Treatment of severe neonatal infections with cefotaxime. Efficacy and pharmacokinetics.
We studied the pharmacokinetics and efficacy of cefotaxime in 32 neonates with severe gram-negative infections. Many of these patients had been treated unsuccessfully with combinations of antibiotics. Eighty-one percent of these patients were cured, 6% improved, and 13% had treatment failures; there were three deaths. Eighteen patients received cefotaxime alone; 16 were cured and two improved. These data indicate an efficacy of cefotaxime sufficient to warrant more rigorous future trials. The elimination half-life of cefotaxime ranged from 2.0 +/- 0.4 hours in term neonates more than one week of age to 5.7 +/- 0.8 hours in preterm neonates less than one week of age. A volume of distribution of approximately 0.63 L was similar for all infants irrespective of age and maturity. These kinetic data can be used in design of future therapeutic regimens in more rigidly controlled trials assessing indications for cefotaxime therapy in neonates. We recommend dosing as follows, using a dose of 25 mg/kg: every 12 hours for preterm infants less than one week of age, every 8 hours for preterm infants one to four and term infants less than one week of age, and every 6 hours for term infants more than one week of age.


Phosphorylation-dependent localization of microtubule-associated protein MAP2c to the actin cytoskeleton.
Microtubule-associated protein 2 (MAP2) is a neuronal phosphoprotein that promotes net microtubule growth and actin cross-linking and bundling in vitro. Little is known about MAP2 regulation or its interaction with the cytoskeleton in vivo. Here we investigate the in vivo function of three specific sites of phosphorylation on MAP2. cAMP-dependent protein kinase activity disrupts the MAP2-microtubule interaction in living HeLa cells and promotes MAP2c localization to peripheral membrane ruffles enriched in actin. cAMP-dependent protein kinase phosphorylates serines within three KXGS motifs, one within each tubulin-binding repeat. These highly conserved motifs are also found in homologous proteins tau and MAP4. Phosphorylation at two of these sites was detected in brain tissue. Constitutive phosphorylation at these sites was mimicked by single, double, and triple mutations to glutamic acid. Biochemical and microscopy-based assays indicated that mutation of a single residue was adequate to disrupt the MAP2-microtubule interaction in HeLa cells. Double or triple point mutation promoted MAP2c localization to the actin cytoskeleton. Specific association between MAP2c and the actin cytoskeleton was demonstrated by retention of MAP2c-actin colocalization after detergent extraction. Specific phosphorylation states may enhance the interaction of MAP2 with the actin cytoskeleton, thereby providing a regulated mechanism for MAP2 function within distinct cytoskeletal domains.


Evaluation of occupational health and safety intervention for the waste and sanitation workers in Bangladesh during COVID-19.
Waste and sanitation workers in South-Asian countries are vulnerable to injuries and diseases, including COVID-19. In Bangladesh, an intervention was implemented during COVID-19 to lower these workers' occupational health risks through training and PPE distribution. We assessed how the intervention affected their occupational health behaviors using a randomized cluster trial in 10 Bangladeshi cities, including seven intervention and three control areas. We conducted 499 surveys (Control-152, Intervention-347) and 47 structured observations (Control:15, Intervention:32) at baseline and 499 surveys (Control:150, Intervention:349) and 50 structured observations (Control:15, Intervention:35) at endline. To evaluate the impact of intervention at the endline, we used the difference in difference (DID) method. Compared to control, workers from intervention areas were more likely to have increased knowledge of using/maintaining PPEs (adjusted DID: 21%, CI: 8, 33), major COVID-19 transmission causes (adjusted DID: 27%, CI: 14, 40), and preventive measures (adjusted DID: 12%, CI: -0.6, 25), and improved attitude about using PPEs (adjusted DID: 36%, CI: 22, 49), washing PPEs (adjusted DID: 20%, CI: 8, 32). The intervention was more likely to improve workers' self-reported practice of taking adequate precautions after getting back from work (adjusted DID: 37%, CI: 27, 47) and changing/cleaning masks every day (adjusted DID: 47%, CI: 0.03, 94), and observed practices of maintaining coughing etiquette (DID: 20%, CI: 0.2, 40) at workplace and handwashing before wearing PPEs (DID: 27%, CI: 2, 52), after finishing work (DID: 31%, CI: -7, 69) & during work intervals (DID: 30%, CI: -33, 93). There was not much improvement in observed practices of mask use (DID: 1%, CI: -40, 42), handwashing before meals (DID: 2%, CI: -61, 65), and after toilet (DID: 7%, CI: -41, 55). This intervention has improved the knowledge, attitude and practice of the workers about critical occupational risk mitigation, which may be replicated in similar settings. Future interventions need to address occupational health-related injuries and health complications, introduce regular health checkups/insurance for the workers, create a balance between the quality and comfort of the PPEs and ensure a mechanism to ensure a regular supply of PPEs.


Reliability and validity of a Swedish language version of the Resilience Scale.
The purpose of this study was to test the reliability and validity of the Swedish language version of the Resilience Scale (RS). Participants were 142 adults between 19-85 years of age. Internal consistency reliability, stability over time, and construct validity were evaluated using Cronbach's alpha, principal components analysis with varimax rotation and correlations with scores on the Sense of Coherence Scale (SOC) and the Rosenberg Self-Esteem Scale (RSE). The mean score on the RS was 142 (SD = 15). The possible scores on the RS range from 25 to 175, and scores higher than 146 are considered high. The test-retest correlation was .78. Correlations with the SOC and the RSE were .41 (p < 0.01) and .37 (p < 0.01), respectively. Personal Assurance and Acceptance of Self and Life emerged as components from the principal components analysis. These findings provide evidence for the reliability and validity of the Swedish language version of the RS.


Stimulatory effect of 8-Epi-PGF2 alpha, an F2-isoprostane, on endothelin-1 release.
8-Epi-prostaglandin F2 alpha (8-epi-PGF2 alpha) is an F2-isoprostane produced in vivo by a cyclooxygenase-independent, free radical-catalyzed lipid peroxidation mechanism. It exhibits renal vasoconstrictor effects by binding to a receptor related to, but distinct from, that of thromboxane A2 (TxA2). In cultured bovine aortic endothelial cells (BAECs), competitive binding assays using [3H]-8-epi-PGF2 alpha indicated the existence of two distinct binding sites. The Kd values were similar to those of cultured rat aortic smooth-muscle cells, suggesting that the high- and the low-affinity binding sites represent isoprostane and TxA2 receptors, respectively. 8-Epi-PGF2 alpha dose-dependently stimulated endothelin-1 (ET-1) secretion from BAECs. These increases were partially inhibited by a TxA2 receptor antagonist, consistent with the premise that isoprostanes and TxA2 recognize closely related receptors. The presence of specific binding sites for F2-isoprostanes on endothelial cells widens the scope of the possible pathophysiologic significance of these eicosanoids, released during oxidant injury, to include alteration of endothelial cell biology. The release of ET-1 by 8-epi-PGF2 alpha may help to explain the large increases in plasma and urinary concentrations for both ET-1 and 8-epi-PGF2 alpha in patients with hepatorenal syndrome.


Biodynamic lighting conditions preserve nocturnal melatonin production in pregnant women during hospitalization: A randomized prospective pilot study.
Maternal circadian rhythms are important for maintaining maternal and fetal homeostasis. The maternal circadian system coordinates the internal clock of the fetus with environmental lighting conditions via the melatonin signal. The intensity and wavelength of daylight influence nocturnal melatonin production. This study aims to evaluate the effect of environmental lighting conditions on melatonin production in pregnant women with reduced mobility during hospitalization. We installed a human-centric lighting system with biodynamic effects (BDL, biodynamic lighting) in the patient rooms. The pregnant women in the patient rooms with standard indoor conditions served as a control group. The illuminance (lux) and dose of effective circadian irradiation (Hec) were recorded every 10 seconds by light dosimeters (Lucerne University, Switzerland) attached to the patients` clothing. We analyzed the illuminance status of 47 pregnant women with a median (IQR) gestational age of 29.9 (25.4-32.3) weeks of gestation. The median illuminance in the control group was significantly lower (p<0.05) than in the BDL group in the morning and afternoon from day 1 to 5. BDL patients had a significantly higher effective circadian irradiation in the morning. The effective circadian irradiation showed a significant daily rhythm only in the BDL group. The BDL group had a significantly higher melatonin production on day 3 (p=0.006) and day 5 (p=0.012) than the control group median (IQR) nocturnal 6-Sulfatoxymelatonin excretion 15840 (10140-22160) ng/12h vs. 6141 (2080-11328) ng/12h on day 3 and 18780 (11320-23562) ng/12h vs. 6380 (3500-17600) ng/12h on day 5). We have demonstrated that dramatically altered lighting conditions of hospitalized pregnant women may be optimized by installing biodynamic lighting systems in the patient rooms resulting in the maintenance of nocturnal melatonin production in pregnant women.


Tumor sponge implantation: an in vivo method for studying syngeneic, primary antitumor lymphocyte responses.
Sponge matrices surgically implanted in the s.c. space of the back of normal BALB/c mice were injected with a "regressor" dose of Moloney virus-induced BALB/c tumor cells. The kinetics of the generation of cytotoxic cells within the sponge was studied over a 22-day period in a short-term 51Cr release assay. Cytotoxic activity peaked on Day 16 and then declined to negligible levels by Day 22. No cytotoxicity was detectable when nontransformed BALB/c blast cells, Moloney leukemia virus-induced tumor (LSTRA) cells, or unrelated chemically induced tumor (EL4) cells were used as targets. When the cellular composition of implanted tumor sponges was examined on Day 16, it was found to be 30 to 40% myeloperoxidase-positive cells, 15 to 25% surface immunoglobulin-positive cells, and 40 to 50% theta-positive cells. Treatment with anti-Thy 1.2 plus complement eliminated the cytotoxic response on Day 16. The ratio of T-cells to tumor cells within the sponge was determined by immunofluorescence. Kinetic studies showed that the number of theta-positive cells increased well before cytolytic activity was detected, possibly reflecting increasing numbers of amplifier T-cells or cytotoxic cell precursors. A later decline in theta-positive cells correlated directly with decreased cytotoxicity. Furthermore, onset of cytotoxic activity also correlated with a decline in the percentage of Moloney murine sarcoma virus tumor cells within the sponge. Sponge cells isolated on Day 16 (peak cytotoxicity), mixed with lethal dosages of moloney murine sarcoma virus tumor cells, successfully neutralized the lethal challenge demonstrating the in vivo antitumor efficacy of these effector cells. Sponges were also implanted in mice which had been immunized with single injection of Moloney murine sarcoma virus cells. Inoculation of the sponge with tumor cells resulted in a second set response in which cytotoxic cells appeared much earlier than in unsensitized animals. Cells from spleen, lymph node, or peritoneal cavity of normal or presensitized animals with tumor sponge implants were not cytotoxic, suggesting a highly localized response.


Dalbavancin in the treatment of complicated skin and soft-tissue infections: a review.
Increasing rates of antimicrobial resistance among strains of Streptococcus, Staphylococcus, and Enterococcus spp. have been widely documented. At least 50% of nosocomial Staphylococcus aureus infections in intensive care units in the US and UK are due methicillin-resistant S. aureus (MRSA). Drug resistance is not confined to hospitals, and community-acquired MRSA (CA-MRSA) strains are now common causes of complicated skin and soft-tissue infections (cSSTIs) in many regions. Dalbavancin is a novel parenterally administered semisynthetic lipoglycopeptide similar to the naturally produced glycopeptides vancomycin and teicoplanin. Dalbavancin features a multifaceted mechanism of action that inhibits bacterial cell wall formation by two different mechanisms that enhances its activity against a wide range of gram-positive bacteria including staphylococci, streptococci, enterococci, and some anaerobes. Additionally, dalbavancin possesses unique pharmacokinetic properties, the most significant of which is a long terminal half-life that allows for once weekly dosing. This attribute may prove to yield clinical and cost benefit. Overall, clinical trials indicate that dalbavancin is a safe, well-tolerated, and effective antimicrobial agent. In the largest investigation evaluating dalbavancin for the treatment of cSSTIs, it appeared to be as effective as linezolid. Dalbavancin, which is expected to receive FDA approval in 2008, appears to be a promising new antimicrobial agent for the treatment of cSSTIs.


[Acute toxicity study of cefpirome sulfate in mice and rats].
Acute toxicity of cefpirome sulfate (CPR) was examined in 6-week-old mice and rats and immature (5-day-old) rats. The LD50 values of CPR (mg/kg) were as follows: (1) mice: intravenous, 2420 (95% confidence limits, 2122-2758) for males and 2400 (2181-2640) for females; intraperitoneal, 3850 (3407-4351) for males and 4200 (3889-4536) for females; and oral, 16200 (14781-17755) for males and 18500 (17290-19795) for females. (2) 6-week-old rats: intravenous, 1900 (1784-2023) for males and 2080 (1953-2215) for females; intraperitoneal, 6550 (6179-6943) for males and 5800 (5311-6334) for females; subcutaneous, more than 10000 for both sexes; and oral, more than 8000 for both sexes. (3) 5-day-old rats: subcutaneous, between 1750 and 2500 for males and 2080 (1651-2621) for females. Major changes in general health conditions observed in 6-week-old mice and rats were decreased spontaneous activity, lying prone, tremor, respiratory changes (slow or deep respiration, gasping), clonic or clonic-tonic convulsions. In the 6-week-old rats dosed subcutaneously, vocalization, writhing and cutaneous changes at the injection site (dark reddening or blackening, swelling, exfoliation, depilation, induration) were also observed. In the 5-day-old rats dosed subcutaneously, the changes noted were slow respiration, writhing, cyanosis, and dark reddening and swelling of the skin at the injection site. After administration, transient depression of body weight gain or loss of body weight was observed in the mice and rats except the rats dosed orally. These changes disappeared at 7 days after administration at latest, and all surviving animals showed favorable body weight gain thereafter. Necropsies revealed hemorrhage under meninges in the brain in many of the mice and rats which died. Other findings included subcutaneous changes at the injection site in the 6-week-old and 5-day-old rats dosed subcutaneously (dark reddening, retention of dark red fluid, retention of red, white or dark red gelatinous material) and changes in the peritoneal cavity in the 6-week-old rats dosed intraperitoneally (red or dark red spots on the serous membrane, reddening of adipose tissues).


Fear of cancer recurrence in adult cancer survivors: a systematic review of quantitative studies.
Fear of cancer recurrence (FCR) is among the most commonly reported problems and one of the most prevalent areas of unmet needs for cancer survivors and their carers. This review aims to provide a comprehensive overview of current scientific knowledge on FCR and to formulate recommendations for future research. A systematic review was undertaken to identify quantitative studies associated with FCR. Relevant studies were identified via Medline, CINAHL, PsycINFO and AMED databases from 1996 through December 2011. Data from 130 eligible papers were extracted and summarized following a systematic scheme. Multiple FCR assessment methods were identified. Survivors reported low to moderate level of FCR but considered it as one of the top greatest concerns and the most frequently endorsed unmet need. FCR remains stable over the survivorship trajectory. Younger age, presence and severity of physical symptoms, psychological distress and lower quality of life were associated with higher FCR. Health behaviours, psychological reactions and functional impairments were identified as FCR consequences. Carers reported higher FCR than the patients. Limited data on interventions were available. FCR research has expanded somewhat haphazardly over the last 20 years. Adopted consensual definition and used well-validated measures will be necessary. Longitudinal research examining the longer-term development and impact of FCR is clearly needed. The proposal and evaluation of theoretical models of FCR is a priority. Identifying the key features of FCR will stimulate the research and the development of targeted interventions for cancer survivors and their carers.


Poly(ADP-ribose) polymerase 1 is indispensable for transforming growth factor-β Induced Smad3 activation in vascular smooth muscle cell.
Transforming growth factor type-β (TGF-β)/Smad pathway plays an essential role in vascular fibrosis. Reactive oxygen species (ROS) generation also mediates TGF-β signaling-induced vascular fibrosis, suggesting that some sort of interaction exists between Smad and redox pathways. However, the underlying molecular mechanism is largely unknown. This study aims to investigate the influence of poly(ADP-ribose) polymerase 1 (PARP1), a downstream effector of ROS, on TGF-β signaling transduction through Smad3 pathway in rat vascular smooth muscle cells (VSMCs). TGF-β1 treatment promoted PARP1 activation through induction of ROS generation in rat VSMCs. TGF-β1-induced phosphorylation and nuclear accumulation of Smad3 was prevented by treatment of cells with PARP inhibitor, 3-aminobenzamide (3AB) or N-(6-oxo-5,6-dihydrophenanthridin-2-yl)-2-(N,N-dimethylamino)acetami (PJ34), or PARP1 siRNA. TGF-β1 treatment promoted poly(ADP-ribosy)lation of Smad3 via activation of PARP1 in the nucleus. Poly(ADP-ribosy)lation enhanced Smad-Smad binding element (SBE) complex formation in nuclear extracts and increased DNA binding activity of Smad3. Pretreatment with 3AB, PJ34, or PARP1 siRNA prevented TGF-β1-induced Smad3 transactivation and expression of Smad3 target genes, including collagen Iα1, collagen IIIα1 and tissue inhibitor of metalloproteinase 1, in rat VSMCs. PARP1 is indispensable for TGF-β1 induced Smad3 activation in rat VSMCs. Targeting PARP1 may be a promising therapeutic approach against vascular diseases induced by dysregulation of TGF-β/Smad3 pathway.


Study protocol: evaluation of a community health promotion program in a socioeconomically deprived city district in the Netherlands using mixed methods and guided by action research.
Voorstad on the Move (VoM) is a community health promotion program implemented in a socioeconomically deprived city district in the Netherlands. Based on exploration of the health situation, concurrent views on health promotion, and insights from literature, VoM is grounded in a social-ecological perspective and puts three action principles center core: citizens' participation, intersectoral collaboration, and a health supportive environment. VoM aims to improve the health of inhabitants, mostly low socioeconomic status (SES) families, and to realize changes in the social and physical environment. This current research, as part of the wider VoM project, aims to study the impacts and action principles of VoM. The main research questions concern the inhabitants' perceptions on health and health supportive environments, the perceived benefits of citizen participation in terms of health literacy and empowerment, and the factors and mechanisms that contribute to citizen participation and intersectoral collaboration. The study has a mixed methods design, including process evaluation and monitoring, and combines qualitative and quantitative data. Research activities include literature study, in-depth interviews, focus group discussions, concept and capacity mapping, document analysis, and health survey data. A prominent strategy is action research, which aims to involve all stakeholders, capturing the different perspectives of citizens and professionals, and engaging low SES groups. The principle of triangulation is continuously applied to optimize the reliability of this study, using multiple methods and multiple sources. Internal validity is enhanced by triangulation of methods and resources. Other verification techniques will also be used, such as expert consultation. The design of the study, with a strong focus on action research, facilitates the involvement of all stakeholders and contributes to the development of capacities, learning, and empowerment, and thus contributes to health. The VoM program is innovative because it adopts an open approach in which activities evolve from citizens' needs, with a focus on action elements. This study will unravel the mechanisms of the action elements at community level, thereby helping to find ways to reduce health inequities. The findings will further elucidate what works and why it works for low SES groups.


Inhibition of Aurora Kinase A Induces Necroptosis in Pancreatic Carcinoma.
Induction of nonapoptotic cell death could be an approach to eliminate apoptosis-resistant tumors. We investigated necroptosis-based therapies in mouse models of pancreatic ductal adenocarcinoma cancer (PDAC). We screened 273 commercially available kinase inhibitors for cytotoxicity against a human PDAC cell line (PANC1). We evaluated the ability of the aurora kinase inhibitor CCT137690 to stimulate necroptosis in PDAC cell lines (PANC1, PANC2.03, CFPAC1, MiaPaCa2, BxPc3, and PANC02) and the HEK293 cell line, measuring loss of plasma membrane integrity, gain in cell volume, swollen organelles, and cytoplasmic vacuoles. We tested the effects of CCT137690 in colon formation assays, and the effects of the necroptosis (necrostatin-1 and necrosulfonamide), apoptosis, autophagy, and ferroptosis inhibitors. We derived cells from tumors that developed in Pdx1-Cre;K-RasG12D/+;p53R172H/+ (KPC) mice. Genes encoding proteins in cell death pathways were knocked out, knocked down, or expressed from transgenes in PDAC cell lines. Athymic nude or B6 mice were given subcutaneous injections of PDAC cells or tail-vein injections of KPC tumor cells. Mice were given CCT137690 (80 mg/kg) or vehicle and tumor growth was monitored; tumor tissues were collected and analyzed by immunohistochemistry. We compared gene expression levels between human pancreatic cancer tissues (n = 130) with patient survival times using the online R2 genomics analysis and visualization platform. CCT137690 induced necrosis-like death in PDAC cell lines and reduced colony formation; these effects required RIPK1, RIPK3, and MLKL, as well as inhibition of aurora kinase A (AURKA). AURKA interacted directly with RIPK1 and RIPK3 to reduce necrosome activation. AURKA-mediated phosphorylation of glycogen synthase kinase 3 beta (GSK3β) at serine 9 inhibited activation of the RIPK3 and MLKL necrosome. Mutations in AURKA (D274A) or GSK3β (S9A), or pharmacologic inhibitors of RIPK1 signaling via RIPK3 and MLKL, reduced the cytotoxic activity of CCT137690 in PDAC cells. Oral administration of CCT137690 induced necroptosis and immunogenic cell death in subcutaneous and orthotopic tumors in mice, and reduced tumor growth and tumor cell phosphorylation of AURKA and GSK3β. CCT137690 increased survival times of mice with orthotopic KPC PDACs and reduced tumor growth, stroma, and metastasis. Increased expression of AURKA and GSK3β mRNAs associated with shorter survival times of patients with pancreatic cancer. We identified the aurora kinase inhibitor CCT137690 as an agent that induces necrosis-like death in PDAC cells, via RIPK1, RIPK3, and MLKL. CCT137690 slowed growth of orthotopic tumors from PDAC cells in mice, and expression of AURKA and GSK3β associate with patient survival times. AURKA might be targeted for treatment of pancreatic cancer.


Biophysical approach toward tumor regression in mice.
An external electrical source of low magnitude was used in a series of experiments to alter inherent tumor potentials in mice. While no significant increase of tumor growth was noted in the acceleration group, total tumor regressions were obtained in the inhibition group. Preliminary studies with leukemia did not yield significant results.


Spatial and temporal codes mediate the tactile perception of natural textures.
When we run our fingers over the surface of an object, we acquire information about its microgeometry and material properties. Texture information is widely believed to be conveyed in spatial patterns of activation evoked across one of three populations of cutaneous mechanoreceptive afferents that innervate the fingertips. Here, we record the responses evoked in individual cutaneous afferents in Rhesus macaques as we scan a diverse set of natural textures across their fingertips using a custom-made rotating drum stimulator. We show that a spatial mechanism can only account for the processing of coarse textures. Information about most natural textures, however, is conveyed through precise temporal spiking patterns in afferent responses, driven by high-frequency skin vibrations elicited during scanning. Furthermore, these texture-specific spiking patterns predictably dilate or contract in time with changes in scanning speed; the systematic effect of speed on neuronal activity suggests that it can be reversed to achieve perceptual constancy across speeds. The proposed temporal coding mechanism involves converting the fine spatial structure of the surface into a temporal spiking pattern, shaped in part by the mechanical properties of the skin, and ascribes an additional function to vibration-sensitive mechanoreceptive afferents. This temporal mechanism complements the spatial one and greatly extends the range of tangible textures. We show that a combination of spatial and temporal mechanisms, mediated by all three populations of afferents, accounts for perceptual judgments of texture.


Forecasting the 2020 COVID-19 Epidemic: A Multivariate Quasi-Poisson Regression to Model the Evolution of New Cases in Chile.
Objectives: To understand and forecast the evolution of COVID-19 (Coronavirus disease 2019) in Chile, and analyze alternative simulated scenarios to better predict alternative paths, in order to implement policy solutions to stop the spread and minimize damage. Methods: We have specified a novel multi-parameter generalized logistic growth model, which does not only look at the trend of the data, but also includes explanatory covariates, using a quasi-Poisson regression specification to account for overdispersion of the count data. We fitted our model to data from the onset of the disease (February 28) until September 15. Estimating the parameters from our model, we predicted the growth of the epidemic for the evolution of the disease until the end of October 2020. We also evaluated via simulations different fictional scenarios for the outcome of alternative policies (those analyses are included in the Supplementary Material). Results and Conclusions: The evolution of the disease has not followed an exponential growth, but rather, stabilized and moved downward after July 2020, starting to increase again after the implementation of the Step-by-Step policy. The lockdown policy implemented in the majority of the country has proven effective in stopping the spread, and the lockdown-relaxation policies, however gradual, appear to have caused an upward break in the trend.


Serpins flex their muscle: II. Structural insights into target peptidase recognition, polymerization, and transport functions.
Inhibitory serpins are metastable proteins that undergo a substantial conformational rearrangement to covalently trap target peptidases. The serpin reactive center loop contributes a majority of the interactions that serpins make during the initial binding to target peptidases. However, structural studies on serpin-peptidase complexes reveal a broader set of contacts on the scaffold of inhibitory serpins that have substantial influence on guiding peptidase recognition. Structural and biophysical studies also reveal how aberrant serpin folding can lead to the formation of domain-swapped serpin multimers rather than the monomeric metastable state. Serpin domain swapping may therefore underlie the polymerization events characteristic of the serpinopathies. Finally, recent structural studies reveal how the serpin fold has been adapted for non-inhibitory functions such as hormone binding.


[The mechanism of interaction between Yersinia pestis and erythrocytes, and its importance for the pathogenesis of plague].
The ability of Yersinia pestis to get inside human and murine red blood cells (RBC) was found both in vivo and in vitro experiments. Due to oxidase and catalase activities, the microorganisms induced the denaturation of hemoglobin (Hb) through RBC oxidation to H2O2 in high concentration providing the formation of haemin and transformation of haem Fe2+ into the utilizable form, Fe3+. This phenomenon was found to be common in vitro for all Y. pestis strains used in the study independently of Pgm phenotype and plasmid content, including vaccine Pgm(-) Y. pestis EV NIIEG and plasmidless Pgm(+) Y. pestis PKR-133 stains. This, probably, allows the bacteria to use Hb as an essential source of iron and porphyrins for de novo synthesis of DNA followed by effective multiplication in the mammalian organism. A correlation between the loss of the ability of RBC to transport O2 to organs and tissues and the development of progressive tissue hypoxia with specific clinical features of metHb accumulation and haemorrhagic syndrome was shown. The participation of Y. pestis phospholipases (A and D) in the destruction of RBC membranes and translocation of plague bacilli into RBC, as well as the phenomenon of polysaccharide chain lengthening depending on cultivation conditions of Y. pestis bacteria, are discussed.


Asleep Robot-Assisted Surgery for the Implantation of Subthalamic Electrodes Provides the Same Clinical Improvement and Therapeutic Window as Awake Surgery.
To study the impact of not performing awake clinical evaluation during the robot-assisted implantation of subthalamic nucleus deep brain stimulation (STN-DBS) electrodes on the stimulation parameters and clinical outcomes in patients with Parkinson disease (PD). A total of 23 patients with PD underwent robot-assisted surgery for the bilateral implantation of STN-DBS electrodes. Thirteen patients received general anesthesia (GA) and a limited intraoperative evaluation (side effects only), and the other 10 patients received local anesthesia (LA) and a full evaluation. The primary endpoint was the therapeutic window (TW), defined as the difference between the mean voltage threshold for motor improvement and the mean voltage threshold for side effects in the active contacts at 12 months after surgery. Motor scores were measured as well. The TW was similar in the LA and GA groups, with mean ± standard deviation values of 2.06 ± 0.53 V and 2.28 ± 0.99 V, respectively (P = 0.32). In the short term, the Unified Parkinson Disease Rating Scale (UPDRS) III score in the "off-drug, on-stim" condition fell to a similar extent in the LA and GA groups (by 40.3% and 49%, respectively; P = 0.336), as did the UPDRS III score in the "on-stim, on-drug" condition (by 57% and 70.7%, respectively; P = 0.36). Asleep, robot-assisted implantation of STN-DBS electrodes (with accurate identification of the STN and positioning of the DBS lead) produced the same motor results and TW as awake surgery.


An overview of swine influenza.
Swine influenza is a highly infectious viral disease of pigs, causing considerable economic impact. The causative agent is known as a type A orthomyxovirus with a segmented RNA genome. Influenza type A virus is a highly contagious pathogen among a limited number of birds and mammals. The objective of this review is to summarize the current knowledge in swine influenza infection in pigs with emphasizing on epidemiology, pathogenesis, diagnostic techniques and control measures.


[A Japanese version of the Type A questionnaire (MYTH) for children].
The reliability and validity of a Japanese version of the Matthews Youth Test for Health (MYTH) are reported. The MYTH is a questionnaire by which the degrees of Type A in children are measured. In Study 1, 23 teachers in kindergartens and day nurseries rated their children (N = 482 in all; 3 to 5 years old) by using the MYTH. Statistical analyses of the data indicate that this questionnaire is reliable and internally consistent, and has two factors, competitiveness and impatience-aggression, just as the American version. In Study 2, children (4 to 5 years old) were divided into two groups, Type-A (N = 24) and Type-B (N = 25), according to the scores of the MYTH. Each child was given three tasks (mailing, discrimination, and putting-in-chips). The results show that in those tasks Type-A children show more time urgency, hard-driving, and competition than Type-B children, which suggests that the Japanese version has a high construct validity. These two studies indicate that the Japanese version can be used in Japan to study Type A of young children.


A non-small cell lung cancer (NSCLC) patient with leptomeningeal metastasis harboring rare epidermal growth factor receptor (EGFR) mutations G719S and L861Q benefited from doubling dosage of osimertinib: a case report.
Leptomeningeal metastasis (LM) is a rare but lethal complication of advanced non-small cell lung cancer (NSCLC) that has a devastating impact on patient survival and quality of life. Osimertinib, an irreversible tyrosine kinase inhibitor, is approved as a therapy for advanced NSCLC with epidermal growth factor receptor (EGFR) mutation. However, the efficacy and optimal dosage of osimertinib in the treatment of NSCLC patients with LM who harbor uncommon EGFR mutations have yet to be fully investigated. Herein, we report a case of an advanced NSCLC patient with LM carrying EGFR G719S and L861Q, who was successfully treated by osimertinib at 160 mg. The patient initially presented with clear cell renal carcinoma and renal metastatic adenocarcinoma, and underwent right nephrectomy. At 2 months after nephrectomy, he developed a disturbance of consciousness and was subsequently diagnosed with NSCLC with LM by meningeal biopsy pathology and cerebrospinal fluid (CSF) cytology. Next-generation sequencing detected the rare EGFR mutations G719S and L861R in the meningeal biopsy tissues. The patient was then administered osimertinib at 80 mg quaque die (QD); after 1 month of treatment, his symptoms were alleviated. However, two months later, he experienced epileptic episode. Subsequently, the osimertinib dosage was doubled to 160 mg QD. After 1 month of treatment, the patient achieved central nervous system (CNS) response, and at the time of this manuscript's submission, he had maintained stable disease (SD) for more than 1 year. To our knowledge, this study provides the first clinical evidence that the administration of osimertinib at 160 mg once daily can achieve an encouraging, durable response in an NSCLC patient with LM carrying EGFR G719S and L861Q.


Amniotic mesenchymal tissue cells inhibit dendritic cell differentiation of peripheral blood and amnion resident monocytes.
Cells derived from the amniotic membranes of human term placenta have drawn much interest for their characteristics of multipotency and low immunogenicity, supporting a variety of possible clinical applications in the field of cell transplantation and regenerative medicine. We have previously shown that cells derived from the mesenchymal region of human amnion (AMTC) can strongly inhibit T-lymphocyte proliferation. In this study, we demonstrate that AMTC can block differentiation and maturation of monocytes into dendritic cells (DC), preventing the expression of the DC marker CD1a and reducing the expression of HLA-DR, CD80, and CD83. The monocyte maturation block resulted in impaired allostimulatory ability of these cells on allogeneic T cells. In attempting to define the mechanisms responsible for these findings, we have observed that the presence of AMTC in differentiating DC cultures results in the arrest of the cells to the G(0) phase and abolishes the production of inflammatory cytokines such as TNF-alpha, CXCL10, CXCL9, and CCL5. Finally, we also demonstrate that the monocytic cells present in the amniotic mesenchymal region fail to differentiate toward the DC lineage. Taken together, our data suggest that the mechanisms by which AMTC exert immumodulatory effects do not only relate directly to T cells, but also include inhibition of the generation and maturation of antigen-presenting cells. In this context, AMTC represent a very attractive source of multipotent allogeneic cells that promise to be remarkably valuable for cell transplantation approaches, not only due to their low immunogenicity, but also because of the added potential of modulating immune responses, which could be fundamental both for controlling graft rejection after transplantation and also for controlling diseases characterized by inflammatory processes.


Post-polymerisation functionalisation of conjugated polymer backbones and its application in multi-functional emissive nanoparticles.
Backbone functionalisation of conjugated polymers is crucial to their performance in many applications, from electronic displays to nanoparticle biosensors, yet there are limited approaches to introduce functionality. To address this challenge we have developed a method for the direct modification of the aromatic backbone of a conjugated polymer, post-polymerisation. This is achieved via a quantitative nucleophilic aromatic substitution (SNAr) reaction on a range of fluorinated electron-deficient comonomers. The method allows for facile tuning of the physical and optoelectronic properties within a batch of consistent molecular weight and dispersity. It also enables the introduction of multiple different functional groups onto the polymer backbone in a controlled manner. To demonstrate the versatility of this reaction, we designed and synthesised a range of emissive poly(9,9-dioctylfluorene-alt-benzothiadiazole) (F8BT)-based polymers for the creation of mono and multifunctional semiconducting polymer nanoparticles (SPNs) capable of two orthogonal bioconjugation reactions on the same surface.


Value-based Practice: Integration of Cancer Rehabilitation and Palliative Care in Oncology Services.
Value-based care model has been evolving to organize medical services around the patient and provide the full cycle of care for a medical condition. The full cycle of care model encompasses inpatient, outpatient, rehabilitation as well as supportive care such as palliative care and nutrition support. Cancer rehabilitation and palliative care have emerged as two important parts of value-based practice for oncology patients. More clinical evidence suggests that early intervention of oncology rehabilitation program and palliative care are likely to improve the patient outcome and reduce the overall medical cost for the patient and his or her family as well as for medical service providers. Although interest has been raised in Chinese oncologists, but effectiveness of incorporating these two services in clinical practices has not been adequately demonstrated. An understanding of scope of cancer rehabilitation and palliative care may help facilitate the integration of both into the oncology care continuum in efforts to improve patients' physical, psychological, cognitive, functional health and quality of life.


New therapy targeting differential androgen receptor signaling in prostate cancer stem/progenitor vs. non-stem/progenitor cells.
The androgen deprivation therapy (ADT) to systematically suppress/reduce androgens binding to the androgen receptor (AR) has been the standard therapy for prostate cancer (PCa); yet, most of ADT eventually fails leading to the recurrence of castration resistant PCa. Here, we found that the PCa patients who received ADT had increased PCa stem/progenitor cell population. The addition of the anti-androgen, Casodex, or AR-siRNA in various PCa cells led to increased stem/progenitor cells, whereas, in contrast, the addition of functional AR led to decreased stem/progenitor cell population but increased non-stem/progenitor cell population, suggesting that AR functions differentially in PCa stem/progenitor vs. non-stem/progenitor cells. Therefore, the current ADT might result in an undesired expansion of PCa stem/progenitor cell population, which explains why this therapy fails. Using various human PCa cell lines and three different mouse models, we concluded that targeting PCa non-stem/progenitor cells with AR degradation enhancer ASC-J9 and targeting PCa stem/progenitor cells with 5-azathioprine and γ-tocotrienol resulted in a significant suppression of the tumors at the castration resistant stage. This suggests that a combinational therapy that simultaneously targets both stem/progenitor and non-stem/progenitor cells will lead to better therapeutic efficacy and may become a new therapy to battle the PCa before and after castration resistant stages.


Thymic regeneration after lethal irradiation evidence for an intra-thymic radioresistant T cell precursor.
The data presented indicate the existence of a significant pool of radioresistant stem cells which are capable of partially restoring the thymus of heavily irradiated mice. 3-H-TdR incorporation by the thymus of lethally irradiated mice begins 48 to 72 hr after irradiation and increases throughout the next 8 days. By the 9th day after 760 rads, typical corticomedullary architecture has been restored. 890 rads markedly suppressed, but did not totally eliminate this regeneration. Injection of large numbers of syngeneic bone marrow cells immediately after irradiation was without effect on the rate or extent of regeneration. Mice whose bone marrow and spleen were shielded from irradiation showed an identical amount of thymic regeneration as those receiving total body irradiation indicating that the precursor cell pool responsible for the early post irradiation phase of thymic regeneration is most likely an intrathymic population. The cells repopulating the thymus were morphologically indistinguishable from normal thymocytes and were susceptible to cytotoxic antisera against the thymic differentiation antigens Thy-1, TL, LyA2 and LyC2.


Confocal Raman microspectrometry: a vectorial electromagnetic treatment of the light focused and collected through a planar interface and its application to the study of a thin coating.
In-depth confocal Raman microspectrometry (CRM) studies through a planar interface between materials of mismatched refraction indices are known to be affected by a decrease of both the collected Raman intensity and the axial resolution as a function of the penetration depth. Following a previous model, which takes the refraction, diffraction, and spherical aberration effects into account when focusing a Gaussian incident laser beam with a high numerical aperture objective lens, a complete vectorial treatment of these phenomena is considered. It is demonstrated that off-axis refraction effects cannot be neglected and that the dimension of the confocal pinhole aperture plays a crucial role on the effective focal plane position and on the collection efficiency. We thus propose a more rigorous and complete approach to the problem, and we find a very good agreement between experimental and theoretical Raman intensity variations for a thick polyethylene sample as a function of the penetration depth. As compared with calculations where only refraction was considered, we confirm that the lengthening of the focus even for a large penetration depth is significantly reduced upon diffraction effects. As an illustrative example, the theoretical Raman responses for a thin coating of approximately 20 microns on a polymer substrate were investigated and compared to experimental results already published. Even though the interfacial region is spread over approximately 5-6 microns when using a 100x objective and a confocal pinhole of 200 microns diameter, it is definitively concluded that the apparent axial resolution is not drastically deteriorated with increasing depth and that the coating thickness may be directly estimated with a precision of approximately 1.0 micron (5%).


Nucleotide excision repair in chromatin and the right of entry.
DNA is packaged with histones and other accessory proteins into chromatin in eukaryotic cells. It is well established that the assembly of DNA into chromatin affects induction of DNA damage as well as repair of the damage. How the DNA repair machinery detects a lesion and 'fixes it' in chromatin has been an intriguing question since the dawn of understanding DNA packaging in chromatin. Direct recognition/binding by damaged DNA binding proteins is one obvious tactic to detect a lesion. Rearrangement of chromatin structure during DNA repair was reported more than two decades ago. This early observation suggests that unfolding of chromatin structure may be required to facilitate DNA repair after lesions are detected. Cells can also exploit DNA processing events to assist DNA repair. Transcription coupled repair (TCR) is such an example. During TCR, an RNA polymerase blocked by a lesion, may act as a signal to recruit DNA repair machinery. Possible roles of histone modification enzymes, ATP-dependent chromatin remodeling complexes and chromatin assembly factors in DNA repair are discussed.


18F-FDG PET/CT Demonstrating Chorioadenoma Destruens After Evacuation of Complete Hydatidiform Mole.
Gestational trophoblastic neoplasias (GTNs) are a group of pregnancy-related neoplasms, which include chorioadenoma destruens (invasive mole), placental site trophoblastic tumor, and choriocarcinoma. Although the role of F-FDG PET/CT is still undefined in GTN, in selected cases, it can have significant impact on patient management. Here, we present the case of a 29-year-old woman with hydatidiform mole suggestive of GTN 3 months after evacuation. F-FDG PET/CT demonstrated chorioadenoma destruens (invasive mole) and ruled out metastasis in this case.


Implantable loop records in paediatric pratice.
Symptoms of syncope and palpitations are not uncommon in children with and without heart disease. They present a diagnostic dilemma when conventional cardiovascular testing is inconclusive. The implantable loop recorder (ILR) has been shown to play an important role in diagnosing recurrent syncope in adult patients. In paediatric practice its role still has to be defined. The aim of this article is to assess the diagnostic yield of the ILR in children and young adults. Seven patients, four male and three female, were included in the study. The mean age at implantation was 12.8 years, with a range from 0.8 to 25.9 years. The symptoms leading to ILR implantation were recurrent syncope or near-syncope (n=3), syncope in combination with palpitations (n=2), and syncope with an acute life-threatening event (ALTE) (n=2). Previous testing included 12-lead ECG (n=7), echo (n=7), 24-hour Holter (n=7), four-week ambulatory Holter (n=3), exercise test (n=4) and invasive electrophysiological study (n=3). Over a mean follow-up period of 7.5 months (range 3 to 16 months), four (57%) patients continued to have symptoms. The ILR enabled the correct diagnosis to be established in all four patients with persistent symptoms allowing appropriate therapy to be given.


IIB osteosarcoma. Current management, local control, and survival statistics--São Paulo, Brazil.
Ninety-two patients with IIB osteosarcoma of the extremities were treated with intraarterial (IA) cisplatinum (CDDP) followed by surgery [amputation (61.6%) or resection with endoprosthesis (38.4%)]. Postoperative chemotherapy alternating adriamycin and CDDP was used. The total three-year survival was 62.1%, and the disease-free survival was 41.1%. The pathologic evaluation of the degree of tumor necrosis in response to the IA CDDP showed that in 53.2%, the necrosis was over 90%. The multivariate analysis of prognostic factors has shown that the highest survival was among females with tumors smaller than 15 cm. Patients with lesions equal to or larger than 15 cm were three times as likely to die of the disease. A second, more aggressive study is now underway, in which high dose methotrexate (HDMTX) is preoperatively combined with adriamycin and CDDP. Following operation, ifosfamide is added to the cases with a smaller degree of tumor necrosis, while the other group of patients will continue with HDMTX, in addition to CDDP and adriamycin (these last two drugs are used in both arms). Until now, complete remission has been achieved in 82% and 86%, respectively, with a follow-up examination varying from four to 26 months (average, 14 months). This is of extreme importance, because the majority of the authors' patients have tumors at initial evaluation larger than 10 cm in diameter.


Genome-wide association study-based prediction of atrial fibrillation using artificial intelligence.
We previously reported early-onset atrial fibrillation (AF) associated genetic loci among a Korean population. We explored whether the AF-associated single-nucleotide polymorphisms (SNPs) selected from the Genome-Wide Association Study (GWAS) of an external large cohort has a prediction power for AF in Korean population through a convolutional neural network (CNN). This study included 6358 subjects (872 cases, 5486 controls) from the Korean population GWAS data. We extracted the lists of SNPs at each p value threshold of the association statistics from three different previously reported ethnical-specific GWASs. The Korean GWAS data were divided into training (64%), validation (16%) and test (20%) sets, and a stratified K-fold cross-validation was performed and repeated five times after data shuffling. The CNN-GWAS predictive power for AF had an area under the curve (AUC) of 0.78±0.01 based on the Japanese GWAS, AUC of 0.79±0.01 based on the European GWAS, and AUC of 0.82±0.01 based on the multiethnic GWAS, respectively. Gradient-weighted class activation mapping assigned high saliency scores for AF associated SNPs, and the PITX2 obtained the highest saliency score. The CNN-GWAS did not show AF prediction power by SNPs with non-significant p value subset (AUC 0.56±0.01) despite larger numbers of SNPs. The CNN-GWAS had no prediction power for odd-even registration numbers (AUC 0.51±0.01). AF can be predicted by genetic information alone with moderate accuracy. The CNN-GWAS can be a robust and useful tool for detecting polygenic diseases by capturing the cumulative effects and genetic interactions of moderately associated but statistically significant SNPs. NCT02138695.


Inventory to go: can stockless deliver efficiency?
Influenced by the Japanese management concept of "just-in-time," healthcare organizations are looking to their departmental inventories for possible cost reductions. Some organizations have developed a materials management technique known as stockless inventory, in which much of the management of an organization's supplies is switched to an outside vendor. By eliminating its storeroom and many of the staffing needs that go along with it, a hospital with a stockless inventory program can realize significant cost savings. Whether these savings offset potentially large service fees is a question each hospital must decide on its own.


Does spatial locative comprehension predict landmark-based navigation?
In the present study we investigated the role of spatial locative comprehension in learning and retrieving pathways when landmarks were available and when they were absent in a sample of typically developing 6- to 11-year-old children. Our results show that the more proficient children are in understanding spatial locatives the more they are able to learn pathways, retrieve them after a delay and represent them on a map when landmarks are present in the environment. These findings suggest that spatial language is crucial when individuals rely on sequences of landmarks to drive their navigation towards a given goal but that it is not involved when navigational representations based on the geometrical shape of the environment or the coding of body movements are sufficient for memorizing and recalling short pathways.


Inequalities in Caries Experience Among Mongolian Children.
Although inequalities in dental caries have been well-reported, there is only one Mongolian study on the association between socioeconomic status (SES) and caries experience, which was published ten years ago. This study aimed to determine the dental health status of Mongolian children living in urban and suburban areas of Ulaanbaatar city and examine its association with income and parental educational attainment. An oral examination was conducted by dentists and caries were measured as deft/DMFT indices. A questionnaire including demographic characteristics and socioeconomic status was completed by their parents or caregiver. Parental educational attainment and household income were used as the measures of SES. The relative index of inequality (RII) and slope index of inequality (SII) were employed to examine the association between SES on deft and DMFT after adjusting for covariates. Dental caries prevalence (those with deft/DMFT > 0) was 89.3% among the total number of participants. The mean deft/DMFT values for age groups 1-6, 7-12, and 13-18 were 5.83 (SD = 4.37, deft), 5.77 (SD = 3.31, deft/DMFT), and 3.59 (SD = 2.69, DMFT), respectively. Rather than residence area and parental educational attainment, significant caries experience inequality was observed in relation to income (RII 0.65 95%, CI 0.52 to 0.82, SII -2.30, 95% CI -4.16 to -0.45). A prevention strategy for lower socioeconomic groups and building integrated oral health surveillance to monitor epidemiological trends for further evaluation of its progress is necessary.


Proteomic modification by nitric oxide.
The role of nitric oxide (NO) in cellular signaling has become one of the most rapidly growing areas in biology during the past two decades. As a gas and free radical with an unshared electron, nitric oxide participates in various biological processes. The interaction between NO and proteins may be roughly divided into two categories. In many instances, NO mediates its biological effects by activating guanylyl cyclase and elevates intracellular cyclic GMP synthesis from GTP. However, the list of cGMP-independent effects of NO is also growing at a rapid rate. In this review, the importance and relevance of nitrotyrosine formation are stressed. The utilization of intact cell cultures, tissues, and cell-free preparations along with the use of pharmacological, biochemical, and molecular biological approaches to characterize, purify, and reconstitute these NO regulatory pathways could lead to the development of new therapies for various pathological conditions that are characterized by unbalanced production of NO.


Plakophilins 1a and 1b: widespread nuclear proteins recruited in specific epithelial cells as desmosomal plaque components.
The cytokeratin-binding, basic 80.5 kDa polypeptide plakophilin 1 ("band 6 protein" of bovine muzzle desmosome fractions) has originally been described as a single molecular species, localized to desmosomal plaques of certain cell types, mostly stratified squamous epithelia and complex epithelia. We now report that this protein exists in at least two different isoforms: 726 amino acids (aa), plakophilin 1a; and 747 aa, plakophilin 1b. This reflects the splicing of the 21 aa-encoding exon 7 of the human plakophilin-1 gene and that each mRNA splice form can occur in two polyadenylation forms of 2.7 kb and 5.3 kb. Antibodies recognizing either isoform and/or others that are specific for the exon-encoded sequence of form 1b have allowed, in combination with immunolocalization protocols minimizing losses of diffusible proteins, the detection of both isoforms in the nucleoplasm of diverse kinds of cultured cells and tissues, including desmosome-forming cells as well as cells that never form desmosomes. The protein has also been identified in manually isolated nuclei (germinal vesicles) of Xenopus laevis oocytes. Plakophilin 1a accumulates in nuclei as shown by suitable immunolocalization protocols and upon overexpression following transfection with cDNAs, but is also located in desmosomes of stratified and complex epithelia. By contrast, isoform 1b has been found exclusively in nuclei, even in cells connected by desmosomes immunostained with plakophilin 1a-reactive antibodies. We conclude that plakophilins 1a and 1b are constitutive nuclear proteins encoded by the same gene, which is not expressed in relation to epithelial differentiation pathways, whereas the additional appearance of plakophilin 1a in desmosomal plaques of stratified and complex epithelia is regulated by an as yet unknown mechanism of differentiation-dependent topogenic recruitment. Possible functions of plakophilins are discussed in relation to recent reports of the involvement of other members of the armadillo/plakoglobin multigene family of proteins in cell surface-gene regulation signalling pathways.


Investigating the relationship between hepatitis B virus infection and postpartum depression in Chinese women: a retrospective cohort study.
Postpartum depression (PPD) is associated with several psychological and obstetric factors. Hepatitis B virus (HBV) infection has been linked with a high risk of depression, but little is known about the relationship between maternal HBV infection and PPD. We aimed to investigate the association between HBV infection and PPD. This retrospective cohort study included 3,808 mothers who gave birth in a hospital in southern China. Self-reported Edinburgh Postnatal Depression Scale (EPDS) was used to assess PPD. Multivariate logistic regression was used to determine whether maternal HBV infection was associated with PPD risk. Of the 3,808 participants, 11.9% of mothers had PPD at 6 weeks postpartum. Two hundred and seventy-eight (7.3%) and 3,530 (92.7%) were in the HBV and control groups, respectively. Women with HBV infection were more likely to test positive for PPD (14.7 vs.11.7%). The multivariate logistic regression analysis showed that HBV-infected women did not have a significantly higher incidence of PPD (OR = 1.23; 95% CI, 0.82-1.84) than those without HBV infection in the study cohort. Parity and postpartum hemorrhage were found to be associated with PPD. In addition, our study showed that e antigen positivity was not associated with PPD risk (OR = 0.56, 95% CI 0.19-1.63). To our knowledge, this is the first investigation of the relationship between maternal HBV infection and PPD. In a cohort of women without prior history or family history of mental illness, having HBV infection was not significantly associated with self-reporting of PPD compared to not having HBV infection.


Immunoinflammatory responses in gastrointestinal tract injury and recovery.
Inflammation is a non-specific immune response to infection, irritation or other injury, the key features being redness, warmth, swelling and pain. A number of mediators are released which alter the resistance of mucosa to injury induced by noxious substances. Oxidative stress is a unifying mechanism of injury in many types of disease processes, including gastrointestinal diseases. It has been defined as an imbalance in the activity of pro and antioxidants. Pro-oxidants favour free radical formation while antioxidants inhibit or retard the same. A number of markers of oxidative stress have been identified. This review provides an overview of various mediators of inflammation and oxidative stress, and diverse approaches for prevention and treatment of gastrointestinal inflammation.


[Comprehensive study of percutaneous transhepatic aspiration bile culture and cholangiography].
In this study, the results of transhepatically aspirated bile culture, and cholangiography done in 220 cases with biliary tract diseases were presented. Aerobes and anaerobes were found in 76.4% and 64.7% of all samples respectively. Patients with partial common bile duct obstruction from stricture and choledocholithiasis had markedly higher positive cultures than that with simple gallbladder stones and complete common duct obstruction secondary to carcinomas of the pancreas or ampulla. Bile culture from patients with symptomatic cholangitis was much more often positive than those with asymptomatic cholangitis. It was also found that patients with positive bile cultures were more prone to after-PTC acute cholangitis. This study suggested that bile organisms are mainly from the gut, bile organisms and bile duct obstruction are two major causes of acute cholangitis, abrupt elevation of bile pressure during PTC procedure was also a causing factor of acute cholangitis. The authors advocate the comprehensive and prophylactic use of antibiotics both effective to aerobes and anaerobes in the treatment of biliary tract infection.


Tunable Diode Laser Absorption Spectroscopy of Carbon Monoxide Around 2.35 microm.
Novel GaInSbAs/GaSb multiple-quantum-well lasers operating near room temperature have been successfully used for tunable diode laser absorption spectroscopy in the vicinity of 2.35 mum. Continuous current tuning over a more than 150-GHz frequency range has been realized. Direct absorption measurements have been carried out on the R, R, R, and R lines of carbon monoxide. Traces of carbon monoxide at the level of 0.3 part in 10(6) in volume at 100 Torr could be detected by the low-frequency wavelength-modulation technique and an astigmatic multipass cell. These results show a potential use of these diode lasers in portable low-cost trace-pollutant sensors.


Genetic testing: implications for professional nursing.
Scientific information emerging from human genome research has significant implications for the practice of professional nursing. Professional nurses assist individuals in making decisions about DNA studies, ensure that consent is informed before genetic testing, and help clients cope with genetic information after test results are known. Nurses with advanced education in genetics identify and counsel people who are candidates for DNA testing. Gene identification can have beneficial as well as harmful outcomes. Education is needed to prepare nurses for new roles regarding genetic testing.


Republished paper: The implications of the NICE guidelines on neurosurgical management for all severe head injuries: systematic review.
Head injury is an important cause of death among young adults in the UK, and a significant burden on NHS resources. However, management is inconsistent, governed largely by local resources. The latest version of the NICE head injury guidelines suggests that more patients with traumatic brain injury should be transferred to receive specialist care. However, this raises issues about the capacity of regional neurosurgical units, particularly to accommodate patients who do not require surgical intervention. Objectives To critically evaluate the basis of the NICE recommendations about transfer for neurosurgical care, and examine the configuration of specialist services to assess the implications of increasing the existing number of transfers. Methods A systematic literature review was conducted of articles discussing the provision of emergency neurosurgical care for adult head injuries in the UK. Results Fifty-eight papers met the criteria for inclusion in the literature review, including seven papers cited in the NICE guidance. Fifty-one papers related to neurosurgical care, including papers on bed occupancy, transfer times and transfer policies. Conclusions The evidence NICE cited is of variable quality. Much of the research was conducted outside the UK, which raises questions about its relevance to the NHS. Care of traumatic brain injuries in the UK is already hampered by the inadequate capacity of regional neurosurgical units to meet demand, and transferring more patients would be likely to exacerbate this. Increasing the number of transfers could also worsen inequalities of access for other groups, such as elective patients, particularly in areas where facilities are most stretched.


Genetic determinants of athletic performance.
An extraordinary revolution in medical research has taken place over the past decade, enabled by the completion of the first human genome sequence in 2001. The Human Genome Project (HGP) has resulted in the 6 billion letter reference human genome sequence and the ultra-high throughput technologies used by medical researchers to identify correlations between positions within the human genome (genotypes) and diseases or traits (phenotypes). Just as every human disease has a genetic component, so too does every human trait. The vast majority of these diseases and traits also have an environmental component that works in conjunction with the body's hardwiring to produce the resultant phenotype- termed "complex genetic traits". A derivative of the HGP has been a deeper understanding not only of diseases but of normal human variability across the population, including aspects of athleticism. The technologies also now exist for consumers to cheaply gain access to variations in the genetic code that are correlated to traits that confer aspects of longevity, memory performance, athleticism and a multitude of others there-through gaining insight into propensities. Communication of propensity to a phenotype such as athletic performance is fraught with technical, legal (e.g., patents), social and ethical issues. That being said, the information is available, has benefit in some cases, and will be utilized in the future. Given that the "genie is out of the bottle" with respect to our ability to deliver this genetic information to individuals, over the past decade our team has worked diligently to craft the appropriate testing and communication paradigms for complex traits. Here we discuss several of the major risks and benefits of this type of testing for athletic performance. It is important to understand the limitations of genetic information in determining the vast majority of traits.


Report of a case with polymicrobial endocarditis related to multiresistant strains.
We present a patient with polymicrobial endocarditis who had been operated on previously for a mycotic aneurysm and was seen at the cardiology clinic because of palpitations related to effort. A transesophageal echocardiogram revealed a 15-mm vegetation on his aortic valve. Staphylococcus epidermidis and Corynebacterium striatum were isolated from the blood cultures. Both strains were multiresistant (susceptible to 3 antibiotics at most) against chemotherapy in vitro. Microbiological eradication was not achieved from blood cultures even after applying antimicrobial therapy with effective antibiotics as determined with an antibiotic susceptibility test. For this reason, the patient underwent valve replacement. He was discharged from hospital in fairly good health.


Decreased coumarin 7-hydroxylase activities and CYP2A6 expression levels in humans caused by genetic polymorphism in CYP2A6 promoter region (CYP2A6*9).
One of seven poor metabolizers of coumarin found in Thai subjects was previously genotyped as heterozygote for the CYP2A6*4 (whole deletion) and CYP2A6*9. Thus, we aimed to investigate the relationship between the genetic polymorphism in the TATA box of the CYP2A6 gene (CYP2A6*9), expression levels of CYP2A6 mRNA and coumarin 7-hydroxylase activities in human livers. Levels of CYP2A6 mRNA were quantified by real-time quantitative reverse transcriptase-polymerase chain reaction. The mean expression levels of CYP2A6 mRNA in individuals with CYP2A6*1/*4, CYP2A6*1/*9 and CYP2A6*4/*9 were 58%, 71% and 21% of the individuals genotyped as CYP2A6*1/*1, respectively. The mean in-vitro coumarin 7-hydroxylase activities in subjects carrying CYP2A6*1/*4, CYP2A6*1/*9 and CYP2A6*4/*9 were 41%, 71% and 12%, respectively, compared to those of the subjects judged as wild-type. Vmax values for coumarin 7-hydroxylation in the liver microsomes from human subjects with genotypes of CYP2A6*1/*1, CYP2A6*1/*4, CYP2A6*1/*9 and CYP2A6*4/*9 were 0.58, 0.26, 0.44 and 0.13 nmol/min/nmol total P450, respectively. CYP2A6 protein levels in human liver microsomes with the CYP2A6*4 and the CYP2A6*9 alleles were markedly decreased. These results suggest that the genetic polymorphism in the promoter region of the CYP2A6 gene (CYP2A6*9) reduced the expression levels of CYP2A6 mRNA and protein in human livers, resulting in the decrease of coumarin 7-hydroxylase activities. Individuals judged as CYP2A6*4/*9 were expected to be poor metabolizers, having extremely low activity of CYP2A6.


Foam elastomer dressings in surgery.
A wound dressing prepared from silicone which is catalysed by a gas-producing activatory is described. The resultant foam elastomer is soft, comfortable and easy to prepare, and can be removed, cleaned and reinserted by the patient with minimal instruction and formality. It promises to be a highly cost-effective dressing, with a particularly wide range of potential applications.


Overcoming Barriers to Agriculture Green Technology Diffusion through Stakeholders in China: A Social Network Analysis.
It is crucial to actively encourage the development of agriculture green technology, which has been regarded as one of the most effective solutions to the environmental degradation caused by agricultural activities. However, agriculture green technology diffusion is indeed a challenging task and still faces numerous barriers. The stakeholders who can potentially deal with these barriers, however, have been overlooked by previous studies. To address these issues, social network analysis was performed to identify critical stakeholders and barriers. Their interactions in agriculture green technology diffusion were analyzed based on the literature, a questionnaire survey and expert judgments. A two-mode network and two one-mode networks were used to analyze the relationships among the identified 12 barriers and 14 stakeholders who can influence these 12 barriers identified. The results show that agricultural research institutes, universities, agribusiness, agencies of township promotion, the government and farmers' relatives are key stakeholders and that the limited market demand for green technology and the high cost of its diffusion are two main barriers. However, poor green technology operability and farmer families in distress are factors that are not as important as previously perceived. Finally, some recommendations and suggestions are provided to promote agriculture green technology diffusion in China.


Temporary Right-Ventricular Assist Devices: A Systematic Review.
Acute right-sided heart failure (RHF) is a complex clinical syndrome, with a wide range of clinical presentations, associated with increased mortality and morbidity, but about which there is a scarcity of evidence-based literature. A temporary right-ventricular assist device (t-RVAD) is a potential treatment option for selected patients with severe right-ventricular dysfunction as a bridge-to-recovery or as a permanent solution. We sought to conduct a systematic review to determine the safety and efficacy of t-RVAD implantation. Thirty-one studies met the inclusion criteria, from which data were extracted. Successful t-RVAD weaning ranged between 23% and 100%. Moreover, 30-day survival post-temporary RAVD implantation ranged from 46% to 100%. Bleeding, acute kidney injury, stroke, and device malfunction were the most commonly reported complications. Notwithstanding this, t-RVAD is a lifesaving option for patients with severe RHF, but the evidence stems from small non-randomized heterogeneous studies utilizing a variety of devices. Both the etiology of RHF and time of intervention might play a major role in determining the t-RVAD outcome. Standardized endpoints definitions, design and methodology for t-RVAD trials is needed. Furthermore, efforts should continue in improving the technology as well as improving the timely provision of a t-RVAD.


[Features of atherosclerosis in the ascending human aorta and the link between its development and the main risk factors of ischemic heart disease in patients after aortocoronary shunting].
Atherosclerosis was found in all ascending aorta biopsies of 125 patients aged 42 to 65 years who underwent aortocoronary bypass surgery. Lipid spots only were found in 91.2% of cases, in 11 patients (8.8%) there were lipid plaques. Three main types of lipid spots were recognized: type I--primary extracellular lipoidosis (40.0%); type II--mainly intracellular lipoidosis (24.8%) and type III--cell lipoidosis with a pronounced component of secondary extracellular lipoidosis (26.4%). A specific feature of ascending aorta atherosclerosis is a frequent combination of intima lipoidosis with media lipoidosis: 92% in type I, 100% in type II and 93.9% in type III. This is probably an important way of lipid elimination from the intima and this predetermines a "mild" course of atherosclerosis in this part of the aorta. Types II and III of lipoidosis occurred more frequently in lipid metabolism disturbances and only under these conditions clusters of foam cells were observed. Arterial hypertension and smoking have a leading role in development of intimal hyperplasia. When assessing atherosclerosis activity in the operated patients not only risk factors of ischemic heart disease but also the results of aorta biopsies studies should be taken into consideration.


Understanding public health informatics competencies for mid-tier public health practitioners: a web-based survey.
The literature suggests that there is a need for measuring public health informatics (PHI) competency to further understand whether current educational modules and modalities meet the needs of PHI practitioners and researchers to perform their jobs more effectively, particularly for mid-tier practitioners that constitute the majority of public health workers in the USA. The present study seeks to update current knowledge of the perceptions and experiences of PHI competencies proposed by the U.S. Council on Linkage in Public Health specifically for mid-tier PH practitioners and researchers. The results were collected and analyzed by using a Web-based survey (WBS) method administered among both practitioners and researchers. Researchers first compiled a draft list of candidate competency set by incorporating existing competency areas provided by: 1) the Council on Linkage; and by 2) those proposed by the USA's Centers for Disease Control CDC Public Health Informatics Work Group. Nine sets of competency statements with 120 competency items and demographic information of respondents were included in the WBS. The online survey instruments were pilot-tested accordingly to incorporate feedback from respondents of the pilot. Fifty-six subjects were recruited from PH experts who were: 1) members of the Health Informatics Information Technology (HIIT) group of American Public Health Association; and, 2) members from the Community of Science (COS) Website who were the first authors published in the PHI field from PubMed. The sample included diverse backgrounds of PHI workers. They expressed an increased need for training to improve their PHI competencies. Respondents agreed that four competency sets should be adequately represented, including Leadership and System Thinking Skills (82%), followed by Financial Planning and Management Skills (79%), Community Dimensions of Practice Skills (77%), and Policy Development/Program Planning Skills (63%). The findings parallel current literature indicating that there exists an expressed need for clarification of the public health practitioner's job-specific informatics competency. Findings of expressed needs for basic computer literacy training and community-based practice were consistent with those of the literature. Additional training and resources should be allocated to address the competency of leadership, management, community-based practice and policy advocacy skills for mid-tier public health practitioners to perform their jobs more effectively. Only when healthcare organizations properly identify PHI competency needs will public health practitioners likely improve their overall informatics skills while improving diversification for contribution across multiple settings.


AAV-mediated gene transfer of DNase I in the liver of mice with colorectal cancer reduces liver metastasis and restores local innate and adaptive immune response.
Liver metastasis is the main cause of colorectal cancer (CRC)-related death. Neutrophil extracellular traps (NETs) play important roles in CRC progression. Deoxyribonuclease I (DNase I) has been shown to alter NET function by cleaving DNA strands comprising the NET backbone. Moreover, DNase I displays high antimetastatic activity in multiple tumor models. To circumvent long-term daily administrations of recombinant DNase I, we have developed an adeno-associated virus (AAV) gene therapy vector to specifically express DNase I in the liver. In this study, we demonstrate AAV-mediated DNase I liver gene transfer following a single intravenous injection suppresses the development of liver metastases in a mouse model of CRC liver metastasis. Increased levels of neutrophils and NET formation in tumors are associated with poor prognosis in many patients with advanced cancers. Neutrophil infiltration and NET formation were inhibited in tumor tissues with AAV-DNase I treatment. This approach restored local immune responses at the tumor site by increasing the percentage of CD8+ T cells while keeping CD4+ T cells similar between AAV-DNase I and AAV-null treatments. Our data suggest that AAV-mediated DNase I liver gene transfer is a safe and effective modality to inhibit metastasis and represents a novel therapeutic strategy for CRC.


Cinnamon extract suppresses tumor progression by modulating angiogenesis and the effector function of CD8+ T cells.
Cinnamon is one of the most widely used herbal medicines with diverse bioactive effects. However, little evidence has been reported about the potential anti-tumor effects of cinnamon. In vitro and in vivo system, cinnamon treatment strongly inhibited the expression of pro-angiogenic factors and master regulators of tumor progression not only in melanoma cell lines but also in experimental melanoma model. In addition, cinnamon treatment increased the anti-tumor activities of CD8(+) T cells by increasing the levels of cytolytic molecules and their cytotoxic activity. In conclusion, cinnamon extract has the potential to be an alternative medicine for tumor treatment.


Nedosiran: First Approval.
Nedosiran (RIVFLOZA™), a once-monthly subcutaneous small interfering RNA (siRNA) therapy, is being developed by Dicerna Pharmaceuticals, a Novo Nordisk company, for the treatment of primary hyperoxaluria (PH). It reduces oxalate overproduction by inhibiting the expression of the hepatic lactate dehydrogenase (LDH) enzyme. Nedosiran received its first approval on 29 September 2023 in the USA to lower urinary oxalate levels in children aged ≥ 9 years and adults with PH type 1 (PH1) and relatively preserved kidney function [e.g. estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2]. This article summarizes the milestones in the development of nedosiran leading to this first approval for PH1.


[Evaluation of the treatment effect of bruxism using two occlusal splint].
To compare the clinical treatment effect of bruxism by using group functional occlusion splint and canine protect occlusion splint. Group functional occlusion splint and canine protect occlusion splint were made, the patients were asked to wear the splint during night,the clinical effect was evaluated and compared using SPSS10.0 software package for Chi-square test. The successful rate of treatment of bruxism was 79.16% in group functional occlusion splint, while the successful rate of treatment of bruxism was 83.33% in canine protect occlusion splint. Two kinds of occlusion splints have similar curative effect for bruxism.


Single nucleotide variants in transcription factors associate more tightly with phenotype than with gene expression.
Mapping the polymorphisms responsible for variation in gene expression, known as Expression Quantitative Trait Loci (eQTL), is a common strategy for investigating the molecular basis of disease. Despite numerous eQTL studies, the relationship between the explanatory power of variants on gene expression versus their power to explain ultimate phenotypes remains to be clarified. We addressed this question using four naturally occurring Quantitative Trait Nucleotides (QTN) in three transcription factors that affect sporulation efficiency in wild strains of the yeast, Saccharomyces cerevisiae. We compared the ability of these QTN to explain the variation in both gene expression and sporulation efficiency. We find that the amount of gene expression variation explained by the sporulation QTN is not predictive of the amount of phenotypic variation explained. The QTN are responsible for 98% of the phenotypic variation in our strains but the median gene expression variation explained is only 49%. The alleles that are responsible for most of the variation in sporulation efficiency do not explain most of the variation in gene expression. The balance between the main effects and gene-gene interactions on gene expression variation is not the same as on sporulation efficiency. Finally, we show that nucleotide variants in the same transcription factor explain the expression variation of different sets of target genes depending on whether the variant alters the level or activity of the transcription factor. Our results suggest that a subset of gene expression changes may be more predictive of ultimate phenotypes than the number of genes affected or the total fraction of variation in gene expression variation explained by causative variants, and that the downstream phenotype is buffered against variation in the gene expression network.


Intraarterial cis-platinum chemotherapy for patients with primary and metastatic brain tumors.
A total of 49 patients were treated using intraarterial cis-platinum infusions at a dose of 100 mg/m2. The patients were separated into three groups. There were 13 patients with metastatic tumors, 10 with recurrent malignant gliomas, and 22 patients with high-grade gliomas who received intraarterial cis-platinum as part of an adjuvant program. In addition, four nongliomatous primary brain tumors were treated in this fashion. Cis-platinum was filtered immediately prior to intraarterial infusion using a 0.22-micron filter. Response to treatment was evaluated by follow-up CAT scans and neurologic examinations. There were three complete and eight partial responses in metastatic tumors, and eight partial responses in recurrent gliomas. The median survival was 19 weeks for patients with metastatic disease, and 16 weeks for patients with recurrent gliomas. Those high-grade glioma patients who received intraarterial cis-platinum as adjuvant chemotherapy along with CCNU and radiation therapy had a projected median survival of 91+ weeks. Toxicity from intraarterial cis-platinum following drug filtration was markedly reduced when compared with previous reports. Only five patients experiencing visual or central nervous system toxicity utilizing filtered cis-platinum and no radiographic or histopathologic evidence of central nervous system toxicity was observed. Bilateral deafness was observed following vertebral artery infusion in both patients treated in this manner and thus vertebral artery infusions should be avoided. Systemic toxicity was mild. Intracarotid infusion is a safe, well-tolerated delivery system for filtered cis-platinum with a high response rate for patients with both metastatic and primary malignant brain tumors.


Label-free quantitative analysis of one-dimensional PAGE LC/MS/MS proteome: application on angiotensin II-stimulated smooth muscle cells secretome.
A widely used method for protein identification couples prefractionation of protein samples by one-dimensional (1D) PAGE with LC/MS/MS. We developed a new label-free quantitative algorithm by combining measurements of spectral counting, ion intensity, and peak area on 1D PAGE-based proteomics. This algorithm has several improvements over other label-free quantitative algorithms: (i) Errors in peak detection are reduced because the retention time is based on each LC/MS/MS run and actual precursor m/z. (ii) Detection sensitivity is increased because protein quantification is based on the combination of peptide count, ion intensity, and peak area. (iii) Peak intensity and peak area are calculated in each LC/MS/MS run for all slices from 1D PAGE for every single identified protein and visualized as a Western blot image. The sensitivity and accuracy of this algorithm were demonstrated by using standard curves (17.4 fmol to 8.7 pmol), complex protein mixtures (30 fmol to 1.16 pmol) of known composition, and spiked protein (34.8 fmol to 17.4 pmol) in complex proteins. We studied the feasibility of this approach using the secretome of angiotensin II (Ang II)-stimulated vascular smooth muscle cells (VSMCs). From the VSMC-conditioned medium, 629 proteins were identified including 212 putative secreted proteins. 26 proteins were differently expressed in control and Ang II-stimulated VSMCs, including 18 proteins not previously reported. Proteins related to cell growth (CYR61, protein NOV, and clusterin) were increased, whereas growth arrest-specific 6 (GAS6) and growth/differentiation factor 6 were decreased by Ang II stimulation. Ang II-stimulated changes of plasminogen activator inhibitor-1, GAS6, cathepsin B, and periostin were validated by Western blot. In conclusion, a novel label-free quantitative analysis of 1D PAGE-LC/MS/MS-based proteomics has been successfully applied to the identification of new potential mediators of Ang II action and may provide an alternative to traditional protein staining methods.


Inhibition of EphA2/EphrinA1 signal attenuates lipopolysaccharide-induced lung injury.
Eph-Ephrin signalling mediates various cellular processes, including vasculogenesis, angiogenesis, cell migration, axon guidance, fluid homoeostasis and repair after injury. Although previous studies have demonstrated that stimulation of the EphA receptor induces increased vascular permeability and inflammatory response in lung injury, the detailed mechanisms of EphA2 signalling are unknown. In the present study, we evaluated the role of EphA2 signalling in mice with lipopolysaccharide (LPS)-induced lung injury. Acute LPS exposure significantly up-regulated EphA2 and EphrinA1 expression. Compared with LPS+IgG mice (IgG instillation after LPS exposure), LPS+EphA2 mAb mice [EphA2 monoclonal antibody (mAb) instillation posttreatment after LPS exposure] had attenuated lung injury and reduced cell counts and protein concentration of bronchoalveolar lavage fluid (BALF). EphA2 mAb posttreatment down-regulated the expression of phosphoinositide 3-kinases (PI3K) 110γ, phospho-Akt, phospho-NF-κB p65, phospho-Src and phospho-S6K in lung lysates. In addition, inhibiting the EphA2 receptor augmented the expression of E-cadherin, which is involved in cell-cell adhesion. Our study identified EphA2 receptor as an unrecognized modulator of several signalling pathways-including PI3K-Akt-NF-kB, Src-NF-κB, E-cadherin and mTOR-in LPS-induced lung injury. These results suggest that EphA2 receptor inhibitors may function as novel therapeutic agents for LPS-induced lung injury.


Reconstruction of the naso-orbital-ethmoid (NOE) complex using the osteocutaneous radial forearm flap (OCRFF).
Describe the utility of osteocutaneous forearm flaps in reconstruction of naso-orbito-ethmoid (NOE) defects. Case series with chart review. Tertiary medical centers. The study was conducted on patients treated between the years 2000 and 2014 undergoing NOE resection with reconstruction using the radial forearm flap. Decision making, technical feasibility, need for revisions, and patient disease outcomes were included to assess the durability of reconstruction over remaining survival period. Fifteen patients underwent NOE reconstruction in the timeframe studied. Five recent patients reported poor nasal airway but no diplopia or immediately clinically evident enopthalmus after NOE reconstruction in mean follow-up of 17.3 months. One-third of patients succumbed to disease in the study period, 3 without revision, and all but 2 surviving patients required revisions. Osteocutaneous radial forearm flap (OCRFF) is a cosmetically acceptable method of reconstructing NOE defects. Though a 1-step reconstruction can be serviceable without multiple additional procedures, longer surviving patients frequently receive revision surgery as with more traditional planned staged procedures.


Variability in instructions for performance of nasopharyngeal swabs across Canada in the era of COVID-19 - what type of swab is actually being performed?
The primary method of surveillance for the presence of SARS-CoV-2 is with nasopharyngeal swabs. Given the significant demand for nasopharyngeal swabs, a large number of previously untrained and unfamiliar staff are now performing this test. It was noted that there was significant heterogeneity in instructions for performing nasopharyngeal swabs in Canada, in contrast to the guidance provided by the Centers for Disease Control and Prevention (CDC), and the Pan American Health Organization (PAHO). The objective of this study was to review the instructions provided across Canada and contrast them to those of the CDC and PAHO. A standard series of steps for nasopharyngeal swab performance was outlined based on the CDC, PAHO, and New England Journal of Medicine instructions. A comprehensive search was performed in August 2020 to identify nasopharyngeal swab guidelines provided by public health in the provinces and territories of Canada. Regional health authority guidance was also collected. Instructions provided were contrasted against the standardized steps. Instructions were identified for all provinces and territories, and for 81 regional health authorities. From the provincial and territorial guidelines, 10/13 (77%) cleared the nasal passages before swab insertion, 11/13 (85%) tilted the patient's head back slightly, 12/13 (92%) inserted the swab parallel to the palate, but only 3/13 (23%) inserted the swab to at least a depth of two-thirds the distance between the patient's nose and ear. A clear majority (81%) of regional health authority guidelines followed their respective provincial guidelines. For depth of insertion, Quebec provided a pictogram but no distance or technique for estimation. Six provinces and territories - Northwest Territories, Nunavut, Ontario, Saskatchewan, Prince Edward Island and Alberta - recommended 4 cm or one-half the distance from nostrils to ear. British Columbia and Manitoba recommended a 7 cm depth of insertion. Nova Scotia recommended one-half to two-thirds the distance from nose to ear. Lastly, Newfoundland, New Brunswick and the Yukon recommended an insertion from nose to the external ear canal. There is significant heterogeneity in guidance for nasopharyngeal swab performance across Canada. The instructions provided by the majority of provinces and territories in Canada would not be effective in reaching the nasopharynx.


Global assessment of small RNAs reveals a non-coding transcript involved in biofilm formation and attachment in Acinetobacter baumannii ATCC 17978.
Many strains of Acinetobacter baumannii have been described as being able to form biofilm. Small non-coding RNAs (sRNAs) control gene expression in many regulatory circuits in bacteria. The aim of the present work was to provide a global description of the sRNAs produced both by planktonic and biofilm-associated (sessile) cells of A. baumannii ATCC 17978, and to compare the corresponding gene expression profiles to identify sRNAs molecules associated to biofilm formation and virulence. sRNA was extracted from both planktonic and sessile cells and reverse transcribed. cDNA was subjected to 454-pyrosequencing using the GS-FLX Titanium chemistry. The global analysis of the small RNA transcriptome revealed different sRNA expression patterns in planktonic and biofilm associated cells, with some of the transcripts only expressed or repressed in sessile bacteria. A total of 255 sRNAs were detected, with 185 of them differentially expressed in the different types of cells. A total of 9 sRNAs were expressed only in biofilm cells, while the expression of other 21 coding regions were repressed only in biofilm cells. Strikingly, the expression level of the sRNA 13573 was 120 times higher in biofilms than in planktonic cells, an observation that prompted us to further investigate the biological role of this non-coding transcript. Analyses of an isogenic mutant and over-expressing strains revealed that the sRNA 13573 gene is involved in biofilm formation and attachment to A549 human alveolar epithelial cells. The present work serves as a basis for future studies examining the complex regulatory network that regulate biofilm biogenesis and attachment to eukaryotic cells in A. baumannii ATCC 17978.


The potential of pregabalin in neurology, psychiatry and addiction: a qualitative overview.
Pregabalin is an anticonvulsant drug that binds to the α₂δ (alpha2delta) subunit of the voltage-dependent calcium channel in central nervous system (CNS). Pregabalin decreases the release of neurotransmitters, including glutamate, norepinephrine, substance P and calcitonin gene-related peptide. Purpose of this paper is to offer a qualitative overview of the studies currently available in literature about this drug, examining the effectiveness of pregabalin in its various fields of application. Our analysis, conducted on a final selection of 349 scientific papers, shows that pregabalin may help to reduce pain in diabetic neuropathy, in post-herpetic neuralgia and in some patients affected by fibromyalgia. It is also effective for the treatment of diverse types of seizures and has similar efficacy to benzodiazepines and venlafaxine in anxiety disorder. Moreover, pregabalin may be a therapeutic agent for the treatment of alcohol abuse, in both withdrawal phase and relapse prevention. Possible implications in the treatment of benzodiazepines dependence are emerging, but a potential abuse or misuse of the drug has also been reported. Range of dosage may fluctuate considerably, from 75 mg to 600 mg per day. Further studies are needed to completely understand pregabalin mechanism of action in the different diseases.


Chloride self-exchange in toad skeletal muscle in vivo and in vitro.
The exchange of cellular Cl with 36Cl has been measured in saline-perfused hindlimb muscles of the pithed toad and compared with cellular Cl exchange in isolated muscles incubated in the vitro either in toad Ringer solution or in toad plasma. In the perfused hindlimb, the rate of 36Cl efflux from muscle cells [17.0 +/- 0.9 pmol Cl.(cm2 plasma membrane.s)-1] was only 40% as fast as that of the 36Cl influx. The discrepancy between Cl influx and efflux was accompanied by a cellular accumulation of Cl against the electrochemical gradient for this anion. Concurrently, the cells took up Na in amounts at least equal to the accumulated Cl. During this accumulation of Na and Cl, the mean resting potential remained constant at a value of -89.2 +/- 1.9 (SE) mV. Na and Cl were taken up by the muscle cells of the perfused hindlimb without a concomitant decrease in cellular K content; i.e., without evidence of inhibition of the Na-K pump. The rate constant for cellular 36Cl efflux from isolated toad muscles preincubated for 3 h in vitro in toad Ringer solution was about five times faster than that of muscles in the perfused hindlimb and similar in magnitude to published values for Cl fluxes in frog muscle. Cellular Cl efflux from muscles briefly preincubated in vitro for 15 min instead of 3 h was significantly slower than after prolonged preincubation. In vitro incubation of isolated toad muscles in toad plasma slowed the cellular 36Cl efflux to values approaching those measured in the perfused hindlimb, without comparably depressing the 36Cl influx. It is suggested that the uptake of NaCl by the cells of perfused hindlimb muscle may proceed by an electroneutral inward cotransport of Na and Cl on the same carrier.


[Occupational accidents in Barcelona (Spain), from 1992 to 1993].
The statistics related to labor accidents as with any other notification system ought to be the basis for programs and policies with a view to the adoption of preventive measures. In order to establish preventive norms, however, the health system needs data from researchers focussing on the dynamics of and the pitfalls revealed by specific events. Within this context the main objective of this study is to proceed with an in-depth analysis of the labor accidents verified in Barcelona (Spain) using for this purpose a descriptive statistics model to test variables such as type of accident, economic sector, economic enterprise and type of labor contract. The data source utilized was the notification system for labor accidents with grave consequences such as death of the victim registered in Barcelona during the period 1992-1993. Labor accidents registered for male workers numbered 848. A log-linear model was applied to this data base. The results show a positive association between traumatic accidents with the construction, traffic and services sectors. A positive association was also found between traumatic accidents and the size of the company concerved the small ones being the worse type in terms of worker's injuries. Regarding the nontraumatic accidents, the study showed a positive correlation between large-sized enterprises and type of temporary worker and the civil construction sector as compared to workers with long term work contracts within industry and services. There was some evidence, also, of a positive association between small and medium sized companies and temporary work and the occurrence of work accidents.