Association of fractalkine with functional severity of heart failure and impact on clopidogrel efficacy in patients with ischemic heart disease.
Patients with heart failure (HF) display elevated levels of soluble fractalkine, a chemokine involved in inflammation processes, atherosclerosis and platelet activation. Further, fractalkine has been associated with reduced pharmacodynamic (PD) responsiveness to clopidogrel. The aim of this study was to investigate the association of fractalkine with the severity of HF and its impact on platelet activation and clopidogrel response in patients with coronary artery disease (CAD) with and without HF. This prospective PD study included 116 stable CAD patients on DAPT with aspirin and clopidogrel. Subjects were classified in two groups: patients with HF and reduced (<40%) left ventricular ejection fraction (HFrEF group, n = 56) and patients without HF (no HF group, n = 60). Clinical severity of HF was graded according to NYHA classification. Platelet function assays included vasodilator-stimulated phosphoprotein assay, multiple electrode aggregometry and light transmittance aggregometry. Fractalkine and P-selectin concentrations were determined by ELISA. Fractalkine levels progressively increased with the severity of the disease in the HFrEF group (NYHA I: 471.2 ± 52.4 pg/ml, NYHA II: 500.5 ± 38.4 pg/ml, NYHA III: 638.9 ± 54.3 pg/ml, p for linear trend 0.023). Numerically higher concentrations of fractalkine were observed in the HFrEF group compared to the no HF group with borderline significance (p = 0.052). No significant differences in clopidogrel-induced platelet inhibition according to fractalkine values were observed in any of the groups. Fractalkine levels were increased in patients with HFrEF and positively associated with the functional severity of the disease. No evident impact of fractalkine on clopidogrel PD efficacy was found.


Partial trisomy 3q.
A new case of partial trisomy 3q is reported in a 5-year-old female with severe congenital malformations and psychomotor retardation. A review of the literature, with a total of 11 patients, allows us to conclude that the clinical picture reminiscent of the Cornelia de Lange syndrome is caused by the trisomic state.


Molecular analysis of the rhabdoid predisposition syndrome in a child: a novel germline hSNF5/INI1 mutation and absence of c-myc amplification.
The authors report a case of the rhabdoid predisposition syndrome (RPS) secondary to a germline hSNF5/INI1 mutation, whose brain tumor was originally unclassified but finally diagnosed as an atypical teratoid/rhabdoid tumor (AT/RT) by molecular analysis. A 7-month-old infant presented with hydrocephalus secondary to a huge pineal tumor and subsequently developed a renal rhabdoid tumor. The histology of the brain tumor was initially undetermined; however, an AT/RT was strongly suspected because of her clinical course. Mutational screening of the hSNF5/INI1 gene by heteroduplex and direct sequence analysis detected a missense mutation at codon 53 (CGA --> TGA, arginine --> stop) in both tumors, as well as in normal tissue of the kidney. Polymerase chain reaction (PCR)-based microsatellite analysis showed in both tumors allelic loss on chromosome arm 22q to which the hSNF5/INI1 gene maps. c-myc amplification was examined by differential PCR but not detected. Histologic review of the brain tumor by immunohistochemistry confirmed focal expression of epithelial membrane antigen and smooth muscle actin. These findings suggest that the brain tumor was really an AT/RT as a component of RPS secondary to a germline hSNF5/INI1 mutation. The present mutation has never been reported in the literature.


Undescended testis: Level of knowledge among potential referring health-care providers.
Studies report that most boys with undescended testis(UDT) are referred and operated beyond the recommended age of 1 year, possibly due to lack of awareness of treatment guidelines. We investigate the level of knowledge of UDT among potential referring health-care providers. We devised a survey on the clinical features and appropriate management of UDT. Using convenience sampling, we approached health-care professionals with regular contact with paediatric patients and final year medical students. Respondents were allowed to remain anonymous. They were categorised according to specialty and level of experience/training. Of 1179 approached, 203 responded. Thirty-six (24%) of 149 qualified doctors had never seen a case of UDT. Median score was 6 (range 1-9). There was no significant difference in scores when comparing specialty. Mean scores decreased significantly in trend according to level of experience. When questioned regarding timings of referral and orchidopexy, 24% of qualified doctors would not refer until 9 months of age, and 66% thought orchidopexy should be done after 1 year old. Half would stop examining for UDT after 2 years old. Inexperience with UDT and outdated knowledge may contribute to delays in referral for UDT. Many would stop examining for UDT at 2 years old, placing undue reliance on accurate physical examination in early childhood and indicating lack of awareness of the ascending testis. Community health initiatives must emphasise recent changes in guidelines for management of UDT.


Clonal cytogenetic abnormalities in donor-derived cells after sex mismatched allogeneic stem cell transplantation.
Clonal cytogenetic abnormalities (CCA) in donor-derived cells after stem cell transplant (SCT) are typically reported in donor-derived cell neoplasms, but CCA also may reflect a constitutional abnormality in the donor or may be present in a recipient without overt hematological malignancy. We reviewed 8515 tests on 2035 patients, who had allogenic sex mismatched SCT and underwent serial cytogenetic analysis between 2006 and 2020 in our institution. A constitutional CCA was observed in 3 patients: inv(10), t(1;5), and t(13;14). A somatic CCA without overt neoplasia was detected in 12 patients: del(7q) (n = 6), del(20q) (n = 3), der(11)t(11;11) (n = 1), t(1;9) (n = 1), dup(6p)(n = 1). In this group, four patients with cytopenia had del(7q), and an association between del(7q) and an adverse overall survival (OS) was observed [HR:5.99; 95%CI 1.23-29.92). Four patients had a donor-derived cell neoplasm: myelodysplastic syndrome (n = 3) and acute myeloid leukemia (n = 1), and all four neoplasms had loss of 7q. In our cohort, ∼1% of the patients (19/2,035) had CCA in donor-derived cells. Balanced constitutional CCA can pose a reproductive risk to donor. Loss of 7q is the most common somatic CCA, in donor-derived cells.


Pyranocoumarins from Zosima absinthifolia (Vent) Link roots.
Zosima absinthifolia (Vent) Link (Apiaceae) is a perennial herb indigenous to Iran. It has been used as a medicinal plant from ancient time in Iran, Turkey and Pakistan. In the present work, air-dried and powdered plant roots were extracted with n-hexane, dichloromethane and methanol, respectively, using Soxhlet apparatus. The dichloromethane extract was subjected to vacuum liquid chromatography (VLC) and preparative thin layer chromatography (P-TLC) to yield two pyranocoumarins, aegelinol and agasyllin. The antimicrobial assay was performed using agar dilution method. The results showed that purified compounds have modest to weak antibacterial and antifungal activity.


Effect of pimobendan on cardiopulmonary baroreflex control of sympathetic nerve activity in healthy young men.
In order to determine the effect of pimobendan on sympathetic nerve activity and cardiopulmonary baroreflex (CPB), electrocardiogram, direct arterial pressure, central venous pressure (CVP) and cardiac output were recorded along with muscle sympathetic nerve activity (MSNA) in 8 healthy young men. CPB function was evaluated before and 60 min after oral administration of 5 mg pimobendan using the response of MSNA to lower body negative pressure (LBNP) of -5 and -10 mm Hg. The same protocol also was performed during handgrip exercise. Cardiac index, MSNA increased and CVP decreased significantly (p<0.01, respectively), but arterial pressure and heart rate unchanged after pimobendan administration. During LBNP, CVP decreased and MSNA increased significantly. CPB sensitivity was augmented from 5.53+/-0.75 to 8.59+/-0.78 burst incidence/mm Hg after pimobendan administration (p<0.01). Pimobendan did not alter the percentage increase of MSNA during handgrip exercise. In conclusion, pimobendan induces an increase in basal sympathetic nerve activity by decreasing CVP and augmenting CPB sensitivity without changing arterial pressure in healthy young men.


The ESSEX (European Scimed Stent Experience) study.
The aim of the study was to assess the safety and feasibility of implantation of the Scimed Radius stent. Secondary objectives were to assess the result of stent placement by quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS). The ESSEX study was a prospective, multicenter, observational study in which candidates for a single elective stent implantation, in a de novo or restenotic lesion, reference diameter 2.75-4.00 mm and target lesion < 14 mm in length, were enrolled. QCA at baseline, postprocedure, and 6-month follow-up was performed. IVUS was used to assess optimal stent implantation. One hundred and three patients were enrolled. Forty-four percent of the patients had unstable angina. Stent implantation was technically successful in all patients. Additional stents were implanted in 17 patients for procedural dissection (16) and spasm (1). Ninety-seven percent of patients were event-free at 1 month and 76% at 6-month follow-up. Angiographic restenosis rates for de novo lesions and for all patients were 19% and 21%, respectively. Clinical events occurred at 1- and 6-month follow-up in 2.9% and 24.3% of patients, respectively. No patients suffered subacute thrombosis. Retrospective analysis of peak balloon inflation pressure (< or = 12 and > 12 atm) as a determinant of clinical, QCA, and IVUS outcomes suggested no benefit or detrimental effect from optimization with high-pressure balloon inflation. Implantation of the self-expanding Radius stent is safe and efficacious. Based on registry data, clinical, angiographic, and IVUS, data comparable with modern balloon-expandable stents were obtained.


Tetra-ammonium bis-(metforminium) di-μ6-oxido-tetra-μ3-oxido-tetra-deca-μ2-oxido-octa-oxidodeca-vanadium(V) hexa-hydrate.
The title compound, (NH4)4(C4H12N5)2[V10O28]·6H2O, crystallizes with the deca-vanadate anion placed on an inversion centre in space group P . This anion is surrounded by a first shell of ammonium cations and water mol-ecules, forming efficient N-H⋯O and O-H⋯O hydrogen bonds. A second shell includes metforminium monocations with a twisted geometry, also forming numerous inter-molecular hydrogen bonds. The complex three-dimensional network of non-covalent inter-actions affords a crystal structure in which the cations and anions are densely packed.


PROspective MEmory Training to improve HEart failUre Self-care (PROMETHEUS): study protocol for a randomised controlled trial.
Cognitive impairment is seen in up to three quarters of heart failure (HF) patients and has a significant negative impact on patients' health outcomes. Prospective memory, which is defined as memory to carry out future intentions, is important for functional independence in older adults and involves application of multiple cognitive processes that are often impaired in HF patients. The objective of this study is to examine the effects of prospective memory training on patients' engagement in HF self-care and health outcomes, carer strain and quality of life. The proposed study is a randomised, controlled trial in which 200 patients diagnosed with HF, and their carers will be recruited from 3 major hospitals across Melbourne. Eligible patients with HF will be randomised to receive either: 1) The Virtual Week Training Program - a computerised prospective memory (PM) training program (intervention) or 2) non-adaptive computer-based word puzzles (active control). HF patients' baseline cognitive function will be compared to a healthy control group (n = 60) living independently in the community. Patients will undergo a comprehensive assessment of PM, neuropsychological functioning, self-care, physical, and emotional functioning. Assessments will take place at baseline, 4 weeks and 12 months following intervention. Carers will complete measures assessing quality of life, strain, perceived control in the management of the patients' HF symptoms, and ratings of the patients' level of engagement in HF self-care behaviours. If the Virtual Week Training Program is effective in improving: 1) prospective memory; 2) self-care behaviours, and 3) wellbeing in HF patients, this study will enhance our understanding of impaired cognitive processes in HF and potentially is a mechanism to reduce healthcare costs. Australian New Zealand Clinical Trials Registry #366376; 27 May 2014. https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366376&isClinicalTrial=False .


Special effects of UDP-sugar binding to bovine liver uridine diphosphoglucose dehydrogenase.
The binding of NADH to uridine diphosphate glucose dehydrogenase has been examined by equilibrium dialysis. There is an absolute requirement for the presence of UDP-glucose for the binding of NADH. Other analogs such as UDPxylose, UDPgalactose and UDPglucuronic acid cannot replace UDPglucose as an effector of NADH binding. UDPxylose competes with UDPglucose for the UDP-sugar-binding site, and in so doing releases the bound NADH. The binding of NADH to UDPglucose dehydrogenase in the presence of UDPglucose reaches a saturation limit of 3 mol NADH bound per enzyme hexamer, and displays positive cooperativity, Hill number = 1.34. The effects of UDP-sugars on the fluorescence of UDPglucose dehydrogenase derivatized at the catalytic sites with a fluorophore have also been studied. Two classes of UDPxylose-binding site have been detected. One class has high affinity (Kdiss = 3 microM, determined by equilibrium dialysis) but does not affect fluorophore fluorescence, and the other has lower affinity (Kdiss = 120 microM) and leads to red-shifted fluorescence quenching, presumably by effecting exposure of the fluorophore to solvent. The high-affinity sites are identified as the UDP-sugar subsites of the underivatized catalytic sites, and the low-affinity sites as UDP-sugar subsites of the fluorophore-labeled catalytic sites.


Changes in medullary glycosaminoglycan histochemistry and microvascular filling during the development of 2-bromoethanamine hydrobromide-induced renal papillary necrosis.
A single dose of 2-bromoethanamine (BEA) hydrobromide induced an apex limited renal papillary necrosis (RPN) at low doses (50 mg/kg, ip and sc, or 100 mg/kg, po), and the total ablation of the medulla at high doses (greater than 150 mg/kg, ip and sc, or 1000 mg/kg, po) in both male and female Wistar rats. BEA (at levels of 50, 100, and 150 mg/kg ip to male rats) caused transient hydropic changes. By 12 to 24 hr the anatomical elements of the medulla were necrosed, and active regeneration and reepithelialization of the viable areas was apparent. The only cortical changes up to 120 hr were dilatation of the nephron and the Bowman's spaces. The medullary glycosaminoglycan matrix (assessed by histochemical staining with colloidal iron) gave an intense granular appearance 2 hr after BEA, which was more marked and diffuse in the apex of the medulla from 8 to 12 hr. The staining was lost from those areas where early necrotic changes had occurred by 12 to 24 hr, and there was no subsequent staining of matrix material up to 120 hr. Vascular filling with colloidal carbon particles suggested an early shift of blood flow to the outer medulla at 2 to 4 hr, followed by the sustained filling of the microvasculature of the medulla well into the period when frank necrotic change was apparent. These data suggest that changes in the medullary matrix might play a previously unrecognized role in the development of 2-bromoethanamine hydrobromide-induced renal papillary necrosis, and these changes may give rise to loss of the material that supports the medullary capillaries.


Relaxation of nonproductive binding and increased rate of coenzyme release in an alcohol dehydrogenase increases turnover with a nonpreferred alcohol enantiomer.
Alcohol dehydrogenase A (ADH-A) from Rhodococcus ruber DSM 44541 is a promising biocatalyst for redox transformations of arylsubstituted sec-alcohols and ketones. The enzyme is stereoselective in the oxidation of 1-phenylethanol with a 300-fold preference for the (S)-enantiomer. The low catalytic efficiency with (R)-1-phenylethanol has been attributed to nonproductive binding of this substrate at the active site. Aiming to modify the enantioselectivity, to rather favor the (R)-alcohol, and also test the possible involvement of nonproductive substrate binding as a mechanism in substrate discrimination, we performed directed laboratory evolution of ADH-A. Three targeted sites that contribute to the active-site cavity were exposed to saturation mutagenesis in a stepwise manner and the generated variants were selected for improved catalytic activity with (R)-1-phenylethanol. After three subsequent rounds of mutagenesis, selection and structure-function analysis of isolated ADH-A variants, we conclude: (a) W295 has a key role as a structural determinant in the discrimination between (R)- and (S)-1-phenylethanol and a W295A substitution fundamentally changes the stereoselectivity of the protein. One observable effect is a faster rate of NADH release, which changes the rate-limiting step of the catalytic cycle from coenzyme release to hydride transfer. (b) The obtained change in enantiopreference, from the (S)- to the (R)-alcohol, can be partly explained by a shift in the nonproductive substrate-binding modes. Structural data are available in the Protein Data Bank with accession codes 5o8q for A2, 5o8h for A2C2, 5o9f for A2C3, and 5o9d for A2C2B1.


All WSe2 1T1R resistive RAM cell for future monolithic 3D embedded memory integration.
3D monolithic integration of logic and memory has been the most sought after solution to surpass the Von Neumann bottleneck, for which a low-temperature processed material system becomes inevitable. Two-dimensional materials, with their excellent electrical properties and low thermal budget are potential candidates. Here, we demonstrate a low-temperature hybrid co-integration of one-transistor-one-resistor memory cell, comprising a surface functionalized 2D WSe2 p-FET, with a solution-processed WSe2 Resistive Random Access Memory. The employed plasma oxidation technique results in a low Schottky barrier height of 25 meV with a mobility of 230 cm2 V-1 s-1, leading to a 100x performance enhanced WSe2 p-FET, while the defective WSe2 Resistive Random Access Memory exhibits a switching energy of 2.6 pJ per bit. Furthermore, guided by our device-circuit modelling, we propose vertically stacked channel FETs for high-density sub-0.01 μm2 memory cells, offering a new beyond-Si solution to enable 3-D embedded memories for future computing systems.


Treatment of type 2 diabetic nephropathy by blockade of the renin-angiotensin system: a comparison of angiotensin-converting-enzyme inhibitors and angiotensin receptor antagonists.
Type 2 diabetes is the most prevalent form of diabetes mellitus worldwide and associated diabetic nephropathy is the most common cause of end-stage renal disease in the USA. Lowering blood pressure and controlling glucose slows the progression to end-stage renal disease or death. Although angiotensin-converting-enzyme inhibitors reduce proteinuria, their effects to slow progression to end-stage renal disease have not been clearly demonstrated in type 2 diabetic nephropathy. Recent clinical trials with angiotensin AT(1) receptor antagonists demonstrate that they reduce proteinuria, stabilize renal function and slow the progression of nephropathy to end-stage renal disease in patients with type 2 diabetes. These are significant benefits beyond those associated with conventional therapy and blood pressure control.


A novel quantification method for the total demethylation potential of aquatic sample extracts from Bohai Bay using the EGFP reporter gene.
The demethylation potential of environmental pollutants is possibly an innate part of their comprehensive health risk. This paper develops a novel method called TDQ to quantify the demethylation epigenetic toxicity, termed the 5-AZA-CdR demethylation toxic equivalency, of aquatic samples from the heavily polluted Bohai Bay using Hep G2 cell lines transiently transfected with the pEGFP-C3 plasmid containing a methylated promoter of the EGFP reporter gene inserted artificially in vitro. If the aquatic sample extract has strong total demethylation potential to the promoter, its methylation level will decrease, and increased green fluorescence will be observed under microscopy after TDQ co-incubation. The 5-AZA-CdR was selected as a representative demethylation agent to validate the principle of the TDQ method on three levels: significant dose-response relationships between the concentration of 5-AZA-CdR and the methylation level of promoters, mRNA expression level of the EGFP gene, and the fluorescence intensity of EGFP proteins. Twenty extracts from aquatic samples are successfully quantified with the TDQ test. Eight of them return meaningful results ranging from 0.00004 to 0.20053 μM 5-AZA-CdR toxicity equivalents. The TDQ method is a reliable and rapid assay for the quantification of the DNA demethylation potential of aquatic sample extracts, which may shed light on the safety evaluation of food material.


Role of noninvasive positive-pressure ventilation in postextubation respiratory failure: a meta-analysis.
There is a need for an intervention that prevents re-intubation in patients who have been weaned off mechanical ventilation. Noninvasive positive-pressure ventilation (NPPV) has been shown to facilitate weaning in mechanically ventilated patients. To assess the effect of NPPV on re-intubation rate and intensive care unit and/or hospital mortality in patients with postextubation respiratory failure. We searched the MEDLINE, EMBASE, OVID, CINAHL, DARE, and CENTRAL databases for relevant studies published from 1980 to 2006, and included randomized controlled trials that evaluated the role of NPPV in patients with postextubation respiratory failure. Independently and in duplicate, two of us abstracted data from these trials. Differences in opinion were settled via consensus or after consultation with a third author. Four studies met our inclusion criteria: two used NPPV in the setting of established postextubation respiratory failure, and two used NPPV in patients "at risk" for postextubation respiratory failure. NPPV, compared to the standard medical therapy, did not decrease the re-intubation rate (relative risk [RR] 1.03, 95% confidence interval [CI]0.84-1.25) or intensive care unit mortality (RR 1.14, 95% CI 0.43-3.0) in patients (n = 302) with postextubation respiratory failure. However, in patients (n = 259) who were defined to be at high risk for developing postextubation respiratory failure, NPPV decreased the re-intubation rate (RR 0.46, 95% CI 0.25-0.84) and intensive care unit mortality (RR 0.26, 95% CI 0.1-0.66), but not the hospital mortality (RR 0.71, 95% CI 0.42-1.20). Current evidence suggests that NPPV should be used judiciously, if at all, in patients with postextubation respiratory failure, but it appears to be promising as a prophylaxis to prevent re-intubation in patients "at risk" for developing postextubation respiratory failure.


Gray and white matter changes linking cerebral small vessel disease to gait disturbances.
To investigate the topographic changes of white matter (WM) integrity and cortical thickness related to gait disturbances and determine whether these neural correlates mediate the association between cerebral small vessel disease (CSVD) and gait disturbances. A total of 129 patients with subcortical vascular cognitive impairment were included. CSVD severity was quantified as global and regional WM hyperintensities (WMH) volume and lacune and microbleed numbers. Amyloid burdens were assessed using Pittsburgh compound B (PiB)-PET scanning. Gait score was measured using a standardized scale. WM integrity was assessed by applying tract-based spatial statistics. Cortical thickness was measured using surface-based methods. Path analysis for gait score was performed using regional CSVD markers as predictors and fractional anisotropy (FA) and cortical thickness as mediators. Periventricular WMH (PWMH) volume was associated with gait score, regardless of other CSVD. PiB retention ratio was not associated with gait score. Gait score was correlated with FA in the frontal and parietal WM and bilateral corpus callosum and with cortical thinning in the bilateral frontal and lateral temporo-parieto-occipital regions. Path analysis for gait score showed that PWMH contributed to gait disturbances with the mediation of mean FA or cortical thickness. Our findings suggest that WMH-related cortical thinning as well as disrupted integrity of periventricular WM is linked to gait disturbances.


Chronically ill children coping with repeated hospitalizations: their perceptions and suggested interventions.
This qualitative research study used grounded theory methodology to learn from chronically ill children who are repeatedly hospitalized how they cope and how they feel others can assist them to cope with their recurrent hospital experiences. Six hospitalized children, ages 10 to 13 years, with various chronic conditions participated in an audiotaped interview, completed a drawing and kept a journal. The subjects identified their perceived stressors of hospitalization; revealed their use of both cognitive and behavioral coping strategies; described how hospital personnel, family, and friends enhanced their coping; and illustrated the impact of the hospital environment on their coping process. From comparison of the data, it is theorized that chronically ill children who are repeatedly hospitalized become adept at identifying and implementing a repertoire of coping strategies, accessing family and friends as resources in the coping process, developing patterns of coping with their parents, and utilizing the hospital environment to promote coping. Their coping is enhanced by familiarity and knowledge and by the respect and patience of gentle, supportive, and competent health care professionals.


Heterologous Protection against Malaria after Immunization with Plasmodium falciparum Sporozoites.
Sterile protection in >90% of volunteers against homologous Plasmodium falciparum infection has been achieved only using the controlled human malaria infection (CHMI) model. This efficient model involves whole parasite immunizations under chloroquine prophylaxis (CPS-immunization), requiring only 30-45 mosquitoes bites infected with P. falciparum-sporozoites. Given the large diversity of P. falciparum parasites, it is essential to assess protection against heterologous parasite strains. In an open-label follow-up study, 16 volunteers previously CPS-immunized and challenged with P. falciparum NF54 (West-Africa) in a dose de-escalation and challenge trial were re-challenged with clone NF135.C10 (Cambodia) at 14 months after the last immunization (NCT01660854). Two out of thirteen NF54 protected volunteers previously fully protected against NF54 were also fully protected against NF135.C10, while 11/13 showed a delayed patency (median prepatent period of 10.5 days (range 9.0-15.5) versus 8.5 days in 5 malaria-naïve controls (p = 0.0005). Analysis of patency by qPCR indicated a 91 to >99% estimated reduction of liver parasite load in 7/11 partially protected subjects. Three volunteers previously not protected against NF54, were also not protected against NF135.C10. This study shows that CPS-immunization can induce heterologous protection for a period of more than one year, which is a further impetus for clinical development of whole parasite vaccines. Clinicaltrials.gov NCT01660854.


Fluid and protein secretion by the submandibular glands of weanling rats in response to cholinergic and peptidergic agonists at various doses.
Fluid and protein secretion by the submandibular glands of 25-day-old rats were examined and compared in response to three cholinergic and four peptidergic sialogogues at various doses. All cholinergic and peptidergic agonists used were potent sialogogues for the submandibular glands of the weanling rats over the wide range of doses used. The cholinergic agonists, bethanechol and methacholine and the peptidergic agonists, substance P, substance PTyr8 and eledoisin-related peptide used intravenously, acted similarly to each other on the submandibular glands of the rats, late in the natural weaning period, but carbachol and physalaemin had slightly different effects. Of the peptidergic agonists, physalaemin was the most potent sialogogue among four tachykinins tested at the low dose. The types of protein secreted by the submandibular glands of the weanling rats in response to all sialogogues used here were typical of the beta-type. These results indicate that all agonists used could mainly stimulate the acinar cells of the submandibular glands of the weanling rats which have already fully developed functionally at this time.


Retromer Stabilization Improves Cognitive Function and Synaptic Plasticity in a Mouse Model of Down Syndrome.
Retromer complex proteins are decreased in postmortem brain tissues from Down syndrome subjects and inversely correlate with the Alzheimer's disease-like neuropathology. However, whether targeting in vivo the retromer system affects cognitive deficits and synaptic function in Down syndrome remains unknown. The aim of the current study was to examine the effects of pharmacological retromer stabilization on cognitive and synaptic functions in a mouse model of Down syndrome. Ts65dn mice were administered the pharmacological chaperone, TPT-172, or vehicle from 4 to 9 months of age and then assessed for changes in cognitive function. To assess the effects of TPT-172 on synaptic plasticity, hippocampal slices from Ts65dn mice were incubated in TPT-172 and used for field potential recordings. Chronic TPT-172 treatment improved performance in cognitive function tests, its incubation with hippocampal slices ameliorated synaptic function response. Pharmacological stabilization of the retromer complex improves synaptic plasticity and memory in a mouse model of Down syndrome. These results support the therapeutic potential of pharmacological retromer stabilization for individual with Down syndrome.


Staged Correction of Severe Recurrent Clubfoot Deformity With Dislocation of the Chopart Joint Using a Hexapod External Fixator and Unconventional Arthrodesis.
Despite success of the Ponseti method, a subset of patients with clubfeet experience residual deformity. Surgical release after unsuccessful serial casting can lead to residual clubfoot deformities, including a flat-top talus. We present a case of a 17-year-old boy with a dysmorphic ankle and a complete dorsal dislocation of the Chopart joint. Because of pain with activities and functional limitations, the patient underwent a staged correction of the dislocation. The deformity was corrected through a staged approach using a Taylor Spatial Frame, navicular excision, talocuneiform arthrodesis, and calcaneocuboid arthrodesis. One year postoperatively, the patient is pain free with notable functional gains.


Clinical significance of anterior mitral leaflet fibrillation in patients with nonvalvular atrial fibrillation: comparison with blood flow and wall motion of the left atrial appendage.
Diastolic fibrillation of the anterior mitral leaflet (AML) is seen in patients with atrial fibrillation (AF). However, its clinical significance has been unclear. On the other hand, reduced blood flow velocity in the left atrial appendage (LAA) may be associated with LA thrombus formation. In this study, we investigate the relationship between the flow velocity and the wall motion velocity of the LAA and diastolic fibrillation of the AML in patients with nonvalvular AF. We performed transthoracic echocardiography (TTE) in 45 consecutive patients with chronic nonvalvular AF. The LAA flow velocity was measured by pulsed Doppler echocardiography with the sample volume positioned at the center of the LAA. The LAA wall motion velocity was measured by pulsed Doppler tissue imaging (DTI) with the sample volume at the medial wall of the LAA. The AML fibrillation velocity was measured by pulsed DTI with the sample volume at the AML tip. The AML fibrillation velocity could be measured in 44 patients (97.8%), and the LAA flow and wall motion velocities were measurable in 35 (77.8%) and 42 (93.3%) patients, respectively. The AML fibrillation velocity had a range from 4 to 21 cm/s and showed significant positive correlation with the LAA flow velocity (r = 0.82, P < 0.001) and the wall motion velocity (r = 0.80, P < 0.001) of the LAA. An AML fibrillation velocity of ≤7 cm/s predicted patients having a tendency to LA thrombus formation (LAA flow velocity ≤20 cm/s) with high sensitivity (87.5%) and specificity (88.9%). The AML fibrillation velocity seems to be a viable substitute for the LAA flow velocity in the detection of flow stagnation in the LA.


Phyllosticta ophiopogonis sp. nov. from Ophiopogon japonicus (Liliaceae).
A leaf spotting disease of an ornamental variety of Ophiopogon japonicus was discovered at several locations in northern Thailand. In all cases a species of Phyllosticta was associated with the lesions. Phyllosticta ophiopogonis sp. nov. is distinguished from Phyllosticta species from Liliaceae in conidia size, mucilaginous sheath and appendage thus the species is introduced as new in this paper. The new species which causes unsightly lesions on this ornamental plant is described, illustrated and compared with other similar Phyllosticta species.


COVID-19 the intruder: A philosophical journey with Jean-Luc Nancy into pandemic strangeness and tourism.
Since the arrival of COVID-19, tourism scholarship has focused its attention on rethinking and restarting the tourism sector. In this urgent search for a 'new normal', the embodied experience of hosting such an unwelcomed virus, the philosophical questions this raises, and the tourism futures already in the making, have not been fully explored. The article introduces Nancy's (2000/2002) philosophy, L'intrus [The Intruder], where he reflects on having a heart transplant operation to give body to the experiences of the self as exteriority and of otherness always already within. We take inspiration from Nancy to think and sense the experience of the COVID-19 virus intrusion in tourism. To do this, we weave personal philosophical reflections with ethnographic material to reflect on three themes of intrusion for tourism scholarship to consider: the experience of a body/self as exposed, the experience of a shattered self, and the experience of uncertain futures.


Dermoscopy of Adnexal Tumors.
Cutaneous adnexal tumors include lesions with apocrine, eccrine, follicular, sebaceous, and mixed differentiation. Most are benign and sporadic, although malignant forms are occasionally observed and some cases develop in the setting of inherited syndromes. These tumors often cause immense diagnostic difficulty. Dermoscopy is a noninvasive technique that has greatly improved the diagnostic accuracy of different skin lesions, including these tumors. We provide a review of the literature on the dermoscopic structures and patterns associated with adnexal tumors. Most patterns associated with this kind of tumor are nonspecific and are observed in other nonadnexal tumors, especially in basal cell carcinomas.


A cross-sectional sero-epidemiological study of canine leishmaniasis in Greek mainland.
Canine leishmaniasis is endemic in Greece as in other countries of the Mediterranean basin. In this study, the regional prevalence of canine seropositivity to Leishmania spp. in Greek mainland was simultaneously assessed in 7 different regions. A total of 2620 serum samples were collected from clinically healthy dogs and were tested for anti-L. infantum antibodies by indirect immunofluorescence antibody test (IFAT) and enzyme linked immunosorbent assay (ELISA). A high degree of agreement (κ=0.96) was observed between these two tests. The seroprevalence rate in the whole study population was nearly 20%, being highest among dogs living in Attiki (30.12%) and lowest for those living in Florina (2.05%). There was no difference in terms of the gender of the dogs, their length of hair coat or their utility; on the contrary, seroprevalence rates were significantly higher among dogs in the age groups of 1-3 years (23.39%) and 3-9 years (23.35%) than in younger (2.26%) or older (6.03%) dogs. Epidemiological data on the seroprevalence of canine leishmaniasis provide indirect information on the prevalence of the infection and the disease and are necessary to implement and then to evaluate the effectiveness of control measures.


Infectious Uveitis.
Infectious uveitis is one of the most common and visually devastating causes of uveitis in the US and worldwide. This review provides a summary of the identification, treatment, and complications associated with certain forms of viral, bacterial, fungal, helminthic, and parasitic uveitis. In particular, this article reviews the literature on identification and treatment of acute retinal necrosis due to herpes simplex virus, varicella virus, and cytomegalovirus. While no agreed-upon treatment has been identified, the characteristics of Ebola virus panuveitis is also reviewed. In addition, forms of parasitic infection such as Toxoplasmosis and Toxocariasis are summarized, as well as spirochetal uveitis. Syphilitic retinitis is reviewed given its increase in prevalence over the last decade. The importance of early identification and treatment of infectious uveitis is emphasized. Early identification can be achieved with a combination of maintaining a high suspicion, recognizing certain clinical features, utilizing multi-modal imaging, and obtaining specimens for molecular diagnostic testing.


Role of 6-phosphogluconate dehydrogenase enzyme 1 in growth and virulence of Toxoplasma gondii and development of attenuated live vaccine.
Toxoplasma gondii is a ubiquitous pathogen that infects all warm-blooded animals, including humans, causing substantial socioeconomic and healthcare burdens. However, there is no ideal vaccine for toxoplasmosis. As metabolism is important in the growth and virulence of Toxoplasma, some key pathways are promising antiparasitic targets. Here, we identified 6-phosphogluconate dehydrogenase 1 (Tg6PGDH1) in the oxidative pentose phosphate pathway as a cytoplasmic protein that is dispensable for tachyzoite growth of T. gondii in vitro but critical for virulence and cyst formation in vivo. The depletion of Tg6PGDH1 causes decreased gene transcription involved in signal transduction, transcriptional regulation and virulence. Furthermore, we analysed the protective effect of the ME49Δ6pgdh1 mutant as an attenuated vaccine and found that ME49Δ6pgdh1 immunization stimulated strong protective immunity against lethal challenges and blocked cyst formation caused by reinfection. Furthermore, we showed that ME49Δ6pgdh1 immunization stimulated increased levels of interferon-gamma, tumour necrosis factor-alpha and Toxoplasma-specific IgG antibodies. These data highlight the role of Tg6PGDH1 in the growth and virulence of T. gondii and its potential as a target for the development of a live-attenuated vaccine.


Radiotherapy for isolated lymph node metastases in patients with locally advanced prostate cancer after primary therapy.
To evaluate the outcome of radiotherapy for isolated lymph node metastases in patients with progression towards castration-resistant prostate cancer (CRPC) after definitive therapy. Between 11/2009 and 06/2014, 18 patients with isolated lymph node metastases after definitive prostate cancer therapy received radiotherapy to the affected lymph nodes with a total dose of 50.4 or 54.0 Gray (Gy). All patients had continuously rising levels of PSA despite androgen deprivation therapy (ADT). Biochemical progression-free survival (BPFS), clinical failure-free survival (CFFS) and freedom from local failure were assessed, as was the toxicity profile. Of the 18 patients, 17 had high-risk prostate cancer. Radiotherapy was performed at a median interval of 64.55 [interquartile range (IQR) 23.2-153.8] months after definitive therapy. ADT was administered for a median (IQR) time of 3.8 (3.2-24.7) months prior to irradiation. The median (IQR) follow-up was 15.59 (5.3-28.5) months with 94.1 % freedom from local failure. The median BPFS and CFFS were 5.85 (IQR 3.0-20.3) and 9.60 months (IQR 5.9-28.8), respectively. No grade III acute or grade II late toxicity was observed. Only two patients developed local relapse. No patients exhibited deterioration of urinary or faecal continence. Radiotherapy of isolated lymph node metastases in patients who develop CRPC provides effective local control, is not associated with clinically important acute or long-term side effects, improves PSA kinetics and may delay the necessity of chemotherapy.


Intravirion cohesion of matrix protein M1 with ribonucleocapsid is a prerequisite of influenza virus infectivity.
Influenza virus has two major structural modules, an external lipid envelope and an internal ribonucleocapsid containing the genomic RNA in the form of the ribonucleoprotein (RNP) complex, both of which are interlinked by the matrix protein M1. Here we studied M1-RNP cohesion within virus exposed to acidic pH in vitro. The effect of acidification was dependent on the cleavage of the surface glycoprotein HA. Acidic pH caused a loss of intravirion RNP-M1 cohesion and activated RNP polymerase activity in virus with cleaved HA (HA1/2) but not in the uncleaved (HA0) virus. The in vitro acidified HA1/2 virus rapidly lost infectivity whereas the HA0 one retained infectivity, following activation by trypsin, suggesting that premature activation and release of the RNP is detrimental to viral infectivity. Rimantadine, an inhibitor of the M2 ion channel, was found to protect the HA1/2 virus interior against acidic disintegration, confirming that M2-dependent proton translocation is essential for the intravirion RNP release and suggesting that the M2 ion channel is only active in virions with cleaved HA. Acidic treatment of both HA0 and HA1/2 influenza viruses induces formation of spikeless bleb-like protrusion of ~ 25 nm in diameter on the surface of the virion, though only the HA1/2 virus was permeable to protons and permitted RNP release. It is likely that this bleb corresponds to the M2-enriched and M1-depleted focus arising from pinching off of the virus during the completion of budding. Cooperatively, the data suggest that the influenza virus has an asymmetric structure where the M1-mediated organization of the RNP inside the virion is a prerequisite for infectious entry into target cell.


Percutaneous cryoablation of benign bony tumours of the mandible.
Treatment of bony tumours of the oral and maxillofacial area usually involve resection. However, access to certain areas may be difficult because of the size or site of the tumour. A poor view of the lesion during operation is another limiting factor, which can lead to incomplete resection in difficult cases. Percutaneous cryoablation is a common procedure for treating benign and malignant bony lesions outside the oral and maxillofacial area, but has to our knowledge never been used as a stand-alone treatment as we describe here. In 2016, three patients with benign bony tumours of the mandible (one a keratocyst, one an angiofibroma, and one a giant cell granuloma) were treated with one session of percutaneous cryoablation. Outcomes were monitored with computed tomography or magnetic resonance imaging at one year. No patient had a procedure-related complication, and there were no other complications. Radiological controls showed complete recovery. Percutaneous cryoablation seems to be an interesting and valuable alternative to resection for bony lesions with its limited access and high operative morbidity.


Malignant peripheral nerve sheath tumor: models, biology, and translation.
Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive, invasive cancer that comprise around 10% of all soft tissue sarcomas and develop in about 8-13% of patients with Neurofibromatosis Type 1. They are associated with poor prognosis and are the leading cause of mortality in NF1 patients. MPNSTs can also develop sporadically or following exposure to radiation. There is currently no effective targeted therapy to treat MPNSTs and surgical removal remains the mainstay treatment. Unfortunately, surgery is not always possible due to the size and location of the tumor, thus, a better understanding of MPNST initiation and development is required to design novel therapeutics. Here, we provide an overview of MPNST biology and genetics, discuss findings regarding the developmental origin of MPNST, and summarize the various model systems employed to study MPNST. Finally, we discuss current management strategies for MPNST, as well as recent developments in translating basic research findings into potential therapies.


Topography and severity of coronary artery disease in white-coat hypertension.
White-coat hypertension (WCH) has been evaluated as a risk factor for cardiovascular disease. In this study, the role of WCH is evaluated in a cohort of patients with suspected coronary artery disease with both coronary angiography and non-invasive techniques. One hundred patients with suspected coronary artery disease underwent coronary angiography, 24-h ambulatory blood pressure monitoring (ABPM), and ultrasound imaging of the myocardium and carotids. The lesions in percentage of stenosis in the left coronary artery stem (LM), left anterior descending ramus (LAD), left circumflex artery (LCX), diagonal artery (D1), and right coronary artery (RCA), along with the Gensini score (GS), were recorded. After a series of manual blood pressure measurements, the patients were divided into two groups (patients with and patients without WCH). GS was higher in the WCH group (P=0.042), a difference that could be attributed to lesions in the LAD (P=0.007). GS correlated significantly with left ventricular end-diastolic diameter (LVEDD - P=0.041), left ventricular end-systolic diameter (LVESD - P=0.005), end-diastolic volume (EDV - P=0.042), end-systolic volume (ESV - P=0.004), LvMass/BSA (P=0.012), right internal carotid artery intima-media thickness (RICA - P=0.018), left internal carotid artery intima-media thickness (LICA - P=0.021), and their mean (MICA - P=0.005) in the WCH group but not in normotensives. Coronary disease may be more severe among patients with WCH than among those without. In this group, data from myocardial and carotid ultrasound may help to estimate coronary artery disease.


Comparison of porphyrin-based, growth factor-based, and biochemical-based testing methods for identification of Haemophilus influenzae.
The accurate identification of Haemophilus spp. is essential for optimizing the role of the clinical microbiology laboratory in the diagnosis and management of Haemophilus infections. One laboratory-prepared medium and eight commercially available test systems were examined in parallel as a means of identifying 378 clinical isolates of Haemophilus spp. as either Haemophilus influenzae or non- Haemophilus influenzae spp. At least one discordant result was noted with 187 (49.5%) of the isolates tested. Discordant results were resolved either by majority rule for isolates with less than three discordant test results or by confirming the identity using conventional biochemical tests for isolates with three or more discordant test results ( n=20). Among these 20 isolates, 2 were judged not to belong to the Haemophilus genus. Comparisons of three porphyrin-based methods, three growth factor-based methods (1 of which also incorporates a porphyrin testing component), and three biochemical-based methods revealed varying discrepancy rates within each testing method. In general, porphyrin-based methods, with overall discrepancy rates of 1.3% or less, outperformed other testing methods. One important exception was the performance of the porphyrin testing component of the Haemophilus Identification Test Kit (Remel, USA), which produced an overall discrepancy rate of 28.5% and a false-negative rate of 52.2% with non- Haemophilus influenzae isolates. Growth factor-based methods yielded overall discrepancy rates ranging from 1.6% ( Haemophilus Identification Agar Quad; Remel) to 10.4% (hemin and nicotinamide adenine dinucleotide disk component of the Haemophilus Identification Test Kit). Biochemical-based assays produced overall discrepancy rates ranging from 4.5% (API NH; bioMérieux Vitek, USA) to 10.1% ( Neisseria Haemophilus Identification Card; bioMérieux Vitek). Collectively, these results suggest that porphyrin-based testing methods represent the most reliable means for identifying Haemophilus spp.


Knowledge embedded.
How should we account for the contextual variability of knowledge claims? Many philosophers favour an invariantist account on which such contextual variability is due entirely to pragmatic factors, leaving no interesting context-sensitivity in the semantic meaning of 'know that.' I reject this invariantist division of labor by arguing that pragmatic invariantists have no principled account of embedded occurrences of 'S knows/doesn't know that p': Occurrences embedded within larger linguistic constructions such as conditional sentences, attitude verbs, expressions of probability, comparatives, and many others, I argue, give rise to a threefold problem of embedded implicatures.


Possible involvement of protein kinase C (PKC) in the regulation of electrically evoked serotonin (5-HT) release from rabbit hippocampal slices.
Protein kinase C (PKC)-activating phorbol esters enhanced the electrically evoked 5-HT release from rabbit hippocampal slices preincubated with [3H]5-HT. The release was diminished by polymyxin B, an inhibitor of PKC. These results are compatible with a stimulatory effect of PKC on the 5-HT release induced by action potentials. The mutual effects of PKC affecting drugs on 5-HT release suggest a functional but not a competitive interaction. The attenuation or the enhancement of effects of 5-HT autoreceptor ligands at various 5-HT biophase concentrations found after PKC-affecting drugs are in line with the view that autoreceptor-mediated events are not directly influenced by the enzyme PKC.


A Systematic Review of the Safety and Efficacy of Inferior Vena Cava Stenting.
Inferior vena cava (IVC) stenting may provide benefit to patients with symptomatic obstruction; however, there are no devices currently licensed for use in the IVC and systematic reviews on the topic are lacking. The aim of this study was to carry out a systematic review of the literature and meta-analysis to investigate the safety and efficacy of IVC stenting in all adult patient groups. The Medline and Embase databases were searched for studies reporting outcomes for safety and effectiveness of IVC stenting for any indication in series of 10 or more patients. A systematic review of the literature was carried out according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Thirty-three studies were included describing 1 575 patients. Indications for stenting were malignant IVC syndrome (229 patients), thrombotic disease (807 patients), Budd-Chiari syndrome (501 patients), and IVC stenosis post liver transplantation (47 patients). The male:female ratio was 2:1 and the median age ranged from 30 to 61 years. The studies included were not suitable for formal meta-analysis as 30/33 were single centre retrospective studies with no control groups and there was considerable inconsistency in outcome reporting. There was significant risk of bias in 94% of studies. Median reported technical success was 100% (range 78 - 100%), primary patency was 75% (38 - 98%), and secondary patency was 91.5% (77 - 100%). Major complications were pulmonary embolism (three cases), stent migration (12 cases), and major bleeding (15 cases), and there were three deaths in the immediate post-operative period. Most studies reported improvement in clinical symptoms but formal reporting tools were not used consistently. The evidence base for IVC stenting consists of predominantly single centre, retrospective, observational studies that have a high risk of bias. Nonetheless the procedure appears safe with few major adverse events, and studies that reported clinical outcomes demonstrate improvement in symptoms and quality of life. Randomised controlled trials and prospective registry based studies with larger patient numbers and standardised outcome are required to improve the evidence base for this procedure.


A novel solvothermal biorefinery for production of lignocellulosic xylooligosaccharides, fermentable sugars and lignin nano-particles in biphasic system.
Biorefinery plays a pivotal role in biomass economy with environmentally benign process. Herein, we report a coupling dihydrolevoglucosenone and aqueous p-toluenesulfonic acid (Cyrene/TsOH aq.) system for efficient saccharification of moso bamboo. More than 87.3 % of cellulose recovery could be observed under mild condition of 120 °C for 60 min, accompanied by 85.5 % hemicellulose removal and 79.4 % lignin extraction, respectively. Notably, 90.6 % of saccharified yield could be obtained including 67.7 % of oligosaccharide and 22.9 % of monosaccharide. Besides, the yielded lignin exhibited high purity of 99.1 % and outstanding uniform polydispersity index of 1.49 with nanoscale particle size around 347 nm, which is of great significance for further application. Furthermore, the synergistic effect between Cyrene and TsOH on efficiency and specificity of biorefinery was proposed by control experiments and verified by molecular dynamics simulation and quantum chemical calculation, which provided a new insight for full components biorefinery of lignocellulosic biomass.


Effect of Multifactorial Balance Rehabilitation Program on Risk of Falls and Functional Fitness in Older Adults with Diabetic Peripheral Neuropathy.
Increasing age and the added disadvantage of diabetic peripheral neuropathy (DPN) put the individual at a higher risk of falls and reduced functional fitness. However, there is a dearth of literature on multifactorial balance intervention, especially targeting the needs of older adults with DPN. The current study aimed to determine the effect of a multifactorial balance rehabilitation program on fall risk and functional fitness in older adults with DPN. In this pre-post experimental study, 30 independently ambulating older adults (71.2 ± 4.70 years) with DPN, who were at risk of falling (timed up and go score ≥ 9.4 seconds), were recruited. Along with the standard care, all the participants received 12 weeks of the multifactorial balance rehabilitation program. Fall risk using the Fullerton Advanced Balance scale and functional fitness using the Senior Fitness Test were measured at baseline and after 12 weeks of the intervention. The intervention reduced the risk of falling score significantly (MD = 6.17, p < .001). All six parameters of functional fitness improved after 12 weeks of intervention. The improvement in lower limb strength (MD = 1.53 times), upper limb strength (MD = 2.48 times), endurance (MD = 16.07 seconds), lower limb flexibility (MD = 2.02 inches), upper limb flexibility (MD = 1.47 inches), and dynamic balance (MD = 1.53 seconds) was statistically significant at p < 0.05. This study provided encouraging evidence about the potential of multifactorial balance rehabilitation to reduce the risk of falling and improve functional fitness in older adults with DPN.


The effect of maternal body condition score before and during pregnancy on the glucose tolerance of adult sheep offspring.
This study investigates the effects of diet-induced changes in maternal body condition on glucose tolerance in sheep. Welsh Mountain ewes were established, by dietary manipulation, at a body condition score of 2 (lower body condition [LBCS], n = 17) or >3 (higher body condition [HBCS], n = 19) prior to and during pregnancy. Birth weight and postnatal growth were similar in LBCS and HBCS offspring. In young adulthood, LBCS offspring had increased fasting glucose levels (3.8 +/- 0.07 vs 3.6 +/- 0.05 mM, P < .05), poorer glucose tolerance (2274 +/- 22.6 vs 2161 +/- 33 min/mM, P < .01), and reduced insulin secretion (0.58 +/- 0.05 vs 0.71 +/- 0.07 nM/min, P = .07). Increased fasting glycemia, mild glucose intolerance, and impaired initial insulin secretory response, as observed in LBCS offspring, are indictors of increased diabetes risk in humans. These findings suggest that altered maternal body composition and an imbalance between the fetal and postnatal environment influence offspring glucose tolerance.


The radiometric assay of alkaline phosphatase activity with 125-I-labelled phenolphthalein monophosphate.
The coupling of 125-I to phenolphthalein monophosphate is described. Hydrolytic cleavage of the phosphate group by alkaline phosphatases (EC 3.1.-3.1) releases labelled phenolphthalein which is extracted into ethyl acetate at pH 10. This forms the basis of a sensitive assay for the enzyme with the advantages of sensitivity and rapidity from the use of a gamma-emitter. Results with Escherichia coli and calf intestine alkaline phosphatases are presented.


The improvement of the antenatal detection of fetal neural tube defects using discriminant analysis.
Discriminant analysis was applied to the antenatal diagnosis of fetal neural tube defects. Alpha-fetoprotein, gestational age, and seven easily assayed biochemical variables were used to generate the discriminant function, which was derived from a retrospective study on data from 130 pregnancies, including 25 which were associated with fetal anencephaly and 13 with fetal spina bifida. This function was used to generate a diagnosis in a blind study of 40 previously unassayed samples: 20 problem samples from another centre interspersed with 20 normal samples. The same function was used over a period of 2 years to predict prospectively the outcome of 669 pregnancies with respect to neural tube defects. Of these 55 were found to be associated with fetal neural tube defects. Classification is shown to be more reliable than using alpha-fetoprotein and gestational age alone. The results demonstrate a successful application of discriminant analysis to medical diagnosis.


Association between well-known histopathological criteria and overall survival in invasive ductal carcinoma.
We investigated the effect of clinical features and well-known histomorphological parameters on survival of breast cancer. 44 patients with invasive ductal carcinoma were included in this study. We investigated the effect of age, breast cancer location (right/left), histological grade, largest diameter of the tumor, lymphovascular and perineural invasion on patient survival. IBM SPSS (Statistical Package for Social Sciences) 20 program was used for statistics. Cox proportional hazard regression model for survival analysis, log-log plot, life function graphs were used. Results were 95% confidence interval, significance (P < 0.05). In univariate analysis, the left breast localization, high histological grade, large tumor size, lymphovascular invasion, perineural invasion has been shown that reduced the overall survival (P < 0.05). In multivariate analysis, only high histological grade, large tumor size and perineural invasion were identified as parameters negatively associated with patient survival (P < 0.05). On univariate and multivariate analysis, age was not associated with survival. The above results should be considered in the follow-up and treatment planning of invasive ductal carcinoma patients.


Emulsion-based synthesis of porous silica.
We review the use of various types of emulsions as media for synthesis of porous silica particles. The use of high internal phase emulsions, i.e. emulsions with a high ratio of dispersed to continuous phase, is an approach that has attracted considerable attention. Polymerization of the continuous phase followed by removal of the dispersed phase leads to a material with an even distribution of pores if the emulsion droplets are uniform in size. Another route is to use particle stabilized emulsions as template. This will lead to either hydrophilic or hydrophobic porous silica particles depending on whether the templating emulsion is oil-in-water or water-in-oil, respectively. Use of double emulsions as templates is a way to obtain porous particles with hierarchical porosity, usually both macropores and mesopores. Templating amphiphiles, which are often polyoxyethylene-polyoxypropylene-polyoxyethylene block copolymers, are needed in order to obtain materials with highly ordered pore structure. Non-ordered mesoporous silica with small particle size and relatively large pores can be obtained by emulsifying a silica precursor together with an inert solvent in water and allowing the silica to gel within the drops. Hollow silica spheres, i.e. spherical particles with a void in the middle, can be prepared by using emulsion drops as templates around which silica polymerizes. The particles have nanometer-sized pores penetrating the shell.


Understanding individual face discrimination by means of fast periodic visual stimulation.
This paper reviews a fast periodic visual stimulation (FPVS) approach developed recently to make significant progress in understanding visual discrimination of individual faces. Displaying pictures of faces at a periodic frequency rate leads to a high signal-to-noise ratio (SNR) response in the human electroencephalogram, at the exact frequency of stimulation, a so-called steady-state visual evoked potential (SSVEP, Regan in Electroencephalogr Clin Neurophysiol 20:238-248, 1966). For fast periodic frequency rates, i.e., between 3 and 9 Hz, this response is reduced if the exact same face identity is repeated compared to the presentation of different face identities, the largest difference being observed over the right occipito-temporal cortex. A 6-Hz stimulation rate (cycle duration of ~170 ms) provides the largest difference between different and repeated faces, as also evidenced in face-selective areas of the ventral occipito-temporal cortex in functional magnetic resonance imaging. This high-level discrimination response is reduced following inversion and contrast-reversal of the faces and can be isolated without subtraction thanks to a fast periodic oddball paradigm. Overall, FPVS provides a response that is objective (i.e., at an experimentally defined frequency), implicit, has a high SNR and is directly quantifiable in a short amount of time. Although the approach is particularly appealing for understanding face perception, it can be generalized to study visual discrimination of complex visual patterns such as objects and visual scenes. The advantages of the approach make it also particularly well-suited to investigate these functions in populations who cannot provide overt behavioral responses and can only be tested for short durations, such as infants, young children and clinical populations.


Reducing the number of rabbits in the Draize eye irritancy test: a statistical analysis of 155 studies conducted over 6 years.
The Draize eye irritancy test in rabbits has been the focus of recent efforts to reduce the use of live animals in toxicity testing. A suitable alternative is not yet available; therefore, we studied the adequacy of reducing the number of rabbits used per test. Data generated from 6-rabbit eye irritation tests of 155 various materials were used to determine the ability of irritation scores from all possible combinations of 5-, 4-, 3-, or 2-rabbit subsets to predict the Draize score derived from six rabbits. There are 930, 2325, 3100, and 2325 possible combinations of 155 studies for the 5-, 4-, 3-, and 2-rabbit subsets, respectively. We classify materials using a four-level adjectival rating system based on (among other factors) the Draize score. Comparisons indicated that 5-, 4-, 3-, and 2-rabbit scores were in 98, 96, 94, and 91% agreement, respectively, with the classification assigned on the basis of the 6-rabbit score. The correlation coefficients for randomly selected subsets of 5-, 4-, 3-, and 2-rabbit scores versus the Draize score for six rabbits were 0.998, 0.996, 0.992, and 0.984, respectively. This study confirms the findings of an earlier report by De Sousa et al. (1984), and indicates that a high level of accuracy can be obtained with reduced numbers of rabbits per test.


The bacteriology of pleural infection by genetic and standard methods and its mortality significance.
Antibiotic choices for pleural infection are uncertain as its bacteriology is poorly described. Pleural fluid from 434 pleural infections underwent standard culture and a screen for bacteria by amplification and sequencing of bacterial 16S ribosomal RNA gene. Approximately 50% of community-acquired infections were streptococcal, and 20% included anaerobic bacteria. Approximately 60% of hospital-acquired infections included bacteria frequently resistant to antibiotics (methicillin-resistant Staphylococcus aureus, 25%; Enterobacteriaceae, 18%; Pseudomonas spp., 5%, enterococci, 12%). Mortality was increased in hospital-acquired infection (hospital, 17/36 [47%]; community, 53/304 [17%]; relative risk, 4.24; 95% confidence interval, 2.07-8.69; p < 0.00001; chi(2), 1 df = 17.47) and in gram-negative (10/22 [45%]), S. aureus (15/34 [44%]), or mixed aerobic infections (13/28 [46%]), compared with streptococcal infection (23/137 [17%]) and infection including anaerobic bacteria (10/49 [20%]; p < 0.00001, chi(2), 4 df = 23.35). Pleural infection differs bacteriologically from pneumonia and requires different treatment. Antibiotics for community-acquired infection should treat aerobic and anaerobic bacteria. Hospital-acquired, gram-negative S. aureus and mixed aerobic infections have a high mortality rate.


Brand-Specific Enhanced Safety Surveillance Study of GSK's Quadrivalent Seasonal Influenza Vaccine, Conducted During the COVID-19 Pandemic, in Belgium, Germany and Spain, for the 2020/21 Season.
Seasonal influenza poses a major public health burden worldwide. Influenza vaccines, updated yearly to match circulating strains based on World Health Organization (WHO) recommendations, are the cornerstone of prevention and require regular monitoring. The COVID-19 pandemic is expected to cause logistical, site access and medical staff constraints and could affect the safety profile of influenza vaccines. Following European Medicines Agency guidance, an enhanced safety surveillance (ESS) study assessed the frequency and severity of predefined and other adverse events (AEs) occurring within 7 days of receiving GSK's inactivated quadrivalent seasonal influenza vaccine (IIV4), in Belgium, Germany and Spain in 2020/21, using adverse drug reaction (ADR) cards. During the 2020/21 influenza season, 1054 participants vaccinated with GSK's IIV4 were enrolled (all adults in Belgium and Germany, 30% adults/70% children in Spain); 96 eligible children received a second dose. Overall, 1042 participants completed the study. After doses 1 and 2, 98.9% and 100% of participants, respectively, returned their completed ADR card. After doses 1 and 2, 37.8% (398/1054) and 13.5% (13/96) of participants, respectively, reported at least one AE. The most frequently reported categories of AEs were "general disorders and administration site conditions" (e.g. injection site pain) and "nervous system disorders" (e.g. headache). There were no deaths or serious AEs deemed related to GSK's IIV4. This ESS study assessed AEs in near real time. The COVID-19 pandemic did not alter the safety profile of GSK's IIV4. No safety signals were detected during the study, which confirms the excellent safety profile of GSK's IIV4.


Method for small routine laboratories for the detection of satratoxins in straw samples.
A method is described for thin-layer chromatographic analysis of field samples for satratoxins G and H, theStachybotrys toxins most soluble under physiological circumstances and representing the majority ofStachybotrys atra produced toxins. Besides brine shrimp bio-assay, the conversion of these macrocyclic trichothecenes to verrucarol is used to support their identification.


Complete genome characterization of enterovirus 104 circulating in Northern Italy shows recombinant origin of the P3 region.
Human enterovirus 104 (EV-C104) is a member of the Human Enterovirus species C (Family Picornaviridae, Genus Enterovirus) and has been associated with mild respiratory syndromes. At present, only two EV-C104 complete genome sequences from strains detected in Switzerland and Japan have been deposited in GenBank. In this study a complete genome analysis of seven Italian EV-C104 strains was carried out. In addition, VP1 sequence analysis was performed in an additional 5 Italian strains (for a total of 12 strains). The genome length of the seven strains was 7406 nucleotides (nt). The seven genomes showed 91.0-96.9% nucleotide identity with respect to other available EV-C104 complete genomes. The P1 and P2 regions of the Italian strains were closely related to EV-C104 identified in Switzerland, while the P3 region was closely related to the EV-C117 strain. In addition, bootscan analysis showed the presence of one putative recombination breakpoint between the P2 and P3 regions. Based on the trees constructed with partial VP1/2A nucleotide sequences, as well as the 3D partial coding region tree, the Italian strains appear to form a single and independent cluster together with the EV-C104 Japanese strain. In conclusion, a complete phylogenetic analysis of the relationship between EV-C104 and other known HEV-C strains was achieved. In addition, the recombinant origin of EV-C104, which has circulated in Italy and Japan, was demonstrated.


Attachment of the ascidian sperm surface egg receptor N-acetylglucosaminidase to the cell membrane.
Ascidian sperm bind to vitelline coat N-acetylglucosamine groups of the egg via sperm surface N-acetylglucosaminidase. This sperm surface egg receptor remains anchored throughout penetration. Localization to the sperm surface was verified by biotinylation of intact sperm followed by solubilization in Triton X-100 and binding to streptavidin agarose. The enzyme was determined to be an integral membrane protein as judged by resistance to release by Kl and high pH. Linkage of the enzyme to the sperm surface was probed through differential solubilization followed by measuring released enzymatic activity with a fluorogenic substrate. Nonionic detergents released 90% of the activity. Proteases released about 40%. No activity was released by a phosphatidylinositol specific phospholipase C. This finding, combined with the similarity of release level by all the detergents, including Triton X-100 and octylglucoside, argues against a phosphatidyl-inositol linkage. The release form enters the hydrophilic phase of a Triton X-114 phase separation experiment. This observation, coupled with the findings of release by nonionic detergents, suggests that the protein is hydrophilic once released from the membrane. Thus, although clearly an integral membrane protein, the enzyme has limited hydrophobicity such as would be present in a single transmembrane sequence or extensive glycosylation.


Expression of lectin-like oxidized low density lipoprotein receptor-1 in human and murine macrophages: upregulated expression by TNF-alpha.
Uptake of oxidized low density lipoprotein (Ox-LDL) and subsequent foam cell transformation have been implicated in early atherogenesis. Although multiple molecules, including class A and B scavenger receptors, have been identified as Ox-LDL receptors, additional receptors may also be involved in this process. Here, we provide evidence that lectin-like Ox-LDL receptor-1 (LOX-1), a novel Ox-LDL receptor initially identified in vascular endothelial cells, is also expressed in macrophages in humans and mice. Expression of LOX-1 can be induced after macrophage-like differentiation in vitro in human peripheral blood monocytes and the related cell line THP-1 cells. Furthermore, LOX-1 expression can also be detected in resident peritoneal macrophages, and can be upregulated by an inflammatory cytokine TNF-alpha. These results suggest that LOX-1 in macrophages may play an important role in Ox-LDL uptake and subsequent foam cell formation in this cell type.


Influence of watering and trenching ponderosa pine on a pine sawfly.
Neodiprion autumnalis (Smith) larvae were caged for two successive years on root-trenched, watered, and untreated ponderosa pine (Pinus ponderosa Doug. ex Laws.) to determine effects of host moisture stress on larval feeding. Levels of moisture stress (as measured by the Scholander pressure chamber) differed significantly among treatment levels during 1984 and 1985 larval feeding periods. Differences in larval feeding success were not detected in 1984. In 1985, however, larvae on trenched (stressed) trees clipped and rejected more foliage, consumed more needles, had lower pupal weights, lower survival, and a longer feeding period than larvae on watered or untreated trees. Frass production did not differ among treatment levels. The length of the feeding period was shorter for larvae on watered trees than for larvae on untreated trees, but other measures of feeding success did not significantly differ between watered and untreated trees.


A new pathologic classification for elbow stiffness based on our experience in 216 patients.
Elbow stiffness commonly causes functional impairment and upper-limb disability. This study aimed to develop a new pathologic classification to further understand and standardize elbow arthrolysis from a new perspective, as well as to determine clinical outcomes. Extension-flexion dysfunction was classified into 4 types: EFI, tethers alone; EFII, tethers with blocks; EFIII, articular malformation; and EFIV, bony ankylosis. Forearm rotation dysfunction was classified into 3 types: FRI, contracture alone; FRII, radial head malunion or nonunion; and FRIII, proximal radioulnar bony ankylosis. A total of 216 patients with elbow stiffness were prospectively included and categorized preoperatively. All surgical procedures were performed by the same chief surgeon; different types underwent specific procedures. Patient data, elbow motion, and functional scores were analyzed. Mean range of motion (ROM) increased from 40° preoperatively to 118° at final follow-up; 88% of patients regained ROM of 100° or greater. The forearm rotation arc (FRA) with forearm rotation dysfunction increased from a preoperative mean of 76° to 128°; 82% of patients regained an FRA of 100° or greater. The mean Mayo Elbow Performance Index (MEPI) increased from 63 to 91 points; the proportion of patients with good or excellent results was 95%. EFI patients had the best ROM (129°) and MEPI (93 points) and EFIV patients achieved the most-changed ROM (116°), whereas EFIII patients had the worst ROM (104°) and MEPI (84 points) and the least-changed ROM (64°). The FRA was best in FRI patients (142°), followed by FRII patients (118°), and worst in FRIII patients (82°); in contrast, the changed FRA was greatest in FRIII patients (82°), followed by FRII patients (64°), and least in FRI patients (37°). This study suggests that the proposed pathologic classification provides a new perspective on the understanding and standardization of elbow arthrolysis, providing satisfactory clinical outcomes.


Evidence for stronger sexual selection in males than in females using an adapted method of Bateman's classic study of Drosophila melanogaster.
Bateman's principles, originally a test of Darwin's theoretical ideas, have since become fundamental to sexual selection theory and vital to contextualizing the role of anisogamy in sex differences of precopulatory sexual selection. Despite this, Bateman's principles have received substantial criticism, and researchers have highlighted both statistical and methodological errors, suggesting that Bateman's original experiment contains too much sampling bias for there to be any evidence of sexual selection. This study uses Bateman's original method as a template, accounting for two fundamental flaws in his original experiments, (a) viability effects and (b) a lack of mating behavior observation. Experimental populations of Drosophila melanogaster consisted of wild-type focal individuals and nonfocal individuals established by backcrossing the brown eye (bw-) eye-color marker-thereby avoiding viability effects. Mating assays included direct observation of mating behavior and total number of offspring, to obtain measures of mating success, reproductive success, and standardized variance measures based on Bateman's principles. The results provide observational support for Bateman's principles, particularly that (a) males had significantly more variation in number of mates compared with females and (b) males had significantly more individual variation in total number of offspring. We also find a significantly steeper Bateman gradient for males compared to females, suggesting that sexual selection is operating more intensely in males. However, female remating was limited, providing the opportunity for future study to further explore female reproductive success in correlation with higher levels of remating.


In-situ observation for natural gas hydrate in porous medium: Water performance and formation characteristic.
Extensive efforts have been made regarding gas hydrate sample reconstruction in the laboratory for a better understanding and development of natural gas resources. Magnetic resonance imaging (MRI) is a useful method for directly observing the reconstruction of methane hydrate, yet relevant studies remain limited. In this study, a 9.4-T 400-MHz MRI instrument was employed to investigate CH4 hydrate formation in porous media involving various initial water saturation levels and sand diameters. Pressure histories and MRI signal variations were monitored to discuss the process of CH4 hydrate growth, and the three main formation stages of induction, rapid growth, and slow formation were determined. Furthermore, the liquid water performance in MRI micro-images was analyzed to predict the characteristics of CH4 hydrate formation. The results indicated that CH4 hydrate formed in a spatially and temporally random manner and that pore plugging occurred owing to the residual water encased in grown hydrate. Additionally, phase saturations, water conversion percentages, and formation rates were defined to evaluate the effect of sand diameter and initial water saturation on CH4 hydrate formation. With the reduction in the diameter of quartz glass beads from 400 μm to 100 μm, the average hydrate formation rate increased from 0.0010 min-1 to 0.0034 min-1, respectively. When the initial water saturation decreased to the optimized value (0.22 in this study), the water conversion percentage and hydrate saturation increased.


Clinical excellence: evidence on the assessment of senior doctors' applications to the UK Advisory Committee on Clinical Excellence Awards. Analysis of complete national data set.
To inform the rational deployment of assessor resource in the evaluation of applications to the UK Advisory Committee on Clinical Excellence Awards (ACCEA). ACCEA are responsible for a scheme to financially reward senior doctors in England and Wales who are assessed to be working over and above the standard expected of their role. Anonymised applications of consultants and senior academic GPs for awards were considered by members of 14 regional subcommittees and 2 national assessing committees during the 2014-2015 round of applications. It involved secondary analysis of complete anonymised national data set. We analysed scores for each of 1916 applications for a clinical excellence award across 4 levels of award. Scores were provided by members of 16 subcommittees. We assessed the reliability of assessments and described the variance in the assessment of scores. Members of regional subcommittees assessed 1529 new applications and 387 renewal applications. Average scores increased with the level of application being made. On average, applications were assessed by 9.5 assessors. The highest contributions to the variance in individual assessors' assessments of applications were attributable to assessors or to residual variance. The applicant accounted for around a quarter of the variance in scores for new bronze applications, with this proportion decreasing for higher award levels. Reliability in excess of 0.7 can be attained where 4 assessors score bronze applications, with twice as many assessors being required for higher levels of application. Assessment processes pertaining in the competitive allocation of public funds need to be credible and efficient. The present arrangements for assessing and scoring applications are defensible, depending on the level of reliability judged to be required in the assessment process. Some relatively minor reconfiguration in approaches to scoring might usefully be considered in future rounds of assessment.


Co-association of Two nir Denitrifiers Under the Influence of Emergent Macrophytes.
Diverse microorganisms perform similar metabolic process in biogeochemical cycles, whereas they are found of highly genomic differentiation. Biotic interactions should be considered in any community survey of these functional groups, as they contribute to community assembly and ultimately alter ecosystem properties. Current knowledge has mainly been achieved based on functional community characterized by a single gene using co-occurrence network analysis. Biotic interactions between functionally equivalent microorganisms, however, have received much less attention. Herein, we propose the nirK- and nirS-type denitrifier communities represented by these two nitrite reductase (nir)-encoding genes, as model communities to investigate the potential interactions of two nir denitrifiers. We evaluated co-occurrence patterns and co-association network structures of nir denitrifier community from an emergent macrophyte-dominated riparian zone of highly active denitrification in Lake Taihu, China. We found a more segregated pattern in combined nir communities than in individual communities. Network analyses revealed a modularized structure of associating nir denitrifiers. An increased proportion of negative associations among combined communities relative to those of individual communities indicated potential interspecific competition between nirK and nirS denitrifiers. pH and NH4+-N were the most important factors driving co-occurrence and mutual exclusion between nirK and nirS denitrifiers. We also showed the topological importance of nirK denitrifiers acting as module hubs for constructing entire association networks. We revealed previously unexplored co-association relationships between nirK and nirS denitrifiers, which were previously neglected in network analyses of individual communities. Using nir denitrifier community as a model, these findings would be helpful for us to understand the biotic interactions and mechanisms underlying how functional groups co-exist in performing biogeochemical cycles.


Secreted Phosphoprotein 1 and Sex-Specific Differences in Silica-Induced Pulmonary Fibrosis in Mice.
Fibrotic lung diseases occur predominantly in males, and reports describe better survival in affected females. Male mice are more sensitive to silica-induced lung fibrosis than silica-treated female mice. Secreted phosphoprotein 1 (SPP1, also known as osteopontin) increases in pulmonary fibrosis, and Spp1 transcription may be regulated by estrogen or estrogen receptor-related receptors. We determined whether differences in silica-induced SPP1 levels contribute to sex differences in lung fibrosis. Male and female mice were treated with 0.2 g/kg intratracheal silica, and lung injury was assessed 1, 3, or 14 days post-exposure. Gene-targeted (Spp1-/-) mice, control Spp1+/+ (C57BL/6J) mice, ovariectomized (OVX) female mice, and estrogen-treated male mice were treated with silica, and lung injury was assessed. Silica-induced SPP1 in lung tissue, bronchoalveolar lavage, and serum increased more in male than in female mice. Following silica treatment, bronchoalveolar lavage cell infiltrates decreased in female Spp1-/- mice compared with female Spp1+/+ mice, and lung hydroxyproline decreased in male Spp1-/- mice compared with male Spp1+/+ mice. OVX female mice had increased lung SPP1 expression in response to silica compared with silica-treated sham female mice. Silica-induced lung collagen and hydroxyproline (markers of fibrosis), and SPP1 levels decreased in estrogen-treated males compared with untreated males. These findings suggest that sex-specific differences in SPP1 levels contribute to the differential sensitivity of male and female mice to the development of silica-induced fibrosis. Latoche JD, Ufelle AC, Fazzi F, Ganguly K, Leikauf GD, Fattman CL. 2016. Secreted phosphoprotein 1 and sex-specific differences in silica-induced pulmonary fibrosis in mice. Environ Health Perspect 124:1199-1207; http://dx.doi.org/10.1289/ehp.1510335.


Distal coronary embolization following acute myocardial infarction increases early infarct size and late left ventricular wall thinning in a porcine model.
Distal coronary embolization (DCE) of thrombotic material occurs frequently during percutaneous interventions for acute myocardial infarction and can alter coronary flow grades. The significance of DCE on infarct size and myocardial function remains unsettled. The aims of this study were to evaluate the effects of DCE sufficient to cause no-reflow on infarct size, cardiac function and ventricular remodeling in a porcine acute myocardial infarction model. Female Yorkshire pigs underwent 60 min balloon occlusion of the left anterior descending coronary artery followed by reperfusion and injection of either microthrombi (prepared from autologous porcine blood) sufficient to cause no-reflow (DCE), or saline (control). Animals were sacrificed at 3 h (n = 5), 3 days (n = 20) or 6 weeks (n = 20) post-AMI. Cardiovascular magnetic resonance (CMR), serum troponin-I, and cardiac gelatinase (MMP) and survival kinase (Akt) activities were assessed. At 3d, DCE increased infarct size (CMR: 18.8% vs. 14.5%, p = 0.04; serum troponin-I: 13.3 vs. 6.9 ng/uL, p < 0.05) and MMP-2 activity levels (0.81 vs. 0.49, p = 0.002), with reduced activation of Akt (0.06 versus 0.26, p = 0.02). At 6 weeks, there were no differences in infarct size, ventricular volume or ejection fraction between the two groups, although infarct transmurality (70% vs. 57%, p< 0.04) and ventricular thinning (percent change in mid anteroseptal wall thickness:-25.6% vs. 0.7%, p = 0.03) were significantly increased in the DCE group. DCE increased early infarct size, but without affecting later infarct size, cardiac function or ventricular volumes. The significance of the later remodelling changes (ventricular thinning and transmurality) following DCE, possibly due to changes in MMP-2 activity and Akt activation, merits further study.


Dermoscopic Pattern of Basal Cell Carcinoma in H- and Non-H-zones.
Basal cell carcinoma (BCC) localized in the H-zone, the region of fusion of embryonic masses, has been associated with a higher risk of deeper invasion and more frequent recurrence. The aim of the study was to compare dermoscopic features of BCC in H and non-H zone that may most appropriately characterize those two locations. Dermoscopy images of histopathologically confirmed BCCs from 120 patients were retro-spectively analyzed. Dermoscopy features of BCC in H- and non-H zone were described and a comparative study of the dermoscopic pattern of BCC between the two locations was performed. Of 120 BCC cases included in this study, 41 (34.2%) were located in the H-zone. The most frequent histological type was nodular (51.3% in H- zone and 61.6 % in non-H-zone) followed by superficial (5.1% and 19.8 % in H and non-H-zone respectively).In dermoscopy, there was a higher prevalence of ulceration (73.2% versus 43.6%, P < 0.001) in H-zone and a lower prevalence of brown globules (26.8% versus 53.2%; P = 0.01), when compared with the non-H-zone. Our results show that dermoscopic features of BCC on the face fulfill a typical pattern regardless of the region, except for the prevalence of the ulceration which is significantly more frequent in H-zone and the brown globules present significantly more often in the non-H-zone It can be hypothesized that H-zone might predispose to more aggressive course of BCC complicated by ulceration and consequently deeper tissue destruction.


Poxvirus infection of the skin of an eastern grey kangaroo.
A solitary cutaneous papillomatous lesion, present for 6 weeks, was surgically removed from the hind limb of an 18-month old eastern grey kangaroo (Macropus giganteus). The lesion did not recur within 6 months of excision. Poxvirus particles were demonstrated in epidermal cells of the lesion by electron microscopy.


Toward Planetary Health Ethics? Refiguring Bios in Bioethics.
In responding to perceived crises-such as the COVID-19 pandemic-in routinized ways, contemporary bioethics can make us prisoners of the proximate. Rather, we need bioethics to recognize and engage with complex configurations of global ecosystem degradation and collapse, thereby showing us paths toward co-inhabiting the planet securely and sustainably. Such a planetary health ethics might draw rewardingly on Indigenous knowledge practices or Indigenous philosophical ecologies. It will require ethicists, with other health professionals, to step up and become public advocates for environmental sustainability. The COVID-19 pandemic should be seen as opening a portal to planetary health ethics or ecologized bioethics.


B7-H4's role "beyond the tumor".
B7-H4 is a ligand in the B7 costimulatory family, executing suppressive function on the immune system in many diseases, such as cancer, allograft rejection, and autoimmune diseases. The receptor for this molecule has yet to be clarified. The engagement of B7-H4 inhibits proliferation of immune cells by stopping the cell cycle at the G0/G1 phase and leads to apoptosis via the Fas/FasL pathway consequently accelerating tumor progression and alleviating allograft rejection. The pathogenic role of B7-H4 in tumors has been widely established, but few studies have focused on its function in other disorders. Here, we review recent advances in our understanding of B7-H4 biology in disease settings other than tumors and document the beneficial values to treat those diseases by targeting this molecule and related signaling pathways.


Parity and Risk of Coronary Heart Disease in Middle-aged and Older Chinese Women.
Pregnancy leads to physiological changes in lipid, glucose levels, and weight, which may increase the risk of coronary heart disease (CHD) in later life. The purpose of this study was to examine whether parity is associated with CHD in middle-aged and older Chinese women. A total of 20,207 women aged 37 to 94 years from Dongfeng-Tongji Cohort who completed the questionnaire, were medically examined and provided blood samples, were included in our analysis. CHD cases were determined by self-report of physician diagnosis through face-to-face interviews. Logistic regression models were used to estimate the association between parity and CHD. The rate of CHD was 15.8%. Parity had a positive association with CHD without adjustment of covariates. After controlling for the potential confounders, increasing risk of coronary heart disease was observed in women who had two (OR, 1.65; 95% CI, 1.41-1.93), three (OR, 1.76; 95% CI, 1.44-2.16), and four or more live births (OR, 1.71; 95% CI, 1.33-2.20) compared with women with just one live birth. High parity was significantly associated with increasing risk of CHD in Chinese women. This suggests that multiparity may be a risk factor for CHD among Chinese women.


High-breathable, antimicrobial and water-repellent face mask for breath monitoring.
Face masks with multiple functionalities and exceptional durability have attracted increasing interests during the COVID-19 pandemic. How to integrate the antibacterial property, comfortability during long-time wearing, and breath monitoring capability together on a face mask is still challenging. Here we developed a kind of face mask that assembles the particles-free water-repellent fabric, antibacterial fabric, and hidden breath monitoring device together, resulting in the highly breathable, water-repellent, and antibacterial face mask with breath monitoring capability. Based on the rational design of the functional layers, the mask shows exceptional repellency to micro-fogs generated during breathing while maintaining high air permeability and inhibiting the passage of bacteria-containing aerogel. More importantly, the multi-functional mask can also monitor the breath condition in a wireless and real-time fashion, and collect the breath information for epidemiological analysis. The resultant mask paves the way to develop multi-functional breath-monitoring masks that can aid the prevention of the secondary transmission of bacteria and viruses while preventing potential discomfort and face skin allergy during long-period wearing.


Concentrator-assisted solar still for improving freshwater yield: an experimental approach.
The present experimental study aims to make advancements in the daily production of freshwater by a single solar still, with the ultimate goal of increasing its efficiency. The experiment was carried out in the solar still with and without integration at four different water masses within the basin, and metrics such as water, glass, basin temperature, and drinkable water generated were measured. The results showed that the daily distillate collected from the integrated system using 2.5 kg/h of mass flow in the parabolic concentrator produced 2.99 kg at the minimum water mass of 20 kg placed in the basin. When the flow velocity of water in the parabolic concentrator is raised from 2.5 to 5 kg/h, the amount of freshwater generated decreases from 2.99 to 2.66 kg. Compared to traditional single slope solar still, the potable water generated increases by roughly 18.24, 18.29, and 18.33% for water mass of 30, 40, and 50 kg, respectively, with the mass flow rate of water in the serpentine tubes as 2.5 kg/h. The results also reveals that, in addition to the PTC collector, the mass flowrate of fluid in the serpentine tube arrangement submerged in the basin affects daily solar efficiency. There is a significant reduction of about 1-2.3% in the daily efficiency of the system with increased mass flow rate of fluid in the serpentine tube arrangement. Similarly, the daily efficiency in all the cases reduces with increased water depth.


Jejunal secretion in response to a duodenal mixed nutrient perfusion.
A multilumen balloon tube constructed to separate duodenal and jejunal perfusion segments was placed in the proximal small bowel of 6 healthy volunteers. The effect of nutrient mixture in the duodenum on net jejunal water and electrolyte flux was then determined. The duodenum was perfused with a balanced electrolyte solution before and after the nutrient perfusion. Net water flux in the perfused jejunum changed from absorption 27.0 +/- 6.0 microliter/min/cm, (mean +/- SEM) to secretion 7.7 +/- 7.3 microliter/min/cm (P less than 0.025) during nutrient perfusion. There was also net chloride secretion and decreased net absorption of Na, K, and HCO3 (P less than 0.05). The jejunal absorption of water and electrolytes before and after the duodenal nutrient perfusion was the same. Results indicate that intestinal secretion may occur under physiologic conditions at sites remote to the application of food in humans.


Sustainable water and sanitation for all: Are we there yet?
The lack of access to water and sanitation services (WSS) of a considerable share of the world population has been challenging the international community for decades. The proposal of the Millennium Development Goals and, later on, the Sustainable Development Goals (SDGs) by the United Nations (UN) intended to act as a blueprint to achieve a more equitable future for all and, in the case of WSS, "Ensure the availability and sustainable management of water and sanitation for all" (SDG 6). However, the current global pandemic further emphasised the importance of WSS, given the increasing asymmetries faced by billions worldwide, and the gaps between high-income and low- and middle-income nations. For this reason, understanding whether low- and middle-income countries have been approximating towards or deviating from the SDG 6 is crucial to derive and communicate key information for the sake of improved public governance and political decision-making. In this paper, we extend a state-of-the-art methodology based on data envelopment analysis for assessing the convergence of the low- and middle-income UN Member States regarding the SDG 6 between 2016 and 2017. We find that, on average, not only did the Member States converge by decreasing the performance spread and the gap between the best and worst practice frontiers, but also the Level of water stress: freshwater withdrawal as a proportion of available freshwater resources was the indicator in which the majority exhibited the worst performances. In the end, we derive possible policy implications, which, as our results show, are aligned with the recent UN reports on the subject.