Perceptions of primary health care service users regarding dental team practices in Brazil.
The Unified Health System (SUS) is the Brazilian set of public health services that offers global access to health care and disease treatments for all citizens. These services have been evaluated by means of a national survey assessing the users' perceptions.AimTo explore and characterize the SUS users' perceptions regarding primary dental team practices in the five Brazilian geographical regions. Descriptive study. The sample consisted of 37 262 subjects. Data were collected by means of the Ministry of Health survey, conducted between 2012 and 2014. Variables used in the present study are associated with SUS users' perspectives of satisfaction, access, and use of services. The study utilized bivariate data analysis, and dichotomous variables were derived for analysis following 95% reliability.FindingsThis study observed similarities and proportionality of perceptions in the Brazilian territory. In most macro-regions, dental teams did not develop an active search for dental treatment absentees. However, the SUS users reported very good and good perceptions, which were homogeneously distributed across five Brazilian regions, thereby showing an overall positive perception of primary dental treatment.


Stress-induced condensate switch awakens sleeping viruses.
In a recent Cell paper, Zhang et al. reveal that stress-induced changes in intra-condensates awaken dormant viruses. These results shed light on the delicate balance between viruses and their hosts, providing avenues for further research in the field.


Purification and characterization of actinomycin synthetase I, a 4-methyl-3-hydroxyanthranilic acid-AMP ligase from Streptomyces chrysomallus.
Actinomycin synthetase I was purified to homogeneiety from actinomycin-producing Streptomyces chrysomallus. The purified enzyme is a single polypeptide chain of M(r) 45,000. It catalyzes the formation of the adenylate of 4-methyl-3-hydroxyanthranilic acid (4-MHA) from the free acid and ATP in an equilibrium reaction. 4-MHA is the precursor of the chromophoric part of actinomycin. By using the 4-MHA analogue, 4-methyl-3-hydroxybenzoic acid, as a model substrate it could be established that the equilibrium constant Keq is independent on enzyme concentration, which suggests that no stoichiometric acyladenylate-enzyme complex is formed in contrast to observations made with aminoacyl adenylates formed by aminoacyl-tRNA synthetases or multifunctional peptide synthetases. Actinomycin synthetase I does not charge itself with substrate carboxylic acid via a covalent thioester bond as is usual for amino acid activation in non-ribosomal peptide synthesis. In addition, the enzyme does not act as an acyl-coenzyme A ligase as revealed by its inability to release AMP in the presence of 4-MHA or other structurally related aromatic carboxylic acids, coenzyme A and ATP. Additional analysis of the activation reaction showed that it is exothermic, whereas the free enthalpy change delta G0 is positive due to a negative entropy change indicating a strong influence of restriction of random motion on the course of the reaction. Determinations of Km and kcat of various substrate carboxylic acids revealed the highest kcat/Km ratio for the natural substrate 4-MHA. From these properties, actinomycin synthetase I represents the prototype of novel chromophore activating enzymes involved in non-ribosomal synthesis of chromopeptide lactones in streptomycetes.


Efficacy and safety of the extraction of cardiostimulation leads using a mechanical dissection tool. A single center experience.
The percutaneous extraction of endovascular cardiostimulation and defibrillation leads is the most frequent technique nowadays. The tools used today must guarantee the success of the procedure, with the minimum of complications. Our objective was to analyze the safety and efficacy of lead extraction using the Evolution mechanical dissection tool (Cook Medical, USA). A retrospective study was carried out in a total of 826 consecutive patients from October 2009 to December 2018 who underwent the procedure with the Evolution mechanical dissection tool. Preoperative study included complete blood tests, echocardiogram, and chest X-ray. The procedures were performed in the operating room, under general anesthesia and echocardiographic control. A total of 1227 leads were extracted with a mean chronicity of 10.3 ± 5.1 years. Clinical success (CS) rate was 99.7%. A total of 16 (1.9%) complications occurred, 2 (0.24%) were major complications and 14 (1.7%) were minor complications. There was no operative mortality. There was no statistically significant relationship between implant chamber and complete efficacy. The complete extraction was achieved in all left ventricular leads, in 762 of 774 (98.45%) of right ventricular lead removal, and in 330 of 334 (98.8%) of right atrial leads (p = .31). In our experience, percutaneous extraction of intravenous leads via the use of the Evolution tool (Cook Medical, USA), is a very effective and safe technique that offers low morbidity and mortality.


Liquid chromatography-tandem mass spectrometry reveals an active response to DNA damage in human spermatozoa.
To investigate how endogenously elevated DNA fragmentation alters the human sperm proteome, and whether this fragmentation contributes to genomic deletions. Research study. Commercial fertility clinic. Men with low (0%-4%, n = 7) or high (≥16%, n = 6) sperm DNA fragmentation, as assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. None. Global sperm proteome, single-nucleotide polymorphism genotyping array. A total of 78 significantly differentially abundant proteins (30 decreased, 48 increased) were observed in control vs. high DNA damage samples. DNA damage resulted in robust proteomic responses, including markers of oxidative stress and apoptosis, DNA damage repair proteins, and transcription/translation and protein turnover machinery. Several key sperm functional proteins were significantly decreased in ejaculates with high DNA damage. We were unable to substantiate a link between increased DNA fragmentation and genomic deletions in human spermatozoa. Developing human spermatozoa initiate an active transcriptional response to endogenous DNA damage, which manifests as alterations in the sperm proteome.


Does Microfluidic Sperm Sorting Affect Embryo Euploidy Rates in Couples with High Sperm DNA Fragmentation?
Male infertility contributes as the main factor in 30-50% of infertility cases. Conventional methods for sperm preparation have induced questioning of sperm recovery rates. The microfluidic sperm sorting (MSS) technique selects highly motile sperm with lower levels of SDF (sperm DNA fragmentation) compared to conventional sperm sorting techniques. This study aimed to determine whether utilizing this technique will reveal better embryo quality and euploidy rates in couples with repeated implantation failure (RIF) and high SDF in a new PGT-A (preimplantation genetic testing for aneuploidies) cycle. This retrospective study included couples referred to PGT-A for previous repeated ART (assisted reproductive techniques) cycle failures and with high SDF. In their new cycles, couples who accepted the technique were assigned to the MSS group, and the rest were managed with DGC (density-gradient centrifugation). Two groups were compared in terms of fertilization and euploidy rates, clinical miscarriage and live birth rates, the total number of blastocysts, and top quality blastocysts. There was no difference between the groups regarding fertilization rates, euploidy rates, clinical miscarriage, and live birth rates. The total number of blastocysts and top quality blastocysts were significantly higher in the MSS group. The MSS technique provides a higher number of top-quality blastocysts than DGC; however, neither euploidy nor live birth rates improved. Studies focusing on confounding factors to embryonic genomic status in the presence of high SDF are needed.


Gene therapy of metastatic cancer by in vivo retroviral gene targeting.
We have achieved efficient transduction of tumour metastases in vivo by the vascular delivery of retroviral producer cells. Experimental liver metastases in mice were created by intrasplenic injection of tumour cells into the portal venous circulation. Following the establishment of micrometastases, delivery of retroviral producer cells by the same route with a vector containing the Escherichia coli beta-galactosidase (lacZ) gene demonstrated selective in vivo gene transfer to tumour deposits. By this approach, two retroviral producer cell lines encoding cytokines (IL-4 and IL-2) directed tumoricidal inflammatory responses to established metastases. Cytokine gene targeting inhibited metastasis formation and caused significant overall reduction in tumour burden. These results suggest a novel therapeutic approach for the treatment of disseminated cancer.


Comparison of two techniques in posterior lens dislocations: Scleral suture fixation vs. modified Yamane intrascleral lens fixation.
To compare the use of Yamane flanged intrascleral haptic fixation and scleral suture fixation (SSF) techniques in combination with pars plana vitrectomy (PPV) for treatment of posterior lens dislocations. Patients who underwent PPV and scleral fixated IOL implantation due to subluxation/luxation of the crystalline lens/intraocular lens (IOL) were included in this retrospective study. The Yamane group included patients who underwent Yamane flanged intrascleral haptic fixation technique, while the SSF group consisted of patients who underwent conventional SSF. All patients underwent comprehensive ophthalmologic examinations preoperatively and postoperatively. Intraoperative and postoperative complications were recorded. The Yamane group comprised of 39 eyes of 39 patients, and the SSF group included 35 eyes of 35 patients. Postoperative complications included hyphema (Yamane group: 2/39 (5.1%); SSF group: 0/35 (0%)) IOL decentration (Yamane group: 5/39 (12.8%); SSF group: 0/35 (0%)), corneal edema (Yamane group: 4/39 (10.2%); SSF group: 0/35 (0%)) cystoid macular edema (CME) (Yamane group: 1/39 (2.5%); SSF group: 3/35 (8.5%)) and retinal detachment (Yamane group: 1/39 (2.5%); SSF group: 1/35 (28.5%). The mean surgery time was significantly lower in the Yamane group compared with the SSF group (P<0.001). No cases of hypotony, conjunctival erosion, haptic exposure or endophthalmitis were encountered throughout follow-up. SSF remains a safe and effective technique for management of posterior lens dislocations. The Yamane intrascleral IOL fixation technique is an effective alternative to conventional SSF, which has a relatively steep learning curve. Postoperative complications, including IOL tilt and decentration, may be experienced in the initial cases.


NMR spectroscopic-based metabonomic investigation on the acute biochemical effects induced by Ce(NO3)3 in rats.
An integrated metabonomic approach based on high-resolution (1)H NMR spectroscopy has been applied to the investigation of the acute biochemical effects caused by Ce(NO(3))(3) in rats. Male Wistar rats were separated into 8 groups and each was treated with one of following compounds, mercury II chloride (HgCl(2)), 2-bromoethanamine hydrobromide (BEA), carbon tetrachloride (CCl(4)), alpha-naphthylisothiocyanate (ANIT), and three doses of Ce(NO(3))(3) (i.p. 2, 10 and 50mg/kg body weight). Urine was collected over a 48-h time course, and serum and tissue samples (liver and kidney) were gained after exposure to Ce(NO(3))(3) for 48 h. Histopathology and plasma clinical chemistry were also performed for all the tissue and plasma samples. Urine and serum samples were analyzed by 600 MHz (1)H NMR spectroscopy. All the (1)H NMR spectra were data-processed and analyzed using principal components analysis or hierarchical clustering analysis to show the time- and dose-dependent biochemical variations induced by Ce(NO(3))(3). Metabolic profiles of urinary (1)H NMR spectra from animals treated with Ce(NO(3))(3) exhibited an increase in trimethylamine N-oxide (TMAO), dimethylamine (DMA), dimethylglycine (DMG), taurine (Tau) and amino acids (valine, leucine and isoleucine), together with a decrease in citrate. The (1)H NMR spectral analysis of serum presented the elevation of acetone, acetoacetate, lactate and creatinine levels. These findings indicated the impairment of fatty acid beta-oxidation in liver mitochondria and renal lesions. This work illustrates the high reliability of NMR-based metabonomic approach on the study of the biochemical effects induced by rare earths.


Infusion tomography and ultrasonography of the gallbladder in the diagnosis of acute cholecystitis.
Sixty-three patients with the clinical suspicion of acute cholecystitis were examined with infusion tomography of the gallbladder. Ultrasonography was performed in 51 of these cases. The technique and diagnostic principles of both methods when used in combination is stressed. Thus in a case of gangrenous cholecystitis when opacification of the gallbladder wall may not appear at infusion tomography, ultrasonography may demonstrate signs of gallbladder disease. Infusion tomography, on the other hand, may be of great value if ultrasonography is not informative.


Alkaloids from Portulaca oleracea L.
Five alkaloids (oleraceins A, B, C, D and E) were isolated from Portulaca oleracea L., and their structures determined by spectroscopic methods as 5-hydroxy-1-p-coumaric acyl-2,3-dihydro-1H-indole-2-carboxylic acid-6-O-beta-D-glucopyranoside, 5-hydroxy-1-ferulic acyl-2,3-dihydro-1H-indole-2-carboxylic acid-6-O-beta-D-glucopyranoside, 5-hydroxy-1-(p-coumaric acyl-7'-O-beta-D-glucopyranose)-2,3-dihydro-1H-indole-2-carboxylic acid-6-O-beta-D-glucopyranoside, 5-hydroxy-1-(ferulic acyl-7'-O-beta-D-glucopyranose)-2,3-dihydro-1H-indole-2-carboxylic acid-6-O-beta-D-glucopyranoside and 8,9-dihydroxy-1,5,6,10b-tetrahydro-2H-pyrrolo[2,1-a]isoquinolin-3-one, respectively.


Gas--liquid chromatographic determination of toloxatone in human plasma. Routine analysis of a wide range of drug concentrations using a nitrogen-selective detector.
A selective and sensitive gas--liquid chromatographic (GLC) method has been developed for the measurement of toloxatone at therapeutic concentrations in plasma. The technique is based on a single extraction from plasma at pH 10, the preparation of a trimethylsilyl derivative and detection by a nitrogen-selective detector. The traditional calibration curve, peak-area ratio of toloxatone to internal standard versus toloxatone plasma concentration, was slightly concave for the wide concentration considered (10-3000 ng/ml). As a consequence, the linear least-squares regression analysis gave a negative intercept on the gamma-axis which affected quantitation accuracy of low plasma concentration values. A calibration method taking into consideration the non-linearity of the calibration curve is proposed. The characteristics of the detector were examined in order to analyse response linearity and sensitivity. A linear relationship was found between background current and detector sensitivity.


Global Assessment of Protein Translation in Mammalian Cells Using Polysome Fractionation.
A character of active protein translation is formation of multiple ribosomes, or polysomes, on translating mRNAs. Polysome intensity reflects global cellular translation activity and can be assessed after biochemical fractionations of polysomes. Polysome fractionation begins with immobilizing ribosomes on mRNAs using inhibitors of translation elongation, for example, cycloheximide. Nuclei-free cell lysates are then isolated and layered on the top of a sucrose gradient for ultracentrifugation to separate ribosomal subunits, monosome, and multiple fractions of polysomes by their different sedimentation rates along the sucrose gradient. A density gradient fractionation system including a spectrophotometer reads the RNA absorbance of the flowed gradient and generates the fractions. These fractions can be subjected to further RNA and protein analyses, for example, polysome profiling and mass spectrometry. Here, we present a detailed protocol of polysome fractionation for mammalian cells.


Developmental imperatives in the latter half of life: some clinical implications.
In the latter half of life men tend to shift from active to passive mastery, women the opposite. Four cases are described clinically and are discussed from the point of view of this thesis.


Prediction model of contact forces and IOP during digital palpation of porcine eyes.
Frequent intraocular pressure (IOP) measurements are desirable in the diagnosis and management of glaucoma. Most current tonometers utilize some form of corneal deformation to estimate the IOP, since trans-scleral tonometry suffers from loss of sensitivity. Tran-scleral and trans-palpebral tonometry, however, offer a pathway towards a non-invasive home tonometry. This article presents a mathematical model capturing the relationship between the IOP and the displacements imposed onto the sclera by externally applied forces. Similar to manual digital palpation tonometry, trans-scleral mechanical palpation makes use of two force probes that are advanced in a specific order and distance. Data from the applied forces and displacements, along with concurrent measurements of IOP is used to produce a phenomenological mathematical model. The experiments were carried out on enucleated porcine eyes. Two models are presented. Model 1 predicts IOP vs forces and displacements, while Model 2 predicts the baseline IOP (prior to applying the forces) as a function of the measured forces and displacements. The proposed models result in IOP errors of 1.65 mmHG and 0.82 mmHg, respectively. Model parameters were extracted using least-squares-based system identification methods. The results show that the proposed models can be used to estimate the baseline IOP with accuracy of ±1 mmHg over a pressure range of 10-35 mmHg, solely from measurement of tactile forces and displacements.


Exogenous doxorubicinol induces cardiotoxic effects in rats.
An investigation was performed in the rat to assess the cardiotoxic effects of exogenous doxorubicinol compared with those induced by an equimolar dose of its parent drug doxorubicin. Rats received synthetic doxorubicinol or doxorubicin 3 mg/kg i.v. weekly for 3 weeks and were observed for a further period of 4 weeks. Survival, body growth, ECG parameters, and heart histopathology were studied. Doxorubicin markedly affected rat body growth, as well as several ECG parameters such as S alpha T, R alpha T, alpha TP and T-wave. Typical cardiac histological alterations were also induced by doxorubicin. In a similar way, doxorubicinol treatment was associated with a significant inhibition of rat body weight increase, and the appearance of ECG alterations as well as both macro- and microscopic signs of cardiac tissue damage. However these effects were delayed in time and their severity was lower compared with doxorubicin. Overall results indicate that doxorubicinol induces a doxorubicin-like toxic syndrome mainly affecting the heart, although to a lower degree of severity than that caused by the parent drug. It is suggested that the lower toxic potential displayed by doxorubicinol might be due at least in part to its greater polarity and a consequently lower cardiac tissue uptake compared with doxorubicin.


Laparophobia: a cognitive perspective on appetite control in anorexia nervosa.
Decades of research have demonstrated that anorexia nervosa (AN) may be associated with aberrant cognition, yet, its role in maintaining stringent dieting has received relatively little attention from mainstream researchers of eating disorders. The purpose of the present article is to highlight cognitive ('top-down') factors that are considered responsible for anticipatory anxiety of stoutness and frank fat-phobia (laparophobia). A cognitive model proposed departs from the formulation suggesting that phobia of over-eating is superimposed on avoidant tendencies ('environmental autonomy syndrome'), whereas excessive exercising becomes a natural coping strategy with laparophobia, an instrument of reward. AN ideation involves complex neuronal circuitries and multiple neurochemical components that may conceivably represent a mirror image of those underlying obesity. The emphasis on phobia and aberrant membrane excitability akin to channelopathies behoves the clinicians to be aware of potential uses of drugs acting at the gamma-aminobutyric acid and the N-methyl-D-aspartate/AMPA [2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl) propionic acid] receptors sites as the adjuncts to conventional agents in managing AN.


Direct-to-Consumer Marketing: A Complementary Approach to Traditional Dissemination and implementation Efforts for Mental Health and Substance Abuse Interventions.
The overall chasm between those who need treatment for mental health and substance abuse (M/SU) and those who receive effective treatment consists of two, interrelated gaps: the research-to-practice gap and the treatment gap. Prior efforts to disseminate evidence-based practice (EBP) for M/SU have predominantly targeted the research-to-practice gap, by focusing efforts toward treatment providers. This article introduces direct-to-consumer (DTC) marketing that targets patients and caregivers as a complementary approach to existing dissemination efforts. Specific issues discussed include: rationale for DTC marketing based on the concept of push versus pull marketing; overview of key stakeholders involved in DTC marketing; and description of the Marketing Mix planning framework. The applicability of these issues to the dissemination of EBP for M/SU is discussed.


Chronic α1-Na/K-ATPase inhibition reverses the elongation of the axon initial segment of the hippocampal CA1 pyramidal neurons in Angelman syndrome model mice.
Angelman syndrome (AS) is a neurodevelopmental disorder caused by the loss of function of the maternal UBE3A gene. The hippocampus is one of the most prominently affected brain regions in AS model mice, manifesting in severe hippocampal-dependent memory and plasticity deficits. Previous studies in AS mice reported an elongated axon initial segment (AIS) in pyramidal neurons (PNs) of the hippocampal CA1 region. These were the first reports in mammals to show AIS elongation in vivo. Correspondingly, this AIS elongation was linked to enhanced expression of the α1 subunit of Na+/K+-ATPase (α1-NaKA). Recently, it was shown that selective pharmacological inhibition of α1-NaKA by marinobufagenin (MBG) in adult AS mice rescued the hippocampal-dependent deficits via normalizing their compromised activity-dependent calcium (Ca+2) dynamics. In the herein study, we showed that a chronic selective α1-NaKA inhibition reversed the AIS elongation in hippocampal CA1 PNs of adult AS mice, and differentially altered their excitability and intrinsic properties. Taken together, our study is the first to demonstrate in vivo structural plasticity of the AIS in a mammalian model, and further elaborates on the modulatory effects of elevated α1-NaKA levels in the hippocampus of AS mice.


Inhibition of Anatid Herpes Virus-1 replication by small interfering RNAs in cell culture system.
RNA interference (RNAi) mediated by double stranded small interfering RNA (siRNA) is a novel mechanism of post-transcriptional gene silencing. It is projected as a potential tool to inhibit viral replication. In the present paper, we demonstrate the suppression of replication of an avian herpes virus (Anatid Herpes Virus-1, AHV-1) by siRNA mediated gene silencing in avian cells. The UL-6 gene of AHV-1 that codes for a protein involved in viral packaging was targeted. Both cocktail and unique siRNAs were attempted to evaluate the inhibitory potential of AHV-1 replication in duck embryo fibroblast (DEF) cell line. DEF cells were chemically transfected with different siRNAs in separate experiments followed by viral infection. The observed reduction in virus replication was evaluated by cytopathic effect, viral titration and quantitative real time PCR (QRT-PCR). Among the three siRNA targets used the unique siRNA UL-B sequence was found to be more potent in antiviral activity than the cocktail and UL6-A-siRNA sequences.


Synthesis, reactive oxygen species generation and copper-mediated nuclease activity profiles of 2-aryl-3-amino-1,4-naphthoquinones.
Here we report a series of 2-aryl-3-amino-1,4-naphthoquinones that generated reactive oxygen species (ROS) such as superoxide and hydrogen peroxide upon incubation in pH 7.4 under ambient aerobic conditions. ROS generation from these compounds was sensitive to structural modifications at the 3-amino position and a 2-aryl substituent promoted ROS generation. A number of these compounds were found to induce DNA damage in the presence of Cu(II) without any added reducing agent. Our data suggests that 2-aryl-3-amino-1,4-naphthoquinones' propensity to produce ROS correlated well with its DNA damage inducing ability. 2-Phenyl-3-pyrrolid-1-yl-1,4-naphthoquinone (22) was found to damage DNA at 1 μM suggesting that these compounds may have therapeutic relevance in targeting cancers which over-express Cu(II).


The PIM1 kinase promotes prostate cancer cell migration and adhesion via multiple signalling pathways.
The ability of cells to migrate and form metastases is one of the fatal hallmarks of cancer that can be conquered only with better understanding of the molecules and regulatory mechanisms involved. The oncogenic PIM kinases have been shown to support cancer cell survival and motility, but the PIM-regulated pathways stimulating cell migration and invasion are less well characterized than those affecting cell survival. Here we have identified the glycogen synthase kinase 3β (GSK3B) and the forkhead box P3 (FOXP3) transcription factor as direct PIM targets, whose tumour-suppressive effects in prostate cancer cells are inhibited by PIM-induced phosphorylation, resulting in increased cell migration. Targeting GSK3B is also essential for the observed PIM-enhanced expression of the prostaglandin-endoperoxide synthase 2 (PTGS2), which is an important regulator of both cell migration and adhesion. Accordingly, selective inhibition of PIM activity not only reduces cell migration, but also affects integrin-mediated cell adhesion. Taken together, these data provide novel mechanistic insights on how and why patients with metastatic prostate cancer may benefit from therapies targeting PIM kinases, and how such approaches may also be applicable to inflammatory conditions.


Treatment of Dissecting Distal Vertebral Artery (V4) Aneurysms With Flow Diverters.
Dissecting aneurysms of the intracranial vertebral arteries are rare; however, treatment of these presents multiple challenges, including high risk of rebleeding, development of thromboembolic strokes, and progressive partial thrombosis. Flow diverters, such as Pipeline Endovascular Devices (PEDs; Covidien, Medtronic Inc, Dublin, Ireland), have emerged as a potential treatment option. To present our experience with patients treated at our institution with PEDs for dissecting distal vertebral artery (V4 segment) aneurysms. A retrospective search of our prospectively maintained database was performed between January 2014 and December 2016. We queried our database for all patients treated with PED for dissecting aneurysms of the V4 segment. Information was gathered including demographics, the location and morphology of the aneurysm, the clinical presentation, specific form of treatment, complications, antiplatelet medication regimen, and follow-up time. There were a total of 9 patients with dissecting V4 aneurysms treated with PED during the study period. All were treated initially with an average of 1.2 PEDs. All patients were followed with at least one repeat diagnostic angiogram and there was no residual aneurysm seen in 8 of 9 cases. In those that presented with neurological deficits, there was an average improvement in modified Rankin Scale of 2.85 points. PED is a safe and effective tool that can be used to treat ruptured dissecting aneurysms of this specific segment of the posterior circulation, but it does require close management of antiplatelet therapy in the setting of subarachnoid hemorrhage and close angiographic follow-up.


Equity of access under Korean national long-term care insurance: implications for long-term care reform.
The national long-term care insurance was implemented in July 2008. Few studies have been conducted with representative national survey data since the long-term care insurance was introduced. Therefore, this study examines the extent to which equity in the use of long-term care has been achieved in Korea. The Aday-Andersen model was used as a conceptual model, based on the Korean Health Panel Study which was conducted in 2011. Descriptive and logistic regression analysis was performed to examine the relationship between the dependent and independent variables and the relative importance of factors as predictors of utilization. The results of this study indicated that those who rated his or her health to be fair, good, and very good, had no limited activities, were disabled, and had insurance coverage were more likely to use long-term care services, respectively. Their decision to use long-term care was primarily affected by need (health status, limited activity, disability) and enabling (insurance coverage) factors. The findings also indicated that the introduction of a national long-term care insurance program did not yield a fully equitable distribution of services. Long-term care reforms in Korea should continue to concentrate on expanding insurance coverage and reducing the inequities reflected in disparities in consumer cost-sharing and associated patterns of utilization across plans. The subsequent impact on managed care and expenditures need to be more fully understood.


The effect of pharmacological modification of gastric emptying and mouth-to-caecum transit time on the absorption of sugar probe marker molecules of intestinal permeability in normal man.
The present study examined the hypothesis that altered motility of the gastrointestinal tract affects absorption of probe markers of intestinal permeability. Seven healthy subjects, aged 32-44 years, received saline, 600 micrograms atropine or 10 mg metoclopramide in randomized order at weekly intervals. After 10 min they ingested a test solution containing 5 g lactulose, 5 g mannitol and 2 g 3-O-methyl glucose in 100 ml tap water. The molarity of the solution was 542 mmol l-1 and the dose administered was 80 ml m-2 body surface area. Gastric emptying was measured by ultrasound, mouth-to-caecum transit time by breath hydrogen analysis and sugar concentrations by gas-liquid chromatography. Gastric emptying half-times (min) were [mean (95% confidence intervals)] 14.9 (11:4-18.5) after saline, 22 (18.7-25.2) after atropine and 10.3 (7.0-12.6) after metoclopramide (P less than 0.002). Transit times (min) were 68.9 (52-85.2) after saline, 143 (126-159) after atropine and 38 (21.2-54.5) after metoclopramide; P less than 0.0001. Analysis of plasma levels of mannitol and 3-O-methyl glucose showed a significant within-subject effect of drug with time (P less than 0.03). Urinary excretion of mannitol in the first 5 h after ingestion of the test solution was 1256 (974-1620) mg after saline, 1560 (1210-2013) mg after atropine and 955 (740-1232) mg after metoclopramide (P less than 0.03). There were no significant differences in lactulose and 3-O-methyl glucose urinary excretion between drug treatments.(ABSTRACT TRUNCATED AT 250 WORDS)


Suicide among childhood cancer survivors in Slovenia.
Suicide is one of the causes of late mortality among childhood cancer survivors. The aim of our study was to analyse the risk of suicide among childhood cancer survivors compared with that of the general population of Slovenia. This retrospective study included patients with childhood cancer registered at the Cancer Registry of Slovenia between 1978-2008, with an observation period of 1978-2010. Childhood cancer patients and control subjects from the general population of Slovenia were matched by sex, year and age at the beginning of follow-up and time of follow-up in years. Data on the general population of Slovenia were obtained from the Statistical Office of the Republic of Slovenia. A total of 1647 patients were recorded in the Cancer Registry as having cancer during childhood, with 3 patients committing suicide. All three were male. Their age at diagnosis of cancer was 12, 13 and 2 years old; their age at suicide was 19, 32 and 28 years old. The mechanism of death was asphyxiation in all three deaths. The calculation of the expected number of suicides in the group of individuals with childhood cancer from the general Slovene population revealed the number of 3.16 persons. The comparison of the observed and expected probability showed that there was no statistically significant difference in the suicide rate between childhood cancer survivors and the general population of Slovenia.


Plasma C-reactive protein as a marker of cardiac allograft vasculopathy in heart transplant recipients.
This study was initiated to determine whether heart transplant recipients (HTRs) with cardiac allograft vasculopathy (CAV) have increased levels of high-sensitivity C-reactive protein (hsCRP) and to examine whether an increase in hsCRP after heart transplantation predicts the development of CAV. Furthermore, the effect of pravastatin on plasma levels of hsCRP in HTRs was investigated. The relationship between CAV and hsCRP, as well as the effect of statins on hsCRP in HTRs, has not been well established. On referral for their annual angiographic control study, 150 consecutive HTRs (mean 6.5 years since transplantation) were included. Plasma levels of hsCRP were measured before angiography and compared with patients with (n = 52) and without (n = 98) CAV. In 49 of these patients, we additionally analyzed hsCRP in blood samples stored from their six-month visit after the transplantation procedure. Furthermore, in a randomized, crossover study, hsCRP was analyzed in 17 male HTRs before and after six weeks of treatment with 20 mg pravastatin. Median levels of CRP were elevated among patients with CAV compared with those with normal angiograms [3.86 (1.78 to 7.00) vs. 1.08 (0.72 to 2.13) mg/l, p < 0.001]. Prospectively evaluated hsCRP levels from six months to follow-up were significantly higher among those who developed CAV compared with those with normal angiograms [+2.76 (1.56 to 5.00) vs. +0.07 (-0.57 to 0.41) mg/l, p < 0.001]. On multivariate analysis, the increase in hsCRP was the only significant predictor of CAV. Six weeks of treatment with pravastatin significantly reduced hsCRP levels by 25%, without any relation to changes in lipid values. Elevated plasma levels of CRP are associated with angiographic evidence of CAV, and the increase in hsCRP is a strong predictor of development of CAV. Statin treatment reduces levels of hsCRP and should be used in HTRs, regardless of their lipid levels.


(3S*,4S*,E)-tert-Butyl 3,4-dibromo-5-oxo-cyclo-oct-1-ene-carboxyl-ate.
The title compound, C(13)H(18)Br(2)O(3), was prepared by a bromination reaction of (1E,3Z)-methyl 5-oxocyclo-octa-1,3-diene-carboxyl-ate, which was obtained by an ep-oxy-dation reaction of tert-butyl cyclo-oct-1,3-diene-carboxyl-ate. The crystal structure confirms unequivocally the absolute configuration of both chiral centres to be S. In the crystal, C-H⋯O inter-actions link the mol-ecules into chains running along the c axis.


A biological method for studying the interaction between platelets and vascular endothelium.
A segment of fresh rabbit thoracic aorta (RbA) was turned inside out and superfused (1.5 ml/min) with citrated (3.8%) or heparinized (10 U/ml) blood of rabbit and the superfusate was discarded. RbA gained in weight due to deposition of thrombi on its endothelial surface. These thrombi were mainly composed of platelets. The interaction between platelets and endothelium was augmented in RbAs from animals with atherosclerosis and in RbAs pretreated with aspirin (110 microM) or 15-HPETE (150 microM) or by the enzymatic system generating oxygen free radicals (xanthine:xanthine oxidase - 100 microM: 0.1 U/ml). On the other hand, this interaction was impaired by superoxide dismutase (20 U/ml) or catalase (0.2 U/ml). Finally, the dissipation of thrombi by thromboxane A2-synthetase inhibitor--dazoxiben was found to be related to an increase in endothelial generation of prostacyclin.


Assessing the impact of urban form and urbanization process on tropospheric nitrogen dioxide pollution in the Yangtze River Delta, China.
Optimizing urban form through urban planning and management policies can improve air quality and transition to demand-side control. Nitrogen dioxide (NO2) in the urban atmosphere, mainly emitted by anthropogenic sources such as industry and vehicles, is a key precursor of fine particles and ozone pollution. Both NO2 and its secondary pollutants pose health risks for humans. Here we assess the interactions between urban forms and airborne NO2 pollution in different cities with various stages of urbanization in the Yangtze River Delta (YRD) in China, by using the machine learning and geographical regression model. The results reveal a strong correlation between urban fragmentation and tropospheric NO2 vertical column density (TVCD) in YRD cities in 2020, particularly those with lower or higher levels of urbanization. The correlation coefficients (R2) between NO2 TVCD and the largest patch index (a metric of urban fragmentation) in different cities are greater than 0.8. For cities at other urbanization stages, population and road density are strongly correlated with NO2 TVCD, with an R2 larger than 0.61. This study highlights the interdependence among urbanization, urban forms, and air pollution, emphasizing the importance of customized urban landscape management strategies for mitigating urban air pollution.


rh-ES and Chemotherapy in Advanced Gastrointestinal Cancer in China: A Meta-analysis.
The purpose of this study was to evaluate the efficacy and safety of recombinant human endostatin (rh-ES) combined with chemotherapy in advanced gastrointestinal tumors in China. A literature search was performed in PubMed, Medline, Springer, Elsevier Science Direct, Weipu, Wanfang, and China National Knowledge Infrastructure (CNKI), with the last report through September 2019. The included research was scored using a modified Jadad scale, and a meta-analysis was performed using RevMan 5.3 software. Twenty articles including 905 participants (experimental group [rh-ES combined with chemotherapy] 459; control group [chemotherapy alone] 446) were considered. The total effective rate for the experimental group in advanced gastrointestinal tumors was higher than that of the control group (P<0.05). No significant difference in adverse reactions was seen between the two groups (P>0.05). The short-term efficacy of rh-ES combined with chemotherapy for advanced gastrointestinal tumors was better, with fewer adverse reactions.


Ion and inhibitor binding of the double-ring ion selectivity filter of the mitochondrial calcium uniporter.
The calcium (Ca2+) uniporter of mitochondria is a holocomplex consisting of the Ca2+-conducting channel, known as mitochondrial calcium uniporter (MCU), and several accessory and regulatory components. A previous electrophysiology study found that the uniporter has high Ca2+ selectivity and conductance and this depends critically on the conserved amino acid sequence motif, DXXE (Asp-X-X-Glu) of MCU. A recent NMR structure of the MCU channel from Caenorhabditis elegans revealed that the DXXE forms two parallel carboxylate rings at the channel entrance that seem to serve as the ion selectivity filter, although direct ion interaction of this structural motif has not been addressed. Here, we use a paramagnetic probe, manganese (Mn2+), to investigate ion and inhibitor binding of this putative selectivity filter. Our paramagnetic NMR data show that mutants with a single carboxylate ring, NXXE (Asn-X-X-Glu) and DXXQ (Asp-X-X-Gln), each can bind Mn2+ specifically, whereas in the WT the two rings bind Mn2+ cooperatively, resulting in ∼1,000-fold higher apparent affinity. Ca2+ can specifically displace the bound Mn2+ at the DXXE site in the channel. Furthermore, titrating the sample with the known channel inhibitor ruthenium 360 (Ru360) can displace Mn2+ binding from the solvent-accessible Asp site but not the inner Glu site. The NMR titration data, together with structural analysis of the DXXE motif and molecular dynamics simulation, indicate that the double carboxylate rings at the apex of the MCU pore constitute the ion selectivity filter and that Ru360 directly blocks ion entry into the filter by binding to the outer carboxylate ring.


Selective dendritic fluorescent sensors for Zn(II).
A series of dendritic 8-hydroxyquinoline (8-HQ) and 5-dialkyl(aryl)aminomethyl-8-HQ derivatives were synthesized and their fluoroionophoric properties toward representative alkali, alkaline earth, group IIIA and transition metal ions were investigated. Among the selected ions, Zn(II) enhanced the fluorescence of N-di-(methoxycarbonylethyl)aminoethyl-3-[4-(8-hydroxyquinolin-5-ylmethyl)piperazin-1-yl]-propanoic amide] (7) by 31-fold, while Al(III) caused enhancement to some extent. The absence of any significant fluorescence enhancement by the other ions examined renders 7a highly useful Zn(II)-selective fluorescent sensor.


Clinical identification of older adults with hypovitaminosis D: Feasibility, acceptability and accuracy of the 'Vitamin D Status Diagnosticator' in primary care.
The 16-item Vitamin D Status Diagnosticator (VDSD) tool was built to diagnose, without resorting to a blood test, hypovitaminosis D among healthy seniors living at home. The objective of this study was to determine the feasibility of the VDSD by general practitioners (GPs), the acceptability to outpatients, and the diagnostic accuracy of the VDSD in primary care. Ten French GPs were asked from March to May 2015 to perform the VDSD in 30 consecutive outpatients aged ≥70years, living at home, presenting with a history of recurrent falls and/or osteomalacia, and taking no vitamin D supplements. Feasibility was defined as a proportion >70% of VDSD forms fully completed. Completing time, acceptance rate and, when applicable, the reasons for non-completing were assessed, together with the metrological properties of the VDSD to identify hypovitaminosis D ≤75nmol/L, or ≤50nmol/L or ≤25nmol/L. Of the 242 enrolled patients, 218 (mean, 79 ± 6years; 46.3% women) received a VDSD, i.e. completing rate of 90.1%, with an average completing time of 1 min and 48s. The acceptance rate by the patients was 98.8%, and all GPs were satisfied with the tool. The VDSD identified hypovitaminosis D≤75nmol/L with an accuracy of 84.7%, hypovitaminosis D≤50nmol/L with accuracy 75.4%, and hypovitaminosis D≤25nmol/L with accuracy 71.0% (n = 183 assays). The 16-item VDSD can be considered as feasible, acceptable and accurate for diagnosing hypovitaminosis D among older outpatients in primary care without resorting to an expensive blood test.


Different signaling pathways inhibit DNA methylation activity and up-regulate IFN-gamma in human lymphocytes.
DNA methylation is recognized increasingly for its prominent role in controlling diverse immune processes. In this study, we show that in Jurkat T cells and fresh peripheral lymphocytes, short-time incubation with protein kinase C activators or phosphatase inhibitors down-regulate DNA methylation activity in a dose-dependent manner. This inhibition correlates with the induction of the interferon-gamma (IFN-gamma) gene, which contains several CG sequences in its promoter. The expression of mRNA and protein of the different DNA methyltransferases did not decrease after the treatment. In addition, sulfydryl reagents have a strong inhibitory effect on DNA methylation activity and also induce IFN-gamma gene expression, thus suggesting a link between both effects.


A longitudinal study of antigen expression in epithelial ovarian cancer.
The extent to which the antigenic phenotype of human epithelial ovarian cancer changes during the course of the disease is an issue that must be addressed in order to maximize the potential of antibody-directed imaging and therapy. We have obtained tumor specimens at two separate operations from ten patients with epithelial ovarian cancer and typed these specimens with a panel of 19 monoclonal antibodies to cell surface glycoprotein and carbohydrate antigens including blood group antigens. Antibodies with relatively high specificity for malignant cells as well as those detecting more widely distributed epithelial antigens were used in the study. Mean time between the two operations was 8.5 months. Five patients received intraperitoneal therapy during the interval between the two operations, including platinum-based regimens (four patients) and tumor necrosis factor (one patient). Four patients received intravenous platinum-based chemotherapy; one received no treatment. Frozen sections of specimens were stained with the antibodies by the indirect immunoperoxidase technique. Antigenic phenotypes were found to be unrelated to the patient's age, stage, tumor grade, histologic cell type, prior chemotherapy, and interval between operations. Most significantly, little difference was seen in antigenic expression between tumors obtained at the two operations for either the cell surface or blood group markers. Variations in the staining pattern were seen with antibody B72.3 and, to some extent, with the anti-blood group antibodies, which are known for producing heterogeneous staining. The antigenic phenotype of the tumor specimens in a given patient as determined immunohistochemically by our panel of antibodies showed only minor variation between operations, even under the selective pressures of chemotherapy and immunotherapy.


Design characteristics and clinical implementation of a newly designed indwelling carotid artery shunt.
The author has developed a new silicone carotid artery shunt (Loftus carotid endarterectomy shunt, Integra NeuroCare, Plainsboro, New Jersey) which offers several advantages over previously available commercial products. It is designed as an indwelling 15 cm (short) shunt, without an external loop. The silicone material makes for simple insertion and the ends are beveled and tapered to minimize dislodgement of any atheromatous material. At its proximal end a built-up bulb has been placed to facilitate securing by a Rummel tourniquet. At the distal end of the shunt no bulb is necessary. A broad black band has been applied to its center to allow for immediate visual inspection of shunt migration or misplacement. In contrast to previous designs, no metal reinforcement is necessary in this shunt. It is supplied in two sizes in a kit which also includes a pair of disposable scissors hooked on the end for easy shunt transection at the time of removal. The shunt is best accompanied by a specialized shunt clamp (Loftus shunt clamp, Scanlan Medical Instruments, St. Paul, Minnesota) which has been designed with atraumatic jaws to secure it with minimal closing force in the internal carotid artery and to prevent back-bleeding around it. Clinical experience with the shunt has been extensive and satisfactory. Both the shunt kit and the shunt clamps are now available for commercial distribution.


Dermasence refining gel modulates pathogenetic factors of rosacea in vitro.
Over the counter cosmetics sold for local treatment of slight to moderate rosacea often state the claim of actively modulating rosacea pathogenesis. Factors involved in the pathogenesis of this common yet complex skin disorder include kallikrein-related peptidase 5 (KLK5), LL-37, as well as protease-activated receptor 2 (PAR2) and vascular endothelial growth factor (VEGF). The objective was to prove the modulating effect of the cosmetic skin care agent Dermasence Refining Gel (DRG) on factors involved in rosacea pathogenesis. We analyzed the effect of DRG on the expression of KLK5, LL-37, PAR2, and VEGF in an in vitro skin model of human reconstituted epidermis. The expression of CAMP (LL-37 gene, fold change -4.19 [±0.11]), VEGFA (fold change -2.55 [±0.12]) and PAR2 (-1.33 [±0.12]) was reduced, KLK5 expression increased (fold change 2.06 (±0.08)) after 18 h of treatment with DRG in comparison to treatment with the matrix gel only. The reduction in CAMP expression was significant (P<.01). The protein expression of all four inflammatory markers was markedly reduced after 18 hours of DRG treatment in comparison to baseline (0 hour), by measure of fluorescence intensity. We show evidence explaining the anti-inflammatory effect of Dermasence Refining Gel in rosacea pathogenesis in vitro. The adjunctive use of DRG in mild to moderate rosacea as a topical cosmetic seems medically reasonable.


Catch-relaxing peptide isolated from Mytilus pedal ganglia.
A peptide that relaxes catch tension of the anterior byssus retractor muscle of Mytilus edulis was purified from pedal ganglion extracts of the mussel. Its primary structure was determined to be H-Ala-Met-Pro-Met-Leu-Arg-Leu-NH2. This peptide was found to have not only catch-relaxing action on the byssus retractor muscle but also modulatory actions on contractions in various molluscan muscles.


Understanding the comorbidity between posttraumatic stress severity and coronary artery disease using genome-wide information and electronic health records.
The association between coronary artery disease (CAD) and posttraumatic stress disorder (PTSD) contributes to the high morbidity and mortality observed for these conditions. To understand the dynamics underlying PTSD-CAD comorbidity, we investigated large-scale genome-wide association (GWA) statistics from the Million Veteran Program (MVP), the UK Biobank (UKB), the Psychiatric Genomics Consortium, and the CARDIoGRAMplusC4D Consortium. We observed a genetic correlation of CAD with PTSD case-control and quantitative outcomes, ranging from 0.18 to 0.32. To investigate possible cause-effect relationships underlying these genetic correlations, we performed a two-sample Mendelian randomization (MR) analysis, observing a significant bidirectional relationship between CAD and PTSD symptom severity. Genetically-determined PCL-17 (PTSD 17-item Checklist) total score was associated with increased CAD risk (odds ratio = 1.04; 95% confidence interval, 95% CI = 1.01-1.06). Conversely, CAD genetic liability was associated with reduced PCL-17 total score (beta = -0.42; 95% CI = -0.04 to -0.81). Because of these opposite-direction associations, we conducted a pleiotropic meta-analysis to investigate loci with concordant vs. discordant effects on PCL-17 and CAD, observing that concordant-effect loci were enriched for molecular pathways related to platelet amyloid precursor protein (beta = 1.53, p = 2.97 × 10-7) and astrocyte activation regulation (beta = 1.51, p = 2.48 × 10-6) while discordant-effect loci were enriched for biological processes related to lipid metabolism (e.g., triglyceride-rich lipoprotein particle clearance, beta = 2.32, p = 1.61 × 10-10). To follow up these results, we leveraged MVP and UKB electronic health records (EHR) to assess longitudinal changes in the association between CAD and posttraumatic stress severity. This EHR-based analysis highlighted that earlier CAD diagnosis is associated with increased PCL-total score later in life, while lower PCL total score was associated with increased risk of a later CAD diagnosis (Mann-Kendall trend test: MVP tau = 0.932, p < 2 × 10-16; UKB tau = 0.376, p = 0.005). In conclusion, both our genetically-informed analyses and our EHR-based follow-up investigation highlighted a bidirectional relationship between PTSD and CAD where multiple pleiotropic mechanisms are likely to be involved.


Intrauterine growth restriction and later cardiovascular function.
Intrauterine growth restriction is one of the most common obstetric conditions, affecting 7-10% of fetuses. Affected fetuses are actually exposed in utero to an adverse environment during the highly critical time of development and may face life-long health consequences such as increased cardiovascular risk in adulthood. Already in utero, fetuses affected by growth restriction show remodeled hearts with signs of systolic and diastolic dysfunction. Cardiovascular remodeling persist into postnatal life, from the neonatal period to adolescence, suggesting a primary fetal cardiac programming that might explain the increased cardiovascular risk later in life. In this review we summarize the current evidence on fetal cardiovascular programming in fetuses affected by growth restriction, its consequences later and possible strategies from which they could benefit to reduce their cardiovascular risk.


Career Paths and Satisfaction of Dental Hygienists Holding Master's and Doctoral Degrees.
Purpose: There is an increased need for dental hygienists with advanced degrees to meet the demands of a complex health care system in addition to advancing the dental hygiene profession. The purpose of this study was to explore the career paths and satisfaction of dental hygienists with master's and doctoral degrees.Methods: A qualitative descriptive phenomenological research design was used with a purposive sample of dental hygienists (n=20) who had master's and doctoral degrees. A virtual web-based videoconferencing platform was used to conduct focus groups and utilize a national sample. Focus groups were audio recorded and transcribed. Data was analyzed for themes manually and with qualitative analysis software.Results: The results showed a wide range of career paths such as: administrator, lawyer, entrepreneur, dental therapist, dentist, nurse, educator, researcher, public speaker, consultant, editor, state oral health program coordinator, and marketing. The results also indicated that participants were satisfied and valued the pursuit of their advanced education. The six themes that emerged included: expanded opportunities; personal growth; professional growth; credibility; it's an investment; and just do it, don't overanalyze or second guess yourself.Conclusion: Findings suggest satisfaction with advanced education as well as a wide variety of career paths. Participants also endorsed more dental hygienists being educated at the master's and doctoral level to advance the profession of dental hygiene.


Patulous Eustachian tube (PET), a practical overview.
Symptoms of patulous Eustachian tube (ET), particularly autophony, can overlap with other conditions, and can arise from a variety of causes. We review the pathophysiology of "speech hyper-resonance syndromes", and possible mechanisms, including resonances in the tympanic membrane, Eustachian tube and nasopharynx. Treatment can be directed at the eardrum or the ET depending on site of pathology. We review typical presentations, examination findings, and useful clinical tests to distinguish PET from other disorders, and our philosophy of management.


Sonographic markers associated with adverse neonatal outcomes among fetuses with gastroschisis: an 11-year, single-center review.
Gastroschisis complicates 1 in 2000 births and is readily identifiable during prenatal ultrasound scans. Outcomes in fetuses that are affected by gastroschisis vary widely from stillbirth or neonatal death to uncomplicated surgical correction, which makes prenatal counseling challenging. The goal of our study was to identify sonographic markers that are associated with perinatal death and morbidity that include significant bowel injury, necrotizing enterocolitis, and the need for bowel resection in fetuses with gastroschisis. We identified a cohort of fetuses that were diagnosed with gastroschisis from 2003-2014. Sonographic markers that were reviewed included growth restriction, abdominal circumference, oligohydramnios, bowel dilation, and gastric bubble characteristics. We evaluated these markers both at diagnosis and near delivery. Four adverse perinatal outcomes were assessed: perinatal death, necrotizing enterocolitis, need for bowel resection, and a composite of significant bowel injury, which included a diagnosis of bowel atresia or necrosis at the time of surgical exploration. Logistic regression was performed to calculate odds ratios and 95% confidence intervals for each marker and outcome. One hundred seventy-seven patients were identified, and 154 of these patients met inclusion criteria after exclusions for delivery <24 weeks gestation, other associated anomalies, lethal karyotype, or lost to follow-up evaluation. Markers at the time of diagnosis (median gestational age, 21 weeks [25th,75th interquartile range, 19, 24 weeks]) that were associated with perinatal death were abdominal circumference <5th percentile (odds ratio, 5.56; 95% confidence interval, 1.25-24.76), abnormal gastric bubble (odds ratio, 11.20; 95% confidence interval, 2.15-58.33), and abnormal stomach location (odds ratio, 17.1; 95% confidence interval, 2.99-97.85). An abnormal stomach location (odds ratio, 5.53; 95% confidence interval, 1.03-29.72) before delivery was associated with perinatal death. Gastric dilation before delivery (odds ratio, 4.36; 95% confidence interval, 1.10-17.34)] was associated with the need for bowel resection. Early sonographic markers of increased perinatal mortality rates include abdominal circumference <5th percentile and an abnormal gastric bubble.


Safety, efficacy and immunogenicity evaluation of the SAG2 oral rabies vaccine in Formosan ferret badgers.
Since 2013, rabies cases have been reported among Formosan ferret badgers in Taiwan, and they have been shown to be the major reservoirs for Taiwanese enzootics. To control and eradicate rabies, the authorities plan to implement a vaccination programme. Before distributing live vaccines in the field, this study assessed the safety, efficacy, and immunogenicity of SAG2 vaccine on ferret badgers by direct oral instillation. After application of 109 TCID50/dose, no virus was excreted into the oral cavity 1-7 days post-application, and safety was also satisfactorily verified over a 266-day period. Moreover, despite the low level of rabies virus neutralising antibodies induced after vaccination of a 108 TCID50/dose, the efficacy assessment revealed a 100% survival rate (15/15) of vaccinees and an 87.5% fatality rate (7/8) in control animals after a challenge on the 198th day post-vaccination. The immunisation and protection rates obtained more than 6 months after a single vaccination dose demonstrated that SAG2 is an ideal vaccine candidate to protect Formosan ferret badgers against rabies in Taiwan.


Heterogeneous electron-transfer rate constants for fe(h(2)o)(6)(3+/2+) at metal oxide electrodes.
The title redox couple, in noncoordinating perchlorate medium, has been used to probe the electrochemical behavior of different IrO2-based electrodes; pure oxide electrodes, as well as IrO2-SnO2 mixtures, have been investigated. The obtained results show that the electrode material strongly affects the electrochemical response. A tentative explanation, based on the different point of zero charge of the considered oxides, is presented.


Aging and glycoxidant stress.
Aging and related diseases are accompanied by increased Oxidative Stress (OS) and accumulation of Advanced Glycation End products (AGEs). One important component of AGEs accumulation with aging appears to be the sustained exposure to dietary AGE (dAGEs), which contributes to overloading of anti-AGE receptors and depletion of anti-oxidant reserves. In this review, we present experimental animal and human data which support this postulation. Lowering the content of AGEs in the normal diet significantly prevents AGEs accumulation and the increased OS caused by aging and also extends lifespan in mice. In humans, short-term trials indicate that a Low AGEs diet reduces oxidant burden and inflammatory markers. Long-term studies are in progress and will help establish definitive causality between age-related disease states and modern dietary practices in Western societies.


Phenome-wide association study and precision medicine of cardiovascular diseases in the post-COVID-19 era.
SARS-CoV-2 infection causes injuries of not only the lungs but also the heart and endothelial cells in vasculature of multiple organs, and induces systemic inflammation and immune over-reactions, which makes COVID-19 a disease phenome that simultaneously affects multiple systems. Cardiovascular diseases (CVD) are intrinsic risk and causative factors for severe COVID-19 comorbidities and death. The wide-spread infection and reinfection of SARS-CoV-2 variants and the long-COVID may become a new common threat to human health and propose unprecedented impact on the risk factors, pathophysiology, and pharmacology of many diseases including CVD for a long time. COVID-19 has highlighted the urgent demand for precision medicine which needs new knowledge network to innovate disease taxonomy for more precise diagnosis, therapy, and prevention of disease. A deeper understanding of CVD in the setting of COVID-19 phenome requires a paradigm shift from the current phenotypic study that focuses on the virus or individual symptoms to phenomics of COVID-19 that addresses the inter-connectedness of clinical phenotypes, i.e., clinical phenome. Here, we summarize the CVD manifestations in the full clinical spectrum of COVID-19, and the phenome-wide association study of CVD interrelated to COVID-19. We discuss the underlying biology for CVD in the COVID-19 phenome and the concept of precision medicine with new phenomic taxonomy that addresses the overall pathophysiological responses of the body to the SARS-CoV-2 infection. We also briefly discuss the unique taxonomy of disease as Zheng-hou patterns in traditional Chinese medicine, and their potential implications in precision medicine of CVD in the post-COVID-19 era.


Sporadic adenoma or ulcerative colitis associated neoplasia? The endoscopist's information has an impact on diagnosis and patient management.
Diagnosing low grade intraepithelial neoplasia (LGIN) in patients with ulcerative colitis (UC) is difficult. Distinguishing between sporadic adenoma (SA) and UC associated LGIN is even more challenging but has clinical impact. We aimed to examine, if the morphological distinction between both entities is reliably possible, how it influences patient's outcome and the role of the endoscopist in this decision with respect to current endoscopy classification schemes. Seven pathologists retrospectively reevaluated 425 cases of LGIN in UC patients, diagnosed between 2009 and 2017 with preceding expert consensus and follow up in two separate readings, based on published morphological differentiation criteria. In the first evaluation, the observers were blinded to any clinical data. In the second evaluation, they knew patients' age as well as endoscopic features. They also rated their subjective diagnostic certainty. Diagnostic correctness improved significantly in the second assessment as did the pathologists' confidence in their diagnoses (p < 0.001 - p = 0.019). Knowledge of clinical and endoscopical data led to a higher percentage of SA (71.8% vs. 85.6%). UC associated LGIN showed significant earlier LGIN relapse as well as more high grade intraepithelial neoplasia and carcinoma during follow up (p < 0.001, p < 0.001, p = 0.005). Distinction between SA and UC associated LGIN is important as it has an impact on patients' follow up and treatment. Morphological distinction remains difficult with moderate interobserver variability. Adequate clinical information significantly improves pathologists' diagnoses as well as their confidence in their diagnoses.


Indoramin-prolongation of repolarization time, a mechanism of bradycardia in man?
The effect of indoramin, a selective alpha 1-adrenoceptor antagonist, on ECG time intervals in normal man was studied. Significant prolongation of QTc was observed after indoramin 100 mg, with no change in QRS duration. In addition, the slope of the RR/QT relationship was changed by indoramin 100 mg. These results suggest that indoramin may have Class III antiarrhythmic activity. If such activity were to affect the SA node, it may explain at least in part the observed lack of reflex tachycardia after indoramin administration.


Brain response to intranasal trimethylamine stimulation: A preliminary human fMRI study.
The trace amine-associated receptors (TAARs) are a second class of olfactory receptors in humans. They are activated by volatile amines, including pheromone-like odors. However, in humans the neural processing of TAAR-associated signals is not known. Using functional magnetic resonance imaging, the current study investigated brain activation following intra-nasal stimulation with trimethylamine (TMA), an agonist of human TAAR5, and three "canonical" odors with varied valence (an unpleasant odor [n-butanol], a neutral to unpleasant odor [civet musk], and a pleasant odor [phenyl ethyl alcohol]) in 12 healthy young participants. Our hypothesis driven analysis showed that TMA induced a trend for stronger left amygdala activation as compared to the other odors (Family-Wise Error corrected p = 0.08). Whole-brain exploratory analyses revealed superior activation of the cerebellum and caudate to TMA compared to canonical odors, and stronger activation of the anterior cingulate and somatosensory regions (postcentral gyrus and mid cingulate) in response to canonical odors compared to TMA. The current results provide initial evidence on differential central processes of a TAAR mediated stimulus compared to odors targeting canonical olfactory receptors. Future research are needed to elucidate the physiological and psychological relevance of TAARs in humans.


Transvaginal sonographic evaluation of subendometrial-myometrial contractility in women using a copper-releasing intrauterine device.
The aim of this study was to determine the effects of a copper-releasing intrauterine device (IUD) on myometrial contractility midway through the menstrual cycle. Uterine peristalsis was studied midway through the cycle with transvaginal sonography in two groups of women, a control group and women in whom a copper-releasing IUD had been inserted. The results showed that 12 months after insertion, no uterine motility could be detected with sonography in any of the women with an IUD, but motility did occur in all the controls. Subendometrial-myometrial contractility midway through the menstrual cycle had been abolished in patients with a copper-releasing IUD. The loss of motility may inhibit sperm transport from the cervix to the oviduct and account for at least part of the contraceptive effect of these devices.


Survey shows all surgical residents have exposure to robotic surgery yet no formalized curricula exist amongst programs: A Southwest Surgical Congress Survey.
Increased robotic surgery exposure during general surgery training occurs at many institutions without a formal education curriculum. Our study evaluates the current state of general surgery robotic training within programs represented by the Southwestern Surgical Congress (SWSC). A web-based survey regarding robot-assisted surgery (RAS) and general surgery training was developed and sent to member institutions of the SWSC. General surgery program directors were asked to voluntarily complete the survey. Results were evaluated in aggregate. Descriptive analysis was used. In total, 28 programs responded. All reported resident exposure to RAS during training. Case mix was diverse with exposure to multiple general surgical subspecialties. 89% of programs reported the presence of a formal RAS curriculum, however, only 53% reported recognition of training completion. Case volumes also varied amongst programs with 46% of programs reporting residents logging 21-40 cases and 35% logging more than 40 cases in total. Exposure to RAS among SWSC residency programs is ubiquitous, however, there is significant variation between programs in case volumes, case types, and elements of RAS curricula.


Counter-regulatory responses to Telfairia occidentalis-induced hypoglycaemia.
Telfairia occidentalis (TO) has many biological activities including blood glucose regulation. Thus, it is being used in the treatment of diabetes mellitus. TO has been shown to cause insulin-mediated hypoglycaemia, which leads to post-hypoglycaemic hyperglycaemia. However, the mechanism involved in the post-hypoglycaemic hyperglycaemia is still poorly understood. This research was designed to determine the response of glucoregulatory hormones and enzymes to TO treatment. Thirty-five male Wistar rats were divided into seven oral treatment groups (n = 5/group), which received either of 100 mg/kg or 200 mg/kg TO for 7-, 10- or 14 days. The 7-day treatment with TO significantly increased the levels of insulin, glucagon, and glucose-6-phosphatase (G6Pase) activity but decreased the levels of glucose, adrenaline, and glucokinase (GCK) activity. The 10-day treatment with 100 mg/kg TO increased glucose and decreased GCK activity while 200 mg/kg for the same duration increased glucose, insulin, GCK and G6Pase activities but reduced glucagon. The 14-day treatment with 100 mg/kg TO decreased glucose and glucagon but increased cortisol, while 200 mg/kg TO for same duration increased insulin, but reduced glucagon and GCK activity. The TO's post-hypoglycaemic hyperglycaemia results from increased glucagon and G6Pase activity, and reduced GCK activity. Moreover, the glucagon response mainly depends on glucose rather than insulin.


Subcellular location of polypeptides that react with anti-Sm and anti-RNP antibodies.
Whole nuclear and cytoplasmic fractions from HeLa cells were analyzed in protein gel blots probed with either monoclonal anti-Sm or polyclonal anti-(U1)RNP antibodies. The cells were fractionated by a nonaqueous procedure, to minimize proteolysis and artifactual leakage of nuclear components to the cytoplasmic fraction. Unexpectedly, more reactive proteins were detected in the nucleus than shown earlier in partially purified small nuclear ribonucleoprotein particles (snRNPs). In addition, reactive polypeptides were now found in the cytoplasm. These results are discussed in reference to the possibility that the nucleus and cytoplasm of adult somatic human cells may have a more complex than anticipated set of populations of polypeptides bearing Sm or RNP antigenic determinants, including some proteins that might not be in snRNP form.


Types of Nursing Intervention on Improving Quality of Life among Patients with Diabetes Mellitus: A Systematic Review.
Long-term treatment of patients with diabetes mellitus (DM) is considered a major factor causing disease complications. DM complications mostly impact the patient's quality of life (QoL). Only a few studies have been conducted summarizing the types of nursing interventions for improving the QoL of DM patients. The objective of this study is to explore the types of nursing interventions that can improve the QoL of DM patients. The online databases, including ScienceDirect, Medline, Google Search, and Pro-Quest, were used to search for the relevant articles. Articles that met the inclusion criteria were analyzed, and their level of evidence was determined and synthesized. A total of 30 articles defining the types of nursing intervention on improving the QoL of DM patients were discovered, comprising the five types of nursing interventions, such as health education (15 articles), exercise (8 articles), WhatsApp/short message service (WA/SMS) gateway (3 articles), blood glucose control (3 articles), and black garlic herbal therapy (1 article). Sequentially, the most common types of nursing interventions to improve the QoL of DM patients was health education, followed by exercise, WA/SMS gateway, and glucose control. A personal approach to health education is a significant point in improving the QoL of DM patients in the future. The findings of this study might not be strongly generalized, so further randomized controlled trial (RCT) studies with larger samples are needed.


[Neurophysiological and functional assessment of patients with difficult-to-control asthma].
Due to the inadequate response to inhaled corticoids, patients with difficult-to-control asthma (DCA) are submitted to oral corticoids or use of Omalizumab. Although it is necessary to treat these patients, a significant relationship between steroid usage and both peripheral and respiratory weakness muscle, results in implications such as loss of quality of life and compromised lung function. Nonetheless, it is not known whether these patients suffer neurophysiological changes due to drug effect. To investigate the neurophysiological and functional characteristics of patients with DCA in order to gain a better understanding of the condition. A cross-sectional study was carried out involving three groups of patients: DCA-C (use of oral corticosteroids), DCA-O (use of omalizumab) and CG (healthy controls matched for age). The assessment involved the six-minute walk test, sit-to-stand test, static balance on a pressure platform, patellar and Achilles reflexes and quadriceps strength in the dominant leg. The results revealed no statistically significant differences between the control group and DCA groups in relation to neurophysiological aspects. However, the DCA groups exhibited a significant reduction in functional capacity [decreased muscle strength (p < 0.05), shorter distance covered on walk test (p < 0.05) and lesser number of repetitions on sit-to-stand test (p < 0.05)] in comparison to the control group. Individuals with DCA exhibited a reduction in functional capacity. The DCA-C group also demonstrated a reduction in muscle strength when compared with control group, likely caused by the continual use of corticoids. However, no neurophysiological alterations were found in the studied population.


NMR-Based Strategies to Elucidate Bioactive Conformations of Weakly Binding Ligands.
Key processes in molecular biology are regulated by interactions between biomolecules. Protein-proteinand protein-ligand interactions, e.g., in signal transduction pathways, rely on the subtle interactionsbetween atoms at the binding interface of the involved molecules. Because biomolecules often havemany interacting partners, these interactions are not necessarily strong. The study of molecularrecognition gives insight into the complex network of signaling in life and is the basis of structure-baseddrug design.In the situation where the interaction is weak, one of the traditional methods that can be appliedto obtain structural information (internuclear distances) of the bound ligand is the so-called transferredNOE (trNOE) method. Recently, it became possible to use transferred cross-correlated relaxation (trCCR)to directly measure dihedral angles. The combined use of these two techniques significantly improvesthe precision of the structure determination of ligands weakly bound to macromolecules.The application of these techniques will be discussed in detail for a peptide derived fromIKKβ bound to the protein NEMO that plays an important rolein the NFκB pathway.


Stereoselective Synthesis of Trisubstituted (Z)-Alkenes from Ketones via the Julia-Kocienski Olefination Using 1-Methyl- and 1-tert-Butyl-1H-tetrazol-5-yl Alkyl Sulfones.
1-Methyl-1H-tetrazol-5-yl (MT) alkyl sulfones 1b, 3b, and 7b react with various unsymmetrical ketones in the presence of LiHMDS in THF at low temperature to give trisubstituted (Z)-alkenes in good yields stereoselectively (Z/E = 91:9 to 99:1). For sterically less demanding ketones, olefination using t-Bu reagents 1d and 3d generated (Z)-alkenes with higher stereoselectivity (93:7-99:1).


Ultrastructural effects of monocular deprivation in the neuropil of nucleus rotundus in the zebra finch: a quantitative electron microscopic study.
Ultrastructural effects of monocular deprivation starting at hatching have been studied in the neuropil of nucleus rotundus, the thalamic visual relay station of the tectofugal pathway in birds. Synaptic density, presynaptic terminal size, and length of postsynaptic density (PSD) have been quantified in juvenile (20-day) and adult (100-day) zebra finches. These parameters are mature in 20-day-old zebra finches when reared under normal conditions. Alterations obtained by monocular deprivation were: The synaptic density increases by 35% in the nucleus rotundus of both sides of the brain above normal values in juvenile birds. In adult birds only the deprived side maintains this hypertrophy of synaptic density (33%), the non-deprived side returns to normal values. The presynaptic terminal size remains small in the deprived nucleus of 20-day- and 100-day-old animals, whereas the non-deprived nucleus is not affected. By the age of 20 days the length of PSD in deprived and non-deprived nuclei is not reduced as much as in normally reared zebra finches. By the age of 100 days, however, the PSDs of both sides of monocularly deprived birds show a further reduction of their median length and do not differ from PSDs of zebra finches reared under normal conditions.


Evaluation of IL-2, IL-4, IL-6, IL-10, TNF-α, and IFN-γ cytokines in HIV/HHV-8 coinfection.
Imbalance in the immune response is one of the main pathogenic mechanisms of diseases related with human immunodeficiency virus (HIV)/human gammaherpesvirus 8 (HHV-8) coinfection, such as Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), multicentric Castleman disease (MCD) and the Kaposi's sarcoma-associated herpesvirus inflammatory cytokine syndrome (KICS). However, significant changes in pro- and anti-inflammatory cytokine levels may be observed in HIV/HHV-8 individuals who are negative for KS, PEL, MCD, and/or KICS. In this study, serum levels of interleukin-2 (IL-2), IL-4, IL-6, IL-10, tumor nucrosis factor α (TNF-α) and interferon γ (IFN-γ) were assessed in 69 HIV and 48 HIV/HHV-8 individuals, all negatives for HHV-8-related diseases. The cytokines were measured by flow cytometry and analyzed by the Mann-Whitney test. The p < .05 and 95% confidence interval were considered in all analyzes. IL-4 (p = .0155), IL-6 (p = .0036), and IL-10 (p = .0036) levels were significantly higher in HIV/HHV-8 patients than in the HIV group. On the other hand, IL-2 (p = .2295), TNF-α (p = .1216) and IFN-γ (p = .1178) did not differ between the groups analyzed. To our knowledge, to date, this is the first report on significant differences in the levels of IL-4 and IL-6 in HIV versus HIV/HHV-8 individuals. Finally, these early findings are important as a prognostic tool and contribute to clarifying the HHV-8-host interaction.


A julolidine-chalcone-based fluorescent probe for detection of Al3+ in real water sample and cell imaging.
A fluorescent probe 1 based on julolidine-chalcone derivative, which can specifically recognize aluminum ion with high selectivity and anti-interference, was developed. Probe 1 has good fluorescence stability and can detect Al3+ with turn-on fluorescence in a wide pH range of 4.0-9.0. The probe has good repeatability for the detection of Al3+ and fluorescence turn-on and off can be repeated with the alternate Al3+ and EDTA. The sensing mechanism is speculated that Al3+ will coordinate with hydroxyl oxygen and carbonyl oxygen on the probe through in situ 1H NMR and HRMS combing with Job's plot. The probe can also detect Al3+ in actual water samples and applied to monitor Al3+ in biological system.


Morphologic changes in hepatitis virus-related liver cirrhosis: Relationship to hemodynamics of portal vein on dynamic contrast-enhanced CT.
The morphologic changes in the compensated stage of liver cirrhosis (cLC) are not diffuse atrophic changes. With cLC lobar or segmental changes combined with atrophy of the right lobe and medial segment together with hypertrophy of the caudate lobe and lateral segment are commonly seen. The purpose of this study was to evaluate the morphologic changes in hepatitis virus-related liver cirrhosis in relationship to haemodynamics of the portal vein on dynamic contrast-enhanced computed tomography (DCE-CT) METHODS: This study included 72 patients, 46 with hepatitis virus-related cirrhosis and 26 with a normally functioning liver, who underwent DCE-CT. In cirrhosis patients, the morphologic change index (MCI) of the liver was calculated and categorised into two groups, high-MCI (MCI ≥ 0.4) (n = 21) and low-MCI (MCI < 0.4) (n = 25). Cross-sectional areas of the main, right and left portal veins and the intra-portal distribution from splenic venous flow were evaluated for their relationships with the MCI and compared among three groups (normal-control, low MCI and high MCI). There was a significant difference in the cross-sectional area of the left portal vein between the high-MCI group and the low-MCI group (p = 0.013) and the control group (p = 0.008). A significant correlation was identified between the cross-sectional area of the left portal vein and the MCI (r = 0.508, p < 0.001). Cross-sectional area of the left portal vein may be a factor related to morphologic changes in hepatitis virus-related liver cirrhosis and could be a possible index of the left portal venous flow volume. This study may be useful for predicting the degree of hepatic morphologic changes and the condition of cirrhosis in association with regional hepatic morphologic changes.


Current Perspectives on the Surgical Management of Perihilar Cholangiocarcinoma.
Cholangiocarcinoma (CCA) represents nearly 15% of all primary liver cancers and 2% of all cancer-related deaths worldwide. Perihilar cholangiocarcinoma (pCCA) accounts for 50-60% of all CCA. First described in 1965, pCCAs arise between the second-order bile ducts and the insertion of the cystic duct into the common bile duct. CCA typically has an insidious onset and commonly presents with advanced, unresectable disease. Complete surgical resection is technically challenging, as tumor proximity to the structures of the central liver often necessitates an extended hepatectomy to achieve negative margins. Intraoperative frozen section can aid in assuring negative margins and complete resection. Portal lymphadenectomy provides important prognostic and staging information. In specialized centers, vascular resection and reconstruction can be performed to achieve negative margins in appropriately selected patients. In addition, minimally invasive surgical techniques (e.g., robotic surgery) are safe, feasible, and provide equivalent short-term oncologic outcomes. Neoadjuvant chemoradiation therapy followed by liver transplantation provides a potentially curative option for patients with unresectable disease. New trials are needed to investigate novel chemotherapies, immunotherapies, and targeted therapies to better control systemic disease in the adjuvant setting and, potentially, downstage disease in the neoadjuvant setting.


Evidence for emerging parasites and pathogens influencing outbreaks of stress-related diseases like chalkbrood.
In agriculture, honey bees play a critical role as commercial pollinators of crop monocultures which depend on insect pollination. Hence, the demise of honey bee colonies in Europe, USA, and Asia caused much concern and initiated many studies and research programmes aiming at elucidating the factors negatively affecting honey bee health and survival. Most of these studies look at individual factors related to colony losses. In contrast, we here present our data on the interaction of pathogens and parasites in honey bee colonies. We performed a longitudinal cohort study over 6 years by closely monitoring 220 honey bee colonies kept in 22 apiaries (ten randomly selected colonies per apiary). Observed winter colony losses varied between 4.8% and 22.4%; lost colonies were replaced to ensure a constant number of monitored colonies over the study period. Data on mite infestation levels, infection with viruses, Nosema apis and Nosema ceranae, and recorded outbreaks of chalkbrood were continuously collected. We now provide statistical evidence (i) that Varroa destructor infestation in summer is related to DWV infections in autumn, (ii) that V. destructor infestation in autumn is related to N. apis infection in the following spring, and most importantly (iii) that chalkbrood outbreaks in summer are related to N. ceranae infection in the preceding spring and to V. destructor infestation in the same season. These highly significant links between emerging parasites/pathogens and established pathogens need further experimental proof but they already illustrate the complexity of the host-pathogen-interactions in honey bee colonies.


Some like it hot: the structure and function of small heat-shock proteins.
Small heat-shock proteins (sHsps) are a widespread and diverse class of molecular chaperones. Recent evidence suggests that they maintain protein homeostasis by binding proteins in non-native conformations, thereby preventing substrate aggregation. Some members of the sHsp family are inactive or only partially active under physiological conditions, and transition toward the active state is induced by specific triggers, such as elevated temperature. Release of substrate proteins bound to sHsps requires cooperation with ATP-dependent chaperones, suggesting that sHsps create a reservoir of non-native proteins for subsequent refolding.


Colorectal cancer screening in patients presenting with an inguinal hernia: is it necessary?
It has been suggested that patients presenting with an inguinal hernia have an increased risk for colorectal cancer. Therefore, surgeons frequently request screening for colorectal cancer before surgery. The aim of this study was to assess the frequency of premalignant and malignant colonic lesions in a group of patients with an inguinal hernia, and to compare this with a control group of subjects undergoing screening colonoscopy. In a case-control study, 243 patients with an inguinal hernia and no history of colonic neoplasia or symptoms suggestive of colorectal cancer underwent perioperative colonoscopy. The patients were stratified into two age groups: less than 50 years old (Group I) and more than 50 years old (Group II). The colonoscopic findings were compared with findings in 534 asymptomatic control patients who underwent screening colonoscopy. The mean age of patients (n=64) and control subjects (n=200) in Group I was similar, at 44 (3) years. The mean age of the patients (n=179) and control subjects (n=334) in Group II was, respectively, 70 (9) years and 64 (7) years (p<0.001). In Group I, no colorectal cancer was found in patients with inguinal hernia, and only one colorectal cancer was found among control subjects (p=0.571). In Group II, a diagnosis of colorectal cancer was made in 7 patients (4%) with inguinal hernia as compared with 10 patients (3%) among the control subjects (p=0.769). In both groups, the size and the histopathologic type of the polyps were not significantly different. In otherwise asymptomatic patients, the presence of inguinal hernia is not associated with an increased risk for colorectal cancer. Therefore, the presence of an inguinal hernia alone does not justify screening colonoscopy before herniorrhaphy.


Crowned dens syndrome: An uncommon mimic of meningitis in the emergency department.
Crowned dens syndrome is characterized by severe neck pain with stiffness of the neck, sometime febrile, due to calcification of the transverse atlas ligament. We describe the case of a 65-year-old woman referred to the emergency department with a suspicion of meningitis. Several anamnestic and clinical signs ruled out this hypothesis. Re-evaluation of the CT images enabled us to reach the final diagnosis of crowned dens syndrome.


Establishment and application of the National Parasitic Resource Center (NPRC) in China.
The National Parasitic Resource Center (NPRC) was created in 2004. It is a first-level platform under the Basic Condition Platform Center of the Ministry of Science and Technology of China. The resource centre involves 21 depository institutions in 15 regions of the country, including human parasite and vector depository, animal parasite depository, plant nematode characteristic specimen library, medical insect characteristic specimen library, trematode model specimen library, parasite-vector/snail model specimen library, etc. After nearly 15 years of operation, the resource centre has been built into a physical library with a database of 11 phyla, 23 classes, 1115 species and 117,814 pieces of parasitic germplasm resources, and three live collection bases of parasitic germplasm resources. A variety of new parasite-related immunological and molecular biological detection and identification technologies produced by the resource centre are widely used in the fields of public health responses, risk assessments on food safety, and animal or plant quarantine. The NPRC is the largest and top level resource centre on parasitology in China, and it is a leading technology platform for collecting and identifying parasitic resources.


Bacterial cellulose flakes loaded with Bi2MoO6 nanoparticles and quantum dots for the photodegradation of antibiotic and dye pollutants.
Effective strategies to improve charge separation in semiconductor particles are critical for improving the photodegradation of organic pollutants at levels sufficient for environmental applications. Herein, Bi2MoO6 (BMOMOF), comprising both nanoparticles (NPs) and quantum dots (QDs), was synthesized from a bismuth-based metal-organic framework (Bi-MOF) precursor. Surface defects on BMOMOF, the combination of NPs and QDs, and modified energy band edges improved photogenerated charge separation and facilitated redox reactions. When compared to BMO derived from uncoordinated Bi, the BMOMOF photocatalyst (PC) was more efficient at photodegrading tetracycline hydrochloride (TCH) and ciprofloxacin (CIP), two widely-used antibiotics ubiquitous in wastewater, as well as the carcinogenic pollutant rhodamine B (RhB). BMOMOF was then loaded on the biopolymer bacterial cellulose (BC) to further enhance photocatalytic performance and facilitate the recovery of the PC after water treatment processes. The novel BMOMOF/BC photocatalytic flakes were significantly larger than pure BMOMOF, and thus easier to recuperate. Furthermore, anchoring BMOMOF on BC flakes augmented significantly the photodegradation of TCH, CIP, and RhB, mainly because hydroxyl groups in BC act as hole traps facilitating photogenerated electron-hole separation. Results obtained with BMOMOF/BC highlight promising approaches to develop optimal PCs for aqueous pollutants degradation.


Mutant p53 in cancer: from molecular mechanism to therapeutic modulation.
TP53, a crucial tumor suppressor gene, is the most commonly mutated gene in human cancers. Aside from losing its tumor suppressor function, mutant p53 (mutp53) often acquires inherent, novel oncogenic functions, which is termed "gain-of-function". Emerging evidence suggests that mutp53 is highly associated with advanced malignancies and poor prognosis, which makes it a target for development of novel cancer therapies. Herein, we provide a summary of our knowledge of the mutp53 types and mutp53 spectrum in cancers. The mechanisms of mutp53 accumulation and gain-of-function are also summarized. Furthermore, we discuss the gain-of-function of mutp53 in cancers: genetic instability, ferroptosis, microenvironment, and stemness. Importantly, the role of mutp53 in the clinic is also discussed, particularly with regard to chemotherapy and radiotherapy. Last, emphasis is given to emerging strategies on how to target mutp53 for tumor therapy. Thus, this review will contribute to better understanding of the significance of mutp53 as a target for therapeutic strategies.


Primary and Secondary Markers of Doxorubicin-Induced Female Infertility and the Alleviative Properties of Quercetin and Vitamin E in a Rat Model.
The incidence of cancer has recently risen among the women at the reproductive age. Therefore, exposure to doxorubicin (DOX) chemotherapy has become a cause of reproductive toxicity followed by secondary destructive effects. The present study aimed to evaluate the effects of quercetin (QCT) and vitamin.E (Vit.E) on doxorubicin-induced toxicity in the ovary and uterus, and the secondary bone-related effects in a rat model. Animals were divided into six groups including control normal saline/corn oil (CON), QCT at 20 mg/Kg, Vit.E at 200 mg/Kg, DOX at accumulative 15 mg/Kg, DOX/QCT, and DOX/Vit.E. After 21 days of treatment, the alterations were analyzed in histoarchitecture, apoptosis, hormones secretion, the gene expression of aromatase and estrogen α-receptor (ER-α) in the uterine and ovarian tissues, and serum levels of bone-related factors. The results demonstrated the ameliorative effects of QCT and Vit.E on doxorubicin caused altered ovarian histology, increased apoptosis, decreased ovarian aromatase and ER-α gene expression (p-value<0.05), decreased estrogen and progesterone levels, decreased ALP (p-value<0.001), and increased osteocalcin (p-value<0.05). The findings suggested that the studied antioxidants administration could be a promising fertility preservation strategy in DOX-treated females.


Prolonged corticosteroid therapy and cytomegalovirus infection in patients with severe COVID-19.
Systemic corticosteroid therapy is frequently used to treat coronavirus disease 2019 (COVID-19). However, its maximum duration without secondary infections remains unclear. We aimed to evaluate the utility of monitoring cytomegalovirus (CMV) infection in patients with COVID-19 and estimate the maximum duration of systemic corticosteroid therapy without secondary infections. We included 59 patients with severe COVID-19 without CMV infection on admission to the intensive care unit (ICU). All patients received systemic corticosteroid therapy under invasive mechanical ventilation, with examination for plasma CMV-deoxyribonucleic acid (DNA) levels during the ICU stay. We analyzed the correlations among patient characteristics, CMV infection, diseases, and patient mortality. CMV infections were newly identified in 15 (25.4%) patients; moreover, anti-CMV treatment was administered to six (10.2%) patients during the ICU stay. Four (6.8%) patients had secondary infection-related mortality. The cumulative incidences of CMV infection and anti-CMV treatment during the ICU stay were 26.8% (95% confidence interval [CI], 15.8%-39.0%) and 12.3% (95% CI, 4.8%-23.4%), respectively. Furthermore, the median duration of systemic corticosteroid therapy without CMV infection was 15 days (95% CI, 13-16 days). The presence of CMV infection was associated with mortality during the ICU stay (p = 0.003). Monitoring plasma CMV-DNA levels could facilitate the detection of secondary CMV infection due to prolonged systemic corticosteroid therapy. The duration of systemic corticosteroid therapy for COVID-19 should be limited.


Genetic studies of 20 Japanese families of dystrophic epidermolysis bullosa.
Dystrophic EB (DEB) is clinically characterized by mucocutaneous blistering in response to minor trauma, followed by scarring and nail dystrophy, and is caused by mutations in the COL7A1 gene encoding type VII collagen. DEB is inherited in either an autosomal dominant (DDEB) or recessive (RDEB) fashion. DDEB basically results from a glycine substitution mutation within the collagenous domain on one COL7A1 allele, while a combination of mutations such as premature stop codon, missense, and splice-site mutations on both alleles causes RDEB. In this study, mutation analysis was performed in 20 distinct Japanese DEB families (16 RDEB and four DDEB). The result demonstrated 30 pathogenic COL7A1 mutations with 16 novel mutations, which included four missense, five nonsense, one deletion, two insertion, one indel, and three splice-site mutations. We confirmed that Japanese COL7A1 mutations were basically family specific, although three mutations, 5818delC, 6573 + 1G > C, and E2857X, were recurrent based on previous reports. Furthermore, the Q2827X mutation found in two unrelated families would be regarded as a candidate recurrent Japanese COL7A1 mutation. The study furthers our understanding of both the clinical and allelic heterogeneity displayed in Japanese DEB patients.


Eleven fetal echocardiographic planes using 4-dimensional ultrasound with spatio-temporal image correlation (STIC): a logical approach to fetal heart volume analysis.
Theoretically, a cross-sectional image of any cardiac planes can be obtained from a STIC fetal heart volume dataset. We described a method to display 11 fetal echocardiographic planes from STIC volumes. Fetal heart volume datasets were acquired by transverse acquisition from 200 normal fetuses at 15 to 40 weeks of gestation. Analysis of the volume datasets using the described technique to display 11 echocardiographic planes in the multiplanar display mode were performed offline. Volume datasets from 18 fetuses were excluded due to poor image resolution. The mean visualization rates for all echocardiographic planes at 15-17, 18-22, 23-27, 28-32 and 33-40 weeks of gestation fetuses were 85.6% (range 45.2-96.8%, N = 31), 92.9% (range 64.0-100%, N = 64), 93.4% (range 51.4-100%, N = 37), 88.7%(range 54.5-100%, N = 33) and 81.8% (range 23.5-100%, N = 17) respectively. Overall, the applied technique can favorably display the pertinent echocardiographic planes. Description of the presented method provides a logical approach to explore the fetal heart volumes.


Mirror neurons through the lens of epigenetics.
The consensus view in mirror neuron research is that mirror neurons comprise a uniform, stable execution-observation matching system. In this opinion article, we argue that, in light of recent evidence, this is at best an incomplete and oversimplified view of mirror neurons, where activity is actually variable and more plastic than previously theorized. We propose an epigenetic account for understanding developmental changes in sensorimotor systems, including variations in mirror neuron activity. Although associative and genetic accounts fail to consider the complexity of genetic and nongenetic interactions, we propose a new evolutionary developmental biology (evo-devo) perspective, which predicts that environmental differences early in development should produce variations in mirror neuron response patterns, tuning them to the social environment.