Role of fine needle aspiration cytology in the management of the discrete parotid lump.
A review of fine needle aspiration cytology (FNAC) indicates that the technique can distinguish benign from malignant parotid, disease in 93% of patients evaluated. However, a surgery of 34 head and neck oncologists revealed that making this distinction when an apparently benign parotid lump was being investigated did not normally alter the surgical management for in the presence of low-grade cancer survival is not improved with radical surgery. As FNAC does not alter treatment of a discrete parotid lump, no consensus is currently possible regarding its most appropriate use. Perhaps its value is as a screening procedure and to provide a little more information when advising the patient.


Dental implants in children: A multidisciplinary perspective for long-term success.
Congenital hypodontia or trauma is a frequent cause of loss of teeth in children. The absence of teeth leads to loss of function and lack of normal alveolar growth, along with unpleasant esthetics that hamper the psychosocial development of the young child. Traditionally, the management of tooth loss in the young child is done by conservative means. None of those methods of treatment are completely satisfactory and have their own drawbacks. Dental implants in a young child would be an ideal mode of treatment for the absence of teeth. One of the main deterring factors for implant placement in children is the impending growth. Growth in the maxilla and mandible does not happen uniformly in one plane. It is multidirectional, occurring in sagittal, vertical, and transverse planes. It does not happen at a fixed pace, slow periods of growth are followed by phases of accelerated growth called the growth spurts. Successful implant treatment in children has been achieved by several clinicians when they incorporated a multidisciplinary approach in their treatment plan. The design and type of implant system used in pediatric patients is also responsible for successful treatment outcome. The purpose of this review is to understand the implications of growth and growth assessment and recommendations for the formulation of the treatment plan in pediatric dental implant patients.


DNA replication-coupled inactivation of DnaA protein in vitro: a role for DnaA arginine-334 of the AAA+ Box VIII motif in ATP hydrolysis.
The DnaA protein, which initiates chromosomal replication in Escherichia coli, is negatively regulated by both the sliding clamp of DNA polymerase III holoenzyme and the IdaB protein. We have found that, when the amount of minichromosome is limited in an in vitro replication system, minichromosomal replication-stimulated hydrolysis of DnaA-bound ATP yields the ADP-bound inactive form. The number of sliding clamps formed during replication was at least five per minichromosome, which is 2.7-fold higher than the number formed during incubation without replication. These results support the notion that coupling of DnaA-ATP hydrolysis to DNA replication is the outcome of enhanced clamp formation. We have also found that the amino acid substitution R334H in DnaA severely inhibits the hydrolysis of bound ATP in vitro. Whereas ATP bound to wild-type DnaA is hydrolysed in a DNA-dependent intrinsic manner or in a sliding clamp-dependent manner, ATP bound to DnaA R334H protein was resistant to hydrolysis under the same conditions. This arginine residue may be located in the vicinity where ATP binds, and therefore may play an essential role in ATP hydrolysis. This residue is highly conserved among DnaA homologues and also in the Box VIII motif of the AAA+ protein family.


[Practice and problem in hospice and home palliative care].
In Yamaguchi Red Cross Hospital, hospice services are provided under coordination of palliative care for outpatients and for inpatients and home palliative care. The Home Nursing Center plays the central roles in home palliative care and needs to exclusively provide home medical services. We served for 25% of the patients who died of terminal cancer in the palliative care unit or at home in Yamaguchi City. In the future hospice and palliative home care services, the system to allow patients to choose in hospital care/outpatient care/home palliative care should be established. Home palliative care should be disseminated under the coordination of local municipalities, medical institutions and welfare service organizations so that patients and families can live meaningful lives at their home where they long lived as the place they chose to live.


Feasibility of smartphone application- and social media-based intervention on college students' health outcomes: A pilot randomized trial.
Objective We evaluated the feasibility of a 10-week program combining a smartphone application and theoretically-based, social media-delivered health education intervention to improve college students' health behaviors and outcomes. Participants: Forty-four college students (32 female; X̅age=21.6 years) in 2015-2016. Methods: Participants were randomized into one of two groups: (1) experimental: used MapMyFitness smartphone application to log and track physical activity (PA) and participated in a Social Cognitive Theory-based, Facebook-delivered health education intervention; (2) comparison: only included in a separate, but content-identical, Facebook intervention. Our primary outcomes pertained to intervention feasibility while our secondary outcomes reflected health behaviors and outcomes. Results: Intervention interest was high, with retention 95.5%. Experimental participants used MapMyFitness 1.71x/week, with both groups implementing the Facebook-delivered health education tips 1-3x/week. We observed a modest sedentary behavior reduction in the experimental group (-29.2-minutes/day). Additionally, both groups demonstrated slight reductions in weight (experimental:-1.2 kg/comparison:-0.6 kg) and body fat percentage (both groups:-0.8%-decrease). Increased PA-related social support and decreased barriers were observed. Conclusions: A low-burden and well-integrated social media-based intervention is feasible and of interest to college students, possibly improving select health behaviors and outcomes. PA-oriented smartphone application offered limited additional benefit.


Intrinsic and extrinsic control of peripheral T-cell tolerance by costimulatory molecules of the CD28/ B7 family.
Positive and negative costimulation by members of the CD28 family is critical for the development of productive immune responses against foreign pathogens and their proper termination to prevent inflammation-induced tissue damage. In addition, costimulatory signals are critical for the establishment and maintenance of peripheral tolerance. This paradigm has been established in many animal models and has led to the development of immunotherapies targeting costimulation pathways for the treatment of cancer, autoimmune disease, and allograft rejection. During the last decade, the complexity of the biology of costimulatory pathways has greatly increased due to the realization that costimulation does not affect only effector T cells but also influences regulatory T cells and antigen-presenting cells. Thus, costimulation controls T-cell tolerance through both intrinsic and extrinsic pathways. In this review, we discuss the influence of costimulation on intrinsic and extrinsic pathways of peripheral tolerance, with emphasis on members of the CD28 family, CD28, cytotoxic T-lymphocyte antigen-4 (CTLA-4), and programmed death-1 (PD-1), as well as the downstream cytokine interleukin-1 (IL-2).


Preoperative Portal Vein Embolization in Hepatic Surgery: A Review about the Embolic Materials and Their Effects on Liver Regeneration and Outcome.
Liver volume and function after hepatectomies are directly correlated to postoperative complications and mortality. Consequently contemporary liver surgery has focused on reaching an adequate future liver remnant so as to diminish postoperative morbidity and mortality. Portal vein embolization has evolved and is the standard of care as a liver regenerative strategy in many surgery departments worldwide before major liver resections. Different embolic materials have been used for portal vein embolization including gelfoam, ethanol, polyvinyl-alcohol particles, calibrated microspheres, central vascular plugs, coils, n-butyl-cyanoacrylate glue, fibrin glue, polidocanol-foam, alcoholic prolamin solution, and ethylene vinyl alcohol copolymer, as sole occluders or in varied combinations. While to date there has been no prospective controlled trial comparing the efficacy of different embolic materials in portal vein embolization, retrospective data insinuates that the use of n-butyl-cyanoacrylate and absolute ethanol produces higher contralateral liver hypertrophies. In this review, we evaluated publications up to August 2019 to assess the technical and regenerative results of portal vein embolization accomplished with different embolic materials. Special attention was given to specific aspects, advantages, and drawbacks of each embolic agent used for portal vein embolization, its liver regenerative performance, and its influence on patient outcome.


Commutability of control materials in glycohemoglobin determinations.
The intermethod variabilities of control materials and patient blood samples for the measurement of glycohemoglobin were compared. Sets of 50 blood samples and 15 control materials were analyzed by HPLC and affinity and immunochemical methods. For each pair of methods, the distances of the materials from the regression line of patient blood results (expressed as normalized residuals) were calculated. Only two of 15 controls had normalized residuals exceeding 3 standard deviations from the regression line. Total hemoglobin (Hb) content, Hb derivatives, and cellulose acetate electrophoresis demonstrated that only a minority of controls could be considered similar to patients' blood samples. We selected Menarini's and our home-prepared controls to simulate calibration of the different techniques by these materials. Intermethod calibration succeeded mostly in harmonizing results obtained by HPLC methods. On the contrary, calibration of the immunochemical techniques (Boehringer and Roche) did not improve intermethod agreement to a clinically useful level.


Cities and health: history, approaches, and key questions.
The majority of the world's population will live in cities in the next few years, and the pace of urbanization worldwide will continue to accelerate over the coming decades. Such a dramatic demographic shift can be expected to have an impact on population health. Although there has been historic interest in how city living is associated with health, this interest has waxed and waned and a cogent framework has yet to evolve that encompasses key issues in urban health. In this article, the authors discuss three alternate approaches to the study of urban health today; these include considering urban health from the perspective of a presumed urban health penalty, from an urban sprawl perspective, and more comprehensively, considering how urban living conditions may be associated with health. The authors also propose three key questions that may help guide the study and practice of urban health in coming decades. These include considering what specific features of cities are causally related to health, the extent to which these features are unique to a particular city or are different between cities, and ultimately, to what extent these features of cities are modifiable in order to allow interventions that can improve the health of urban populations.


A chronic myeloid leukemia case with a unique variant Philadelphia translocation: t(9;22;21)(q34;q11;p12).
The so-called Philadelphia (Ph) chromosome is present in more than 90% of chronic myeloid leukemia (CML) patients. Approximately, 5-10% of these patients show complex translocations involving a third chromosome in addition to chromosomes 9 and 22. Since at present the majority of CML cases are treated with imatinib, variant rearrangements do not exhibit specific prognostic significance. However, events of therapy resistance remain to be studied. In this study, we report a unique case of CML exhibiting an uncommon t(21;22)(p12;q11). This translocation has been characterized by fluorescence in situ hybridization (FISH) and array-proven multicolor banding (aMCB). Using specific probes for the BCR and ABL genes, results of FISH showed a three-way variant Philadelphia translocation (9;22;21)(q34;q11;p12) with a BCR/ABL fusion residing on the der(22) and the 3'BCR region translocated on the short arm of the derivative chromosome 21. In addition, the aMCB technique is significant in the detection of the breakpoints of genetic changes. The underlying mechanisms and prognostic significance of these changes are discussed.


[Comparative characteristics of adhesion of chemically hardened composite materials].
Marginal leakage in class I cavities restored with chemically hardened resin composites (Talan, Charisma PPF, Esterfill) and adhesive strength were studied in vitro. The results indicate the least marginal leakage and best adhesive strength of the Talan composite.


Characterization of the binding of human low-density lipoprotein to primary monolayer cultures of rat hepatocytes.
The binding of human low-density lipoprotein labelled with 125I to rat hepatocytes in monolayer culture was measured at 4 degrees C. Evidence for two different specific binding sites was obtained. Binding to Site 1 was characterized by: being displaced by dextran sulphate or heparin; being dependent on Ca2+; having a Kd value of about 15 micrograms of protein/ml; not being significantly displaced by a 20-fold excess unlabelled low-density lipoprotein that had been reductively methylated; being displaced by approx. 40% by a 20-fold protein excess of unlabelled human high-density lipoprotein, HDL3, and increasing with time in culture when newborn-calf serum was present in the medium. The binding to Site 2 had the following properties: it was not displaced by sulphated polysaccharides; it was only partially Ca2+-dependent, and the presence of EDTA increased the Kd value; the apparent Kd value in the presence of Ca2+ was approx. 30 micrograms of protein/ml, which was significantly higher than for Site 1; it was displaced by approx. 30% with a 20-fold excess of low-density lipoprotein that had been methylated; it was displaced by unlabelled HDL3 to a similar extent to Site 1; it did not increase significantly with time in culture. The characteristics of binding to Sites 1 and 2 are discussed in relation to the receptors for low-density lipoproteins that have previously been described in various cell types. It is proposed that the experimental system described in this paper is suitable for studying the regulation of the binding of low-density lipoproteins to hepatocytes.


Comprehensive stiffness regulation on multi-section snake robot with considering the parasite motion and friction effects.
Snake robots have been widely used in challenging environments, such as confined spaces. However, most existing snake robots with large length/diameter ratios have low stiffness, and this limits their accuracy and utility. To remedy this, a novel 'macro-micro' structure aided by a new comprehensive stiffness regulation strategy is proposed in this paper. This improves the positional accuracy when operating in deep and confined spaces. Subsequently, a comprehensive strategy for regulating the stiffness of the system is then developed, along with a kinetostatic model for error prediction. The internal friction, variation of cable stiffness as a function of tension, and their effects on the structural stiffness of the snake arm under different configurations have been incorporated into the model to increase the modelling accuracy. Finally, the proposed models were validated experimentally on a physical prototype and control system (error: 4.3% and 2.5% for straight and curved configurations, respectively). The improvement in stiffness due to the adjustment of the tension in the driving cables (i.e. average 183.4%) of the snake arm is shown.


Reducing unmet need and unwanted childbearing: evidence from a panel survey in Pakistan.
Pakistan's high unmet need for contraception and low contraceptive prevalence remain a challenge, especially in light of the country's expected contribution to the FP2020 goal of expanding family planning services to an additional 120 million women with unmet need. Analysis of panel data from 14 Pakistani districts suggests that efforts to reduce unmet need should also focus on empowering women who are currently practicing contraception to achieve their own reproductive intentions through continuation of contraceptive use of any method. Providing women with better quality of care and encouraging method switching would bridge the gap that exists when women are between methods and thus would reduce unwanted births. This finding is generalizable to other countries that, like Pakistan, are highly dependent on short-acting modern and traditional methods. The approach of preventing attrition among current contraceptive users would be at least as effective as persuading nonusers to adopt a method for the first time.


Home-inhaled nitric oxide in a child with pulmonary arterial hypertension associated with post-operative pulmonary venous obstruction.
Home-inhaled nitric oxide therapy was effective and feasible in the patients with intractable pulmonary arterial hypertension. We present the case of a child with severe pulmonary arterial hypertension associated with post-operative pulmonary venous obstruction who was treated with home-inhaled nitric oxide therapy.


Contribution to the improvement of a porridge made with fermented maize: effect of selected foods and lemon on energy density, pH, viscosity and nutritional quality.
The objective of the present study was to use lemon and selected foods to improve the nutritional characteristics, quality and the nutrient content of a traditional complementary porridge made of lactic acid fermented yellow maize. Boiled egg yolk, roasted peanut paste, dry crayfish flour, roasted soybean flour and lemon juice were used as food additions. Amounts of food added were calculated on the basis of World Health Organization estimated energy needs from complementary foods of well-nourished children in developing countries, aged 9-11 months, at four servings per day and a low amount of breast milk energy. The pH and viscosity increased in porridges with food addition, but lemon juice contributed to lowering them. Energy and nutrient densities/100 g porridge improved with food addition regardless of the use of lemon juice. An increase in iron, zinc and calcium in vitro availability was observed (P < 0.05) with the addition of lemon juice.


Cancer Screening among immigrants living in urban and regional Australia: results from the 45 and up study.
Over 25% of the Australian population are immigrants, and are less active participants in cancer screening programmes. Most immigrants live in urban areas of Australia, but a significant proportion (~20%), live in regional areas. This study explored differences in cancer screening participation by place of birth and residence. Self-reported use of mammogram, faecal occult blood test (FOBT), and/or prostate specific antigen (PSA) tests was obtained from 48,642 immigrants and 141,275 Australian-born participants aged 50 years or older in the 45 and Up Study (New South Wales, Australia 2006-2010). Poisson regression was used to estimate relative risks of test use, adjusting for key socio-demographic characteristics. Overall, immigrants from Asia and Europe were less likely to have had any of the tests in the previous two years than Australian-born participants. Regional Australian-born participants were more likely to have had any of the tests than those living in urban areas. Regional immigrant participants were more likely to have had an FOBT or PSA test than those living in urban areas, but there were no differences in mammograms. This report identifies key immigrant groups in urban and regional areas that policymakers and healthcare providers should target with culturally appropriate information to promote cancer screening.


Smoking and asthma in men and women with normal weight, overweight, and obesity.
There is a complex interrelationship among smoking, body weight, and asthma. It needs to be clarified whether smoking is related to an increased risk of asthma after taking into account for relative body weight. To examine the association between cigarette smoking and the prevalence of asthma in Canadian men and women with normal weight, overweight, and obesity. The analysis was based on data from 112,830 Canadians aged 18 years or more who participated in a national survey in 2007-2008. A questionnaire covered the information on prevalent asthma, smoking status, height, weight, and other factors. Logistic regression analysis was used to determine the association between smoking and the prevalence of asthma stratified by sex and body mass index (BMI). The crude prevalence of asthma was 6.6% for men and 9.3% for women. After adjustment for covariates, the odds ratios (ORs) for current smoking associated with asthma was 1.20 [95% confidence interval (CI): 1.01-1.43] for men with normal weight, 0.98 (95% CI: 0.81, 1.18) for overweight men, and 1.02 (95% CI: 0.80-1.30) for obese men. For women, the corresponding adjusted ORs were 1.41 (95% CI: 1.23-1.62), 1.27 (95% CI: 1.05-1.54), and 1.28 (95% CI: 1.03-1.59), respectively. Current smoking was significantly associated with prevalent asthma in all women regardless of their relative body weight. In men, however, the association was only observed in those with under- or normal weight.


EDAP LT-01 piezoelectric lithotriptor.
This is a first-rate, well thought out lithotriptor. It is very user friendly. Although not as powerful as some of the earlier devices, it has the distinct advantage of not causing any tissue damage during treatment. The advantage is the ability to vary the delivery of the amount of power according to the needs of the situation. The learning curve for the operator is steep, and he/she very quickly becomes very proficient. Patience is needed with some stones to give enough shocks for total fragmentation, but that comes with experience. Balancing the ease of treatment against the occasional need for retreatment results in a definite bias for the patient being treated with this machine, and avoiding the reported problems attendant with spark gap equipment. This, in my opinion, is an excellent machine.


A prospective study of plasma nitrates following human heart transplantation-relevance to myocardial function.
Nitric oxide (NO) has been shown to affect myocardial function in positive and negative inotropic ways. Expression of inducible nitric oxide synthase and release of nitric oxide into the circulation has been associated with acute rejection in animal studies. The role of NO and the associated myocardial dysfunction seen during acute rejection in humans has not been adequately defined. In a prospective sequential study, we have studied the relationship between plasma nitrate and biopsy-proven acute rejection, and systolic and diastolic function after heart transplantation. Biopsies were performed weekly and then fortnightly up to 12 weeks after transplantation and on clinical indication of rejection in 37 patients. Plasma nitrates were obtained on the morning of each biopsy (total 341). An echocardiogram was performed immediately prior to each biopsy in which the systolic parameters, ejection fraction (EF) and fractional shortening (fs), and the diastolic parameters, isovolumetric relaxation time (IVRT), mitral valve pressure half-time (MVPHT), mitral valve deceleration time (MVDT), e:a ratio, and a wave duration, were measured. Plasma-nitrate level showed no significant correlation with the systolic parameters, EF or fs, or with changes in EF or fs. No significant correlation was found between plasma-nitrate level and the diastolic parameters IVRT, MVPHT, MVDT, mitral valve a wave duration, or e:a ratio. This study has shown no correlation between plasma nitrate and impaired systolic or diastolic function after heart transplantation. Instead there was a weak trend for elevated nitrate to be associated with better systolic function.


Application of VirCapSeq-VERT and BacCapSeq in the diagnosis of presumed and definitive neuroinfectious diseases.
Unbiased high-throughput sequencing (HTS) has enabled new insights into the diversity of agents implicated in central nervous system (CNS) infections. The addition of positive selection capture methods to HTS has enhanced the sensitivity while reducing sequencing costs and the complexity of bioinformatic analysis. Here we report the use of virus capture-based sequencing for vertebrate viruses (VirCapSeq-VERT) and bacterial capture sequencing (BacCapSeq) in investigating CNS infections. Thirty-four samples were categorized: (1) patients with definitive CNS infection by routine testing; (2) patients meeting clinically the Brighton criteria (BC) for meningoencephalitis; (3) patients with presumptive infectious etiology highest on the differential. RNA extracts from cerebrospinal fluid (CSF) were used for VirCapSeq-VERT, and DNA extracts were used for BacCapSeq analysis. Among 8 samples from known CNS infections in group 1, VirCapSeq and BacCapSeq confirmed 3 expected diagnoses (42.8%), were negative in 2 (25%), yielded an alternative result in 1 (11.1%), and did not detect 2 expected negative pathogens. The confirmed cases identified HHV-6, HSV-2, and VZV while the negative samples included JCV and HSV-2. In groups 2 and 3, 11/26 samples (42%) were positive for at least one pathogen; however, 27% of the total samples (7/26) were positive for commensal organisms. No microbial nucleic acids were detected in negative control samples. HTS showed limited promise for pathogen identification in presumed CNS infectious diseases in our small sample. Before conducting larger-scale prospective studies to assess the clinical value of this novel technique, clinicians should understand the benefits and limitations of using this modality.


Characterization of antiproliferative potential and biological targets of a copper compound containing 4'-phenyl terpyridine.
Several copper complexes have been assessed as anti-tumor agents against cancer cells. In this work, a copper compound [Cu(H2O){OS(CH3)2}L](NO3)2 incorporating the ligand 4'-phenyl-terpyridine antiproliferative activity against human colorectal, hepatocellular carcinomas and breast adenocarcinoma cell lines was determined, demonstrating high cytotoxicity. The compound is able to induce apoptosis and a slight delay in cancer cell cycle progression, probably by its interaction with DNA and induction of double-strand pDNA cleavage, which is enhanced by oxidative mechanisms. Moreover, proteomic studies indicate that the compound induces alterations in proteins involved in cytoskeleton maintenance, cell cycle progression and apoptosis, corroborating its antiproliferative potential.


The impact of exacerbations on the asthmatic patient's preference scores.
The purpose of this study was to examine the effect of exacerbations on mild to moderate asthmatic patients' preference-based, health-related, quality of life scores and also to describe the effect of these exacerbations on daily life. In a survey, 100 mild to moderate asthmatic patients in the United Kingdom were asked to rate three different health marker states on a scale between 0 (death) and 100 (perfect health), defined as: your asthma of today, a mild exacerbation, and a severe exacerbation of asthma. They were also asked to describe their symptoms and what they did when experiencing an exacerbation. During exacerbations the vast majority of asthmatic patients have significant symptoms and consume a considerable amount of health care resources, which often overlap. The health marker state "your asthma of today" was given a mean score of 81.0, a mild exacerbation a score of 62.1, and a severe exacerbation a score of 25.6, indicating a large impact on patients' daily life and their health-related quality of life. In conclusion, asthmatic patients are severely affected in their health and daily living by mild and severe exacerbations. Considerable effort should be made to reduce the number and severity of exacerbations.


Attention set for number: expectation and perceptual load in inattentional blindness.
Inattentional blindness is the failure to detect unexpected events when attention is otherwise engaged. Previous research indicates that inattentional blindness increases as perceptual demands intensify. The authors present 6 cuing experiments that manipulated both the perceptual demands of a primary letter-naming task and the expectations of the individual. Inattentional blindness was greatest for individuals who held a numerical expectation that was consistent with the number of primary-task items presented. Expectation also affected detection differentially at various levels of perceptual load: Detection at moderate and high perceptual load was significantly affected by expectation, whereas detection at low perceptual load was not. The authors suggest that at moderate to high levels of perceptual load, individuals whose numerical expectations are fulfilled terminate processing when the primary task is complete, at the expense of the unexpected visual event. These experiments provide compelling evidence that expectations do affect detection of an unexpected stimulus, and they are the first to demonstrate that individuals set their attention for the number of items to be detected and are vulnerable to inattentional blindness whenever their primary-task numerical expectation is fulfilled.


Neuroanatomy of childhood disruptive behavior disorders.
Our aims were to (1) examine possible neuroanatomical abnormalities associated with the Disruptive Behavior Disorders (DBDs) as a group and (2) assess neuroanatomical anomalies specific to each DBD (i.e., conduct disorder [CD] and oppositional defiant disorder). Cortical thickness analysis and voxel-based morphometry were analyzed in 47 8-year-old boys (22 DBDs with and without CD and/or ODD and 25 healthy controls) from Magnetic Resonance Imaging brain scans. DBD symptoms were assessed using the Dominic-R. In DBD subjects relative to controls, we found (1) a decreased overall mean cortical thickness; (2) thinning of the cingulate, prefrontal and insular cortices; and (3) decreased gray matter density (GMd) in the same brain regions. We also found that scores on the Dominic-R were negatively correlated with GMd in the prefrontal and precuneus/superior temporal regions. There was a subdiagnostic main effect for CD, related to thinning of the middle/medial frontal, and for ODD in the left rectal/orbitofrontal. Findings suggest that thinning and decreased GMd of the insula disorganizes prefrontal circuits, diminishing the inhibitory influence of the prefrontal cortex on anger, aggression, cruelty, and impulsivity, and increasing a person's likelihood of aggressive behavior. These findings have implications for pathophysiologic models of the DBDs, their diagnostic classification system, and for designing more effective intervention programs.


Bone Transport with the Taylor Spatial Frame Technique: A Case Series.
Bone transport is a beneficial reconstructive method for bone defects caused by infected non-unions or bone tumours. The Taylor Spatial Frame (TSF) is a three-dimensional corrective external fixator that can be used to achieve bone transport and correct any residual deformities easily at any time. This study reports the results of bone transport using TSF. This is a retrospective study of ten patients who underwent bone transport using the TSF. The mean age was 32.3 years; the femur was affected in one case and the lower leg in nine. Bone defects were due to infected non-unions in seven cases and bone tumours in three. The duration of external fixation, bone transport distance, distraction index (DI), alignment at the end of correction, leg length discrepancy, and complications were investigated. The average bone transport distance was 76.0 mm. The external fixation period averaged 367 days with the DI at 20.8 days/cm. Deformity at the docking site was assessed to have an average 2.6° deformity and 2.0 mm translation in the frontal view, as well as 3.3° deformity and 3.7 mm translation in the lateral view. The mean leg length discrepancy was 10.9 mm and the percentage of the mechanical axis (%MA) was 40.6%. Four patients underwent plate conversion after correction and two required additional surgery for non-union at the docking site. Bone union was achieved in all patients and there was no reaggravation of infection or tumour recurrence. The TSF allowed for the correction of deformities and translations that occurred during bone transport giving excellent results. However, as with bone transport using this or other devices, additional procedures are often needed to obtain consolidation or docking site union. Shimokawa K, Matsubara H, Hikichi T, et al. Bone Transport with the Taylor Spatial Frame Technique: A Case Series. Strategies Trauma Limb Reconstr 2023;18(2):117-122.


Nucleotide sequence of the fnr gene and primary structure of the Enr protein of Escherichia coli.
The nucleotide sequence of a 1.64 kb fragment of E. coli DNA containing the fnr gene (regulatory gene for fumarate and nitrate reduction) was determined using the dideoxy chain termination method. The fnr coding region (750 bp) was identified, and the initiation and termination points of fnr transcription were located by RNA:DNA hybridisation with single-stranded M13 probes. The DNA fragment also contained the 5' end of a separately transcribed gene of unknown function. The deduced molecular weight (27947) of the Fnr protein was in agreement with that of the protein identified by the maxicell procedure, and the primary structure contained regions of homology with several transcriptional regulator proteins.


Post-colonoscopy colorectal cancers in Sweden: room for quality improvement.
Post-colonoscopy colorectal cancer (PCCRC), a cancer occurring within a short interval of a colonoscopy, might be partly explained as missed or incompletely resected lesions. Associated risk factors are age, sex, comorbidity, cancer location, and colonoscopy volume. There is a gap in the knowledge of prevalence of PCCRC and the impact of different risk factors in Sweden. This is a retrospective population-based observational cohort study of the colonoscopies performed on adults during the years 2001-2010 that were identified from Swedish health registers. The rate of PCCRC (diagnosed 6-36 months after the first colonoscopy) was defined as the number of PCCRCs divided by the number of colorectal cancers (CRC) in the interval of 0-36 months. Univariate and multivariate Poisson regression analyses examined associations with PCCRC. There were 289 729 colonoscopies performed on 249 079 individuals included in the study. There were 16 319 individuals with a colorectal cancer diagnosis 0-36 months after a colonoscopy. Of these, 1286 (7.9%) were PCCRCs. In the multivariate analysis, young age (18-30 years) and former polyp diagnosis had the highest risks [relative risk (RR)=3.3; 95% confidence interval: 2.1-5.2 and RR=3.1; 95% confidence interval: 2.7-3.6]. The impact of other risk factors, such as female sex, comorbidity, right sided colorectal cancer location, and time period, was consistent with the finding in other studies. The prevalence of PCCRC in Sweden seems to be relatively high, indicating that there is room for improvement in colonoscopy quality. The high RR of PCCRC in the youngest age group, even though there were only a few cases, has not been described in other studies.


Who gets custody?
Changes in the living arrangements of children have implications for social policy and children's well-being. Understanding who gets custody on divorce--mother, father, or both sharing custody--can also inform our understanding of family organization and the merits of alternative theories of marriage and divorce. We examine physical-custody outcomes among recent Wisconsin divorces in an effort to understand the factors associated with shared custody as well as mother-sole custody and father-sole custody. Although mother-sole custody remains the dominant arrangement, shared custody has increased over a nine-year period. We find that the probability of shared custody increases with parent's income. Prior marital history, parents' ages, the age and gender of children, and the legal process also have an impact on the probability of shared custody. In contrast to shared custody, the probability of father-sole custody decreases with parent's income, while the relationship with other significant factors is generally similar. The notable exception is that, unlike shared custody, we find no evidence for an increase over time in the probability of father-sole custody. We also find that when the father has a higher proportion of the couple's total income, both shared custody and father-sole custody are more likely.


Applications of Resting-State fNIRS in the Developing Brain: A Review From the Connectome Perspective.
Early brain development from infancy through childhood is closely related to the development of cognition and behavior in later life. Human brain connectome is a novel framework for describing topological organization of the developing brain. Resting-state functional near-infrared spectroscopy (fNIRS), with a natural scanning environment, low cost, and high portability, is considered as an emerging imaging technique and has shown valuable potential in exploring brain network architecture and its changes during the development. Here, we review the recent advances involving typical and atypical development of the brain connectome from neonates to children using resting-state fNIRS imaging. This review highlights that the combination of brain connectome and resting-state fNIRS imaging offers a promising framework for understanding human brain development.


The Impact of Integrated Multidisciplinary Palliative Care Program on Symptoms in Patients at the Palliative Care Ward-An Audit and a Protocol of Prospective Controlled Investigation.
An integrated multidisciplinary palliative care (IMPC) program is a promising tool to improve symptom control in patients at the end of life. The aim was to study the feasibility of the IMPC program in patients at the palliative care (PC) ward. A retrospective audit, using the extended Edmonton Symptom Assessment Scale (ESAS), was conducted on the PC ward of the university hospital. Consecutive patients who were admitted for the IMPC program during 1 year were considered. One hundred forty-eight cases (93% with underlying cancer) were analyzed. The intensity of pain levels, nausea, vomiting, shortness of breath, and sleep disorders decreased at least by 50% ( P < .0001) during the 13 (median) days of IMPC. Integrated multidisciplinary PC program was associated with symptom improvements in patients at the PC ward. The information generated supports sample size calculation for a prospective controlled trial.


Some coral diseases track climate oscillations in the Caribbean.
Disease outbreaks continue to reduce coral populations worldwide. Understanding coral diseases and their relationships with environmental drivers is necessary to forecast disease outbreaks, and to predict future changes in coral populations. Yet, the temporal dynamics of coral diseases are rarely reported. Here we evaluate trends and periodicities in the records of three common coral diseases (white-band disease, yellow-band disease, and dark-spot syndrome) that were surveyed between 1997 and 2014 at 2082 sites throughout the Caribbean. The relationship between the periodicities of disease prevalence and El Niño Southern Oscillation (ENSO) cycles was examined using cross-wavelet analyses and convergent cross mapping (CCM). The prevalence of the diseases peaked every two to four years, and matched periodicities in ENSO conditions. CCM models suggested that environmental conditions associated with recent ENSO cycles may have influenced the patterns in disease prevalence. We also found no increasing trends in disease prevalence through time. Instead, our work suggests that the prevalence of coral diseases is dynamic and complex. The gradual increase in sea-surface temperature, a consequence of increasing greenhouse gas emissions, progressively raises the modal temperature threshold of each ENSO cycle. These dynamic cycles and the increasing modal temperatures appear to influence the dynamics of coral diseases.


Impaired secretion of mutant alpha 2-plasmin inhibitor (alpha 2 PI-Nara) from COS-7 and HepG2 cells: molecular and cellular basis for hereditary deficiency of alpha 2-plasmin inhibitor.
The elongated mutant of alpha 2-plasmin inhibitor (alpha 2 PI) designated as alpha 2 PI-Nara is caused by a frameshift mutation found near the 3' end of the coding region of the alpha 2 PI gene. To elucidate the mechanism by which this molecular abnormality leads to alpha 2 PI deficiency in plasma, we transfected an expression plasmid for alpha 2 PI-Nara into a monkey kidney cell line COS-7 or human hepatoma cell line HepG2 synthesizing alpha 2 PI, and analyzed the secretory process of the expressed alpha 2 PI-Nara by radioimmunoprecipitation followed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and fluorography. The results obtained showed that the recombinant alpha 2 PI-Nara was retained within the cells for prolonged periods as an endoglycosidase H-sensitive precursor form, and only a small portion of the recombinant protein was secreted into the medium as a neuraminidase-sensitive mature form. These results suggest that instead of being secreted from the cells, most of the alpha 2 PI-Nara undergoes degradation within the cells while its transport is retarded in the intracellular secretory pathway; thus, alpha 2 PI-Nara should lead to the alpha 2 PI deficiency primarily by causing a block in the intracellular transport from the endoplasmic reticulum to the Golgi complex.


Comparison of next generation technologies and bioinformatics pipelines for capsular typing of Streptococcus pneumoniae.
Whole genome sequencing (WGS)-based approaches for pneumococcal capsular typing have become an alternative to serological methods. In silico serotyping from WGS has not yet been applied to long-read sequences produced by third-generation technologies. The objective of the study was to determine the capsular types of pneumococci causing invasive disease in Catalonia (Spain) using serological typing and WGS and to compare the performance of different bioinformatics pipelines using short- and long-read data from WGS. All invasive pneumococcal pediatric isolates collected in Hospital Sant Joan de Déu (Barcelona) from 2013 to 2019 were included. Isolates were assigned a capsular type by serological testing based on anticapsular antisera and by different WGS-based pipelines: Illumina sequencing followed by serotyping with PneumoCaT, SeroBA, and Pathogenwatch vs MinION-ONT sequencing coupled with serotyping by Pathogenwatch from pneumococcal assembled genomes. A total of 119 out of 121 pneumococcal isolates were available for sequencing. Twenty-nine different serotypes were identified by serological typing, with 24F (n = 17; 14.3%), 14 (n = 10; 8.4%), and 15B/C (n = 8; 6.7%) being the most common serotypes. WGS-based pipelines showed initial concordance with serological typing (>91% of accuracy). The main discrepant results were found at the serotype level within a serogroup: 6A/B, 6C/D, 9A/V, 11A/D, and 18B/C. Only one discrepancy at the serogroup level was observed: serotype 29 by serological testing and serotype 35B/D by all WGS-based pipelines. Thus, bioinformatics WGS-based pipelines, including those using third-generation sequencing, are useful for pneumococcal capsular assignment. Possible discrepancies between serological typing and WGS-based approaches should be considered in pneumococcal capsular-type surveillance studies.


Reduced expression of hemopoietic cytokine receptors on cord blood progenitor cells in neonates at risk for atopy.
Recent findings point to an association between allergic asthma in adults and increased responsiveness of myeloid progenitor cells to certain hemopoietic growth factors. However, it is not clear at what age these changes in progenitor cells first become manifest, although increasing evidence suggests that the allergic phenotype may begin to emerge in very early life. We sought to compare expression of hemopoietic cytokine receptors on CD34(+) progenitor cells in cord blood from normal infants ("low risk" for subsequent atopy) and infants with at least one atopic first degree relative ("at risk" for subsequent atopy). Cord blood was obtained from 21 neonates. Nonadherent mononuclear cells were stained with mAbs directed against CD45, CD34, and the alpha-chains of the GM-CSF, IL-3, and IL-5 receptors and analyzed by flow cytometry. No differences in absolute CD34(+) numbers were observed between the 2 groups. However, expression of GM-CSF receptor on CD34(+) cells was reduced in the "at-risk" compared with the "low- risk" group (P =.021), although no significant differences were noted between the 2 groups with respect to IL-3 and IL-5 receptor expression. The functional sequelae of reduced GM-CSF receptor expression on CD34(+) cells remain to be determined. Nonetheless, these findings show an association between genetic risk for atopy and changes in the expression of hemopoietic cytokine receptors on cord blood progenitor cells and support the notion that the allergic phenotype may begin to evolve in the perinatal period.


Discharge patterning in rat olfactory bulb mitral cells in vivo.
Here we present a detailed statistical analysis of the discharge characteristics of mitral cells of the main olfactory bulb of urethane-anesthetized rats. Neurons were recorded from the mitral cell layer, and antidromically identified by stimuli applied to the lateral olfactory tract. All mitral cells displayed repeated, prolonged bursts of action potentials typically lasting >100 sec and separated by similarly long intervals; about half were completely silent between bursts. No such bursting was observed in nonmitral cells recorded in close proximity to mitral cells. Bursts were asynchronous among even adjacent mitral cells. The intraburst activity of most mitral cells showed strong entrainment to the spontaneous respiratory rhythm; similar entrainment was seen in some, but not all nonmitral cells. All mitral cells displayed a peak of excitability at ~25 msec after spikes, as reflected by a peak in the interspike interval distribution and in the corresponding hazard function. About half also showed a peak at about 6 msec, reflecting the common occurrence of doublet spikes. Nonmitral cells showed no such doublet spikes. Bursts typically increased in intensity over the first 20-30 sec of a burst, during which time doublets were rare or absent. After 20-30 sec (in cells that exhibited doublets), doublets occurred frequently for as long as the burst persisted, in trains of up to 10 doublets. The last doublet was followed by an extended relative refractory period the duration of which was independent of train length. In cells that were excited by application of a particular odor, responsiveness was apparently greater during silent periods between bursts than during bursts. Conversely in cells that were inhibited by a particular odor, responsiveness was only apparent when cells were active. Extensive raw (event timing) data from the cells, together with details of those analyses, are provided as supplementary material, freely available for secondary use by others.


Prognostic Factors for Return to Sport After High Tibial Osteotomy: A Directed Acyclic Graph Approach.
High tibial osteotomy (HTO) is increasingly used in young and physically active patients with knee osteoarthritis. These patients have high expectations, including return to sport (RTS). By retaining native knee structures, a return to highly knee-demanding activities seems possible. However, evidence on patient-related outcomes, including RTS, is sparse. Also, time to RTS has never been described. Furthermore, prognostic factors for RTS after HTO have never been investigated. These data may further justify HTO as a surgical alternative to knee arthroplasty. To investigate the extent and timing of RTS after HTO in the largest cohort investigated for RTS to date and to identify prognostic factors for successful RTS. Case-control study; Level of evidence, 3. Consecutive patients with HTO, operated on between 2012 and 2015, received a questionnaire. First, pre- and postoperative sports participation questions were asked. Also, time to RTS, sports level and frequency, impact level, the presymptomatic and postoperative Tegner activity score (1-10; higher is more active), and the postoperative Lysholm score (0-100; higher is better) were collected. Finally, prognostic factors for RTS were analyzed using a logistic regression model. Covariates were selected based on univariate analysis and a directed acyclic graph. We included 340 eligible patients of whom 294 sufficiently completed the questionnaire. The mean follow-up was 3.7 years (± 1.0 years). Out of 256 patients participating in sports preoperatively, 210 patients (82%) returned to sport postoperatively, of whom 158 (75%) returned within 6 months. We observed a shift to participation in lower-impact activities, although 44% of reported sports activities at final follow-up were intermediate- or high-impact sports. The median Tegner score decreased from 5.0 (interquartile range [IQR], 4.0-6.0) presymptomatically to 4.0 (IQR, 3.0-4.0) at follow-up (P < .001). The mean Lysholm score at follow-up was 68 (SD, ± 22). No significant differences were found between patients with varus or valgus osteoarthritis. The strongest prognostic factor for RTS was continued sports participation in the year before surgery (odds ratio, 2.81; 95% CI, 1.37-5.76). More than 8 of 10 patients returned to sport after HTO. Continued preoperative sports participation was associated with a successful RTS. Future studies need to identify additional prognostic factors.


Tobacco tax evasion in Western Balkan countries: tax evasion prevalence and evasion determinants.
Tobacco tax evasion undermines the goal of tobacco taxes as a tobacco control measure to make tobacco products less affordable, increases the health risks for those who smoke and decreases the government revenue. This paper analyses the tobacco tax evasion in six Western Balkan (WB) countries: Albania, Bosnia and Herzegovina, Kosovo, Montenegro, North Macedonia and Serbia. The aim of this research is to estimate the size of the illicit market and identify the main determinants of tax evasion activities in the Southeastern European region. Data from 2019 Survey on Tobacco Consumption in Southeastern Europe (STC-SEE) are used. STC-SEE provides uniquely comparable nationally representative data on smoking behaviour for adult (18-85 years old) population for each country. Tax evasion is defined on the basis of available information on tax stamps, health warnings, price and the place of purchase, in accordance with the previous research on tax evasion. In order to estimate the determinants of illicit purchases we use binary choice model of tax evasion. The study finds that 20.4% of all current smokers in WB countries evade taxes on tobacco products, with evasion being much more frequent for hand-rolled (HR) tobacco (86.7%) than for the manufactured cigarettes (MC) (8.6%). While HR is predominantly illicit in all six countries, MC evasion varies significantly, with evasion being significantly higher in Montenegro and Bosnia and Herzegovina. Results further suggest that tax evasion is higher in the statistical regions where institutional capacities to tackle illicit trade are lower, in municipalities bordering countries with high MC evasion, as well as among smokers with low income, women and elderly. We also provide evidence that higher tobacco taxes and prices do not increase illicit consumption. The findings from the research suggest that in order to decrease tax evasion, governments should put additional effort to strengthen institutional capacities to tackle illicit tobacco markets. Furthermore, improving regional coordination in development and implementation of tobacco control policies, including the prevention of illicit market, is essential in lowering evasion in all WB countries. Finally, WB countries should regulate and enforce excise tax stamp requirements on the HR tobacco market to a much higher degree.


Further psychometric evaluation of the self-stigma scale-short: measurement invariance across mental illness and gender.
This study cross-validated the factor structure of the Self-Stigma Scale-Short (SSS-S) in a cohort of patients with mental illness in southern Taiwan. The measurement invariance of the SSS-S factor structure across mental illness and gender was also examined. The sample consisted of 161 patients with schizophrenia (51.6% males; mean age ± SD = 40.53 ± 10.38 years) and 189 patients with other mental illnesses (34.9% males; mean age = 46.52 ± 11.29 years). The internal reliability (total score: α = 0.948) and concurrent validity (r = 0.335 to 0.457 with Depression and Somatic Symptoms Scale; r = -0.447 to -0.556 with WHOQOL-BREF) of the SSS-S were both satisfactory, and the results verified that the factor structure in our Taiwan sample (RMSEA = 0.0796, CFA = 0.992) was the same as that of the Hong Kong population. In addition, the results supported the measurement invariance of the SSS-S across mental illness (ΔRMSEAs = -0.0082 to -0.0037, ΔCFAs = 0.000) and gender (ΔRMSEAs = -0.0054 to -0.0008, ΔCFAs = -0.001 to 0.000). Future studies can use the SSS-S to compare self-stigma between genders and between patients with different kinds of mental illnesses.


Adhesion of Phospholipid Bilayers to Hydroxylated Silica: Existence of Nanometer-Thick Water Interlayers.
Lipid bilayers attached to solid surfaces play an important role in bioinspired materials and devices and serve as model systems for studies of interactions of cell membranes with particles and biomolecules. Despite active experimental and theoretical studies, the interactions of lipid membranes with solid substrates are still poorly understood. In this work, we explore, using atomistic molecular dynamics simulations, the equilibrium and stability of a phospholipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine membrane supported on hydroxylated amorphous silica. We reveal two distinct types of thermodynamically stable states, characterized by different widths of the water layer between the membrane and the substrate. In α-states, the membrane is closely attached with the lipid head groups interacting directly with surface hydroxyls; however, because of the molecular level roughness of the amorphous silica surface, there exists an inhomogeneous water layer trapped between the substrate and the membrane. In β-states, the membrane is separated from the silica surface by a water film of ∼2.5 nm in thickness. The thermodynamic equilibrium is quantified in terms of the disjoining pressure isotherm as a function of membrane-substrate separation, which has a double sigmoidal shape with two minima and one maximum, which correspond to the limits of stability of α- and β-states. The thermodynamic properties and bilayer structure are compared with experimental findings and simulation results for relevant systems.


Restricted gene flow and incipient speciation in disjunct Pacific Ocean and Sea of Cortez populations of a reef fish species, Girella nigricans.
Population disjunctions have been proposed to play an important role in speciation processes. In this study, we have examined the possible role of the Pacific Ocean-Sea of Cortez disjunction as a contributing factor to cryptic speciation in a reef fish, the opaleye, Girella nigricans. Mitochondrial control region (D-loop) sequences (380 bp) of 117 individuals completely separated opaleye populations from the Pacific Ocean and the Sea of Cortez. Although opaleye exhibit pelagic larval stages that remain in the water column for several months, gene flow between the Pacific Ocean and the Sea of Cortez was found to be extremely limited (FST = 0.84, Nm = 0.10). Whereas limited gene flow and reciprocal monophyly suggest that the observed physical and genetic disjunction are potentially contributing to the incipient speciation of Pacific and Sea of Cortez opaleye, moderate levels of D-loop sequence divergence (3.3%) and the absence of fixed allozyme markers challenge this idea. Pacific Coast populations also exhibited restricted gene flow levels (FST = 0.25, Nm = 1.49) across Punta Eugenia, a recognized oceanographic boundary along the Baja California coast. Thus, opaleye individuals grouped into three clades: one clade in the Sea of Cortez, one Pacific clade south of Punta Eugenia, and one Pacific clade north of Punta Eugenia. Future work in this region will determine if our results can be generalized to other disjunct populations.


Bisphenol A and nonylphenol have the potential to stimulate the migration of ovarian cancer cells by inducing epithelial-mesenchymal transition via an estrogen receptor dependent pathway.
Epithelial-mesenchymal transition (EMT) is an important process appearing in embryo development and tumor migration or progression, which is influenced by 17β-estradiol (E2). Bisphenol A (BPA) and nonylphenol (NP) are suspected as endocrine disrupting chemicals (EDCs) because they can exert estrogenic properties. In this study, we examined whether E2, BPA, and NP can lead to the EMT process in BG-1 ovarian cancer cells expressing estrogen receptors (ERs). To confirm the effect of E2, BPA, and NP, BG-1 cells were cultured under treatment with E2, BPA, or NP, and the alteration of EMT markers such as vimentin was examined at mRNA levels by using real-time and reverse-transcription (RT)-PCR. The expressions of snail, slug, and vimentin were enhanced by the treatment of E2, BPA, or NP compared to a control (DMSO). In protein levels, vimentin protein was increased by E2 and two EDCs, while E-cadherin was decreased. In addition, the expression of snail protein was enhanced by the treatment of E2 and the two EDCs in comparison with that of the control. Since EMT response in cancer cells can affect metastasis, we also performed a scratch assay and Western blot assay to show the migration ability caused by E2, BPA, or NP. Consequently, E2, BPA, and NP enhanced the migration capability of BG-1 cells and increased the expression of MMP-9 protein. Furthermore, to examine whether EMT and migration of BG-1 cancer cells are induced by BPA or NP via the ER dependent pathway, we cotreated the cells with ER-antagonist, ICI 182,780, in the presence of E2, BPA, or NP. As a result, the expressions of E-cadherin, vimentin, snail, and slug were reversed following treatment with an ER antagonist. Moreover, we confirmed that ICI 182,780 reduced the migration ability of BPA and NP to the control level. Taken together, these results indicate that BPA and NP, the potential EDCs, may have the ability to influence ovarian cancer metastasis via regulating EMT markers and migration in ER-expressing BG-1 ovarian cancer cells.


Massively parallel pyrosequencing highlights minority variants in the HIV-1 env quasispecies deriving from lymphomonocyte sub-populations.
Virus-associated cell membrane proteins acquired by HIV-1 during budding may give information on the cellular source of circulating virions. In the present study, by applying immunosorting of the virus and of the cells with antibodies targeting monocyte (CD36) and lymphocyte (CD26) markers, it was possible to directly compare HIV-1 quasispecies archived in circulating monocytes and T lymphocytes with that present in plasma virions originated from the same cell types. Five chronically HIV-1 infected patients who underwent therapy interruption after prolonged HAART were enrolled in the study. The analysis was performed by the powerful technology of ultra-deep pyrosequencing after PCR amplification of part of the env gene, coding for the viral glycoprotein (gp) 120, encompassing the tropism-related V3 loop region. V3 amino acid sequences were used to establish heterogeneity parameters, to build phylogenetic trees and to predict co-receptor usage. The heterogeneity of proviral and viral genomes derived from monocytes was higher than that of T-lymphocyte origin. Both monocytes and T lymphocytes might contribute to virus rebounding in the circulation after therapy interruptions, but other virus sources might also be involved. In addition, both proviral and circulating viral sequences from monocytes and T lymphocytes were predictive of a predominant R5 coreceptor usage. However, minor variants, segregating from the most frequent quasispecies variants, were present. In particular, in proviral genomes harboured by monocytes, minority variant clusters with a predicted X4 phenotype were found. This study provided the first direct comparison between the HIV-1 quasispecies archived as provirus in circulating monocytes and T lymphocytes with that of plasma virions replicating in the same cell types. Ultra-deep pyrosequencing generated data with some order of magnitude higher than any previously obtained with conventional approaches. Next generation sequencing allowed the analysis of previously inaccessible aspects of HIV-1 quasispecies, such as co-receptor usage of minority variants present in archived proviral sequences and in actually replicating virions, which may have clinical and therapeutic relevance.


Does exercise therapy improve patient-reported outcomes in rheumatoid arthritis? A systematic review and meta-analysis for the update of the 2020 JCR guidelines for the management of rheumatoid arthritis.
This study aimed to evaluate the impact of exercise therapy on patient-reported outcomes (PROs) in rheumatoid arthritis (RA) as part of the process of updating the 2020 Japanese guidelines for the management of RA according to the Grading of Recommendations, Assessment, Development, and Evaluation system. We searched PubMed, Japana Centra Revuo Medicina Web, and the Cochrane Library (from 2009 to 2018) to identify articles that evaluated PROs of exercise therapy and RA disease activity. A total of 662 articles were identified, including nine RCTs, and meta-analyses were performed on six RCTs on systemic exercise therapy and three RCTs on upper extremity exercise therapy. Analyzed exercise therapies were diverse, differing in target population, intervention method, and duration. Significant improvements were observed in the Health Assessment Questionnaire Disability Index (mean difference -0.35, 95% confidence interval (CI): -0.60 to -0.10), pain (standardized mean difference -2.04, 95% CI: -3.77 to -0.32), and SF-36. For upper extremity exercise therapy, significant improvements in PROs (Disabilities of the Arm, Shoulder, and Hand Questionnaire, Michigan Hand Outcome Questionnaire) were observed. Exercise therapy in RA treatment improves patient subjective assessment of pain, physical function, and quality of life.


Early-life stress does not alter spatial memory performance, hippocampal neurogenesis, neuroinflammation, or telomere length in 20-month-old male mice.
Early-life stress (ES) increases the risk for psychopathology and cognitive decline later in life. Because the neurobiological substrates affected by ES (i.e., cognition, neuroplasticity, and neuroinflammation) are also altered in aging, we set out to investigate if and how ES in the first week of life affects these domains at an advanced age, and how ES modulates the aging trajectory per se. We subjected C57BL/6j mice to an established ES mouse model from postnatal days 2-9. Mice underwent behavioral testing at 19 months of age and were sacrificed at 20 months to investigate their physiology, hippocampal neuroplasticity, neuroinflammation, and telomere length. ES mice, as a group, did not perform differently from controls in the open field or Morris water maze (MWM). Hippocampal neurogenesis and synaptic marker gene expression were not different in ES mice at this age. While we find aging-associated alterations to neuroinflammatory gene expression and telomere length, these were unaffected by ES. When integrating the current data with those from our previously reported 4- and 10-month-old cohorts, we conclude that ES leads to a 'premature' shift in the aging trajectory, consisting of early changes that do not further worsen at the advanced age of 20 months. This could be explained e.g. by a 'floor' effect in ES-induced impairments, and/or age-induced impairments in control mice. Future studies should help understand how exactly ES affects the overall aging trajectory.


Characterization of two distinct primary T cell populations that secrete interleukin 2 upon recognition of class I or class II major histocompatibility antigens.
This study has characterized the primary T cell subpopulations that secrete IL-2 in response to recognition of either class I or class II MHC encoded determinants. The addition to culture of anti-IL-2-R mAb inhibited the consumption of IL-2 by activated lymphocytes during the response period, permitting a much more accurate assessment of the amount of IL-2 produced in the response cultures. Using this response system, we found that primary T cell populations contain two IL-2-secreting T cell subsets that express reciprocal phenotypes and different MHC recognition specificities: an L3T4+, Lyt-2- T cell subset responsive to both class I and class II MHC alloantigens, and an L3T4-Lyt-2+ T cell subset responsive only to class I MHC alloantigens. The L3T4+ T cell subset expressed a broad functional response repertoire in that L3T4+ T cells were triggered to secrete IL-2 upon recognition of unmodified self-Ia determinants, allogeneic Ia determinants, and class I alloantigens presented by self-Ia determinants. The activation of L3T4+ IL-2-secreting T cells, even those responsive to class I MHC alloantigens, could be blocked completely by anti-Ia mAbs, confirming that the L3T4+ T cell subset was in fact class II restricted. In contrast, the Lvt-2+ T cell subset expressed a narrow functional response repertoire in that they were triggered to secrete IL-2 only in response to allogeneic class I MHC determinants, and were not triggered to secrete IL-2 even in response to TNP-modified self-MHC determinants. The specificity of Lyt-2+ IL-2-secreting T cells for class I MHC allodeterminants was confirmed by the observations that: (a) their activation could be blocked completely by anti-class I mAbs, (b) they could be triggered by Ia- cell lines which expressed class I MHC alloantigens and possessed accessory function, and (c) they responded to class I MHC alloantigens but failed to respond to class II MHC alloantigens, even in the presence of exogenously added second signals that circumvented the requirement for alloantigen-bearing accessory cells. Finally, the frequency of primary Lyt-2+ T cells that secreted IL-2 in response to class I (Kbm1) MHC alloantigens was shown to be only minimally lower than that of L3T4+ T cells that secreted IL-2 in response to class II (I-Abm12) MHC alloantigens.(ABSTRACT TRUNCATED AT 400 WORDS)


Gutta-percha softening: "Hemo-De" as a xylene substitute.
The putative hazardous nature of chloroform and xylene implies that safer substitutes should be considered. Standard cylindrical gutta-percha samples were immersed in Hemo-De, a xylene substitute, for 60 s at 37 degrees C. Weight loss of a sample, after drying, was used as a measure of its solubility. Master and accessory cone gutta-percha of three brands were compared. The highest solubility of all kinds of gutta-percha was in chloroform, which served as a positive control. The average solubility of all samples in xylene and Hemo-De was 61% and 52% of that in chloroform, respectively. DMS gutta-percha was more soluble than of Hygienic and DeTrey. Master cone gutta-percha of all brands was more soluble than that of their accessory cones. These results indicate that (a) large differences exist in the solubility of gutta-percha and (b) Hemo-De dissolved gutta-percha in a range similar to that of xylene and may be considered as a potential substitute for this organic solvent.


The effect of iron substrate on mitochondrial haem synthesis in copper deficiency.
Studies of iron utilization and haem synthesis were carried out with hepatic mitochondria obtained from copper-deficient and pair-fed control rats. Ferric chloride can be used as Fe substrate for mitochondrial haem synthesis in the presence of succinate. Utilization is further enhanced by the addition of FMN. Ferritin does not support haem synthesis in the presence of succinate alone, but does support haem synthesis when FMN is added. Mitochondrial haem synthesis is impaired in Cu deficiency when either FeCl3 or homologous ferritin is used as Fe substrate. The results of the present study suggest that impaired haem synthesis in Cu deficiency occurs at a step following the chemical reduction of Fe substrate.


Respiratory problems in full term newborns, which parameters are related to the length of in-patient stay?
To analyze respiratory problems of full term newborn babies during their first hours of life, compare parameters related to the length of neonatal intensive care unit (NICU) in-patient stay, and discuss perinatal care practices, which could prevent consequences, and/or reduce associated costs of NICU hospitalization. Retrospective chart review between July 31st 2017 and March 2nd 2018 in a tertiary maternity hospital. Chi-square testing analyzed qualitative data. Mann-Whitney test was used for quantitative variables. Multiple linear regression models determined odds ratios for associations were found to be significant in univariate analyses. 86 babies with respiratory problems were studied. Delivery mode was vaginal in 11.6% and caesarean section in 88.4% of newborns. About 52.3% of admitted newborns had transient tachypnea and improved relatively quickly. Newborns resuscitated in (P = 0.004) or admitted to the NICU from the delivery room (P = 0.000) displayed greater need for O2 administration. Twenty neonates were intubated; 16 of them were administered surfactant. Infection (P < 0.05), abnormal chest x-ray (P = 0.022), and the severity of respiratory system morbidity (P < 0.05) prolonged neonatal in-patient stay. Respiratory problems (P = 0.003) and intubation (P = 0.032) incurred greater hospitalization costs. Breastfeeding initiation before the 3rd day of life (P = 0.031), and O2 administration for more than 72 h (P = 0.036) were significantly associated with the length of in-patient stay in the multivariate regression analysis. Mandating the presence of a pediatrician in the delivery room would optimize justified direct NICU admissions and reduce the possibility of delayed diagnosis of respiratory distress during rooming-in. NICU in-patient stay in full term neonates should be based on combining diagnostic markers of sepsis, such as procalcitonin or interleukin-6. A specific protocol regarding surfactant administration in intubated full term infants is also necessary. The severity of respiratory system morbidity is not the key determinant of infant feeding. Maternal information regarding infant health and breastfeeding abilities may improve breastfeeding rates.


Prognosis of West Nile virus associated acute flaccid paralysis: a case series.
Little is known about the long-term health related quality of life outcomes in patients with West Nile virus associated acute flaccid paralysis. We describe the quality of life scores of seven patients with acute flaccid paralysis who presented to hospital between 2003 and 2006, and were followed for up to two years. Between 2003 and 2006, 157 symptomatic patients with West Nile virus were enrolled in a longitudinal cohort study of West Nile virus in Canada. Seven patients (4%) had acute flaccid paralysis. The first patient was a 55-year-old man who presented with left upper extremity weakness. The second patient was a 54-year-old man who presented with bilateral upper extremity weakness. The third patient was a 66-year-old woman who developed bilateral upper and lower extremity weakness. The fourth patient was a 67-year-old man who presented with right lower extremity weakness. The fifth patient was a 60-year-old woman who developed bilateral lower extremity weakness. The sixth patient was a 71-year-old man with a history of Parkinson's disease and acute onset bilateral lower extremity weakness. The seventh patient was a 52-year-old man who presented with right lower extremity weakness. All were Caucasian. Patients were followed for a mean of 1.1 years. At the end of follow-up the mean score on the Physical Component Summary of the Short-Form 36 scale had only slightly increased to 39. In contrast, mean score on the Mental Component Summary of the Short-Form 36 scale at the end of follow-up had normalized to 50. Despite the poor physical prognosis for patients with acute flaccid paralysis, the mental health outcomes are generally favorable.


siRNAs from miRNA sites mediate DNA methylation of target genes.
Arabidopsis microRNA (miRNA) genes (MIR) give rise to 20- to 22-nt miRNAs that are generated predominantly by the type III endoribonuclease Dicer-like 1 (DCL1) but do not require any RNA-dependent RNA Polymerases (RDRs) or RNA Polymerase IV (Pol IV). Here, we identify a novel class of non-conserved MIR genes that give rise to two small RNA species, a 20- to 22-nt species and a 23- to 27-nt species, at the same site. Genetic analysis using small RNA pathway mutants reveals that the 20- to 22-nt small RNAs are typical miRNAs generated by DCL1 and are associated with Argonaute 1 (AGO1). In contrast, the accumulation of the 23- to 27-nt small RNAs from the miRNA-generating sites is dependent on DCL3, RDR2 and Pol IV, components of the typical heterochromatic small interfering RNA (hc-siRNA) pathway. We further demonstrate that these MIR-derived siRNAs associate with AGO4 and direct DNA methylation at some of their target loci in trans. In addition, we find that at the miRNA-generating sites, some conserved canonical MIR genes also produce siRNAs, which also induce DNA methylation at some of their target sites. Our systematic examination of published small RNA deep sequencing datasets of rice and moss suggests that this type of dual functional MIRs exist broadly in plants.


Anaerobic degradation of naphthalene and 2-methylnaphthalene by strains of marine sulfate-reducing bacteria.
The anaerobic biodegradation of naphthalene, an aromatic hydrocarbon in tar and petroleum, has been repeatedly observed in environments but scarcely in pure cultures. To further explore the relationships and physiology of anaerobic naphthalene-degrading microorganisms, sulfate-reducing bacteria (SRB) were enriched from a Mediterranean sediment with added naphthalene. Two strains (NaphS3, NaphS6) with oval cells were isolated which showed naphthalene-dependent sulfate reduction. According to 16S rRNA gene sequences, both strains were Deltaproteobacteria and closely related to each other and to a previously described naphthalene-degrading sulfate-reducing strain (NaphS2) from a North Sea habitat. Other close relatives were SRB able to degrade alkylbenzenes, and phylotypes enriched anaerobically with benzene. If in adaptation experiments the three naphthalene-grown strains were exposed to 2-methylnaphthalene, this compound was utilized after a pronounced lag phase, indicating that naphthalene did not induce the capacity for 2-methylnaphthalene degradation. Comparative denaturing gel electrophoresis of cells grown with naphthalene or 2-methylnaphthalene revealed a striking protein band which was only present upon growth with the latter substrate. Peptide sequences from this band perfectly matched those of a protein predicted from genomic libraries of the strains. Sequence similarity (50% identity) of the predicted protein to the large subunit of the toluene-activating enzyme (benzylsuccinate synthase) from other anaerobic bacteria indicated that the detected protein is part of an analogous 2-methylnaphthalene-activating enzyme. The absence of this protein in naphthalene-grown cells together with the adaptation experiments as well as isotopic metabolite differentiation upon growth with a mixture of d(8)-naphthalene and unlabelled 2-methylnaphthalene suggest that the marine strains do not metabolize naphthalene by initial methylation via 2-methylnaphthalene, a previously suggested mechanism. The inability to utilize 1-naphthol or 2-naphthol also excludes these compounds as free intermediates. Results leave open the possibility of naphthalene carboxylation, another previously suggested activation mechanism.


Effective Young's modulus of bacterial and microfibrillated cellulose fibrils in fibrous networks.
The deformation micromechanics of bacterial cellulose (BC) and microfibrillated cellulose (MFC) networks have been investigated using Raman spectroscopy. The Raman spectra of both BC and MFC networks exhibit a band initially located at ≈ 1095 cm(-1). We have used the intensity of this band as a function of rotation angle of the specimens to study the cellulose fibril orientation in BC and MFC networks. We have also used the change in this peak's wavenumber position with applied tensile deformation to probe the stress-transfer behavior of these cellulosic materials. The intensity of this Raman band did not change significantly with rotation angle, indicating an in-plane 2D network of fibrils with uniform random orientation; conversely, a highly oriented flax fiber exhibited a marked change in intensity with rotation angle. Experimental data and theoretical analysis shows that the Raman band shift rate arising from deformation of networks under tension is dependent on the angles between the axis of fibrils, the strain axis, the incident laser polarization direction, and the back scattered polarization configurations. From this analysis, the effective moduli of single fibrils of BC and MFC in the networks were estimated to be in the ranges of 79-88 and 29-36 GPa, respectively. It is shown also that for the model to fit the data it is necessary to use a negative Poisson's ratio for MFC networks and BC networks. Discussion of this in-plane "auxetic" behavior is given.


The role of Holter monitoring in detecting digitalis-provoked arrhythmias.
Certain arrhythmias detected on the electrocardiogram are considered to be reliable indicators of digitalis intoxication. We have evaluated the incidence of these arrhythmias on 24-hour electrocardiographic monitoring (Holter monitoring) in 69 consecutive patients who had serum levels of digoxin determined within 24 hours of the onset of continuous electrocardiographic monitoring. According to teh serum level of digoxin, the patients were divided into the following three groups: (1) group 1 had 0 to 1.0 ng/ml (31 patients); (2) group 2 had 1.1 to 2.0 ng/ml (27 patients); and group 3 had greater than or equal to 2.1 ng/ml (11 patients). The following arrhythmias were considered to reflect digitalis-provoked arrhythmias: (1) persistent sinus bradycardia or sinus pauses (or both); (2) atrioventricular block; (3) paroxysmal atrial tachycardia with block; (4) accelerated junction rhythm; (5) complex ventricular arrhythmias (multifocal ventricular premature beats, bigeminy and trigeminy, and pairs); and (6) ventricular tachycardia. There was no significant difference in the incidence of these six categories of arrhythmias among the three groups. In addition, there was no significant difference in the mean serum level of digoxin for patients with and without the arrhythmias within each category. Ten of the 69 patients had combinations of three of the so-called digitalis-provoked arrhythmias, with incidences among the three groups showing no significant differences. In conclusion, rhythms considered to be potentially due to digitalis intoxication are frequently observed in hospitalized patients undergoing 24-hour electrocardiographic monitoring, are frequently unrelated to the serum level of digoxin, and appear unlikely to reflect true digitalis intoxication in many of these patients.


[Antioxidant system activation in rats with experimental cirrhosis after injection of cryopreserved fetal liver cells].
The possibility to recover the antioxidant system in rats with experimental liver cirrhosis (LC) after allo- and xenotransplantation of cryopreserved fetal liver cells (FLC) was investigated. It was shown that the content of lipid peroxidation products in the blood serum of animals with LC four weeks after FLC transplantation decreased significantly as compared to control group. Such changes were accompanied by a significant increase of catalase (CAT), glutathione reductase (GR), Se-dependent glutathione peroxidase (GP) activity in the liver and total anti-oxidative activity (AOA) of blood. Obtained results demonstrate that the main direction of FLC effects in animals with LC agree with that we observed previously in other experimental models (partial hepatectomy, chronic alcohol poisoning and hypercholesterolemia). In conclusion, cell therapy may be considered as the universal method for correction of disorders in regulation of free-radical processes in various experimental pathologies.


AMP-activated protein kinase alpha2 deficiency affects cardiac cardiolipin homeostasis and mitochondrial function.
AMP-activated protein kinase (AMPK) plays an important role in controlling energy homeostasis and is envisioned as a promising target to treat metabolic disorders. In the heart, AMPK is involved in short-term regulation and in transcriptional control of proteins involved in energy metabolism. Here, we investigated whether deletion of AMPKalpha2, the main cardiac catalytic isoform, alters mitochondrial function and biogenesis. Body weight, heart weight, and AMPKalpha1 expression were similar in control littermate and AMPKalpha2(-/-) mice. Despite normal oxygen consumption in perfused hearts, maximal oxidative capacity, measured using saponin permeabilized cardiac fibers, was approximately 30% lower in AMPKalpha2(-/-) mice with octanoate, pyruvate, or glutamate plus malate but not with succinate as substrates, showing an impairment at complex I of the respiratory chain. This effect was associated with a 25% decrease in mitochondrial cardiolipin content, the main mitochondrial membrane phospholipid that is crucial for complex I activity, and with a 13% decrease in mitochondrial content of linoleic acid, the main fatty acid of cardiolipins. The decrease in cardiolipin content could be explained by mRNA downregulation of rate-limiting enzymes of both cardiolipin synthesis (CTP:PA cytidylyltransferase) and remodeling (acyl-CoA:lysocardiolipin acyltransferase 1). These data reveal a new role for AMPKalpha2 subunit in the regulation of cardiac muscle oxidative capacity via cardiolipin homeostasis.


Does playing football (soccer) lead to SARS-CoV-2 transmission? - A case study of 3 matches with 18 infected football players.
The risk of viral transmission of SARS-CoV-2 associated with football (soccer) training and match play is unknown. Therefore, studies on infection-relevant contacts in football are of utmost importance.A retrospective video-based analysis was performed over 3 matches with 18 SARS-CoV-2 positive players (age: 17.6 ± 3.1 years; 2 professional, 2 semi-professional and 14 youth academy players) during the pre-season in August and September 2020 in Germany. Repeated RT-PCR tests were performed in 5 of 6 teams and pre-match RT-PCR tests in 4 of 6 teams. The last RT-PCR test ranged between 5 - 14 days post-match. The most important result was that no case of virus transmission was found as documented by RT-PCR tests (and symptom monitoring up to 14 days post-match). Physical contact between contagious and non-infected players never lasted longer than 3 seconds each and the position of players during duels was almost exclusively laterally or behind each other.In conclusion, very low risk of SARS-CoV-2 transmission during football match play has been documented. Nevertheless, due to the observational retrospective design of the study, which was based on ethical reasons, inconsistent RT-PCR testing should be regarded as limitation and larger studies are needed to confirm a low probability of virus transmission.


Awareness and uptake of family screening in patients diagnosed with colorectal cancer at a young age.
Background. One-fifth of people who develop colorectal cancer (CRC) have a first-degree relative (FDR) also affected. There is a large disparity in guidelines for screening of relatives of patients with CRC. Herein we address awareness and uptake of family screening amongst patients diagnosed with CRC under age 60 and compare guidelines for screening. Study Design. Patients under age 60 who received surgical management for CRC between June 2009 and May 2012 were identified using pathology records and theatre logbooks. A telephone questionnaire was carried out to investigate family history and screening uptake among FDRs. Results. Of 317 patients surgically managed for CRC over the study period, 65 were under age 60 at diagnosis (8 deceased). The mean age was 51 (30-59). 66% had node positive disease. 25% had a family history of colorectal cancer in a FDR. While American and Canadian guidelines identified 100% of these patients as requiring screening, British guidelines advocated screening for only 40%. Of 324 FDRs, only 40.9% had been screened as a result of patient's diagnosis. Conclusions. Uptake of screening in FDRs of young patients with CRC is low. Increased education and uniformity of guidelines may improve screening uptake in this high-risk population.


Pseudophosphatase MK-STYX: the atypical member of the MAP kinase phosphatases.
The regulation of the phosphorylation of mitogen-activated protein kinases (MAPKs) is essential for cellular processes such as proliferation, differentiation, survival, and death. Mutations within the MAPK signaling cascades are implicated in diseases such as cancer, neurodegenerative disorders, arthritis, obesity, and diabetes. MAPK phosphorylation is controlled by an intricate balance between MAPK kinases (enzymes that add phosphate groups) and MAPK phosphatases (MKPs) (enzymes that remove phosphate groups). MKPs are complex negative regulators of the MAPK pathway that control the amplitude and spatiotemporal regulation of MAPKs. MK-STYX (MAPK phosphoserine/threonine/tyrosine-binding protein) is a member of the MKP subfamily, which lacks the critical histidine and nucleophilic cysteine residues in the active site required for catalysis. MK-STYX does not influence the phosphorylation status of MAPK, but even so it adds to the complexity of signal transduction cascades as a signaling regulator. This review highlights the function of MK-STYX, providing insight into MK-STYX as a signal regulating molecule in the stress response, HDAC 6 dynamics, apoptosis, and neurite differentiation.


Impact of frailty on long-term outcomes after liver resection for hepatocellular carcinoma in elderly patients: A prospective study.
sFrailty affects short-term outcomes after liver resection in elderly patients. However, frailty's effects on long-term outcomes after liver resection in elderly patients with hepatocellular carcinoma (HCC) are unknown. This prospective, single-center study included 81 independently living patients aged ≥65 years scheduled to undergo liver resection for initial HCC. Frailty was evaluated according to the Kihon Checklist, a phenotypic frailty index." We investigated and compared postoperative long-term outcomes after liver resection between patients with and without frailty. Of the 81 patients, 25 (30.9%) were frail. The proportion of patients with cirrhosis, high serum alpha-fetoprotein level (≥200 ng/mL), and poorly differentiated HCC was higher in the frail group than in the nonfrail group (n = 56). Among the patients with postoperative recurrence, the incidence of extrahepatic recurrence was higher in the frail group than in the nonfrail group (30.8% vs. 3.6%, P = 0.028). Moreover, the proportion of patients who underwent repeat liver resection and ablation for recurrence who met the Milan criteria tended to be lower in the frail group than in the nonfrail group. Although there was no difference in disease-free survival between the two groups, the overall survival rate in the frail group was significantly worse than that in the nonfrail group (5-year overall survival: 42.7% vs. 77.2%, P = 0.005). Results of the multivariate analysis indicated that frailty and blood loss were independent prognostic factors for postoperative survival. Frailty is associated with unfavorable long-term outcomes after liver resection in elderly patients with HCC.


Quantitative Structure-Activity Relationship in the Series of 5-Ethyluridine, N2-Guanine, and 6-Oxopurine Derivatives with Pronounced Anti-Herpetic Activity.
A quantitative analysis of the relationship between the structure and inhibitory activity against the herpes simplex virus thymidine kinase (HSV-TK) was performed for the series of 5-ethyluridine, N2-guanine, and 6-oxopurines derivatives with pronounced anti-herpetic activity (IC50 = 0.09 ÷ 160,000 μmol/L) using the GUSAR 2019 software. On the basis of the MNA and QNA descriptors and whole-molecule descriptors using the self-consistent regression, 12 statistically significant consensus models for predicting numerical pIC50 values were constructed. These models demonstrated high predictive accuracy for the training and test sets. Molecular fragments of HSV-1 and HSV-2 TK inhibitors that enhance or diminish the anti-herpetic activity are considered. Virtual screening of the ChEMBL database using the developed QSAR models revealed 42 new effective HSV-1 and HSV-2 TK inhibitors. These compounds are promising for further research. The obtained data open up new opportunities for developing novel effective inhibitors of TK.


Quantum interference of large organic molecules.
The wave nature of matter is a key ingredient of quantum physics and yet it defies our classical intuition. First proposed by Louis de Broglie a century ago, it has since been confirmed with a variety of particles from electrons up to molecules. Here we demonstrate new high-contrast quantum experiments with large and massive tailor-made organic molecules in a near-field interferometer. Our experiments prove the quantum wave nature and delocalization of compounds composed of up to 430 atoms, with a maximal size of up to 60 Å, masses up to m=6,910 AMU and de Broglie wavelengths down to λ(dB)=h/mv≃1 pm. We show that even complex systems, with more than 1,000 internal degrees of freedom, can be prepared in quantum states that are sufficiently well isolated from their environment to avoid decoherence and to show almost perfect coherence.


Advances on Aryldiazonium Salt Chemistry Based Interfacial Fabrication for Sensing Applications.
Aryldiazonium salts as coupling agents for surface chemistry have evidenced their wide applications for the development of sensors. Combined with advances in nanomaterials, current trends in sensor science and a variety of particular advantages of aryldiazonium salt chemistry in sensing have driven the aryldiazonium salt-based sensing strategies to grow at an astonishing pace. This review focuses on the advances in the use of aryldiazonium salts for modifying interfaces in sensors and biosensors during the past decade. It will first summarize the current methods for modification of interfaces with aryldiazonium salts, and then discuss the sensing applications of aryldiazonium salts modified on different transducers (bulky solid electrodes, nanomaterials modified bulky solid electrodes, and nanoparticles). Finally, the challenges and perspectives that aryldiazonium salt chemistry is facing in sensing applications are critically discussed.


Novel lncRNA AL033381.2 Promotes Hepatocellular Carcinoma Progression by Upregulating PRKRA Expression.
Hepatocellular carcinoma (HCC) is a common malignant tumor that is characterized by aggressiveness and poor prognosis. Accumulating evidence indicates that oxidative stress plays a crucial role in carcinogenesis, whereas the potential mechanism between oxidative stress and carcinogenic effects remains elusive. In recent years, long noncoding RNAs (lncRNAs) in cancers have attracted extensive attention and have been shown to be involved in oxidative stress response and carcinogenesis. Nevertheless, the roles of lncRNA AL033381.2 in regulating the development and progression of HCC still remain unclear. The purpose of our study was to evaluate the potential effects and molecular mechanisms of AL033381.2 that may be involved in oxidative stress response in HCC. Using bioinformatics analyses based on the TCGA database, we screened and identified a novel lncRNA AL033381.2 in HCC, which may be involved in oxidative stress responses. qRT-PCR analysis revealed that AL033381.2 is upregulated in HCC tissues. Through in vitro and in vivo experiments, we found that AL033381.2 dramatically facilitates the growth and metastasis of HCC. Mechanistically, RNA pull-down experiments, mass spectrometry, PathArray™, and RIP were used to determine that AL033381.2 binds to PRKRA and may be involved in AL033381.2-mediated oncogenic functions in HCC cells. Moreover, rescue experiments demonstrated that PRKRA overexpression rescues the abilities of HCC cell proliferation, migration, and invasion that were affected by AL033381.2 knockdown. Furthermore, we produced a nanoparticle-based siRNA delivery system and tested its therapeutic effects in vivo. The results showed that the in vivo growth rate of the tumors treated with the nanoparticle/AL033381.2 siRNA complexes was dramatically lower than those treated with the nanoparticle/scramble siRNA complexes. Taken together, our results suggest that the novel lncRNA AL033381.2 may be involved in oxidative stress response by targeting oxidative stress-related genes in HCC. AL033381.2 plays vital oncogenic roles in HCC progression and may be a novel therapeutic marker for HCC diagnosis and treatment.


The new nonsteroidal anti-inflammatory drugs.
Most physicians regard to newer short-acting anti-inflammatory drugs as a substitute for aspirin because they are less toxic. Although these drugs cannot induce remissions of rheumatoid arthritis, they do afford symptomatic relief and exert both a moderate algesic and anti-inflammatory effect in conditions like osteoarthritis, gout, pseudogout, and a variety of musculoskeletal syndromes. The many adverse reactions and toxic effects associated with these drugs are probably related to the inhibition of prostaglandin synthetase, which in turn reduces the biosynthesis of prostaglandins in widespread areas of the body. Thus limited in number, these compounds cannot play an effective role in the body's defense mechanisms. Researchers postulate that this failure accounts for the gastrointestinal and renal lesions--as well as other, as yet unexplained toxic manifestations--noted in patients taking these drugs. For safety's sake, the newer anti-inflammatory drugs should be used with large doses of aspirin, other agents that inhibit prostaglandin synthetase, or drugs that are potentially nephro-toxic.


DECIMER 1.0: deep learning for chemical image recognition using transformers.
The amount of data available on chemical structures and their properties has increased steadily over the past decades. In particular, articles published before the mid-1990 are available only in printed or scanned form. The extraction and storage of data from those articles in a publicly accessible database are desirable, but doing this manually is a slow and error-prone process. In order to extract chemical structure depictions and convert them into a computer-readable format, Optical Chemical Structure Recognition (OCSR) tools were developed where the best performing OCSR tools are mostly rule-based. The DECIMER (Deep lEarning for Chemical ImagE Recognition) project was launched to address the OCSR problem with the latest computational intelligence methods to provide an automated open-source software solution. Various current deep learning approaches were explored to seek a best-fitting solution to the problem. In a preliminary communication, we outlined the prospect of being able to predict SMILES encodings of chemical structure depictions with about 90% accuracy using a dataset of 50-100 million molecules. In this article, the new DECIMER model is presented, a transformer-based network, which can predict SMILES with above 96% accuracy from depictions of chemical structures without stereochemical information and above 89% accuracy for depictions with stereochemical information.


Zopiclone to geriatric patients. A parallel double-blind dose-response clinical trial of zopiclone as a hypnotic to geriatric patients - a study in a geriatric hospital.
Zopiclone was given for 14 nights to 68 geriatric patients (mean age 81 years) with sleep problems. The patients were randomly allocated to four treatment groups: 3.75 mg, 5.0, 7.5, or 10.0 mg of zopiclone. Sleep quantity and quality, side effects, and influence on psychomotor performance (digit symbol substitution and letter cancellation test) were studied before treatment, during active treatment, and after withdrawal of the drug. All patients slept better on zopiclone compared to placebo. There were only slight differences between the different dose levels as regards quantity and quality. No influence on psychomotor performance could be shown. The side effects were mild. Zopiclone showed a good hypnotic efficacy, and 7.5 mg is probably the best dose for elderly patients.