Synthesis, cytotoxicity and carbonic anhydrase inhibitory activities of new pyrazolines.
A series of polymethoxylated-pyrazoline benzene sulfonamides were synthesized, investigated for their cytotoxic activities on tumor and non-tumor cell lines and inhibitory effects on carbonic anhydrase isoenzymes (hCA I and hCA II). Although tumor selectivity (TS) of the compounds were less than the reference compounds 5-Fluorouracil and Melphalan, trimethoxy derivatives 4, 5, and 6 were more selective than dimethoxy derivatives 2 and 3 as judged by the cytotoxicity assay with the cells both types originated from the gingival tissue. The compound 6 (4-[3-(4-methoxyphenyl)-5-(3,4,5-trimethoxyphenyl)-4,5-dihydro-1H-pyrazol-1-yl] benzene sulfonamide) showed the highest TS values and can be considered as a lead molecule of the series for further investigations. All compounds synthesized showed superior CA inhibitory activity than the reference compound acetazolamide on hCA I, and II isoenzymes, with inhibition constants in the range of 26.5-55.5 nM against hCA I and of 18.9-28.8 nM against hCA II, respectively.


[Migrating subcutaneous swellings due to dirofilariasis after a visit to the South of France].
In two women, aged 59 and 31 years, who suffered from an itching cutaneous nodule, subcutaneous dirofilariasis was diagnosed. The disease is characterised by recurrent migrating subcutaneous nodules and swellings. Both patients recently visited the South of France. Laboratory examination revealed a moderate eosinophilia. In both patients, filaria antibodies were demonstrated during the course of the disease and a nodule was eventually resected. Parasitological examination revealed Dirofilaria repens. After this the swellings did not recur. Dirofilariasis is a zoonosis common in dogs and cats, and is transmitted by mosquitoes. In humans, the most common clinical manifestation is a migrating subcutaneous nodule in the case of D. repens, and a pulmonary infiltrate (coin lesion on radiographs) in the case of Dirofilaria immitis. Filarial serology is often positive. The diagnosis is confirmed by parasitological examination of the excised nodule. Dirofilariasis is usually innocuous; it disappears after the worm has died but can cause patients to worry.


Perinatal S100B Protein Assessment in Human Unconventional Biological Fluids: A Minireview and New Perspectives.
Growing evidence is now available on the use of S100B protein as a valuable marker of brain damage and its role as a neurotrophic factor. Bearing in mind, among different S100B protein properties that are still being investigated, the possibility of measuring this protein in different biological fluids renders it suitable for use in several disciplines. This is the case with perinatal medicine where even more noninvasive techniques are particularly desirable in order to ensure the minimal handling diagnostic and therapeutic strategies. In this setting, the present minireview reports data on the presence and the usefulness of S100B protein as brain damage marker and as a neurotrophic factor in the so-called unconventional biological fluids such as saliva and human milk, respectively. Results offer new possibilities for the use of S100B in perinatal medicine as a key-protein for the investigations focusing on central nervous system development and damage.


Comprehensive vision care: a model.
This paper suggests a model for the practice of vision care in which the optometrist and ophthalmologist are each used to maximum advantage. It is demonstrated how the present antagonism between the two fields can be removed with a resultant enhancement of the practice of both optometry and ophthalmology. The natural outcome of the new relationship will be better vision care for the public.


Fimbriae and the hemagglutinating adhesin HA-Ag2 mediate adhesion of Porphyromonas gingivalis to epithelial cells.
The mechanisms by which Porphyromonas gingivalis, a gram-negative anaerobic bacterium, is pathogenic for the periodontium remain largely hypothetical. Invasion of host tissues by P. gingivalis is believed to require adhesion of the bacterium to host cells. The aim of this study was to use monoclonal antibodies (MAbs) to characterize the bacterial cell surface component(s) acting as a ligand binding to a receptor on epithelial cells. Surface antigens of P. gingivalis ATCC 33277 were obtained as a glass bead-EDTA extract (GBE), and antiserum against the GBE was produced in rabbits. Epithelial cell membrane proteins (ECMP) were prepared from a homogenate of the SK-MES-1 cell line with Triton X-100. The antigen/ligand profile of GBE was resolved by crossed immunoaffinity electrophoresis by using ECMP in the first-dimension gel. The migration of one immunoprecipitate (IP) was retarded, indicating a ligand-receptor interaction between a surface antigen of P. gingivalis and a complementary binding site on the epithelial cell membrane. The corresponding IP in the GBE/anti-GBE immunoelectrophoresis profile was excised from replicate gels to immunize mice for production of MAbs specific for the bacterial ligand. Five MAbs were obtained and tested for reactivity with GBE in immunoblots and for inhibition of the interaction between GBE and ECMP. Immunoblots revealed polypeptides at 28, 42, 43, and 49 kDa. Inhibition tests were positive for all five MAbs. These results are conclusive evidence that the MAbs recognize functional epitopes involved in the adherence of P. gingivalis to epithelial cells and that the adhesins are likely associated with fimbriae and the hemagglutinating adhesin HA-Ag2.


Has snake fang evolution lost its bite? New insights from a structural mechanics viewpoint.
Venomous snakes-the pinnacle of snake evolution-are characterized by their possession of venom-conducting fangs ranging from grooved phenotypes characterizing multiple lineages of rear-fanged taxa to tubular phenotypes present in elapids, viperids and atractaspidines. Despite extensive research, controversy still exists on the selective pressures involved in fang phenotype diversification. Here, we test the hypothesis that larger fangs and consequently a shift to an anterior position in the maxilla evolved to compensate for the costs of structural changes, i.e. higher stress upon impact in tubular fangs compared to grooved fangs. Direct voxel-based stress simulations conducted on high-resolution µCT scans, analysed within a phylogenetic framework, showed no differences in stress distribution between the three fang phenotypes, despite differences in (relative) fang length. These findings suggest that additional compensatory mechanisms are responsible for the biomechanical optimization and that fang length might instead be related to differential striking behaviour strategies.


Excess PrPC inhibits muscle cell differentiation via miRNA-enhanced liquid-liquid phase separation implicated in myopathy.
The cellular prion protein (PrPC) is required for skeletal muscle function. Here, we report that a higher level of PrPC accumulates in the cytoplasm of the skeletal muscle of six myopathy patients compared to controls. PrPC inhibits skeletal muscle cell autophagy, and blocks myoblast differentiation. PrPC selectively binds to a subset of miRNAs during myoblast differentiation, and the colocalization of PrPC and miR-214-3p was observed in the skeletal muscle of six myopathy patients with excessive PrPC. We demonstrate that PrPC is overexpressed in skeletal muscle cells under pathological conditions, inhibits muscle cell differentiation by physically interacting with a subset of miRNAs, and selectively recruits these miRNAs into its phase-separated condensate in living myoblasts, which in turn enhances liquid-liquid phase separation of PrPC, promotes pathological aggregation of PrP, and results in the inhibition of autophagy-related protein 5-dependent autophagy and muscle bundle formation in myopathy patients characterized by incomplete muscle regeneration.


Evaluation of three commercial screening tests for AIDS virus antibodies.
Three commercial enzyme-linked immunosorbent assays (ELISA) for acquired immune deficiency syndrome (AIDS) virus antibodies were evaluated using serum that had been characterized by an ELISA and western blot procedure developed at the University of California at Davis (UCD). Each of the commercial tests was more specific than the UCD ELISA, but the UCD ELISA was more sensitive in the detection of sera that lacked reactivity by western blot to the envelope glycoprotein (gp-41). The HTLV-III Bio-EnzaBead (Litton Bionetics, Charleston, SC) was less sensitive and specific than the Abbott HTLV-III EIA (Abbott Laboratories, North Chicago, IL) or the Virgo HTLV-III ELISA (Electro-Nucleonics Inc., Columbia, MD). Overall, 22.9% (57 of 250) and 51.0% of sera that were repeatedly (X2) positive by commercial screening kits tested at blood donor centers and clinical laboratories, respectively, were confirmed by western blot. These results indicate that the screening assays for AIDS virus antibodies are not equal in performance and that positive screening test results must be confirmed by a more specific test like western blot before results are released.


Preoperative hair removal with clippers does not increase infection rate in clean surgical wounds.
For a one year period, hair was removed from the operative site with clippers rather than by shaving with a razor or by application of depilatories. The study involved comparison of clean (Class I) wound infection rates in 2,580 patients after clipping was instituted compared with 17,424 patients studied in seven preceding years. There was no significant change in the wound infection rate (1 per cent) when compared with the three years immediately preceding. There was no change in the identified distribution of the infecting organism. Failure to show a clear reduction in wound infection rate was probably related to the low historic base line rate. There were definite benefits achieved by avoiding cancellation of elective operations, by using operating room personnel more efficiently and by expediating the surgical schedule.


Oxidative myocytes of heart and skeletal muscle express abundant sarcomeric mitochondrial creatine kinase.
Sarcomeric mitochondrial creatine kinase catalyzes the reversible transfer of a high energy phosphate between ATP and creatine. To study cellular distribution of the kinase, we performed immunocytochemical studies using a peptide antiserum specific for the kinase protein. Our results demonstrated that the sarcomeric mitochondrial creatine kinase gene is abundantly expressed in heart and skeletal muscle, with no protein detected in other tissues examined, including brain, lung, liver, spleen, kidney, bladder, testis, stomach, intestine, and colon. RNA blot study showed that there is no detectable expression of the kinase mRNA in the thymus gland. In heart and skeletal muscle, the kinase protein is expressed in atrial and ventricular cardiomyocytes and a subpopulation of skeletal myofibres. In skeletal muscle, fast myosin heavy chain co-localization studies demonstrated that the sarcomeric mitochondrial creatine kinase is highly expressed in type 1, slow-oxidative and type 2A, fast-oxidative-glycolytic myofibres. We conclude that the kinase gene is abundantly expressed in oxidative myocytes of heart and skeletal muscle and may contribute to oxidative capacity of these cells.


Five years of monitoring for the emergence of oseltamivir resistance in patients with influenza A infections in the Influenza Resistance Information Study.
The Influenza Resistance Information Study (IRIS) was initiated in 2008 to study the emergence of neuraminidase inhibitor (NAI) resistance and the clinical course of influenza in immunocompetent treated and untreated patients. Patients had throat/nose swabs collected on days 1, 3, 6 and 10 for analyses of influenza type, subtype and virus susceptibility to NAIs. RT-PCR-positive samples were cultured and tested for NAI resistance by specific RT-PCR and phenotypic testing. Scores for influenza symptoms were recorded on diary cards (Days 1-10). This study focuses on influenza A-infected cases only. Among 3230 RT-PCR-positive patients, 2316 had influenza A of whom 1216 received oseltamivir monotherapy within 2 days of symptom onset (9 seasonal H1N1; 662 H3N2; 545 H1N1pdm2009). Except for 9 patients with naturally resistant seasonal H1N1 (2008/9), no resistance was detected in Day 1 samples. Emergence of resistance (post-Day 1) was detected in 43/1207 (3.56%) oseltamivir-treated influenza A-infected patients, with a higher frequency in 1- to 5-year-olds (11.8%) vs >5-year-olds (1.4%). All N1- and N2-resistant viruses had H275Y (n = 27) or R292K (n = 16) substitutions, respectively. For 43 patients, virus clearance was significantly delayed vs treated patients with susceptible viruses (8.1 vs 10.9 days; P < .0001), and 11 (23.2%) remained RT-PCR positive for influenza at Day 10. However, their symptoms resolved by Day 6 or earlier. Oseltamivir resistance was only detected during antiviral treatment, with the highest incidence occurring among 1- to 5-year-olds. Resistance delayed viral clearance, but had no impact on symptom resolution.


Different Morphologies of Leishmania major Amastigotes with No Molecular Diversity in a Neglected Endemic Area of Zoonotic Cutaneous Leishmaniasis in Iran.
Molecular diversity of Leishmania major and its morphological changes have become a controversial issue among researchers. Some aspects of polymorphic shapes of amastigotes in clinical manifestations along with molecular variation were evaluated among suspected patients of some exceptional zoonotic cutaneous leishmaniasis locations in Northern Khuzestan, Southwestern Iran. Suspected patients (n = 165) were sampled in zoonotic cutaneous leishmaniasis foci over two consecutive years during 2012-2014. Prepared smears were stained, scaled and measured by ocular micrometer. DNA was extracted from smears; ITS-rDNA and Cytochrome b (Cyt b) markers were amplified, and PCR products were digested by BsuR1 restriction enzyme. Then the RFLP and sequencing were employed. Only L. major was identified in patients containing regular amastigotes' shapes (oval or round) with a size of 2-4 µm in each of classical wet, dry, mixed lesions. Meanwhile, irregular shapes (spindle, pear, or cigarette) were observed separately in non-classical wet lesions with more than 4 µm. Interestingly, a few amastigotes with an external flagellum were observed in some lesions. All sequenced ITS-rDNA and Cyt b genes of L. major did not show any molecular variation (χ 2 P > 0.05), including only one common haplotype (GenBank access no. EF413075). Findings proved that unlike other endemic foci, there is not a meaningful correlation between phenotypic and genotypic features of L. major isolates. This study is considered as the first comprehensive report to incriminate morphometric shapes of L. major amastigotes, which enhances our knowledge concerning their relevance with various clinical appearances and genotypic traits.


RAAS-deficient organoids indicate delayed angiogenesis as a possible cause for autosomal recessive renal tubular dysgenesis.
Autosomal Recessive Renal Tubular Dysgenesis (AR-RTD) is a fatal genetic disorder characterized by complete absence or severe depletion of proximal tubules (PT) in patients harboring pathogenic variants in genes involved in the Renin-Angiotensin-Aldosterone System. To uncover the pathomechanism of AR-RTD, differentiation of ACE-/- and AGTR1-/- induced pluripotent stem cells (iPSCs) and AR-RTD patient-derived iPSCs into kidney organoids is leveraged. Comprehensive marker analyses show that both mutant and control organoids generate indistinguishable PT in vitro under normoxic (21% O2) or hypoxic (2% O2) conditions. Fully differentiated (d24) AGTR1-/- and control organoids transplanted under the kidney capsule of immunodeficient mice engraft and mature well, as do renal vesicle stage (d14) control organoids. By contrast, d14 AGTR1-/- organoids fail to engraft due to insufficient pro-angiogenic VEGF-A expression. Notably, growth under hypoxic conditions induces VEGF-A expression and rescues engraftment of AGTR1-/- organoids at d14, as does ectopic expression of VEGF-A. We propose that PT dysgenesis in AR-RTD is primarily a non-autonomous consequence of delayed angiogenesis, starving PT at a critical time in their development.


Defects in lymphocyte telomere homeostasis contribute to cellular immune phenotype in patients with cartilage-hair hypoplasia.
Mutations in the long noncoding RNA RNase component of the mitochondrial RNA processing endoribonuclease (RMRP) give rise to the autosomal recessive condition cartilage-hair hypoplasia (CHH). The CHH disease phenotype has some overlap with dyskeratosis congenita, a well-known "telomere disorder." RMRP binds the telomerase reverse transcriptase (catalytic subunit) in some cell lines, raising the possibility that RMRP might play a role in telomere biology. We sought to determine whether a telomere phenotype is present in immune cells from patients with CHH and explore mechanisms underlying these observations. We assessed proliferative capacity and telomere length using flow-fluorescence in situ hybridization (in situ hybridization and flow cytometry) of primary lymphocytes from patients with CHH, carrier relatives, and control subjects. The role of telomerase holoenzyme components in gene expression and activity were assessed by using quantitative PCR and the telomere repeat amplification protocol from PBMCs and enriched lymphocyte cultures. Lymphocyte cultures from patients with CHH display growth defects in vitro, which is consistent with an immune deficiency cellular phenotype. Here we show that telomere length and telomerase activity are impaired in primary lymphocyte subsets from patients with CHH. Notably, telomerase activity is affected in a gene dose-dependent manner when comparing heterozygote RMRP carriers with patients with CHH. Telomerase deficiency in patients with CHH is not mediated by abnormal telomerase gene transcript levels relative to those of endogenous genes. These findings suggest that telomere deficiency is implicated in the CHH disease phenotype through an as yet unidentified mechanism.


Magnetic Hamiltonian parameter estimation using deep learning techniques.
Understanding spin textures in magnetic systems is extremely important to the spintronics and it is vital to extrapolate the magnetic Hamiltonian parameters through the experimentally determined spin. It can provide a better complementary link between theories and experimental results. We demonstrate deep learning can quantify the magnetic Hamiltonian from magnetic domain images. To train the deep neural network, we generated domain configurations with Monte Carlo method. The errors from the estimations was analyzed with statistical methods and confirmed the network was successfully trained to relate the Hamiltonian parameters with magnetic structure characteristics. The network was applied to estimate experimentally observed domain images. The results are consistent with the reported results, which verifies the effectiveness of our methods. On the basis of our study, we anticipate that the deep learning techniques make a bridge to connect the experimental and theoretical approaches not only in magnetism but also throughout any scientific research.


Mechanism of urate and p-aminohippurate transport in rat renal microvillus membrane vesicles.
The transport of urate and p-aminohippurate (PAH) was evaluated in brush border membrane vesicles from the rat renal cortex. The binding of urate to the membranes was 6% of total uptake and no conversion of urate to allantoin was detected. The binding of PAH to the membranes was 24% of total uptake. In the presence of an outwardly directed hydroxyl ion gradient (pHi = 7.5, pHo = 6.0), the uptake of urate and PAH was stimulated relative to the absence of a hydroxyl ion gradient (pHi = pHo = 7.5) and the influx of urate resulted in a transient overshoot of the equilibrium value. The hydroxyl ion gradient-stimulated uptake of urate and PAH was not solely due to a change in membrane potential. Probenecid, DIDS, furosemide, and pyrazinoate inhibited the hydroxyl ion gradient-stimulated uptake of urate and PAH in a dose-dependent manner. The uptake of [14C]urate and [3H]PAH could be cis-inhibited and trans-stimulated by either unlabeled urate or PAH. In the presence of an outwardly directed bicarbonate gradient and 10% CO2 (outside HCO-3 = 5.4 mM, inside HCO-3 = 54 mM, pHo = 6.5, pHi = 7.5), the initial rate of urate uptake was faster and the initial rate of urate efflux was slower compared with vesicles that had the same pH gradient without bicarbonate or CO2. The effects of bicarbonate gradients on organic anion transport were not dependent on diffusion potentials. Finally, 100 mM extravesicular Na+, K+, Li+, or Cs+ did not affect urate or PAH uptake. These results indicate that brush border membrane vesicles from the rat kidney contain an anion exchange transport system with affinity for urate, PAH, hydroxyl ions, and bicarbonate. In addition there is no evidence for a sodium-urate or sodium-PAH cotransport mechanism in these membranes.


High-fidelity large-diversity monoclonal mammalian cell libraries by cell cycle arrested recombinase-mediated cassette exchange.
Mammalian cells carrying defined genetic variations have shown great potentials in both fundamental research and therapeutic development. However, their full use was limited by lack of a robust method to construct large monoclonal high-quality combinatorial libraries. This study developed cell cycle arrested recombinase-mediated cassette exchange (aRMCE), able to provide monoclonality, precise genomic integration and uniform transgene expression. Via optimized nocodazole-mediated mitotic arrest, 20% target gene replacement efficiency was achieved without antibiotic selection, and the improved aRMCE efficiency was applicable to a variety of tested cell clones, transgene targets and transfection methods. As a demonstration of this versatile method, we performed directed evolution of fragment crystallizable (Fc), for which error-prone libraries of over 107 variants were constructed and displayed as IgG on surface of CHO cells. Diversities of constructed libraries were validated by deep sequencing, and panels of novel Fc mutants were identified showing improved binding towards specific Fc gamma receptors and enhanced effector functions. Due to its large cargo capacity and compatibility with different mutagenesis approaches, we expect this mammalian cell platform technology has broad applications for directed evolution, multiplex genetic assays, cell line development and stem cell engineering.


High-resolution 3D light fluence mapping for heterogeneous scattering media by localized sampling.
We demonstrate an innovative concept for three-dimensional optical fluence mapping in heterogeneous highly scattering media as, e.g., biomedical tissues. We propose to use the relative light extinction analysis principle together with a miniaturized collection fiber in a direct fluence measurement setup as a method to obtain the spatially resolved light intensity distribution under transversally inhomogeneous light propagation conditions and provide local characterization of the transport medium. System performance is validated in two extreme conditions: an optically thin scattering medium and an absorption-dominated light transport. Both extremes demonstrate good agreement to theoretical expectations. Finally, we successfully prove the ability of the system to deliver high-resolution fluence maps through a model study of the light distribution induced in a scattering medium by a vertical diode laser stack with individual bars pitched only 500 μm apart.


Generalization of the hierarchical equations of motion theory for efficient calculations with arbitrary correlation functions.
The hierarchical equations of motion (HEOM) theory is one of the standard methods to rigorously describe open quantum dynamics coupled to harmonic environments. Such a model is used to capture non-Markovian and non-perturbative effects of environments appearing in ultrafast phenomena. In the regular framework of the HEOM theory, the environment correlation functions are restricted to linear combinations of exponential functions. In this article, we present a new formulation of the HEOM theory including treatment of non-exponential correlation functions, which enables us to describe general environmental effects more efficiently and stably than the original theory and other generalizations. The library and its Python binding we developed to perform simulations based on our approach, named LibHEOM and PyHEOM, respectively, are provided as the supplementary material.


A Low-Cost Instrumented Shoe System for Gait Phase Detection Based on Foot Plantar Pressure Data.
This paper presents a novel low-cost and fully-portable instrumented shoe system for gait phase detection. The instrumented shoe consists of 174 independent sensing units constructed based on an off-the-shelf force-sensitive film known as the Velostat conductive copolymer. A zero potential method was implemented to address the crosstalk effect among the matrix-formed sensing arrays. A customized algorithm for gait event and phase detection was developed to estimate stance sub-phases including initial contact, flat foot, and push off. Experiments were carried out to evaluate the performance of the proposed instrumented shoe system in gait phase detection for both straight-line walking and turning walking. The results showed that the mean absolute time differences between the estimated phases by the proposed instrumented shoe system and the reference measurement ranged from 45 to 58 ms during straight-line walking and from 51 to 77 ms during turning walking, which were comparable to the state of art.Clinical and Translational Impact Statement-By allowing convenient gait monitoring in home healthcare settings, the proposed system enables extensive ADL data collection and facilitates developing effective treatment and rehabilitation strategies for patients with movement disorders.


Polydrug use, cannabis, and psychosis-like symptoms.
To examine psychosis-like symptoms in users of legal and illicit drugs. Schizotypal Personality Questionnaire (SPQ) scores were compared in groups of people with different exposure to cannabis, with the use of other drugs serving as a covariate. Supplemental analyses compared users of legal and illicit drugs with cannabis use as a covariate. Weekly (n = 111) and monthly (n = 136) cannabis users had higher scores on the SPQ than former (n = 143) and non-users (n = 81). The use of other drugs accounted for the links between cannabis and schizotypy. Lifetime use of psychomotor stimulant drugs plus ecstasy accounted for associations between cannabis and scores on the SPQ and its different subscales. Dividing groups by type of drug use revealed that those who used only cannabis and legal drugs (CLDs) (n = 126) were no different from those who used only legal drugs (LDs) (n = 74) but both groups scored significantly lower on the SPQ than polydrug users (n = 247). When controlling for marijuana use in the last month, the significant difference across drug use groups remained. The results suggest that research on marijuana and schizotypy requires careful assessment of the use of other drugs, especially psychomotor stimulants and ecstasy.


Psychometric comparison of the Motivation Assessment Scale (MAS) and the Questions About Behavioral Function (QABF).
The Motivation Assessment Scale (MAS) and the Questions About Behavioral Function (QABF) are frequently used to assess the learned function of challenging behaviour in people with intellectual disability (ID). The aim was to explore and compare the psychometric properties of the MAS and the QABF. Seventy adults with ID and challenging behaviour and their disability support workers participated in the study. Support workers completed the MAS and QABF regarding a challenging behaviour that they identified as causing most concern. Both measures demonstrated good internal consistency. Based on the intra-class correlation coefficient, inter-rater reliability of the MAS and QABF was acceptable for sub-scale scores, but not for individual items. Convergent validity, as reflected by correlations between functionally analogous scales, was satisfactory, but there was low agreement between the MAS and QABF on the function of challenging behaviour. Factor analysis of the QABF revealed factors that clearly corresponded to the five factors reported by the developers, four of which were well determined. Similar analyses of the MAS yielded a four-factor solution, however, only one factor was well determined. The psychometric properties of the MAS and QABF were similar, and item-by-item reliability was problematic. The results suggest that both measures may prove unreliable for assessing the function of challenging behaviour among adults with ID. In developing interventions to address challenging behaviour, other techniques (e.g. observations) should be used to supplement information from these measures.


Nurse-provided screening and brief intervention for risky alcohol consumption by sexual health clinic patients.
Brief intervention for excessive alcohol consumption is effective yet not implemented widely. Alcohol misuse is implicated in unsafe sex and sexually transmitted infections and is common in clients of sexual health services. Our aims were to assess feasibility, acceptability and effectiveness of screening and brief intervention for risky alcohol consumption by a nurse in a sexual health clinic. Patients completed the AUDIT questionnaire on handheld computers. Those scoring >or=8 on AUDIT were asked to participate in the study and the 3 months' follow-up and were randomised to intervention or control groups. The Drink-less package (based on WHO validated methods) was used to implement the brief intervention by a trained registered nurse. Of 519 (87%) who completed screening, 204 (39%) scored >or=8 on AUDIT (eligible), 184 agreed to follow-up and 133 completed it. At follow-up, both groups showed significant reductions in AUDIT scores. Mean scores decreased from 13.7 to 11.5 (control group) and 14.0 to 10.7 (intervention group); most (94%) recalled the intervention and 62% reported reducing drinking compared with 47% of controls (p<0.001). The nurse screening and intervention process was reported acceptable by 74% of patients at follow-up and a majority (71%) of staff. Screening and brief intervention in a sexual health clinic for risky alcohol consumption is feasible, acceptable and effective in producing significant reductions in drinking as measured by AUDIT. Both intervention and control groups decreased consumption, suggesting that screening alone is sufficient to influence behaviour. Further study of brief intervention in this setting is appropriate.


Inhibition of telomerase activity enhances hyperthermia-mediated radiosensitization.
Hyperthermia is a potent sensitizer of cell killing by ionizing radiation (IR); however, hyperthermia also induces heat shock protein 70 (HSP70) synthesis and HSP70 expression is associated with radioresistance. Because HSP70 interacts with the telomerase complex and expression of the telomerase catalytic unit (hTERT) extends the life span of the human cells, we determined if heat shock influences telomerase activity and whether telomerase inhibition enhances heat-mediated IR-induced cell killing. In the present study, we show that moderate hyperthermia (43 degrees C) enhances telomerase activity. Inhibition of telomerase activity with human telomerase RNA-targeted antisense agents, and in particular GRN163L, results in enhanced hyperthermia-mediated IR-induced cell killing, and ectopic expression of catalytic unit of telomerase (TERT) decreased hyperthermia-mediated IR-induced cell killing. The increased cell killing by heat and IR exposure in telomerase-inhibited cells correlates with delayed appearance and disappearance of gamma-H2AX foci as well as decreased chromosome repair. These results suggest that inactivation of telomerase before combined hyperthermia and radiotherapy could improve tumor killing.


Taiwanese nursing students' perceived knowledge and clinical comfort with genetics.
To examine perceived knowledge and clinical comfort with genetics among Taiwanese undergraduate nursing students. Information about the integration of genetics into the nursing curriculum was also assessed. A descriptive, cross-sectional study. A self-report survey designed to assess perceived knowledge and clinical comfort with genetics was distributed to 501 Taiwanese undergraduate nursing students; 434 returned the completed survey. The survey also included questions concerning the integration of genetics in the nursing curriculum. Descriptive statistics and a one-way analysis of variance were used for data analysis. Perceptions of genetic knowledge differed significantly among the different levels of nursing students; juniors had the highest genetic knowledge mean scores, followed by seniors, sophomores, and freshmen. Juniors also reported receiving the greatest number of hours of genetic content in lecture. Clinical comfort with genetics did not vary significantly among the different levels of nursing students. The majority of nursing students considered lectures to be the most effective method for learning genetic information. Findings reinforced evidence that perceived knowledge and clinical comfort with genetics among Taiwanese undergraduate nursing students are limited. It is imperative for practicing nurses and nursing students to promote the use of genetic information and technologies as a central science in the context of health care. More effort must be made to integrate genetic content into the Taiwanese nursing school curricula. With the increasing pace of the genomic revolution, nursing students are required to integrate genetic information into the art of nursing practice with the goal of promoting the health of individuals, families, and communities.


Topographical analyses of homonuclear multiple bonds between main group elements
Recent experiments have resulted in the completion of the series of Group 14 and Group 15 element double-bond systems, R(n)E=ER(n) (E = C - Pb, n = 2; E = N - Bi, n = 1). Furthermore, new families of multiple-bonded species have been discovered, such as the radical anion [RSnSnR](-) , the close ion pairs [RE(mu2Na)2ER] (E = Ge,Sn), and a digallyne [RGa(mu2Na)2GaR] for which a Ga=Ga triple bond was formulated. Some of these compounds show classical multiple bond features (i.e. the dipnictogens RE=ER, E=N-Bi) in the sense that planar structures with short E-E distances are observed. However, many (i.e. R2E=ER2, E = Si - Pb) do not behave as expected for compounds with multiple bonds. They have trans bent structures, show enormous variation in their E-E distances, and some dissociate easily under E-E bond cleavage in solution. These properties raised doubts as to whether these compounds can be formulated as multiple-bonded systems. Using the electron localization function (ELF) it is possible to clearly show the topographical similarities between classical and nonclassical multiple bonds; ELF divides these systems into unslipped (classical) and slipped (nonclassical) systems. ELF can also be employed to confirm the nonexistence of multiple bonds. Therefore, topographical analyses using ELF are useful to categorize a bonding system. In particular, the bonds in the heavier Group 14 double systems and the Ga-Ga bond in digallyne are clearly shown by this method as slipped double and triple bonds, respectively.


The effect of victim impact panels on DUI/DWI rearrest rates: a twelve-month follow-up.
Various interventions have been implemented as components of sentencing for driving under the influence of alcohol. This study assessed the effectiveness of the Victim Impact Panel (VIP) in reducing the probability of an offender being rearrested for drinking and driving. The study was conducted in an urban/suburban county in the Southeastern United States. Rearrest rates of DUI offenders who attended a VIP presentation as part of their sentencing (n = 404) were compared with an equivalent comparison group (n = 431) who did not have the VIP presentation. Arrest records of offenders were searched and rearrest rates (%) were calculated for the periods 0-6 months, 7-12 months, and 0-12 months after the arrest. Chi-square cross-tabulations indicate that rearrest rates were lower for the VIP group than the comparison group in all categories. Three categories where the differences were significant and of the greatest magnitude were white men, ages 26-35 years, and one prior DUI arrest. Additionally, logistic regression was used to compare the importance of specific independent variables on rearrest. Whether or not a subject was in the VIP group was the most powerful contributor to the results. After considering alternative explanations for the results, we conclude that the VIPs can be a cost-effective way of reducing the probability of rearrest in DUI offenders. When costs of DUI in human misery and dollars are considered, the potential benefits of large-scale implementation of VIP programs appear to be well worth the effort.


Association between childhood adversities and long-term suicidality among South Africans from the results of the South African Stress and Health study: a cross-sectional study.
Suicide and suicidal behaviours are significant public health problems and a leading cause of death worldwide and in South Africa. We examined the association between childhood adversities and suicidal behaviour over the life course. A national probability sample of 4351 South African adult participants (aged 18 years and older) in the South African Stress and Health (SASH) study was interviewed as part of the World Mental Health Surveys initiative. Respondents provided sociodemographic and diagnostic information, as well as an account of suicide-related thoughts and behaviours. Suicidality or suicidal behaviour were defined as were defined as suicide attempts and suicidal ideation in the total sample, and suicide plans and attempts among ideators. Childhood adversities included physical abuse, sexual abuse, parental death, parental divorce, other parental loss, family violence, physical illness and financial adversity. The association between suicidality and childhood adversities was examined using discrete-time survival models. More than a third of the respondents with suicidal behaviour experienced at least one childhood adversity, with physical abuse, parental death and parental divorce being the most prevalent adversities. Physical abuse, sexual abuse and parental divorce were identified as significant risk markers for lifetime suicide attempts, while physical abuse and parental divorce were significantly correlated with suicidal ideation. Two or more childhood adversities were associated with a twofold higher risk of lifetime suicide attempts. Sexual abuse (OR 9.3), parental divorce (OR 3.1) and childhood physical abuse (OR 2.2) had the strongest associations with lifetime suicide attempts. The effect of childhood adversities on suicidal tendencies varied over the life course. For example, sexual abuse was significantly associated with suicide attempts during childhood and teen years, but not during young and later adulthood. Childhood adversities, especially sexual abuse, physical abuse and parental divorce, are important risk factors for the onset and persistence of suicidal behaviour, with this risk being greatest in childhood and adolescence.


Patient perception and localization of dysphagia -- barium study correlation.
We assessed the accuracy of patient localization of the site of dysphagia and its implications for radiological practice during the barium swallow examination. Several current texts dispute the value of such information. Fifty-two consecutive patients with dysphagia were asked to localize the site of discomfort on the skin surface. The ability of each patient to do so precisely or vaguely was noted. A detailed barium examination of the pharynx, esophagus and stomach was performed. Results suggested that patients who had symptoms more cranial than the sternal notch were highly accurate at localizing disease. Localization became less precise as symptoms moved caudally towards the epigastrium. Lateralization of symptoms was highly accurate in determining the site of pathology. In conclusion, we feel that in certain circumstances the barium examination can be usefully tailored to accelerate examination times, thus reducing radiation exposure and cost whilst improving diagnostic accuracy.


Signal transduction networks and the biology of plant cells.
The development of plant transformation in the mid-1980s and of many new tools for cell biology, molecular genetics, and biochemistry has resulted in enormous progress in plant biology in the past decade. With the completion of the genome sequence of Arabidopsis thaliana just around the corner, we can expect even faster progress in the next decade. The interface between cell biology and signal transduction is emerging as a new and important field of research. In the past we thought of cell biology strictly in terms of organelles and their biogenesis and function, and researchers focused on questions such as, how do proteins enter chloroplasts? or, what is the structure of the macromolecules of the cell wall and how are these molecules secreted? Signal transduction dealt primarily with the perception of light (photomorphogenesis) or hormones and with the effect such signals have on enhancing the activity of specific genes. Now we see that the fields of cell biology and signal transduction are merging because signals pass between organelles and a single signal transduction pathway usually involves multiple organelles or cellular structures. Here are some examples to illustrate this new paradigm. How does abscisic acid (ABA) regulate stomatal closure? This pathway involves not only ABA receptors whose location is not yet known, but cation and anion channels in the plasma membrane, changes in the cytoskeleton, movement of water through water channels in the tonoplast and the plasma membrane, proteins with a farnesyl tail that can be located either in the cytosol or attached to a membrane, and probably unidentified ion channels in the tonoplast. In addition there are highly localized calcium oscillations in the cytoplasm resulting from the release of calcium stored in various compartments. The activities of all these cellular structures need to be coordinated during ABA-induced stomatal closure. For another example of the interplay between the proteins of signal transduction pathways and cytoplasmic structures, consider how plants mount defense responses against pathogens. Elicitors produced by pathogens bind to receptors on the plant plasma membrane or in the cytosol and eventually activate a large number of genes. This results in the coordination of activities at the plasma membrane (production of reactive oxygen species), in the cytoskeleton, localized calcium oscillations, and the modulation of protein kinases and protein phosphatases whose locations remain to be determined. The movement of transcription factors into the nucleus to activate the defense genes requires their release from cytosolic anchors and passage through the nuclear pore complexes of the nuclear envelope. This review does not cover all the recent progress in plant signal transduction and cell biology; it is confined to the topics that were discussed at a recent (November 1998) workshop held in Santiago at which lecturers from Chile, the USA and the UK presented recent results from their laboratories.


Evaluation of a TrkB agonist on spatial and motor learning in the Ube3a mouse model of Angelman syndrome.
Angelman syndrome is a rare neurodevelopmental disorder caused by a mutation in the maternal allele of the gene Ube3a The primary symptoms of Angelman syndrome are severe cognitive deficits, impaired motor functions, and speech disabilities. Analogous phenotypes have been detected in young adult Ube3a mice. Here, we investigate cognitive phenotypes of Ube3a mice as compared to wild-type littermate controls at an older adult age. Water maze spatial learning, swim speed, and rotarod motor coordination and balance were impaired at 6 mo of age, as predicted. Based on previous findings of reduced brain-derived neurotrophic factor in Ube3a mice, a novel therapeutic target, the TrkB agonist 7,8-DHF, was interrogated. Semichronic daily treatment with 7,8-DHF, 5 mg/kg i.p., did not significantly improve the impairments in performance during the acquisition of the water maze hidden platform location in Ube3a mice, after training with either massed or spaced trials, and had no effect on the swim speed and rotarod deficits. Robust behavioral phenotypes in middle-aged Ube3a mice appear to result from continued motor decline. Our results suggest that motor deficits could offer useful outcome measures for preclinical testing of many pharmacological targets, with the goal of reducing symptoms in adults with Angelman syndrome.


Are Sports-Related Factors Correlated to the Prevalence and Initiation of Illicit Drug Misuse in Adolescence? Prospective Study in Older Adolescents.
Sport participation is considered as a factor of potential influence on illicit drug misuse (IDM) in adolescence, but there is an evident lack of studies which prospectively investigated this problem. This study aimed to prospectively investigate the sports-related factors related to IDM and the initiation of IDM among older adolescents. The participants were 436 adolescents (202 females; 16 years old at study baseline). They were tested at baseline and follow-up (two years later). The predictors included variables associated with different facets of sports participation and success in sports. The criteria were (i) baseline IDM, (ii) follow-up IDM, and (iii) initiation of IDM between baseline and follow-up. Crude and adjusted (controlled for parental conflict, age, socioeconomic status, and gender) logistic regressions were applied to establish correlations between predictors and criteria. There were higher odds for baseline IDM in adolescents who quit individual sports (OR: 4.2, 95% CI: 1.3-13.9), who had better competitive sports achievements (OR: 1.8, 95% CI: 1.0-3.3), and those involved in sports for a longer time (OR: 1.6, 95% CI: 1.0-2.5). The IDM at follow-up was more prevalent in adolescents who were involved in sports for a longer time (OR: 1.7, 95% CI: 1.1-2.6). Initiation of drug use was predicted by longer experience in sports (OR: 1.8, 95% CI: 1.1-3.1). Sports-related factors were more negatively than positively related to illicit drug use. Most probably, the transition from junior to senior level in sports put specific stress on those adolescents who were highly committed to sports until that time, but who then had to question their own sports abilities and future potential in sports. Sport-authorities should be informed on established results and specific public-health efforts aimed at preventing IDM in athletic adolescents are urgently needed.


Remodeling of elastic fiber components in scleroderma skin.
The skin of patients with scleroderma is characterized by an excess accumulation of collagen in the extracellular matrix of the fibrotic reticular dermis. Elastic fibers are also disrupted in this disease, however, in contrast to collagen, relatively few studies have provided information concerning the changes that occur to elastic fiber components in scleroderma. In the present study, the extracellular matrix in scleroderma skin was examined with a specific focus on the integrity of elastic fibers. Electron microscopic observations confirmed an excess of 10 nm microfibrils present in small bundles independent of amorphous elastin in the fibrotic reticular dermis. In the same area, a population of stellate-shaped fibroblasts was identified in close association with the dermal elastic fibers. In contrast to the uniform black appearance of the elastic fibers seen in the papillary dermis and in areas of the reticular dermis not infiltrated by these cells, the elastic fibers apposed to the cells were mottled in density and often almost electron-lucent. These observations suggest that the elastic fibers in the reticular dermis were being actively degraded. Results from this study provide evidence for disintegration of elastic fibers in the skin of scleroderma patients and suggest the possibility that degradation products from the elastic matrix in the diseased tissues may act as a feedback signal for increased matrix production.


Glucose-regulated protein 78 regulates multiple malignant phenotypes in head and neck cancer and may serve as a molecular target of therapeutic intervention.
Glucose-regulated protein 78 (Grp78) is an endoplasmic reticulum chaperone protein and is overexpressed in various cancers. However, it is unclear how significance of this molecule play an active role contributing to the oncogenic effect of head and neck cancer (HNC). To investigate the potential function of Grp78, six HNC cell lines were used. We found that Grp78 is highly expressed in all six cell lines and many of the proteins were localized in the periphery regions, implying other function of this molecule aside from endoplasmic reticulum stress response. Knockdown of Grp78 by small interfering RNA significantly reduced cell growth and colony formation to 53% to 12% compared with that of controls in all six HNC cell lines. Using in vitro wound healing and Matrigel invasion assays, we found that cell migration and invasive ability were also inhibited to 23% to 2% in all these cell lines tested. In vivo xenograft studies showed that administration of Grp78-small interfering RNA plasmid into HNC xenografts significantly inhibited both tumor growth in situ (>60% inhibition at day 34) and liver metastasis (>90% inhibition at day 20). Our study showed that Grp78 actively regulates multiple malignant phenotypes, including cell growth, migration, and invasion. Because knockdown Grp78 expression succeeds in the reduction of tumor growth and metastatic potential, this molecule may serve as a molecular target of therapeutic intervention for HNC.


Kinetics of lamellar formation on sparsely stripped patterns.
Chemical epitaxy based on the self-assembly of block copolymers is viewed as a promising technique to achieve ordered patterns on a large scale. Herein, we study the kinetics of lamellar formation of block copolymers under the direction of sparsely stripped patterns using cell dynamics simulations of the time-dependent Ginzburg-Landau theory. First, a scaling law is unveiled with the ordering time of lamellae, tp, with respect to the multiples between the periods of lamellae and stripe patterns, which is consistent with the power law evolution of the correlation length existing in the bulk phase of lamellae. Second, the tolerative windows of perfect order, with deviation from integer multiples, are also estimated from the aspect of kinetics. The results of the ordering time and tolerative windows are of great interest for relevant experiments or applications. Finally, a two-stage evolution is explored during the pattern formation of chemical epitaxy by probing into the evolution of defects, which is of fundamental interest for us to understand the coarsening kinetics of block copolymers under the direction of chemical patterns.


Mother trees, altruistic fungi, and the perils of plant personification.
There are growing doubts about the true role of the common mycorrhizal networks (CMN or wood wide web) connecting the roots of trees in forests. We question the claims of a substantial carbon transfer from 'mother trees' to their offspring and nearby seedlings through the CMN. Recent reviews show that evidence for the 'mother tree concept' is inconclusive or absent. The origin of this concept seems to stem from a desire to humanize plant life but can lead to misunderstandings and false interpretations and may eventually harm rather than help the commendable cause of preserving forests. Two recent books serve as examples: The Hidden Life of Trees and Finding the Mother Tree.


T-wave alternans patterns during sleep in healthy, cardiac disease, and sleep apnea patients.
T-wave alternans (TWA) activity is known to be a function of heart rate and condition, as well as perhaps physiological state. A recently published nonparametric nonstationary TWA analysis method has been shown to reject nonstationary noise accurately using phase-randomized surrogates and has been shown to estimate TWA accurately. This new method was evaluated on multiple databases over a range of heart rates and in healthy subjects, cardiac disease patients, and obstructive sleep apnea (OSA) patients. We hypothesized that TWA would be lower than previously reported when measured with our new technique and that higher levels of TWA would be observed in OSA patients when compared with healthy subjects. Five databases were analyzed, as follows: (1) healthy subjects from PhysioNet's Normal Sinus Rhythm Database, (2) arrhythmia patients from PhysioNet's Chronic Heart Failure Database and (3) PhysioNet's Sudden Cardiac Death Database, (4) OSA patients from PhysioNet's MIT-BIH Polysomnographic Database, and (5) 85 subjects from a private Sleep Apnea Database. T-wave alternans magnitudes were calculated for 7 heart rate decades (intervals of 10 beats/min (bpm) between 40 and 110 bpm) for each database. The Mann-Whitney U test and the 2-sample Kolmogorov-Smirnov test were applied to test for significant differences between data from each database in each heart rate decade interval. In the healthy population, TWA activity level tended to increase with heart rate. Moreover, there appeared to be an unexpected nadir in TWA activity around 60 to 70 bpm and a small but significant rise in TWA above and below these heart rates. The rise in TWA at lower heart rates has not been previously reported, to our knowledge. We also observed that TWA is unexpectedly lower in OSA patients and did not increase with heart rate. Although the physiological mechanisms underlying our observations are unclear, there may be clinical implications for TWA testing, particularly at low heart rates, a previously overlooked aspect of TWA.


Epidemiological profile of Plasmodium ovale spp. imported from Africa to Anhui Province, China, 2012-2019.
Although autochthonous malaria cases are no longer reported in Anhui Province, China, imported malaria has become a major health concern. The proportion of reported malaria cases caused by Plasmodium ovale spp. increased to levels higher than expected during 2012 to 2019, and showed two peaks, 19.69% in 2015 and 19.35% in 2018. A case-based retrospective study was performed using data collected from the China Information System for Disease Control and Prevention (CISDCP) and Information System for Parasitic Disease Control and Prevention (ISPDCP) from 2012 to 2019 to assess the trends and differences between Plasmodium ovale curtisi (P. o. curtisi) and Plasmodium ovale wallikeri (P. o. wallikeri). Epidemiological characteristics were analyzed using descriptive statistics. Plasmodium o. curtisi and P. o. wallikeri were found to simultaneously circulate in 14 African countries. Among 128 patients infected with P. ovale spp., the proportion of co-infection cases was 10.16%. Six cases of co-infection with P. ovale spp. and P. falciparum were noted, each presenting with two clinical attacks (the first attack was due to P. falciparum and the second was due to P. ovale spp.) at different intervals. Accurate identification of the infecting species was achieved among only 20.00% of cases of P. ovale spp. infection. At the reporting units, 32.17% and 6.96% of cases of P. ovale spp. infection were misdiagnosed as P. vivax and P. falciparum infections, respectively. The present results indicate that the potential of P. ovale spp. to co-infect with other Plasmodium species has been previously underestimated, as is the incidence of P. ovale spp. in countries where malaria is endemic. P. o. curtisi may have a long latency period of > 3 years and potentially cause residual foci, thus posing challenges to the elimination of malaria in P. ovale spp.-endemic areas. Considering the low rate of species identification, more sensitive point-of-care detection methods need to be developed for P. ovale spp. and introduced in non-endemic areas.


Transverse fracture of the distal femoral metadiaphysis: a plausible accidental mechanism.
This study describes the mechanism of injury of an impacted transverse fracture of the distal femoral metadiaphysis. Individual experience by child abuse pediatricians with this fracture type has suggested that it is less associated with inflicted trauma than was described in a prior case series. Case contributions were solicited from an international group of child abuse clinicians. Eighteen cases were accepted for analysis. Cases were categorized as abuse or nonabuse by a predefined categorization scheme. Differences in the 2 groups were analyzed by Fischer exact test. Thirteen cases (72%) were determined to be nonabusive, and 5 (28%) were determined to be from abuse. Additional skeletal injuries on skeletal radiograph survey, absence of any explanatory history, and significant changes in repeated histories identified cases of abuse. A short fall was accepted as the explanation for the nonabuse cases, with some indication that direct impact on the knee explained the injury. Impacted transverse fracture of the distal femoral metadiaphysis may occur as a result of an accidental short fall of young children. A traditional abuse evaluation should be pursued in these cases, but with an absence of additional skeletal findings, and a history of a fall, it is likely that an accidental mechanism accounts for the injury.


Systems level profiling of arginine starvation reveals MYC and ERK adaptive metabolic reprogramming.
Arginine auxotrophy due to the silencing of argininosuccinate synthetase 1 (ASS1) occurs in many carcinomas and in the majority of sarcomas. Arginine deiminase (ADI-PEG20) therapy exploits this metabolic vulnerability by depleting extracellular arginine, causing arginine starvation. ASS1-negative cells develop resistance to ADI-PEG20 through a metabolic adaptation that includes re-expressing ASS1. As arginine-based multiagent therapies are being developed, further characterization of the changes induced by arginine starvation is needed. In order to develop a systems-level understanding of these changes, activity-based proteomic profiling (ABPP) and phosphoproteomic profiling were performed before and after ADI-PEG20 treatment in ADI-PEG20-sensitive and resistant sarcoma cells. When integrated with metabolomic profiling, this multi-omic analysis reveals that cellular response to arginine starvation is mediated by adaptive ERK signaling and activation of the Myc-Max transcriptional network. Concomitantly, these data elucidate proteomic changes that facilitate oxaloacetate production by enhancing glutamine and pyruvate anaplerosis and altering lipid metabolism to recycle citrate for oxidative glutaminolysis. Based on the complexity of metabolic and cellular signaling interactions, these multi-omic approaches could provide valuable tools for evaluating response to metabolically targeted therapies.


Use of an aquarium as a novel enrichment item for singly housed rhesus macaques (Macaca mulatta).
Locomotor stereotypies are behaviors often seen in singly housed rhesus macaques (Macaca mulatta) and are considered to represent a maladaptive response to captive environments. Active and passive enrichment items are commonly used to mitigate these and other abnormal behaviors. Active enrichment items allow physical manipulation and may be temporarily successful in reducing stereotypies, but their beneficial effects usually are confined to relatively short periods of active use. Passive enrichment items that do not involve physical manipulation are less well studied, and the results are mixed. This study evaluated an aquarium with live fish for use as a novel passive enrichment item in a common facility setting as a means to decrease locomotor stereotypy. We hypothesized that the introduction of the aquarium would decrease the frequency of locomotor stereotypy in a group of singly housed rhesus macaques (n = 11) with a known history of abnormal behaviors. Unexpectedly, locomotor stereotypy increased with the introduction of the aquarium and then decreased over time. Furthermore, when the aquarium was removed, the frequency of stereotypy decreased to below baseline levels. These unexpected results are best explained by neophobia, a common phenomenon documented in many animal species. The increase in abnormal behavior is likely to result from the addition of a novel object within the environment. This study demonstrates that, in the context of reducing abnormal behavior, presumably innocuous enrichment items may have unexpected effects and should be evaluated critically after their introduction to a captive population.


[Doppler ultrasound sonography of the supratrochlear artery in temporal arteritis (author's transl)].
The risk of ocular involvement in temporal arteritis is difficult to assess in the individual case. Using Doppler ultrasound sonography a clearly reduced flow or arrest of flow in the supratrochlear artery of the amaurotic side could be demonstrated in three patients. Attempts to compress branches of the external carotid artery caused no change of flow behaviour. Doppler sonography thus permits assessment of involvement of orbital vessels. This indicates the risk of loss of vision.


The classic: Tendon transplants in orthopedic practice by A Codvilla.
Alessandro Codavilla (1861-1912), Director of the famous Rizzoli Institute of Bologna, was one of the leading figures in orthopedic surgery at the turn of the century. The surgical transplantation of tendons and muscles was being widely practiced in most of the leading centers at that time with very variable success. Codavilla is credited by many of his contemporaries including Bielsalski, Mayer and Steindler for his classic and fundamental studies in the physiological aspects of tendon transfer. Published in 1899, this article generally established the physiologic concepts of modern tendon transplantation surgery.


SUBFOVEAL CHOROIDAL THICKNESS CHANGE AFTER PARS PLANA VITRECTOMY IN RECENT ONSET RHEGMATOGENOUS RETINAL DETACHMENT.
To evaluate changes in subfoveal choroidal thickness (SCT) after recent onset rhegmatogenous retinal detachment (RRD) and primary pars plana vitrectomy (PPV) using spectral-domain optical coherence tomography (SD-OCT). This retrospective study included 22 eyes of 22 patients who had primary PPV for the management of recent onset RRD. Best corrected visual acuity (BCVA), intraocular pressure (IOP), central foveal thickness (CFT), and subfoveal choroidal thickness (SCT) were measured before and 1 week, 1 month, and 3 months after the surgery. The changes in measurements were compared between operated and fellow eyes. The preoperative mean SCT of eyes with RRD was 350.2 ± 47.8 μm and of fellow eyes was 258.9 ± 46.7 μm, respectively. The postoperative mean SCT of operated eyes at 1 week, 1 month, and 3 months were 265.1 ± 45.1, 260.9 ± 46.6 and 261.1 ± 46.7 μm and of fellow eyes 256.9 ± 45.8, 257 ± 46.1 and 256.8 ± 46.6 μm, respectively. A statistically significant decrease in SCT (P < 0.001), an increase in IOP (P < 0.001), and an improvement in BCVA (P < 0.001) were observed in eyes with RRD 3 months after the surgery (Friedman test). The mean preoperative SCT of eyes with RRD was found to be greater than that of fellow eyes without any ocular surgery or disease. The increased mean SCT showed a tendency to decrease after PPV. This may be related to increased uveoscleral outflow and intraocular inflammation after RRD, and it may be concluded that vitrectomy does not affect choroidal thickness.


Neurosurgical training and global health education: systematic review of challenges and benefits of in-country programs in the care of neural tube defects.
The recognition that neurosurgeons harbor great potential to advocate for the care of individuals with neural tube defects (NTDs) globally has sounded as a clear call to action; however, neurosurgical care and training in low- and middle-income countries (LMICs) present unique challenges that must be considered. The objective of this study was to systematically review publications that describe the challenges and benefits of participating in neurosurgery-related training programs in LMICs in the service of individuals with NTDs. Using MEDLINE (PubMed), the authors conducted a systematic review of English- and Spanish-language articles published from 1974 to 2019 that describe the experiences of in-country neurosurgery-related training programs in LMICs. The inclusion criteria were as follows-1) population/exposure: US residents, US neurosurgeons, and local in-country medical staff participating in neurosurgical training programs aimed at improving healthcare for individuals with NTDs; 2) comparison: qualitative studies; and 3) outcome: description of the challenges and benefits of neurosurgical training programs. Articles meeting these criteria were assessed within a global health education conceptual framework. Nine articles met the inclusion criteria, with the majority of the in-country neurosurgical training programs being seen in subregions of Africa (8/9 [89%]) and one in South/Central America. US-based residents and neurosurgeons who participated in global health neurosurgical training had increased exposure to rare diseases not common in the US, were given the opportunity to work with a collaborative team to educate local healthcare professionals, and had increased exposure to neurosurgical procedures involved in treating NTDs. US neurosurgeons agreed that participating in international training improved their own clinical practices but also recognized that identifying international partners, travel expenses, and interference with their current practice are major barriers to participating in global health education. In contrast, the local medical personnel learned surgical techniques from visiting neurosurgeons, had increased exposure to intraoperative decision-making, and were given guidance to improve postoperative care. The most significant challenges identified were difficulties in local long-term retention of trained fellows and staff, deficient infrastructure, and lower compensation offered for pediatric neurosurgery in comparison to adult care. The challenges and benefits of international neurosurgical training programs need to be considered to effectively promote the development of neurosurgical care for individuals with NTDs in LMICs. In this global health paradigm, future work needs to investigate further the in-country professionals' perspective, as well as the related outcomes.


Alterations in the chondrocyte surfaceome in response to pro-inflammatory cytokines.
Chondrocytes are exposed to an inflammatory micro-environment in the extracellular matrix (ECM) of articular cartilage in joint diseases such as osteoarthritis (OA) and rheumatoid arthritis (RA). In OA, degenerative changes and low-grade inflammation within the joint transform the behaviour and metabolism of chondrocytes, disturb the balance between ECM synthesis and degradation, and alter the osmolality and ionic composition of the micro-environment. We hypothesize that chondrocytes adjust their physiology to the inflammatory microenvironment by modulating the expression of cell surface proteins, collectively referred to as the 'surfaceome'. Therefore, the aim of this study was to characterize the surfaceome of primary equine chondrocytes isolated from healthy joints following exposure to the pro-inflammatory cytokines interleukin-1-beta (IL-1β) and tumour necrosis factor-alpha (TNF-α). We employed combined methodology that we recently developed for investigating the surfaceome in stem cells. Membrane proteins were isolated using an aminooxy-biotinylation technique and analysed by mass spectrometry using high throughput shotgun proteomics. Selected proteins were validated by western blotting. Amongst the 431 unique cell surface proteins identified, a high percentage of low-abundance proteins, such as ion channels, receptors and transporter molecules were detected. Data are available via ProteomeXchange with identifier PXD014773. A high number of proteins exhibited different expression patterns following chondrocyte stimulation with pro-inflammatory cytokines. Low density lipoprotein related protein 1 (LPR-1), thrombospondin-1 (TSP-1), voltage dependent anion channel (VDAC) 1-2 and annexin A1 were considered to be of special interest and were analysed further by western blotting. Our results provide, for the first time, a repository for proteomic data on differentially expressed low-abundance membrane proteins on the surface of chondrocytes in response to pro-inflammatory stimuli.


Direct evidence of Parkinson pathology spread from the gastrointestinal tract to the brain in rats.
The cellular hallmarks of Parkinson's disease (PD) are the loss of nigral dopaminergic neurons and the formation of α-synuclein-enriched Lewy bodies and Lewy neurites in the remaining neurons. Based on the topographic distribution of Lewy bodies established after autopsy of brains from PD patients, Braak and coworkers hypothesized that Lewy pathology primes in the enteric nervous system and spreads to the brain, suggesting an active retrograde transport of α-synuclein (the key protein component in Lewy bodies), via the vagal nerve. This hypothesis, however, has not been tested experimentally thus far. Here, we use a human PD brain lysate containing different forms of α-synuclein (monomeric, oligomeric and fibrillar), and recombinant α-synuclein in an in vivo animal model to test this hypothesis. We demonstrate that α-synuclein present in the human PD brain lysate and distinct recombinant α-synuclein forms are transported via the vagal nerve and reach the dorsal motor nucleus of the vagus in the brainstem in a time-dependent manner after injection into the intestinal wall. Using live cell imaging in a differentiated neuroblastoma cell line, we determine that both slow and fast components of axonal transport are involved in the transport of aggregated α-synuclein. In conclusion, we here provide the first experimental evidence that different α-synuclein forms can propagate from the gut to the brain, and that microtubule-associated transport is involved in the translocation of aggregated α-synuclein in neurons.


Chromatographic and traditional albumin isotherms on cellulose: a model for wound protein adsorption on modified cotton.
Albumin is the most abundant protein found in healing wounds. Traditional and chromatographic protein isotherms of albumin binding on modified cotton fibers are useful in understanding albumin binding to cellulose wound dressings. An important consideration in the design of cellulosic wound dressings is adsorption and accumulation of proteins like albumin at the solid-liquid interface of the biological fluid and wound dressing fiber. To better understand the effect of fiber charge and molecular modifications in cellulose-containing fibers on the binding of serum albumin as observed in protease sequestrant dressings, albumin binding to modified cotton fibers was compared with traditional and chromatographic isotherms. Modified cotton including carboxymethylated, citrate-crosslinked, dialdehyde and phosphorylated cotton, which sequester elastase and collagenase, were compared for their albumin binding isotherms. Albumin isotherms on citrate-cellulose, cross-linked cotton demonstrated a two-fold increased binding affinity over untreated cotton. A comparison of albumin binding between traditional, solution isotherms and chromatographic isotherms on modified cellulose yielded similar equilibrium constants. Application of the binding affinity of albumin obtained in the in vitro protein isotherm to the in vivo wound dressing uptake of the protein is discussed. The chromatographic approach to assessment of albumin isotherms on modified cellulose offers a more rapid approach to evaluating protein binding on modified cellulose over traditional solution approaches.


One-dimensional peptide mapping of the subunits of pertussis toxin.
Pertussis toxin (pertussigen) purified from the cytoplasmic fraction of Bordetella pertussis strain 18334, phase 1, consisted of five subunits which included an additional subunit (S1a) not previously reported. Subunits S1, S1a and S2 showed extensive structural homology when analysed by one-dimensional peptide mapping, indicating that the latter two were probably derived from proteolytic cleavage of the largest subunit, S1. Subunits S3 and S4,5 generated only a limited number of peptides following chemical and enzymic degradation, but these subunits differed structurally from each other and from those showing structural homology.


Larval competition of Chrysomya megacephala and Chrysomya rufifacies (Diptera: Calliphoridae): behavior and ecological studies of two blow fly species of forensic significance.
Chrysomya megacephala and Chrysomya rufifacies are two predominant necrophagous species in Taiwan. Larvae of the latter can prey on other maggots, including that of their own species as facultative food. This facultative characteristic of C. rufifacies may enhance its competitive advantage over other maggots and could also change the situation of other coexisting colonies. In this study, these two species were colonized in the laboratory, and the main objective was to try to understand the effect of competition on larval development. According to our results, intraspecific competition mostly occurred as competition for food; when the rearing density was increased, larvae pupated earlier, resulting in a lighter adult dry weight. The tendencies were similar in both species, but C. megacephala developed smaller viable adults and had higher survivorship at high densities. Although C. rufifacies could use the food resource of cannibalism, its survivorship was still low. Our results also showed there were significant interactions between intraspecific competition and the density factor. However, with interspecific competition, the first-instar larvae of C. rufifacies invaded maggot masses of C. megacephala to feed together. The third instars of C. rufifacies were able to expel C. megacephala larvae from food by using a fleshy protrusion on their body surface; C. megacephala was usually forced to pupate earlier by shortening its larval stages. The results indicated that a temporary competitive advantage could only be obtained by C. rufifacies under a proper larval density. In addition, the effects on different larval stages, the responses to different competition intensities, and the temperature-dependent effects on interspecific competition are also discussed. In general, under mixed-species rearing at different temperatures and densities, larval duration, adult dry weight, and survivorship of both species decreased. However, our results did not completely agree with previous studies, and we suspect that the difference was partially caused by different experimental designs and different biological characters of different blow fly colonies. Our results also suggest that both the predation ability and defense or escape activity should be taken into account when evaluating larval competitive advantages. The durations of larval stages of these two species could be decreased by approximately 54 h when a single species was reared alone and food was limited; the largest reduction in larval duration, approximately 25 h in C. megacephala and 34 h in C. rufifacies, caused by interspecific competition was under a high larval density. In conclusion, competition decreased the larval duration of these two species by up to 2 d; this also draws attention to justifying the postmortem interval estimation of using larval developmental data when larval competition exists.


Fourier transform Raman spectroscopy of polyacrylamide gels (PAGs) for radiation dosimetry.
Polyacrylamide gels (PAGs) are used for magnetic resonance imaging radiation dosimetry. Fourier transform (FT) Raman spectroscopy studies were undertaken to investigate cross-linking changes during the copolymerization of polyacrylamide gels in the spectral range of 200-3500 cm(-1). Vibrational bands of 1285 cm(-1) and 1256 cm(-1) were assigned to acrylamide and bis-acrylamide single CH2 deltaCH2 binding modes. Bands were found to decrease in amplitude with increasing absorbed radiation dose as a result of copolymerization. Principal component regression was performed on FT-Raman spectra of PAG samples irradiated to 50 Gy. Two components were found to be sufficient to account for 98.7% of the variance in the data. Cross validation was used to establish the absorbed radiation dose of an unknown PAG sample from the FT-Raman spectra. The calculated correlation coefficient between measured and predictive samples was 0.997 with a standard error of estimate of 0.976 and a standard error of prediction of 1.140. Results demonstrate the potential of FT-Raman spectroscopy for ionizing radiation dosimetry using polyacrylamide gels.


Evolution of a species' range.
Gene flow from the center of a species' range can stymie adaptation at the periphery and prevent the range from expanding outward. We study this process using simple models that track both demography and the evolution of a quantitative trait in a population that is continuously distributed in space. Stabilizing selection acts on the trait and favors an optimum phenotype that changes linearly across the habitat. One of three outcomes is possible: the species will become extinct, expand to fill all of the available habitat, or be confined to a limited range in which it is sufficiently adapted to allow population growth. When the environment changes rapidly in space, increased migration inhibits local adaptation and so decreases the species' total population size. Gene flow can cause enough maladaptation that the peripheral half of a species' range acts as a demographic sink. The trait's genetic variance has little effect on species persistence or the size of the range when gene flow is sufficiently strong to keep population densities far below the carrying capacity throughout the range, but it can increase the range width and population size of an abundant species. Under some conditions, a small parameter change can dramatically shift the balance between gene flow and local adaptation, allowing a species with a limited range to suddenly expand to fill all the available habitat.


Qualitative research and its place in psychological science.
In discussing the place of diverse qualitative research within psychological science, the authors highlight the potential permeability of the quantitative-qualitative boundary and identify different ways of increasing communication between researchers specializing in different methods. Explicating diversity within qualitative research is facilitated, initially, through documenting the range of qualitative data collection and analytic methods available. The authors then consider the notion of paradigmatic frame and review debates on the current and future positioning of qualitative research within psychological science. In so doing, the authors argue that the different ways in which the concept of paradigm can be interpreted allow them to challenge the idea that diverse research paradigms are prima facie incommensurate. Further, reviewing the ways in which proponents of qualitative research are seeking to reconfigure the links between paradigms helps the authors to envisage how communication between research communities can be enhanced. This critical review allows the authors to systematize possible configurations for research practice in psychology on a continuum of paradigm integration and to specify associated criteria for judging intermethod coherence.


Diversity of bacterial endophytes in roots of Mexican husk tomato plants (Physalis ixocarpa) and their detection in the rhizosphere.
Endophytic bacterial diversity was estimated in Mexican husk tomato plant roots by amplified rDNA restriction analysis and sequence homology comparison of the 16S rDNA genes. Sixteen operational taxonomic units from the 16S rDNA root library were identified based on sequence analysis, including the classes Gammaproteobacteria, Betaproteobacteria, Actinobacteria, and Bacilli. The predominant genera were Stenotrophomonas (21.9%), Microbacterium (17.1%), Burkholderia (14.3%), Bacillus (14.3%), and Pseudomonas (10.5%). In a 16S rDNA gene library of the same plant species' rhizosphere, only common soil bacteria, including Stenotrophomonas, Burkholderia, Bacillus, and Pseudomonas, were detected. We suggest that the endophytic bacterial diversity within the roots of Mexican husk tomato plants is a subset of the rhizosphere bacterial population, dominated by a few genera.


The histidine kinase PdhS controls cell cycle progression of the pathogenic alphaproteobacterium Brucella abortus.
Bacterial differentiation is often associated with the asymmetric localization of regulatory proteins, such as histidine kinases. PdhS is an essential and polarly localized histidine kinase in the pathogenic alphaproteobacterium Brucella abortus. After cell division, PdhS is asymmetrically segregated between the two sibling cells, highlighting a differentiation event. However, the function(s) of PdhS in the B. abortus cell cycle remains unknown. We used an original approach, the pentapeptide scanning mutagenesis method, to generate a thermosensitive allele of pdhS. We report that a B. abortus strain carrying this pdhS allele displays growth arrest and an altered DivK-yellow fluorescent protein (YFP) polar localization at the restrictive temperature. Moreover, the production of a nonphosphorylatable PdhS protein or truncated PdhS proteins leads to dominant-negative effects by generating morphological defects consistent with the inhibition of cell division. In addition, we have used a domain mapping approach combined with yeast two-hybrid and fluorescence microscopy methods to better characterize the unusual PdhS sensory domain. We have identified a fragment of the PdhS sensory domain required for protein-protein interaction (amino acids [aa] 210 to 434), a fragment sufficient for polar localization (aa 1 to 434), and a fragment (aa 527 to 661) whose production in B. abortus correlates with the generation of cell shape alterations. The data support a model in which PdhS acts as an essential regulator of cell cycle progression in B. abortus and contribute to a better understanding of the differentiation program inherited by the two sibling cells.


[The use of attachments for the fixation of removable dentures].
A new design of OT-cap system attachment for removable denture fixation is offered improving fixation reliability, functional and esthetic characteristics of dentures. Establishment of attachments when the jaws are maximally tightly compressed helps evenly distribute the masticatory loading of the underlying tissues and abutment teeth individually for each patient.


Platinum(IV)-Gold(I) Agents with Promising Anticancer Activity: Selected Studies in 2D and 3D Triple-Negative Breast Cancer Models.
New heterometallic binuclear and trinuclear platinum(IV)-gold(I) compounds of the type [Pt(L)n Cl2 (OH){(OOC-4-C6 H4 -PPh2 )AuCl}x ] (L=NH3 , n=2; x=1, 2; L=diaminocyclohexane, DACH, n=1; x=2) are described. These compounds are cytotoxic and selective against a small panel of renal, bladder, ovarian, and breast cancer cell lines. We selected a trinuclear PtAu2 compound containing the PtIV core based on oxaliplatin, to further investigate its cell-death pathway, cell and organelle uptake and anticancer effects against the triple-negative breast cancer (TNBC) MDA-MB-231 cell line. This compound induces apoptosis and accumulates mainly in the nucleus and mitochondria. It also exerts remarkable antimigratory and antiangiogenic properties, and has a potent cytotoxic effect against TNBC 3D spheroids. Trinuclear compounds do not seem to display relevant interactions with calf thymus (CT) DNA and plasmid (pBR322) even in the presence of reducing agents, but inhibit pro-angiogenic enzyme thioredoxin reductase (TrxR) in TNBC cells.


Assessment of the quality of frozen serum by spectrophotometric analysis and sperm bioassay.
Serum is an integral part of media used for in vitro fertilization (IVF) and andrology work. Previous studies showed that the IVF results could benefit if sera were screened for deleterious effects before use. Such screening is impractical when fresh sera are used but may be feasible if the serum is frozen prior to use. This study assessed the impact of freezing on the quality of serum. A total of 158 serum samples, prepared in a university-based andrology-IVF center, were included in the study. The frozen sera were thawed in batches to be used in a series of laboratory experiments. Serum quality was evaluated by spectrophotometric analysis and sperm bioassay under several defined conditions: fresh, frozen, pre- and postfiltration, pre- and postcentrifugation, and the patients' fertility condition. Although all sera were filtered through 0.22-micron filter, more than 10% frozen sera required 0.4- or a combination of 0.8- and 0.4-micron filters before they could be passed through the 0.22-micron filter. Frozen sera that were directly filtrable with a 0.22-micron filter lost 13% turbidity upon filtration. The turbidity of the frozen sera were higher compared to fresh ones as revealed by optical density (OD) and relative light scattering (RLS) spectrophotometry. The freeze/storage-induced spectrophotometric changes did not correlate with the storage time. The centrifugation caused precipitation of sera components. The rate of precipitation of the serum components correlated with the duration of freezing. Spectrophotometric analysis and sperm bioassay did not differentiate the sera of pregnancy-positive and pregnancy-negative subjects. The sperm bioassay failed to detect any biological impact of freezing-induced spectrophotometric changes in the sera, suggesting that the freezing-induced changes did not significantly diminish the serum's capability of supplementing the culture media.


Differences in Cardiovascular Health Metrics in Emergency Medical Technicians Compared to Paramedics: A Cross-Sectional Study of Emergency Medical Services Professionals.
Emergency Medical Services (EMS) professionals face high physical demands in high-stress settings; however, the prevalence of cardiovascular health (CVH) risk factors in this health care workforce has not been explored. The primary objective of this study was to compare the distribution of CVH and its individual components between a sample of emergency medical technicians (EMTs) and paramedics. The secondary objective was to identify associations between demographic and employment characteristics with ideal CVH in EMS professionals. A cross-sectional survey based on the American Heart Association's (AHA; Dallas, Texas USA) Life's Simple 7 (LS7) was administered to nationally-certified EMTs and paramedics. The LS7 components were scored according to previously described cut points (ideal = 2; intermediate = 1; poor = 0). A composite CVH score (0-10) was calculated from the component scores, excluding cholesterol and blood glucose due to missing data. Multivariable logistic regression was used to estimate odds ratios (OR; 95% CI) for demographic and employment characteristics associated with optimal CVH (≥7 points). There were 24,708 respondents that were currently practicing and included. More EMTs achieved optimal CVH (n = 4,889; 48.8%) compared to paramedics (n = 4,338; 40.6%). Factors associated with higher odds of optimal CVH included: higher education level (eg, college graduate or more: OR = 2.26; 95% CI, 1.97-2.59); higher personal income (OR = 1.26; 95% CI, 1.17-1.37); and working in an urban versus rural area (OR = 1.31; 95% CI, 1.23-1.40). Paramedic certification level (OR = 0.84; 95% CI, 0.78-0.91), older age (eg, 50 years or older: OR = 0.65; 95% CI, 0.58-0.73), male sex (OR = 0.54; 95% CI, 0.50-0.56), working for a non-fire-based agency (eg, private service: OR = 0.68; 95% CI, 0.62-0.74), and providing medical transport service (OR = 0.81; 95% CI, 0.69-0.94) were associated with lower odds of optimal CVH. Several EMS-related characteristics were associated with lower odds of optimal CVH. Future studies should focus on better understanding the CVH and metabolic risk profiles for EMS professionals and their association with incident cardiovascular disease (CVD), major cardiac events, and occupational mortality.Cash RE, Crowe RP, Bower JK, Foraker RE, Panchal AR. Differences in cardiovascular health metrics in emergency medical technicians compared to paramedics: a crosssectional study of Emergency Medical Services professionals. Prehosp Disaster Med. 2019;34(3):288-296.


A 52-Year-Old Man With Progressive Weakness and Incontinence.
Here we report a challenging case of a 52-year-old man presenting with subacute constipation, urinary retention, impotence, absent Achilles reflexes, and hypoesthesia in S2-S5 dermatomes. We review the clinical decision-making as the symptoms evolved and diagnostic testing changed over time. Once the diagnosis is settled, we discuss the sign and symptoms, additional diagnostic tools, treatment options and prognosis.


Photocatalytic Hydrogen Generation from a Visible-Light-Responsive Metal-Organic Framework System: Stability versus Activity of Molybdenum Sulfide Cocatalysts.
We report the use of two earth abundant molybdenum sulfide-based cocatalysts, Mo3S132- clusters and 1T-MoS2 nanoparticles (NPs), in combination with the visible-light active metal-organic framework (MOF) MIL-125-NH2 for the photocatalytic generation of hydrogen (H2) from water splitting. Upon irradiation (λ ≥ 420 nm), the best-performing mixtures of Mo3S132-/MIL-125-NH2 and 1T-MoS2/MIL-125-NH2 exhibit high catalytic activity, producing H2 with evolution rates of 2094 and 1454 μmol h-1 gMOF-1 and apparent quantum yields of 11.0 and 5.8% at 450 nm, respectively, which are among the highest values reported to date for visible-light-driven photocatalysis with MOFs. The high performance of Mo3S132- can be attributed to the good contact between these clusters and the MOF and the large number of catalytically active sites, while the high activity of 1T-MoS2 NPs is due to their high electrical conductivity leading to fast electron transfer processes. Recycling experiments revealed that although the Mo3S132-/MIL-125-NH2 slowly loses its activity, the 1T-MoS2/MIL-125-NH2 retains its activity for at least 72 h. This work indicates that earth-abundant compounds can be stable and highly catalytically active for photocatalytic water splitting, and should be considered as promising cocatalysts with new MOFs besides the traditional noble metal NPs.


Self-reported maternal morbidity and associated factors among Brazilian women.
Demographic health surveys may constitute a valuable source of information on maternal morbidity, particularly in locations where an integrated system of epidemiological surveillance with wide geographic coverage has not yet been developed. This study analyzed the database obtained from a national Demographic Health Survey carried out in Brasil in 1996. Data regarding how the survey was conducted, characteristics of the women interviewed who had given birth to live infants in the five preceding years, characteristics of the obstetrical care received and complications reported were evaluated. Responses from a weighted total of 3,635 women were analyzed. Statistically significant differences (p<0.001) were found between geographic domains for most characteristics studied. Deliveries were predominantly hospital-based throughout the whole country. Prevalence of self-reported maternal morbidity ranged from 15.5-22.9% in the various geographic domains analyzed. This geographic factor was found to be associated to differences in the occurrence of complications, generally and specifically, for cases of prolonged labour. Differences in morbidity may reflect the intricate relationship between determinants of human development and maternal health conditions.


[Study of antiglycolipid antibodies in IgM monoclonal dysglobulinemias associated with peripheral neuropathy].
An immunological mechanism may be responsible for the peripheral neuropathies related to IgM monoclonal gammopathies. Myelin-associated glycoprotein (MAG) has been found to be one the main target antigens for these paraproteinemias. Glycosphingolipids of peripheral nerve have been also found to be targets for these antibodies, especially a sulfated glycosphingolipid containing glucuronic acid (GLSG) specific for peripheral nerve. Crossed reactivity has been found between MAG and GLSG. Anti-glycolipid antibodies were determined in 14 patients with IgM gammopathy and polyneuropathy. Glycosphingolipids from human peripheral nerve were purified and chromatographed by thin-layer chromatography for immunodetection of the antibodies. The 12 patients who had GLSG antibody activity had a clinical status identical to the reported cases of dysglobulinemic neuropathies with anti-MAG antibodies.


Earlier age at menarche is associated with higher diabetes risk and cardiometabolic disease risk factors in Brazilian adults: Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).
Early menarche has been linked to higher risk of type 2 diabetes in Western and Asian societies, yet whether age at menarche is associated with diabetes in Latin America, where puberty and diabetes may have different life courses, is unknown. We tested the hypothesis that earlier menarche is associated with higher diabetes risk in Brazilian adults. We used data from 8,075 women aged 35-74 years in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) who had complete information on age at menarche, diabetes status, and covariates. Diabetes was defined based on self-reported physician diagnosis, medication use, and laboratory variables (fasting glucose, 2-hour glucose, and glycated hemoglobin). Poisson regression was used to generate risk ratios (RR) and 95% confidence intervals (CI). Menarche onset < 11 years [vs. 13-14 years (referent)] was associated with higher risk of diabetes (RR = 1.34; 95% CI: 1.14-1.57) after adjusting for sociodemographic factors, maternal education, maternal and paternal diabetes, and birth weight. This persisted after further control for BMI at age 20 years and relative leg length. Additionally, among those not taking diabetes medications, earlier menarche [<11 years vs. 13-14 years (referent)] was associated with higher % glycated hemoglobin (p < 0.001), alanine aminotransferase (p < 0.001), triglycerides (p < 0.001), C-reactive protein (p = 0.003), waist circumference (p < 0.001), and BMI measured at baseline exam (p < 0.001). These findings support the hypothesis that earlier menarche is associated with greater risk for adult diabetes and cardiometabolic disease in the Brazilian context.


[Diagnosis of coronary disease using multiplane transesophageal echocardiography and atrial pacing].
The diagnostic value of echo-pacing has been previously report. Recently, monoplanar transesophageal echocardiography (TEE) has been used to improve the reliability of this stress procedure. Therefore, in 40 consecutive patients undergoing coronary angiography for suspected coronary artery disease (CAD) we tested the accuracy of atrial pacing (TAP) during multiplane TEE as a stress procedure. TAP was performed during TEE using a circular, adhesive electrode installed at the tip of the echoscope and connected to the pulse generator. In all patients TAP was firstly attempted by positioning the TEE probe in the esophagus and, if not successful, in the stomach. Left ventricular wall motion was monitored by means of 4, 2 chamber and long axis views from the esophagus and short axis scan from the stomach, in baseline conditions, at peak pacing and immediately after maximal heart rate. The test was considered positive if wall motion abnormalities developed during TAP. Stable capture of the atrium was obtained in 28 patients from the esophagus and in 6 patients from the stomach. Thus, TEE-TAP was performed in 34/40 patients (feasibility 85%). Wall motion abnormalities were detected during TAP in 20/24 with and in 2/10 patients without CAD. Thus, sensitivity and specificity of TEE-TAP were 83% and 80% respectively. The sensitivity of the test in single and multivessel disease resulted 72% and 92%. The 12 lead electrocardiogram during TAP showed a sensitivity of 66% and a specificity of 40% (p < 0.01 vs TEE-TAP). In conclusion, TEE-TAP is a new approach for CAD evaluation providing a complete and accurate imaging of left ventricular wall motion.


Inhibition of the fungal fatty acid synthase type I multienzyme complex.
Fatty acids are among the major building blocks of living cells, making lipid biosynthesis a potent target for compounds with antibiotic or antineoplastic properties. We present the crystal structure of the 2.6-MDa Saccharomyces cerevisiae fatty acid synthase (FAS) multienzyme in complex with the antibiotic cerulenin, representing, to our knowledge, the first structure of an inhibited fatty acid megasynthase. Cerulenin attacks the FAS ketoacyl synthase (KS) domain, forming a covalent bond to the active site cysteine C1305. The inhibitor binding causes two significant conformational changes of the enzyme. First, phenylalanine F1646, shielding the active site, flips and allows access to the nucleophilic cysteine. Second, methionine M1251, placed in the center of the acyl-binding tunnel, rotates and unlocks the inner part of the fatty acid binding cavity. The importance of the rotational movement of the gatekeeping M1251 side chain is reflected by the cerulenin resistance and the changed product spectrum reported for S. cerevisiae strains mutated in the adjacent glycine G1250. Platensimycin and thiolactomycin are two other potent inhibitors of KSs. However, in contrast to cerulenin, they show selectivity toward the prokaryotic FAS system. Because the flipped F1646 characterizes the catalytic state accessible for platensimycin and thiolactomycin binding, we superimposed structures of inhibited bacterial enzymes onto the S. cerevisiae FAS model. Although almost all side chains involved in inhibitor binding are conserved in the FAS multienzyme, a different conformation of the loop K1413-K1423 of the KS domain might explain the observed low antifungal properties of platensimycin and thiolactomycin.