurin and autophagy may be possible therapeutic targets for neuroinflammation in neurodegeneration diseases including prion disease.


Lethal Giardia from a wild-caught sulphur-crested cockatoo (Cacatua galerita) established in vitro chronically infects mice.
An axenic culture of Giardia was established from a sample of infected intestine obtained following autopsy of a sulphur-crested cockatoo (Cacatua galerita). The cockatoo recently captured in the wild and with good muscle tone died along with several other cage mates, apparently of an overwhelming, acute infection of Giardia. Trophozoites which established in the traditional, axenic Giardia medium (TYI-S-33 with supplementary bile) were morphologically identical to G. duodenalis. When outbred Quackenbush Swiss neonatal mice were infected with trophozoites a chronic infection was established and parasites were still present at 38 days post-inoculation. Weight gain by infected mice was reduced by 20%, thus mimicking failure-to-thrive syndrome in children, and maximum parasite load was more than 3-fold higher in comparison with other G. duodenalis strains. Analysis of the electrophoretic karyotype, rDNA and hybridization studies together with Giemsa- and trichrome-stained samples, and scanning electron microscopy indicated that the bird-derived Giardia belonged to the duodenalis group. This is the first report of infection of mammals with Giardia isolated from a bird. These data may have potentially serious implications for contamination of watersheds and establishment of zoonotic infections.


Marketing principles and the future of preventive health care.
Whether preventive programs are advanced as complementary to therapy or as partial substitutes to lower costs, public resistance makes the cost effectiveness of these programs questionable. "Marketing" may be helpful in differentiating among the nature of products, services, and ideas of prevention, on the one hand, and heterogeneous consumer needs, attitudes, and responsibilities on the other. Making policy for marketing will involve new strategies and use of leverage: the "message' is not the only medium.


Development and preliminary validation of the Level of Care Index (LOCI) from the Personality Assessment Inventory (PAI) in a psychiatric sample.
Research over the last decade has been promising in terms of the incremental utility of psychometric tools in predicting important clinical outcomes, such as mental health service utilization and inpatient psychiatric hospitalization. The purpose of this study was to develop and validate a new Level of Care Index (LOCI) from the Personality Assessment Inventory (PAI). Logistic regression was initially used in a development sample (n = 253) of psychiatric patients to identify unique PAI indicators associated with inpatient (n = 75) as opposed to outpatient (n = 178) status. Five PAI variables were ultimately retained (Suicidal Ideation, Antisocial Personality-Stimulus Seeking, Paranoia-Persecution, Negative Impression Management, and Depression-Affective) and were then aggregated into a single LOCI and independently evaluated in a second validation sample (n = 252). Results indicated the LOCI effectively differentiated inpatients from outpatients after controlling for demographic variables and was significantly associated with both internalizing and externalizing risk factors for psychiatric admission (range of ds = 0.46 for history of arrests to 0.88 for history of suicidal ideation). The LOCI was additionally found to be meaningfully associated with measures of normal personality, performance-based tests of psychological functioning, and measures of neurocognitive (executive) functioning. The clinical implications of these findings and potential utility of the LOCI are discussed.


The need for national medical licensing examination in Saudi Arabia.
Medical education in Saudi Arabia is facing multiple challenges, including the rapid increase in the number of medical schools over a short period of time, the influx of foreign medical graduates to work in Saudi Arabia, the award of scholarships to hundreds of students to study medicine in various countries, and the absence of published national guidelines for minimal acceptable competencies of a medical graduate. We are arguing for the need for a Saudi national medical licensing examination that consists of two parts: Part I (Written) which tests the basic science and clinical knowledge and Part II (Objective Structured Clinical Examination) which tests the clinical skills and attitudes. We propose this examination to be mandated as a licensure requirement for practicing medicine in Saudi Arabia. The driving and hindering forces as well as the strengths and weaknesses of implementing the licensing examination are discussed in details in this debate.


Symposium in honor of Ralph L. Brinster celebrating 50 years of scientific breakthroughs.
The Symposium speakers comprised a distinguished group of scientists from North America, Europe and Asia. The Keynote address was presented by Michael Brown, Nobel Laureate in Physiology or Medicine (1985), and a plenary lecture was presented by John Gurdon, who within the next months would receive the Nobel Prize in Physiology or Medicine (2012). The first lecture in the series was presented by Richard Palmiter, Ralph's collaborator for more than 15 years, and he provided an overview of their work together followed by Richard's subsequent exciting contributions in the area of neurobiology. Seventeen lectures were presented over the two-day Symposium by distinguished scientists, including several of Ralph's former colleagues and students. The topics covered studies on germ cells, the germline, early embryos and their differentiation, as well as exciting and unpublished studies on stem cells and reprogramming. Many of the topics presented arose from foundation experiments in which Ralph participated, and these new developments indicate the dramatic progression of studies in this area. The Symposium program and the complete lectures can be found at the following link: www.vet.upenn.edu/BrinsterSymposium.


Systemic over-secretion of growth hormone in transgenic mice results in a specific pattern of skeletal modeling and adaptation.
The effects of growth hormone (GH) over-secretion on bone modeling and remodeling in transgenic mice were investigated using systematic and hierarchical methods. The results showed that continual systemic stimulation of GH over-secretion in mice resulted in an initial increase in bone mass, but its bone quality was not comparable with that of the littermate controls. Further continual over-stimulation of GH resulted in an increase in bone resorption leading to thinner cortices with inferior tissue mechanical properties. Three biological mechanisms following GH over-production are formulated to explain the observed results: GH over-secretion stimulated the production of inferior bone matrices, i.e., woven bone and cartilage, in addition to the production of normal lamellar bone; the increased bone formation stimulated by GH was followed by an exaggerated bone resorption process, resulting in cortical tissue with inferior mechanical properties; and a cortical shift occurred following GH over-stimulation that appeared to be caused by the combined effects of GH over-secretion and a variation in mechanical stimuli in the metallothionein-1 growth hormone regulating hormone transgenic mice. An "Optimal Strain Environment" model is proposed to help explain the observed results. From the results of the present and previous studies, we believe that the primary goal of bone adaptation to a biological perturbation, at least in mice, is to ensure proper mechanical function by maintaining structural integrity. In the process of maintaining a targeted whole bone structural integrity, the mechanical integrity of tissue may be sacrificed.


[Nail susceptibility to fungal infections in patients with hypothyroidism and hyperthyroidism].
Onychomycosis is a frequent disorder in adults. The objective of the study was evaluation of finger and toe nails susceptibility to Candida albicans and a dermatophyte Trichophyton mentagrophytes infection in patients with symptomatic hypothyroidism and hyperthyroidism as compared with healthy persons. The materials comprised finger and toe nails from 23 patients with hypothyroidism (in 8 cases postoperative, and in 15 cases caused by Hashimoto type thyroiditis), and from 27 patients with hyperthyroidism (including 17 cases of Graves-Basedow disease, and 10 with nodular goitre). Nails from 22 healthy persons of similar sex and age distribution served as controls. A significantly more frequent and more intensive than in control group toe nail infection with C. albicans was found in the patients with both hypothyroidism and hyperthyroidism. The enhanced toe nail susceptibility to C. albicans infection did not depend on autoimmunological aetiology of both hypothyroidism and hyperthyroidism.


Management of anemia in inflammatory bowel disease: a challenge in everyday clinical practice.
Anemia is the most common extraintestinal manifestation and complication of inflammatory bowel disease (IBD). Its etiology is multifactorial and mostly is a combination of iron deficiency anemia (IDA) and chronic anemia (ACD). Because of its high incidence in patients with IBD and its influence on their quality of life, regular screening is recommended. In case of IDA type of medication and route of administration should be determined by many factors such as general condition of the patient, IBD activity or anemia severity. Intravenous iron supplementation is the preferred route but may be associated with phosphate drop or even severe hypophosphatemia (HP). The mechanism of HP related to the intravenous iron infusions is not clearly known yet, but it might be related to the change of FGF-23 levels. What more not all parenteral forms of iron are equal and some may have a higher risk of HP than others.


Therapeutic uses of metronidazole and its side effects: an update.
Metronidazole is an antibiotic widely used in different medical conditions such as trichomoniasis, amoebiasis, and giardiasis among others. Its use has been associated with toxicity; however, it is not well characterized. In this review, we discuss the different therapeutic uses of metronidazole and its side effects in order to aid future investigation in this field. Relevant information, original research articles, clinical trials, and reviews were collected from PubMed to know the state of the art of the different therapeutic uses of metronidazole and the reported side effects. Metronidazole was used by the first time in 1959, to treat an infection caused by Trichomonas vaginalis; subsequently, new therapeutic properties were discovered. Nowadays, Metronidazole is used to treat infections caused by Bacteroides, Fusobacteria and Clostridia, rosacea, oral and dental infections, bone and joint infections, gynecologic infections, endocarditis, septicemia, and respiratory tract infections. It also can be used to treat Crohn´s disease or even like prophylaxis, before surgical procedures. Metronidazole is well tolerated with mild to moderate side effects such as nausea, abdominal pain, and diarrhea. Nevertheless, serious neurotoxicity, optic neuropathy, peripheral neuropathy, and encephalopathy have been reported in rare cases. Their genotoxic effects observed in animal models are controversial in humans. The therapeutic use of metronidazole had increased worldwide. Even though it is widely used, metronidazole has been associated with neurotoxicity and genotoxicity; however, its side effects are not well established. Conversely, its veterinary use is restricted in some countries because of its tumor association. Subsequently, further studies are needed to discover the secure use of metronidazole and describe new usages for this drug.


A systematic review and evidence-based analysis of ingredients in popular male testosterone and erectile dysfunction supplements.
The objective was to study available evidence for ingredients of popular over-the-counter testosterone and erectile dysfunction (ED) supplements. The top 16 male testosterone and 16 ED supplements in the USA were identified from the most popular online retailers: A1 Supplements, Amazon, Vitamin Shoppe, and Walmart. In total, 37 ingredients were identified and PUBMED online database was reviewed for randomized-controlled trials (RCT) studying their efficacy. Ingredients were categorized based on evidence quantity using an adapted version of the American Heart Association scoring system. In total, 16 ingredients from testosterone supplements and 21 from ED supplements were identified. Tribulus, Eurycoma longifolia, Zinc, L-arginine, Aspartate, Horny goat weed, and Yohimbine were most common. In all, 105 RCTs studying the identified ingredients were found. No whole supplement products have published RCT evidence. 19% of ingredients received an A grade for strong positive evidence with net positive evidence in two or more RCTs. In total, 68% received C or D grades for contradicting, negative, or lacking evidence. Overall, 69% of ingredients in testosterone supplements and 52% of ingredients in ED supplements have published RCT evidence. Many male supplements claim to improve testosterone or ED parameters; however, there is limited evidence, which should be considered when counseling patients.


The complete mitochondrial genome of the whiting, Merlangius merlangus and the haddock, Melanogrammus aeglefinus: a detailed genomic comparison among closely related species of the Gadidae family.
We determined the first complete mitochondrial DNA (mtDNA) sequences for the whiting (Merlangius merlangus, family Gadidae, order Gadiformes) and the haddock (Melanogrammus aeglefinus, family Gadidae, order Gadiformes). The entire mitogenomes were amplified and sequenced by primer walking using newly designed specific internal primers. Lengths were 16,569 and 16,585 bases for whiting and haddock respectively, lengths which lie within the range of previously reported gadiform sequences from Atlantic cod (Gadus morhua, 16,696 bases) and walleye pollock (Theragra chalcogramma, 16,570 bases). Gene arrangement in both species conformed to the order seen in most vertebrate mitochondrial genomes. We identified a long intergenic spacer located between the tRNA(Thr) and tRNA(Pro) genes (of 100 and 70 bp long for whiting and haddock, respectively), as previously described for other species of the order Gadiformes. Using nucleotide and amino acid divergence data of four complete gadoid mitogenomes (M. merlangius, M. aeglefinus, G. morhua and T. chalcogramma), we examined in detail the relative mtDNA mutation patterns across genes and among Gadidae species and tested for the performance of each protein-coding, transfer RNA and ribosomal RNA gene in depicting the expected phylogeny among the four species, as compared with the whole genome dataset. This comparison may be particularly useful in phylogenetic analyses of such a diverse fish family, as well as for the understanding of the patterns of nucleotide substitution of the mtDNA at low levels of divergence.


Early and midterm outcomes of hybrid first line treatment in patients with chronic limb threatening ischemia.
The aim of the study was to evaluate the outcome of first line hybrid treatment in patients with chronic limb threatening ischemia (CLTI) and to evaluate possible predictors of primary patency (PP) loss and limb clinical improvement (LCI). This was a retrospective non-randomized study. All patients underwent one-stage hybrid common femoral artery (CFA) endarterectomy combined with an inflow and/or outflow endovascular revascularization procedure. Demographic, clinical, and lesion characteristics for each patient were reported. Primary patency analysis was performed using Kaplan-Meier life tables, and univariate and multivariate analysis was used to assess possible predictors of PP loss and clinical improvement. Complete data were obtained from 132 patients. Patients were divided into two groups according to their Rutherford's category (RC), group 1 (Rutherford 4) and group 2 (Rutherford 5 and 6). Technical success was 98%. The overall surgical peri-operative complication rate was 8%. At a mean follow-up of 32 ± 23 months, the rate of major adverse limb events (MALE) was 30%; only the rate of major amputation between two groups was significant statistically different (p = .006). Group 1 had significantly lower amputation rate at 36 months (p = .01). The presence of high iliac peripheral artery calcium scoring system (PACCS) grade (HR 9.43, 95% CI 2.40-36.9, p = .001), the poor run-off of leg vessels (HR 0.15, 95% CI 0.02-0.92, p = .04), and undergoing CFA endarterectomy combined with outflow endovascular revascularization procedure (HR 4.25, 95% CI 1.07-16.89, p = .04) were independent predictors of PP loss, while severe iliac artery stenosis (OR 0.09, 95% CI 0.02-0.32, p = <.001) and the presence of pre-operative patent leg vessels (OR 8.03, 95% CI 2015-29.95, p = .002) were the significant independent predictors of LCI. The use of hybrid first line approach in patients with CLTI is a safe and feasible technique. From the analysis of the current study, it is clear that any effort should be made to achieve as many patency leg vessels as possible in order to obtain better and longer lasting clinical outcomes.


Effect of adalimumab on an enterocutaneous fistula in patients with Crohn's disease: a case series.
Crohn's disease (CD) is characterized by transmural inflammation of the gastrointestinal tract, which predisposes patients to the formation of a fistula. The efficacy of adalimumab (ADA) for an enterocutaneous fistula remains unclear. In this report, we present a case series of 3 patients with enterocutaneous fistulizing CD treated with ADA. ADA treatment achieved sustained complete fistula closure in one patient. The other two cases, which failed to achieve fistula closure, had intestinal stenosis and were not receiving concomitant azathioprine. Combination therapy with ADA and azathioprine may be a useful option and an alternative to surgery for enterocutaneous fistulizing CD.


Oscillations of chiral preference in proline clusters.
Ion mobility/mass spectrometry techniques are used to study the chiral preferences of small proline clusters (containing 2 to 23 proline monomers) produced by electrospray ionization. By varying the composition of the electrospray solution from enantiomerically pure (100% L or 100% D) to racemic (50:50 L:D), it is possible to delineate which cluster sizes prefer homochiral (resolved) or heterochiral (antiresolved) compositions. The results show a remarkable oscillation in chiral preference. Singly protonated clusters, [xPro+H](+) (where x corresponds to the number of prolines), favor homochiral assemblies (for x = 4, 6, 11 and 12); heterochiral structures are preferred (although the preferences are not as strong) for x = 5 and 7. Larger, doubly protonated clusters [xPro+2H](2+) favor homochiral assemblies for x = 18, 19, and 23 and heterochiral structures for x = 14, 16, 17, 20, 21, and 22. Some of the variations that are observed can be rationalized through simple structures that would lead to especially stable geometries. It is suggested that some antiresolved clusters, such as [22Pro+2H](2+), may be comprised of resolved D- and L-proline domains.


Treatment of Discoid Lupus Erythematosus with Upadacitinib: A Case Report.
Cutaneous lupus erythematosus (CLE) is a group of diseases within the spectrum of lupus that primarily manifests with skin lesions. Discoid lupus erythematosus (DLE) is the most common subtype of CLE. Currently, there is no specific medication available for the treatment of CLE. Here, we reported the efficacy and safety of upadacitinib, a JAK1 selective inhibitor, in treating one DLE patient for 28 weeks. Upadacitinib 15mg QD alone improved DLE lesions significantly, while reduction of the drug to 15mg QOD led to a relapse of the skin lesions. Upadacitinib showed favorable safety in this DLE patient in the 28-week period, except for acne, which was controlled by topical application of benzoyl peroxide gel. In this case, we observed rapid and sustained improvement of DLE lesions using upadacitinib with favorable safety, which provided the opportunity to use upadacitinib as an alternative therapy for DLE.


Sleeping patterns of Afghan unaccompanied asylum-seeking adolescents: a large observational study.
Unaccompanied asylum-seeking children (UASC) have experienced multiple traumas and are a high-risk group for posttraumatic stress disorder (PTSD). The effects of trauma are known to be associated with sleep problems; indeed sleeping problems are core features of PTSD. However, there has been no systematic research examining the sleep of this high risk group of children. This study presents the first evidence on the sleeping patterns of Afghan UASC living in the UK. A total of 222 male Afghan children, aged 13-18, were interviewed using validated self-report questionnaires measuring sleeping patterns and PTSD. Overall, UASC patterns for bed time and rise time appear acculturated to the country of asylum. Mean UASC sleep onset latency scores were approximately 20 minutes greater compared with normative scores, which may be a reflection of UASC pre-migration and post-migration experiences. As expected, UASC who screened above the clinical cut-off for PTSD reported significantly greater sleep onset latency, increased nightmares, and less total sleep time compared to the non-PTSD group. The results may be of particular interest to clinicians given that, compared to screening for PTSD, screening for sleep problems may be a less culturally disputed form of initial assessment indicating distress in UASC. Similarly, the field of UASC and refugee child interventions is largely focused on trauma, yet sleep may provide a novel avenue for equally or more effective treatment.


Studies of a molecular hourglass: synthesis and magnetic characterisation of a cyclic dodecanuclear {Cr10Cu2} complex.
The synthesis, structure, EPR, and magnetic studies of two dodecanuclear heterometallic cyclic clusters are reported. The compounds have the general formula [R(2)NH(2)](2)[Cr(10)Cu(2)F(14)(O(2)CCMe(3))(22)] (R=Me, 1 or iPr, 2). Both structures contain an array of metal centers which describe an approximate "hourglass", with an ammonium cation in the center of each half of the figure. The chromium sites are all six-coordinate, with the two copper sites five-coordinate. The majority of metal-metal edges are bridged by a single fluoride and two pivalate ligands, while two Cr--Cu edges are bridged by a single fluoride and a single pivalate. Magnetic studies show that 1 and 2 exhibit similar (but not identical) behavior, which can be attributed to ten antiferromagnetic and two ferromagnetic exchange interactions around the ring which gives an S=0 ground state. Quantum Monte Carlo calculations have been used to quantify the exchange interactions by successfully simulating the susceptibility for the full temperature range and thus clarifying the distinction between 1 and 2. EPR spectroscopy shows signals due to excited states, and a variable-temperature study has provided an estimate of the energy gap between the first excited state (S=1) and second excited state (S=2) for 1 that is consistent with the value obtained using the QMC method.


Practice Patterns and Perioperative Outcomes of Laparoscopic Pancreaticoduodenectomy in China: A Retrospective Multicenter Analysis of 1029 Patients.
The aim of the study was to analyze the outcomes of patients who have undergone laparoscopic pancreaticoduodenectomy (LPD) in China. LPD is being increasingly used worldwide, but an extensive, detailed, systematic, multicenter analysis of the procedure has not been performed. We retrospectively reviewed 1029 consecutive patients who had undergone LPD between January 2010 and August 2016 in China. Univariate and multivariate analyses of patient demographics, changes in outcome over time, technical learning curves, and the relationship between hospital or surgeon volume and patient outcomes were performed. Among the 1029 patients, 61 (5.93%) required conversion to laparotomy. The median operation time (OT) was 441.34 minutes, and the major complications occurred in 511 patients (49.66%). There were 21 deaths (2.43%) within 30 days, and a total of 61 (5.93%) within 90 days. Discounting the effects of the early learning phase, critical parameters improved significantly with surgeons' experience with the procedure. Univariate and multivariate analyses revealed that the pancreatic anastomosis technique, preoperative biliary drainage method, and total bilirubin were linked to several outcome measures, including OT, estimated intraoperative blood loss, and mortality. Multicenter analyses of the learning curve revealed 3 phases, with proficiency thresholds at 40 and 104 cases. Higher hospital, department, and surgeon volume, as well as surgeon experience with minimally invasive surgery, were associated with a lower risk of surgical failure. LPD is technically safe and feasible, with acceptable rates of morbidity and mortality. Nonetheless, long learning curves, low-volume hospitals, and surgical inexperience are associated with higher rates of complications and mortality.


Polarity-assisted formation of hollow-frame sheathed nitrogen-doped nanofibrous carbon for supercapacitors.
Heteroatom-doped carbon nanostructures with uniform size and morphology, well-designed architectures, and minimized interfacial resistance have been recognized as promising electrode materials for energy storage, but remain a crucial challenge. Herein, we develop a general approach of polarity-induced decoration of a monolayer sheath of metal-organic framework (MOF) particles with excellent uniformity in size and morphology on electrospun polymer nanofibers. These hybrid nanofibers are facilely converted into nitrogen-doped nanofibrous carbon (denoted as N-NFC) during pyrolysis. The thus-obtained N-NFC features (1) a one-dimensional nanofibrous structure with a highly conductive core, (2) a monolayer sheath of hollow carbon-frames with uniform size and morphology, (3) plenty of micro/mesopores with a highly accessible surface area, and (4) a high N-doping level, all of which guarantee its good electrochemical performance with a high capacitance of 387.3 F g-1 at 1 A g-1. In a solid-state supercapacitor, it delivers excellent rate capability (78.0 F g-1 at 0.2 A g-1 and 64.0 F g-1 at 1 A g-1), an enhanced energy density of 7.9 W h kg-1 at a power density of 219 W kg-1, and outstanding cycling stability with 90% capacity retained over 10 000 cycles at 1 A g-1.


Direct resin composites for 2002 and beyond.
Photocured resin composites have come a long way since they were introduced in the early 1970s. Advances have been made in many areas and many general dentists are placing these types of restorations routinely. On the horizon are tooth-colored materials that may not shrink and may be able to withstand destructive occlusal forces. Currently, though, prudent case selection with very judicious use of posterior composites in molars and avoiding occlusal stops on the restorations or margins is highly recommended.