Distribution of organophosphate esters influenced by human activities and fluvial-tidal interactions in the Dong Nai River System, Vietnam.
Limited information is known about organophosphate esters (OPEs) in sediments of the Dong Nai River System (DNRS) in Vietnam and the influences of complex hydro-sedimentary dynamics on their fate. In this study, 48 surface sediment samples were collected from the Dong Nai-Soai Rap River and its tributary Vam Co River for the determination of 11 target OPEs, together with grain size and total organic carbon (TOC). The total concentrations of OPEs were in the range of 39.4 ng/g dw-373 ng/g dw (mean: 128 ng/g dw), and tris(1-chloro-2-propyl) phosphate (TCPP) was the predominant one with an average contribution of 81%, followed by tri-n-butyl phosphate (TNBP), tris(2-ethylhexyl) phosphate (TEHP). The composition profiles of OPEs at different locations of the DNRS showed no significant differences (p > 0.05). In addition, the distribution of OPEs had been influenced by both human activities and the fluvial-tidal interactions. The highly frequent and various human activities in Ho Chi Minh City (HCMC) leaded to the highest total concentration of OPEs in the midstream site. Based on our dataset, TOC content and grain size of sediments had significant correlation with certain OPEs (p < 0.05), and sediments with higher TOC content and finer grain size in the DNRS were more likely to be deposited in the downstream reach, contributing to the estuary of the DNRS was identified as another hotspot with the second highest concentration of OPEs. Furthermore, the distribution of OPEs in the transects had distinct characteristics, which reflected the joint influence of the human activities and fluvial-tidal interaction as well. However, the mechanism of their influence needed further investigation.


The Lanz endotracheal tube decreases tracheal injury in dogs.
To determine, in dogs anesthetized with nitrous oxide (N2O), (whether the endotracheal tube (ETT) cuffed with a Lanz pressure regulating valve decreases the tracheal consequences of tracheal intubation. Sixteen mixed-breed dogs were allocated to two groups according to the ETT used: Control group (n = 8) - Rüsch ETT, and Lanz group (n = 8) - ETT with Lanz pressure regulating valve. The ETT cuffs in both groups were inflated with air to an intracuff pressure of 30 cm H2O. Anesthesia was induced and maintained with pentobarbitone and N2O (1.5 L x min(-1)) and O2 (1 L x min(-1)). ETT cuff pressures were measured before (control) and 60, 120, and 180 min during N2O administration. The dogs were sacrificed, and biopsy specimens from four predetermined areas of the tracheal mucosa in contact with the ETT were collected for light and scanning electron microscopy (SM) examination. Cuff pressures in the Control group were higher than in the Lanz group at all time points studied (P < 0.001), with an increase over time only in the Control group (P < 0.001). Median neutrophilic inflammatory infiltration values of the epithelial surface, and in the subepithelial layer in contact with the cuff, were higher in the Control group as compared to the Lanz group (3.0 vs 1.0 and 3.0 vs 1.5 respectively) (P < 0.05). On SM examination, median histological grades were higher in the Control group compared to Lanz group (2.9 vs 1.9 respectively), (P < 0.05). The Lanz ETT decreases tracheal mucosal injury in dogs.


Split-bolus injection protocol with optimized timings of contrast medium injection and CT scanning for 3D CT angio-venography before laparoscopic gastrectomy.
To propose an optimization method of contrast medium injection for the split-bolus protocol based on the contrast medium pharmacokinetics and investigate the utility of the optimized split-bolus protocol in 3D CT angio-venography for laparoscopic gastrectomy. A pharmacokinetic relationship between injection duration and time to the peak enhancement was taken into account in the protocol design. The first 20 consecutive patients underwent a multi-phase scan with a single-bolus injection (single-bolus protocol), and the next 20 underwent the proposed split-bolus protocol. CT attenuations of the arteries and veins and dose-length products (DLPs) were compared between the two protocols. Two radiologists visually assessed arterial and venous depictions and the misregistrations. Mean arterial CT attenuations were not significantly different between the two protocols. Though mean venous CT attenuations for the split-bolus protocol were 7-11% lower than those of the single-bolus protocol, they were visually evaluated as similar. The mean DLP of the split-bolus protocol was 46% lower than that of the single-bolus protocol. Misregistration between the arteries and veins occurred 35-80% during the single-bolus protocol, but was not indicated in the split-bolus protocol. The split-bolus protocol with optimized timing was more effective for providing improved image quality with reduced radiation dose compared with the single-bolus protocol in 3D CT angio-venography for laparoscopic gastrectomy.


Cladosporium species causing "Cladosporium rot" on "Bosc" pear fruit in Argentina.
"Cladosporium rot" on "Bosc" pear fruit during cold storage causes significant economic losses and has been reported in recent years in the productive valleys of Río Negro and Neuquén. The species involved were not determined. During 2016-2017, "Bosc" pears (Pyrus communis) in cold storage chambers exhibited external brownish black circular spots caused by Cladosporium spp. The objective of this work was to determine the Cladosporium species that caused the above mentioned symptoms. The morphological and molecular analyses of the partial sequence of the actin gene (ACT) supported the identification. Cladosporium macrocarpum, Cladosporium subtilissimum and Cladosporium floccosum were determined as the species involved in the disease. Although Cladosporium has been reported to cause pear rot, this is the first report to identify these species as causal agents of this fruit disease.


Postoperative spindle-cell nodule of urinary bladder with unusual intracytoplasmic inclusions.
Postoperative spindle-cell nodule of the urinary bladder (or in the absence of previous surgical procedure, inflammatory pseudotumor) is a reactive process of unknown etiology mimicking a sarcoma. Intracytoplasmic inclusion bodies were noted inside the atypical spindle cells on Diff-Quik stained smears in a recent case of this entity. Although fluorescence was noted in the inclusion bodies with monoclonal antibodies against the major outer membrane protein of the Chlamydia species, the exact nature of these inclusion bodies remains unknown.


Two Novel C₃N₄ Phases: Structural, Mechanical and Electronic Properties.
We systematically studied the physical properties of a novel superhard (t-C₃N₄) and a novel hard (m-C₃N₄) C₃N₄ allotrope. Detailed theoretical studies of the structural properties, elastic properties, density of states, and mechanical properties of these two C₃N₄ phases were carried out using first-principles calculations. The calculated elastic constants and the hardness revealed that t-C₃N₄ is ultra-incompressible and superhard, with a high bulk modulus of 375 GPa and a high hardness of 80 GPa. m-C₃N₄ and t-C₃N₄ both exhibit large anisotropy with respect to Poisson's ratio, shear modulus, and Young's modulus. Moreover, m-C₃N₄ is a quasi-direct-bandgap semiconductor, with a band gap of 4.522 eV, and t-C₃N₄ is also a quasi-direct-band-gap semiconductor, with a band gap of 4.210 eV, with the HSE06 functional.


Inclusion of men in health services and educational activities: the fathers' perceptions.
To learn about the perception of fathers regarding their inclusion in health services and/or educational activities. Qualitative, exploratory, and descriptive study addressing 22 fathers participating in a group of pregnant women in Rio Grande, RS, Brazil. Data were collected through semi-structured interviews and analyzed using the content analysis technique. The following categories emerged from the participants' reports: fathers' perceptions regarding their presence in health services and fathers' perceptions regarding their participation in the group of pregnant women. Additionally, they provided contributions and suggestions regarding their experiences with the group's meetings. The participants felt excluded from the services, which shows that health intervention strategies need to be (re)constructed to implement actions that include fathers as active participants in care, so they recognize the importance of their role in healthy human development.


Alloplasmic male sterility in Brassica napus (CMS 'Tournefortii-Stiewe') is associated with a special gene arrangement around a novel atp9 gene.
To identify regions of the mitochondrial genome potentially involved in the expression of alloplasmic 'Tournefortii-Stiewe' cytoplasmic male sterility (CMS) in Brassica napus, transcripts of 25 mitochondrial genes were analysed in fertile and near isogenic male-sterile plants (BC(8) generation). Differences were detected in the transcription of genes for subunit 9 of ATP synthase (atp9), cytochrome b (cob) and subunit 2 of NADH dehydrogenase (nad2). Structural analysis of these gene regions revealed differences in genome organisation around atp9 between male-sterile and fertile plants. Three atp9 genes, two of which were hitherto unknown, are present in the mitochondria of CMS plants, and rearrangements upstream of one of these genes have generated a chimeric 193-codon ORF, designated orf193. This region is transcribed as a CMS specific bi-cistronic mRNA of 1.58 kb comprising orf193 and atp9. The level of the aberrant 1.58-kb transcript is reduced in plants restored to fertility by as yet uncharacterized nuclear genes. orf193 encodes a polypeptide of 22.7 kDa which exhibits partial sequence identity to the subunit 6 of the ATP synthase complex. However, as it forms an uninterrupted ORF with one of the newly discovered atp9 genes it may also be translated as a chimeric 30.2-kDa protein. It is likely that either or both gene products interfere with the function or assembly of the mitochondrial F(0)F(1)-ATP synthase, thus impairing the highly ATP-dependent process of pollen development. The novel molecular features of alloplasmic 'Tournefortii-Stiewe' CMS are discussed with respect to the other known mechanisms of CMS in B. napus.


The effect of vasectomy on serum lipids.
The effects of vasectomy on serum lipids and free fatty acids were followed. The concentration of serum cholesterol was lower one year after vasectomy than one week after and immediately before vasectomy (p less than 0.01). The LDL-cholesterol concentration decreases by 16 per cent (p less than 0.01) within one year after vasectomy. The concentration of serum free fatty acids was significantly higher (p less than 0.001) before vasectomy than after it.


Neural-tube defect in dizygotic twins.
Despite the strong association between twinning and neural-tube defects (NTD), concordance of twins with NTDs is very rare. A case of concordant NTDs in dizygotic twins is reported in view of its extreme rarity.


Osteoclasts from medullary bone of egg-laying Japanese quail do not express the putative calcium 'receptor'.
The present study reports the contrasting effects of extracellular calcium ([Ca2+]e) elevation on cytosolic free calcium levels ([Ca2+]i) of osteoclasts, freshly isolated either from medullary bone of the egg-laying Japanese quail or from rat cortical bone. [Ca2+]i was measured in single osteoclasts using the Ca(2+)-sensitive fluorochrome, Indo-1. We found that elevation of [Ca2+]e failed to induce a rise of [Ca2+]i in quail osteoclasts, whilst causing an elevation of [Ca2+]i in rat osteoclasts. The calcium ionophore, ionomycin, led to a sustained elevation of [Ca2+]i in both cell types. These findings suggest that osteoclasts isolated from egg-laying quail do not possess the calcium sensor or 'receptor' that appears to be vital for the survival and function of rat osteoclasts.


Chronically administered Agave americana var. marginata extract ameliorates diabetes mellitus, associated behavioral comorbidities and biochemical parameters in alloxan-induced diabetic rats.
Diabetes mellitus causes hyperglycemia and associated complications to the brain. In current study, the traditionally reported remedial claims of Agave americana var. marginata has been scientifically investigated in diabetic rats. The methanolic extract of leaves of Agave americana var. marginata (Aa.Cr) was characterized for total phenols, flavonoids, and antioxidant potential through in-vitro testing. The rats chronically pre-treated with Aa.Cr (400 and 600 mg/kg) for 45 days were challenged with alloxan-induced hyperglycemia. The dose-dependent effects of Aa.Cr on blood glucose levels and body weights were compared with diabetic rats using glibenclamide (0.6 mg/kg) as a standard. The animals were tested for diabetes-associated neurological comorbidities through behavioral and biochemical evaluation. The phenols and flavonoids enriched Aa.Cr caused a significant dose-dependent hypoglycemic effect. Aa.Cr showed protection from comorbid anxiety, depression and cognitive impairment as compared to diabetic rats. The alanine aminotransferase, total cholesterol, triglycerides and low-density lipoprotein were prominently reduced, and high-density lipoprotein was increased in rats treated with Aa.Cr. Moreover, the oxidative stress in isolated brains was reduced by Aa.Cr. These findings suggest that Aa.Cr is enriched with antioxidant and anti-inflammatory phytoconstituents valuable for diabetes and related neurological complications.


Overcoming the Cost of Positive Autoregulation by Accelerating the Response with a Coupled Negative Feedback.
A fundamental trade-off between rapid response and optimal expression of genes below cytotoxic levels exists for many signaling circuits, particularly for positively autoregulated systems with an inherent response delay. Here, we describe a regulatory scheme in the E. coli PhoB-PhoR two-component system, which overcomes the cost of positive feedback and achieves both fast and optimal steady-state response for maximal fitness across different environments. Quantitation of the cellular activities enables accurate modeling of the response dynamics to describe how requirements for optimal protein concentrations place limits on response speed. An observed fast response that exceeds the limit led to the prediction and discovery of a coupled negative autoregulation, which allows fast gene expression without increasing steady-state levels. We demonstrate the fitness advantages for the coupled feedbacks in both dynamic and stable environments. Such regulatory schemes offer great flexibility for accurate control of gene expression levels and dynamics upon environmental changes.


Inactivation of the type IV secretion system reduces the Th1 polarization of the immune response to Brucella abortus infection.
The Brucella abortus type IV secretion system (T4SS), encoded by the virB operon, is essential for establishing persistent infection in the murine reticuloendothelial system. To gain insight into the in vivo interactions mediated by the T4SS, we compared host responses elicited by B. abortus with those of an isogenic mutant in the virB operon. Mice infected with the B. abortus virB mutant elicited smaller increases in serum levels of immunoglobulin G2a, gamma interferon (IFN-gamma), and interleukin-12p40 than did mice infected with wild-type B. abortus. Despite equal bacterial loads in the spleen, at 3 to 4 days postinfection, levels of IFN-gamma were higher in mice infected with wild-type B. abortus than in mice infected with the virB mutant, as shown by real-time PCR, intracellular cytokine staining, and cytokine levels. IFN-gamma-producing CD4(+) T cells were more abundant in spleens of mice infected with wild-type B. abortus than in virB mutant-infected mice. Similar numbers of IFN-gamma-secreting CD8(+) T cells were observed in the spleens of mice infected with B. abortus 2308 or a virB mutant. These results suggest that early differences in cytokine responses contribute to a stronger Th1 polarization of the immune response in mice infected with wild-type B. abortus than in mice infected with the virB mutant.


Usefulness of measurement of carotid arterial wall elasticity distribution in detection of early-stage atherosclerotic lesions caused by cigarette smoking.
The aim of this study was to evaluate early-stage changes in the arterial wall caused by smoking. A newly developed real-time ultrasonic measurement system was used to measure the elasticity distribution of the carotid arterial intima-media complex in 53 healthy male volunteers (mean age: 37.6 years), including 27 smokers. Simultaneous measurement of the elasticity distribution and intima-media thickness (IMT) was performed at six locations in the bilateral carotid arteries. The mean elastic modulus in the radial direction (Er) of the carotid arterial area where the IMT was less than 1.1 mm in smokers was larger than that in age-matched nonsmokers. There were no significant correlations between IMT and Er at the same location. However, a significant positive correlation was observed between the maximum IMT (maxIMT) and that of Er (maxEr) in six locations. In smokers, maxEr had a better correlation with the smoking index, and areas of IMT less than 1.1 mm containing harder lesions of Er ≥ 160 kPa were significantly more frequent than in nonsmokers. Measurement of carotid arterial wall elasticity is useful for detecting distortion in the intramural elasticity distribution that occurs prior to IMT thickening caused by smoking as an early-stage atherosclerotic sign.


Support provision in a digitalized world: The consequences of social sharing across different communication channels.
People tend to share their emotional experiences with others, with sharing increasingly done online. This raises questions about the quality of computer-mediated vs. face-to-face sharing. The present review (1) outlines conditions for sharing to improve emotional and relational well-being, (2) discusses when computer-mediated sharing with other people may (not) be conducive to these conditions, and (3) reviews recent research on the effectiveness of computer-mediated sharing with humans and virtual agents. It is concluded that the emotional and relational consequences of sharing are dependent on the responsiveness of the listener, regardless of the communication channel. Differences exist, however, in the extent to which channels are conducive to various forms of responding, with implications for speakers' emotional and relational well-being.


Positive persistent visual symptoms (visual snow) presenting as a migraine variant in a 12-year-old girl.
Migraine is a common neurological disorder affecting children, in which the headache is often preceded or accompanied by a complex of neurological symptoms known as an aura. Persistent visual symptoms are rare, with typical visual aura sometimes being poorly distinguished from other visual disturbances. We describe the case of a 12-year-old girl who has experienced persistent, constant symptoms throughout the visual fields of white, bright, jagged spots and black and white flashes with sparkles and dots since May 2010. She also has palinopsia, squiggles, and photophobia. The child's drawing of her visual symptoms helps illustrate the case and illuminate her ordeal. The child's visual symptoms have so far been resistant to pharmacological therapy. Further insight is needed into this debilitating condition to allow effective management in the pediatric population.


Death receptor 6 (DR6) is required for mouse B16 tumor angiogenesis via the NF-κB, P38 MAPK and STAT3 pathways.
Although death receptor 6 (DR6) is aberrantly expressed in certain cancer cell lines, its function, signaling pathway and potential clinical significance in tumor progression are not well characterized. We report here that knocking down DR6 in the mouse B16 cell line has no effect on B16 cell death in vitro but suppresses xenograft B16 tumor growth by preventing tumor blood vessel formation in vivo. Deficiency of DR6 changes cytokine expression and secretion; in particular, it inhibits the proinflammatory cytokine interleukin-6 (IL-6), which is able to induce the expression of the angiogenesis-related factors: vascular endothelial growth factor-A, platelet-derived growth factor-β, vascular endothelial growth factor-D and platelet-derived growth factor receptor-α. Further experiments demonstrate that DR6-dependent angiogenesis is involved in the IL-6/P38 MAPK and IL-6/STAT3 pathways. Our novel findings demonstrate for the first time that DR6 expression in B16 cells facilitates tumor growth by accelerating tumor angiogenesis. Moreover, these results suggest that DR6 is involved in three important intracellular pathways that lead to homeostatic angiogenesis in tumor growth.


The Charlottesville blood pressure survey: the role of the physician in hypertension case finding.
The population of a community of 29,608 adults was screened door-to-door for elevated blood pressure. A questionnaire was administered and analyzed to profile the hypertensive person who is most likely to be unaware of his problem. One hundred and one people with documented sustained hypertension were "unaware" of their problem. Of these, 58% had a diastolic blood pressure consistently greater than 100 mm Hg. Sixteen per cent of all hypertensive males were unaware of their problem compared to 5% of hypertensive females. Of those less than 35 years old, 38% of males were unaware compared with 4% of females. White (11%) persons were more apt to be unaware than non-white persons (6%). No person with a positive family history of hypertension was unaware. Ninety-one per cent of all unaware hypertensives had a regular physician. Sixty per cent had consulted a physician within 18 months, and 92% had consulted a physician within 60 months of the survey. The screening process was completed on only 21% of all adults in the target community. These data suggest that the young, white, hypertensive male with no family history of hypertension is most likely to be unaware of his problem. Routine measurement of blood pressure by physicians may be more efficient than door-to-door surveys in contacting the unaware hypertensive person.


Echocardiographic assessment of epicardial fat tissue thickness in patients with severe periodontitis.
This study aims to assess the thickness of epicardial fat tissue (EFT), a sign of cardiovascular risk, using echocardiography in patients with severe periodontitis. Thirty-three patients with stage III or IV periodontitis and 33 healthy participants were enrolled into the study. Epicardial fat tissue thickness was measured perpendicularly via echocardiography of the free wall of the right ventricular at end-diastole in three cardiac cycles. Body mass index (BMI) was calculated by dividing weight in kilograms by the height in meters squared. EFT to BMI ratio (EFT/BMI) was measured by dividing EFT by the BMI. There was no significant difference between study patients and the control group as regards to the frequency of diabetes, hypertension, smoking, and hyperlipidemia. The EFT and EFT/ BMI ratio were significantly different in the control and periodontitis groups (0.51±0.17 vs. 0.77±0.16, respectively; p ≤0.001) (0.021±0.008 vs. 0.030±0.006, respectively; p≤0.001). Pearson's correlation coefficient demonstrated a significant relationship between EFT and the clinical parameters of periodontitis (p<0.001) CONCLUSIONS: EFT thickness measured by echocardiography appears to be associated with severe periodontitis and may thus be an indirect sign of cardiovascular disease in periodontitis patients.


The SSG XVIII/AIO trial: results change the current adjuvant treatment recommendations for gastrointestinal stromal tumors.
Although adjuvant imatinib (IM) for high risk GIST is an accepted treatment consideration, the duration of therapy remains controversial. The recently published SSGXVIII/AIO randomized clinical trial of 3 years vs. 1 year of adjuvant IM has established a benefit of RFS and OS for the 3 year cohort. Future studies are necessary to continue to further delineate risk variables for GIST recurrence.


Chromatin-Associated Membraneless Organelles in Regulation of Cellular Differentiation.
Membrane-free intracellular biocondensates are enclosures of proteins and nucleic acids that form by phase separation. Extensive ensembles of nuclear "membraneless organelles" indicate their involvement in genome regulation. Indeed, nuclear bodies have been linked to regulation of gene expression by formation of condensates made of chromatin and RNA processing factors. Important questions pertain to the involvement of membraneless organelles in determining cell identity through their cell-type-specific composition and function. Paraspeckles provide a prism to these questions because they exhibit striking cell-type-specific patterns and since they are crucial in embryogenesis. Here, we outline known interactions between paraspeckles and chromatin, and postulate how such interactions may be important in regulation of cell fate transitions. Moreover, we propose long non-coding RNAs (lncRNAs) as candidates for similar regulation because many form foci that resemble biocondensates and exhibit dynamic patterns during differentiation. Finally, we outline approaches that could ascertain how chromatin-associated membraneless organelles regulate cellular differentiation.


Validating a common tick survey method: cloth-dragging and line transects.
Cloth-dragging is the most widely-used method for collecting and counting ticks, but there are few studies of its reliability. By using cloth-dragging, we applied a replicated line transects survey method, in two areas in Sweden with different Ixodes ricinus tick-densities (low at Grimsö and high at Bogesund) to evaluate developmental stage specific repeatability, agreement and precision in estimates of tick abundance. 'Repeatability' was expressed as the Intraclass Correlation Coefficient (ICC), 'agreement' with the Total Deviation Index (TDI) and 'precision' by the coefficient of variation (CV) for a given dragging distance. Repeatability (ICC) and agreement (TDI) were higher for the most abundant instar (nymphs) and in the area of higher abundance. At Bogesund tick counts were higher than at Grimsö and so also repeatability, with fair to substantial ICC estimates between 0.22 and 0.75, and TDI ranged between 1 and 44.5 counts of difference (thus high to moderate agreement). At Grimsö, ICC was poor to moderate and ranged between 0 and 0.59, whereas TDI remained low with estimates lower or equal to 1 count (thus high agreement). Despite a 100-fold lower abundance at Grimsö, the same level of precision for nymphs could be achieved with a 70% increase of dragging effort. We conclude that the cloth-dragging technique is useful for surveying ticks' and primarily to estimate abundance of the nymphal stage, whereas it rarely will be recommended for larvae and adults.


The effect of cyproterone acetate on adrenal cortical function in children with precocious puberty.
8 children with precocious puberty were treated with cyproterone acetate (CPA). During treatment there were no definite clinical signs of depressed adrenocortical function. The plasma cortisol concentrations were grossly depressed and the diurnal cortisol rhythm was abolished. Two months after discontinuation of CPA treatment the adrenocortical function had greatly improved. The lysin-vasopressin stimulation test revealed in one child a normal, in another child an exaggerated ACTH response during CPA therapy. Fasting plasma ACTH concentrations were elevated compared with normal controls, but they were very low compared with patients with Addison's disease. The results suggest that CPA has a twofold effect leading to adrenocortical insufficiency: i.e., inhibition of cortisol secretion by the adrenals themselves and inhibition of ACTH secretion at the hypothalamopitiuitary level.


Retinal function in eyes with proliferative diabetic retinopathy treated with intravitreal ranibizumab and multispot laser panretinal photocoagulation.
To compare retinal function changes in eyes with proliferative diabetic retinopathy (PDR) after intravitreal ranibizumab (IVR), combined or not with conventional (ETDRS) or multispot laser panretinal (PASCAL) photocoagulation (PRP). This study included laser-naive PDR patients that required PRP. Eyes were randomly and prospectively assigned to receive IVR or IVR combined with PASCAL or EDTRS. PRP was performed at baseline in 1 (PASCAL) or 2 (ETDRS) sessions. In eyes with macular edema, macular short pulse grid laser was associated with IVR at baseline and IVR was repeated monthly or quarterly if neovascularization was detected on angiography. Comprehensive ophthalmological evaluations, including SD-OCT, were performed at baseline and every 4 weeks after treatment. Full-field electroretinography (ERG: extended ISCEV standard) was performed at baseline and at 12, 24 and 48 weeks. IVR = 13, PASCAL = 15 and ETDRS = 15 eyes finished 48-week follow-up. There was a statistically significant BCVA improvement of 0.1-0.3 logMAR in all groups, and fluorescein angiography leakage area (FLA) reduced in 56%, 73%, and 73% from baseline for ETDRS, IVR and PASCAL, respectively, up to 48 weeks without significant differences between groups (p > 0.05). A significant a- and b-wave amplitudes reduction was observed for dark- and light-adapted ERG for ETDRS and PASCAL, but only minor dark-adapted b-wave reduction was found for IVR, up to 48 weeks. As an example, at week 48, combined response b-wave amplitude reduced in 181.5 ± 31.4 µV, 128.0 ± 27.9 µV and 82.4 ± 15.2 µV for ETDRS, PASCAL and IVR (p < 0.05 each group), respectively. No significant difference was observed between ETDRS and PASCAL for any ERG parameter. IVR combined with single or multiple spot PRP causes similar retinal function impairment during 48 weeks of observation, while IVR alone seems to be similarly effective controlling FLA without changing retinal function.


Association between different screening strategies for SARS-CoV-2 and deaths and severe disease in Italy.
The WHO recommends testing any suspected person with Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2), in order to limit the spread of the epidemic. In Italy, some Regions opted for extensive testing, whereas others limited tests to selected subjects. To assess the influence of different strategies, we examined the incidence of death and severe cases in Italy. Data on new cases of SARS-CoV-2, number of tests, deaths and admissions to Intensive Care Units (ICU) were retrieved in each Italian Region, from 24 February to 18 March 2020. As an index of different screening strategies, the number of tests/positive test results (P/T) ratio as of 7 March 2020, was considered. The cumulative number of deaths and of new severe cases, between March 23 and 25 was recorded. The association of those two outcomes with the number of P/T ratio was assessed using linear regression models. In the interval between March 23 and 25, recorded deaths (*million inhabitants) were 14 (3-54), whereas severe cases were 31 (10-112). Both the number of deaths and that of severe cases showed a significant correlation (R2 .57 and .41, with P < .01) with the P/T ratio. Deaths and severe cases were associated with higher mean personal income and lower density of General Practioners (GPs). The association of P/T with severe cases and deaths retained statistical significance after adjusting for mean personal income (R2 .30 and .41, respectively; both P = .04) and GPs density (R2 .21 and .19, respectively; both P = .03). A more aggressive screening strategy for SARS-Cov-2, was associated with lower rates of death and severe disease in Regions of Italy.


An investigation of a spread energy method for medical ultrasound systems. Part one: theory and investigation.
A medical ultrasound device using a Golay code is proposed and investigated theoretically. The code enables the spread energy method to be used to help overcome the restraints of the parameters of resolution, peak power and penetration.


Computerized interpretation of laboratory tests: an overview of systems, basic principles and logic techniques.
The ever-increasing volume and complexity of laboratory testing demands that interpretive reporting schemes be initiated. However, because of the massive volume of laboratory data, computers must be employed in this task. To design such programs, a clear understanding of the diagnostic process is required. There are numerous factors which must be respected for reports to be designed in an optimal fashion. Reports can vary in complexity from simple normal range listings to elaborate mathematical modelling of physiologic processes. A variety of well-studied logic techniques can be employed. These features have been studied during the development of the LABDOC computerized reporting system.


Importance of most frequent needs of the disabled in shaping areas of support in public health. Part 1. Analysis of selected demographic and social characteristics of the disabled with consideration of the causes of body dysfunction, legal disability status, and selected characteristics of the state of health.
The disabled are a group with a heterogeneous structure of causes and needs. The occurring physical, health, and social barriers constitute areas of public health. Assessment of these barriers requires systematic studies in order to use results supporting the tasks of public health, indispensable for pursuing the challenges of sustainable development. The aim of the study was to discuss the selected demographic, social, living and housing, as well as economic characteristics of the disabled rural and urban inhabitants, which are important for shaping the tasks of public health. The study group consisted of 676 disabled aged 19 - 98 years, including 56.4% of females and 43.6% of males, 38.0% of whom lived in rural areas. The disabled were qualified into a study group by the method of targeted sampling. The research instruments were an author-constructed Disability Questionnaire, and the Research Protocol. Statistical analysis was performed using the software IBM SPSS Statistics v. 27. The p values p < 0.05 were considered statistically significant. The level of risk of the phenomenon of disability was similar among both males and females. Higher risk was observed among widows and widowers, females with a low level of education, the disabled in older age groups, as well as those living in rural areas, maintaining themselves on non-earned sources of income, and running a single person household. The main causes of disability were diseases. 1. The majority of the population in the study were disabled with a legal grade of disability. 2. The analyzed characteristics fell within two groups: demographic and social, and health characteristics with difficult to separate health and social problems. 3. The most important problems in the area of public health were specified. 4. It is necessary to conduct studies considering demographic and social variables in order to level-up health inequalities between the disabled and those able-bodied. Effective solving of barriers and risks embedded in the social, family, and occupational situation prevents secondary disability, and also provides an opportunity for sustainable development in this population group.


Influence of three-dimensional culture in a type II collagen sponge on primary cultured and dedifferentiated chondrocytes.
Once articular cartilage is destroyed, the intrinsic reparative ability is poor. Therefore, various techniques have been developed to repair articular defects. Many kinds of scaffolds have been used for cultured chondrocyte transplantation. In this study, we developed a sponge consisting of type II collagen. We investigated the influence of three-dimensional culture on the maintenance of the chondrocyte phenotype and on the redifferentiation of dedifferentiated chondrocytes. Chondrocytes were isolated from the rib cartilage of rats and were cultured in plastic dishes for a week (P0). The cells were then dissociated with trypsin and subcultured for another 2 weeks (P1). Primary isolated chondrocytes were cultured in the type II collagen sponges for 3 weeks (S1). We compared the gene expression of S1 for chondrogenic markers with the expression of P0 and P1 by reverse transcription-polymerase chain reaction (RT-PCR). The cells were then dissociated with trypsin and subcultured for another 2 weeks (P1) and then another 6 weeks (P3). Cells of P1 were subsequently cultured in type II collagen sponges for 4 weeks (P1r). At each time point, gene expression of chondrogenic markers was examined by RT-PCR. Gene expression of COL2A1, COL10A1, and aggrecan in S1 was the same as in P0. Gene expression of COL10A1 and aggrecan in P1r was higher than in P1 and P3. Gene expression of COL1A1, COL2A1, and SOX9 in P1r was lower than in P1 and P3. Gene expression of ALP and osteocalcin in P1r was detected. These results show that culture in type II collagen sponges could maintain the chondrocyte phenotype; however, dedifferentiated chondrocytes differentiated to hypertrophic chondrocytes. These finding suggest that the complex of cells and scaffolds with primary cells was more useful than that with dedifferentiated chondrocytes in laboratory and clinical application.


Decrease in apparent Km for oxygen after stimulation of respiration of rat polymorphonuclear leukocytes.
The respiratory burst of polymorphonuclear leukocytes, induced by the addition of chemotactic peptide (N-formyl-methionyl-leucyl-phenylalanine) and cytochalasin B was found to consist of two phases. The first phase of very rapid oxygen uptake lasted 1-3 min. and was followed by a second more prolonged phase of lower magnitude. The apparent Km for oxygen of unstimulated cells was 9.6 +/- 0.67 microM, while that of the second phase of stimulation was 3.7 +/- 1.6 microM oxygen. The possibility that lowered oxygen concentrations may regulate polymorphonuclear leukocyte activity in some pathological conditions is discussed.


Liquid chromatographic determination of flunarizine dihydrochloride in the presence of its degradation product.
A simple, stability-indicating liquid chromatographic method has been developed for the assay of flunarizine dihydrochloride in the presence of its acid-induced degradation product. A Bondapak-C18 column was used with a mobile phase consisting of methanol-water (75:25, v/v) containing 0.5% w/v sodium chloride and 0.2% v/v triethanolamine adjusted to pH 6.6 with 30% hydrochloric acid at a flow rate 2 ml min-1. Quantitation was achieved with UV detection at 254 nm based on peak area or peak height ratios. The proposed method was successfully applied to the determination of the drug in laboratory-prepared mixtures in the presence of its degradation product and in capsules. Moreover, the method was utilized to investigate the kinetics of the degradation process at different temperatures and the apparent first-order rate constant, half-life and activation energy calculated.


CSF3R truncation mutations in a patient with B-cell acute lymphoblastic leukemia and a favorable response to chemotherapy plus dasatinib.
Activating mutations in the gene encoding for receptor of colony stimulating factor 3 (CSF3R) are drivers of pathogenesis in chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML). We describe a patient with newly diagnosed B-cell acute lymphoblastic leukemia (ALL) and three unique CSF3R truncating mutations which are predicted to be activating. After a slow early response to induction chemotherapy, dasatinib was added based on data from in vitro experiments demonstrating that dasatinib effectively targets key downstream kinases in CSF3R-mutated CNL/aCML. The patient subsequently achieved complete remission with minimal residual disease negativity that has been durable.


The factors of enhancing Graduate Teaching Assistants' Technological Pedagogical Content Knowledge (TPACK) performance in engineering curriculum teaching.
Graduate teaching assistants (GTAs) play important roles in engineering education at the undergraduate level. Since there are lots of technological content knowledge (TCK) in engineering curriculums, the improvements of GTAs' teaching skills on TCK will help the teaching effectiveness of the curriculums. As the instructor's knowledge about technology-infused instruction for TCK is the core of the teaching skill, Technological Pedagogical Content Knowledge (TPACK) is taken as a framework to measure the extent to which instructor can teach with technology. In this study, an online questionnaires survey covering GTAs' program coordinator, teacher, graduate student and undergraduate student has done to explore the factors of enhancing GTAs' TPACK performance. The quantitative analyses through a structural equation modeling approach indicates that the roles of the GTAs should be clearly recognized by the teacher, program coordinators and GTAs themselves. An evaluating procedure for GTAs should be established; The attitude and self-efficacy of GTAs should be improved through the training courses and the field trips while the promising expectation from the undergraduate student on the roles of GTAs can improve the performance of GTAs' program. Our results will be helpful not only for engineering curriculum, but also for other curriculums.


3-Hydroxy-3-methylglutaric acid (HMGA) reduces dietary cholesterol induction of saturated bile in hamster.
3-Hydroxy-3-methylglutaric acid (HMGA) is a competitive inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCoAR) and strongly reduces cholesterol biosynthesis both in vitro and in vivo. Since the effects of this compound on biliary lipid composition are hitherto unknown, we have investigated whether it prevents dietary cholesterol induction of saturated bile in the hamster. Female Golden Syrian hamsters have been divided into four groups and treated for 10 weeks as follows: I) Standard diet, containing 0.8 mg cholesterol/g food; II) Standard diet plus HMGA (100 mg/kg b.w./day per os); III) Lithogenic diet containing 2.4 mg cholesterol/g food; IV) Lithogenic diet plus HMGA as above. The results indicate that HMGA is effective in reducing both bile cholesterol supersaturation and hypercholesterolemia. Inhibition of hepatic cholesterogenesis at the level of mevalonate synthesis by HMGCoAR and reduction of intestinal cholesterol absorption may be responsible for these effects.


The balance of thrombosis and hemorrhage in STEMI patients with or without associated cardiac arrest: An observational study.
Data is scarce on hemorrhagic and thrombotic complications in patients with ST-elevation myocardial infarction (STEMI) associated with out-of-hospital cardiac arrest (OHCA). This is a monocentric, retrospective study conducted from January 2012 to December 2017 in a tertiary university hospital, which serves as a cardiac arrest center for a large urban area. Over the study period, all consecutive patients who were treated with stent implantation for STEMI with or without OHCA were included. Baseline characteristics, treatments, hemorrhagic and thrombotic events were compared between STEMI patients with and without OHCA. Univariate and multivariate analysis were performed in order to identify predictors of 30-day mortality, occurrence of major bleeding (MB), and early stent thrombosis (ST). A total of 549 patients treated for STEMI without OHCA and 146 patients for STEMI with OHCA were included. The incidence of definite ST and MB after coronary angioplasty was significantly higher in patients with OHCA (2.6% vs. 7.5%, p = 0.004 and 3.3% vs. 19.2%, p < 0.001, respectively). Independent predictors of MB in OHCA patients were anticoagulation therapy (HR = 3.11, 95%CI [1.22-7.98], p = 0.02) and the use of glycoprotein IIb/IIIa inhibitors (HR = 4.16, 95%CI [1.61-10.79], p = 0.003). Independent predictors of mortality in OHCA patients were age (HR = 1.05, 95%CI [1.02-1.09], p = 0.004) and ST (HR = 5.62, 95%CI [1.61-19.65], p = 0.007, with a protective effect of new anti-P2Y12 treatments (HR = 0.20, 95%CI [0.08-0.46], p < 0.001). Patients treated for STEMI associated with OHCA are at higher-risk of ST and MB than those who did not experience cardiac arrest. In this subset of patients, prospective studies are needed to better evaluate the balance of thrombosis and hemorrhage.


Utilizing Technology for Dermatology Care in Tajikistan: A Health Systems Perspective.
In Tajikistan, dermatologic services are available across the country. Yet, the most experienced dermatologists work at the National Republic Center for Dermatology and Venereology (NRCDV). Patients from across the country bypass local dermatologists and self-refer to NRCDV. Furthermore, no formal mechanisms exist for dermatologists in different cities to consult with experts at NRCDV. The authors designed a teledermatology program linking dermatologists across Tajikistan to NRCDV. They used the World Health Organization health systems framework to plan this program and define objectives. To date, 228 teledermatology consultations have taken place. The authors find that good governance is key to program implementation.


Prevalence of risk factors and estimation of 10-year risk for cardiovascular diseases among male adult population of Tamil Nadu India-an insight from the National Family Health Survey-5.
Cardiovascular diseases (CVD) are one of the most addressed preventable diseases of public health importance. However, the risk estimates and use of these risk scores for CVD prevention are the least explored areas. So, in this study, we explored the different categories of Framingham heart study (FHS) 10-year-CVD risk score and their associated factors among the adult male population in Tamil Nadu, India. We used the risk factor level data for male adults aged 18 years and above from the National Family Health Survey (NFHS-5) of Tamil Nadu state, India. Sociodemographic variables, behavioral factors, and physiological/biochemical factors were considered as the risk factor and were estimated using the world health organization (WHO) STEPS categories. FHS 10-year-CVD risk score was calculated using a body-mass index-based published Cox regression equation. Out of 2289 adult males, only 1.12% of the participants had a 10-year CVD risk score greater than 30% and ∼4% of the total participants require statin treatment (FRS-CVD risk score ≥20). Educational status (aOR:14.21, 95 CI: 4.36-46.22- no formal schooling when compared to 10th and above standard), weekly fruit intake (aOR:0.51, 95 CI: 0.27-0.97 when compared to daily fruit intake) and abdominal obesity (aOR:2.43, 95 CI: 1.58-3.74) were found to be associated with higher FRS scores when adjusted for all other factors not involved in FRS calculation. Widespread use of this score needs to be encouraged in clinical practices and patients with a higher risk of CVD events should be counselled for lifestyle modifications and compliance with treatment for decreasing the burden due to CVDs.


Efficacy of liraglutide in patients with diabetic nephropathy: a meta-analysis of randomized controlled trials.
The efficacy of liraglutide to treat type 2 diabetic nephropathy (T2DN) remains controversial. Thus, we conducted this meta-analysis to systematically evaluate the clinical effect of liraglutide on T2DN patients. Eight databases (PubMed, Web of Science, the Cochrane Library, EMBASE, Chinese National Knowledge Infrastructure (CNKI), Wanfang database, China Science and Technology Journal Database, and China Biology Medicine Database (CBM)) were searched for published articles to evaluate the clinical efficacy of liraglutide in subjects with T2DN. The Revman 5.3 and Stata 13 software were used for analyses and plotting. A total of 18 randomized controlled trials (RCTs) with 1580 diabetic nephropathy patients were screened. We found that the levels of UACR, Scr, Cysc were lower in the experimental group of T2DN patients treated with liraglutide than in the control group intervened without liraglutide. Liraglutide also reduced the levels of blood glucose (including FBG, PBG, and HbA1c), body mass index (BMI), and anti-inflammatory indicators (TNF-α, IL-6). However, there was no significant difference in BUN and eGFR between the experimental group and the control group. Liraglutide reduced the levels of Blood Glucose, BMI, renal outcome indicators, and serum inflammatory factors of patients with T2DN, suggesting the beneficial effects of liraglutide on renal function.


Protein "AGEing"--cytotoxicity of a glycated protein increases with its degree of AGE-modification.
Non-enzymatic glycation of proteins with reducing sugars and subsequent transition metal-catalyzed oxidations leads to the formation of protein-bound "advanced glycation endproducts" (AGEs). They accumulate on long-lived proteins including on and in the vicinity of the beta-amyloid plaques in Alzheimer's disease (AD). Since the AGE modification of a protein increases with time, and such a "long-term incubation" might also occur in the AD brain, we investigated whether an increase in the cytotoxic effects of an AGE-modified model protein occurs over time. Bovine serum albumin (BSA) was modified by glucose for defined time periods, and the viability of SH-SY5Y neuroblastoma cells, incubated with the differentially AGE-modified BSA samples, was measured with the MTT assay. Cytotoxicity of the AGE-modified BSAs increased in correlation to the incubation time with glucose. Among the AGE-specific markers, browning (OD 400) correlated best with cytotoxicity, followed by AGE-specific fluorescence and the defined AGE, carboxymethyllysine. Since AGEs accumulate in AD over time, they may be one of the "age-related" factors contributing to neuronal cell death in Alzheimer's disease.


Incorporation of Halogenated Amino Acids into Antibody Fragments at Multiple Specific Sites Enhances Antigen Binding.
Expansion of the amino-acid repertoire with synthetic derivatives introduces novel structures and functionalities into proteins. In this study, we improved the antigen binding of antibodies by incorporating halogenated tyrosines at multiple selective sites. Tyrosines in the Fab fragment of an anti-EGF-receptor antibody 059-152 were systematically replaced with 3-bromo- and 3-chlorotyrosines, and simultaneous replacements at four specific sites were found to cause a tenfold increase in the affinity toward the antigen. Structure modeling suggested that this effect was due to enhanced shape complementarity between the antigen and antibody molecules. On the other hand, we showed that chlorination in the constant domain, far from the binding interface, of Rituximab Fab also increased the affinity significantly (up to 17-fold). Our results showed that antigen binding is tunable with the halogenation in and out of the binding motifs.


Characterization of unknown compounds from stainless steel plates in matrix-assisted laser desorption/ionization mass spectrometry.
Peaks originating from unknown compounds on stainless steel plates used in matrix-assisted laser desorption/ionization (MALDI) mass spectrometers are observed around m/z 304.3, 332.3, 360.4, and 388.4 regardless of the matrix and/or solvent, and are even observed with bare plates. These peaks were characterized using three different types of MALDI-MS instrumentation: MALDI-TOF MS, MALDI-TOF/TOF MS, and MALDI-FTMS. The fragmentation data from MALDI-TOF/TOF MS and accurate mass determination by MALDI-FTMS enabled identification of the chemical formulae and structures. The unknown compounds are, in fact, likely benzylalkylmethylammonium salts, as confirmed by closely matching fragmentation patterns with a commercially available benzalkonium chloride.


Nanomaterials with dual immunomodulatory functions for synergistic therapy of breast cancer brain metastases.
A long-standing paucity of effective therapies results in the poor outcomes of triple-negative breast cancer brain metastases. Immunotherapy has made progress in the treatment of tumors, but limited by the non-immunogenicity of tumors and strong immunosuppressive environment, patients with TNBC brain metastases have not yet benefited from immunotherapy. Dual immunoregulatory strategies with enhanced immune activation and reversal of the immunosuppressive microenvironment provide new therapeutic options for patients. Here, we propose a cocktail-like therapeutic strategy of microenvironment regulation-chemotherapy-immune synergistic sensitization and construct reduction-sensitive immune microenvironment regulation nanomaterials (SIL@T). SIL@T modified with targeting peptide penetrates the BBB and is subsequently internalized into metastatic breast cancer cells, releasing silybin and oxaliplatin responsively in the cells. SIL@T preferentially accumulates at the metastatic site and can significantly prolong the survival period of model animals. Mechanistic studies have shown that SIL@T can effectively induce immunogenic cell death of metastatic cells, activate immune responses and increase infiltration of CD8+ T cells. Meanwhile, the activation of STAT3 in the metastatic foci is attenuated and the immunosuppressive microenvironment is reversed. This study demonstrates that SIL@T with dual immunomodulatory functions provides a promising immune synergistic therapy strategy for breast cancer brain metastases.


Methaemoglobin formation after the use of EMLA cream in term neonates.
EMLA cream 5% (a eutectic mixture of lidocaine and prilocaine) is a topical anaesthetic that has become widely used to minimize pain from venipuncture in children. It has not, however, been recommended in neonates owing to the potential risk of methaemoglobinaemia induced by prilocaine. The aim of this study was to establish the safety of 1 g EMLA cream 5% used on intact skin in term neonates. Forty-seven neonates, aged 0-3 months, with a postconceptual age of > or = 37 weeks and a body weight between 2.8 and 5.7 kg, were included in a double-blind, randomized, placebo-controlled study. After baseline observations a total dose of 1.0 g EMLA/placebo was applied to two sites (0.5 g site(-1)) for 60-70 min. Venous methaemoglobin (metHb) levels were determined in each patient at baseline and at three randomly assigned times, 0.5-18 h after application. Following application of the cream, the mean metHb levels were 1.17% (range 0.50-2.53) in the EMLA group and 0.96% (range 0.50-1.53) in the placebo group. The metHb concentrations were significantly higher in the EMLA group in the intervals from 3.5 to 13 h after application than in the placebo group, but were well below potentially harmful levels. Based on these results, a 1-h application of 1 g EMLA cream is safe when used on the intact skin of term neonates below 3 months of age.


Double-lumen endobronchial tube intubation in patients with difficult airways using Trachlight and a modified technique.
We present a modified method for the insertion of double-lumen endobronchial tubes with Trachlight in patients with difficult airways. We also discuss whether our method is applicable to smaller double-lumen endobronchial tubes.


Mucosal repair in the gastrointestinal tract.
The epithelial response to injury in the intestinal mucosa will be described. A comprehensive evaluation of the literature was performed to provide a thorough review of mucosal injury and repair. The intestinal mucosa is a rapidly proliferating sheet of epithelial cells that sustains injury in response to stresses ranging from physiologic daily digestive trauma to severe insults associated with ischemia, chemicals, and infection. Breaks in epithelial continuity impair mucosal barrier function, perturb normal absorptive and secretory transport properties, and render the host susceptible to local infection and distant organ pathology. Minor breaches are rapidly repaired by epithelial restitution, a process independent of cell proliferation. Restitution is regulated by a variety of cytokines and growth factors and is modulated by integrin-dependent interactions with the extracellular matrix. The intracellular mechanisms that control restitution are complex and involve signaling pathways that control dynamic remodeling of the actin cytoskeleton. Emerging understanding of reparative processes suggest several possible therapeutic strategies to enhance gastrointestinal wound healing. Minor epithelial injuries are repaired with the complex process of epithelial restitution independent of cell proliferation.


Successful Preoperative Endovascular Embolization of an Extreme Hypervascular Glioblastoma Mimicking an Arteriovenous Malformation.
Preoperative endovascular embolization as a treatment for hypervascular glioblastomas has not been established. We report the case of an extreme hypervascular glioblastoma mimicking an arteriovenous malformation that was successfully treated with preoperative embolization and subsequent removal. A 66-year-old man presented with progressive right hemiparesis and sensory aphasia. Cranial computed tomography and magnetic resonance imaging revealed a left parietooccipital tumor with ring enhancement. Digital subtraction angiography revealed an extreme high-flow arteriovenous shunt. The patient underwent presurgical endovascular embolization using N-butyl cyanoacrylate in a manner similar to embolization for arteriovenous malformations. Subsequent tumor removal was achieved with minimal blood loss. This is the first reported case of presurgical embolization of a glioblastoma with a high-flow shunt. Embolization of a malignant tumor with a high-flow shunt, in a manner similar to embolization of arteriovenous malformations, is feasible and effective.


Should H. pylori be eradicated in non-ulcer dyspepsia?
Around half of patients with dyspepsia have no abnormal findings on endoscopy ('non-ulcer dyspepsia') yet, of these, 55% have Helicobacter pylori infection of the gastric mucosa. The eradication of H. pylori infection cures most patients with duodenal and gastric ulcer. Here, we discuss whether H. pylori eradication cures patients with non-ulcer dyspepsia.


Environmental etiology of gastric cancer in Iran: a systematic review focusing on drinking water, soil, food, radiation, and geographical conditions.
The aim of this systematic review study was to investigate the causal relationship between environmental factors and gastric cancer (GC) in Iran. In a narrow definition, the environment includes water, soil, air, and food. This definition was the main criterion for the inclusion of articles in this study. In addition, exposure to radiation and geographical conditions were considered as less investigated environmental factors in the literatures. International (PubMed, Web of Science, ScienceDirect, Scopus, and Cochran) and national (Scientific Information Database) databases were searched for articles on GC and environmental risk factors in Iran. Twenty-six articles were found to meet the inclusion criteria after title, abstract, and full text review. Risk factors identified for GC include consumption of red meat; high fat, fried, and salted meat; smoked, salted, and fried foods; some dairy products; roasted and fried seeds; strong and hot tea; and un-piped and unchlorinated drinking water, as well as exposure to radiation, loess sediment, soft and grassy soil, soil containing low concentration of molybdenum, and proximity to volcanos. Fresh fruits and vegetable, fresh fish, and honey consumption were recognized as protective agents. Given the risk factors identified, strategies to prevent GC would be educating people to choose a healthy diet and to cook and store food properly, providing access to safe drinking water, taking into account topographical and geographical conditions in choosing a right location to build residential areas, and regulating the use of radiation-emitting devices.


[Psychotherapy aspects of inpatient treatment of adolescents with acute psychiatric illnesses].
In the inpatient treatment of acute psychiatric episodes in children and adolescents, the psychiatrist must set up an initial treatment plan incorporating one or more psychotherapeutic modalities and adapt this plan to the patient's clinical course. This article summarises the clinical experience of a model unit at the University of Heidelberg, the result of a collaboration between the Department of General Psychiatry and the Department of Child and Adolescent Psychiatry at the Clinic of Psychiatry. A series of 116 adolescent admissions was reviewed for clinical diagnosis, the nature and frequency of psychotherapeutic modalities, and the role of family involvement in patient care. Differential and adaptative approaches to the selection of treatment modalities in the context of an acute care setting are emphasised.


Radiation-free 3D head shape and volume evaluation after endoscopically assisted strip craniectomy followed by helmet therapy for trigonocephaly.
Radiation-free 3D post-operative sequential follow-up in craniosynostosis is hindered by the lack of consistent markers restricting evaluation to subjective comparison. However, using the computed cranial focal point (CCFP), it is possible to perform correct sequential image superposition and objective evaluation. We used this technique for mean volume and shape change evaluation of the head utilizing 3D photos after endoscopically assisted trigonocephaly surgery. We performed a mean head shape and volume evaluation on age grouped 3D photos (n = 86) of children who underwent endoscopically assisted strip craniectomy with helmet therapy. We used CT-scans of healthy children as reference. We performed a mean shape evolution analysis and calculated the anterior fossa to total volume ratio (A/T-ratio). The volume- and A/T-ratio pattern were compared with the reference group. The mean anterior fossa volume evolved from 336 ml (33.4% A/T-ratio) pre-surgery to 664 ml (36.0% A/T-ratio) at 37-48 months post-surgery. Both groups have a near similar volume- and A/T-ratio pattern over time. The first 18 months show a predominant growth around the resected metopic suture. Between 18 and 24 months we observed mostly anterior orbital rim growth. From 24 months till 36-48 months the head grows predominantly at the temporal area. The least outward growth was observed at the temporal bones. Using a novel technique we were able to objectively evaluate head shape and volume using stereophotogrammetry after endoscopically assisted strip craniectomy. The A/T-ratio and volume growth pattern of endoscopically treated patients is near identical to that of the normal reference group.


Unified approach to growth and aging in biological, technical and biotechnical systems.
Complex systems, in many different scientific sectors, show coarse-grain properties with simple growth laws with respect to fundamental microscopic algorithms. We propose a classification scheme of growth laws which includes human aging, tumor (and/or tissue) growth, logistic and generalized logistic growth and the aging of technical devices. The proposed classification permits to evaluate the aging/failure of combined new bio-technical "manufactured products", where part of the system evolves in time according to biological-mortality laws and part according to technical device behaviors. Moreover it suggests a direct relation between the mortality leveling-off for humans and technical devices and the observed small cure probability for large tumors.


Stationary bike injuries prompting emergency department presentation in pediatric patients: an epidemiological study.
Potential harms of stationary bike injuries in pediatric patients have been highlighted in the literature, but prior work is limited to case series and without population-level analysis. The purpose of this study is to examine the epidemiology of pediatric stationary bike injuries occurring in the US over the last decade using a national database. Injuries resulting from stationary bike use in pediatric patients from 2012 to 2021 were identified using coding from the National Electronic Injury Surveillance System (NEISS) database. Patient demographics, injury characteristics, and case narratives were examined. National annual estimates of injury frequency/incidence were calculated using weighting and survey package in R. Univariate analyses were used to compare injuries among groups. We identified 525 stationary bike injuries representing an estimated total of 15,509 injuries in the population. Pediatric patients sustained an average of 1,551 injuries annually, with an estimated yearly increase of 288 injuries (p < 0.01) after 2019. While males sustained more injuries, there were age-dependent differences in frequency of injuries between sexes (p < 0.01). The upper extremity was the most commonly injured body region overall, but children 5 and under sustained more injuries to the head/neck. The most common overall injury type was lacerations, while fractures predominated in the 6 to 11-year-old age group. Fifty-six percent of injuries were sustained not while riding the bike, most notably among children under 12. Our findings indicate that the impact of stationary bike injury in the pediatric population is not insignificant, and most injuries are related to improper play rather than traditional exercise use. Gender and age-related patterns differed in regard to the type and mechanism of injury sustained. Children 5 and under sustain a disproportionate amount of injuries to the head, neck, and upper extremity. As stationary bikes grow in popularity, preventative measures should be considered to reduce injuries to young children.


Coronavirus disease 2019: favorable outcome in an immunosuppressed patient with multiple sclerosis.
The rapid and global spread of severe acute respiratory syndrome coronavirus 2, a viral pathogen responsible for the development of the "coronavirus disease of 2019" (COVID-19), has developed into an unprecedented health crisis with considerable case fatality rate. Patients with comorbidities are considered to be at higher risk for severe disease with acute respiratory failure, intensive care unit admission, and/or death. Particular vigilance has been warranted regarding the continuation of immunosuppressive treatments since viral clearing may be hampered in such cases. In contrast, it has also been hypothesized that overactive immune responses may trigger a cytokine storm associated with clinical deterioration, which has generated an interest in certain immunosuppressant drugs as potential treatment for COVID-19. We would like to present the first case report of a patient who was formally diagnosed with COVID-19 while being under disease-modifying treatment with rituximab, an anti-CD20 B cell depleting agent, for multiple sclerosis. The clinical picture was mild for which we have tried to provide an immunopathological framework.


Breast cancer survivors' physical activity, psychosocial beliefs, daily trip behaviors, and subjective well-being: A descriptive study.
Physical inactivity has been a great public health concern among breast cancer survivors (BCS), especially during the COVID-19 pandemic, as it is closely related to a higher risk of cancer recurrence and mortality. The positive impacts of psychosocial beliefs in promoting physical activity (PA) have been well acknowledged. Therefore, this study aimed to explore the effects of psychosocial beliefs on PA in BCS to prevent physical inactivity. Furthermore, we examined the relationships between daily activities, trip behaviors, and associated subjective well-being. This study used a cross-sectional, descriptive study design. Female BCS who were able to exercise regularly completed the battery of assessments in March 2021. Specifically, the international PA questionnaires and the adapted PA-related psychosocial beliefs questionnaires were used to assess BCS's PA and psychosocial beliefs, respectively. In addition, the smartphone-based Day Reconstruction Method was utilized to measure subjective well-being. Data were analyzed using descriptive statistics, Chi-squared test, analyses of variance, and correlation analysis. In the context of investigations during the COVID-19 pandemic, our study showed that 77.8% of BCS reported meeting PA guidelines. As the components of psychosocial beliefs, the change strategies, social support, and confidence were significantly associated with higher PA levels. Additionally, the protective effect of leisure/recreation activities among BCS on their emotional well-being was observed. Overall, this study demonstrated the importance of understanding the relationship between BCS's psychosocial beliefs and PA during the pandemic. Notably, this study is unique because it used an application-based method to assess BCS' subjective well-being objectively.


The role of spouse reinforcement, perceived pain, and activity levels of chronic pain patients.
Levels of pain, activity, marital satisfaction, and contingent reinforcement for expressions of pain and suffering were assessed in chronic pain patients. In addition, spouses' marital satisfaction, mood, life control, and self-reported responses to the patient's pain were examined. Multiple regression analyses revealed that spouse reinforcement of overt expressions of pain was significantly related to both perceived pain and activity levels of chronic pain patients. The best predictor of patients' pain and activity levels was patients' perception of spouse reinforcement, followed by spouses' self-reported responses to the patients' pain. Spouse reinforcement of pain was not associated with spouses' marital satisfaction or perception of patients' pain levels. Rather, spouse reinforcement was associated with high interference of patients' pain with spouses' lives, spouses' positive mood, spouses' perception of more life control, as well as longer duration of the pain problem. The data support the importance of the spouse as a potential source of reinforcement of pain behavior.


The renal perfusion/excretion determination renogram: a new method of individual renal function determination in obstructive renal disease.
The divided renal function of 10 patients with unilateral renal obstruction was measured with the renal perfusion/excretion determination renogram, a computerized radioisotope function study, and with endogenous creatinine clearances. Functional impairment of the obstructed kidney when estimated by the effective renal plasma flow determination of the renal perfusion/excretion determination renogram correlated closely with that measured by creatinine clearance. The clinical applications of the renal perfusion/excretion determination renogram in unilateral renal obstruction include the preoperative evaluation of individual renal function and serial estimates of individual renal function in chronic obstructive processes.


[Hymenal examination of under age children with a context of sexual assault].
The hymeneal examination is often considered as the key of the gyneacological examination of a young girl victim of sexual assault, mainly because the concept of penetration is important under the French criminal code. However, the amount medical literature related to this topic is poor. The hymen examination must be conducted under strict conditions, by qualified personnel and as soon as possible after the alleged assault.The only kind of anomaly that can confirm a penetration is an injury to the posterior hymen extending up its base. The sensitivity of this sign is, however, low and its absence does not suggest that of penetration. A vaginal penetration does not always break the hymen, especially among adolescents. Moreover, the hymen can heal and thus it makes the examination difficult when it occurs a long time after the facts. Examination of the hymen is rarely the decisive factor in the forensic assessment of a young victim of sexual assault.


Regulation of interleukin-8 expression in porcine alveolar macrophages by bacterial lipopolysaccharide.
Interleukin (IL)-8 is a macrophage-derived neutrophil chemotactic factor that plays an important role in the recruitment of neutrophils to inflammatory loci. Hence, expression of IL-8 by alveolar macrophages may be a significant factor in host defense in the lung and in the pathogenesis of pneumonia in swine. To initiate molecular studies of IL-8 regulation in pigs, we cloned IL-8 cDNA and examined the regulation of its mRNA in alveolar macrophages. The porcine IL-8 cDNA consists of 1491 base pairs including a coding region of 309 base pairs. The deduced amino acid sequence was 75 and 81% similar to human and rabbit IL-8, respectively. Resting macrophages contained low levels of IL-8 mRNA, which increased markedly after exposure to bacterial lipopolysaccharide (LPS). LPS induction of IL-8 was direct, not mediated through elevation of tumor necrosis factor or interleukin-1. The effect of LPS on IL-8 expression was dose dependent, and induction was observed at a concentration of 10 pg/ml. IL-8 mRNA expression was detectable within 0.5 h after stimulation with LPS, peaked at 3-6 h at about 30-fold higher levels than in resting cells, and was maintained for 24 h. Secreted IL-8, measured by neutrophil chemotaxis, was induced within 4 h by LPS, and accumulated in the media throughout the 24-h period. The mechanism of induction of IL-8 mRNA appeared to involve transcription and RNA processing. Nuclear run-on analysis showed that the IL-8 gene was actively transcribed in noninduced cells; upon stimulation with LPS, the rate of IL-8 transcription was increased about 4-fold. A single mature mRNA species was detected by primer extension analysis. The half-life of IL-8 mRNA transcripts in aveolar macrophages was approximately 2 h and did not change after LPS stimulation. The ability of LPS to induce IL-8 expression was suppressed by recombinant human IL-4 and dexamethasone in a concentration-dependent manner. These observations indicate that the expression of IL-8 is an early event in the sequelae to bacterial infection in the lung.


Assessment of the Correlations Between Brain Weight and Brain Edema in Experimental Subarachnoid Hemorrhage.
Because brain edema is correlated with poor outcome in clinical subarachnoid hemorrhage (SAH), appropriate evaluation methods for brain edema are important in experimental SAH studies. Although brain water content (BWC) is widely used to evaluate brain edema in stroke research, the usefulness of brain weight is undetermined. In this study, we examined the role of brain weight in the evaluation of brain edema in experimental SAH. The endovascular perforation model of SAH was used, and rats were assessed by neurological scoring (NS). The brains were quickly removed at 24 h after the operation, and the weights of wet cerebrum (WWC) and dry cerebrum (WDC) were measured to determine the brain water content (BWC). The correlations of those values with each other and to body weight (BW) were then examined to reveal the significance of brain weight. The rats were assigned to sham-operated (n = 8) and SAH (n = 16) groups. There were no significant differences in WWC between the groups (p = 0.61). WWC was correlated with BWC but not with NS in all rats. In addition, WWC was clearly correlated with BW and WDC, which is thought to substitute for the original brain weight. From these results, we suggest that the measurement of brain weight as an evaluation of brain edema is limited and that BW and original brain volume can be confounding factors in evaluation.


The policy context for child and adolescent mental health services: implications for systems reform and basic science development.
Significant state and national policy initiatives are focusing on strategies for financing and structuring the delivery of evidence-based services for children. These initiatives reflect, in part, an increased awareness of and respect for scientific standards about effective treatments and services. At the same time, major studies of system reform and organizational behavior are calling into question the effectiveness of current practices and identifying the complexities of taking science-based services to scale. Four major policy initiatives are described and the implications of scientific developments within the basic neurosciences for improving policy, practice, and service in children's mental health is discussed.


Synthesis and biological properties of C-terminal vinyl ketone pseudotripeptides.
The ubiquitin-proteasome pathway responsible for the turnover of many cellular proteins represents an attractive target in the development of new drug therapies: In particular, modulation of the proteasome activity by specific inhibitors may represent a useful tool for the treatment of tumours. Here, we report synthesis and activity of a new series of oligopseudopeptide analogues bearing a vinyl ketone pharmacophoric unit at the C-terminal position. Some derivatives showed inhibition in the µM range of the trypsin-like (T-L) active site of the proteasome.


A randomised controlled trial of intrapleural balloon intercostal chest drains to prevent drain displacement.
Chest drain displacement is a common clinical problem that occurs in 9-42% of cases and results in treatment failure or additional pleural procedures conferring unnecessary risk. A novel chest drain with an integrated intrapleural balloon may reduce the risk of displacement. A prospective randomised controlled trial comparing the balloon drain to standard care (12 F chest drain with no balloon) with the primary outcome of objectively defined unintentional or accidental chest drain displacement. 267 patients were randomised (primary outcome data available in 257, 96.2%). Displacement occurred less frequently using the balloon drain (displacement 5 of 128, 3.9%; standard care displacement 13 of 129, 10.1%) but this was not statistically significant (OR for drain displacement 0.36, 95% CI 0.13-1.0, Chi-squared 1 degree of freedom (df)=2.87, p=0.09). Adjusted analysis to account for minimisation factors and use of drain sutures demonstrated balloon drains were independently associated with reduced drain fall-out rate (adjusted OR 0.27, 95% CI 0.08-0.87, p=0.028). Adverse events were higher in the balloon arm than the standard care arm (balloon drain 59 of 131, 45.0%; standard care 18 of 132, 13.6%; Chi-squared 1 df=31.3, p<0.0001). Balloon drains reduce displacement compared with standard drains independent of the use of sutures but are associated with increased adverse events specifically during drain removal. The potential benefits of the novel drain should be weighed against the risks, but may be considered in practices where sutures are not routinely used.


3D-printing-assisted synthesis of paclitaxel-loaded niosomes functionalized by cross-linked gelatin/alginate composite: Large-scale synthesis and in-vitro anti-cancer evaluation.
Breast cancer is one of the most lethal cancers, especially in women. Despite many efforts, side effects of anti-cancer drugs and metastasis are still the main challenges in breast cancer treatment. Recently, advanced technologies such as 3D-printing and nanotechnology have created new horizons in cancer treatment. In this work, we report an advanced drug delivery system based on 3D-printed gelatin-alginate scaffolds containing paclitaxel-loaded niosomes (Nio-PTX@GT-AL). The morphology, drug release, degradation, cellular uptake, flow cytometry, cell cytotoxicity, migration, gene expression, and caspase activity of scaffolds, and control samples (Nio-PTX, and Free-PTX) were investigated. Results demonstrated that synthesized niosomes had spherical-like, in the range of 60-80 nm with desirable cellular uptake. Nio-PTX@GT-AL and Nio-PTX had a sustained drug release and were biodegradable. Cytotoxicity studies revealed that the designed Nio-PTX@GT-AL scaffold had <5 % cytotoxicity against non-tumorigenic breast cell line (MCF-10A) but showed 80 % cytotoxicity against breast cancer cells (MCF-7), which was considerably more than the anti-cancer effects of control samples. In migration evaluation (scratch-assay), approximately 70 % reduction of covered surface area was observed. The anticancer effect of the designed nanocarrier could be attributed to gene expression regulation, where a significant increase in the expression and activity of genes promoting apoptosis (CASP-3, CASP-8, and CASP-9) and inhibiting metastasis (Bax, and p53) and a remarkable decrease in metastasis-enhancing genes (Bcl2, MMP-2, and MMP-9) were observed. Also, flow cytometry results declared that Nio-PTX@GT-AL reduced necrosis and increased apoptosis considerably. The results of this study prove that employing 3D-printing and niosomal formulation is an effective approach in designing nanocarriers for efficient drug delivery applications.


Corpus gastritis in patients with endoscopic diagnosis of reflux oesophagitis and Barrett's oesophagus.
A high level of gastric acid secretion is considered to be a risk factor for reflux oesophagitis or Barrett's oesophagus. Corpus gastritis may have a protective effect on the oesophagus, because of decreased gastric acid output. To determine if corpus gastritis is associated with reflux oesophagitis or Barrett's oesophagus. Three antral and two corpus biopsies were taken from consecutive patients in whom Helicobacter pylori testing was requested during endoscopy at a single centre between January 1995 and May 1997. Antral and corpus gastritis was studied by histology; H. pylori was studied by histology, culture and CLO test. A regression model was used to test for correlation between reflux oesophagitis, Barrett's oesophagus and risk factors. During the study period, 676 patients had biopsies taken during upper gastrointestinal endoscopy. Endoscopic signs of reflux oesophagitis and Barrett's oesophagus were observed in 125 and 23 patients, respectively. Corpus gastritis was found in 59% of patients without reflux oesophagitis or Barrett's oesophagus, 45% of patients with reflux oesophagitis and 30% of patients with Barrett's oesophagus. Two hundred and fifty-seven patients underwent follow-up endoscopy after H. pylori therapy. During a mean follow-up of 3 months, the incidence of reflux oesophagitis was not statistically different for patients with healing of corpus gastritis (10/98; 10%) and patients with persistent gastritis (8/97; 8%). Corpus gastritis was less common in patients with an endoscopic diagnosis of reflux oesophagitis or Barrett's oesophagus.


Reduction of glycemic potentiation. Sensitive indicator of beta-cell loss in partially pancreatectomized dogs.
To determine which test of islet function is the most sensitive indicator of subclinical beta-cell loss, we studied six conscious dogs before and 1 and 6 wk after removal of the splenic and uncinate lobes [64 +/- 2% pancreatectomy (PX)]. To assess hyperglycemic potentiation, acute insulin secretory responses (AIR) to 5 g i.v. arginine were measured at the fasting plasma glucose (FPG) level after PG was clamped at approximately 250 mg/dl and after PG was clamped at a maximally potentiating level of 550-650 mg/dl. FPG levels were unaffected by PX (112 +/- 4 mg/dl pre-PX vs. 115 +/- 5 mg/dl 6 wk after PX, P NS). Similarly, basal insulin levels remained constant after PX (11 +/- 2 microU/ml pre-PX vs. 11 +/- 1 microU/ml 6 wk after PX, P NS). The AIR to 300 mg/kg i.v. glucose decreased slightly from 42 +/- 9 microU/ml pre-PX to 32 +/- 5 microU/ml 6 wk after PX (P NS), and thus the beta-cell loss was underestimated. In contrast, insulin responses to arginine declined markedly after PX. The AIR to arginine obtained at FPG levels declined from 23 +/- 3 microU/ml pre-PX to 13 +/- 2 microU/ml 6 wk after PX (P = .04). The AIR to arginine obtained at PG levels of approximately 250 mg/dl declined even more, from a pre-PX value of 56 +/- 7 microU/ml to 21 +/- 4 microU/ml 6 wk after PX (P = .02).(ABSTRACT TRUNCATED AT 250 WORDS)


Suicidal ideation in the Finnish general population. A 12-month follow-up study.
The epidemiology of suicidal ideation has remained a relatively unstudied area. The aim of this study was to investigate the incidence, prevalence and persistence of and recovery from suicidal ideation in a sample of the Finnish general population. Postal questionnaires including the Beck Depression Inventory (BDI) were mailed to the study subjects (n = 1,593) at baseline and on follow-up after 12 months. The suicidality item of BDI was used to screen suicidal ideation. The 12-month incidence (4.6%) and prevalence of suicidal ideation (14.7%) were higher in men than in women (3.1% and 9.2%, respectively). Sixty-nine per cent of those men and 59% of those women who had suicidal ideation at baseline continued to have suicidal thoughts on follow-up. Suicidal ideation and the severity of depression associated strongly. Over half of the men and women who had persistent suicidal ideation had not visited any health services for help with psychological distress during the 12-month follow-up period. Daily smoking associated with a decreased probability of recovery from suicidal ideation. Suicidal ideation is common and persistent at the population level. Seeking professional help for depression with suicidal tendencies is disproportionately low in relation to the high prevalence of suicidal ideation.


Phlorotannin and its Derivatives, a Potential Antiviral Molecule from Brown Seaweeds, an Overview.
Research on seaweeds provides a continual discovery of natural bioactive compounds. The review presents new information on studies of the potential and specific antiviral action of phlorotannin and their derivatives from marine brown algae. Phlorotannin is a polyphenolic derivative and a secondary metabolite from marine brown algae which exhibits a high quality of biological properties. Phlorotannin has a variety of biological activities that include antioxidant, anticancer, antiviral, anti-diabetic, anti-allergic, antibacterial, antihypertensive and immune modulating activities. These phlorotannin properties were revealed by various biochemical and cell-based assays in vitro. This distinctive polyphenol from the marine brown algae may be a potential pharmaceutical and nutraceutical compound. In this review, the extraction, quantification, characterization, purification, and biological applications of phlorotannin are discussed, and antiviral potential is described in detail.


A simulation study on beam property of 124Sb-Be isotope-based neutron for BNCT.
The 9Be(γ,n) neutrons with the energies at 21-24 keV generated by 1.691 MeV photons from 124Sb was investigated as a source of epithermal neutrons for BNCT, using PHITS code. A beam shaping assembly composed of 13 mm thick Be target, a gamma ray shield made of 30 cm thick Bi, and a reflector of 30 cm thick Pb satisfied the beam requirements of IAEA-TECDOC-1223. The needed 124Sb activity was estimated in the order of 1016-1017 Bq. Feasibility of BNCT using 124Sb-Be neutrons would be influenced by the capability of periodic supply of short-lived 124Sb (half-life: 60 days) with such high activity.


Impairments of glycogen and drug metabolisms by chloropeptide, a hepatotoxic mycotoxin of Penicillium islandicum sopp.
Administration of chloropeptide, a hepatotoxic cyclic pentapeptide of Penicillium islandicum Sopp, caused a marked decline in the hepatic glycogen synthetase activity with concomitant increase in NADP-dependent G-6-P dehydrogenase activity. The microsomalmixed function oxygenases were also reduced in the liver of rats following chloropeptide treatment.


Activator of G protein signaling 3 null mice: I. Unexpected alterations in metabolic and cardiovascular function.
Activator of G protein signaling (AGS)-3 plays functional roles in cell division, synaptic plasticity, addictive behavior, and neuronal development. As part of a broad effort to define the extent of functional diversity of AGS3-regulated-events in vivo, we generated AGS3 null mice. Surprisingly, AGS3 null adult mice exhibited unexpected alterations in cardiovascular and metabolic functions without any obvious changes in motor skills, basic behavioral traits, and brain morphology. AGS3 null mice exhibited a lean phenotype, reduced fat mass, and increased nocturnal energy expenditure. AGS3 null mice also exhibited altered blood pressure control mechanisms. These studies expand the functional repertoire for AGS3 and other G protein regulatory proteins providing unexpected mechanisms by which G protein systems may be targeted to influence obesity and cardiovascular function.


Association of metabolic dysfunction with cognitive decline and Alzheimer's disease: A review of metabolomic evidence.
The discovery of new biomarkers that can distinguish Alzheimer's disease (AD) from mild cognitive impairment (MCI) in the early stages will help to provide new diagnostic and therapeutic strategies and slow the transition from MCI to AD. Patients with AD may present with a concomitant metabolic disorder, such as diabetes, obesity, and dyslipidemia, as a risk factor for AD that may be involved in the onset of both AD pathology and cognitive impairment. Therefore, metabolite profiling, or metabolomics, can be very useful in diagnosing AD, developing new therapeutic targets, and evaluating both the course of treatment and the clinical course of the disease. In addition, studying the relationship between nutritional behavior and AD requires investigation of the role of conditions such as obesity, hypertension, dyslipidemia, and elevated glucose level. Based on this literature review, nutritional recommendations, including weight loss by reducing calorie and cholesterol intake and omega-3 fatty acid supplementation can prevent cognitive decline and dementia in the elderly. The underlying metabolic causes of the pathology and cognitive decline caused by AD and MCI are not well understood. In this review article, metabolomics biomarkers for diagnosis of AD and MCI and metabolic risk factors for cognitive decline in AD were evaluated.


Reviews on sun exposure and artificial light and melanoma.
Melanoma is the most common form of cancer among young adults aged 25-29 years and the second most common cancer in those aged 15-29 years. We reviewed all the evidence regarding risk factors for melanoma, looking in particular at childhood exposure to ultraviolet radiation (UV). UV radiation is clearly the predominant environmental and thus potentially modifiable risk factor for melanoma. All activities related to tan-seeking behaviour and history of sunburns were shown to be significantly associated to melanoma. Host factors, such as pigmentary characteristics, and genetic predisposition plays also an important role. UV exposure is not only due to the sun but also to indoor tanning devices that have been shown to lead to an elevated risk of melanoma. The strongest evidence for a link between artificial UV and melanoma is found among individuals who had their first exposure to indoor tanning before the age of 30: they have a 75% increase risk of developing melanoma than individuals who had no exposure to indoor tanning. Prevention is very important, especially for children and young adults, as childhood and adolescence are critical periods in the development of later melanoma. Indoor tanning is a widespread practice in most developed countries, particularly in Northern Europe and the USA. In the recent decades more and more people, especially teenagers and women, are exposed to substantially high radiant exposures of UV through artificial sources and these trends raised a considerable concern. In fact the International Agency for Research on Cancer concluded that the association between skin cancer and exposure to solar radiation and the use of UV-emitting tanning devices are causal. Interesting analyses carried out in Iceland showed that when interventions to discourage sunbed use were introduced the incidence of melanoma among women decreased. All this evidence encouraged many countries to introduce regulations on sunbed use to avoid exposure before the age of 18.


Patent omphalomesenteric duct of the vermiform appendix in a neonate: congenital appendicoumbilical fistula.
Umbilical anomalies arise from fetal structures such as the omphalomesenteric duct (OMD) or urachus or from failure of closure of the umbilical fascial ring. Persistence of the OMD may lead to several anomalies including umbilical sinus, umbilical cyst, Meckel's diverticulum, or patent OMD (POMD). A POMD is usually associated with the ileum, but rarely may be with the caecum or appendix. We describe a POMD of the vermiform appendix and discuss the possible pathogenesis and management.


Correlation of the Beta-trace protein and inflammatory cytokines with magnetic resonance imaging in chronic subdural hematomas : a prospective study.
Magnetic resonance imaging (MRI) of chronic subdural hematoma (CSDH) detects various patterns, which can be attributed to many factors. The purpose of this study was to measure the level of interleukin-6 (IL-6), interleukin-8 (IL-8), and highly specific protein [beta-trace protein (βTP)] for cerebrospinal fluid (CSF) in CSDHs, and correlate the levels of these markers with the MRI findings. Thirty one patients, treated surgically for CSDH, were divided on the basis of MRI findings into hyperintense and non-hyperintense groups. The concentrations of IL-6, IL-8, and βTP in the subdural fluid and serum were measured. The βTP was considered to indicate an admixture of CSF to the subdural fluid if βTP in the subdural fluid (βTPSF)/βTP in the serum (βTPSER)>2. The mean concentrations of IL-6 and IL-8 of the hyperintense group (n=17) of T1-WI MRI were 3975.1±1040.8 pg/mL and 6873.2±6365.4 pg/mL, whereas them of the non-hyperintense group (n=14) were 2173.5±1042.1 pg/mL and 2851.2±6267.5 pg/mL (p<0.001 and p=0.004). The mean concentrations of βTPSF and the ratio of βTPSF/βTPSER of the hyperintense group (n=13) of T2-WI MRI were 7.3±2.9 mg/L and 12.6±5.4, whereas them of the non-hyperintense group (n=18) were 4.3±2.3 mg/L and 7.5±3.9 (p=0.011 and p=0.011). The hyperintense group on T1-WI MRI of CSDHs exhibited higher concentrations of IL-6 and IL-8 than non-hyperintense group. And, the hyperintese group on T2-WI MRI exhibited higher concentrations of βTPSF and the ratio of βTPSF/βTPSER than non-hyperintense group. These findings appear to be associated with rebleeding and CSF admixture in the CSDHs.


Perspectives of pharmacists on facilitating experiential learning placements for pharmacy students in non-patient facing settings.
Recently, the model of pharmacy education in Ireland changed to a five-year pharmacy degree, with three distinct blocks of experimental placements dispersed throughout the degree. The United Kingdom is also considering the introduction of a similar five-year pharmacy degree, while the United States is looking to further expand non-clinical experiential learning opportunities. This study was carried out to ascertain the perspectives of pharmacists working in non-patient facing roles on the barriers to and facilitators of placements to aid in identifying placement recruitment strategies for non-patient facing placements. A questionnaire was distributed to pharmacists employed in non-patient facing settings, including in pharmaceutical industry, education, and regulation. Quantitative responses were analyzed using descriptive statistics, while qualitative questions were analyzed thematically. Regardless of experience in the practice setting or supervision, the majority expressed a preference for offering paid placements of six months' duration. There was divided opinion regarding whether students should be given study leave, whether the student's supervisor should be a pharmacist, and whether students should undertake specialized postgraduate training. The main barriers to placements were time, the placement structure, availability of suitable projects or supervisors, and awareness of placement opportunities. Prior experience in the practice area, developing the talent pipeline, and personal interests were all placement facilitators. Given the increasing roles for pharmacists in non-patient facing practice settings, this study highlights the importance of stakeholder involvement during the implementation of a new model of education to ensure that placements in all settings are feasible.


Suicidal ideation and attempts in patients who seek treatment for substance use disorder.
Patients with substance dependence have a great risk of suicidal ideation and attempts. The study of the specific risk characteristics of patients with substance use disorders who present with suicidal ideation and/or attempts becomes a crucial clinical issue in order to develop prevention strategies. The main goals of this study were to determine the prevalence rate of both suicidal ideation and attempts among patients receiving treatment for substance use disorder and to analyse the differential characteristics between these patients with and without suicidal behaviours. A sample of 334 patients (263 men-71 women) who sought treatment for substance use disorder in a Spanish clinical centre was assessed. In total, 43.7% of the patients presented with lifetime suicidal ideation (8.7% in the last month) and 17.7% with suicide attempts (1.5% in the last month). Patients with suicidal ideation or attempts showed a more severe addiction profile (assessed by the EuropASI), and more psychopathological symptoms (assessed by the SCL-90-R). Moreover the rate of suicidal ideation and attempts was significantly higher in inpatients than in outpatients. According to these results, systematic screening of suicidal risk in patients seeking treatment for substance use disorders is recommended, especially in those with a greater addiction severity.