Effects of Probiotics in Conditions or Infections Similar to COVID-19 on Health Outcomes: An Evidence Analysis Center Scoping Review.
Probiotics have been suggested as a potential intervention for improving outcomes, particularly ventilatory-associated pneumonia, in patients infected with coronavirus disease 2019 (COVID-19). However, with the rapid development of the COVID-19 pandemic, there is little direct evidence available in infected patients. The objective of this scoping review is to examine the availability and nature of literature describing the effect of probiotics in adults with conditions or infections similar to COVID-19 infection on related health outcomes. MEDLINE, Cumulative Index to Nursing & Allied Health Literature, and Cochrane Databases were searched for studies published from 1999 to May 1, 2020, examining the effect of probiotics in conditions applicable to individuals infected with COVID-19, including, but not limited to, other forms of coronavirus, critical illness, and mechanical ventilation. The databases search identified 1925 unique articles, 77 full-text articles were reviewed, and 48 studies were included in this scoping review, including 31 primary studies and 17 systematic reviews. Primary studies examined a range of interventions that varied by probiotic diversity and types, including 8 studies that focused on synbiotics, which include both pre- and probiotics. Several systematic reviews examined the effect of probiotics on ventilator-associated pneumonia and other infections. Although most systematic reviews concluded probiotics may improve these outcomes, most systematic review authors concluded that the evidence was low in quality and high in heterogeneity. In the absence of direct evidence with patients infected with COVID-19, studies in comparable populations are currently the best resource to guide probiotics interventions in conjunction with clinical expertise and multidisciplinary health care planning.


Retrograde lymphatic spread of colonic carcinoma to the liver.
Retrograde lymphatic permeation of the liver by a malignant neoplasm is an unusual phenomenon and has apparently not been reported with colonic carcinoma. This paper presents such a case: the features of the lesion are similar to those described for other primary sites.


Hospital admission as first-contact with a community-based psychiatric service. A 2 year study in South-Verona.
The aim of this study was to understand the decision to hospitalize at the first contact, rather than utilize the other services of a community-based system of care. Using the South Verona Psychiatric Case Register, 46 first-contact patients admitted to hospital were compared to all other in-patients (n = 187) over a 2-year span with respect to socio-demographic characteristics, diagnosis (ICD-9) and symptoms (on the Present State Examination Syndrome Check List). Results suggested that first-contact hospitalized patients have significantly more neurotic depressive features. Alternatives to admission were investigated in only about one-third of depressive neurosis patients, compared to two-thirds of patients with other affective disorder diagnoses. In contrast, for patients with psychoses, admission is a second choice (except for patients with organic psychoses).


Synthesis of stilbene carboxylic acids as scaffolds for calcium sensors.
This communication describes the synthesis and characterization of calcium binding stilbene carboxylic acids.


Cholinergic stimulation and nonadrenergic, noncholinergic relaxation of human colonic circular muscle in idiopathic chronic constipation.
The aim of our study was to further investigate the pathophysiological mechanism underlying idiopathic chronic constipation (ICC), a disorder of colonic motility. A possible alteration of excitatory and inhibitory neurotransmission and also the role of inhibitory neurotransmitters such as nitric oxide (NO), 5'-adenosine triphosphate (ATP), and vasoactive intestinal peptide (VIP) has been evaluated on preparations of distal colon from patients with or without ICC. The isometric tension was recorded from isolated circular muscle strips of both experimental groups during pharmacological and electrical field stimulation (EFS). The contractile response obtained by acetylcholine (ACh 20 microM), EFS (20 Hz, 20 V, 1 msec, pulse trains lasting 1 min) and substance P (SP 1 microM) was significantly lower in ICC than in control preparations. The effect of inhibitory nonadrenergic, noncholinergic innervation was evaluated using EFS at low frequencies (0.5-8 Hz), after cholinergic and sympathetic blockade with atropine (3 microM) and guanethidine (3 microM). The maximum relaxation value expressed as percentage of inhibition of SP-induced contraction was significantly higher in ICC than in control preparations (87+/-2.4 and 67+/-6.3, respectively; P<0.05). Experiments with substances that antagonize or reduce the effect of putative inhibitory mediators (VIP 6-28, apamin and N(G)-nitro-L-arginine) suggest that an alteration in NO and ATP release is present in ICC preparations. In particular at a higher inhibitory frequency NO-mediated relaxation is enhanced in ICC vs control, supporting the hypothesis that excessive NO production may be involved in pathophysiological mechanism of constipation.


Overnutrition during lactation leads to impairment in insulin signaling, up-regulation of GLUT1 and increased mitochondrial carbohydrate oxidation in heart of weaned mice.
Several studies have demonstrated that overnutrition during early postnatal period can increase the long-term risk of developing obesity and cardiac disorders, yet the short-term effects of postnatal overfeeding in cardiac metabolism remains unknown. The aim of our study was to investigate the cardiac metabolism of weaned mice submitted to overnutrition during lactation, particularly as to mitochondrial function, substrate preference and insulin signaling. Postnatal overfeeding was induced by litter size reduction in mice at postnatal day 3. At 21 days of age (weaning), mice in the overfed group (OG) presented biometric and biochemical parameters of obesity, including increased body weight, visceral fat, liver weight and increased left ventricle weight/tibia length ratio; indicating cardiac hypertrophy, hyperglycemia, hyperinsulinemia and increased liver glycogen content compared to control group. In the heart, we detected impaired insulin signaling, mainly due to decreased IRβ, pTyr-IRS1, PI3K, GLUT4 and pAkt/Akt and increased PTP1B, GLUT1 and pAMPKα/AMPKα content. Activities of lactate dehydrogenase and citrate synthase were increased, accompanied by enhanced carbohydrate oxidation, as observed by high-resolution respirometry. Moreover, OG hearts had lower CPT1, PPARα and increased UCP2 mRNA expression, associated with increased oxidative stress (4-HNE content), BAX/BCL2 ratio and cardiac fibrosis. Ultrastructural analysis of OG hearts demonstrated mild mitochondrial damage without alterations in OXPHOS complexes. In conclusion, overnutrition during early life induces short-term metabolic disturbances, impairment in heart insulin signaling, up-regulates GLUT-1 and switch cardiac fuel preference in juvenile mice.


Claudin-2 in hyperproliferative migrating keratinocytes and migration inhibition via siRNA knockdown.
Claudin-2 is a tight junction protein found in various tissues including the epidermis of the skin. Intracellular signalling via claudin-2 may have an effect on cell proliferation and migration. While the role of claudin-2 in the epidermis has not been established, here we show an increase in claudin-2 expression in hyperproliferative archival skin samples. To further examine the role of claudin-2 in cell migration we examined its expression in cultured keratinocytes and found it was increased in wound margins in an in vitro scratch test assay. We then used a claudin-2 knockdown assay using small interfering ribonucleic acid (siRNA) with a 77% transfection efficiency and decrease in claudin-2 protein via Western blot analysis to examine cell migration, which was inhibited following claudin-2 knockdown over a 5-day period. Cells transfected with claudin-2 siRNA also showed a decreased size compared to controls and a more diffuse staining pattern. Lastly we examined claudin-2 expression in migrating keratinocytes by Western blot analysis and found a significant decrease in protein staining in scratch-test assay cultures after 4 h, followed by a significant increase in claudin-2 protein after 24 h. Taken together these results indicate a role for claudin-2 signalling in proliferation and cell migration in the epidermis of the skin.


Neospora caninum in crows from Israel.
A cross-sectional Neospora caninum seroprevalence study was performed on free ranging crows (Corvus cornix, Corvus monedula and Corvus splendens) from Israel in order to assess their exposure to this pathogen and evaluate their role as potential hosts or as sentinels of infection. Using the modified agglutination test (MAT) with a cutoff titer of 1:100, 30 out of 183 crows (16.4%) were found to be N. caninum seropositive. Positive results were validated and confirmed by the indirect fluorescent antibody test (IFAT). There was 100% agreement between tests when cut-off titers of 1:50 and 1:100 were applied for the IFAT and MAT, respectively. PCR analysis of brain extracts from all crows resulted in the detection of N. caninum DNA for the first time in crows belonging to two species, C. cornix and C. monedula. The high N. caninum seroprevalence in crows suggests that widespread exposure to infection with N. caninum exists especially in central and northern Israel and that crows may act as suitable markers for disease prevalence in the areas in which they are found.


Identification of solubility-limited absorption of oral anticancer drugs using PBPK modeling based on rat PK and its relevance to human.
Solubility is one of the key parameters that is optimized during drug discovery to ensure sufficient drug concentration in systemic circulation and to achieve the desired pharmacological response. We recently reported the application of PBPK analysis of early clinical pharmacokinetic data to identify drugs whose absorption are truly limited by solubility. In this work, we selected ten anticancer drugs that exhibit poor in vitro solubility to explore the utility of this approach to identify solubility-limited absorption based on rat pharmacokinetic data and compare the findings to human data. Oral rat pharmacokinetic studies were performed at the body weight-scaled doses of the model drugs' human food effect studies, and analyzed using a top-down PBPK modeling approach. A good correlation of solubility-limited absorption in rat and human was observed. These results allow an early identification of drugs with truly solubility-limited absorption, with the potential to guide decisions and save valuable resources in drug development.


[The pharmacokinetics and metabolism of heptapeptide--a prospective synthetic analog of tuftsin with psychostimulating action in rats].
The pharmacokinetics of a new heptapeptide with psychotropic activity was studied in rats in experiments in vitro and in vivo by means of high-performance liquid chromatography. The heptapeptide was detected in its natural form in rat blood plasma for 7-10 min; its T1/2 exceeded that of other oligopeptides of similar structure. The structure of the main pharmacologically active heptapeptide metabolite was identified by high performance liquid chromatography; it proved to be tetrapeptide Thr-Lys-Pro-Arg (taphtsin). The heptapeptide was distributed in well vascularized organs of rats: liver > kidneys > heart.


Remodeling of sinus node function after catheter ablation of right atrial flutter.
The purpose of this study was to investigate the effect of ablation of right atrial flutter upon sinus node function in humans. This study enrolled 35 patients. Twenty-four patients (16 men and 8 women; age 68 +/- 11 years) were referred for ablation of persistent atrial flutter (duration 8 +/- 11 months). After ablation, there was abnormal sinus node function defined as a corrected sinus node recovery time (CSNRT) > or = 550 msec. The control group consisted of 11 patients who were undergoing pacemaker implantation for sinus node disease but did not have a history of atrial dysrhythmias or ablation. Within 24 hours of ablation or pacemaker implantation, baseline maximal CSNRT was measured through a permanent pacemaker by AAI pacing at six cycle lengths: 600, 550, 500, 450, 400, and 350 msec. CSNRT then was measured in the same manner at 48 hours, 14 days, and 3 months after ablation/pacemaker implantation. P wave amplitude and duration, and percent atrial sensing also were assessed at the same intervals. For patients undergoing atrial flutter ablation, there was progressive temporal recovery of CSNRT (1,204 +/- 671 msec at baseline vs 834 +/- 380 msec at 3 months; P < 0.001) and a significant increase in the percent atrial sensing and P wave amplitude at 3 months compared with baseline (P < 0.001). In control subjects, there was no change in the CSNRT, percent atrial pacing, or P wave amplitude. After ablation of persistent atrial flutter, there is temporal recovery of CSNRT and increase in spontaneous atrial activity. These findings suggest that atrial flutter induces reversible changes in sinus node function.


Asians compared to Whites show increased response to d-amphetamine on select subjective and cardiovascular measures.
Identifying factors that moderate subjective response to stimulants is important for understanding individuals at risk for abusing these drugs. Some research suggests that Asians may respond differently to stimulants than other races, but controlled human laboratory research of stimulant administration effects in Asians is scant. In this double-blind counterbalanced within-subject study, healthy stimulant-naïve participants (N = 65; 55% Asian; 63% female; age 18-35) received a single dose of 20-mg oral d-amphetamine or placebo on separate days. At each testing day, subjective measures of abuse liability and cardiovascular assessments were administered at repeated intervals before and after drug administration over a 4-hour period. Asians (vs. Whites) demonstrated greater d-amphetamine-induced increases in diastolic blood pressure and ratings of 'Feel High' and 'Like Drug'. Asian and White healthy young adults may differ in certain subjective and cardiovascular responses to acute doses of d-amphetamine. Such individual differences could help explain between-person differences in abuse potential of d-amphetamine and other stimulants.


An ancestral MAGUK protein supports the modulation of mammalian voltage-gated Ca2+ channels through a conserved CaVβ-like interface.
Eukaryote voltage-gated Ca2+ channels of the CaV2 channel family are hetero-oligomers formed by the pore-forming CaVα1 protein assembled with auxiliary CaVα2δ and CaVβ subunits. CaVβ subunits are formed by a Src homology 3 (SH3) domain and a guanylate kinase (GK) domain connected through a HOOK domain. The GK domain binds a conserved cytoplasmic region of the pore-forming CaVα1 subunit referred as the "AID". Herein we explored the phylogenetic and functional relationship between CaV channel subunits in distant eukaryotic organisms by investigating the function of a MAGUK protein (XM_004990081) cloned from the choanoflagellate Salpingoeca rosetta (Sro). This MAGUK protein (Sroβ) features SH3 and GK structural domains with a 25% primary sequence identity to mammalian CaVβ. Recombinant expression of its cDNA with mammalian high-voltage activated Ca2+ channel CaV2.3 in mammalian HEK cells produced robust voltage-gated inward Ca2+ currents with typical activation and inactivation properties. Like CaVβ, Sroβ prevents fast degradation of total CaV2.3 proteins in cycloheximide assays. The three-dimensional homology model predicts an interaction between the GK domain of Sroβ and the AID motif of the pore-forming CaVα1 protein. Substitution of AID residues Trp (W386A) and Tyr (Y383A) significantly impaired co-immunoprecipitation of CaV2.3 with Sroβ and functional upregulation of CaV2.3 currents. Likewise, a 6-residue deletion within the GK domain of Sroβ, similar to the locus found in mammalian CaVβ, significantly reduced peak current density. Altogether our data demonstrate that an ancestor MAGUK protein reconstitutes the biophysical and molecular features responsible for channel upregulation by mammalian CaVβ through a minimally conserved molecular interface.


Evaluating the effectiveness of clinical ethics committees: a systematic review.
Clinical Ethics Committees (CECs), as distinct from Research Ethics Committees, were originally established with the aim of supporting healthcare professionals in managing controversial clinical ethical issues. However, it is still unclear whether they manage to accomplish this task and what is their impact on clinical practice. This systematic review aims to collect available assessments of CECs' performance as reported in literature, in order to evaluate CECs' effectiveness. We retrieved all literature published up to November 2019 in six databases (PubMed, Ovid MEDLINE, Scopus, Philosopher's Index, Embase and Web of Science), following PRISMA guidelines. We included only articles specifically addressing CECs and providing any form of CECs performance assessment. Twenty-nine articles were included. Ethics consultation was the most evaluated of CECs' functions. We did not find standardized tools for measuring CECs' efficacy, but 33% of studies considered "user satisfaction" as an indicator, with 94% of them reporting an average positive perception of CECs' impact. Changes in patient treatment and a decrease of moral distress in health personnel were reported as additional outcomes of ethics consultation. The highly diverse ways by which CECs carry out their activities make CECs' evaluation difficult. The adoption of shared criteria would be desirable to provide a reliable answer to the question about their effectiveness. Nonetheless, in general both users and providers consider CECs as helpful, relevant to their work, able to improve the quality of care. Their main function is ethics consultation, while less attention seems to be devoted to bioethics education and policy formation.


Higher OAK (Oral Anticoagulation Knowledge) score at baseline associated with better TTR (Time in Therapeutic Range) in patients taking warfarin.
A lack in patient knowledge of warfarin therapy is associated with poor adherence. This knowledge gap may result in a lower INR Time in Therapeutic Range (TTR). To investigate association between patient anticoagulation knowledge and warfarin control. Michigan Anticoagulation Quality Improvement Initiative (MAQI2) is a Blue Cross Blue Shield of Michigan sponsored consortium of six anticoagulation management services. Patients prescribed warfarin at two MAQI2 sites completed a voluntary Oral Anticoagulation Knowledge (OAK) questionnaire at warfarin initiation and 6-month follow-up. The results of 20 OAK questions and TTRs (excluding 1st month post-initiation) were compared using chi-square tests, t-tests and multivariate analysis adjusting for SAMe-TT2R2 and days on warfarin. Of 1836 surveys distributed at warfarin initiation, 481 (26.2%) patients completed the baseline questionnaire (within 1 month post-initiation): mean OAK score: 14.6 ± 3.4. Of those, 147 (30.6%) completed 6-month follow-up surveys (OAK: 12.7 ± 5.8). Patients with TTR ≥ 70% at baseline scored higher on OAK tests than patients with TTR < 70% in unadjusted analyses (15.1 ± 3.2 v. 14.2 ± 3.5, p = 0.003) and adjusted analysis (p = 0.020). There was no unadjusted or adjusted difference in OAK scores at 6-month follow-up between patients with TTR ≥ 70% and TTR < 70%. For patients who completed baseline and follow-up surveys, there was a decrease of 2.4 points in OAK score between baseline and 6-month follow up (p < 0.001). Higher baseline, but not follow-up, OAK score is associated with better warfarin control and average OAK scores decreased between baseline and follow-up. Further studies are needed to determine what type of patient education may improve patient knowledge retention and warfarin control.


Effects of taprostene, a stable prostacyclin analogue, on haemodynamics, platelet function and arachidonate metabolism in healthy volunteers.
In order to assess the effect of taprostene on haemodynamics, platelet function and arachidonate metabolism in 4 healthy volunteers an intravenous infusion of 25 ng.kg-1.min-1 was given for 6 h. During the infusion period systolic blood pressure dropped from 130 to 111 mm Hg and diastolic blood pressure from 77 to 69 mm Hg. The heart rate rose from 77 to 84 beats/min. During the taprostene infusion the slope and height of the ADP and collagen induced platelet aggregation curves were significantly inhibited and the sensitivity of platelets to PGI2 and PGE1 was increased. Plasma and serum thromboxane B2, conversion of exogenous radiolabelled arachidonic acid, WU-test, circulating endothelial cell count, concentration of platelet factor 4, beta-thromboglobulin, malondialdehyde and the PGI2-synthesis stimulating plasma factor did not show any clear drug-related alteration. It is concluded that infusion of taprostene 25 ng.kg-1.min-1 caused measurable inhibition of platelet function ex vivo.


Hypoxia is associated with a lower expression of genes involved in lipogenesis in visceral adipose tissue.
A key role for HIF-1α in the promotion and maintenance of dietary obesity has been proposed. We analyzed the association between hypoxia and de novo lipogenesis in human adipose tissue. We studied HIF-1α mRNA and protein expression in fasting status in visceral adipose tissue (VAT) from non-obese and morbidly obese subjects, and in VAT from wild-type and ob/ob C57BL6J mice in both fasting and feeding status. We also analyzed the effect of hypoxia on the VAT mRNA expression of genes involved in lipogenesis. HIF-1α was increased in VAT from morbidly obese subjects. In fasting status, C57BL6J ob/ob mice had a higher VAT HIF-1α mRNA expression than C57BL6J wild-type mice. In feeding status, VAT HIF-1α mRNA expression significantly increased in C57BL6J wild-type, but not in C57BL6J ob/ob mice. In humans, HIF-1α mRNA expression correlated positively with body mass index and insulin resistance. VAT HIF-1α mRNA expression correlated negatively with ACC1, PDHB and SIRT3 mRNA expression, and positively with PPAR-γ. VAT explants incubated in hypoxia showed reduced SIRT3 and increased PPAR-γ, SREBP-1c, ACLY, ACC1 and FASN mRNA expression. Morbidly obese subjects have a higher level of VAT HIF-1α. Postprandial status is associated with an increase in HIF-1α mRNA expression in C57BL6J wild-type mice. Hypoxia alters the mRNA expression of genes involved in de novo lipogenesis in human VAT.


Biological characterization of human bone tumors. IV. Combined biochemical and histological analyses of different osteosarcomas.
A new technique was applied to the study of human osteosarcoma. Ten slices of 10 micron were cut serially from 2 X 2 X 6 mm shock frozen blocks of human osteosarcoma for chemical analysis. Before and after each series of 10 slices, one slice of 10 micron was separated for morphological analysis. Four different types of osteosarcoma were investigated: Case 1 was an atypical osteoblastic osteosarcoma, case 2 a small cell sclerosing osteosarcoma, case 3 a well-differentiated parosteal osteosarcoma grade I, and case 4 a highly malignant anaplastic osteosarcoma. Alkaline phosphatase, acid phosphatase, beta-glucuronidase and proteolytic activities were analysed as well as matrix collagen and hexosamine, phosphorus (Pi and Po), protein, DNA, and water content. In accordance with the morphology, the obtained data illustrate the great heterogeneity of osteosarcomas. Although case 1, 2 and 3 all represent calcifying types of the tumor, characteristic differences exist with regard to the matrix and the degree of calcification. In contrast to these three, case 4 presents a noncalcified type of osteosarcoma whose matrix contains relatively high amounts of hexosamine and low amounts of collagen, whereas DNA and water contents are high. The data from the analysis of osteosarcoma were compared with previous results from the calf epiphyseal growth plate in order to define differences and similarities between the formation of tumor bone and the physiological formation of hard tissue.


Changes in thickness of central macula and retinal nerve fibre layer in severe hypertensive retinopathy: a 1-year longitudinal study.
To analyse the longitudinal changes in the thickness of the central macula and retinal nerve fibre layer (RNFL) in patients with hypertensive retinopathy (HTNR) using spectral-domain optical coherence tomography (SD-OCT). This was a prospective cohort study. We studied 18 eyes of patients with HTNR of grade IV who had been followed up for more than 1 year, and 36 normal eyes (without any relevant medical history; the control group). Antihypertensive treatment successfully normalized the blood pressure of HTNR patients. The RNFL thickness and that of the central macula of HTNR patients were measured using a Cirrus HD-OCT instrument, and compared with those of the control group. At 12 months of follow-up, the mean thickness of the RNFL and central macula was significantly lower in the HTNR group than in the control group (the RNFL was measured first, and then the central macular thickness (CMT): 77.4 ± 9.1 and 233.8 ± 30.8 μm versus 94.1 ± 7.8 and 256.3 ± 28.1 μm, respectively; p < 0.05). With time, the RNFL thickness and CMT became significantly less than that at the initial diagnosis (p < 0.05). Severe HTNR causes a decrease in the thickness of the RNFL and central macula over time. Therefore, the impact of retinal changes associated with systemic diseases such as hypertension should be considered in analysing the thicknesses of the RNFL and central macula in ocular disorders, including retina, glaucoma and neuro-ophthalmologic diseases.


Twin Studies in Brazil: Projects and Plans / Twin Research: Infant Twins' Viewing of Social Scenes; Religiosity and Substance Abuse; Down Syndrome Among Twins; Twin Case of Chronic Periodontitis / In the News: The Twin 'Property Brothers', Twins With Cerebral Palsy; Twins Affected With the Zika Virus; Twin Writers Derek and Roddy; Twins on Sports Teams; Local Quads.
Twin research in Brazil twin has expanded enormously in recent years, engaging the interests and efforts of many investigators, students and twins. Descriptions and brief summaries of this work and talks given by investigators at local conferences are presented, based on my four-city lecture tour. This is followed by summaries of twin research on infants' viewing of social scenes, religiosity and substance abuse, Down syndrome, and chronic periodontitis. This article concludes with twin-related news and information of general interest, including identical twin property designers, twins with cerebral palsy, twins affected with the Zika virus, a pair of twin writers, twins in sports, and a set of quadruplets from my childhood neighborhood in Riverdale, New York.


Antimicrobial and immunomodulatory effects of tedizolid against methicillin-resistant Staphylococcus aureus in a murine model of hematogenous pulmonary infection.
Tedizolid (TZD) is a second-generation oxazolidinone and demonstrates potent in-vitro activity against multidrug-resistant Gram-positive bacteria. Phase III studies in patients with acute bacterial skin and skin structure infections (ABSSSI) have demonstrated the non-inferiority of TZD to linezolid (LZD). However, there are only a few studies that show the effect of TZD in pulmonary infections. In this study, we investigated the effect of TZD in a murine model of hematogenous pulmonary infection caused by methicillin-resistant Staphylococcus aureus (MRSA). The mice were treated either twice daily with saline (control), 25mg/kg of vancomycin (low-VAN), 110mg/kg of vancomycin (high-VAN), 120mg/kg of LZD or once daily with 20mg/kg of TZD. As compared to the control, the low- and high-VAN treatment groups, LZD and TZD significantly improved the survival rate, reduced the bacterial count in the lungs. Furthermore, TZD decreased the area of central bacterial colony zone (CBCZ) at 36h post-inoculation, compared with the control. In addition, we investigated the immunomodulatory effect of TZD by evaluating the plasma concentrations of the inflammatory cytokines. Although there were no significant differences in the bacterial count in the lungs amongst the drugs at 26h post-inoculation, TZD and LZD significantly improved the plasma concentrations of TNF-alpha, IL-6 and MIP-2, in comparison with the control. In this study, both TZD and LZD demonstrated antimicrobial and immunomodulatory efficacy in a murine model of hematogenous pulmonary infection caused by MRSA.


Preoperative prediction of sinonasal papilloma by artificial intelligence using nasal video endoscopy: a retrospective study.
Sinonasal inverted papilloma (IP) is at risk of recurrence and malignancy, and early diagnosis using nasal endoscopy is essential. We thus developed a diagnostic system using artificial intelligence (AI) to identify nasal sinus papilloma. Endoscopic surgery videos of 53 patients undergoing endoscopic sinus surgery were edited to train and evaluate deep neural network models and then a diagnostic system was developed. The correct diagnosis rate based on visual examination by otolaryngologists was also evaluated using the same videos and compared with that of the AI diagnostic system patients. Main outcomes evaluated included the percentage of correct diagnoses compared to AI diagnosis and the correct diagnosis rate for otolaryngologists based on years of practice experience. The diagnostic system had an area under the curve of 0.874, accuracy of 0.843, false positive rate of 0.124, and false negative rate of 0.191. The average correct diagnosis rate among otolaryngologists was 69.4%, indicating that the AI was highly accurate. Evidently, although the number of cases was small, a highly accurate diagnostic system was created. Future studies with larger samples to improve the accuracy of the system and expand the range of diseases that can be detected for more clinical applications are warranted.


Thumb carpometacarpal osteoarthritis: A musculoskeletal physiotherapy perspective.
To perform a literature review to provide the practitioner with a description of the information and techniques to enhance the provision of conservative interventions in clinical practice. Studies were obtained from MEDLINE, CINAHL, Embase, PEDro and CENTRAL databases from their inception to December 2017. Authors independently selected studies, conducted quality assessment, and extracted results. There is evidence to support a multimodal approach to the therapeutic management of the patient with CMC OA. This distinct approach includes: patient education, manual therapy, therapeutic exercise programs, and orthotic provision. There is evidence to support some of the commonly performed conservative interventions to improve hand function and decrease hand pain.


Early angiography in the management of post-renal biopsy hematuria.
A case is reported in which the value of early angiography in the management of post-renal biopsy hematuria is exemplified. The decision of whether treatment should be conservative or surgical is based on the precise anatomical delineation of the cause of hematuria and the chances of spontaneous remission. When necessary an operation guided by the angiogram can be limited to partial resection of the lesion-bearing region.


Remnant cholesterol, but not other cholesterol parameters, is associated with gestational diabetes mellitus in pregnant women: a prospective cohort study.
No evidence has been found of a relationship between remnant cholesterol (RC) and the likelihood of gestational diabetes mellitus (GDM) in pregnant women. The aim of our study was to investigate the link between serum RC at 12-14 weeks of gestation and the risk of GDM. This was a secondary analysis with data from a prospective cohort study in Korea. A total of 590 single pregnant women attending two hospitals in Korea, up to 14 weeks gestation, from November 2014 to July 2016 were included in the study. The formula used to calculate RC in detail was RC (mg/dL) = TC (mg/dL)-HDL-c (mg/dL)-LDL-c (mg/dL). Logistic regression models were employed to examine the relationship between RC and GDM and explore the association between other lipoprotein cholesterol parameters and the risk of GDM. Furthermore, receiver operating characteristic (ROC) analysis was performed to assess the ability of RC to identify GDM. Additionally, sensitivity and subgroup analyses were conducted. The mean age of participants was 32.06 ± 3.80 years. The median of RC was 34.66 mg/dL. 37 pregnant women (6.27%) were eventually diagnosed with GDM. Multivariate adjusted logistic regression analysis showed that RC was positively associated with the risk of GDM (OR = 1.458, 95% CI 1.221, 1.741). There was no significant association between other lipoprotein cholesterols (including TC, LDL-c, HDL-c) and the risk of GDM. The area under the ROC curve for RC as a predictor of GDM was 0.8038 (95% CI 0.7338-0.8738), and the optimal RC cut-off was 24.30 mg/dL. Our findings were demonstrated to be robust by performing a series of sensitivity analyses. Serum RC levels at 12-14 weeks of gestation are positively associated with GDM risk in pregnant women. RC in early pregnancy is an early warning indicator of GDM in pregnant women, especially those with normal HDL-c, LDL-c, and TC that are easily overlooked. There is a high risk of developing GDM in pregnant women whose RC is more than 24.30 mg/dL. This study may help optimize GDM prevention in pregnant women and facilitate communication between physicians, pregnant patients, and their families.


Development of a multi-residue method for fast screening and confirmation of 20 prohibited veterinary drugs in feedstuffs by liquid chromatography tandem mass spectrometry.
A simple multiresidue method was developed for detecting and quantifying twenty analytes from 5 classes of prohibited veterinary drugs (β-agonists (9), anabolic hormones (4), quinoxalines (4), tranquilizers (1), cyproheptadine, and clonidine in animal feeds using a QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) approach. Feed samples were extracted by ultrasonic-assisted extraction with a mixture of methanol-acetonitrile (50:50, v/v), followed by a cleanup using a dispersive solid-phase extraction with PSA (primary secondary amine). Target compounds were separated and determined by a liquid chromatography tandem quadrupole mass spectrometer operating in positive electrospray ionization mode, using multiple reaction monitoring (MRM). The recoveries of these compounds were between 56.7% and 103% at three spiked levels. The repeatability was lower than 10%, whereas reproducibility was no more than 15% except for nandrolone (17% at 10μgkg(-1)) and diazepam (19% at 10μgkg(-1)). Decision limits (CCαs) and detection capabilities (CCβs) ranged from 0.42 to 5.74μgkg(-1) and 5.70-9.81μgkg(-1), respectively. The method was successfully applied to screening of real samples obtained from local feed markets and confirmation of the suspected target analytes.


Cost-effectiveness of school support for orphan girls to prevent HIV infection in Zimbabwe.
This cost-effectiveness study analyzes the cost per quality-adjusted life year (QALY) gained in a randomized controlled trial that tested school support as a structural intervention to prevent HIV risk factors among Zimbabwe orphan girl adolescents. The intervention significantly reduced early marriage, increased years of schooling completed, and increased health-related quality of life. By reducing early marriage, the literature suggests the intervention reduced HIV infection. The intervention yielded an estimated US$1,472 in societal benefits and an estimated gain of 0.36 QALYs per orphan supported. It cost an estimated US$6/QALY gained, about 1 % of annual per capita income in Zimbabwe. That is well below the maximum price that the World Health Organization (WHO) Commission on Macroeconomics and Health recommends paying for health gains in low and middle income countries. About half the girls in the intervention condition were boarded when they reached high school. For non-boarders, the intervention's financial benefits exceeded its costs, yielding an estimated net cost savings of $502 per pupil. Without boarding, the intervention would yield net savings even if it were 34 % less effective in replication. Boarding was not cost-effective. It cost an additional $1,234 per girl boarded (over the 3 years of the study, discounted to present value at a 3 % discount rate) but had no effect on any of the outcome measures relative to girls in the treatment group who did not board. For girls who did not board, the average cost of approximately 3 years of school support was US$973.


Urinary tract infection prophylaxis in transurethral surgery: oral lomefloxacin versus parenteral cefuroxime.
The purpose of this study was to compare the efficacy and safety of single-dose oral lomefloxacin and single-dose parenteral cefuroxime for the prevention of urinary tract infection following transurethral surgery. A total of 63 patients were enrolled in this prospective, randomized open-label study, which was conducted at two medical centers in France. Patients were randomized to receive either 400 mg of oral lomefloxacin 2-6 hours before surgery or 1.5 g parenteral cefuroxime 30-90 minutes before surgery. Postoperative clinical evaluation was performed daily, and bacteriologic evaluation included urine cultures performed 24 hours after surgery, just before and 1 day after removal of the indwelling catheter, and 3-5 days after surgery. Another urine culture was optionally performed 1-3 months after surgery. Infection was defined as a urinary bacteria count greater than or equal to 10(5) colony-forming units (CFU)/mL of urine. Of the 63 patients enrolled, 54 were evaluable for efficacy, 27 in each group. The success rate of prophylaxis was 88.9% in the lomefloxacin group and 88.5% in the cefuroxime group (p = nonsignificant). None of the 16 lomefloxacin-treated patients who were re-cultured at 1-3 months was found to be infected. Adverse events were minor in both groups. A single oral dose of lomefloxacin was as efficacious and as safe as a single intravenous dose of cefuroxime for prevention of postoperative urinary tract infection in patients undergoing transurethral surgery.


Combinatorial effects of amoxicillin and metronidazole on selected periodontal bacteria and whole plaque samples.
The aim of the present study was to analyze in vitro the combinatorial effects of the antibiotic combination of amoxicillin plus metronidazole on subgingival bacterial isolates. Aggregatibacter (Actinobacillus) actinomycetemcomitans, Prevotella intermedia/nigrescens, Fusobacterium nucleatum and Eikenella corrodens from our strain collection and subgingival bacteria isolated from patients with periodontitis were tested for their susceptibility to amoxicillin and metronidazole using the Etest. The fractional inhibitory concentration index (FICI), which is commonly used to describe drug interactions, was calculated. Synergy, i.e. FICI values ≤ 0.5, between amoxicillin and metronidazole was shown for two A. actinomycetemcomitans (FICI: 0.3), two F. nucleatum (FICI: 0.3 and 0.5, respectively) and one E. corrodens (FICI: 0.4) isolates. Indifference, i.e. FIC indices of >0.5 but ≤4, occurred for other isolates and the 14 P. intermedia/nigrescens strains tested. Microorganisms resistant to either amoxicillin or metronidazole were detected in all samples by Etest. Combinatorial effects occur between amoxicillin and metronidazole on some strains of A. actinomycetemcomitans, F. nucleatum and E. corrodens. Synergy was shown for a few strains only.


Solvent-assisted stir bar sorptive extraction and gas chromatography-mass spectrometry with simultaneous olfactometry for the characterization of aroma compounds in Japanese Yamahai-brewed sake.
Yamahai-brewed sake, a Japanese alcoholic beverage brewed from rice and produced via natural lactic acid fermentation, has a complex and rich flavor compared with Sokujo-brewed sake, brewed with a general method using pure lactic acid. This study aimed to characterize the aroma compounds in Yamahai-brewed sake using solvent-assisted stir bar sorptive extraction (SA-SBSE) with gas chromatography-olfactometry/mass spectrometry (GC-O/MS) and to confirm the enhanced sensitivity of GC-O/MS with SA-SBSE compared with SBSE alone. SA-SBSE with GC-O/MS increased the number of detected odor-active compounds and improved the FD factor sensitivity of Yamahai-brewed sake. SA-SBSE-GC-MS analysis of three pairs of Yamahai-brewed and Sokujo-brewed sake showed higher polar aroma compound content in Yamahai-brewed sake with a low rice polishing ratio. Quantification of 11 characteristic aroma compounds with a wide range of log Kow values revealed that several compounds, including ethyl mandelate, ethyl 2-hydroxy-4-methylvalerate, and the newly identified γ-6-(Z)-dodecenolactone, were more abundant in Yamahai-brewed sake.


High prevalence of clonally related ST182 NDM-1-producing Enterobacter cloacae complex clinical isolates in Greece.
NDM-type metallo-β-lactamase (MBL)-producing Enterobacterales remain uncommon in the European region, especially among species other than Klebsiella pneumoniae and Escherichia coli. The aim of this study was to describe epidemiological and molecular characteristics of a widespread NDM-1-producing Enterobacter cloacae complex outbreak in Greece. Over a 6-year period (March 2016-March 2022), a retrospective study was conducted in a tertiary care Greek hospital. Ninety single-patient carbapenem-non-susceptible E. cloacae complex clinical isolates were recovered consecutively. The isolates were subjected to further investigation, including antimicrobial susceptibility testing and combined disc tests for carbapenemase production, polymerase chain reaction and sequencing for resistance genes, molecular fingerprinting by pulsed-field gel electrophoresis (PFGE), plasmid profiling, replicon typing, conjugation experiments, genotyping by multi-locus sequence typing (MLST), whole-genome sequencing and phylogenetic analysis. Phenotypic and molecular testing confirmed the presence of blaNDM-1 in 47 (52.2%) of the E. cloacae complex isolates. MLST analysis clustered all but four of the NDM-1 producers into a single MLST sequence type (ST182), whereas single isolates belonged to different sequence types (ST190, ST269, ST443 and ST743). PFGE analysis revealed that ST182 isolates were clustered into a single clonal type, with three subtypes, which differed from the clonal types detected among the remaining carbapenem non-susceptible E. cloacae complex isolates identified during the study period. All ST182 blaNDM-1-carrying isolates also harboured the blaACT-16 AmpC gene, while the blaESBL, blaOXA-1 and blaTEM-1 genes were detected in most cases. In all clonal isolates, the blaNDM-1 gene was located on an IncA/C-type plasmid, and flanked upstream by an ISAba125 element and downstream by bleMBL. Conjugation experiments failed to produce carbapenem-resistant transconjugants, indicating a low dynamic for horizontal gene transfer. Application of enforced infection control measures led to the absence of new NDM-positive cases for periods of time during the survey. This study represents the largest clonal outbreak of NDM-producing E. cloacae complex in Europe.


Engaging My Gen Z Class: Teaching with Memes.
Fostering engagement in a traditional setting with Generation Z learners was difficult enough; to do so online, while most educators are battling with technology, poses an even harder challenge amid the pandemic. In an unconventional assignment, students were asked to create an Internet meme to explain any immunology class themes.


A subchronic oral toxicity study of Salacia reticulata extract powder in rats.
The safety of Salacia plant (Salacia reticulata) extract powder, which is used in Ayurvedic medical practices, was studied in a dose range-finding subchronic toxicity study in Crl:CD Sprague-Dawley rats. Male and female rats were randomly assigned to 4 treatment groups and were treated by oral gavage with 0, 10, 65, and 400 mg/kg body weight/day of the powder for 91 days. Body weight, food consumption, and clinical signs were assessed during the treatment period. Urinalysis, hematology, blood chemistry, and organ weights were determined one day after the final treatment. The animals were euthanized at the end of the treatment and were examined for necropsy and histopathological purposes. No adverse toxicity was observed in the Salacia powder-treated groups with a No Observed Adverse Effect Level of ≧400 mg/kg body weight/day in both male and female SD rats.


Minimally invasive puncture versus conventional craniotomy for spontaneous supratentorial hemorrhage: A meta-analysis.
Minimally invasive puncture and conventional craniotomy are both utilized in the treatment of spontaneous supratentorial hemorrhage. The purpose of this study is to review evidence that compares the safety and effectiveness of these two techniques. We searched EMBASE, Cochrane Library, Web of Science, and PubMed for studies published between 2000 and 2019 that compared the minimally invasive puncture procedure with the conventional craniotomy for the treatment of spontaneous supratentorial hemorrhage. Seven trials (2 randomized control trials and 5 observational studies) with a total of 970 patients were included. The odds ratio indicated a statistically significant difference between the minimally invasive puncture and conventional craniotomy in terms of good functional outcome (OR 2.36, 90% CI 1.24-4.49). The minimally invasive puncture procedure was associated with lower mortality rates (OR 0.61, 90% CI 0.44-0.85) and rebleeding rates (OR 0.48, 95%CI 0.24-0.99; P=0.003). The use of the minimally invasive puncture for the management of spontaneous supratentorial hemorrhage was associated with better functional outcome results, a lower mortality rate, and decreased rebleeding rates. However, because insufficient data has been published thus far, we need more robust evidence to provide a better guide for future management.


The composition of the depressive syndrome in acute schizophrenia.
The composition of the depressive syndrome was examined at both the acute and chronic phases of schizophrenic illness in 86 newly admitted patients. A subgroup with pronounced depression was defined, and a discriminant analysis was performed using symptoms from the Hamilton Rating Scale for Depression (HRSD) as discriminant variables. At the acute phase, the following nine symptoms from the HRSD were significant: depressed mood, guilt, suicide, retardation, three types of insomnia, and two somatic symptoms. At the chronic stable phase, only four symptoms were significant: depressed mood, suicide, general somatic symptoms, and loss of weight. Initial insomnia, middle insomnia, genital symptoms, and loss of insight were poorly correlated. The positive and negative symptoms and extrapyramidal side-effects were not discriminators at either phase. These findings suggest that only certain items from the HRSD may be crucial when assessing depression in schizophrenia.


Evaluation of right ventricle pulmonary artery coupling on right ventricular function in post operative tetralogy of Fallot patients underwent for pulmonary valve replacement.
To evaluate RV-PA coupling in post operative TOF patients with ventricular dilatation underwent for PVR and investigate the correlation between ventricular functions measuring Ea/Emax ratio using cardio magnetic resonance and the effect of surgical type at primary repair of TOF on coupling. RV-PA coupling was measured noninvasively by Ea/Emax ratio from CMRI and ECHO. From CMRI results the patients were divided in two groups, RV-PA coupling and RV-PA uncoupling. Ea/Emax ≤1 was considered for coupling patients and Ea/Emax > 1 for uncoupling patients. Ninety patients were uncoupled (Ea/Emax: 1.55 ± 0.46) and 45 were coupled (Ea/Emax: 0.81 ± 0.15). Out of 75 TAP repaired patients 60 were uncoupled RV-PV. In addition, higher pro-BNP is an important factor for uncoupled RV-PV (P = 0.001). CMR evaluation for right ventricular function between uncoupling and coupling were RVEDVi (196.65 ± 63.57 vs. 154.28 ± 50.07, P = 0.001), RVESVi (121.19 ± 51.47 vs. 83.94 ± 20.43, P = 0.001), RVSVi (67.19 ± 19.87 vs. 106.31 ± 33.44, P = 0.001), and RVEF (40.90 ± 8.73 vs. 54.63 ± 4.76, P = 0.001). The increased RVEDVi, RVESVi and RVSVi and decreased RVEF have significant correlation with Ea/Emax. Ea/Emax was also found positively correlated with RVEDVi (P = < 0.05, r = 0.35), RVESVi (P = < 0.001, r = 0.41) and negatively correlated with RVSVi (P = < 0.05, r = 0.22) and RVEF (P = < 0.05, r = 0.78). Unfavorable RV-PA coupling is present in post operative TOF patients and it is affected by several factors. Our results explain a new concept of RV-PA interactions as a contributing mechanism for the observed decline in RV function.


A phase I/II trial of twice daily irradiation and concurrent chemotherapy for locally advanced squamous cell carcinoma of the head and neck.
This study was designed to test the toxicity and efficacy of a regimen of twice daily irradiation and concurrent multiagent chemotherapy for patients with locally advanced squamous cell carcinoma of the head and neck. This was a prospective Phase I/II trial. Patients received 125 cGy b.i.d. to 7000 cGy with a 6 hr interfraction interval. Chemotherapy was given during weeks 1 and 6 of irradiation and consisted of a 5 day infusion of 5-fluorouracil at 600 mg/M2/day and 5 daily injections of cisplatin at 12 mg/M2/day. Two additional cycles of chemotherapy were given after the completion of radiotherapy. Forty-six patients were evaluable: 28 had technically unresectable disease and 18 had resectable tumors. All had Stage III or IV disease: 84% had T3 or T4 primaries while 53% had > or = N2 neck disease. The primary acute toxicity, confluent mucositis, was seen in 74% of patients. Late side effects occurred in four patients. Median follow-up is 36 months (range 25-44 months). Kaplan-Meier estimates of 2-year disease-free survival and overall survival are 65% and 73%, respectively, while 2-year local regional control and distant disease-free survival are 72% and 88%, respectively. Multivariate analysis revealed that resectability and receiving > 2 cycles of chemotherapy significantly influenced local regional control while age < 60 significantly influenced disease-free survival. This form of treatment can be delivered safely. The encouraging results have led to the initiation of a Phase III trial comparing this regimen with b.i.d. radiation alone.


[Castleman's disease : a rare differential diagnosis for Heerfordt's syndrome].
A 50-year-old male patient demonstrated an existing left proptosis for several weeks. The patient was suffering from physical exhaustion and had lost considerable weight. Furthermore, we observed greatly enlarged parotid and submandibular glands on both sides. MRI of the neck showed multiple, sharply circumscribed lesions in the major salivary glands and both lacrimal glands as well as in the orbit. Initially we suspected Heerfordt's syndrome, a manifestation of sarcoidosis, but laboratory diagnosis could not reveal a pathological erythrocyte sedimentation rate or an increased ACE titer. After exploratory excision from the right submandibular gland, histological examination revealed Castleman's disease. Therefore, we initiated an immunomodulatory therapy with interleukin-6 receptor antagonists.Castleman's disease is one of the very rare, benign, lymphoproliferative processes that have a tendency to turn malignant. Isolated findings of Castleman's disease should be completely resected. There are no clear treatment strategies for multiple localizations of Castleman's disease. The approaches range from systemic glucocorticoid therapy with chemotherapy to immunomodulatory treatment. In contrast to isolated findings, the prognosis for multicentric occurrence is unfavorable.


Understanding alterations in serotonin connectivity in a rat model of depression within the monoamine-deficiency and the hippocampal-neurogenesis frameworks.
The monoamine-deficiency and the hippocampal-neurogenesis hypotheses of depression propose that alterations in the serotonin system and of hippocampal functionality are critical in the pathogenesis of depression. We measured the alterations in the connectivity level of the raphe nucleus in the chronic mild stress (CMS) rat model of depression using the manganese enhanced MRI method (MEMRI). Manganese ions were injected into the median raphe and their anterograde intracellular propagation was followed. Depression-like behavior was demonstrated using the sucrose preference tests. We show that the raphe's connectivity is differentially altered through chronic stress. In line with the monoamine-deficiency hypothesis, the connectivity of the raphe with the basal ganglia (BG) output nuclei, the hippocampus, the habenula and the entorhinal and insular cortices was reduced in CMS rats, suggesting an overall reduction in raphe excitability. Connectivity reductions were predominantly found in the right hemisphere, strengthening previous evidence pointing at a-symmetric hemispheric involvement in depression. Despite the general reduction in raphe connectivity, enhanced connectivity was found between the raphe and the septum, suggesting that alterations are connection-specific. On the basis of our results - while yet equivocal - we further discuss the possible coupling between the serotonergic and dopaminergic systems and two distinct mechanisms (direct and indirect) in which alterations in raphe connectivity may affect hippocampal dysfunction in chronic stress, thus linking the monoamine-deficiency and the hippocampal-neurogenesis hypotheses.


Dopamine receptor DRD3 codes for trait aggression as Mendelian recessive.
The dopamine receptor gene DRD3 and in particular the single nucleotide polymorphism Ser9Gly has been extensively investigated and found to have potential association with a wide variety of conditions. These include essential tremor, unipolar and bipolar depression, as well as a loose association with schizophrenia. Evaluation of (1) these known associations with DRD3, (2) the recent finding of Costas and colleagues that a haplotype containing Ser-9 is associated with protection from schizophrenia, and (3) an extant trait model of personality, leads to the hypothesis that an allele DRD3/Ser codes for trait aggression by Mendelian recessive inheritance. The implications of this hypothesis are that (1) DRD3 is a pleiotropic gene having allelic polymorphism related to both behavior and disease, and (2) models of personality based on genetic traits hold promise. In the area of schizophrenia, the hypothesis implies that schizophrenic patients can be divided into two broad classes: those having genotype DRD3/Ser/Ser and those who lack this homozygosity. The hypothesis of the association of DRD3 with trait aggression could be readily evaluated by testing groups of healthy individuals by personality inventory focused on aggression and by biochemical assay of neurotransmitter levels.


RANKL synthesized by both stromal cells and cancer cells plays a crucial role in osteoclastic bone resorption induced by oral cancer.
The molecular mechanisms underlying bone destruction by invading oral cancer are not well understood. Using IHC, we demonstrated that receptor activator of nuclear factor-κB ligand (RANKL)-positive fibroblasts and cancer cells were located at sites of bone invasion in human oral cancers. HSC3 and HO-1-N-1, human oral cancer cell lines, expressed RANKL and stimulated Rankl expression in the UAMS-32 murine osteoblastic cell line. We discriminated the roles of RANKL synthesized by stromal cells and cancer cells in cancer-associated bone resorption by using species-specific RANKL antibodies against murine RANKL and human RANKL, respectively. Osteoclastogenesis induced by the conditioned medium of HSC3 and HO-1-N-1 cells in a co-culture of murine bone marrow cells and UAMS-32 cells was inhibited by the addition of antibodies against either mouse or human RANKL. HSC3-induced bone destruction was greatly inhibited by the administration of anti-mouse RANKL antibody in a xenograft model. HO-1-N-1-induced bone destruction was inhibited by the administration of either anti-mouse or anti-human RANKL antibody. Bone destruction induced by the transplantation of human RANKL-overexpressing cells (HSC3-R2) was greatly inhibited by the injection of anti-human RANKL antibody. The present study revealed that RANKL produced by both stromal and cancer cells is involved in oral cancer-induced osteoclastic bone resorption. These results provide important information for understanding the cellular and molecular basis of cancer-associated bone destruction and the mechanism of action underlying RANKL antibody (denosumab) therapy.


A scoring system to predict complex transanal endoscopic surgery.
Since the introduction of screening for colorectal cancer, the use of transanal endoscopic surgery (TEM) has become increasingly popular. However, the technical difficulty of this surgery varies widely. The few studies of learning curve in TEM have produced very disparate results. The aim of this study is to distinguish between straightforward and complex procedures, in order to refer more difficult cases to centers with greater experience. Observational study with prospective data collection and retrospective analysis was carried out between June 2004 and January 2019. All TEMs performed on rectal tumors were included. The complexity of the procedure was defined according to the weighted mean surgical time for each surgeon. A predictive model of complexity was established, with a score higher than 5 indicating a complex lesion. During the study period, 773 TEMs were performed, 708 of which met the study's inclusion criteria. One hundred and three tumors were defined as complex. Predictors of complexity were as follows: male sex (OR: 1.78, 95% CI 1.1-2.9, score: 1), tumor size > 5 cm (OR: 5.1, 95% CI 3.2-8.2, score: 4), TEM for recurrence (OR: 6.3, 95% CI 2.3-16.7, score: 5), and distance from the upper margin of the tumor to the anal verge > 15 cm (OR: 1.6, 95% CI 0.96-2.7, score: 1). Rather than establishing the learning curve merely in terms of the number of TEM procedures performed, it is important to consider the surgical difficulty of the interventions. To this end, it is essential to differentiate simple TEMs from the complex ones.


Multiple intracranial arterial stenosis influences the long-term prognosis of symptomatic middle cerebral artery occlusion.
Large intracranial occlusive vascular disease is a major contributor to the incidence of stroke worldwide, especially when it involves the middle cerebral artery (MCA). The data on the prognosis of symptomatic atherosclerotic MCA occlusions (MCAO) with concomitant intracranial arterial disease (MCAO-AIS) are limited. MCAO-AIS may reflect the extent of the atherosclerotic intracranial disease, we hypotheses that coexisting intracranial arterial disease influenced the prognosis of MCAO. Patients having survived at least one month after the initial ischemic stroke who suffered from atherosclerotic occlusion of the MCA were enrolled. According to their concomitant atherosclerotic intracranial arterial disease, the patients were assigned to one of two groups: the MCAO or the MCAO-AIS. All of the patients' cerebrovascular risk factors were recorded. Recurrent ischemic stroke and death were the end-point events during the follow-up. A total of 232 patients (mean age 57.68 ± 9.50 years; 69% male) were analyzed. The mean follow-up time was 17.65 months. The end-point events occurred in 35 (15.09%) patients, resulting in an annual rate of 10.26%. The presence of MCAO- AIS was an independent risk factor associated with the patient's prognosis in the cohort (OR = 3.426, 95% CI 1.261 to 9.308; p = 0.016), as well as gender and diabetes mellitus. The MCAO-AIS were more likely to experience ipsilateral ischemic strokes, but the difference was not statistically significant. Concomitant intracranial arterial disease may influence the prognosis of patients with atherosclerotic MCAO. The result warrants further research in larger sample population.


Static and dynamic changes in body orientation modulate spinal reflex excitability in humans.
In the present study, we investigated the modulation pattern of the soleus H reflex in healthy subjects in response to imposed static and dynamic changes in body angle, referenced to the vertical plane. Soleus H reflexes were recorded using conventional methods with subjects either supine or while they were erect. Changes in body angle were initiated with subjects lying supine on a tilt table. Table position was controlled via a motor and could move from the horizontal to the upright position and beyond. Elastic bands around the trunk (upper and lower part) and around the thigh and shank secured subjects' position. In the vertical position, the soleus H reflex exhibited a strong depression in all subjects tested, reaching amplitudes as low as 40+/-8.1% of the control reflex (Ho). With subjects supine, positioning the body at 10 degrees, 20 degrees, 40 degrees, 60 degrees, 90 degrees, -50 degrees and -20 degrees all resulted in a significant facilitation of the soleus H reflex. The reflex magnitude at these angles ranged from 140+/-17.2% to 180+/-10.9% of the Ho. Reflex facilitation was also observed following dynamic tilt of the body in the sagittal plane (at 1.8 degrees /s) with the H reflex reaching amplitudes as high as 300+/-18.3% of Ho. Our findings indicate that changes in body orientation induced a significant facilitation of the H reflex magnitude in soleus motoneurones that were essentially independent of angular change in body orientation or of movement direction. In addition, they highlight the potent modulatory effects that natural stimulation of the vestibular system can have on reflex excitability. The implications of our findings are discussed in relation to the maintenance of body posture.


α-Ketoglutarate Attenuates Hyperlipidemia-Induced Endothelial Damage by Activating the Erk-Nrf2 Signaling Pathway to Inhibit Oxidative Stress and Mitochondrial Dysfunction.
Aims: α-Ketoglutarate (AKG) is an intermediate of the tricarboxylic acid cycle and a key hub linking amino acid metabolism and glucose oxidation. Previous studies have shown that AKG improved cardiovascular diseases such as myocardial infarction and myocardial hypertrophy through antioxidant and lipid-lowering characteristics. However, its protective effect and mechanism on endothelial injury caused by hyperlipidemia have not been elucidated yet. In this study, we tested whether AKG possesses protective effects on hyperlipidemia-induced endothelial injury and studied the mechanism. Results: AKG administration both in vivo, and in vitro significantly suppressed the hyperlipidemia-induced endothelial damage, regulated ET-1 and nitric oxide levels, and reduced the inflammatory factor interleukin-6 and matrix metallopeptidase-1 by inhibiting oxidative stress and mitochondrial dysfunction. The protective effects were achieved by the mechanism of activating the Nrf2 phase II system through the ERK signaling pathway. Innovation: These results reveal the role of the AKG-ERK-Nrf2 signaling pathway in the prevention of hyperlipidemia-induced endothelial damage, and suggest that AKG, as a mitochondria-targeting nutrient, is a potential drug for the treatment of endothelial damage in hyperlipidemia. Conclusion: AKG ameliorated the hyperlipidemia-induced endothelial damage and inflammatory response by inhibiting oxidative stress and mitochondrial dysfunction. Antioxid. Redox Signal. 39, 777-793.


Transforming growth factor-beta bound to soluble derivatives of the beta amyloid precursor protein of Alzheimer's disease.
Transforming growth factors beta (TGF beta) are multifunctional polypeptides that participate in regulation of growth, differentiation and function of many cell types. The mature TGF beta molecule is a 25 kDa protein composed of two 12.5 kDa monomers linked by disulfide bonds. Human glioblastoma cells secrete biologically active TGF beta 2. Here we report that in addition to the free form of TGF beta 2, a stable complex between a approximately 110 kDa binding protein and TGF beta 2 was isolated from glioblastoma cell supernatant. This binding protein was purified and was found to show sequence identity to part of the beta amyloid precursor protein (beta APP), to be specifically labeled by several different antisera to beta APP, and to be affinity labeled with TGF beta by crosslinking. The complex formation between TGF beta and beta APP may have important implications in regulation of biological activity of the two proteins and in delivery or clearance of TGF beta and beta APP in the brain and other compartments.


Toxic effects of nonsteroidal antiinflammatory drugs on the small bowel, colon, and rectum.
The gastrointestinal toxicity of conventional nonsteroidal antiinflammatory drugs (NSAIDs) is not confined to the stomach and proximal duodenum but extends also to the rest of the small bowel, colon, and rectum. Long-term NSAID therapy usually induces clinically silent enteropathy characterized by increased intestinal permeability and inflammation. Chronic occult bleeding and protein loss may result in iron-deficiency anemia and hypoalbuminemia. NSAIDs can also induce small bowel ulcers that infrequently lead to acute bleeding, perforation, or chronic scarring responsible for diaphragm-like strictures. At the colon and rectum, NSAID use can result in de novo lesions such as nonspecific colitis and rectitis, ulcers, and diaphragm-like strictures. NSAIDs have been implicated in the development of segmental ischemic colitis. In patients with diverticular disease, NSAID use increases the risk of severe diverticular infection and perforation. NSAIDs can trigger exacerbations of ulcerative colitis or Crohn's disease. With selective COX-2 inhibitors, the risk of gastrointestinal toxicity is reduced as compared to conventional NSAIDs but is not completely eliminated. Experimental studies suggest that long-term COX-2 inhibitor therapy may cause damage to the previously healthy small bowel. Similar to conventional NSAIDs, COX-2 inhibitors may be capable of triggering exacerbations of inflammatory bowel disease.


The prolonged and enhanced immune response in the non-obese diabetic mouse is dependent on genes in the Idd1/24, Idd12 and Idd18 regions.
In non-obese diabetic (NOD) mice B cells are an absolute requirement for T1D development. NOD mice display various B cell related immune deviations when compared to normal mice such as an enhanced and prolonged immune response towards several antigens, including non-self immunoglobulins. We hypothesized that this trait contributes to diabetes pathogenesis, and investigated the genetic factor(s) governing the altered immune response. A (NODxC57BL/6)F(2) cohort (n = 214) were analyzed for its primary immune response against a BALB/c derived monoclonal antibody, and a genome wide linkage analysis was performed. Significant linkage to the Idd1/Idd24, Idd12 and Idd18.1 regions as well as to a proximal region (marker D2Mit367, 33.5 Mb) on chromosome 2 was detected. We verified the observed linkage by analyzing a set of H2 congenic NOD and C57BL/6 mice and narrowed down the region to 8 Mb. Interaction between Idd1/24 and Idd12, as well as the novel locus on chromosome 2 was observed. However, the action by Idd18.1 was not influenced by any of the other loci. In addition to the known H2 I-Aβ(g7) allelic variant of Idd1 in NOD, candidate gene analysis revealed a significant difference in the transcription of the H2-O/DO molecule. We hypothesize that multiple mechanisms contribute to the loss of immune response control, including that peptide loading on MHC class II in B cells of NOD is altered.


Role of chemokines in ischemic neuronal stress.
Chemokines constitute a large family of structurally related small cytokines originally identified as the factors regulating the migration of leukocytes in inflammatory and immune responses. Enhanced production and release of chemokines are observed also in the central nervous system under diverse neuronal stresses including ischemia, axonal injury, and neurotoxic substances such as an Abeta-peptide. There is growing evidence that brain chemokines play crucial roles in the neuro-glio-vascular interaction underlying the pathology of various brain disorders. Here the evidence of the involvement of chemokines in ischemic brain injury is reviewed.


Connexins and their channels in cell growth and cell death.
Direct communication between cells, mediated by gap junctions, is nowadays considered as an indispensable mechanism in the maintenance of cellular homeostasis. In fact, gap junctional intercellular communication is actively involved in virtually all aspects of the cellular life cycle, ranging from cell growth to cell death. For a long time, it was believed that this was merely a result of the capacity of gap junctions to control the direct intercellular exchange of essential cellular messengers. However, recent data show that the picture is more complicated than initially thought, as structural precursors of gap junctions, connexins and gap junction hemichannels, can affect the cellular homeostatic balance independently of gap junctional intercellular communication. In this paper, we summarize the current knowledge concerning the roles of connexins and their channels in the control of cellular homeostasis, with the emphasis on cell growth and cell death. We also briefly discuss the role of gap junctional intercellular communication in carcinogenesis and the potential use of connexins as tools for cancer therapy.


Reoperative transmyocardial laser revascularization for late recurrent angina.
Transmyocardial laser revascularization (TMR) reduces anginal class and is indicated for severely symptomatic patients who are not candidates for conventional revascularization. This report describes a 72-year-old man who presented 4 years following initially successful TMR with recurrent angina refractory to maximal medical management. Reoperative TMR was performed with substantial improvement in angina and functional class.


Cesarean section rates according to the Robson Classification and its association with adequacy levels of prenatal care: a cross-sectional hospital-based study in Brazil.
The rate of Cesarean section (CS) deliveries has been increasing worldwide for decades. Brazil exhibits high rates of patient-requested CS deliveries. Prenatal care is essential for reducing and preventing maternal and child morbidity and mortality, ensuring women's health and well-being. The aim of this study was to verify the association between the level of prenatal care, as measured by the Kotelchuck (APNCU - Adequacy of the prenatal care utilization) index and CS rates. We conducted a cross-sectional study based on data from routine hospital digital records and federal public health system databases (2014-2017). We performed descriptive analyses, prepared Robson Classification Report tables, and estimated the CS rate for the relevant Robson groups across distinct levels of prenatal care. Our analysis also considered the payment source for each childbirth - either public healthcare or private health insurers - and maternal sociodemographic data. CS rate by level of access to prenatal care was 80.0% for no care, 45.2% for inadequate, 44.2% for intermediate, 43.0% for adequate, and 50.5% for the adequate plus category. No statistically significant associations were found between the adequacy of prenatal care and the rate of cesarean sections in any of the most relevant Robson groups, across both public (n = 7,359) and private healthcare (n = 1,551) deliveries. Access to prenatal care, according to the trimester in which prenatal care was initiated and the number of prenatal visits, was not associated with the cesarean section rate, suggesting that factors that assess the quality of prenatal care, not simply adequacy of access, should be investigated.


Protecting mental health of young adults in COVID-19 pandemic: Roles of different structural and functional social supports.
Concerning rates of psychological disorders are increasingly recognized in young adults during the COVID-19 pandemic. This study aimed to examine the associations of different structural and functional social supports on depression, anxiety, and stress among young adults in Vietnam. An online cross-sectional study was performed on 236 respondents aged 16 to 30 years in Vietnam from June to July 2020. The Depression, Anxiety and Stress Scale-21 Items (DASS-21); the Multidimensional Scale of Perceived Social Support (MSPSS), and the LUBBEN Social Network Scale (LSNS-6) was used to measure psychological health, functional and structural social support characteristics. Multi-level mixed-effect logistic regression was used to identify associations between social support and anxiety, depression, and stress. The rate of at least mild depression, anxiety, and stress were 30.1%, 34.8%, and 35.6%, respectively. Structural supports measured by LSNS-6 were not associated with the likelihood of having depression, anxiety, and stress (p>0.05). Respondents having friends with whom they could share joys and sorrows were less likely to have anxiety (aOR = 0.61, 95%CI = 0.41-0.90) and stress (aOR = 0.66, 95%CI = 0.45-0.96). Having family support in decision-making was also negatively associated with depression, anxiety, and stress. Meanwhile, those having family and friends who tried to help them were more likely to suffer stress (aOR = 1.94, 95%CI = 1.16-3.24) and depression (aOR = 2.09; 95%CI = 1.11-3.92), respectively. This study highlighted a high rate of psychological problems among young adults during the COVID-19 pandemic in Vietnam. Emotional support from friends and advice support from family were important components that should be considered in further interventions to mitigate the psychological problems in young adults.


Eating disorder and socioeconomic class. Anorexia nervosa and bulimia in nine communities.
To compare the prevalence of eating disorders in lower income vs. upper income communities, we administered a previously validated questionnaire to 394 women at nine state-regulated bingo tournaments. Surprisingly, eating disorders were more commonly reported by lower income respondents.


The process of ultrastructural changes from nuclei to apoptotic body.
There have been many reports on the formation of apoptotic bodies, but little is known about the cellular pathological processes and the morphological changes involved. We induced apoptotic cell death by administering nivalenol (NIV), a trichothecene mycotoxin produced by Fusarium species, and investigated the ultrastructural process of formation of apoptotic bodies. The thymus was examined by electron microscopy 6, 12, and 18 h after administration. Apoptotic cell death was induced in the thymus of NIV-treated mice. The nuclei became invaginated and pinched off to give fragments, and crescent-shaped spaces (CSS) were found around the nuclear envelopes of these cells at quite an early stage. In some of these spaces, myelin figures were observed. We divided the process of formation into four stages and characterized each of them. These are easily recognized in morphological stages and are also useful for clarifying the apoptotic mechanism.


[Study on the professional procedures, experiences and needs of parents when they are told their child has a disability or developmental disorder. Breaking the news].
Both the moment and the way chosen to break the news that a child aged 0-6 years is suffering, or may suffer, from a developmental disorder or disability have an effect on the parents and on the familial system that goes beyond the actual fact of knowing about the circumstance in itself. It is a very significant social act that represents the first encounter in which the parents explore and anticipate the social attitudes of inclusion or exclusion towards the child. To gather information about the practices usually employed by professionals when it comes to breaking the news to the families, to evaluate what aspects of the process could be improved, to determine the families' needs in these circumstances and to gain a deeper understanding of the affective-emotional processes experienced by the parents. The research was conducted using a questionnaire with 43 items, which was specifically designed for the population under examination in the study. Altogether, 418 parents from 15 different autonomous regions of Spain took part in the study. At the same time, the existing literature on diagnostic information in Spanish was reviewed. It can be concluded that, to 'break the bad news', professionals must know the family; they must take the utmost care in choosing when, where and how to give that news; the parents must be together when they are told; and they must take into account the type of disability the child suffers from as well as its intensity. These guidelines of conduct become manifest in strategies and keys to be applied to each situation, in the contents of the messages to be communicated and in the attitudes of professionals.


Retrospective reinterpretation and reclassification of BRCA1/2 variants from Chinese population.
The accurate interpretation of BRCA1/2 variants becomes increasingly important in breast cancer and other related cancers including ovarian cancer, prostate cancer, pancreatic cancer and so forth. In the past decades, especially before year 2015, limitations of techniques and lack of databases and guidelines have led to possible misinterpretation of the clinical significance of sequence variants of BRCA1/2. A published study reported reclassification of some BRCA1/2 variants previously classified as variants of uncertain significance (VUS) to likely pathogenic in breast or ovarian cancer patients from Korea. However, little is known about the situation in Chinese population. We retrospectively retrieved 109 publications studying about BRCA1/2 variants of Chinese population from the year 1999 to year 2019 (March). After excluding publications of meta-analysis and publications with missing data, 72 publications were eventually retained for subsequent analysis. In total, 1,351 BRCA variants (673 BRCA1 variants and 678 BRCA2 variants) derived from 42,430 Chinese cancer patients were standardized and reinterpreted using ACMG/AMP 2015 guidelines and China Expert Consensus on BRCA variant interpretation by genetic counselors. Among the 1,351 BRCA variants, the majority of interpretation (91.7%, 1,239/1,351) remained the same as previously published. However, there were 112 (8.3%, 112/1,351) variants (64 BRCA1, 48 BRCA2) reclassified with different categories. Our results demonstrated that clinical significance of not only VUS, but also pathogenic/likely pathogenic variants varied from time to time in the Chinese population. Precise reinterpretation of BRCA1/2 variants is of crucial importance to genetic counseling or clinical decision-making for risk individuals or patients.


[Perspective of peer helpers regarding their experience animating a self-treatment program for panic disorders].
Support groups can help to reach individuals with anxiety disorders who are not or are only partly obtaining health services. The present study is based on a program that involves peer helpers as animators of a self-treatment group (Zéro-ATAQ). Their perspective has been documented in order to identify the aspects of the program which can be improved. Eleven peer helpers led the 12 sessions of the program, which was dispensed in four regions of Quebec for 32 persons having panic disorders with agoraphobia. The perspectives of ten peer animators were documented based on a semi-structured interview that took place at the end of the program, and a focus group that was held over six months later with peer animators from each of the groups. Their comments were transcribed and a thematic content analysis was conducted. All of the peer helper animators reported that they enjoyed participating in the program, that they appreciated being able to help others having an anxiety disorder, and that the program helped them in their role as animators of these types of activities. Nearly all of the peer helpers emphasized the importance of being able to count on the supervision of a professional when needed. This study revealed (1) the feasibility of implementing a program of this kind in partnership with peers, (2) the qualifications necessary to lead this type of program, (3) the requirements in terms of training and available material, and (4) the importance of supervision.


Policy prescriptions to preserve mobility for seniors--A dose of realism.
This paper advocates policy change in three key areas: infrastructure, driver licensing, and access to private resources for transportation alternatives. Policy makers are encouraged to plan for the transportation future of our aging society by prioritizing public expenditures for roads and highways according to design and engineering practices already proven to assist older drivers and pedestrians. By adopting minimum, evidence-based requirements for visual, mental and physical capability for licensure and uniformly applying them at all ages, across all states, policy makers can improve the safety of older drivers without unfairly restricting their mobility-and need not increase the regulatory burden in doing so. By reviewing and replicating already successful state policies that either create incentives or remove barriers to the use of private resources for non-profit, senior transportation, policy makers can help communities access the labor and capital, as well as manage the risks of market-oriented, non-profit mobility solutions.


Diversity study of 12 X-chromosomal STR loci in Hui ethnic from China.
X-chromosomal STRs (X-STRs) have been used as complements of autosomal STR application in recent years. In this work, we present population genetic data of 12 X-STRs including DXS101, DXS10159, DXS10162, DXS10164, DXS6789, DXS7133, DXS7423, DXS7424, DXS8378, DXS981, GATA165B12, and GATA31E08 loci in a sample of 231 unrelated healthy individuals from the Hui ethnic group in Ningxia Hui Autonomous Region, China. Allelic frequencies of the 12 X-STR loci and haplotypic frequencies of the reported linkage groups (DXS7424-DXS101 and DXS10159-DXS10164-DXS10162) were investigated in the group, respectively. No STR loci showed significant deviations from the Hardy-Weinberg equilibriums and no linkage disequilibriums of pairwise loci were found after Bonferroni correction, respectively. A combined power of discrimination in female individuals was 0.999999999985 and that in male individuals was 0.99999967, respectively. The combined mean exclusion chance in deficiency cases, normal trios and duo cases were 0.999934, 0.995754, and 0.999796, respectively. Significant differences were observed from 0 to 8 loci, when making comparisons between the data of Hui ethnic group and previously reported data from other 16 populations. The results indicated the new panel of 12 X-STR loci might be useful for forensic science application.


Photosensitive hydrogels: from structure, mechanisms, design to bioapplications.
Hydrogel is a smart material with a three-dimensional network structure and has been widely used in various fields due to its good biodegradability, biocompatibility, and modification. Photosensitive hydrogel is a smart hydrogel, and its amenability to remote, precise control, and flexible and convenient regulation of stimulating factors make it an ideal candidate for use in fields such as biological materials, drug carriers, and sensors. In this review, we discuss the structure, mechanisms, design principles, and bioapplications of photosensitive hydrogels as developed in recent years. Finally, their potential for development and potential future challenges are outlined.


The respiratory chain in a ubiquinone-deficient mutant of Saccharomyces cerevisiae.
1. Two allelic mutants of Saccharomyces cerevisiae with a deficiency in the biosynthesis of ubiquinone have been isolated. The properties of one particular mutant strain were investigated. Submitochondrial particles of this strain contain maximally 3% of the amount of ubiquinone in wild-type particles; the amounts of other components of the respiratory chain are essentially normal. 2. The respiratory rates of mutant cells, mitochondria and submitochondrial particles are low with ubiquinone-dependent substrates, but are restored to normal levels by addition of Q-1; the restored respiration is antimycin sensitive. Intact cells and mitochondria show respiratory control both in the absence and presence of Q-1. 3. The NADH:Q-1 oxidoreductase of submitochondrial particles of the mutant followspseudo first-order kinetics in [Q-1]. QH2-1 inhibits competitively with respect to Q-1, the Ki for QH2-1 being equal to the Km for Q-1. 4. Succinate dehydrogenase in both wild-type and mutant submitochondrial particles can be activated by NADH. 5. The turnover number of succinate dehydrogenase in the mutant, measured with phenazine methosulphate as primary electron acceptor, is about one-half that of wild-type particles. The turnover numbers measured with Q-1 as electron acceptor are about the same in the two types of particles. 6. The kinetics of redox changes in cytochrome b, in the presence of antimycin and oxygen, are distinctly different in the mutant and wild-type particles. They indicate that ubiquinone plays an important role in the phenomenon of the increased reducibility of cytochrome b induced by antimycin plus oxygen.


Photocontrol of DNA duplex formation by using azobenzene-bearing oligonucleotides.
The duplex-forming activities of oligonucleotides can be photomodulated by incorporation of an azobenzene unit. Upon isomerizing the trans-azobenzene to the cis form by irradiation with UV light, the T(m) value of the duplex (with the complementary DNA) is lowered so that the duplex is dissociated. The duplex is formed again when the cis-azobenzene is converted to the trans-azobenzene by irradiation with visible light. The photoregulation is successful irrespective of the position of the azobenzene unit in the oligonucleotides. The trans-azobenzene in the oligonucleotides intercalates between two DNA base pairs in the duplexes and stabilizes them because of a favorable enthalpy change. The nonplanar structure of a cis-azobenzene is unfavorable for such an interaction. These photoresponsive oligonucleotides are promising candidates for the regulation of various bioreactions.


Changing patient health-risk behavior requires new investment in primary care.
Evidence supports the effectiveness of primary care interventions to improve nutrition, increase physical activity levels, reduce alcohol intake, and stop tobacco use. However, implementing these interventions requires considerable practice expense. If we hope to change behavior to reduce chronic illness, the way we pay for primary care services must be modified to incorporate these expenses.


[Cancer pain, a challenge for the nurse's own role].
Because of its many specific features, cancer pain requires special management and a sound knowledge base. This article aims to take a fresh look at this type of pain, and share some of the elements that make it so specific. It also aims to provide a reminder of what cancer pain is, as well as clarifying the specific role of the state-registered nurse in its management.


Alkalimonas amylolytica gen. nov., sp. nov., and Alkalimonas delamerensis gen. nov., sp. nov., novel alkaliphilic bacteria from soda lakes in China and East Africa.
Two related novel alkaliphilic and slightly halophilic bacteria are described. They are strain N10 from Lake Chahannor in China and strain 1E1 from Lake Elmenteita in East Africa. Both strains are strictly aerobic, heterotrophic, alkaliphilic, mesophilic, and require NaCl for growth. The optimal conditions for growth were at pH 10-10.5 and 2-3% (w/v) NaCl. Cells of both strains were Gram-negative, rod-shaped, non-spore-forming, and motile with a single polar flagellum. Cellular fatty acids in both strains were predominantly saturated and mono-unsaturated straight-chain fatty acids (16:0, 16:1omega7c and 18:1omega7c). The major isoprenoid quinone of both strains was Q8. The major polar lipids are phosphatidylglycerol, diphosphatidylglycerol, phosphatidylglycerol phosphate and phosphatidylethanolamine. The guanine plus cytosine (G + C) content of the DNA was 52.5 mol% and 55.4 mol%, respectively. Phylogenetic analysis revealed that the two strains formed a distinct lineage within the gamma-3 subclass of the Proteobacteria. The strains shared a 16S rDNA sequence similarity of 96.1% and showed less than 93.7% of sequence similarity to any other known species. Based on polyphasic data, the two strains were differentiated from currently recognized genera and represent a new genus, Alkalimonas gen. nov., with two species, Alkalimonas amylolytica sp. nov. (type strain is N10T = AS 1.3430) and Alkalimonas delamerensis sp. nov. ( type strain is 1E1(P, T) = CBS 391.94). The GenBank accession numbers for the 16S rRNA gene sequence of strains N10 and 1E1 are AF250323 and X92130, respectively.


Renal artery aneurysm: successful exclusion with a stent graft.
Renal artery aneurysms are uncommon. They are either incidentally discovered or identified during workup for secondary hypertension. An association with rupture at sizes greater than 1.5 cm exists. In this case report, the exclusion of a renal aneurysm with a covered stent is described. In spite of compromise of a side-branch vessel, there were no deleterious effects on renal function at 6-month follow-up.


Dental myths, oral hygiene methods and nicotine habits in an ageing rural population: an Indian study.
Though, increased emphasis is being given on spreading dental care facilities and awareness in Indian villages, the target population is unfortunately less literate and is not financially equipped compared to their urban counterparts. The rural aged additionally may have to face problems like desertion by the educated youth to follow better opportunities in cities, disease, and lack of mobility. The present study strived to evaluate dental myths, oral hygiene methods, and tobacco habits awareness in a rural ageing population in the perspective of a changing India. The study area consisted of a group of ten villages, situated in district Lucknow, Uttar Pradesh, India. The subjects were questioned about dental myths, tobacco habits, and oral hygiene methods and then divided into groups on the basis of age, sex, and educational status. The number of sound teeth in each subject was also counted. Mean-values, standard deviation, Chi-square test and P values were used to make inter-group comparisons. Forty percent of the subjects considered oral hygiene unnecessary, 60.8% of the population was relying on simple mouth rinsing for maintaining oral hygiene, 48% had either the habit of smoking and chewing tobacco or both and 81% of the subjects had one dental myth or the other. We concluded that the rural aged is a deprived lot and a targeted program to infuse scientific dental practices in them is necessary.


Electric permittivity and dielectric dispersion of low-molecular weight DNA at low ionic strength.
The dielectric properties of sonicated calf-thymus DNA (MW approximately 3 X 10(5) g mol-1) have been investigated in a frequency range between a few kHz and 100 MHz. Two samples, sonicated in a different way were used after proper characterization including light-scattering, viscometry and contour length distribution by electron microscopy. Dielectric measurements were performed at several concentrations between 10(-4) and 3 X 10(-3) monomol 1-1 and 22 degrees C. Under all circumstances two separated dispersion regions were observed, the corresponding specific increments of which decreased with increasing concentration. The same was observed with the mean relaxation time of the high frequency dispersion. Both the frequency and concentration dependence was largely analogous to what is observed with other polyelectrolytes. Values of the dielectric parameters extrapolated to infinite dilution could also be interpreted in the same manner as for more simple, charged macromolecules and no specific effects had to be taken into account.


The distributions, contamination status, and health risk assessments of mercury and arsenic in the soils from the Yellow River Delta of China.
The surface soils were collected from four areas in the Yellow River Delta (YRD), including three functional areas in the natural reserve of the YRD (the core area, buffer area, and experimental area) and a neighboring area of the natural reserve. The total concentrations, speciations, contamination status, and health risk assessments of the mercury (Hg) and arsenic (As) in surface soils of the YRD were investigated. The average Hg concentration was about three times that of the background value, while As was just slightly higher than the background. Hg levels in the sites of experimental area were significantly higher than those in the core area and buffer area, which was consistent with the human activity intensities of the three functional areas. However, no significant differences of As levels were observed across different areas. According to the sequential extraction experiments, only less than 5% of Hg and As were associated with the exchangeable fraction, while over 80% of them were found in the residual fraction, indicating low mobility and bioavailability of both Hg and As. The soil contamination status assessments suggested a "good state," and the health risk assessments indicated a "low risk" of Hg and As in the soils of YRD.


Identifying a suitable model for predicting hourly pollutant concentrations by using low-cost microstation data and machine learning.
Accurately predicting the concentration of PM2.5 (fine particles with a diameter of 2.5 μm or less) is essential for health risk assessment and formulation of air pollution control strategies. At present, there is also a large amount of air pollution data. How to efficiently mine its hidden features to obtain the future concentration of pollutants is very important for the prevention and control of air pollution. Therefore we build a pollutant prediction model based on Lightweight Gradient Boosting Model (LightGBM) shallow machine learning and Long Short-Term Memory (LSTM) neural network. Firstly, the PM2.5 pollutant concentration data of 34 air quality stations in Beijing and the data of 18 weather stations were matched in time and space to obtain an input data set. Subsequently, the input data set was cleaned and preprocessed, and the training set was obtained by methods such as input feature extraction, input factor normalization, and data outlier processing. The hourly PM2.5 concentration value prediction was achieved in accordance with experiments conducted with the hourly PM2.5 data of Beijing from January 1, 2018 to October 1, 2020. Ultimately, the optimal hourly series prediction results were obtained after model comparisons. Through the comparison of these two models, it is found that the RMSE predicted by LSTM model for each pollutant is nearly 50% lower than that of LightGBM, and is more consistent with the fitting curve between the actual observations. The exploration of the input step size of LSTM model found that the accuracy of 3-h input data was higher than that of 12-h input data. It can be used for the management and decision-making of environmental protection departments and the formulation of preventive measures for emergency pollution incidents.


Circular RNA circ_0000119 promotes cervical cancer cell growth and migration via miR-433-3p/PAK2 axis.
The purpose of this study was to investigate the role of circ_0000119 on CC progression and its molecular mechanism. The expression levels of circ_0000119, miR-433-3p, and p21-activated kinase 2 (PAK2) in CC tissues and cell lines were measured by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was assessed using 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, 5-Ethynyl-2'-deoxyuridine (EdU) assay and colony formation assay. Cell cycle and apoptosis were assessed by flow cytometry. Cell migration and invasive ability were examined by Transwell assays. Downstream binding targets of circ_0000119 were predicted by online bioinformatics tools and confirmed by dual luciferase reporter gene assay, RNA immunoprecipitation (RIP) assay, and RNA pull-down assay. The role of circ_0000119/miR-433-3p/PAK2 axis in regulating the CC process was explored by rescue experiments. A xenograft model was constructed to further determine the effect of circ_0000119 on CC tumor growth in vivo. Immunohistochemistry (IHC) assay was conducted for Ki67 expression. Circ_0000119 was aberrantly upregulated in CC tissues and cell lines. Knockdown of circ_0000119 inhibited CC cell proliferation, cell cycle progress, migration, invasion, and promoted apoptosis of CC cells. MiR-433-3p was a binding target of circ_0000119, and PAK2 was a downstream gene of miR-433-3p. MiR-433-3p inhibition reversed the inhibitory effect of silencing circ_0000119 on CC progression. In addition, PAK2 overexpression reversed the effect of miR-433-3p on CC progression. PAK2 expression was regulated by circ_0000119 and miR-433-3p. Moreover, circ_0000119 knockdown reduced tumor growth of CC in vivo. Circ_0000119 was upregulated in CC, and circ_0000119 knockdown suppressed CC malignant development through the miR-433-3p/PAK2 axis.


Association of generalized dystrophic epidermolysis bullosa with positive acetylcholinesterase and markedly elevated maternal serum and amniotic fluid alpha-fetoprotein.
A case of fatal generalized dystrophic epidermolysis bullosa is described in a prematurely born female whose mother had strikingly elevated mid-trimester serum and amniotic fluid alpha-fetoprotein concentrations, a positive amniotic fluid acetylcholinesterase band, and negative serial ultrasound studies. This case lends further support to an association between autosomal recessive generalized dystrophic epidermolysis bullosa and increased levels of alpha-fetoprotein, positive amniotic fluid acetylcholinesterase, and normal ultrasound findings.