Gene editing and elimination of latent herpes simplex virus in vivo.
We evaluate gene editing of HSV in a well-established mouse model, using adeno-associated virus (AAV)-delivered meganucleases, as a potentially curative approach to treat latent HSV infection. Here we show that AAV-delivered meganucleases, but not CRISPR/Cas9, mediate highly efficient gene editing of HSV, eliminating over 90% of latent virus from superior cervical ganglia. Single-cell RNA sequencing demonstrates that both HSV and individual AAV serotypes are non-randomly distributed among neuronal subsets in ganglia, implying that improved delivery to all neuronal subsets may lead to even more complete elimination of HSV. As predicted, delivery of meganucleases using a triple AAV serotype combination results in the greatest decrease in ganglionic HSV loads. The levels of HSV elimination observed in these studies, if translated to humans, would likely significantly reduce HSV reactivation, shedding, and lesions. Further optimization of meganuclease delivery and activity is likely possible, and may offer a pathway to a cure for HSV infection.


Mid-infrared spectroscopy for the rapid quantification of eucalyptus oil adulteration in Australian tea tree oil (Melaleuca alternifolia).
Essential oil distilled from Melaleuca alternifolialeaves, commonly known as tea tree oil, is well known for its biological activity, principally its antimicrobial properties. However, many samples are adulterated with other, cheaper essential oils such as eucalyptus oil. Current methods of detecting such adulteration are costly and time-consuming, making them unsuitable for rapid authentication screening. This study investigated the use of mid-infrared (MIR) spectroscopy for detecting and quantifying the level of eucalyptus oil adulteration in spiked samples of pure Australian tea tree oil. To confirm the authenticity of the tea tree oil samples, GC-MS analysis was used to profile 37 of the main volatile constituents present, demonstrating that the samples conformed to ISO specifications. Three chemometric regression techniques (PLSR, PCR and SVR) were trialled on the MIR spectra, along with a variety of pre-processing techniques. The best-performing full-wavelength PLSR model showed excellent prediction of eucalyptus oil content, with an R2CV of 0.999 and RMSECV of 1.08 % v/v. The RMSECV could be further improved to 0.82 % v/v through a moving window wavenumber optimisation process. The results suggest that MIR spectroscopy combined with PLSR can be used to predict eucalyptus oil adulteration in Australian tea tree oil samples with a high level of accuracy.


Periurethral Lidocaine Does Not Decrease Pain After Urodynamic Testing in Women: A Double-Blinded Randomized Control Trial.
Urodynamic testing of women is a common procedure to evaluate lower urinary tract symptoms but may cause discomfort. The objective of our study was to determine the effect of externally applied periurethral 2% lidocaine gel on pain scores after complex urodynamic testing in women. This prospective, double-blinded, placebo-controlled randomized trial compared 2% lidocaine gel to water-based lubricant applied to the periurethral area before urodynamic testing in women. Discomfort was measured using a visual analog pain scale (VAS) ranging from 0 to 100. The primary outcome was the difference in VAS from baseline to 4 to 6 hours after urodynamic testing. Secondary outcomes included: VAS difference from baseline to immediately postprocedure and 24 hours after urodynamic testing; VAS scores: at baseline, immediately postprocedure, after 4-6 hours, and after 24 hours; urodynamic testing results; and any adverse events. Sixty-four women per group were needed to provide a power of 80% to detect a 10-mm difference on a 100-point VAS. From January 2018 to March 2019, 134 subjects were randomized, 6 subjects were excluded, which resulted in 64 subjects in both the water-based lubricant group and 2% lidocaine gel group. There was no difference in baseline demographics. There was no significant difference in the change in VAS from baseline to 4 to 6 hours after UDT (0, 0 P = 0.88). No difference in secondary outcomes was noted. Topically applied 2% lidocaine gel does not decrease pain compared with water-based lubricant. For most women, complex urodynamic testing is not associated with any significant pain.Clinical Trial Registration:www.ClinicalTrials.gov,-NCT03390790, "Lidocaine for Pain After Urodynamic Testing".


Chronic pulmonary disease due to Mycobacterium monacense infection: the first case from Iran.
We herein report a case in which the recently characterized species Mycobacterium monacense was isolated from the sputum of an Iranian patient. This case represents the first isolation of M. monacense from Iran. The isolate was identified by conventional and molecular techniques. Our findings show that M. monacense infection is not restricted to developed countries.


The role of mother-daughter sexual risk communication in reducing sexual risk behaviors among urban adolescent females: a prospective study.
To prospectively examine the relationship between mother-daughter communication about sex and selected sexual risk behaviors among inner-city adolescent females. Participants were 219 sexually experienced females, 12 to 19 years of age, recruited from an inner-city adolescent medicine clinic in Philadelphia, PA, and randomly assigned to the control group of an HIV-risk reduction intervention study. Analyses were limited to data from control group participants to avoid confounding intervention effects. Poisson regression was employed to model three self-reported sexual risk behaviors: number of male sexual partners, number of episodes of sexual intercourse, and number of episodes of unprotected intercourse. Mediation effects were evaluated using variables from the Theory of Planned Behavior. Data were analyzed using Poisson regression. Higher levels of mother-daughter sexual risk communication were associated with fewer episodes of sexual intercourse and unprotected intercourse at 3-month follow-up. There was evidence that the relationship of communication to unprotected intercourse was mediated by condom use self-efficacy. Mother-daughter sexual risk communication was not significantly associated with adolescents' reports of numbers of male sexual partner. This prospective study supports the notion that mothers who communicate with their daughters about sex can affect their daughters' sexual behaviors in positive ways. These findings lend support for the design and implementation of family-based approaches to improve parent-adolescent sexual risk communication as one means of reducing HIV-related sexual risk behaviors among inner-city adolescent females.


A CLINICAL STUDY OF FALCIPARUM MALARIA - 302 CASES.
Three hundred and two cases of falciparum malaria including 30 cases of severe falciparum malaria admitted between Jan 93 - Dec 93 were studied for their clinical features and response to treatment. Intermittent or remittent fever with chills and headache were the commonest presentation noted (99.3%). Cough (46.4%), hyperbilirubinemia (31.8%), and pyuria (52.9%) were the other notable features. Anaemia was uncommon (16.6%). Hypoglycacmia was detected in none of the cases. Quinine for 3 days along with tetracycline and sulfadoxine - pyrimethamine achieved a 100 per cent cure rate in uncomplicated chloroquine resistant falciparum malaria. Amodiaquine along with tetracycline and sulfadoxine - pyrimethamine was effective in 76.2 per cent of uncomplicated cases.


Assessing quality of life in pediatric gastroschisis patients using the Pediatric Quality of Life Inventory survey: An institutional study.
The purpose of this study was to quantify quality of life (QOL) outcomes in gastroschisis children using a validated QOL inventory survey. A chart review and prospective survey (2012 Pediatric Quality of Life Inventory™ (PedsQL™)) were performed for gastroschisis patients from 2005 to 2011. Demographics and scores were compared between patents with simple versus complicated gastroschisis and patients with and without bowel resection. One hundred nineteen patients (>2years of age) were identified. Twenty-eight families participated in the prospective survey with an average patient age of 5.8±2.3years. There were 11 complicated and 17 simple cases. Children with simple gastroschisis had lower rates of reoperation (0.06% versus 90%, p<0.001) and bowel resection (12% and 64%, p=0.004) than complicated patients. Average QOL scores for children with simple and complicated gastroschisis were 81.69/100±19.50 and 78.7/100±20.14 (p=0.70), respectively. Scores were also similar in children with and without bowel resection (74.72/100±19.94 and 83.29/100±19.10, p=0.171). Cronbach's alpha correlation was 0.912 for the overall survey. Despite increased need for reoperation and bowel resection, at >2years of age, PedsQL™ scores were similar between patients with simple and complicated gastroschisis. This study provides preliminary data on QOL outcomes for antenatal counseling of gastroschisis families.


Generation of Viable Mice from Induced Pluripotent Stem Cells (iPSCs) Through Tetraploid Complementation.
Tetraploid complementation assay is the most rigorous criteria for pluripotency characterization of pluripotent stem cells including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). Pluripotent stem cells could complement the developmental deficiency of tetraploid embryos and thus support the full-term mice development. Here we describe the protocol for tetraploid complementation using iPSCs to produce viable all-iPSC mice.


Oral anti-inflammatory action of NPC 18884, a novel bradykinin B2 receptor antagonist.
This study describes the anti-inflammatory actions of NPC 18884, a non-peptide bradykinin B2 receptor antagonist in bradykinin and carrageenan-induced inflammation in the mouse model of pleurisy. The selectivity of NPC 18884 was assessed in the pleurisy caused by histamine, substance P and des-Arg9-bradykinin. NPC 18884 given intraperitoneally or orally inhibited bradykinin-induced leukocytes influx (ID50 value of 63 nmol/kg and 141 nmol/kg, respectively). The NPC 18884 also inhibited the exudation induced by bradykinin (P < 0.05). NPC 18884 given either intraperitoneally or orally caused dose-dependent inhibition of the exudation and total and differential cell content caused by intrapleural injection of carrageenan (1%, assessed 4 h after), with mean ID50, values of 132 and 295 nmol/kg, respectively. The NPC 18884 actions installs rapidly (0.5 h), lasted for up to 4 h and were selective for the bradykinin B2 receptors; at similar doses it had no significant effect against the inflammatory responses induced by des-Arg9-bradykinin, histamine or substance P. These results indicate that the novel non-peptide bradykinin B2 receptor antagonist, NPC 18884, exhibited selective intraperitoneal and oral anti-inflammatory properties when assessed in the inflammatory reaction induced by bradykinin and carrageenan in the mice model of pleurisy.


Pharmacologic agents for the treatment of obesity.
Obesity guidelines state that pharmacologic therapy can be considered if a patient fails to lose 10 percent of their original body weight after 6 months of adhering to a low calorie diet, exercise, and behavior modification. Many published trials have shown sibutramine and orlistat to be effective for weight loss and weight maintenance when used with lifestyle modifications. However, few trials have studied the efficacy and safety of these medications in the elderly. This article provides a review of the FDA approved medications currently available for the treatment of obesity. Pertinent clinical trials are also reviewed and recommendations regarding the use of these agents in the elderly are discussed.


Impact of β-blocker therapy on right ventricular function in heart failure patients with reduced ejection fraction. A prospective evaluation.
Beta-blocker (β-blocker) therapy has been shown to improve mortality and reduce hospitalizations in patients with heart failure (HF) with reduced ejection fraction (HFrEF). Although the physiological action mechanisms of β-blockers are well described, their effects on right ventricular (RV) function have not been prospectively studied. This prospective study aimed to (a) evaluate whether β-blocker therapy impacts RV remodeling based on echo parameters and (b) determine the predictive echo factors of β-blocker therapy response. From September 2017 to September 2018, HF patients were prospectively enrolled using CIBIS criteria: Class II, III, or IV HF; left ventricular ejection fraction (LVEF) of ≤40%; hospitalized for HF within the previous 12 months. Echo evaluation was performed before initiating β-blocker therapy and 3 months after optimal dose adjustment. Based on previous studies, patients with (absolute) LVEF ≥ 5% improvement were considered significant β-blocker therapy responders. Overall, 40 patients (pts) completed the study, characterized as follows by age: 70 ± 10 years; gender: 10 women; cardiomyopathy etiology: idiopathic in 24 and ischemic in 16; NYHA Class: II in 22 and III in 10; LVEF: 32 ± 5%; and NTProBNP: 2665 ± 2400 pg/mL. The final population comprised 32 pts (79%), with eight (21%) excluded: two because of β-blocker therapy intolerance, one lost to follow-up, and five withdrew from the study. Under β-blocker therapy, several echo parameters significantly improved: LVEF from 31.7 ± 9 to 40.5 ± 9 (P < .0001); LV end-diastolic volume (EDV) from 154 ± 54 to 143 ± 45 mL (P = .06); LV end-systolic volume (ESV) from 107 ± 49 to 88 ± 37 mL (P = .0006); LV ES from 46 ± 11 to 64 ± 13 mL (P = .008); LV end-diastolic diameter (EDD) from 57 ± 9 to 54 ± 6 mm (P = .04); LV end-systolic diameter (ESD) from 48 ± 10 to 44 ± 7 mm (P = .007); and right ventricular systolic pressure (RV SP) from 39 ± 10 to 32 ± 8 mm Hg (P = .0001). Significant modifications were observed in terms of RV echo parameters: right ventricular (RV) size decreased from 30 ± 4 to 27 ± 5 mm (P = .03), while RV systolic function significantly improved based on tricuspid annular plane systolic excursion (TAPSE) (16.5 ± 4 vs. 19 ± 4 mm; 0.0006); DTI-derived tricuspid lateral annular systolic velocity wave (S') (10 ± 2 vs. 11.3 ± 3 cm/s; P = .03); and RIMP (Tei index) (0.5 ± 0.1 vs 0.46 ± 0.1; P = .04). RV 2D fractional area change (%) did not significantly differ despite a clear improvement tendency (35 ± 6 vs. 37 ± 4%; P = .1). No significant modifications were observed concerning LV diastolic parameters. Overall, β-blocker echo responders (n = 23/32; 72%) exhibited the same left and right echo parameters. No echo variables predicted the β-blocker response. In HFrEF pts, β-blocker therapy significantly improves LV and RV systolic remodeling. Accordingly, β-blocker therapy could be applied as soon as possible in HFrEF patients with right ventricular dysfunction so as to limit RV remodeling.


Genioplasty in Contemporary Orthognathic Surgery.
In contemporary orthognathic surgery planning, the genium/chin constitutes an important part that contributes to the maxillofacial profile. The aesthetics of the lower face is affected by the position of the genium which makes reestablishment of genial morphology an essential component. It is hence necessary to evaluate the genium objectively on its individual merit, and any discrepancy is addressed accordingly. This review presents an overview of contemporary genioplasty techniques, their applications, and considerations on stability, osteosynthesis, complications, and the future developments.


Codex dietary fibre definition - Justification for inclusion of carbohydrates from 3 to 9 degrees of polymerisation.
The main controversy about the DF definition, adopted by the commission of Codex Alimentarius, refers to the inclusion of carbohydrates of 3-9 degrees of polymerisation (DP), decision which may be made individually by the authorities of each country. Due to the possibility of having two definitions and the negative impact it would cause over the harmonisation of nutritional information, a bibliographic review was carried, from 2009 to 2011, aiming to gather justifications for the inclusion of carbohydrates of 3-9 DP in the definition. The current review presents scientific bases that are directed to three topics: physiological aspects; repercussion over the analytical method; and impact on consumers and other users. The decision of including unavailable carbohydrates of 3-9 DP in the definition of DF may cause effective global harmonisation in the nutritional labelling, considering that the main goal is to help consumers choose healthy foods.


Anatomy and Embryology of the Thoracic Outlet.
The thoracic outlet is the space between the thorax and axilla through which the subclavian vein, subclavian artery, and brachial plexus travel from their central origins to their peripheral termini. Its bounds include the clavicle, first thoracic rib, insertion of the pectoralis minor muscle onto the coracoid process of the humerus, and the sternum. It contains three areas: the scalene triangle, the costoclavicular space, and the subcoracoid or pectoralis minor space. Aberrant anatomy is common in the thoracic outlet and may predispose patients to compression of the neurovascular bundle and development of clinical thoracic outlet syndrome (TOS). Much of this aberrancy is explained by the embryologic origins of the structures that comprise the thoracic outlet. A thorough understanding of this anatomy and embryology is therefore critical to the understanding of TOS.


Examining the psychometric properties of the expressions of moral injury scale in a sample of first responders.
There is emerging evidence that first responders, like military personnel, are at risk for exposure to potentially morally injurious events. However, studies examining expressions of moral injury in first responders are nascent, in large part due to the limited number of measures validated for use in this population. To address this gap, the present study sought to investigate the psychometric properties of the Expressions of Moral Injury Scale-Military Version (EMIS-M) in a sample of first responders. The psychometric properties of the EMIS-M were investigated in a sample of 228 first responders to determine reliability, convergent validity, discriminative validity, and divergent validity. In addition, confirmatory factor analysis was conducted to test the bifactor model identified in a veteran sample (Currier et al., 2018). Results yielded an excellent fit for the bifactor model with correlated self-directed and other-directed subscales identified in the EMIS-M development study. In addition, the measure evidenced strong reliability, convergent validity, discriminative validity, and divergent validity. The findings of the present study suggest that the Expressions of Moral Injury Scale-First Responder Version is a psychometrically sound measure capable of assessing self- and other-directed expressions of moral injury in first responders. The significance of these findings to our understanding of moral injury in first responders and their implications for future research are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Residential combustion of coal: Effect of the fuel and combustion stage on emissions.
Worldwide coal is still used for household heating purposes not only because it is available and cheap but also due to behavioural issues. Regional variability in fuels and combustion appliances make accurate emission estimates from this source hard to achieve. In the present study, gaseous (CO, VOCs, SO2 and NOX) and particulate matter (TSP) emission factors (EFs) were determined for Spanish household coal combustion covering three commercial coals and distinct combustion stages and mimicking usage patterns in real households. TSP samples were analysed to determine water-soluble inorganic ions, metal(loid)s, and organic and elemental carbon (OC and EC). Additionally, the morphology of the emitted particles was also characterised. CO (3.43-169 g kg-1), NOX (1.29-6.00 g kg-1) and SO2 (8.96-22.3 g kg-1) EFs showed no trend regarding the combustion stage or coal type tested. On the other hand, VOC, TSP and EC EFs were higher for the ignition/devolatilisation combustion stage, regardless of the fuel tested. TSP EFs (0.085-1.08 g kg-1) increased with increasing coal volatile matter while the opposite trend was recorded for VOC emissions (0.045-3.39 gC kg-1). TSP carbonaceous matter was dominated by EC while OC represented a small fraction of the particulate mass emitted (less than 8 %wt.). Inorganic compounds composed an important fraction of the TSP samples. Sulphate particulate mass fractions (8.66-22.9 %wt.) appeared to increase with coal S-content. Coal combustion released particles with diverse morphologies, including silicate-rich particles, ferro- and glassy-spheres. This study provides novel emission factors to update emission inventories of residential coal combustion. Additionally, detailed chemical profiles were obtained for source apportionment.


Benign breast disease in the postmenopausal woman.
Breast symptoms are surprisingly common in the postmenopausal period, especially (but not only) when taking hormonal therapy. All of the common conditions of the premenopausal period may be seen. Clinical examination is usually easier and more precise in the postmenopausal woman. The importance of accurate clinical observation is stressed, as a diagnosis can usually be made in this way, supplemented by mammography and aspiration cytology where reliable services exist.


Localization of Prp8, Brr2, Snu114 and U4/U6 proteins in the yeast tri-snRNP by electron microscopy.
The U4/U6-U5 tri-small nuclear ribonucleoprotein (snRNP) is a major, evolutionarily highly conserved spliceosome subunit. Unwinding of its U4/U6 snRNA duplex is a central event of spliceosome activation that requires several components of the U5 portion of the tri-snRNP, including the RNA helicase Brr2, Prp8 and the GTPase Snu114. Here we report the EM projection structure of the Saccharomyces cerevisiae tri-snRNP. It shows a modular organization comprising three extruding domains that contact one another in its central portion. We have visualized genetically tagged tri-snRNP proteins by EM and show here that U4/U6 snRNP forms a domain termed the arm. Conversely, a separate head domain adjacent to the arm harbors Brr2, whereas Prp8 and the GTPase Snu114 are located centrally. The head and arm adopt variable relative positions. This molecular organization and dynamics suggest possible scenarios for structural events during catalytic activation.


Analysis of the active components and metabolites of Taohong Siwu decoction by using ultra high performance liquid chromatography quadrupole time-of-flight mass spectrometry.
Taohong Siwu Decoction is a classic Chinese medicine prescription for treatment of cerebral ischemia and gynecological diseases. However, the active ingredients of Taohong Siwu Decoction have not been identified. In this study, a ultra performance liquid chromatography quadrupole time-of-flight mass system was used to analyze the active components and metabolites of Taohong Siwu Decoction absorbed into the blood and the brain. A total of 39 active compounds and 90 metabolites were identified in the blood and brain by comparing retention times, accurate masses, fragmentation patterns, and literature data. The results showed that flavonoids (Carthamus tinctorius L), aromatic organic acids, and benzoquinones (Angelica sinensis (Oliv.) Diels and Ligusticumchuanxiong hort) were prominent active ingredients in Taohong Siwu Decoction. Furthermore, hydrolysis, glucuronidation, and sulfation were identified as the main metabolic pathways of Taohong Siwu Decoction in vivo. This was the first study to characterize the active components and metabolites of Taohong Siwu Decoction in the blood and brain using ultra performance liquid chromatography quadrupole time-of-flight mass.


Growth inhibition of cultured human glioma cells by beta-interferon is not dependent on changes in ganglioside composition.
This investigation tested the hypothesis that the growth inhibiting effects of human beta-interferon on cultured human glioma cells involves changes in the ganglioside composition of these cells. Four cell lines derived from human malignant gliomas (12-18, U-251 MG, I29-A, 7-24) and two lines from human fetal brain (CHI, CHII) were cultured in the presence and in the absence of human beta-interferon (HuIFN-beta), 1,000 units per ml medium for three days before harvesting. Human beta-interferon had an inhibitory effect on growth of glioma but not fetal brain cells. Total ganglioside sialic acid for all cell lines ranged between 3.5 and 13.8 micrograms/10(7) cells (0.6-3.9 micrograms/mg protein). No distinct difference in the amount of total ganglioside per cell was observed between neoplastic and non-neoplastic cells, but the latter had more ganglioside per mg total protein. All cell lines displayed different patterns of gangliosides determined by high performance thin layer chromatography, but there was no distinct difference between glioma and fetal brain cells. Human beta-interferon increased the total amount of ganglioside per cell in one fetal brain and two glioma lines, but on a protein basis in only one glioma cell line (I29-A); HuIFN-beta had only minor effects on ganglioside patterns. There was a slight shift towards a greater proportion of structurally simpler gangliosides in both fetal brain and two glioma cell lines exposed to HuIFN-beta, but the reverse occurred in glioma U-251 MG. None of these changes strongly correlated with the degree of growth inhibition due to HuIFN-beta.(ABSTRACT TRUNCATED AT 250 WORDS)


Positive family history for coronary heart disease and 'midband lipoproteins' are potential risk factors of carotid atherosclerosis in familial hypercholesterolemia.
Patients with heterozygous familial hypercholesterolemia (FH) were examined with B-mode ultrasound in order to determine intima-media thickness (IMT) in the common carotid artery, and to uncover potential risk factors responsible for the development of IMT. Ninety seven FH subjects and 132 non FH type IIa hyperlipidemic subjects were involved in the present study. Age was found to correlate positively with IMT in both FH and non FH groups. FH individuals showed a higher IMT, along with elevated low density lipoprotein (LDL) cholesterol levels, compared with age-matched non FH individuals. To clarify potential factors contributing to the formation and development of carotid atherosclerosis, we divided the FH subjects into two subgroups, namely FH with high IMT group (HIG), and those with low IMT group (LIG). We investigated those two subgroups on the presence of angiographically documented coronary heart disease (CHD), of family history of CHD and of 'midband lipoproteins' by polyacrylamide gel electrophoresis (PAGE) analysis, by matching for age and LDL-cholesterol (LDL-C) level. Fifty percent of FH men in HIG was found to have CHD, whereas only 14% of those in LIG had CHD (P<0.05). Thirty-three percent of FH women in HIG was found to have CHD, whereas only 12% of those in LIG had CHD (P<0.05). Fifty percent of FH men in HIG was found to have 'midband lipoproteins', whereas only 7% of those in LIG had 'midband lipoproteins' (P<0.01). Seventy-three percent of FH women in HIG had 'midband lipoproteins', whereas only 21% of those in LIG had 'midband lipoproteins' (P<0.0005). Fifty-five percent of FH men in HIG was had positive family history for CHD, whereas only 14% of those in LIG had positive family history for CHD (P<0.05). Sixty-three percent of FH women in HIG was found to have positive family history for CHD, whereas only 29% of those in LIG had positive family history for CHD (P<0.05). Based on these findings, we propose that, besides age and elevated levels of LDL-C, positive family history for CHD and 'midband lipoproteins' are important determinants for the development of carotid atherosclerosis in FH individuals in Japanese population.


Post-endarterectomy carotid ultrasonic duplex scanning concordance with contrast angiography.
The results of ultrasonic duplex scanning combined with spectral analysis are compared with the results of contrast angiography in patients after endarterectomy in which recurrence of carotid arterial disease was suspected. Thirty-six patients underwent a duplex scan study within 3 months of their post-operative angiogram, performed at their physician's discretion (44 studies). The overall accuracy of the method was 80%. Our ability to predict a greater than 50% diameter reduction along with total occlusion was 94%. The measure of agreement corrected for chance between arteriography and duplex scanning as expressed by the Kappa statistic was 0.675 +/- SE (K) 0.096. This level of agreement compared favorably to that of inter- and intra-observer variability in reading cerebral angiograms. The accuracy reported justifies the clinical use of ultrasonic duplex scanning in the detection of recurrent stenosis after carotid endarterectomy.


Swedish translation, cultural adaptation and psychometric evaluation of the pressure ulcer knowledge assessment tool for use in the operating room.
The aim of this study was to psychometrically evaluate the Swedish operating room version of PUKAT 2.0. In total, 284 Swedish operating room nurses completed the survey of whom 50 completed the retest. The item difficulty P-value of 14 items ranged between 0.38 and 0.96 (median 0.65). Three items were found to be too easy (0.90-0.96). The D-value of 14 items ranged between 0.00 and 0.42 (median 0.46). Three items had a D-value lower than 0.20 (0.11-0.16) and eight items scored higher than 0.40 (0.45-0.61). The quality of the response alternatives (a-value) ranged between 0.00 and 0.42. This showed that nurses with a master's degree had a higher knowledge than nurses with a professional degree (respectively 9.4/14 versus 8.6/14; t = -2.4, df = 199, P = 0.02). The ICC was 0.65 (95% CI 0.45-0.78). The ICCs for the domains varied from 0.12 (95% CI = -0.16-0.39) to 0.59 (95% CI = 0.38-0.75). Results indicated that 11 of the original items contributed to the overall validity. However, the low participation in the test-retest made the reliability of the instrument low. An extended evaluation with a larger sample should be considered in order to confirm aspects of the psychometric properties of this instrument.


Gene disruption of the calcium channel Orai1 results in inhibition of osteoclast and osteoblast differentiation and impairs skeletal development.
Calcium signaling plays a central role in the regulation of bone cells, although uncertainty remains with regard to the channels involved. In previous studies, we determined that the calcium channel Orai1 was required for the formation of multinucleated osteoclasts in vitro. To define the skeletal functions of calcium release-activated calcium currents, we compared the mice with targeted deletion of the calcium channel Orai1 to wild-type littermate controls, and examined differentiation and function of osteoblast and osteoclast precursors in vitro with and without Orai1 inhibition. Consistent with in vitro findings, Orai1(-/-) mice lacked multinucleated osteoclasts. Yet, they did not develop osteopetrosis. Mononuclear cells expressing osteoclast products were found in Orai1(-/-) mice, and in vitro studies showed significantly reduced, but not absent, mineral resorption by the mononuclear osteoclast-like cells that form in culture from peripheral blood monocytic cells when Orai1 is inhibited. More prominent in Orai1(-/-) mice was a decrease in bone with retention of fetal cartilage. Micro-computed tomography showed reduced cortical ossification and thinned trabeculae in Orai1(-/-) animals compared with controls; bone deposition was markedly decreased in the knockout mice. This suggested a previously unrecognized role for Orai1 within osteoblasts. Analysis of osteoblasts and precursors in Orai1(-/-) and control mice showed a significant decrease in alkaline phosphatase-expressing osteoblasts. In vitro studies confirmed that inhibiting Orai1 activity impaired differentiation and function of human osteoblasts, supporting a critical function for Orai1 in osteoblasts, in addition to its role as a regulator of osteoclast formation.


Erectile dysfunction in patients with haemophilia.
Patients with haemophilia (PWH) are experiencing a nearly normal life span with safe factor replacement therapy and effective antiviral treatments for co-infections. As a result, many ageing-related health issues are starting to emerge. One rarely discussed health issue is erectile dysfunction (ED). ED can affect overall well-being and predict future cardiac events, but is not well studied in PWH. This prospective study aims to examine the prevalence and risk factors for ED in PWH using the validated International Index of Erectile Function (IIEF) questionnaire. Patients with haemophilia A and B at all severities were invited to participate in IIEF questionnaire at the provincial Hemophilia Treatment Centre. Risk factors for ED including cardiovascular risk factors, prior surgeries, viral infections, medications and haemophilia-specific factors were obtained. Fasting laboratory tests including but not limited to renal function, haemoglobin, lipid profile, glucose and CRP were performed the same day. Blood pressure and anthropomorphic indices were measured. Endothelial function was assessed by brachial artery flow-mediated dilation (FMD and hyperaemic velocity time integral [VTI]). Out of the 56 subjects approached, 44 completed the IIEF. Median age was 49 years. About 38.6% of the cohort reported ED symptoms. There was no significant difference in endothelial function measured by FMD and VTI between patient with ED and without. IIEF score correlated with age in multivariable analysis. Erectile dysfunction symptoms appear prevalent in PWH, particularly in the older group. This disorder along with the underlying causes needs to be explored further in future larger observational study.


Sequential quantitative scintigraphy of parotid glands with chronic inflammatory diseases.
A practical, time-saving procedure for sequential quantitative scintigraphy is introduced and 4 parameters chosen from 12 parameters by discriminant analysis are used to evaluate the function of the parotid gland. The examination was performed in 120 cases, including 16 cases with recurrent parotitis in childhood, 33 with chronic obstructive parotitis (COP), 37 with Sjögren's syndrome (SS), 4 with sialadenosis, and 30 normal controls. The scintigraphic findings were analyzed and compared with the histologic findings. The diagnostic value of this method was investigated and scaling for differential diagnosis of COP and SS was established. Scintigraphy is considered to be a useful method for evaluation of parotid function and as a diagnostic aid for SS and COP, especially in patients in whom sialography cannot be performed.


Melanosis of bladder: A rare entity.
Melanosis of the bladder, also known as melanosis vesicae, refers to presence of pigment in bladder mucosa. A rare phenomenon, however, it can be confused with the primary or metastatic melanoma of the bladder. Therefore, knowledge of the entity can prevent over diagnosis of this benign entity. We are reporting a case of melanosis of bladder in a 69 year old male with prolonged history of LUTS and bladder diverticulae. Cystoscopic examination showed black patches and biopsy revealed pigmentation in the epithelium and underlying lamina propria. Special stains identified the pigment to be melanin. No malignant cells were identified.


Idiopathic dilated cardiomyopathy exhibits defective vascularization and vessel formation.
Ultrastructural findings of idiopathic dilated cardiomyopathy (IDCM) include myocyte atrophy and myofilament loss, yet little is known about the vascular abnormalities present in IDCM. Patients with IDCM and controls underwent multi-slice CT to examine length and diameter of epicardial vasculature. The levels of mobilizing cytokines and circulating EPCs were assessed by endothelial colony formation assay and flow cytometry. Immunohistochemistry and Western blot were used to examine microvessel density and expression of HIF-1alpha and beta-catenin. Main epicardial coronary arteries were shorter and smaller, and microvascular density was reduced in the epicardium in IDCM. Epicardial vessel paucity was associated with increased numbers of HIF-1alpha(+) cells (46.8+/-13.1% vs. 19.4+/-9.4%, p=0.006) indicating local epicardial hypoxia and elevation of circulating VEGF-A (394 pg/mL vs. 22 pg/mL, p=0.001). The number of mobilized progenitors CD133(+)/VEGF-R2(+) was 21-fold higher in IDCM compared with controls (6.5+/-3.3% vs. 0.3+/-0.2%; p<0.001). Moreover, this defective vascularization was associated with reduced myocardial expression of vascular beta-catenin, an important angiogenic regulator. This study shows defective vascularization and impaired vasculogenesis (the de novo vascular organization of mobilized endothelial progenitors) and angiogenesis (by which new blood vessels are formed from pre-existing mature endothelial cells) in human IDCM.


Clinical and electrophysiological studies of diphtheritic neuritis in Jordan.
Eleven patients with acute diphtheritic neuritis were studied clinically and electrophysiologically. Decreased conduction velocity and increased distal motor latency were present in most patients within two weeks of the onset of neurological symptoms. Velocities later fell to approximately 45% of mean normal values. Wasting with electrophysiological evidence of denervation was present in 3 patients. Nerve conduction studies had returned to normal within 3 months in 8 patients. There was a striking dissociation between the time course of the clinical and the neurophysiological abnormalities: early in the illness, peripheral nerve conduction was normal in some patients despite the presence of severe weakness, and later, the maximum electrophysiological abnormalities were sometimes found after clinical recovery had commenced. The nature and sequence of the clinical and electrophysiological changes are in accord with the known pattern and distribution of the pathological changes in the disease.


A systematic review of cross-cultural comparison studies of child, parent, and health professional outcomes associated with pediatric medical procedures.
The purpose of this review was to evaluate systematically all published and unpublished research concerning culture and medical procedural pain in children. Databases, reference lists, and electronic list servers were searched as data sources. Fifteen studies met the inclusion criteria. Most studies (80%) were conducted solely in the United States comparing Caucasian American groups to other local subculture(s) (ie, African American, Hispanic, or Japanese). The studies compared, cross culturally, pediatric pain-related outcomes in children, parents and/or health professionals. The medical procedural experiences included surgery, immunization, spinal tap, bone marrow aspiration, needle procedures, orthopedic, and wound-related injuries. The evidence published to date suggests that cultural factors may be associated with children's pain experiences when elicited by medical procedural pain, specifically children's pain behavior. Nevertheless, research using more sophisticated research methods is needed to develop culturally sensitive behavioral pain measures. Measures that include physiological pain parameters in addition to other behavioral outcomes may be helpful. Culturally comparative research would benefit from the use of theoretical frameworks to advance our understanding of the cultural underpinnings of child pain development and guide future research. The current evidence supports that children and parents belonging to cultural minority groups, and in need of health care, are a vulnerable population. Together, researchers and clinicians are encouraged to explore this understudied area, and take advantage of sophisticated methods developed by disciplines like cross-cultural psychology.


New ligands for L-type Ca2+ channels.
Although the clinically important categories of drug represented by verapamil, nifedipine and diltiazem are defined as acting at three major and discrete sites on the L class of voltage-dependent Ca2+ channel, it is likely that some new classes of drug modulate channel activity by acting at additional sites. David Rampe and David Triggle describe the actions of some of these new drugs, which may both offer improved therapeutic and side-effect profiles over existing agents and provide information to define further the structure and function of this channel class. These drugs may mimic the actions of endogenous ligand(s) and such ligands could provide new directions for Ca2+ channel drug structures.


Preoperative pathologic findings associated with residual disease at radical hysterectomy in women with stage IA2 cervical cancer.
To correlate findings on pathologic examination of loop electroexcisional procedure (LEEP) or cone biopsy specimens with residual disease in radical hysterectomy specimens in patients with stage IA2 cervical cancer to determine whether a subset of such patients may be eligible for conservative, fertility-sparing treatment. We performed a retrospective chart review of patients diagnosed with stage IA2 cervical cancer who had undergone LEEP or cone biopsy before radical hysterectomy. Surgicopathologic features of LEEP and cone biopsy specimens were correlated with the presence or absence of residual tumor in radical hysterectomy specimens. Forty-two patients met the inclusion criteria. At radical hysterectomy, 22 patients (52%) had no residual tumor, while 20 patients (48%) had residual disease. Margin status was the only statistically significant predictor of the presence or absence of residual disease at radical hysterectomy; positive margins predicted the presence of residual disease (P<0.001). Women with stage IA2 cervical cancer and negative margins on LEEP or cone biopsy specimens should be counseled that they may be at low risk for having residual disease in the final radical hysterectomy specimen.


Personal relationships with an intelligent interactive telephone health behavior advisor system: a multimethod study using surveys and ethnographic interviews.
The burgeoning of consumer health informatics and virtual health care can help people improve their health. However, little is known about individuals' reactions to such systems. We conducted an evaluation of the telephone-linked care (TLC) system, a computer-based telecommunications system, that functions as an at home monitor, educator, and counselor for patients with chronic health conditions. Our multimethod assessment of individuals' reactions to using TLC included both quantitative and qualitative methods. Ethnographic in-depth open-ended interviews indicated more subtle and surprising reactions to TLC than the overall positive responses from surveys: individuals formed personal relationships with this technology. This relationship formation suggests that TLC designers may have been successful in their attempts to emulate a conversation with a human being. Our study adds to evidence that technology can serve as a projective device for peoples' values and psychological issues. Both designers and users project values and goals onto computer-based technologies and take on different identities through it. Different groups of users, therefore, may see the same technology differently. People also form relationships with technologies, as they did with TLC. These findings, as well as implications for system design and health outcomes, need to be explored in additional studies.


Patient with Recurrent Anterior Cerebral Artery Dissecting Aneurysm After Stent-Assisted Coil Embolization Successfully Treated with A3-A3 Anastomosis.
With recent advances in endovascular devices and techniques, the use of endovascular treatment has been reported for intracranial dissecting aneurysms. However, the efficacy of this endovascular approach for intracranial dissection is still unknown. We report the case of a patient with a recurrent anterior cerebral artery (ACA) dissecting aneurysm after endovascular treatment. A 67-year-old woman underwent stent-assisted coil embolization for a ruptured ACA dissecting aneurysm of the left A2 segment. Aneurysmal dilatation was completely occluded after embolization. However, follow-up angiography 40 days after treatment showed compaction of the coil mass and reenlargement of the aneurysm. Open surgery was performed, considering the risk of rebleeding from the recurrent dissecting aneurysm. A3-A3 anastomosis followed by trapping of the coiled aneurysm along with the stent was successfully performed through the interhemispheric approach. The postoperative course was uneventful, and angiography 6 months after surgery revealed disappearance of the aneurysm and patency of the A3-A3 anastomosis. Stent-assisted coil embolization for an ACA dissecting aneurysm may not be curative, and the coiled aneurysm may recur within a short time period. Microsurgical bypass trapping can be considered as the alterative or salvage treatment because of curability. Revascularization surgery, such as A3-A3 anastomosis, should be performed before trapping to avoid ischemic complications.


Mucin methods: genes encoding mucins and their genetic variation with a focus on gel-forming mucins.
Mucin genes encode the polypeptide backbone of the mucin glycoproteins which are expressed on all epithelial surfaces and are major constituents of the mucus layer. Mucins are, thus, expressed at the interface between the external and the internal environment of the organism, and represent the first line of defence of our body. These genes often have an extensive region of repetitive exonic sequence which codes for the heavily glycosylated domain, whose roles include bacterial interactions and gel hydration. This region shows, in several of the genes, considerable inter-individual variation in repeat number and sequence. Because of their site of expression and their high variability in this important domain, mucin genes are good candidates for conferring differences in genetic susceptibility to multifactorial epithelial and inflammatory disease. However, progress in characterizing the genes has been considerably slower than the rest of the genome because of their size and the GC-rich content of the large, repetitive variable region. Some of the issues relating to the study of these genes are discussed in this chapter. In addition, methods and approaches that have been used successfully are described.


JAC1 targets YY1 mediated JWA/p38 MAPK signaling to inhibit proliferation and induce apoptosis in TNBC.
Triple negative breast cancer (TNBC) is a type of breast cancer with poor prognosis, and has no ideal therapeutic target and ideal medicine. Downregulation of JWA is closely related to the poor overall survival in many cancers including TNBC. In this study, we reported at the first time that JWA gene activating compound 1 (JAC1) inhibited the proliferation of TNBC in vitro and in vivo experimental models. JAC1 specifically bound to YY1 and eliminated its transcriptional inhibition of JWA gene. The rescued JWA induced G1 phase arrest and apoptosis in TNBC cells through the p38 MAPK signaling pathway. JAC1 also promoted ubiquitination and degradation of YY1. In addition, JAC1 disrupted the interaction between YY1 and HSF1, and suppressed the oncogenic role of HSF1 in TNBC through p-Akt signaling pathway. In conclusion, JAC1 suppressed the proliferation of TNBC through the JWA/P38 MAPK signaling and YY1/HSF1/p-Akt signaling. JAC1 maybe a potential therapeutic agent for TNBC.


Inhibition of the CoREST Repressor Complex Promotes Wound Re-Epithelialization through the Regulation of Keratinocyte Migration.
Wound healing is a complex process involving phases of hemostasis, inflammation, proliferation, and remodeling. The regenerative process in the skin requires coordination between many regulators, including signaling molecules, transcription factors, and the epigenetic machinery. In this study, we show that chromatin regulators HDAC1 and LSD1, key components of the CoREST repressor complex, are upregulated in the regenerating epidermis during wound repair. We also show that corin, a synthetic dual inhibitor of the CoREST complex and HDAC1/LSD1 activities, significantly accelerates wound closure through enhanced re-epithelialization in a mouse tail wound model. Acetylated H3K9 (methylation of histone H3 at lysine 9) expression, a histone modification targeted by HDAC1, is increased in keratinocytes after topical treatment with 100 nM and 1 μM of corin. In vitro experiments demonstrate that corin promotes migration and inhibits the proliferation of human keratinocytes. Furthermore, expression levels of genes promoting keratinocyte migration, such as AREG, CD24, EPHB2, ITGAX, PTGS, SCT1, SERPINB2, SERPINE1, SLPI, SNAI2, and TWIST, increased in keratinocytes treated with corin. These data demonstrate that dual inhibition of class I histone deacetylases and LSD1 by corin may serve as a new approach for promoting wound re-epithelialization and provide a platform for further applications of corin for the treatment of chronic wounds.


Pharmacist-Driven Dosing Services and Pharmaceutical Care Increase Probability of Teicoplanin Target Concentration Attainment and Improve Clinical and Economic Outcomes in Non-Critically Ill Patients.
Pharmacist-driven (PD) dosing and monitoring services have been shown to improve the clinical and economic outcomes in patients treated with different antibiotics, other than teicoplanin. This study investigates the impact of PD dosing and monitoring services on the clinical and economic outcomes of non-critically ill patients receiving teicoplanin treatment. A single-center retrospective study was conducted. Patients were divided into the PD group and the non-PD (NPD) group. Primary outcomes included the achievement of target serum concentration, and a composite endpoint of all-cause mortality, intensive care unit (ICU) admission, and sepsis or septic shock development during hospitalization or within 30 days of hospital admission. The cost of teicoplanin, overall medication cost, and total cost during hospital stay were also compared. A total of 163 patients from January to December 2019 were included and assessed. Seventy patients were assigned to the PD group and 93 to the NPD group. The PD group had a higher percentage of patients reaching the target trough concentration (54% versus 16%, p < 0.001). Around 26% of the patients in the PD group and 50% of the patients in the NPD group met the composite endpoint during their hospital stay (p = 0.002). The PD group exhibited a significantly lower incidence of sepsis or septic shock, shorter hospital stays, reduced drug costs, and lower total expenses. Our study demonstrates that pharmacist-driven teicoplanin therapy can improve the clinical and economic outcomes for non-critically ill patients. https://www.chictr.org.cn ; identifier, ChiCTR2000033521.


Studies on the synthesis, characterisation and antimicrobial activity of new Co(II), Ni(II) and Zn(II) complexes of Schiff base derived from ninhydrin and glycine.
For the first time, Co(II), Ni(II) and Zn(II) complexes have been synthesized involving an intermediate Schiff base, indane-1,3-dione-2-imine-N-acetic acid the condensed product of ninhydrin and glycine. These coloured complexes were characterised by elemental analysis, molar conductivity, thermogravimetric analyses/differential thermal analysis, infrared, magnetic susceptibility, NMR and electronic spectral studies. Mechanisms for their formation have been proposed. The experimental studies reveal that the complexes possess octahedral stereochemistry whereas the Schiff base behaves as a monobasic tridentate ligand. A molecular structure for the metal complexes is also proposed. A comparative study of the antimicrobial activity of ninhydrin and the corresponding metal complexes against Escherichia coli, Proteus mirabilis, Staphylococcus aureus and Streptococcus faecalis has been undertaken and the results are discussed.


How users make judgements about the quality of online health information: a cross-sectional survey study.
People increasingly use the Internet to seek health information. However, the overall quality of online health information remains low. This situation is exacerbated by the unprecedented "infodemic", which has had negative consequences for patients. Therefore, it is important to understand how users make judgements about health information by applying different judgement criteria. The objective of this study is to determine how patients apply different criteria in their judgement of the quality of online health information during the pandemic. In particular, we investigate whether there is consistency between the likelihood of using a particular judgement criterion and its perceived importance among different groups of users. A cross-sectional survey was conducted in one of the leading hospitals in a coastal province of China with a population of forty million. Combined-strategy sampling was used to balance the randomness and the practicality of the recruiting process. A total of 1063 patients were recruited for this study. Chi-square and Kruskal-Wallis analyses were used to analyse the survey data. In general, patients make quality judgement of health information more frequently based on whether it is familiar, aesthetic, and with expertise. In comparison, they put more weights on whether health information is secure, trustworthy, and with expertise when determining its quality. Criteria that were considered more important were not always those with a higher likelihood of being used. Patients may not use particular criteria, such as familiarity, identification, and readability, more frequently than others even if they consider them to be more important than other do and vice versa. Surprisingly, patients with a primary school degree put more weight on whether health information is comprehensive than those with higher degrees do in determining its quality. However, they are less likely to use this guideline in practice. To the best of our knowledge, this is the first study to investigate the consistency between the likelihood of using certain quality judgement criteria and their perceived importance among patients grouped by different demographic variables and eHealth literacy levels. The findings highlight how to improve online health information services and provide fine-grained customization of information for users.


Use of a Computer Program for Advance Care Planning with African American Participants.
The authors wish to acknowledge the support and assistance of Dr. William Lawrence for his contribution to the M.A.UT model used in the decision aid, Making Your Wishes Known: Planning Your Medical Future (MYWK), Dr. Cheryl Dellasega for her leadership in focus group activities, Charles Sabatino for his review of legal aspects of MYWK, Dr. Robert Pearlman and his collaborative team for use of the advance care planning booklet "Your Life, Your Choices," Megan Whitehead for assistance in grant preparation and project organization, and the Instructional Media Development Center at the University of Wisconsin as well as JPL Integrated Communications for production and programming of MYWK. For various cultural and historical reasons, African Americans are less likely than Caucasians to engage in advance care planning (ACP) for healthcare decisions. This pilot study tested whether an interactive computer program could help overcome barriers to effective ACP among African Americans. African American adults were recruited from traditionally Black churches to complete an interactive computer program on ACP, pre-/post-questionnaires, and a follow-up phone interview. Eighteen adults (mean age =53.2 years, 83% female) completed the program without any problems. Knowledge about ACP significantly increased following the computer intervention (44.9% → 61.3%, p=0.0004), as did individuals' sense of self-determination. Participants were highly satisfied with the ACP process (9.4; 1 = not at all satisfied, 10 = extremely satisfied), and reported that the computer-generated advance directive accurately reflected their wishes (6.4; 1 = not at all accurate, 7 = extremely accurate). Follow-up phone interviews found that >80% of participants reported having shared their advance directives with family members and spokespeople. Preliminary evidence suggests that an interactive computer program can help African Americans engage in effective advance care planning, including creating an accurate advance directive document that will be shared with loved ones.


Differentiating the associations between sleep quality and suicide behaviors: A population-based study in China.
Although the association between sleep problems and suicidal behaviors were found in many studies, their associations are not built until now. One of the reasons may be the identified differences among different suicide behaviors, which also implied that sleep quality may play different roles on these suicidal behaviors. However, absent study explores the possible distinguishing associations between sleep quality and different suicidal behaviors. This is a population-based study conducted in Hebei province, China. Totally, 21,376 valid questionnaires were analyzed in this study. Pittsburgh Sleep Quality Index (PSQI) was used to evaluate sleep quality. Suicidal behaviors, living alone, and social-demographic variables were assessed for all the participants. The prevalence of suicidal ideation, plan, and attempt were 1.4%, 0.3%, and 0.2%, respectively. The PSQI scores were separately associated with suicidal ideation (OR=1.25, p<0.001), plan (OR=1.19, p<0.001), and attempt (OR=1.18, p<0.001). The similar results were also supported when we compared conditional suicidal behaviors with general population without any suicidal behaviors. However, when we compared suicide attempters with suicidal ideators (with or without suicide plan), the associations between PSQI scores and suicide attempt were not supported (OR=1.93, P>0.05 or OR=1.02, p>0.05). The cross-sectional design made us cannot get any causal relationships. The self-reported sleep quality may also produce some influence on the results. The results imply us that improving sleep quality may be not effective to control further suicidal behaviors, when people have considered or planned to suicide. The findings also can be translated into the clinical and preventive practice for suicide control.


Effects of chitosan combined with nisin treatment on storage quality of large yellow croaker (Pseudosciaena crocea).
Effects of chitosan combined with different concentrations of nisin on quality enhancement of large yellow croaker (Pseudosciaena crocea) stored at 4 °C were evaluated for 8 days. Changes in sensory score and volatile spoilage products, total viable counts (TVC), and physiochemical indexes including weight loss, colour, pH, total volatile basic nitrogen (TVB-N), and K-value were examined. Results demonstrated that nisin-treated samples presented better quality preservation effects than chitosan alone. 1% chitosan combined with 0.6% nisin presented optimal quality enhancement effects, such as moisture loss control, volatile spoilage inhibition, TVB-N reduction, TVC growth control, and colour and sensory acceptability maintenance. Therefore, chitosan combined with nisin is promising in large yellow croaker shelf life extension.


Dynamics of land cover changes and condition of soil and surface water quality in a Mining-Altered landscape, Ghana.
This study investigated the dynamics of mining effects on land use land cover changes and the chemical and physical characteristics of soil and surface water in the Ahafo mining area in Ghana. Landsat imagery was used to analyze land use-land cover changes (LULC) using a supervised classification technique. Soil samples were collected within 600 m from active mining operations and at depths of up to 75 cm, as well as surface water samples from upstream and downstream of the mine. Atomic Absorption Spectrometry was used to determine the concentration of heavy metals in the soil and water samples. The results demonstrated a significant loss of forest and other vegetation covers, which decreased from 44% to 31% to 8% and 20%, respectively, with corresponding increases in the mining site, mine water, settlement/bare surface, cropland and plantation. Organic matter, organic carbon, exchangeable bases, cation exchange capacity, available phosphorus, and pH were all moderate in the soil surrounding the mine. Except for As (4.027 mg/kg) and Hg (1 mg/kg), all heavy metals found in the soil were within FAO/WHO guidelines. Total Dissolved Solids (TDS) (416.18 mg/L), Total Suspended Solids (55.08 mg/L), Turbidity (54.49 NTU), Ca (84.49 mg/L), Mg (31.97 mg/L), nitrate (10.23 mg/L), and sulphate (606.83 mg/L) in the downstream water were higher than those in the upstream and USEPA/WHO limits for drinking water except for TDS. Because of the geology of the area, there were high concentrations of iron, manganese, and aluminum in the surface water. The results show that mining induced severe land cover changes and impaired surface water and soil quality in the mine's vicinity. The findings have implications for stakeholder education, appropriate community water interventions, and company-community-regulator participatory monitoring to avoid health risk exposure and further water and soil quality and vegetation degradation.


The Eurasian shrew and vole tick Ixodes trianguliceps: geographical distribution, climate preference, and pathogens detected.
The Eurasian shrew and vole tick Ixodes trianguliceps Birula lives in the nests and burrows of its small mammalian hosts and is-along with larvae and nymphs of Ixodes ricinus or Ixodes persulcatus-one of the most commonly collected tick species from these hosts in its Eurasian range. Ixodes trianguliceps is a proven vector of Babesia microti. In this study, up-to-date maps depicting the geographical distribution and the climate preference of I. trianguliceps are presented. A dataset was compiled, resulting in 1161 georeferenced locations in Eurasia. This data set covers the entire range of I. trianguliceps for the first time. The distribution area between 8[Formula: see text] W-105[Formula: see text] E and 40-69[Formula: see text] N extends from Northern Spain to Western Siberia. To investigate the climate adaptation of I. trianguliceps, the georeferenced locations were superimposed on a high-resolution map of the Köppen-Geiger climate classification. The Köppen profile for I. trianguliceps, i.e., a frequency distribution of the tick occurrence under different climates, shows two peaks related to the following climates: warm temperate with precipitation all year round (Cfb), and boreal with warm or cold summers and precipitation all year round (Dfb, Dfc). Almost 97% of all known I. trianguliceps locations are related to these climates. Thus, I. trianguliceps prefers climates with warm or cold summers without dry periods. Cold winters do not limit the distribution of this nidicolous tick species, which has been recorded in the European Alps and the Caucasus Mountains up to altitudes of 2400 m. Conversely, I. trianguliceps does not occur in the Mediterranean area with its hot and dry summers.


Assessing and mitigating the interference of ALX148, a novel CD47 blocking agent, in pretransfusion compatibility testing.
ALX148, a novel CD47 blocking agent, is in clinical development for the treatment of advanced solid tumors and lymphoma. Because CD47 is highly expressed on red blood cells (RBCs), its therapeutic blockade can potentially interfere with pretransfusion compatibility testing. This study describes the interference of ALX148 in pretransfusion compatibility testing and evaluates the methods used for mitigating such interference. Routine serologic tests were performed on six samples from four patients treated with ALX148. Antibody screening tests were performed on ALX148-spiked plasma, and RBC testing including antigen typing was performed on ALX148-coated RBCs. Soluble CD47 or high-affinity signal regulatory protein α (SIRPα) monomers were used to remove the false-positive reactivity of ALX148-spiked plasma with or without anti-E. ALX148 caused false-positive reactivity in antibody screening using indirect antiglobulin testing (IAT) and two-stage papain testing. However, false-positive reactivity was not observed at the immediate spin (IS), room temperature (RT), and 37°C phases. Direct antiglobulin testing, autologous controls, and eluates showed positive results. ALX148 did not affect blood group antigen typing performed at the IS or RT phases. The use of 50- to 100-fold molar excess of soluble CD47 or 300-fold molar excess of high-affinity SIRPα monomers removed false-positive reactivity in IAT without affecting anti-E detection. ALX148 generates false-positive reactivity in IAT, interfering with pretransfusion compatibility testing. The use of soluble CD47 or high-affinity SIRPα monomers can resolve the interference without possibly missing clinically significant alloantibodies.


A nutraceutical combination of Cinnamomum cassia &Nigella sativa for Type 1 diabetes mellitus.
Nigella sativa (black cumin) and Cinnamomum cassia (Cinnamon) are an integral part of the Indian diet, and have also been sourced in the ayurveda, the traditional Indian system of medicine, for their medicinal properties. Both the herbs individually have been successfully evaluated for their preliminary antidiabetic potential. Herein, we dived deeper into antidiabetic properties of these herbs, by investigating the combinatorial effect of both herbs, on parameters of diabetes and further, as an adjunct to metformin therapy, for assessing the pharmacodynamics of herb-drug interaction in diabetes mellitus. The objectives were to screen the combinatorial extract of Nigella sativa & Cinnamomum cassia's (NSCCe) alone and in combination with metformin for its potential in mitigating symptoms of diabetes mellitus-alone, and as an adjunct therapy with metformin. Diabetes was induced in the animals by a single intraperitoneal injection of streptozotocin. Animals were divided into seven groups with 6 animals each: Vehicle control, Negative control, Positive control (Metformin 50 mg/kg), treatment groups 4 and 5 received NSCCe at the doses of 100 mg/kg and 200 mg/kg, respectively. Groups 6 and 7 received the same doses, in combination with Metformin (50 and 25 mg/kg). Following a 28-day dosing period, plasma glucose levels, lipid profile and renal function profile were evaluated. Histopathological examinations were performed to measure any morphological change in kidney, liver and pancreatic tissue. Combination of Nigella sativa & Cinnamomum cassia extracts significantly normalized plasma glucose levels, lipid profile and kidney function parameters, compared to the diabetic control group. Animals treated with the combinatorial extract and metformin showed more prominent effects on these parameters. Significant reversal in the pancreatic cell damage was observed on treatment with NSCCe. This study generates evidence to support Nigella sativa & Cinnamomum cassia as an adjunctive in diabetes treatment protocols.


Synthesis and automated detection of fluorescently labeled primer extension products.
Common methods for determination of transcription initiation sites are based on the extension of radioactively labeled primers or internal labeling of extension products with reverse transcriptase. Here, we describe a modification of this procedure, adapted for automated detection of extension products by using fluorescent primers and an optimized reaction protocol. This facilitates high-throughput screening to detect mRNA start-points of large DNA regions and significantly reduces the time required to determine sites of transcription initiation.


Ligand size is a major determinant of specificity in periplasmic oxyanion-binding proteins: the 1.2 A resolution crystal structure of Azotobacter vinelandii ModA.
. Periplasmic receptors constitute a diverse class of binding proteins that differ widely in size, sequence and ligand specificity. Nevertheless, almost all of them display a common beta/alpha folding motif and have similar tertiary structures consisting of two globular domains. The ligand is bound at the bottom of a deep cleft, which lies at the interface between these two domains. The oxyanion-binding proteins are notable in that they can discriminate between very similar ligands. . Azotobacter vinelandii is unusual in that it possesses two periplasmic molybdate-binding proteins. The crystal structure of one of these with bound ligand has been determined at 1.2 A resolution. It superficially resembles the structure of sulphate-binding protein (SBP) from Salmonella typhimurium and uses a similar constellation of hydrogen-bonding interactions to bind its ligand. However, the detailed interactions are distinct from those of SBP and the more closely related molybdate-binding protein of Escherichia coli. . Despite differences in the residues involved in binding, the volumes of the binding pockets in the A. vinelandii and E. coli molybdate-binding proteins are similar and are significantly larger than that of SBP. We conclude that the discrimination between molybdate and sulphate shown by these binding proteins is largely dependent upon small differences in the sizes of these two oxyanions.


Induction of protective immunity and neutralizing antibodies to pseudorabies virus by immunization of anti-idiotypic antibodies.
Xenogenic anti-idiotypic antibodies (anti-Id) were prepared in rabbits against three murine neutralizing monoclonal antibodies (MAbs) directed to pseudorabies virus glycoproteins. These anti-Id were highly specific to idiotopes on the corresponding MAb molecules. Because the binding of MAb to the corresponding anti-Id was inhibited by the addition of viral envelope protein, these anti-Id seemed to contain a subpopulation of antibodies against the antigen-combining site (paratope) or the region related to the paratope of the MAb molecules. One of the anti-Id to a MAb directed against glycoprotein gp50 induced neutralizing antibodies to PrV. Mice immunized with the anti-Id were protected from lethal infection of PrV.


Weather, microclimate, and energy costs of thermoregulation for breeding Adélie Penguins.
We measured meteorological conditions and estimated the energy costs of thermoregulation for young and adult Adélie Penguins (Pygoscelis adeliae) at a breeding colony near the Antarctic Peninsula. Air temperatures averaged < 5°C and strong winds were frequent. Operative temperatures (Te) for adults ranged from -8 to 28°C, averaging 5-6°C, for the period from courtship to fledging of chicks. The average energy cost of thermoregulation (Cth) for adult penguins was equivalent to 10-16% of basal metabolism. Cth comprised about 15% of the estimated daily energy budget (DEB) of incubating adults, but only about 1% of the DEB of adults feeding chicks. The Te's for chicks older than 14 days ranged from 0 to 31°C, averaging 8.0 C. The Cth for downy chicks ranged from about 31% of minimal metabolic rate (MMR) in 1 kg chicks to about 10% of MMR in 3 kg chicks. Between initial thermal independence (age 12-14 days) and the cessation of parental feeding (age 35-40 days), chicks use about 10-11% of assimilated energy for thermoregulation. Cth is equivalent to about 17% of the MMR of fledglings during their 2-3 week fast. We observed no indication of thermal stress (i.e., conditions in which birds cannot maintain stable Tb) in adults and no indication of cold stress in any age class. However, on clear, calm days when air temperature exceeds 7-10°C for several hours, downy chicks are vulnerable to lethal hyperthermia.


Number and Location of Mini-Implants Retaining a Mandibular Overdenture to Resist Lateral Forces: A Preliminary In Vitro Study.
The aim of this study was to determine the optimal number and location of mini-implants retaining an overdenture to resist lateral forces. A strain gauge was attached to a mini-implant and placed in an edentulous mandible model. The following different implant locations were evaluated: one mini-implant at the midline, two mini-implants in the lateral incisor regions, two mini-implants in the canine regions, and four mini-implants. Lateral forces on mandibular overdentures retained by one mini-implant at the midline or two mini-implants in the lateral incisor regions appeared to be advantageous when compared with placing two mini-implants in the canine regions or four mini-implants. Fewer mini-implants resulted in less lateral stress, while four were associated with an unequal stress distribution.


Niclosamide-loaded nanoparticles (Ncl-NPs) reverse pulmonary fibrosis in vivo and in vitro.
Idiopathic pulmonary fibrosis (IPF), a life-threatening interstitial lung disease, is characterized by excessive activation and proliferation of fibroblasts and epithelial-mesenchymal transition (EMT) of alveolar epithelial cells (AEC) accompanied by a large amount of extracellular matrix aggregation. There are no therapies to reverse pulmonary fibrosis, and nintedanib and pirfenidone could only slow down the decline of lung function of IPF patients and delay their survival time. Niclosamide (Ncl) is an antihelminthic drug approved by FDA, which has been reported to have pleiotropic pharmacological activities in recent years, but it's almost complete insolubility in water limits its clinical application. To improve the water solubility of Ncl, explore its ability to reverse BLM-induced pulmonary fibrosis and its specific mechanism of action. The Niclosamide-loaded nanoparticles (Ncl-NPs) were formed by emulsification solvent evaporation method. A mouse model induced by bleomycin (BLM) was established to evaluate its effects and mechanisms of inhibiting and reversing fibrosis in vivo. The cell models treated by transforming growth factor-β1 (TGF-β1) were used to examine the mechanism of Ncl-NPs inhibiting fibrosis in vitro. Flow cytometry, IHC, IL-4-induced macrophage model and co-culture system were used to assess the effect of Ncl-NPs on M2 polarization of macrophages. The Ncl-NPs improved the poor water solubility of Ncl. The lower dose of Ncl-NPs (2.5 mg/kg) showed the same effect of reversing established pulmonary fibrosis as free Ncl (5 mg/kg). Mechanistic studies revealed that Ncl-NPs blocked TGF-β/Smad and signaling transducer and activator of transcription 3 (Stat3) signaling pathways and inhibited the M2 polarization of macrophages. Additionally, H&E staining of the tissues initially showed the safety of Ncl-NPs. These results indicate Ncl-NPs may serve as a new idea for the treatment of pulmonary fibrosis.


Clinical Outcomes by Race and Ethnicity in the Systolic Blood Pressure Intervention Trial (SPRINT): A Randomized Clinical Trial.
The Systolic Blood Pressure Intervention Trial (SPRINT) showed that targeting a systolic blood pressure (SBP) of ≤ 120 mm Hg (intensive treatment) reduced cardiovascular disease (CVD) events compared to SBP of ≤ 140 mm Hg (standard treatment); however, it is unclear if this effect is similar in all racial/ethnic groups. We analyzed SPRINT data within non-Hispanic White (NHW), non-Hispanic Black (NHB), and Hispanic subgroups to address this question. High-risk nondiabetic hypertensive patients (N = 9,361; 30% NHB; 11% Hispanic) 50 years and older were randomly assigned to intensive or standard treatment. Primary outcome was a composite of the first occurrence of a myocardial infarction, acute coronary syndrome, stroke, decompensated heart failure, or CVD death. Average postbaseline SBP was similar among NHW, NHB, and Hispanics in both treatment arms. Hazard ratios (HRs) (95% confidence interval) (intensive vs. standard treatment groups) for primary outcome were 0.70 (0.57-0.86), 0.71 (0.51-0.98), 0.62 (0.33-1.15) (interaction P value = 0.85) in NHW, NHB, and Hispanics. CVD mortality HRs were 0.49 (0.29-0.81), 0.77 (0.37-1.57), and 0.17 (0.01-1.08). All-cause mortality HRs were 0.61 (0.47-0.80), 0.92 (0.63-1.35), and 1.58 (0.73-3.62), respectively. A test for differences among racial/ethnic groups in the effect of treatment assignment on all-cause mortality was not significant (Hommel-adjusted P value = 0.062) after adjustment for multiple comparisons. Targeting a SBP goal of ≤ 120 mm Hg compared to ≤ 140 mm Hg led to similar SBP control and was associated with similar benefits and risks among all racial ethnic groups, though NHBs required an average of ~0.3 more medications. Trial Number NCT01206062, ClinicalTrials.gov Identifier at https://clinicaltrials.gov/ct2/show/NCT01206062.


Prevalence of dermatophytic fungal infections in children: a recent study in Anambra state, Nigeria.
We conducted a recent survey of dermatological fungal infections amongst children in both urban and rural parts of Anambra State in the south-east geographical flank of Nigeria during the period January 2003 to December 2003. Samples were collected from 1624 children with clinically suggestive lesions and also between the ages of 4 and 16. Young children aged 7-11 and 4- 6 years had significantly higher incidences (P < 0.05) than their older colleagues aged 12-16 years among samples proved to be mycologically positive by microscopy, culture or both. There was a significant difference in the incidence of dermatophytoses amongst children in urban and rural areas investigated (P < 0.05). Tinea capitis was the predominant clinical type. Trichophyton tonsurans was the most prevalent etiological agent while Microsporum audouinii was the least in occurrence. We compared our result with a recent study in the northern geographical zone and observed that although incidence of dermatophytoses is higher in northern Nigeria, tinea capitis was the predominant clinical type in both regions. In addition, the etiological agents appear to vary from time to time in their occurrence and the reasons for these observations are discussed. A regular surveillance and assessment of the etiologic agent and its prevalence by medical mycologists is strongly recommended to facilitate monitoring, reduce/prevent transmission and spread of dermatophytes in countries like Nigeria where they constitute a public health problem.


Social media use among children and teenagers with asthma bronchiale
Introduction: The health behavior of patients with asthma bronchiale can be influenced by the virtual world (es., Facebook). It is often used to compensate their attachment deficits. Objective: In this study, the use of social media is analyzed among asthmatic children compared to a healthy control group. Method: 250 asthmatic and 250 healthy children were interviewed from the age of 10 to 18. The Facebook Intensity Scale, the Ten Item Personality Inventory, the Rosenberg Self-Esteem Scale, the short version of the Beck Depression Inventory and the Multidimensional Anxiety Scale for Children were used in the study. Results: Asthmatic children's social media time was significantly lower compared to that of healthy children (p<0.001). However, their feeling of being part of the Facebook community is the main motivation to use it (p<0.001). Higher scores of anxiety and depression, and the lower self-esteem compared to the healthy control group can be detected among asthmatic children (p<0.001). The increased use of Facebook can be shown in both groups of girls. The increased use of Facebook among girls is in connection with a higher score of depression and anxiety (p<0.05). Conclusion: Social media plays a very important role in the life of asthmatic children. The psychoeducation and prevention is of basic importance, because the age group of 10-18-year-old children is vulnerable to the addictive effect of social media.


Dimethyl isotope labeling assisted de novo peptide sequencing.
Here, we explore a de novo sequencing strategy in which we combine Lys-N protein digestion with differential isotopic dimethyl labeling to facilitate the (de novo) identification of multiply charged peptides in ESI-MS, both under CID and ETD conditions. For a large fraction of the Lys-N generated peptides, all primary amines are present at the N-terminal lysine, enabling specific labeling of the N-terminus. Differential derivatization of only the peptide N-terminus in combination with the simultaneous fragmentation of the corresponding isotopologues allows the straightforward distinction of N-terminal fragments from C-terminal and internal fragments. Furthermore, also singly and multiply charged N-terminal fragments can easily be distinguished due to the mass differences of the isotope labeled fragment pairs. As a proof of concept, we applied this approach to proteins isolated from an avocado fruit, and were able to partially de novo sequence and correctly align, with green plant homologues, a previously uncharacterized avocado ascorbate peroxidase.


Lymphocyte ectoenzymes in childhood idiopathic nephrotic syndrome.
Lymphocyte ectoenzymes with immunomodulatory function were investigated in 11 children with minimal change disease (MCD), 9 with primary focal segmental glomerulosclerosis (FSGS), and 17 age- and sex-matched healthy children. Basal, concanavalin A (Con A)-, and pokeweed mitogen (PWM)-stimulated lymphocyte ecto-5'-nucleotidase (5'-Nu), dipeptidyl peptidase IV (DPP IV), and alkaline phosphodiesterase I (APD) activities were determined. In MCD relapse ecto-APD activity of unstimulated lymphocytes was higher than controls. Ecto-APD of Con A-stimulated lymphocytes was below controls (23.0, range 7.2-48.7 nmol/min per 10(6) lymphocytes) in all active MCD (18.7, range 7.6-32.6), during corticosteroid treatment (14.6, range 4.5-54), and in remission (13.1, range 6.1-19.6), but was significant only in remission. Con A-stimulated DPP IV was significantly lower from controls (53.8, range 19.3-85.7 nmol/min per 10(6) lymphocytes) in all active MCD (38.1, range 10.8-82.1), during treatment (37.5, range 20.2-58.7), and in remission (39.4, range 24.3-69.6). In FSGS, unstimulated lymphocyte ecto-APD activity was greater than controls. However, Con A-stimulated lymphocyte ecto-APD and DPP IV activities were not significantly different from controls. Con A stimulation of lymphocyte ecto-APD and DPP IV activity was significantly reduced in MCD relapse and in remission, but not in FSGS. Basal, Con A-, and PWM-stimulated ecto-5'-Nu in MCD and FSGS were not different from controls. These results suggest a role for abnormal T cell function in MCD but not in FSGS. The difference in mitogen-stimulated expression of these ectoenzymes suggests a different pathogenesis of childhood MCD and primary FSGS.


Cytomegalovirus DNA stability in EDTA anti-coagulated whole blood and plasma samples.
Cytomegalovirus (CMV) DNA viral load testing is routinely performed in centers that serve patients that are immunosuppressed from organ or hematopoietic stem cell transplantation. Clinical laboratories that offer this testing often face practical concerns about the storage of these specimens to ensure accurate measurement for patient care. The published studies that assess CMV DNA stability at 4°C have done so only up to 72 h. Our objective was to determine the stability of CMV DNA in whole blood and plasma for clinical viral load testing over a 14 day period. Twenty-one plasma samples that were CMV-positive and twenty whole blood samples (including eleven CMV-negative whole blood samples spiked with CMV-positive plasma) were stored at 4°C and underwent extraction and amplification at 3 time points: Day 0, Day 7, and Day 14. Log(10) values were calculated and t-test was performed on the values comparing Day 0 to Day 14 for plasma and whole blood. There was no statistically significant difference between Day 0 and Day 14 for both specimen types, including the CMV-negative whole blood specimens that were spiked with CMV-positive plasma. CMV DNA in plasma and whole blood is stable for 14 days at a temperature of 4°C.


PET O-15 cerebral blood flow and metabolism after acute stroke in spontaneously hypertensive rats.
Hypertension is a major stroke risk factor and is correlated with worse outcome after stroke. Thus, the effects of hypertension on cerebral hemodynamics and metabolism within an hour after stroke must be evaluated in detail. Cerebral blood flow (CBF), oxygen extraction fraction (OEF), cerebral metabolic rate for oxygen (CMRO2) and cerebral metabolic rate for glucose (CMRglc) were measured 1 h after the occlusion of the right middle cerebral artery (MCA) in male spontaneously hypertensive rats (SHR) and male normotensive Wistar Kyoto rats (WKY). Physiological responses were determined by positron emission tomography (PET) using 15O-H2O and radiolabeled 15O-O2 blood (methodology previously developed in this laboratory) and by autoradiography (ARG) using 18F-FDG. The right hemisphere of SHR showed lower CBF values than the left hemisphere after stroke (right: 0.17+/-0.07 mL/min/g; left: 0.29+/-0.08 mL/min/g), CMRO2 (right: 2.55+/-0.80 mL/min/100 g; left: 4.11+/- 0.84 mL/min/100 g) and CMRglc (right: 52.4+/-16.2 mg/min/100 g; left: 65.6+/-10.2 mg/min/100 g). WKY rats exhibited significant decreases only in CBF and CMRO2. These results suggest greater underlying physiologic disturbances in SHR. Also, the occlusion significantly reduced CBF in both hemispheres of SHR compared with WKY, suggesting a disturbance of the autoregulatory mechanism in SHR. In summary, our results indicate that hypertension intensifies metabolic disturbances after the onset of stroke, at least in the first hour. Therefore, we suggest that hypertension not only increases the incidence of stroke but also exacerbates stroke-mediated damage.


Segmentation of paracentral acute middle maculopathy lesions in spectral-domain optical coherence tomography images through weakly supervised deep convolutional networks.
Spectral-domain optical coherence tomography (SD-OCT) is a valuable tool for non-invasive imaging of the retina, allowing the discovery and visualization of localized lesions, the presence of which is associated with eye diseases. The present study introduces X-Net, a weakly supervised deep-learning framework for automated segmentation of paracentral acute middle maculopathy (PAMM) lesions in retinal SD-OCT images. Despite recent advances in the development of automatic methods for clinical analysis of OCT scans, there remains a scarcity of studies focusing on the automated detection of small retinal focal lesions. Additionally, most existing solutions depend on supervised learning, which can be time-consuming and require extensive image labeling, whereas X-Net offers a solution to these challenges. As far as we can determine, no prior study has addressed the segmentation of PAMM lesions in SD-OCT images. This study leverages 133 SD-OCT retinal images, each containing instances of paracentral acute middle maculopathy lesions. A team of eye experts annotated the PAMM lesions in these images using bounding boxes. Then, labeled data were used to train a U-Net that performs pre-segmentation, producing region labels of pixel-level accuracy. To attain a highly-accurate final segmentation, we introduced X-Net, a novel neural network made up of a master and a slave U-Net. During training, it takes the expert annotated, and pixel-level pre-segment annotated images and employs sophisticated strategies to ensure the highest segmentation accuracy. The proposed method was rigorously evaluated on clinical retinal images excluded from training and achieved an accuracy of 99% with a high level of similarity between the automatic segmentation and expert annotation, as demonstrated by a mean Intersection-over-Union of 0.8. Alternative methods were tested on the same data. Single-stage neural networks proved insufficient for achieving satisfactory results, confirming that more advanced solutions, such as the proposed method, are necessary. We also found that X-Net using Attention U-net for both the pre-segmentation and X-Net arms for the final segmentation shows comparable performance to the proposed method, suggesting that the proposed approach remains a viable solution even when implemented with variants of the classic U-Net. The proposed method exhibits reasonably high performance, validated through quantitative and qualitative evaluations. Medical eye specialists have also verified its validity and accuracy. Thus, it could be a viable tool in the clinical assessment of the retina. Additionally, the demonstrated approach for annotating the training set has proven to be effective in reducing the expert workload.


Combined lidocaine 1% and hydroxypropyl methylcellulose 2.25% as a single anesthetic/ viscoelastic agent in phacoemulsification.
To evaluate the use of a mixture of hydroxypropyl methylcellulose 2.25% (HPMC) and lidocaine 1% (final concentrations) as a single viscoelastic/anesthetic agent to achieve proper anesthesia and viscoelastic properties during phacoemulsification. Department of Ophthalmology, Cairo University, Cairo, Egypt. This prospective randomized study comprised 70 eyes having routine phacoemulsification. Patients had the HPMC-lidocaine mixture (n = 35) or pure HPMC 2.25% (n = 35) injected before capsulorhexis and again before intraocular lens implantation. The results were evaluated by a pain/discomfort score postoperatively. The difference in medians of the overall intraoperative pain/discomfort scores between the 2 groups was not statistically significant. However, mild pain/discomfort was reported by 60.0% in the pure HPMC group and by 31.4% in the HPMC-lidocaine mixture group. Moderate pain/discomfort was reported by 28.6% and 5.7%, respectively. The difference between the 2 groups was statistically significant (P =.001). The use of a mixture of HPMC 2.25% and lidocaine 1% rather than a regular viscoelastic agent resulted in clinically and statistically significantly reduced pain/discomfort during phacoemulsification.


Yeast community associated with the solid state fermentation of traditional Chinese Maotai-flavor liquor.
Yeasts are the most important group of microorganisms contributing to liquor quality in the solid-state fermentation process of Chinese Maotai-flavor liquor. There occurred a complex yeast community structure during this process, including stages of Daqu (the starter) making, stacking fermentation on the ground and liquor fermentation in the pits. In the Daqu making stage, few yeast strains accumulated. However, the stacking fermentation stage accumulated nine yeast species with different physio-biochemical characteristics. But only four species kept dominant until liquor fermentation, which were Zygosaccharomyces bailii, Saccharomyces cerevisiae, Pichia membranifaciens, and Schizosaccharomyces pombe, implying their important functions in liquor making. The four species tended to inhabit in different locations of the stack and pits during stacking and liquor fermentation, due to the condition heterogeneity of the solid-state fermentation, including the different fermentation temperature profiles and oxygen density in different locations. Moreover, yeast population was much larger in the upper layer than that in the middle and bottom layers in liquor fermentation, which was in accordance with the profile of reducing sugar consumption and ethanol production. This was a systematical investigation of yeast community structure dynamics in the Maotai-flavor liquor fermentation process. It would be of help to understand the fermentative mechanism in solid-state fermentation for Maotai-flavor liquor.


Emergent lineages of mumps virus suggest the need for a polyvalent vaccine.
Mumps outbreaks among vaccinated patients have become increasingly common in recent years. While there are multiple conditions driving this re-emergence, convention has suggested that these outbreaks are associated with waning immunity rather than vaccine escape. Molecular evidence from both the ongoing American and Dutch outbreaks in conjunction with recent structural biology studies challenge this convention, and suggest that emergent lineages of mumps virus exhibit key differences in antigenic epitopes from the vaccine strain employed: Jeryl-Lynn 5. The American and Dutch 2016-2017 outbreak lineages were examined using computational biology through the lens of diversity in immunogenic epitopes. Findings are discussed and the laboratory evidence indicating neutralization of heterologous mumps strains by serum from vaccinated individuals is reviewed. Taken together, it is concluded that the number of heterologous epitopes occurring in mumps virus in conjunction with waning immunity is facilitating small outbreaks in vaccinated patients, and that consideration of a polyvalent mumps vaccine is warranted.


In situ hydrothermal synthesis of a novel hierarchically porous TS-1/modified-diatomite composite for methylene blue (MB) removal by the synergistic effect of adsorption and photocatalysis.
Hierarchically porous TS-1/modified-diatomite composites with high removal efficiency for methylene blue (MB) were prepared via a facile in situ hydrothermal route. The surface charge state of the diatomite was modified to enhance the electrostatic interactions, followed by in situ hydrothermal coating with TS-1 nanoparticles. The zeolite loading amount in the composites could be adjusted by changing the hydrothermal time. The highest specific surface area and micropore volume of the obtained composites were 521.3m(2)/g and 0.254cm(3)/g, respectively, with an optimized zeolite loading amount of 96.8%. Based on the synergistic effect of efficient adsorption and photocatalysis resulting from the newly formed hierarchically porous structure and improved dispersion of TS-1 nanoparticles onto diatomite, the composites' removal efficiency for MB reached 99.1% after 2h of photocatalytic reaction, even higher than that observed using pure TS-1 nanoparticles. Moreover, the superior MB removal kinetics of the composites were well represented by a pseudo-first-order model, with a rate constant (5.28×10(-2)min(-1)) more than twice as high as that of pure TS-1 nanoparticles (2.43×10(-2)min(-1)). The significant dye removal performance of this novel TS-1/modified-diatomite composite indicates that it is a promising candidate for use in waste water treatment.


Income-related health inequalities across regions in Korea.
In addition to economic inequalities, there has been growing concern over socioeconomic inequalities in health across income levels and/or regions. This study measures income-related health inequalities within and between regions and assesses the possibility of convergence of socioeconomic inequalities in health as regional incomes converge. We considered a total of 45,233 subjects (≥ 19 years) drawn from the four waves of the Korean National Health and Nutrition Examination Survey (KNHANES). We considered true health as a latent variable following a lognormal distribution. We obtained ill-health scores by matching self-rated health (SRH) to its distribution and used the Gini Coefficient (GC) and an income-related ill-health Concentration Index (CI) to examine inequalities in income and health, respectively. The GC estimates were 0.3763 and 0.0657 for overall and spatial inequalities, respectively. The overall CI was -0.1309, and the spatial CI was -0.0473. The spatial GC and CI estimates were smaller than their counterparts, indicating substantial inequalities in income (from 0.3199 in Daejeon to 0.4233 Chungnam) and income-related health inequalities (from -0.1596 in Jeju and -0.0844 in Ulsan) within regions.The results indicate a positive relationship between the GC and the average ill-health and a negative relationship between the CI and the average ill-health. Those regions with a low level of health tended to show an unequal distribution of income and health. In addition, there was a negative relationship between the GC and the CI, that is, the larger the income inequalities, the larger the health inequalities were. The GC was negatively related to the average regional income, indicating that an increase in a region's average income reduced income inequalities in the region. On the other hand, the CI showed a positive relationship, indicating that an increase in a region's average income reduced health inequalities in the region. The results suggest that reducing health inequalities across regions require a more equitable distribution of income and a higher level of average income and that the higher the region's average income, the smaller its health inequalities are.