Anterior pituitary hormone abnormalities following traumatic brain injury.
Traumatic brain injury (TBI) leads to approximately 100 hospitalizations per 100,000/year. Whereas diabetes insipidus is a well-known complication of TBI, anterior hypopituitarism as a consequence of TBI has been regarded as rare. More recent studies, however, suggest a prevalence of at least 30% of anterior pituitary dysfunction after TBI. Clinical signs of anterior hypopituitarism are often subtle and may be masked by sequalae of TBI. Therefore, post-traumatic anterior pituitary dysfunction may remain undiagnosed and, possibly, aggravate symptoms of brain injury. Moreover it may, if undiagnosed, lead to potentially fatal endocrine crises. This review updates clinical researchers, physicians, and other healthcare providers on the relationship between TBI and subsequent anterior pituitary insufficiency.


Grey and white matter atrophy 1 year after stroke aphasia.
Dynamic whole-brain changes occur following stroke, and not just in association with recovery. We tested the hypothesis that the presence of a specific behavioural deficit after stroke would be associated with structural decline (atrophy) in the brain regions supporting the affected function, by examining language deficits post-stroke. We quantified whole-brain structural volume changes longitudinally (3-12 months) in stroke participants with (N = 32) and without aphasia (N = 59) as assessed by the Token Test at 3 months post-stroke, compared with a healthy control group (N = 29). While no significant difference in language decline rates (change in Token Test scores from 3 to 12 months) was observed between groups and some participants in the aphasic group improved their scores, stroke participants with aphasia symptoms at 3 months showed significant atrophy (>2%, P = 0.0001) of the left inferior frontal gyrus not observed in either healthy control or non-aphasic groups over the 3-12 months period. We found significant group differences in the inferior frontal gyrus volume, accounting for age, sex, stroke severity at baseline, education and total intracranial volume (Bonferroni-corrected P = 0.0003). In a subset of participants (aphasic N = 14, non-aphasic N = 36, and healthy control N = 25) with available diffusion-weighted imaging data, we found significant atrophy in the corpus callosum and the left superior longitudinal fasciculus in the aphasic compared with the healthy control group. Language deficits at 3 months post-stroke are associated with accelerated structural decline specific to the left inferior frontal gyrus, highlighting that known functional brain reorganization underlying behavioural improvement may occur in parallel with atrophy of brain regions supporting the language function.


A programmable CRISPR/Cas9-based phage defense system for Escherichia coli BL21(DE3).
Escherichia coli BL21 is arguably the most popular host for industrial production of proteins, and industrial fermentations are often plagued by phage infections. The CRISPR/Cas system is guided by a gRNA to cleave a specific DNA cassette, which can be developed into a highly efficient programable phage defense system. In this work, we constructed a CRISPR/Cas system targeting multiple positions on the genome of T7 phage and found that the system increased the BL21's defense ability against phage infection. Furthermore, the targeted loci on phage genome played a critical role. For better control of expression of CRISPR/Cas9, various modes were tested, and the OD of the optimized strain BL21(pT7cas9, pT7-3gRNA, prfp) after 4 h of phage infection was significantly improved, reaching 2.0, which was similar to the control culture without phage infection. Although at later time points, the defensive ability of CRISPR/Cas9 systems were not as obvious as that at early time points. The viable cell count of the engineered strain in the presence of phage was only one order of magnitude lower than that of the strain with no infection, which further demonstrated the effectiveness of the CRISPR/Cas9 phage defense system. Finally, the engineered BL21 strain under phage attack expressed RFP protein at about 60% of the un-infected control, which was significantly higher than the parent BL21. In this work, we successfully constructed a programable CRISPR/Cas9 system to increase the ability of E. coli BL21's to defend against phage infection, and created a resistant protein expression host. This work provides a simple and feasible strategy for protecting industrial E. coli strains against phage infection.


Solvatochromic effect on the photoluminescence of MoS₂ monolayers.
The effect of surrounding solvents on the photoluminescence (PL) of MoS2 monolayers on Si/SiO2 substrates is studied. A redshift (up to -60 meV) is observed for MoS2 monolayers with nonhalogenated solvent surroundings. A blueshift (up to 60 meV) and intensity increase (2-50 times) are observed for monolayers with halogenated solvent surroundings.


Voluntary Exercise Prevents Oxidative Stress in the Brain of Phenylketonuria Mice.
High phenylalanine levels in phenylketonuria (PKU) have been associated with brain oxidative stress and amino acid imbalance. Exercise has been shown to improve brain function in hyperphenylalaninemia and neurodegenerative diseases. This study aimed to verify the effects of exercise on coordination and balance, plasma and brain amino acid levels, and brain oxidative stress markers in PKU mice. Twenty wild-type (WT) and 20 PAH(enu2) (PKU) C57BL/6 mice were placed in cages with (exercise, Exe) or without (sedentary, Sed) running wheels during 53 days. At day 43, a balance beam test was performed. Plasma and brain were collected for analyses of amino acid levels and the oxidative stress parameters superoxide dismutase (SOD) activity, sulfhydryl and reduced glutathione (GSH) contents, total radical-trapping antioxidant potential (TRAP), and total antioxidant reactivity (TAR). SedPKU showed poor coordination (p < 0.001) and balance (p < 0.001), higher plasma and brain phenylalanine (p < 0.001), and increased brain oxidative stress (p < 0.05) in comparison to SedWT. ExePKU animals ran less than ExeWT (p = 0.018). Although no improvement was seen in motor coordination and balance, exercise in PKU restored SOD, sulfhydryl content, and TRAP levels to controls. TAR levels were increased in ExePKU in comparison to SedPKU (p = 0.012). Exercise decreased plasma and brain glucogenic amino acids in ExePKU, but did not change plasma and brain phenylalanine in both WT and PKU. Exercise prevents oxidative stress in the brain of PKU mice without modifying phenylalanine levels. Hence, exercise positively affects the brain, demonstrating its value as an intervention to improve brain quality in PKU.


Endothelial colony forming units: are they a reliable marker of endothelial progenitor cell numbers?
Flow cytometry and cell culture, the two main laboratory techniques employed for counting endothelial progenitor cells (EPCs), have serious limitations. Mononuclear cells cultured in media favouring endothelial growth allow cells to replicate and differentiate/mature. EPCs under these circumstances tend to form groups of cells called endothelial colony forming units (EC-CFUs). EC-CFUs are widely accepted as a surrogate as an estimate of EPC number and function in cell culture. However, some important limitations may restrict the assumption that EC-CFUs reflect EPC numbers accurately. Our own experience of EPC culture in atrial fibrillation has demonstrated that: 1) the size of EC-CFUs and proportion of single cells fluctuate significantly, even on the same culture plate; 2) the ability of EPCs to migrate towards one another to form EC-CFUs varies; and 3) the rate of EPC differentiation and proliferation may significantly affect the number of EC-CFUs, despite similarities in EPC counts on separate plates. In contrast, the count of differentiated cultured EPCs by flow cytometry with specific mature endothelial markers (e.g. CD146, vascular endothelial (VE) cadherin) is a potentially more objective alternative. Endothelial CFU counts represent the cumulative characteristics of EPC quantity and their functional characteristics, and cannot be reliably used for the estimation of EPC numbers in peripheral blood or the bone marrow. Until stronger definition(s) of bone marrow or peripheral blood population(s) of EPCs are developed, flow cytometry may be the more optimal technique for EPC quantification.


Randomized controlled trial of emergency department initiated smoking cessation counselling and referral to a community counselling service.
Worldwide, tobacco smoke is still the leading cause of preventable morbidity and mortality. Many smokers develop chronic smoking-related conditions that require emergency department (ED) visits. However, best practices for ED smoking cessation counselling are still unclear. A randomized controlled trial was conducted to determine whether an "ask, advise, and refer" approach increases 12-month, 30-day quit rates in the stable adult ED smoking population compared to usual care. Patients in the intervention group were referred to a community counselling service that offers a quitline, a text-based program, and a Web-based program. Longitudinal intention-to-treat analyses were performed. From November 2011 to March 2013, 1,295 patients were enrolled from one academic tertiary care ED. Six hundred thirty-five were allocated to usual care, and 660 were allocated to intervention. Follow-up data were available for 70% of all patients at 12 months. There was no statistically significant difference in 12-month, 30-day quit rates between the two groups. However, there was a trend towards higher 7-day quit attempts, 7-day quit rates, and 30-day quit rates at 3, 6, and 12 months in the intervention group. In this study, there was a trend towards increased smoking cessation following referral to a community counselling service. There was no statistically significant difference. However, if ED smoking cessation efforts were to provide even a small positive effect, such an intervention may have a significant public health impact given the extensive reach of emergency physicians.


On the Challenges of Identifying Benthic Dominance on Anthropocene Coral Reefs.
The concept of dominance is frequently used to describe changes in rapidly reconfiguring ecosystems, but the definition of dominance can vary widely among studies. Using coral reefs as a model, we use extensive benthic composition data to explore how variability in applying dominance concepts can shape perceptions. We reveal that coral dominance is sensitive to the exclusion of key algal groups and the categorization of other benthic groups, with ramifications for detecting an ecosystem phase shift. For example, ignoring algal turf inflates the dominance of hard and soft corals in the benthic habitats underpinning reef ecosystems. We need a consensus on how dominance concepts are applied so that we can build a more comprehensive understanding of ecosystem shifts across a broad range of aquatic and terrestrial settings. For reefs, we highlight the benefits of comprehensive and inclusive surveys for evaluating and managing the altered ecosystem states that are emerging in the Anthropocene.


Interaction of Escherichia coli translation-initiation factor IF-1 with ribosomes.
The interaction between Escherichia coli translation-initiation factor IF-1 and ribosomes was studied in binding experiments by Airfuge centrifugation. IF-1 binds to the 30S, but not to the 50S, ribosomal subunit and its binding is strongly stimulated by IF-3 and IF-2, either alone or in combination. From the dependence of the Kd of the 30S-subunit--IF-1 complex on ionic strength, it can be concluded that IF-1 binds primarily via an ionic interaction, most likely with the 16S rRNA, with the minimum number of ion pairs involved being 2.7-3.6. The 30S-subunit--IF-1 interaction is unaffected by temperature changes between 11 degrees C and 44 degrees C and is thus accompanied by a negligible enthalpy change. It is concluded that the interaction is an entropy-driven process triggered mainly by the release of counter ions from the RNA phosphates. Titration of 30S-subunit--IF-1 complexes with 50S subunits causes the ejection of the factor indicating that IF-1 is released from the ribosomes during the subunit association step which marks the transition from a 30S-initiation-complex to a 70S initiation complex.


Nerve Coaptation Improves the Sensory Recovery of the Breast in DIEP Flap Breast Reconstruction.
Restoring the sensation of the reconstructed breast has increasingly become a goal of autologous breast reconstruction. The aim of this study was to analyze the sensory recovery of the breast and donor site of innervated compared to noninnervated deep inferior epigastric perforator (DIEP) flap breast reconstructions, to assess associated factors, and to compare the differences between preoperative and postoperative sensation. A prospective cohort study was conducted, including patients who underwent innervated or noninnervated DIEP flap breast reconstruction between August of 2016 and August of 2018. Nerve coaptation was performed to the anterior cutaneous branch of the third intercostal nerve. Preoperative and postoperative sensory testing of the breast and donor site was performed with Semmes-Weinstein monofilaments. A total of 67 patients with 94 innervated DIEP flaps and 58 patients with 80 noninnervated DIEP flaps were included. Nerve coaptation was significantly associated with lower mean monofilament values for the breast (-0.48; p < 0.001), whereas no significant differences were found for the donor site (-0.16; p = 0.161) of innervated compared to noninnervated DIEP flaps. Factors positively or negatively associated with sensory recovery of the breast and donor site were identified. Preoperative versus postoperative comparison demonstrated significantly superior sensory recovery of the breast in innervated flaps (adjusted difference, -0.48; p = 0.017). This study demonstrated that nerve coaptation in DIEP flap breast reconstruction significantly improved the sensory recovery of the breast compared to noninnervated flaps. The sensory recovery of the donor site was not compromised in innervated reconstructions. The results support the role of nerve coaptation in autologous breast reconstruction. Therapeutic, II.


Retinal identification based on an Improved Circular Gabor Filter and Scale Invariant Feature Transform.
Retinal identification based on retinal vasculatures in the retina provides the most secure and accurate means of authentication among biometrics and has primarily been used in combination with access control systems at high security facilities. Recently, there has been much interest in retina identification. As digital retina images always suffer from deformations, the Scale Invariant Feature Transform (SIFT), which is known for its distinctiveness and invariance for scale and rotation, has been introduced to retinal based identification. However, some shortcomings like the difficulty of feature extraction and mismatching exist in SIFT-based identification. To solve these problems, a novel preprocessing method based on the Improved Circular Gabor Transform (ICGF) is proposed. After further processing by the iterated spatial anisotropic smooth method, the number of uninformative SIFT keypoints is decreased dramatically. Tested on the VARIA and eight simulated retina databases combining rotation and scaling, the developed method presents promising results and shows robustness to rotations and scale changes.


Dual selection pressure by drugs and HLA class I-restricted immune responses on human immunodeficiency virus type 1 protease.
To determine the influence of human immunodeficiency virus type 1 (HIV-1)-specific CD8+ T cells on the development of drug resistance mutations in the HIV-1 protease, we analyzed protease sequences from viruses from a human leukocyte antigen class I (HLA class I)-typed cohort of 94 HIV-1-positive individuals. In univariate statistical analyses (Fisher's exact test), minor and major drug resistance mutations as well as drug-associated polymorphisms showed associations with HLA class I alleles. All correlations with P values of 0.05 or less were considered to be relevant without corrections for multiple tests. A subset of these observed correlations was experimentally validated by enzyme-linked immunospot assays, allowing the definition of 10 new epitopes recognized by CD8+ T cells from patients with the appropriate HLA class I type. Several drug resistance-associated mutations in the protease acted as escape mutations; however, cells from many patients were still able to generate CD8+ T cells targeting the escape mutants. This result presumably indicates the usage of different T-cell receptors by CD8+ T cells targeting these epitopes in these patients. Our results support a fundamental role for HLA class I-restricted immune responses in shaping the sequence of the HIV-1 protease in vivo. This role may have important clinical implications both for the understanding of drug resistance pathways and for the design of therapeutic vaccines targeting drug-resistant HIV-1.


Role of Ca²⁺ and ion channels in the regulation of apoptosis under hypoxia.
Hypoxia is a kind of common pathological condition existing in various diseases such as sleep apnea syndrome, myocardial infarction and stroke, which can precipitate the onset of diseases through inducing cell apoptosis. Ca²⁺ is the ubiquitous message in cell. Given the crucial role of Ca2²⁺ in physiology, intracellular Ca²⁺ overload is a significant regulator of apoptosis. Numerous experiments show that hypoxia may cause changes of multiple cellular Ca²⁺ channels, for instance, Na⁺/ Ca²⁺ Exchanger (NCX), L-type voltage dependent Ca²⁺ channel (L-VDCC), inositol triphosphate receptors (IP3R) and so on, which contribute to intracellular Ca²⁺ overload, thus eventually triggering cell apoptosis. However, the mechanisms underlying different Ca²⁺ channels involved in hypoxic apoptosis are complex. For example, chronic hypoxia or acute hypoxia may select different Ca²⁺ channels to influence cell apoptosis. In addition, intracellular Ca²⁺ overload may initiate different apoptotic pathways due to hypoxic duration. Furthermore, different locations in the cell of specific Ca²⁺ channels activated by hypoxia will determine different apoptosis signaling pathways. Moreover, activation of different Ca²⁺ channel isoforms will result in different outcomes of the cell under hypoxia. Hence, we aim to highlight the potential mechanisms of the main Ca²⁺ channels in regulation of apoptosis under hypoxic stress.


Assessment of factors impacting cervical cancer screening among low-income women living with HIV-AIDS.
Very little is currently known about factors impacting the prevalence of cervical cancer screening among women living with HIV-AIDS (WLHA). To better understand this issue, we surveyed low-income, medically underserved women receiving subsidized gynecologic care through an integrated HIV clinic. A self-administered questionnaire was completed by 209 women who self-identified as HIV positive. A total of 179 subjects (85.7%) reported having had a Pap test in the last three years. The majority of WLHA (95%) knew that the Pap test screens for cervical cancer. However, overall knowledge of cervical cancer risk factors, such as multiple sexual partners or sex with a man with multiple partners, was low (43% and 35%, respectively). Unscreened women were younger and more likely to be single with multiple current sexual partners. In multivariable analyses, the only factors associated with Pap testing were a woman's perception that her partner wants her to receive regular screening (aOR 4.64; 95% CI: 1.15-23.76; p = .04), number of clinic visits during the past year (aOR 1.36, 95% CI: 1.05-1.94; p = .04) and knowledge that the need for a Pap test does not depend on whether or not a woman is experiencing vaginal bleeding (aOR 6.52, 95% CI: 1.04-49.71; p = .05). We conclude that support from male partners in addition to effective contact with the health system and knowledge of cervical cancer risk factors influence Pap utilization among low-income WLHA. Future measures to improve the care for this population should increase knowledge of cervical cancer risk factors and encourage social support for cervical cancer screening among WLHA.


Enantioselective synthesis of indole-based unnatural β-Alkynyl α-amino acid derivatives via chiral phosphoric acid catalysis.
The synthesis of unnatural α-amino acid derivatives has attracted considerable interest in recent years, as they are ubiquitous in protein synthesis and peptide-based drug discovery. Herein, we reported the chiral phosphoric acid catalyzed asymmetric reaction of indoles with β,γ-alkynyl-α-imino esters for the enantioselective synthesis of unnatural indole-based α-amino acid derivatives. This asymmetric organocatalysis protocol enables efficient synthesis of unnatural α-amino acid derivatives with a tetrasubstituted stereogenic center and an alkyne moiety with up to 99% yield and 98% ee, resulting in operationally simple conditions, short reaction time, and broad substrate scope.


Diagnostic clues in the idiopathic pulmonary fibrosis of children.
Idiopathic pulmonary fibrosis (IPF) in children is a heterogeneous group of progressive disorders characterized by variable extents of inflammation and interstitial deposition of collagen fibers with numerous putative triggers. Children affected with this condition show breathlessness, non-productive cough and bibasilar/inspiratory dry rales. Diagnosis can be obtained by the exclusion of all known causes of fibrosing alveolitis such as neoplasms, toxic treatments, collagen vascular diseases, occupational exposure or granulomatous diseases.


"Columnlike" structure of the cross-sectional morphology of bulk heterojunction materials.
The cross-sectional morphology of the bulk heterojunction (BHJ) films comprising regio-regular poly(3-hexylthiophene) (rrP3HT) and [6,6]-phenyl-C61 butyric acid methyl ester (PCBM) was observed with transmission electron microscopy (TEM). The cross-sectional TEM images of the BHJ film provide information on the pathways for charge transport through the film thickness. The length scale of the phase separation was obtained from spatial Fourier transform analysis of the TEM images and from calculations of the autocorrelation function.


Effects of an Additional Liquid Based Cytology Prepate on Cytological Diagnosis in High-Risk HPV Positive, PaP Test Negative Cases.
To investigate the effects of a second cytology preparation on cytological diagnosis in high-risk HPV positive and PaP smear-negative cases. This retrospective study was conducted with 57 cases who underwent cytological evaluation and cotest in our center in 2016-2017. All of these cases were high-risk HPV positive, PaP smear-negative and had a second preparation. All preparations were re-evaluated by a cytopathologist and a pathologist. Twenty-five of the cases who had a positive diagnosis in the second preparation had a cervical biopsy. In 46 (80%) of the cases, the cytological diagnosis was the same and negative in the first and second preparations. Second preparations of 11 cases (19.2%) were positive. Twenty of 25 patients (77%) with cervical biopsy had premalignant lesion. In high-risk HPV positive and PaP smear-negative cases, patient management is different from cases where these two tests are positive together. According to our results, 19.2% of high-risk HPV positive and PaP smear-negative cases were given positive cytological diagnosis by second cytology preparation. Biopsy results support our cytological findings. The incidence of positive cytological diagnosis increases in PaP smear with the second preparation. With this protocol, patient management changes, follow-up time and number can be reduced.


Rapid learning of predictive maps with STDP and theta phase precession.
The predictive map hypothesis is a promising candidate principle for hippocampal function. A favoured formalisation of this hypothesis, called the successor representation, proposes that each place cell encodes the expected state occupancy of its target location in the near future. This predictive framework is supported by behavioural as well as electrophysiological evidence and has desirable consequences for both the generalisability and efficiency of reinforcement learning algorithms. However, it is unclear how the successor representation might be learnt in the brain. Error-driven temporal difference learning, commonly used to learn successor representations in artificial agents, is not known to be implemented in hippocampal networks. Instead, we demonstrate that spike-timing dependent plasticity (STDP), a form of Hebbian learning, acting on temporally compressed trajectories known as 'theta sweeps', is sufficient to rapidly learn a close approximation to the successor representation. The model is biologically plausible - it uses spiking neurons modulated by theta-band oscillations, diffuse and overlapping place cell-like state representations, and experimentally matched parameters. We show how this model maps onto known aspects of hippocampal circuitry and explains substantial variance in the temporal difference successor matrix, consequently giving rise to place cells that demonstrate experimentally observed successor representation-related phenomena including backwards expansion on a 1D track and elongation near walls in 2D. Finally, our model provides insight into the observed topographical ordering of place field sizes along the dorsal-ventral axis by showing this is necessary to prevent the detrimental mixing of larger place fields, which encode longer timescale successor representations, with more fine-grained predictions of spatial location.


Prevalence of human rhinovirus in children admitted to hospital with acute lower respiratory tract infections in Changsha, China.
Human rhinovirus (HRV) is a causative agent of acute respiratory tract infections. This study analyzed the prevalence and clinical characteristics of three HRV groups (HRV-A, -B, and -C) among 1,165 children aged 14 years or younger who were hospitalized with acute lower respiratory tract infection in China. PCR or reverse transcription-PCR was performed to detect 14 respiratory viruses in nasopharyngeal aspirates collected from September 2007 to August 2008 in Changsha, China. HRV was detected in 202 (17.3%) of the 1,165 children; 25.3% of the HRV-positive children were 13-36 months of age (χ(2) = 22.803, P = 0.000). HRV was detected year round and peaked between September and December. Fifty-three percent of the HRV-positive samples were also positive for other respiratory viruses; respiratory syncytial virus (RSV) was the most common secondary virus. Phylogenetic analysis using the VP4/VP2 region grouped the HRV-positive strains as follows: 101 HRV-A (50.0%), 21 HRV-B (10.4%), and 80 HRV-C (39.6%). HRV-A infections occurred predominantly in spring and autumn, and the peak prevalence of HRV-C was in early winter and late autumn. HRV-B infections were less common in spring (χ(2) = 31.914, P = 0.000). No significant difference in clinical severity or presentation was found between patients with HRV single infection and HRV co-detections. Furthermore, the clinical characterizations did not differ among the three HRV species. These results suggest that HRV-C is an important viral agent along with HRV-A and HRV-B and that among hospitalized children with acute lower respiratory tract infection in China, the three HRV genotypes have similar clinical characteristics.


Tracheal resection for critical tracheal occlusion due to intraluminal tumour.
Anaesthesia for tracheal resection requires careful planning by an experienced team. We report a case of urgent tracheal resection for a vascular tumor in a 41-year-old man who was a heavy smoker The tumour occupied most of his trachea. A CT reconstruction of the tumor assisted in planning. Perioperative tracheal laser therapy and cardiopulmonary bypass were not used due to concerns about excessive bleeding. Intraoperative airway management involved an upper endotracheal tube placed by the anaesthetist and a second, lower, endotracheal tube placed by the surgeon. The existing evidence for anaesthesia management of tracheal resection is currently limited to case reports. This case illustrates how preoperative imaging and careful planning can lead to a successful outcome, despite the potentially life-threatening nature of the pathology and the surgery.


Role of human salivary enzymes in bitter taste perception.
The molecules that elicit taste sensation are perceived by interacting with the taste receptors located in the taste buds. Enzymes involved in the detoxification processes are found in saliva as well as in type II cells, where taste receptors, including bitter taste receptors, are located. These enzymes are known to interact with a large panel of molecules. To explore a possible link between these enzymes and bitter taste perception, we demonstrate that salivary glutathione transferases (GSTA1 and GSTP1) can metabolize bitter molecules. To support these abilities, we solve three X-ray structures of these enzymes in complexes with isothiocyanates. Salivary GSTA1 and GSTP1 are expressed in a large panel of subjects. Additionally, GSTA1 levels in the saliva of people suffering from taste disorders are significantly lower than those in the saliva of the control group.


An atom interferometer inside a hollow-core photonic crystal fiber.
Coherent interactions between electromagnetic and matter waves lie at the heart of quantum science and technology. However, the diffraction nature of light has limited the scalability of many atom-light-based quantum systems. We use the optical fields in a hollow-core photonic crystal fiber to spatially split, reflect, and recombine a coherent superposition state of free-falling 85Rb atoms to realize an inertia-sensitive atom interferometer. The interferometer operates over a diffraction-free distance, and the contrasts and phase shifts at different distances agree within one standard error. The integration of phase coherent photonic and quantum systems here shows great promise to advance the capability of atom interferometers in the field of precision measurement and quantum sensing with miniature design of apparatus and high efficiency of laser power consumption.


Symptom patterns in unipolar and bipolar depression correlating with monoamine metabolites in the cerebrospinal fluid: II. Suicide.
Suicidality scores from the Schedule for Affective Disorders and Schizophrenia on 21 unipolar and 12 bipolar depressives were correlated with monoamine metabolites in the cerebrospinal fluid using multiple regression analyses. The single item of Suicidal Tendencies Worst Week correlated highly significantly and negatively with 3-methoxy-4-hydroxyphenylglycol (MHPG) and only to a very slight degree with 5-hydroxyindoleacetic acid (5HIAA). Seriousness of Intent of Worst Suicide Attempt earlier in life correlated significantly and negatively with both MHPG and 5HIAA. Subjective Anger was positively and Overt Anger negatively associated with thoughts of suicide. The results support earlier reports that depressives with low 5HIAA are prone to violent suicides, but also point to the equal, if not even greater involvement of MHPG and noradrenergic neuronal systems in carrying out a wish for death.


Additional balloon aortic valvuloplasty to overcome the difficult removal of a self-expandable transcatheter aortic valve system due to valve infolding.
Transcatheter aortic valve replacement (TAVR) is a well-established treatment for severe aortic stenosis. Advances in the devices used and operators' technique have reduced the frequency of complications. However, valve infolding is a rare but serious outcome after the implantation of self-expanding prostheses. We report a case of a successful bailout of a device that was difficult to remove because of valve infolding. TAVR using a 26 mm Evolut PRO+ system (Medtronic) was planned for a 91-year-old woman with severe aortic stenosis. After the valve was deployed in a satisfactory position on the second release, the system could not be removed because the nose cone was hooked to the basal frame of the deployed valve. To overcome this situation, an additional balloon was inserted from the contralateral femoral side and inflated, and we extracted the system successfully by pulling out the device while simultaneously deflating the balloon. Postoperative computed tomography revealed valve infolding, which was considered to cause the difficulty in system removal. Infoldings of self-expandable prostheses should be considered when faced with difficulty in removing the catheter system, and the method elucidated in this case report can be effective to manage it.


Effects of chronic cocaine, morphine and methamphetamine on the mobility, immobility and stereotyped behaviors in crayfish.
The worth of crayfish as a model system for studies of addiction was not previously recognized because a drug-reward phenomenon had not been documented in this model system. In our previous experiments, we demonstrate that the crayfish natural reward pathways are sensitive to human drugs of abuse. This finding supports crayfish as a suitable model to characterize specific behaviors that are relevant in drug addiction research, and the current study builds on our previous findings. The aim of the present study was to investigate unconditioned neurobehavioral effects of repeated treatment regimens using cocaine, morphine, and methamphetamine for three consecutive days. We analyzed mobility, immobility and characterized stereotypic behaviors following intracardial infusions of 2.0μg/g or 10.0μg/g doses of cocaine, morphine, and methamphetamine for three days. The results showed that systemic cocaine, morphine, and methamphetamine increased mobility at a low dose of 2.0μg/g more effectively than a high dose of 10.0μg/g, while simultaneously showing that the high dose exerted a more prominent effect in increasing immobility. Moreover, systemic cocaine, morphine, and methamphetamine injections have discerning effects towards a group of defined unconditioned stereotyped behavioral patterns associated with each drug, rather than a shared universal behavioral effect. These findings provide insight into the behavioral and pharmacological basis responsible for the unconditioned effects of these drugs in crayfish.


A Survey on Current Practice of Management of Early Onset Neonatal Sepsis.
It was a survey type of cross sectional study where the participants were from different teaching/referral hospital across the country and was done to gather information regarding current practice of management of neonatal sepsis among paediatricians and neonatologists and was conducted on the spot during a national conference of Bangladesh Perinatal Society in December 2013. Specialists in neonatology, paediatrics, and some other disciplines working in different institutes across the country were requested to respond. Out of 150 physicians, 92 (61.33%) were neonatologists. Physicians suspected early onset neonatal sepsis (EONS) when there is history suggestive of prolonged rupture of membrane (74.77%), prolonged labour (9.33%), chorioamnionitis (7.33%) and maternal fever (2%). Clinical sepsis is found commonly (53.33%) which is later proved by laboratory evidences such as Hb%, TC, DC PBF (peripheral blood film), C-reactive protein, chest X-ray etc. Injection Ampicillin and Gentamycin are still the first choice of antibiotics (61.3%). Preferred route was intravenous (95.3%). Antibiotics were given for 7-10 days by most of the physicians (48.77%). However there is lack of uniformity among the participants in regard to taking decision about antibiotics, the choice of first line and the subsequent options of antibiotics. So, neonatal sepsis is the most important cause of neonatal mortality in the community. Therefore a standard protocolized approach for diagnosis and management of Early Onset Neonatal Sepsis may prove critical which is currently not in practice uniformly.


Secondary neoplasms as a consequence of transplantation and cancer therapy.
A complication of various therapies is an increased incidence of cancers. We present data on 3117 types of cancer that developed in 2915 immunosuppressed organ-transplant recipients. The predominant tumors are lymphomas, skin and lip carcinomas, vulvar and perineal carcinomas, in situ uterine-cervical carcinomas, and Kaposi's sarcoma (KS). Tumors appear a relatively short time after transplantation, the earliest being KS at an average of 23 months and the latest vulvar and perineal cancers presenting an average of 98 months after transplantation. Cytotoxic drugs given to cancer patients may cause secondary neoplasms either by a direct carcinogenic effect or, indirectly, through depression of immunity. The most common secondary malignancies are leukemias, lymphomas, and bladder carcinomas. Ionizing radiation causes cancer, either by a direct carcinogenic effect on cells in the radiation field, or indirectly by depressing immunity. The most common malignancies are leukemias and bone sarcomas.


Behavioural development and mental health in infancy: object retrieval.
In order to assess poor mental development, we must be aware of the normal development against which to measure up what is supposed to be delayed, deviant or malfunctioning. Experimental Child Psychology has traced parameters of the developing cognitive system of the infant which are important factors that influence the configuration of a normally balanced, or equilibrated, composition of intelligence in later life. The Developmental Neuroscience approach gives a scientific explanation to what parents might experience as unresponsiveness, lack of distress and rage control, or excessive clinging of a demanding child.


A spectrophotometric method for the determination of heparan sulfate.
A simple and reliable spectrophotometric method for the determination of heparan sulfate is described. The method is based on the 1,9-dimethylmethylene blue assay for sulfated glycosaminoglycans. Addition of bovine serum albumin, together with a specific NaCl concentration and pH, results in a specific decrease of heparan sulfate-based absorbance. The amount of heparan sulfate can be calculated by subtracting the values obtained in the presence of albumin from those obtained in its absence. The sensitivity is 0.5 microgram heparan sulfate. Two applications are given: the quantification of heparan sulfate in urine, including urine from patients with mucopolysaccharidosis, and the evaluation of fractions from gel filtration and ion exchange column chromatography for isolation of heparan sulfate proteoglycans.


Radiology training in United Kingdom: current status.
Clinical radiology has always been one of the most competitive specialties in UK. Due to the increasing demand for radiology services the number of training posts in the UK has been increased. Clinical radiology training takes 5 years and requires completion of the Fellowship of Royal College of Radiologists (FRCR) exams, adequate evidence to demonstrate completion of the curriculum and successful appraisals. On completing training and receiving the Certificate for Completion of Training (CCT) a select proportion of trainees choose to embark on a fellowship program. This gives trainees the opportunity to further develop their subspecialty interest generating a high level of confidence in diagnostic and procedural skills.


Robert Neumann: a pioneer in periodontal flap surgery.
The contributions of Robert Neumann to the development of periodontal flap surgery are acknowledged. Neumann, born in 1882 was the leader of the Berlin group of dentists who advocated "the radical surgical treatment of pyorrhea". This approach was widely reported in European journals and sometimes referred to as the "Neumann operation". A biographical sketch and detailed descriptions of his operative procedures are included. Some of the historical background surrounding the priority question in the development of flap surgery is outlined.


Effects of ethanol on protein kinase C alpha activity induced by association with Rho GTPases.
Previous studies have shown that n-alkanols have biphasic chain length-dependent effects on protein kinase C (PKC) activity induced by association with membranes or with filamentous actin [Slater, S. J., et al. (1997) J. Biol. Chem. 272, 6167-6173; Slater, S. J., et al. (2001) Biochim. Biophys. Acta 1544, 207-216]. Recently, we showed that PKCalpha is also activated by a direct membrane lipid-independent interaction with Rho GTPases. Here, the effects of ethanol and 1-hexanol on Rho GTPase-induced activity were investigated using an in vitro assay system to provide further insight into the mechanism of the effects of n-alkanols on PKC activity. Both ethanol and 1-hexanol were found to have two competing concentration-dependent effects on the Ca(2+)- and phorbol ester- or diacylglycerol-dependent activities of PKCalpha associated with either RhoA or Cdc42, consisting of a potentiation at low alcohol levels and an attenuation of activity at higher levels. Measurements of the Ca(2+), phorbol ester, and diacylglycerol concentration-response curves for Cdc42-induced activation indicated that the activating effect corresponded to a shift in the midpoints of each of the curves to lower activator concentrations, while the attenuating effect corresponded to a decrease in the level of activity induced by maximal activator levels. The presence of ethanol enhanced the interaction of PKCalpha with Cdc42 within a concentration range corresponding to the potentiating effect, whereas the level of binding was unaffected by higher ethanol levels that were found to attenuate activity. Thus, ethanol may either enhance activation of PKCalpha by Rho GTPases by enhancing the interaction between the two proteins or attenuate the level of activity of Rho GTPase-associated PKCalpha by inhibiting the ensuing activating conformational change. The results also suggest that the effects of ethanol on Rho GTPase-induced activity may switch between an activation and inhibition depending on the concentration of Ca(2+) and other activators.


Immunohistochemical demonstration of carbonic anhydrase isoenzyme VI (CA VI) expression in rat lower airways and lung.
Carbonic anhydrase isoenzyme VI (CA VI), which is transported in high concentrations in saliva and milk into the alimentary tract, is an important element of mucosal protection in the upper alimentary tract. Like alimentary tract mucosa, the respiratory tract mucosa is also exposed to heavy microbial, physical, and chemical stress. The protective and renewal-promoting factors present in the surface mucus of the respiratory tract are mainly produced by the seromucous tracheobronchial glands. Here we studied the secretion of CA VI by these glands in adult and developing rats using immunohistochemical techniques. The serous acinar and duct cells of the tracheobronchial glands stained for CA VI. The presence of the enzyme also in the duct content indicates its active secretion into the surface mucus. CA VI was also visible in the secretory cells and at the base of the ciliated cells of the tracheobronchial surface epithelium. Moreover, the Clara cells of the bronchiolar surface epithelium stained for CA VI. These findings are consistent with the hypothesis that CA VI has a mucosa-protective role not only in the gastrointestinal tract but also in the respiratory tract, where CA VI may act as a pivotal pH neutralizer and growth factor.


Attention speeds binocular rivalry.
During binocular rivalry, incompatible images presented dichoptically compete for perceptual dominance. It has long been debated whether binocular rivalry can be controlled by attention. Most studies have shown that voluntary control over binocular rivalry is limited. We sought to remove attention from binocular rivalry by presenting a concurrent task. Diverting attention slowed the rivalry alternation rate, and did so in proportion to the difficulty of the concurrent task. Even a very demanding distractor task, however, did not arrest rivalry alternations completely. Given that diverting attention was equivalent to lowering the contrast of the rival stimuli, the ability of attention to speed binocular rivalry is most likely due to an increase in the effective contrast of the stimuli through boosting the gain of the cortical response. This increase in effective contrast will ultimately lead to a perceptual switch, thereby limiting voluntary control. Thus, attention speeds rivalry alternations, but has no inherent control over the rivalry process.


"It Gives You a Feeling of Pride when You Touch Her": The Role of Masculinity in Sexual Harassment of Adolescent Schoolgirls in Tanzania.
Sexual harassment or the unwanted offensive behaviours that women and girls experience is a pervasive global challenge. Yet, there is limited evidence on the lived experiences of sexual harassment from school-based settings in sub-Saharan Africa. We explore students' perceived experiences, perpetration, and drivers of sexual harassment in schools in Mwanza, Tanzania. This study employed a qualitative research design involving 30 in-depth interviews and seven focus group discussions with 30 male and 40 female secondary school pupils aged 13-19 years. Data was analysed using a thematic approach. The findings show that experiences of sexual harassment among schoolgirls were widespread. Common forms of harassment were verbal and non-verbal gestures of a sexual nature. The desire to prove one's masculinity and peer pressure were key drivers of perpetration among schoolboys. Teachers took advantage of their positions of authority to sexually harass female pupils and employed corporal punishment to those who resisted their advances. Sexual harassment had multiple negative outcomes, including schoolgirls dropping out of school and mental health issues, such as anxiety, stress and poor academic performance. Girls rarely reported sexual harassment for fear of further victimisation and stigma from others. Sexual harassment of girls is common in secondary schools in Mwanza and is mainly driven by peer pressure and the desire to prove one's masculinity. Given its harmful effects, there is a need to implement clear policies to protect girls, support confidential disclosure and reporting and to address toxic masculinity norms among young men.


Investigation of an outbreak of chikungunya in Malegaon Municipal areas of Nasik district, Maharashtra (India) and its control.
An outbreak of chikungunya fever occurred in Malegaon town of Nasik district of Maharashtra state, India during February and March 2006. A total of 4530 fever cases were reported during this period including 1781 cases which were admitted in different hospitals of the town. An entomological and epidemiological investigation was carried out in the affected villages during the outbreak to study the possible causes of the outbreak and to isolate the virus responsible. Entomological evaluation was done as per WHO guidelines. Sera samples were collected by venipuncture from clinically suspected chikungunya patients in hospitals and also during house-to-house survey in affected villages. IgM antibodies to dengue virus were detected using IgM capture ELISA (PANBIO) and by "Haemagglutination inhibition test" for detection of antibodies against Chikungunya virus. Acute sera samples were inoculated in cell lines for virus isolation. The isolates were confirmed by RT-PCR. On investigation, it was found that water storage containers like cement tanks, plastic containers or earthen pots placed in front of the individual houses were the potential breeding sites for Aedes aegypti. Entomological survey carried out in the most affected areas revealed high Aedes indices. House, container and breteau indices were found to be 27.2, 16.19 and 35.1, respectively. Out of the 13 acute sera samples collected, virus was isolated in 10 samples. The isolates were confirmed by RT-PCR and sequencing using primers from nsP1 gene of Chikungunya virus (CHIKV, Accession No. EF077609, EF077610). Of the 17 convalescent sera tested, significant level of HI antibodies to CHIKV was detected in five samples. One sample was positive for IgM antibodies against dengue virus. Based on clinico-epidemiological features and laboratory findings, the illness was confirmed to be of chikungunya viral disease. Control measures targeting the vector population and personal protective measures against the mosquito bites were instituted. Extensive IEC campaign with the involvement of community and religious leaders helped in containment of the disease.


Ultrafast time-resolved contrast-enhanced 3D pulmonary venous cardiovascular magnetic resonance angiography using SENSE combined with CENTRA-keyhole.
To evaluate the diagnostic benefit of time-resolved CENTRA-keyhole contrast-enhanced cardiovascular magnetic resonance angiography (CE-CMRA) for improving arterial-venous separation of pulmonary vessels. Twenty-three patients (18 males; age = 58 +/- 11y) after radiofrequency pulmonary vein isolation to treat atrial fibrillation were examined using CENTRA-keyhole based multi-phase 3D CE-CMRA yielding 6 near-isotropic 3D datasets every 1.6 s (50-60 coronal partitions, 1.4 x 1.4 x 1.3 mm, SENSE-factor 3). Results were compared with conventional non-keyhole CE-CMRA (identical parameters, SENSE-factor 2). Data acquisition was accelerated by a speedup factor of approximately 9 compared with the reference CE-CMRA (SENSE 1.5*, keyhole 6*). No pulmonary venous stenoses were detected by either method, overall pulmonary venous diameters were 17.1 +/- 3.6 mm. Applying Bland-Altman analysis, vessel diameters differed by a mean of 0.1 mm + 2.1 mm/-2.0 mm (mean +/- 2 SD), indicating close agreement between both techniques. Interobserver variability was higher for CENTRA-keyhole (mean = 0.1 mm; mean +/- 2 SD: +2.5 mm/-2.3 mm) compared to conventional technique (0.0 mm; +1.6 mm/-1.5 mm), corresponding to a percentual deviation (mean +/- 2 SD) of the mean diameter of approximately +/- 15% (keyhole CE-CMRA) and +/- 10% (conventional CE-CMRA), respectively. Using keyhole-based time-resolved CE-CMRA, the contrast between pulmonary veins versus aorta/pulmonary artery was significantly increased (p < 0.05), which improved vessel depiction. In 12 cases, the contrast bolus arrival was delayed in one of the pulmonary veins by 1 dynamic frame (= 1.6 seconds); in 7 cases by 2 frames (= 3.2 seconds) and in 1 subject by 3 frames (= 4.8 seconds). The bolus usually appeared first in the upper right pulmonary vein whereas a delay occurred most often in the lower left pulmonary vein. Conventional CE-CMRA may be advantageous for accurate vessel size measures as evidenced by superior interobserver reproducibility in this study. Multi-dynamic CE-CMRA using CENTRA-keyhole with SENSE, however, allows for improved arterio-venous separation of pulmonary vessels and additional dynamical information on pulmonary venous perfusion, while maintaining high spatial resolution. Exact bolus timing is no longer needed.


Coronavirus Disease 2019 and Acute Hemorrhagic Edema of Infancy.
Acute hemorrhagic edema of infancy (AHEI) is a small-vessel leukocytoclastic vasculitis, presented with low-grade fever and edema in the face and upper and lower limbs, as well as purpuric/ecchymotic lesions in these regions. AHEI was also reported after viral infections, including herpes simplex virus, rotavirus, and adenovirus. Case Presentation. Herein, we reported a case of a 20-month-old boy presented with low-grade fever. Additionally, mild cough and progressive purpuric/ecchymotic lesions were observed in some independent regions and extremity swelling. Laboratory testing showed leukopenia, lymphopenia, and the elevation of both C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Thereafter, the result of the reverse-transcriptase polymerase chain reaction (RT-PCR) test on the obtained specimen samples, including nasopharyngeal swab for COVID-19, was positive. The patient was treated with supportive care, and two weeks later, the serology test for COVID-19 resulted positive. We should think about children infected with COVID-19, particularly those with skin manifestations.


The growth of potential food poisoning organisms on chicken and pork muscle surfaces.
Muscle surfaces of pork were inoculated with a mixture of Yersinia enterocolitica and Staphylococcus aureus, and chicken muscle with Campylobacter jejuni or a mixture of Salmonella typhimurium and Staph. aureus. The surface growth at 20 degrees C was followed microscopically. Organisms grew as discrete colonies bound together by a glycocalyx which differed between bacterial species. On prolonged incubation colonies spread peripherally and tended to coalesce, while still retaining their colony structure. Staphylococcus aureus colonies were very small and remained so. The glycocalyx was considered critical in maintaining the dense populations of bacteria on the meat surfaces.


Improved Optimization for the Cluster Jastrow Antisymmetric Geminal Power and Tests on Triple-Bond Dissociations.
We present a novel specialization of the variational Monte Carlo linear method for the optimization of the recently introduced cluster Jastrow antisymmetric geminal power ansatz, achieving a lower-order polynomial cost scaling than would be possible with a naive application of the linear method and greatly improving optimization performance relative to that of the previously employed quasi-Newton approach. We test the methodology on highly multireference triple-bond stretches, achieving accuracy superior to those of the traditional coupled cluster theory and multireference perturbation theory in both the typical example of N2 and the transition-metal-oxide example of [ScO](+).


Metazoan parasites of Plagioscion squamosissimus (Osteichthyes: Sciaenidae) of two rivers from the eastern Amazon (Brazil).
Plagioscion squamosissimus, commonly known as "white hake" or "corvina", is among the most commercially important fish in the Amazon and host to a great diversity of endoparasites. The aim of the present study was to compare the communities and infracommunities of metazoan parasites that infect P. squamosissimus in two rivers from the eastern Brazilian Amazon. A total of 75 specimens of P. squamosissimus were collected from Lago Grande do Curuái and the mouth of the Tapajós River. Morphological analysis revealed the presence of 16 parasite species, three myxozoans (Myxobolus sp., Ceratomyxa sp., Henneguya sp.), two trematodes (Austrodiplostomum compactum, Digenea gen. sp. (metacercariae), two monogeneans (Diplectanum sp., Euryhaliotrema sp.), three nematodes (Procamallanus (S.) sp., Anisakis sp., Pseudoproleptus sp. (larva), two acanthocephalans (Rhadinorhynchus plagioscionis and Neoechinorhynchus sp.), one Cestoda Ptychobothriidae gen. sp. and three crustaceans (Therodamas sp., Ergasilus sp., Dolops sp.). Six new records of parasites of P. squamosissimus were made, of which three were myxozoan species, one nematode species and two crustacean species. There were differences in the component communities of parasites of both rivers studied and these were discussed.


Internal travel and risk of dengue transmission in Colombia.
Human behavior plays a key role in the dynamics of dengue transmission. However, research on the relationship between human movement and dengue transmission within endemic countries is limited. From January 2008 to December 2011, the authors of this study conducted a retrospective analysis of imported dengue infections in Bogotá, Colombia. Bogotá is a vector-transmission-free city that is also the capital district and most populated municipality in Colombia. The study revealed that 1) Bogotá inhabitants acquired dengue infection in diverse localities throughout the country but the largest proportion of cases (35.6%) were contracted at popular tourist destinations in dengue-endemic areas near Bogotá (<200-km radius from city limits), and 2) the number of imported dengue cases increased after major holidays, a transmission pattern not seen in dengue-endemic areas, where disease incidence correlates with rainy periods. It is therefore recommended that physicians consider the effect of travel when diagnosing their patients' illnesses, especially outside dengue-endemic areas where diagnosis of the disease can be challenging due to its nonspecific symptoms. The study also showed that analysis of dengue cases imported to regions free of vector transmission can generate an evidence-based model for characterizing the impact of human movement on the spread of diseases like dengue in countries where they are endemic.


A tractable method to account for high-dimensional nonignorable missing data in intensive longitudinal data.
Despite the need for sensitivity analysis to nonignorable missingness in intensive longitudinal data (ILD), such analysis is greatly hindered by novel ILD features, such as large data volume and complex nonmonotonic missing-data patterns. Likelihood of alternative models permitting nonignorable missingness often involves very high-dimensional integrals, causing curse of dimensionality and rendering solutions computationally prohibitive to obtain. We aim to overcome this challenge by developing a computationally feasible method, nonlinear indexes of local sensitivity to nonignorability (NISNI). We use linear mixed effects models for the incomplete outcome and covariates. We use Markov multinomial models to describe complex missing-data patterns and mechanisms in ILD, thereby permitting missingness probabilities to depend directly on missing data. Using a second-order Taylor series to approximate likelihood under nonignorability, we develop formulas and closed-form expressions for NISNI. Our approach permits the outcome and covariates to be missing simultaneously, as is often the case in ILD, and can capture U-shaped impact of nonignorability in the neighborhood of the missing at random model without fitting alternative models or evaluating integrals. We evaluate performance of this method using simulated data and real ILD collected by the ecological momentary assessment method.


[Tuberculosis contact tracing among children and adolescents, Brazil].
To detect tuberculosis (TB) disease or infection among contacts of pulmonary TB patients. Cross-sectional study in a Primary Healthcare unit in Rio de Janeiro (Brazil) with 184 child and adolescent contacts of pulmonary TB patients between March 1995 and March 1997. Subjects underwent clinical evaluation, chest radiographs, and tuberculin skin tests (TST); sputum smears were performed whenever possible. TB cases found were submitted to treatment and infected patients to chemoprophylaxis. Tuberculin converters, who tested positive for TST eight weeks after an initial negative result, received chemoprophylaxis. The sample included 98 boys and 86 girls; age ranged from 0 to 15 years; 26.9% were malnourished according to the Gomez criteria. Concerning the source of infection, 170 cases (92.4%) had household contacts, of which 66.5% were the child's parents. BCG vaccination was verified in 98.4% of children, and 14.7% of children had been revaccinated. Strong TST reactions were observed in 110/181 children. Seventy-six children (41.3%) were considered as infected by M. tuberculosis and 25 cases (13.6%) of TB were detected, of which seven (28%) were asymptomatic. There was greater occurrence of disease when the contact lived with more than one source of infection (p=0.02). The detection of TB disease and infection was high in the studied population. Contact control must be emphasized, for it allows for the diagnosis of TB in children who are still asymptomatic, in addition to identifying infected subjects who may profit from chemoprophylaxis.


Factors affecting the prevalence of chronic diseases in Palestinian people: an analysis of data from the Palestinian Central Bureau of Statistics.
This study determined whether there are significant differences in the prevalence of diabetes, hypertension, cardiovascular disease (CVD) and cancer among Palestinians with respect to different demographic variables using secondary data from the Palestinian Central Bureau of Statistics. Living in the Gaza Strip was a protective factor, with this group being 21% less likely to have diabetes, 35% less likely to have hypertension, and 48% less likely to have CVD than those living in the West Bank. No significant difference was found for cancer. Being a refugee was a significant risk factor for diabetes and CVD while being married/engaged or divorced/ separated/widowed was a risk factor for diabetes and hypertension. Gender was a risk factor for hypertension with females being 60% more likely to have hypertension than males. Living in a rural setting was protective against hypertension. As expected, age was a risk factor for diabetes, hypertension and CVD; the magnitude of this increased risk was alarming, 36 to 434 times greater in those aged 40-65 years compared with those aged 0-19 years.


Hematopoietic progenitor content of fetal cord blood collected using citrate-phosphate-dextrose: influence of holding temperature and delays.
Storage of unseparated fetal cord blood collected into citrate-phosphate-dextrose (CPD) for 48 hours has been studied using progenitor cell assays [plasma clot technique with plasma-conditioned medium, erythropoietin (EPO), erythropoietin + IL-3 as growth factors]; collected fetal blood volume was low [61 +/- 4 ml, mean +/- 95% confidence interval (CI)]. The CFU-GM concentration in total cord blood was 2460 +/- 1476 CFU-GM/ml, comparable to normal bone marrow collected into medium RPMI + heparin (2350 +/- 1258); 2 of 12 samples contained fewer than 10(3) CFU-GM. Storage of unseparated cord blood CFU-GM in CPD was better at 4 degrees C (rapid decrease at day (D) 2 from 15 +/- 9 x 10(4) at D0; 14 +/- 11 x 10(4) at D1 to 6 +/- 4 x 10(4) at (D2) than at 22 degrees C (strong decrease since D1: 5 +/- 4 x 10(4) CFU-GM). The CFU-GEMM content remained steady at 4 degrees C: from 16 +/- 16 x 10(4) at D0 to 18 +/- 16 at D2. Cryopreservation and thawing of unfractionated cord blood at D0 did not affect the CFU-FM cloning rates. Whether mature progenitors are more affected than stem cells by storage in CPD remains to be determined.


Niemann-Pick disease-type C: a case report.
We report a case, with foamy histocytes in the bone marrow and eye movement abnormalities which is characteristic for Niemann Pick disease Type-C.


X-linked hypogammaglobulinemia and isolated growth hormone deficiency: an update.
X-linked hypogammaglobulinemia and isolated growth hormone deficiency (XLH-GHD, OMIM # 307200) is a primary immunodeficiency disorder characterized by pan-hypogammaglobulinemia and isolated growth hormone deficiency. The disease, which is only known to occur in a single family, shares many features with X-linked agammaglobulinemia (XLA, OMIM # 300300). The current review summarizes the clinical, laboratory and genetic features of the disease as they have unfolded over the past quarter century since its description.


Stereoselective pharmacokinetics of BOF-4272 racemate after oral administration to rats and dogs.
The stereoselective pharmacokinetics of BOF-4272 enantiomers in rats and dogs was investigated by simultaneously measuring concentrations in arterial, portal, and venous plasma, the liver, and the kidney at 2 h after the oral administration of the racemic drug. The concentrations of BOF-4272 enantiomers were measured using high-performance liquid chromatography. The concentrations of the S(-) enantiomer in arterial, portal, and venous plasma were higher than those of the R(+) enantiomer in rats, but the opposite was found in dogs. In rats, absorption from the intestinal tract into the portal system was almost the same for the two enantiomers, whereas the hepatic uptake of the R(+) enantiomer was greater than that of the S(-) enantiomer. In dogs, absorption from the intestinal tract into the portal system was greater for the R(+) enantiomer than for the S(-) enantiomer, whereas hepatic uptake was comparable for the two enantiomers. The stereoselectivity of the renal uptake of BOF-4272 enantiomers had little effect on the stereoselectivity of enantiomers in the systemic circulation in both rats and dogs. The stereoselectivity in the systemic circulation of BOF-4272 enantiomers is therefore related to hepatic uptake in rats, and to absorption from the intestinal tract into the portal system in dogs.


Structure-function relationships in glucosidase I: amino acids involved in binding the substrate to the enzyme.
As the enzyme that initiates the maturation phase of the oligosaccharide moiety of N-linked glycoproteins, glucosidase I controls the flux of carbohydrate during the biosynthesis of these proteins. In a previous study to elucidate the structure-function relationships, we reported the presence of a cysteine residue at or near the active site of the enzyme from the bovine mammary gland (Pukazhenthi,B.S., Muniappa,N. and Vijay,I.K., 1993, J. Biol. Chem., 268, 6445-6452). We have now extended this approach to identify the participation of an arginine and a tryptophan residue in the enzyme that may play an important role in binding the substrate. The data have been combined with the results of the previous study and the cDNA-derived sequence to propose a ERHLDLRCW motif in the active site of the enzyme in the rat mammary gland that is involved in binding the incipient glycoprotein substrate for processing.


CADMIUM AND ZINC BIOAVAILABILITY TO SELENASTRUM CAPRICORNUTUM (CHLOROPHYCEAE): ACCIDENTAL METAL UPTAKE AND TOXICITY IN THE PRESENCE OF CITRATE.
Toxicities of cadmium (Cd) and zinc (Zn) to the green alga Selenastrum capricornutum Printz were determined over 72 h in defined synthetic media buffered by citrate (FRAQCIT ; [citrate] = 100 μM or 5 μM) or nitrilotriacetate (FRAQNTA ; [NTA] = 5 μM). Algal sensitivity to free Cd2 + or free Zn2 + in FRAQCIT was much higher than in FRAQNTA . In parallel experiments, short-term intracellular uptake of radiolabeled 109 Cd was measured as a function of time (0-30 min) in FRAQCIT and FRAQNTA ; for a given free Cd2 + concentration (8, 250, or 610 nM), intracellular accumulation of Cd was consistently higher in FRAQCIT than in FRAQNTA . Under the same conditions, the alga accumulated 14 C-labeled citrate almost linearly over a 2-h period. Loss of 109 Cd from algal cells that had been prelabeled with the radionuclide occurred slowly, and the loss rate was insensitive to the presence or absence of citrate, indicating that the overall permeability of the algal membrane to Cd was unaffected by citrate. The enhanced bioavailability of Cd in the presence of citrate could be explained by membrane transport of a charged Cd-citrate complex, presumably by accidental transport.


Biliary atresia with situs inversus: an experience shared.
Biliary Atresia (BA) is a well-known entity and can present with multiple congenital anomalies. BA is one of the most common conditions in which pediatric liver transplant is performed. Identification of Biliary atresia with situs inversus (SI) has not been documented in Pakistan. We report two such cases. First was an eighty-day-old baby boy, icteric from day of birth. On further evaluation had dextrocardia, SI, gross hydronephrosis (HN) of left kidney and stasis at pelvi ureteric junction (PUJ). Liver biopsy showed biliary cirrhosis secondary to extra hepatic biliary atresia (EHBA). The second baby presented at two months of age. Ultrasound abdomen and hepatobiliary scintigraphy confirmed liver in left hypochondrium (SI) and findings suggestive of BA. Echocardiography confirmed SI with mesocardia. In this paper we have described the association of BA with SI in two patients presenting at the pediatric Gastroenterology, hepatology and nutrition unit.


[Skating fun and fractures of the maxillofacial bones].
Skating is a favourite sport in the Netherlands. Injury data on skating were collected from the emergency departments of 6 hospitals in the province of Friesland in the Netherlands during the Eleven Cities ice skating marathon over 200 kilometers in January 1997, with 16,688 participants. Among a total of 55 fractures, the maxillofacial skeleton had a relative high fracture frequency (n = 7; 13%), especially the zygomatic complex (n = 6); one patient had a mandibular fracture. An innocent-looking black eye, unilateral numbness of the upper lip and malocclusion following a skating accident merit full medical attention.


DESFLURANE COMPARED TO SEVOFLURANE FOR CIRRHOTIC PATIENTS UNDERGOING MAJOR LIVER RESECTION. A RANDOMIZED CONTROL STUDY.
Major liver resection is associated with haemodynamic, hepatic and renal changes as a result of the procedure. To compare Desflurane (D) versus Sevoflurane (S) on hepatic, renal functions, haemodynamics and perioperative course for cirrhotic patients undergoing major liver resection. A prospective randomized control study with 50 patients (Child A) (D, n = 25 and S, n = 25). End tidal D or S adjusted with Entropy (40-60). Haemodynamics monitored with invasive blood pressure and trans-oesophageal Doppler (TED). Liver and kidney function tests, blood Glutathione-S-transferase (GST), urinary microalbuminuria (Microalb) were assayed. Extubation time and anaesthetic consumption were recorded. Systemic vascular resistance (SVR) post-resection and stroke volume of D vs S were 835.04 ± 12.02 vs 778.16 ± 11.97 dyn.sec.cm(-5), P < 0.01, and 85.72 ± 2.95 vs 76.16 ± 6.52 ml, P < 0.01 respectively. Doppler corrected flow time (FTc) between groups were comparable (P > 0.05). No difference post-operatively regarding hepatic and renal functions, and urine Microalb (14.76 ± 3.95 vs l4.24 ± 8.65 µg/ml, P = 0.78), but a statistically difference was found with GST (0.046 ± [symbols: see text], vs 0.043 ± [symbols: see text] IU/ml, P < 0.01). Despite a higher D consumption (73 ± 17 vs 64 ± 22 ml, P = 0.102), cost in Egyptian pounds (LE) was lower with D (141.14 ± 32.90 vs 320.60 ± 114.01, LE, P < 0.01). Extubation time and ICU stay with D vS (4.52 ± 2 vs 7.72 ± 2 min, P < 0.01) and (1.40 0.50 vs 1.64 ± 0.48, days P = 0.09) respectively. Neither D nor S were clinically superior to the other with respect to liver and kidneys functions, but D was found to preserve better the haemodynamic parameters and enhance recovery at a lower cost.


Obstetric management of a fetus with nonlethal osteogenesis imperfecta.
Osteogenesis imperfecta is the common term for a heterogeneous group of heritable disorders of connective tissue with lethal and nonlethal forms. Prenatal diagnosis presents difficult medical and ethical issues. Of concern are the following: 1) the certainty of diagnosis, 2) the severity of disease, 3) the prognosis for survival and ambulation, and 4) the appropriate mode of delivery. A case of nonlethal fetal osteogenesis imperfecta managed by vaginal delivery is discussed.


Increase of Ki-67 index and influence on mortality in patients with neuroendocrine neoplasms.
An increase in the Ki-67 index in neuroendocrine neoplasms over time in relation to prognosis has scarcely been investigated. We aimed to assess whether the Ki-67 index changed over time and also whether a change influenced prognosis. Second, we investigated the difference in the Ki-67 index between primary tumour and metastases. From 1 January 1995 to 31 December 2019, 108 consecutive patients with gastroenteropancreatic tumours were included. Patients were followed with regard to an increase in the Ki-67 index and all-cause mortality. Ki-67 determination of the primary tumour at diagnosis and at the time of radiological progression, including developed metastases, was performed. A significant increase in the Ki-67 index was defined as a doubling of the value at disease progression compared to the value at diagnosis. In addition, in 14 patients, the Ki-67 index of the primary tumour and present metastases at the time of diagnosis was investigated. At diagnosis, there were no differences in the Ki-67 index between primary tumours and metastases (P = .41). Sixty-five patients had a doubling of the Ki-67 index. The median Ki-67 index at the time of progression 17% (1%-90%) vs 5% (1%-60%) at the time of diagnosis (P = .006). A doubling of the Ki-67 index was independently associated with all-cause mortality (hazard ratio = 2.7 [1.3-6.3], P = 0.02), after adjustment for relevant co-variables including the Ki-67 index at baseline. Doubling of the Ki-67 index at the time of disease progression was associated with a significantly higher risk of all-cause mortality. We recommend that a Ki-67 index is obtained whenever disease progression is recorded by demonstrated progression because it may have impact on the choice of treatment.


Randomized, double-blind, multicenter comparison of oral cefditoren 200 or 400 mg BID with either cefuroxime 250 mg BID or cefadroxil 500 mg BID for the treatment of uncomplicated skin and skin-structure infections.
Uncomplicated skin and skin-structure infections are commonly observed in medical practice. Because these infections typically are confined to the superficial layers and seldom lead to the destruction of skin structures and resultant systemic dissemination, in general they can be treated with an oral antibiotic with potent microbiologic activity against gram-positive pathogens. This paper compares the efficacy and tolerability of 3 beta-lactam antibiotics in patients with uncomplicated skin and skin-structure infections. Two double-blind, multicenter, parallel-group studies were conducted, in which patients aged > or = 12 years with uncomplicated skin and skin-structure infections were randomized to receive cefditoren 200 or 400 mg, cefuroxime 250 mg, or cefadroxil 500 mg, each BID for 10 days. Study 1 compared cefditoren with cefuroxime; Study 2 compared cefditoren with cefadroxil. Clinical and microbiologic responses were assessed at a posttreatment visit (within 48 hours of treatment completion) and test-of-cure visit (7-14 days after treatment completion). Patients were monitored closely throughout the study with the use of physical examinations, clinical laboratory tests, and assessment of adverse events. A total of 1,685 patients (855 males, 830 females; mean age, 41.1 years [range, 12-95 years]) were enrolled. Within both studies, the 3 treatment groups were similar at baseline based on demographic characteristics and types of infection. Cellulitis (26%), wound infection (25%), and simple abscess (15%) were the most common infections. Clinical cure rates at the test-of-cure visit were 85% (443/523) for cefditoren 200 mg, 83% (427/516) for cefditoren 400 mg, 88% (234/265) for cefuroxime, and 85% (211/248) for cefadroxil. At the test-of-cure visit, cefditoren 200 mg had eradicated significantly fewer of the causative pathogens isolated before treatment in microbiologically evaluable patients than did cefuroxime in Study 1 (P = 0.043) but significantly more of the pathogens than did cefadroxil in Study 2 (P = 0.018). Eradication rates for the most commonly isolated pathogens were generally similar in the 3 treatment groups in both studies, with the only significant difference favoring cefditoren 200 and 400 mg over cefadroxil for Peptostreptococcus species in Study 2 (P = 0.016 and P = 0.003, respectively). A minority of patients (< or = 5% in any treatment group) discontinued study-drug treatment prematurely due to a treatment-related adverse event, with statistically higher rates for cefditoren 400 mg than for cefditoren 200 mg and the comparator cephalosporins (each P < 0.05). All 3 cephalosporins were generally well tolerated. Most adverse events (>93%) were categorized as mild to moderate, with the most common being diarrhea, nausea, and headache. In this population of patients with uncomplicated skin and skin-structure infections, including those due to Staphylococcus aureus or Streptococcus pyogenes, the clinical cure rate and tolerability of cefditoren were comparable to those of cefuroxime and cefadroxil.


Salivary lysozyme levels in patients with primary immunodeficiencies.
Lysozyme is a muramidase that acts on the peptideoglycan wall of Gram positive bacteria, causing cell death. It plays part in innate immunity and is present in blood, external fluid, as well in lysossomal granules of the phagocytes. Primary Immunodeficiencies are a diverse group of illnesses that, as a result of abnormalities of the immune system, increase susceptibility to infection. Among the examples of impaired natural immunity are defects in phagocytes and in the complement system. Innate immunity could be important in protecting mucosas against infections in patients with different forms of primary immunodeficiencies. The aim of this study was to investigate lysozyme concentrations in saliva from patients with primary immunodeficiencies. Lysozyme levels in saliva samples from 34 patients with primary immunodeficiency (30 children and adolescents between the age of 3-13 years and 4 adults between the age of 20-33) and 60 age-matched healthy controls (49 children and adolescents between the ages of 3-15 and 11 adults between the ages of 22-42) were determined by the lysoplate method. There was no statistically significant difference between the lysozyme concentrations in the saliva of the immunodeficient subjects and those of the healthy controls. The results in the present work clearly show that salivary lysozyme levels in primary immunodeficient patients are equivalent to those found in healthy controls, suggesting that this enzyme still represents a remaining (but not a compensatory mechanism), contributing to the protection of there patients against infections.


Identification of class I MHC-associated phosphopeptides as targets for cancer immunotherapy.
Alterations in phosphorylation of cellular proteins are a hallmark of malignant transformation. Degradation of these phosphoproteins could generate cancer-specific class I MHC-associated phosphopeptides recognizable by CD8+ T lymphocytes. In a comparative analysis of phosphopeptides presented on the surface of melanoma, ovarian carcinoma, and B lymphoblastoid cells, we find 5 of 36 that are restricted to the solid tumors and common to both cancers. Differential presentation of these peptides can result from differential phosphorylation of the source proteins. Recognition of the peptides on cancer cells by phosphopeptide-specific CD8+ T lymphocytes validates the potential of these phosphopeptides as immunotherapeutic targets.


Central blood pressure variability is increased in hypertensive patients with target organ damage.
We aimed to evaluate the association of aortic and brachial short-term blood pressure variability (BPV) with the presence of target organ damage (TOD) in hypertensive patients. One-hundred seventy-eight patients, aged 57 ± 12 years, 33% women were studied. TOD was defined by the presence of left ventricular hypertrophy on echocardiogram, microalbuminuria, reduced glomerular filtration rate, or increased aortic pulse wave velocity. Aortic and brachial BPV was assessed by 24-hour ambulatory BP monitoring (Mobil-O-Graph). TOD was present in 92 patients (51.7%). Compared to those without evidence of TOD, they had increased night-to-day ratios of systolic and diastolic BP (both aortic and brachial) and heart rate. They also had significant increased systolic BPV, as measured by both aortic and brachial daytime and 24-hours standard deviations and coefficients of variation, as well as for average real variability. Circadian patterns and short-term variability measures were very similar for aortic and brachial BP. We conclude that BPV is increased in hypertensive-related TOD. Aortic BPV does not add relevant information in comparison to brachial BPV.


Sexual Attitudes, Erotophobia, and Sociosexual Orientation Differ Based on Relationship Orientation.
Consensual nonmonogamy (CNM) is an overarching term for relationship orientations that differ based on the degree to which consensual sexual and emotional needs are fulfilled outside of a dyad. Despite the diversity of CNM relationship orientations and growing research examining CNM, it is unclear whether the sexual attitudes, inclination to approach/avoid sexual stimuli (i.e., erotophobia-erotophilia), and sociosexuality differ among individuals who identify with distinct CNM relationships. Further, as the agreements made in CNM relationships permit extradyadic relationships, important differences might emerge for CNM and monogamous individuals. A convenience sample (N = 641) of individuals who self-identified as monogamous (n = 447), open (n = 80), polyamorous (n = 62), or swinger (n = 52) provided ratings of their sexual attitudes, erotophobia-erotophilia, and sociosexuality. Results indicated that swingers had the most permissive and instrumental attitudes, were the most erotophilic, and were the most unrestricted sexually. Conversely, monogamists scored the lowest on these traits. No differences emerged between relationship orientations for attitudes toward communion and birth control. These findings have important implications for sexuality research because they reinforce the view that some underlying differences and similarities exist between monogamous and CNM individuals.


The Diagnostic Potential of the Human Blood Microbiome: Are We Dreaming or Awake?
Human blood has historically been considered a sterile environment. Recently, a thriving microbiome dominated by Firmicutes, Actinobacteria, Proteobacteria, and Bacteroidetes phyla was detected in healthy blood. The localization of these microbes is restricted to some blood cell populations, particularly the peripheral blood mononuclear cells and erythrocytes. It was hypothesized that the blood microbiome originates from the skin-oral-gut axis. In addition, many studies have evaluated the potential of blood microbiome dysbiosis as a prognostic marker in cardiovascular diseases, cirrhosis, severe liver fibrosis, severe acute pancreatitis, type 2 diabetes, and chronic kidney diseases. The present review aims to summarize current findings and most recent evidence in the field.


Intraoperative hyperglycemia during liver resection: predictors and association with the extent of hepatocytes injury.
Patients undergoing liver resection are at risk for intraoperative hyperglycemia and acute hyperglycemia is known to induce hepatocytes injury. Thus, we aimed to evaluate whether intraoperative hyperglycemia during liver resection is associated with the extent of hepatic injury. This 1 year retrospective observation consecutively enrolled 85 patients undergoing liver resection for hepatocellular carcinoma. Blood glucose concentrations were measured at predetermined time points including every start/end of intermittent hepatic inflow occlusion (IHIO) via arterial blood analysis. Postoperative transaminase concentrations were used as surrogate parameters indicating the extent of surgery-related acute hepatocytes injury. Thirty (35.5%) patients developed hyperglycemia (blood glucose > 180 mg/dl) during surgery. Prolonged (≥ 3 rounds) IHIO (odds ratio [OR] 7.34, P = 0.004) was determined as a risk factors for hyperglycemia as well as cirrhosis (OR 4.07, P = 0.022), lower prothrombin time (OR 0.01, P = 0.025), and greater total cholesterol level (OR 1.04, P = 0.003). Hyperglycemia was independently associated with perioperative increase in transaminase concentrations (aspartate transaminase, β 105.1, standard error 41.7, P = 0.014; alanine transaminase, β 81.6, standard error 38.1, P = 0.035). Of note, blood glucose > 160 or 140 mg/dl was not associated with postoperative transaminase concentrations. Hyperglycemia during liver resection might be associated with the extent of hepatocytes injury. It would be rational to maintain blood glucose concentration < 180 mg/dl throughout the surgery in consideration of parenchymal disease, coagulation status, lipid profile, and the cumulative hepatic ischemia in patients undergoing liver resection for hepatocellular carcinoma.


The modification of hemoglobin by a long crosslinking reagent: bis(3,5-dibromosalicyl) sebacate.
Bis(3,5-dibromosalicyl) sebacate is a bifunctional protein crosslinking reagent. It reacts with oxy form of human hemoglobin A to produce a crosslinked hemoglobin between two beta chains in the 2,3-bisphosphoglycerate binding cleft, decreasing the oxygen affinity. The oxygen binding curve of crosslinked hemoglobin had a P50 of 18.5 mmHg compared to a P50 of 11.0 mmHg for native hemoglobin and remains highly cooperative, n = 2.2. Crosslinking hemoglobin between the two beta chains also results in a 12.5 degrees C increase in the thermal denaturation temperature. The crosslinked hemoglobin is oxidized more rapidly to methemoglobin. Its autoxidation rate in 0.01 M MOPS, pH 7.4, at 37 degrees C was 1.4 times as fast as that of Hb A.


Host-Specialist Dominated Ectomycorrhizal Communities of Pinus cembra are not Affected by Temperature Manipulation.
Ectomycorrhizae (EM) are important for the survival of seedlings and trees, but how they will react to global warming or changes in soil fertility is still in question. We tested the effect of soil temperature manipulation and nitrogen fertilization on EM communities in a high-altitude Pinus cembra afforestation. The trees had been inoculated in the 1960s in a nursery with a mixture of Suillus placidus, S. plorans and S. sibircus. Sampling was performed during the third year of temperature manipulation in June and October 2013. Root tips were counted, sorted into morphotypes, and sequenced. Fungal biomass was measured as ergosterol and hyphal length. The EM potential of the soil was assessed with internal transcribed spacers (ITS) clone libraries from in-growth mesh bags (MB). Temperature manipulation of ± 1 °C had no effect on the EM community. A total of 33 operational taxonomic units (OTUs) were identified, 20 from the roots, 13 from MB. The inoculated Suillus spp. colonized 82% of the root tips, thus demonstrating that the inoculation was sustainable. Nitrogen fertilization had no impact on the EM community, but promoted depletion in soil organic matter, and caused a reduction in soil fungal biomass.


Bicyclic (amino)(borata)carbene derived from diazadiborinine and isonitrile.
The reaction of 1,4,2,5-diazadiborinine (1) with two equivalents of an aryl isonitrile afforded a bicyclic product containing an indole unit (2) or ketenimine moiety (3), suggesting the generation of a B,N-carbene intermediate formed via a [4+2] cycloaddition reaction in the initial step. The employment of the tolyl(phenyl isonitrile)gold complex (PhNCAuTol) as the substrate allowed the bicyclic (amino)(borata)carbene gold complexes (4, 5) to be accessed.


Cocrystals of the DNA-binding domain of phage 434 repressor and a synthetic phage 434 operator.
The amino-terminal domain of the phage 434 repressor forms cocrystals with a synthetic phage 434 operator. The cocrystals diffract to at least 4 A, and x-ray crystallographic analysis of them is in progress. An analysis of the packing in the cocrystals shows that complexes consisting of dimers of amino-terminal domain bound specifically to operators are stacked end to end in longer protein-DNA rods parallel to the unit cell body diagonals. The DNA in the complexes has 10.5 base pairs per turn and a rise per base of 3.26 A--values consistent with B-form DNA--indicating that DNA is neither unwound nor overwound by bound repressor. The packing analysis suggests an approach that might facilitate the cocrystallization of other DNA-binding proteins with the DNA they recognize.


Flail anterior tricuspid valve leaflet in a neonate: association with maternal antiphospholipid syndrome.
This brief report describes a case of flail anterior tricuspid valve leaflet in a neonate associated with maternal antiphospholipid syndrome. Fetal echocardiography at 27 weeks of gestation showed competent atrioventricular valves with biventricular echogenic chordae. Fetal distress was noted at delivery, and echocardiography showed a flail anterior leaflet of the tricuspid valve with severe regurgitation. Possible causation and implications of maternal antiphospholipid syndrome are discussed.


Monte Carlo model of a prototype flat-panel detector for multi-energy applications in radiotherapy.
The incorporation of multi-energy capabilities into radiotherapy flat-panel detectors offers advantages including enhanced soft tissue visualization by reduction of signal from overlapping anatomy such as bone in 2D image projections; creation of virtual monoenergetic images for 3D contrast enhancement, metal artefact reduction and direct acquisition of relative electron density. A novel dual-layer on-board imager offering dual energy processing capabilities is being designed. As opposed to other dual-energy implementation techniques which require separate acquisition with two different x-ray spectra, the dual-layer detector design enables simultaneous acquisition of high and low energy images with a single exposure. A computational framework is required to optimize the design parameters and evaluate detector performance for specific clinical applications. In this study, we report on the development of a Monte Carlo (MC) model of the imager including model validation. The stack-up of the dual-layer imager (DLI) was implemented in GEANT4 Application for Tomographic Emission (GATE). The DLI model has an active area of 43×43 cm2 , with top and bottom Cesium Iodide (CsI) scintillators of 600 and 800 μm thickness, respectively. Measurement of spatial resolution and imaging of dedicated multi-material dual-energy (DE) phantoms were used to validate the model. The modulation transfer function (MTF) of the detector was calculated for a 120 kVp x-ray spectrum using a 0.5 mm thick tantalum edge rotated by 2.5o . For imaging validation, the DE phantom was imaged using a 140 kVp x-ray spectrum. For both validation simulations, corresponding measurements were done using an initial prototype of the imager. Agreement between simulations and measurement was assessed using normalized root mean square error (NRMSE) and 1D profile difference for the MTF and phantom images respectively. Further comparison between measurement and simulation was made using virtual monoenergetic images (VMIs) generated from basis material images derived using precomputed look-up tables. The MTF of the bottom layer of the dual-layer model shows values decreasing more quickly with spatial frequency, compared to the top layer, due to the thicker bottom scintillator thickness and scatter from the top layer. A comparison with measurement shows NRMSE of 0.013 and 0.015 as well as identical MTF50 of 0.8 mm1 and 1.0 mm1 for the top and bottom layer respectively. For the DE imaging of the DE-phantom, although a maximum deviation of 3.3% is observed for the 10 mm aluminum and Teflon inserts at the top layer, the agreement for all other inserts is less than 2.2% of the measured value at both layers. Material decomposition of simulated scatter-free DE images gives an average accuracy in PMMA and aluminum composition of 4.9% and 10.3% for 11-30 mm PMMA and 1-10 mm aluminum objects respectively. A comparison of decomposed values using scatter containing measured and simulated DE images shows good agreement within statistical uncertainty. Validation using both MTF and phantom imaging shows good agreement between simulation and measurements. With the present configuration of the digital prototype, the model can generate material decomposed images and virtual monoenergetic images.


Vision-based technique for circle detection and measurement using lookup table and bitwise center accumulator.
In this paper, we proposed a fast algorithm for circle detection and measurement, which uses a lookup table and bitwise center accumulator (LUT-BCA). The LUT-BCA is a two-stage procedure. The first stage determines the candidate circle centers with normal lines produced by the lookup table and recorded by the bitwise center accumulator. The second stage computes the radius of each candidate circle center and validates these centers, which eliminates the false detections. The proposed LUT-BCA can also be easily implemented on massively parallel high-performance graphics hardware using the compute unified device architecture. Experimental results indicate that the LUT-BCA can locate circle centers and measure their radii accurately and is very suitable for real-time circle detection and measurement.


Impaired Annulus Fibrosus Development and Vertebral Fusion Cause Severe Scoliosis in Mice with Deficiency of c-Jun NH2-Terminal Kinases 1 and 2.
Mitogen-activated protein kinases, including c-Jun NH2-terminal kinase (JNK), play an important role in the development and function of a large variety of tissues. The skeletal phenotype of JNK1 and JNK2 double-knockout (dKO) mice (JNK1fl/flCol2-Cre/JNK2-/-) and control genotypes were analyzed at different embryonic and postnatal stages. JNK1/2 dKO mice displayed a severe scoliotic phenotype beginning during development that was grossly apparent around weaning age. Alcian blue staining at embryonic day 17.5 showed abnormal fusion of the posterior spinal elements. In adult mice, fusion of vertebral bodies and of spinous and transverse processes was noted by micro-computed tomography, Alcian blue/Alizarin red staining, and histology. The long bones developed normally, and histologic sections of growth plate and articular cartilage revealed no significant abnormalities. Histologic sections of the vertebral column at embryonic days 15.5 and 17.5 revealed an abnormal organization of the annulus fibrosus in the dKOs, with chondrocyte-like cells and fusion of dorsal processes. Spinal sections in 10-week-old dKO mice showed replacement of intervertebral disk structures (annulus fibrosus and nucleus pulposus) by cartilage and bone tissues, with cells staining for markers of hypertrophic chondrocytes, including collagen X and runt-related transcription factor 2. These findings demonstrate a requirement for both JNK1 and JNK2 in the normal development of the axial skeleton. Loss of JNK signaling results in abnormal endochondral bone formation and subsequent severe scoliosis.


Type 1 Diabetes Management With Technology: Patterns of Utilization and Effects on Glucose Control Using Real-World Evidence.
This retrospective cohort study evaluated diabetes device utilization and the effectiveness of these devices for newly diagnosed type 1 diabetes. Investigators examined the use of continuous glucose monitoring (CGM) systems, self-monitoring of blood glucose (SMBG), continuous subcutaneous insulin infusion (CSII), and multiple daily injection (MDI) insulin regimens and their effects on A1C. The researchers identified 6,250 patients with type 1 diabetes, of whom 32% used CGM and 37.1% used CSII. A higher adoption rate of either CGM or CSII in newly diagnosed type 1 diabetes was noted among White patients and those with private health insurance. CGM users had lower A1C levels than nonusers (P = 0.039), whereas no difference was noted between CSII users and nonusers (P = 0.057). Furthermore, CGM use combined with CSII yielded lower A1C than MDI regimens plus SMBG (P <0.001).


Two high-resolution structures of potato endo-1,3-β-glucanase reveal subdomain flexibility with implications for substrate binding.
Endo-1,3-β-glucanases are widely distributed among bacteria, fungi and higher plants. They are responsible for hydrolysis of the glycosidic bond in specific polysaccharides with tracts of unsubstituted β-1,3-linked glucosyl residues. The plant enzymes belong to glycoside hydrolase family 17 (GH17) and are also members of class 2 of pathogenesis-related (PR) proteins. X-ray diffraction data were collected to 1.40 and 1.26 Å resolution from two crystals of endo-1,3-β-glucanase from Solanum tuberosum (potato, cultivar Désirée) which, despite having a similar packing framework, represented two separate crystal forms. In particular, they differed in the Matthews coefficient and are consequently referred to as higher density (HD; 1.40 Å resolution) and lower density (LD; 1.26 Å resolution) forms. The general fold of the protein resembles that of other known plant endo-1,3-β-glucanases and is defined by a (β/α)(8)-barrel with an additional subdomain built around the C-terminal half of the barrel. The structures revealed high flexibility of the subdomain, which forms part of the catalytic cleft. Comparison with structures of other GH17 endo-1,3-β-glucanases revealed differences in the arrangement of the secondary-structure elements in this region, which can be correlated with sequence variability and may suggest distinct substrate-binding patterns. The crystal structures revealed an unusual packing mode, clearly visible in the LD structure, caused by the presence of the C-terminal His(6) tag, which extends from the compact fold of the enzyme molecule and docks in the catalytic cleft of a neighbouring molecule. In this way, an infinite chain of His-tag-linked protein molecules is formed along the c direction.


Cocaine self-administration specifically increases A2AR-D2R and D2R-sigma1R heteroreceptor complexes in the rat nucleus accumbens shell. Relevance for cocaine use disorder.
Adenosine 2A receptor (A2AR) agonists were indicated to reduce cocaine reward and cocaine seeking mainly through activation of antagonistic allosteric A2AR-dopamine D2R (D2R) interactions in A2AR-D2R heteroreceptor complexes. Furthermore, it was shown that modulation of cocaine reward involves antagonistic A2AR-D2R interactions in the ventral but not the dorsal striatum in rats. In the current work the proximity ligation assay (PLA) was used to further study the A2AR-D2R heteroreceptor complexes in the nucleus accumbens shell and core as well as the dorsal striatum under the influence of cocaine self-administration in rats. A significant increase in the A2AR-D2R PLA positive clusters was observed in the nucleus accumbens shell but not in the other regions vs yoked saline controls using the duolink software. Additionally, cocaine self-administration evoked a selective and significant increase in the density of D2R-sigma1R positive clusters in the nucleus accumbens shell vs yoked saline controls, while a significant reduction of the density of the D2R-sigma1R positive clusters was found in the dorsal part of the dorsal striatum. The results suggest that cocaine self-administration can reorganize A2AR and D2R into increased A2AR-D2R heteroreceptor complexes in the nucleus accumbens shell associated with increases in the D2R-sigma1R heteroreceptor complexes in this region. This reorganization can contribute to the demonstrated anti-cocaine actions of A2A receptor agonists and the putative formation of A2AR-D2R-sigma1R heterocomplexes.