Prediction of cognitive decline in healthy aging based on neuropsychiatric symptoms and PET-biomarkers of Alzheimer's disease.
Neuropsychiatric symptoms (NPS) have been associated with a risk of accelerated cognitive decline or conversion to dementia of the Alzheimer's Disease (AD) type. Moreover, the NPS were also associated with higher AD biomarkers (brain tau and amyloid burden) even in non-demented patients. But the effect of the relationship between NPS and biomarkers on cognitive decline has not yet been studied. This work aims to assess the relationship between longitudinal cognitive changes and NPS, specifically depression and anxiety, in association with AD biomarkers in healthy middle-aged to older participants. The cohort consisted of 101 healthy participants aged 50-70 years, 66 of whom had neuropsychological assessments of memory, executive functions, and global cognition at a 2-year follow-up. At baseline, NPS were assessed using the Beck Depression and Anxiety Inventories while brain tau and amyloid loads were measured using positron emission topography. For tau burden, THK5351 uptake is used as a proxy of tau and neuroinflammation. Participants, declining or remaining stable at follow-up, were categorized into groups for each cognitive domain. Group classification was investigated using binary logistic regressions based on combined AD biomarkers and the two NPS. The results showed that an association between anxiety and prefrontal amyloid burden significantly classified episodic memory decline, while the classification of global cognitive decline involved temporal and occipital amyloid burden but not NPS. Moreover, depression together with prefrontal and hippocampal tau burden were associated with a decline in memory. The classification of participants based on executive decline was related to depression and mainly prefrontal tau burden. These findings suggest that the combination of NPS and brain biomarkers of AD predicts the occurrence of cognitive decline in aging.


Hemin/nitrite/H2O2 induces brain homogenate oxidation and nitration: effects of some flavonoids.
Oxidative injury has been implicated in the pathogenesis of numerous neurodegenerative diseases. Recently, it has been found that with the existence of hydrogen peroxide and nitrite, hemin catalyzes protein nitration. We hypothesize under certain pathological conditions, hemin catalyzed protein nitration may happen in the brain. In this paper, the effects of three flavonoids, i.e. quercetin, catachin and baicalein on hemin/nitrite/H2O2 induced brain homogenate oxidation and nitration were studied. The results showed that hemin/nitrite/H2O2 system could effectively induce brain homogenate protein oxidation and nitration. Quercetin, catachin and baicalein dose-dependently inhibited hemin/nitrite/H2O2 system-induced protein nitration in a dose-dependent manner, the inhibition of protein nitration was in the order of quercetin>catachin>baicalein. These compounds also inhibited hemin/H2O2 system-induced lipid peroxidation, the inhibition order was baicalein >quercetin>catachin. However, these flavonoids showed marginal effect on hemin/nitrite/H2O2 system caused protein oxidation and thiol oxidation. The inhibition activities of flavonoids on hemin/nitrite/H2O2 system-induced protein nitration may closely relate to their radical scavenging activities, since the inhibition order of protein nitration is the same as the radical scavenging order. These results indicate hemin/nitrite/H2O2 system induces different types of oxidative assault on bio-molecules. Flavonoids could act as antioxidants inhibiting ROS and RNS caused brain damage.


Cytotoxicity and genotoxicity in human lung epithelial A549 cells caused by airborne volatile organic compounds emitted from pine wood and oriented strand boards.
Due to the massive reduction of air-change rates in modern, energy-saving houses and dwellings, the contribution of volatile organic compound (VOCs) emissions from wood-based materials to indoor air quality has become increasingly important. To evaluate toxicity of VOC mixtures typically emitted from pine wood and oriented strand boards (OSB) and their main constituents (selected terpenes and aldehydes), cytotoxicity and genotoxicity were investigated in human A549 lung cells. To facilitate exposure directly via gas phase, a 250 L emission chamber was combined with a Vitrocell exposure system. VOC exposure concentrations were measured by GC/MSD. Biological effects were determined after an exposure time of 1h by measuring cytotoxicity (erythrosine B staining) and genotoxicity (comet assay). Neither cytotoxic nor genotoxic effects were observed for VOC mixtures emitted from pine wood or OSB at loading factors of approximately 13 m(2)/m(3) (worst case conditions) of the panels (with maximum VOC levels of about 80 mg/m(3)) in comparison to clean air. While alpha-pinene and Delta(3)-carene did not induce toxic effects even at exposure concentrations of up to 1800 mg/m(3) and 600 mg/m(3), respectively, hexanal showed a cytotoxic effect at 2000 mg/m(3). The alpha,beta-unsaturated aldehydes 2-heptenal and 2-octenal caused genotoxic effects in concentrations exceeding 100mg/m(3) and 40 mg/m(3), respectively. In conclusion, high concentrations of VOCs and VOC mixtures emitted from pine wood and OSB did not lead to adverse effects in A549 human lung cells even at concentrations 10(2) to 10(5)-fold higher than those found in normal indoor air. Attention must be paid to mutagenic and possibly carcinogenic alpha,beta-unsaturated aldehydes.


An MSFIA system for mercury speciation based on an anion-exchange membrane.
A new methodology for the in-line preconcentration, clean-up and speciation of mercury by use of an anion-exchange membrane is proposed. The speciation of mercury is based on retention of its tetrachloro complex onto the membrane while organic mercury flows freely through it. A multisyringe is used as a liquid driver and a cold vapour atomic fluorescence detector is employed to ensure a high sensitivity. Organic mercury is decomposed into to inorganic mercury by using a UV lamp. The carrier and reductant streams consist of 1.5% (m/v) hydrochloric acid and 2% (m/v) tin chloride, respectively. Certified reference material DORM-2 was digested with 37% hydrochloric acid and analysed directly without the need for extraction. The proposed system is more environmental friendly than the classical liquid-liquid extraction procedure. Mercury recoveries from spiked samples and the reference material were all close to 100%. An LOD of 14 and 16 ng/L was obtained for total and organic mercury, respectively, both with an RSD less than 1.3%.


Fluorinated chloramphenicol acetyltransferase thermostability and activity profile: improved thermostability by a single-isoleucine mutant.
A lysate-based thermostability and activity profile is described for chloramphenicol acetyltransferase (CAT) expressed in trifluoroleucine, T (CAT T). CAT and 13 single-isoleucine CAT mutants were expressed in medium supplemented with T and assayed for thermostability on cell lysates. Although fluorinated mutants, L82I T and L208I T, showed losses in thermostability, the L158I T fluorinated mutant demonstrated an enhanced thermostability relative to CAT T. Further characterization of L158I T suggested that T at position 158 contributed to a portion of the observed loss in thermostability upon global fluorination.


The treatment of osteitis pubis with heparin.
We treated 7 patients with osteitis pubis by heparinization. Of the 7 patients 2 had a dramatic improvement. Small doses of heparin given routinely preoperatively and postoperatively were not found to prevent the development of osteitis pubis. In view of these results as well as the fact that there presently is no effective method of treatment of this disorder, it is considered justifiable to subject all patients with postoperative osteitis pubis to a therapeutic trial with heparinization.


[Pulmonary hypertension in end-stage renal disease: three case reports].
Within three months, three patients with end-stage renal disease presented for evaluation of pulmonary hypertension (PH): a 72-year-old woman (case 1), a 67-year-old patient (case 2) and a 75-year-old patient (case 3), each with increasing dyspnea (WHO functional class III). In all three cases, there was echocardiographic evidence of right heart failure; right heart catheterization was completed before and after dialysis. In case 1, we found a postcapillary PH (PH group 2 - PH with left heart diseases/diastolic dysfunction). Case 2 also showed a postcapillary PH and a high cardiac output of 9.7 l/min. In case 3, unmasked after dialysis, a precapillary, pulmonary arterial hypertension (PAH - group 1) was detected. In patient 1, no relevant improvement of symptoms was observed, despite optimized cardiac therapy. There was a significant clinical improvement in patient 2 after surgical reduction of the arteriovenous shunt. In patient 3, relevant clinical and hemodynamic improvement was seen under treatment with bosentan. These cases confirm the role of right heart catheterization in the differential diagnosis of unclear PH in patients with end-stage renal failure. Moreover, the three cases point to three different causes. Specific therapies can result in significant symptomatic improvement.


[The effect of long-term calcitonin administration on bone cells and bone mineralization in the rat (author's transl)].
The effect of calcitonin on bone tissue was studied in rat cortical and trabecular bone after long-term treatment. The aim of this study was to get exact data on calcitonin action on bone tissue by histomorphometry. Histomorphometric analysis of bone alterations was performed using undecalcified longitudinal as well as grounded cross sections of the tibial metaphysis and diaphysis. In agreement with other authors our experimental results show that calcitonin inhibits clasts but by a reduced cellular resorption activity of osteoclasts. Bone formation is not affected by calcitonin in intact as well as in parathyroidectomized animals. On the contrary bone mineralization is clearly improved under calcitonin administration in parathyroidectomized rats. This favourable effect is probably caused by a direct hormonal influence on calcium transport in the osteoblast.


Potential airborne asbestos exposures in dentistry: a comprehensive review and risk assessment.
Chrysotile was formerly used in the manufacture of casting ring liner (CRL) and periodontal dressing powder (PDP). The purpose of this study was to describe the potential for airborne asbestos exposure among dental professionals who may have used these products and to assess their risk of asbestos-related disease (ARD). Task-specific exposure data associated with CRL and PDP were identified and compared to regulatory standards for asbestos and health-based benchmarks. Personal airborne fiber concentrations ranged from 0.008-3.5 f/cc by PCM (duration: 3-420 minutes) for CRL (tearing, placement), and from <0.0044-<0.297 f/cc by PCM (duration: 5-28 minutes) for PDP (mixing). Eight-hour time-weighted average (TWA) exposures were calculated using the reported task-based airborne fiber concentrations and associated sampling durations. For CRL tasks, the upper-bound calculated 8-hour TWA of 0.022 f/cc (tearing, placement) did not exceed regulatory standards for asbestos (≥0.1 f/cc). All samples collected during the mixing of PDP resulted in non-measurable fiber concentrations. The greatest estimated cumulative asbestos exposure for dental professionals using CRL (tearing, placement) of 0.33 f/cc-years is well below "best estimate", published chrysotile no-observed-adverse-effect-levels (NOAEL) for ARD (lung cancer = 89-168 f/cc-years; pleural mesothelioma = 208-415 f/cc-years). As such, the use of asbestos-containing CRL and/or PDP is not expected to pose an increased risk of ARD among dental professionals. This conclusion is consistent with the lack of an increased risk of ARD reported in epidemiological studies of these occupations.


Role of respiratory and non-respiratory neurones in the region of the NTS in the elaboration of the sneeze reflex in cat.
Extracellular recordings were made in the dorsal respiratory group (DRG) and adjacent reticular formation following single-shock stimulation of the anterior ethmoidal nerve (AEN) and during sneeze evoked by repetitive stimulation of the AEN in nembutal-anaesthetized, curarized and ventilated cats. These neurones were characterised according to (i) their activity during the respiratory cycle (as inspiratory augmenting or decrementing (I Aug or I Dec), expiratory augmenting or decrementing (E Aug or E Dec), silent or tonic), and (ii) their axonal projection (bulbospinal or non-bulbospinal-non-vagal (BS or NBS-NV)). Following single-shock stimulation of the AEN, most of the inspiratory neurones were transiently inhibited, whereas E Aug neurones were activated and E Dec neurones were activated and then inhibited. Silent neurones responded with a multispike or a paucispike pattern. Following repetitive stimulation of the AEN and during the resulting sneeze reflex, I Aug neurones increased their activity in parallel with the phrenic activity, I Dec neurones fired at the onset and at the end of the inspiration, E Dec and some silent neurones fired either during the compressive phase or after the expulsive phase, whereas E Aug and some silent neurones fired during the expulsive phase. We conclude that sneeze involves a reconfiguration of the central respiratory drive which uses, at least partly, the respiratory network to trigger a non-ventilatory defensive motor act.


[Traumatic physeal separations of the distal tibia. Occurrence, forms, treatment strategies].
Traumatic physeal separations (SH I/II) of the lower extremities are rare. Complications are reported in 2.2-39.6%. The current study is intended to provide recent data concerning epidemiology and treatment decisions in physeal separation of the distal tibia. All patients who suffered a physeal separation of the distal tibia in a 36-month period were included in a multicenter study. Age, gender, mechanism of injury, classification, therapeutic decision, and early complications were recorded online. There were 150 cases (64.6% male, 35.4% female, average age 11.8 years). The most frequent mechanism of injury was sportive activity (42%); 76% of cases needed reduction. Antecurvation was tolerated up to 10° (p=0.0021) and valgus up to 7° (p=0.0155). Tolerance ranges up to 5° of retrocurvation and varus were not statistically significant. The investigation confirmed epidemiological data of former studies. For the first time data concerning the treatment reality of physeal separations of the distal tibia were recorded. They consistently follow the recommendations of the appropriate literature.


Pulmonary functional abnormalities in asymptomatic patients with systemic sclerosis.
BACKGROUND: Systemic sclerosis (SSc) is a disease characterized by widespread fibrosis of the skin and multiple organs, including the lungs. This study was designed to evaluate pulmonary function in SSc patients without symptoms of lung involvement. METHODS: Spirometric measurements were done in 26 female SSC patients without symptoms of pulmonary involvement. RESULTS: Maximal voluntary ventilation was found to be decreased in half of the patients, and forced vital capacity was decreased in 23% of the patients. Forced expiratory flow rate was impaired in about half of the SSc patients, especially the flow at 50-75% of forced vital capacity. Peak expiratory flow rate was decreased in 77% of asymptomatic patients. CONCLUSIONS: A functional defect, mainly of the restrictive type, was observed in the majority of asymptomatic patients with SSc. Pulmonary function testing is recommended for all SSc patients.


Age-related changes in secretion rate and post-secretory metabolism of growth hormone in swine.
The effect of age on growth hormone (GH) metabolism and GH-releasing factor (GRF)-induced GH concentrations were studied in 7 young (3 mo, 39 kg) and 7 old (30 mo, 156 kg) Yorkshire x Landrace female pigs. Jugular catheters were surgically inserted and 60 hr later total serum volume was determined. The following day, all animals were infused for 3 hr with GH (30.3 ng.min/kg B.W.) in order to calculate GH metabolic clearance rate (MCR), secretion rate (SR) and half-life (t 1/2). Two days later, 15 micrograms/kg of GRF was injected i.v. into all pigs. On a per animal basis, aging increased (P < .01) MCR (299 vs 132 ml/min), SR (714 vs 422 ng/min) and serum volume (6.6 vs 2.01), whereas t1/2 was unaltered (P > .1). Basal GH concentrations were lower in older pigs (P < .10) but the GRF-induced GH concentrations (measured as GH peak or area under the curve, AUC) were not affected by age (P > .1). Yet, when induced total GH secretion (AUC x MCR) and average total serum GH (mean GH post-injection x serum volume) were calculated per pig, these variables significantly increased between 3 and 30 mo of age. Basal IGF-I concentrations were lower in older pigs (P < .01), yet, there was a tendency (P = .10) for these pigs to show a greater IGF-I response to GH infusion. The present data therefore indicate that age alters both SR and post-secretory metabolism of GH.(ABSTRACT TRUNCATED AT 250 WORDS)


Laser beam steering of 532 nm using a power-efficient focal plane array.
Laser beam steering is important for classical and quantum information processing. On-chip beam steering is a major motivation for developing large-scale photonic integrated circuits such as optical phased arrays. A major challenge for such arrays is to simultaneously control a large number of on-chip phase shifters, which requires a complicated analog control algorithm and rapidly increasing power consumption. We report a green light (532 nm) 1 × 16 focal plane array photonic integrated circuit with simple control and low power consumption. Fabricated on a silicon nitride platform, the focal plane array achieves angular beam steering over a 10° field of view, with ultra-low electrical power consumption (4 × 3.1 mW).


[Early detection of occupational skin diseases in sewer workers].
Skin diseases affect 30-70% of the world population, and globally, skin cancer rates are continuously increasing. In this respect, prevention programs and early detection of skin diseases are of particular importance. To screen sewer workers for skin diseases with regard to their work-related risk. Employees of the municipal utilities in Munich (Münchner Stadtentwässerung) underwent a whole-body examination of the skin, conducted by two dermatologists. In addition, all employees completed a paper-based questionnaire on risk behavior and preventive measures. We examined 81 employees (79 men, 2 women, mean age 45.7 ± 9.5 years). Skin lesions in need of treatment were found in 30.9% (n = 25): the most frequent diagnosis was mycosis pedis (16.1%). In addition, one employee was diagnosed with basal cell carcinoma and two with actinic keratoses. According to the questionnaire, 43.5% of the employees had undergone a physician-led skin cancer screening in the past, whereas sun-protection practices were rarely applied. According to our findings, employee skin cancer screening seems to be beneficial for the detection of work-related skin diseases and is associated with a high participation rate. Furthermore, the study suggests that sewer workers have a high rate of mycosis pedis, possibly a work-related effect.


Early Resumption of Sexual Intercourse after First Childbirth and Unintended Pregnancy within Six Months.
We aimed to evaluate factors associated with early resumption of sexual intercourse after first childbirth and assess whether early intercourse is associated with unprotected intercourse, subsequent pregnancy, and unintended pregnancy over 6 months. This secondary analysis used data from the First Baby Study, a prospective study of women aged 18-35 years with singleton pregnancies who delivered at 76 hospitals in Pennsylvania. At 1 and 6 months postpartum, women were asked about intercourse and the use of birth control since childbirth. We compared women who resumed intercourse in the first month after childbirth (early resumption) with those who resumed intercourse later, via multivariable logistic regression models. In our cohort, 261 of 2,643 women (9.9%) reported first intercourse within the first postpartum month (7-31 days). Women who resumed intercourse early were less educated, younger, and less likely to breastfeed, have had a perineal laceration, or have had an episiotomy than those who resumed intercourse later. In addition, they were more likely to have unprotected intercourse in at least one of the first 6 months after first childbirth (adjusted odds ratio [aOR], 2.33; 95% confidence interval [CI], 1.76-3.09); to be pregnant by 6 months postpartum (aOR, 3.03; 95% CI, 1.48-6.20); and to report that pregnancy as unintended (aOR, 3.32; 95% CI, 1.50-7.36). Nearly 10% of women resumed intercourse in the first month after childbirth. Because early resumption of intercourse was associated with a greater likelihood of unprotected intercourse and unintended pregnancy within 6 months of first childbirth, clinicians should focus efforts on comprehensive family planning and contraception counseling beginning in the prenatal period.


Polydopamine supported preparation method for solid-phase microextraction coatings on stainless steel wire.
In this paper, we introduced a novel and versatile route to prepare solid-phase microextraction coatings on the chemically inert stainless steel wire. Polydopamine films can be created on metallic substrates by an oxidant-induced polymerization and subsequently support various secondary reactions to prepare functional surfaces. In the present work, polydopamine-bioactivated stainless steel wire was successfully modified by nanostructured hydroxyapatite. Extraction performance of the fiber was assessed on several polycyclic aromatic hydrocarbons in water solutions. Extraction mechanism was suggested based on the correlation of partition coefficients and LogPs. Both aqueous and solid real life samples were used to test the reliability of the solid-phase microextraction-gas chromatography method; some analytes were detected and quantified.


Bladder muscle contractility. Comparative effects and mechanisms of action of atropine, propantheline, flavoxate, and imipramine.
The anticholinergic and antispasmodic activity of atropine, propantheline, imipramine, and flavoxate were judged by each drug's ability to inhibit bethanechol chloride and barium chloride-induced canine detrusor contractions. In this in vitro model, atropine and propantheline are pure anticholinergic agents. Imipramine significantly decreases both bethanechol and barium-induced contractions, while flavoxate only minimally inhibits the response to either stimulant.


Proteomics of dedifferentiation of SK-N-BE2 neuroblastoma cells.
Neuroblastoma develops through processes which include cellular dedifferentiation. Ability of tumors to form spheroids is one of the manifestations of dedifferentiation and carcinogenic transformation. To study mechanisms of dedifferentiation of neuroblastoma cells, we generated spheroids and performed a proteomics study to compare the spheroids with parental SK-N-BE2 cells. We observed that dedifferentiation induced extensive changes in the proteome profiles of the cells, which affected more than 30% of detected cellular proteins. Using mass spectrometry, we identified 239 proteins affected by dedifferentiation into spheroids as compared to the parental cells. These proteins represented such regulatory processes as transcription, cell cycle regulation, apoptosis, cell adhesion, metabolism, intracellular transport, stress response, and angiogenesis. A number of potent regulators of stemness, differentiation and cancer were detected as subnetworks formed by the identified proteins. Our validation tissue microarray study of 30 neuroblastoma cases confirmed that two of the identified proteins, DISC1 and DNA-PKcs, had their expression increased in advanced malignancies. Thus, our report unveiled extensive changes of the cellular proteome upon dedifferentiation of neuroblastoma cells, indicated top subnetworks and clusters of molecular mechanisms involved in dedifferentiation, and provided candidate biomarkers for clinical studies.


Percutaneous Posterior Pelvic Fixation of Spinopelvic Dissociation: A Multicenter Series of Displaced Patterns.
To characterize the success and complications of percutaneous posterior pelvic fixation in the treatment of displaced spinopelvic dissociation patterns. Retrospective cohort study. Three Level I trauma centers. 53 patients with displaced spinopelvic patterns were enrolled. Percutaneous iliosacral screw fixation was used. Main outcome measures include incidence of union, fixation failure, and soft tissue complications. All patients had displaced, unstable patterns with a mean preoperative kyphosis of 29.7 ± 15.4 degrees (range, 0-70). Most of the patients treated were neurologically intact (72%) or had an unknown examination at the time of fixation (15%). The median follow-up was 254 days (interquartile range, 141-531). The union rate was 98%. Radiographic and clinical follow-up demonstrated 1 case (2%) of nonunion. Two patients (4%) had radiographic evidence of screw loosening at the final follow-up, both of whom had fixation with a single sacroiliac-style screw placed bilaterally and went on to uneventful union. Neurologic recovery occurred at an average of 195 ± 114 days (range, 82-363 days). When present, long-term neurologic sequelae most commonly consisted of radicular pain and paresthesias at the final follow-up (n = 3, 6%). Percutaneous posterior pelvic fixation of select displaced spinopelvic dissociation seems to be safe with a low complication rate and reliable union. In a cohort of displaced fractures that were fixed in situ, we found a 2% rate of fixation failure/nonunion. Although rare, radicular pain and paresthesias were the most common long-term neurologic sequela. Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Heavy metals in eight edible fish species from two polluted tributaries (Aik and Palkhu) of the River Chenab, Pakistan.
Concentration of heavy metals (lead (Pb), cadmium (Cd), chromium (Cr), and copper (Cu)) was determined in the liver, gills, kidneys, and muscles of eight edible fish species (Channa punctata, Cirrhinus reba, Labeo rohita, Heteropneustes fossilis, Mystus cavasius, Oreochromis niloticus, Puntius sophore, and Wallago attu) from upstream and downstream zones of the Nullah Aik and Palkhu tributaries of the River Chenab located in the Sialkot district known for its tanning industries worldwide. The pattern of metal accumulation in studied organs was in the order: Cr > Pb > Cu > Cd. Liver showed greater metal accumulation, followed by gills, kidneys, and muscles. Accumulation of Pb and Cr was significantly different in organs between upstream and downstream zones. Accumulation was greater in fish species dwelling downstream, indicating impairment of ambient stream water due to untreated discharge of industrial and municipal effluents into studied streams. Highest concentration of Pb and Cr and lowest of Cd was detected in H. fossilis whereas Cu showed higher concentration and Cr lowest concentration in P. sophore. In contrast, lower concentration of Pb and Cu was recorded in M. cavasius, O. niloticus, and W. attu. Mean concentrations of Cd, Cr, and Cu were higher in pre-monsoon compared to post-monsoon season. Measured concentrations of Pb, Cd, and Cr in muscles of species such as C. punctata, W. attu, L. rohita, P. sophore, and O. niloticus were above permissible limits of heavy metals for human consumption, indicating potential health risks. Therefore, these fish species from studied locations should be avoided for human diet.


Heart toxicity from breast cancer radiotherapy : Current findings, assessment, and prevention.
Late cardiac toxicities caused by (particularly left-sided) breast radiotherapy (RT) are now recognized as rare but relevant sequelae, which has prompted research on risk structure identification and definition of threshold doses to heart subvolumes. The aim of the present review was to critically discuss the clinical evidence on late cardiac reactions based on dose-dependent outcome reports for mean heart doses as well as doses to cardiac substructures. A literature review was performed to examine clinical evidence on radiation-induced heart toxicities. Mean heart doses and doses to cardiac substructures were focused upon based on dose-dependent outcome reports. Furthermore, an overview of radiation techniques for heart protection is given and non-radiotherapeutic aspects of cardiotoxicity in the multimodal setting of breast cancer treatment are discussed. Based on available findings, the DEGRO breast cancer expert panel recommends the following constraints: mean heart dose <2.5 Gy; DmeanLV (mean dose left ventricle) < 3 Gy; V5LV (volume of LV receiving ≥5 Gy) < 17%; V23LV (volume of LV receiving ≥23 Gy) < 5%; DmeanLAD (mean dose left descending artery) < 10 Gy; V30LAD (volume of LAD receiving ≥30 Gy) < 2%; V40LAD (volume of LAD receiving ≥40 Gy) < 1%. In addition to mean heart dose, breast cancer RT treatment planning should also include constraints for cardiac subvolumes such as LV and LAD. The given constraints serve as a clinicians' aid for ensuring adequate heart protection. The individual decision between sufficient protection of cardiac structures versus optimal target volume coverage remains in the physician's hand. The risk of breast cancer-specific mortality and a patient's cardiac risk factors must be individually weighed up against the risk of radiation-induced cardiotoxicity.


Zang Siwei Qingfei Mixture Alleviates Inflammatory Response to Attenuate Acute Lung Injury by the ACE2/NF-κB Signaling Pathway in Mice.
Acute lung injury (ALI) is a serious lung disease characterized by acute and severe inflammation. Upregulation of ACE2 and inhibition of the NF-κB signaling pathway attenuate LPS-induced ALI. To explore whether Zang Siwei Qingfei Mixture inhibits the development of ALI through the ACE2/NF-κB signaling pathway. Alveolar type II epithelial cells (AEC II) were identified by immunofluorescence staining and flow cytometry. C57BL/6J mice were treated with LPS to establish an ALI model. Cell viability was assessed using CCK8 assays. The levels of ACE, ACE2, p-p38/p38, p- ERK1/2/ERK1/2, p-JNK/JNK, p-IκBα/IκB-α, p-NF-κBp65 were analyzed by Western blotting. ELISA was applied to detect the levels of TNF-a, IL-6, AGT, and Ang1-7. HE staining was used to observe lung injury. The mRNA expression of ACE, ACE2, and Mas was measured by RTqPCR. AEC II cells were successfully isolated. Treatment with Zang Siwei Qingfei mixture resulted in a decrease in ACE, p-p38/p38, p-ERK1/2/ERK1/2, p-JNK/JNK, p-IκBα/IκB-α, p- NF-κBp65 levels, while increasing ACE2 levels. Zang Siwei Qingfei mixture also led to a reduction in TNF-α, IL6, and AGT levels, while increasing Ang1-7 level. Histological analysis showed that Zang Siwei Qingfei Mixture treatment improved the alveolar structure of ALI mice and reduced inflammatory infiltration. The pretreatment with MLN-4760, an ACE2 inhibitor, resulted in opposite effects compared to Zang Siwei Qingfei Mixture treatment. Zang Siwei Qingfei mixture attenuates ALI by regulating the ACE2/NF-κB signaling pathway in mice. This study provides a theoretical foundation for the development of improved ALI treatments.


Nonalcoholic fatty liver disease in women with polycystic ovary syndrome.
Polycystic ovary syndrome (PCOS) affects 6-15% of women of reproductive age. Nonalcoholic fatty liver disease (NAFLD) affects 25-30% of the general population and its prevalence increases in parallel with the epidemics of obesity and type 2 diabetes mellitus. A growing body of evidence suggests that NAFLD and PCOS quite often co-exist. The aim of this article is to summarize and critically appraise the literature regarding: (1) the rates of co-existence of the two entities, (2) the possible pathophysiological links, (3) the proper diagnostic assessment and (4) the appropriate management of women with NAFLD and PCOS. Data from clinical studies and meta-analyses indicate a higher prevalence of NAFLD in women with PCOS ranging from 34% to 70% compared with 14% to 34% in healthy women. Inversely, women with NAFLD are more often diagnosed with PCOS. Insulin resistance (IR) and hyperandrogenism are two main potential pathophysiological links between the two entities. In this regard, IR seems to interplay with obesity and hyperandrogenism, thus affecting NAFLD and PCOS and being affected by them. Women with PCOS, particularly those with IR and/or hyperandrogenism, are suggested to be screened for NAFLD, while premenopausal women with NAFLD is suggested to be screened for PCOS. Lifestyle recommendations with a change in dietary habits, weight loss and exercise, constitute currently the cornerstone of the management of both NAFLD and PCOS. Insulin sensitizers maybe used for the treatment of these women, while there are limited promising data for the use of liraglutide.


Biological properties of avian coronavirus RNA.
RNA with a sedimentation coefficient of 64S was isolated from infectious bronchitis virus, an avian coronavirus. The SNA contained a polyadenylic acid tract and was found to be infectious.


Microbiome of permeable sandy substrate in headwater river is shaped by water chemistry rather than grain size and heterogeneity.
The reservoir of microbial communities within the soil and the sediment performs many ecological functions and offers many ecosystem services. It has been suggested that its diversity and community structure could be explained by different grain size and heterogeneity. However, most of these conclusions come from studies conducted in terrestrial soil, impermeable marine and freshwater sediment (substrate). It remains to be seen whether these conclusions hold true in permeable substrate, especially in headwater river ecosystems. To address this, a field experiment was aimed to evaluate the link between grain median size and distribution heterogeneity and microbial diversity and community structure. Permeable substrate with gradient grain sizes and heterogeneities was inoculated in a headwater river in central China, while the diversity and community composition of the total microbial community and three denitrifier communities were investigated by high throughput sequencing three months later. The total microbial community was sequenced by 16S rRNA, a marker for taxonomic diversity. Three denitrifier communities were sequenced using three functional gene markers: nirK, nirS, and nosZ. The result showed that both the diversity and community structure of the total microbial community and three denitrifier communities were determined by water chemistry rather than grain size and size distribution heterogeneity, although grain size and heterogeneity positively influenced the nutrient concentrations of the substrate. Compared to the total microbial community, denitrification functional groups had more unique species proportions, indicating that functional genes were more sensitive to environmental change than the 16S rRNA gene. Our study fills a gap in understanding microbial communities in permeable sediment in a headwater river and highlights the less importance of grain size and heterogeneity on mm-scale in shaping the diversity and structure of microbiome.


How have casemix, cost and hospital stay of inpatients in the last year of life changed over the past decade? Evidence from Italy.
Healthcare utilisation and expenditure are highly concentrated in hospital inpatient services, in particular in end-of-life care with the peak occurring in the very last year of life, regardless of patient age. Few scientific studies have investigated hospital costs and stays of patients at the end of life, and even fewer studies have analysed their evolution over time. In this paper, we exploit hospitalisation data for the Lombardy region of Italy with the aim of studying the evolution of hospital casemix, costs and stays of chronic patients, and compare the last year of life of two cohorts of patients who died in 2005 and 2014. Despite an overall three-year increase in the age at death, the results showed a significant decrease in hospital costs and use due to reduced interventions and length of hospital stays. However, this was not associated with an increase in quality of life/conditions (as indicated by clinical casemix as a proxy) for end-of-life patients; patients' casemix characteristics and clinical condition, as measured by the number of comorbidities, disease severity, prevalence of pulmonary disease and heart failure diagnosis, significantly worsened over the decade. This gives rise to important health policy concerns on how to identify effective policies and possible changes in healthcare system organisation to move from hospital-centred care to a community-centred approach whose value has been demonstrated during the COVID-19 pandemic.


Early diagnosis of tuberculosis using an INF-gamma assay in a child with HIV-1 infection and a very low CD4 count.
An 11-y-old girl diagnosed with HIV-1, presented with prolonged pyrexia and a non-reactive tuberculin skin test. An INF-gamma assay (ELISpot) was positive and led to administration of tuberculosis treatment. Positive cultures for Mycobacterium tuberculosis followed 6 weeks later. INF-gamma assays should be considered as first line investigations in HIV-1 infected subjects when TB is a diagnostic possibility.


Kidney Replacement Therapy for Fluid Management.
Emerging evidence from observational studies suggests that both slower and faster net ultrafiltration rates during kidney replacement therapy are associated with increased mortality in critically ill patients with acute kidney injury and fluid overload. Faster rates are associated with ischemic organ injury. The net ultrafiltration rate should be prescribed based on patient body weight in milliliters per kilogram per hour, with close monitoring of patient hemodynamics and fluid balance. Randomized trials are required to examine whether moderate net ultrafiltration rates compared with slower and faster rates are associated with reduced risk of hemodynamic instability, organ injury, and improved outcomes.


Application of sialidase antibodies for the diagnosis of clostridial infections.
Two immunological methods, a sialidase-inhibition test and an ELISA, had been developed for a species-specific detection of sialidases (EC 188.8.131.52) secreted by growing cells of Clostridium perfringens, C. septicum, and C. sordellii. These assays were applied to samples from the infected tissues and cotton wool plugs soaked with wound exudate from patients suspected to be suffering from gas gangrene. The results from 72 patients were compared with bacteriological investigations of 67 homologous samples. From these, 35 patients were found to be infected with one or two of the clostridial species: thirty patients contained C. perfringens, six samples showed an immunologically positive reaction for C. septicum and eight for C. sordellii. In the case of C. perfringens, a high degree of coincidence between the immunological and the bacteriological analyses was obtained. However, in infections with C. septicum or C. sordellii the bacteriological and immunological tests did not agree well. The simple and rapid sialidase inhibition test or the slightly more time-consuming ELISA, which even detects low quantities of sialidase, can be applied for the specific diagnosis of infections caused by C. perfringens, thus allowing a species-specific detection of this bacterial species in two or six hours, respectively, even at an early stage of infection. This early diagnosis is a prerequisite for a specific and life-saving therapy of this severe disease.


Left atrial and left ventricular diastolic function during acute myocardial ischaemia.
To study indices of diastolic left ventricular function during the first few seconds of myocardial ischaemia. Isovolumic and total relaxation times and left atrial and left ventricular dP/dt were identified from high fidelity (micromanometer) pressure recordings in the left ventricle and left atrium during percutaneous transluminal angioplasty of the left anterior descending coronary artery. 20 patients with isolated disease of the left anterior descending artery and normal left ventricular function. The isovolumic relaxation time lengthened during the first seven to nine seconds of ischaemia; then it shortened by an average of 15% up to the twentieth second, initially as a result of increased left atrial contractility and subsequently because of impaired ventricular relaxation. Ventricular ischaemia resulted in impaired left ventricular diastolic compliance, as shown by an increase in the total relaxation time, before there was evidence of systolic impairment. Minimum dP/dt decreased progressively (by -37% at the twentieth second of ischaemia), whereas maximum dP/dt fell only after 20 seconds of ischaemia (by -11%). Relaxation and filling of the left ventricle (indices of diastolic function) are more sensitive to myocardial ischaemia than myocardial contractility and systolic function. Left atrial contractility increases during left ventricular ischaemia.


Ginsenoside Compound K Promotes Proliferation, Migration and Differentiation of Schwann Cells via the Activation of MEK/ERK1/2 and PI3K/AKT Pathways.
The proliferation and differentiation of Schwann cells are critical for the remyelination of injured peripheral nerve. Ginsenoside compound K (CK) is a metabolite produced from ginsenoside Rb1 which has strong anti-inflammatory effects. However, the potential effects of CK on Schwann cells have not been studied systematically before. Therefore, this study was aimed to explore the functions of CK in Schwann cell proliferation, migration and differentiation and its potential regulatory mechanism. Primary Schwann cells and RSC96 cells were treated with or without CK at different doses. The proliferation and migration of primary Schwann cells and RSC96 cells were examined by Cell Counting Kit-8 (CCK-8) and Transwell assays, respectively. The mRNA expression of myelin-associated glycoprotein (MAG) and myelin basic protein (MBP) was tested by quantitative real-time polymerase chain reaction (qRT-PCR). The levels of all proteins were examined by Western blot. CK could promote cell proliferation, migration and induce MAG and MBP expression in primary Schwann cells and RSC96 cells. Furthermore, CK activated MEK/ERK1/2 and PI3K/AKT pathways, and the beneficial effects of CK on primary Schwann cells and RSC96 cells were distinctly suppressed by inhibitor PD98059 or LY294002. Ginsenoside compound K induced cell proliferation, migration and differentiation via the activation of MEK/ERK1/2 and PI3K/AKT pathways in cultured primary Schwann cells and RSC96 cells.


Damage to the innervation of the pelvic floor musculature in chronic constipation.
Constipation and defecation straining have been implicated in the pathogenesis of anorectal incontinence. We have studied 24 women with chronic constipation and 20 age- and parity-matched control subjects. Electrophysiologic techniques were used to study the innervations of the puborectalis and external anal sphincter muscles. The results show that damage can occur to the nerve supply of both these muscles in chronic constipation, and that this probably is due to perineal descent during defecation straining.


Demographic, socio-economic and clinical characteristics: implications for time to presentation at a Nigerian tertiary ophthalmic outpatient population.
To investigate the associations between time to presentation, and sociodemographic and clinical characteristics of new adult ophthalmic outpatients at the University of Nigeria Teaching Hospital (UNTH), Enugu, between March and August 2010. Hospital-based case-control study. Consecutive new ophthalmic outpatients at UNTH were categorized into controls (early presenters, i.e. <3 months after onset of current eye disease) and cases (late presenters, i.e. >3 months after onset of current eye disease). Relevant data were obtained from the participants' case notes and interviews. Descriptive statistics yielded frequency distributions; bivariate and multivariate comparisons were used to test the significance of associations. P < 0.05 was considered to indicate significance. Eight hundred and twenty-four subjects [454 males and 370 females, mean age 39.2 (standard deviation 1.2) years, range 19-82 years] participated in this study. There were 370 early presenters and 454 late presenters. Multivariate analysis found that late presentation was significantly associated with age >50 years [odds ratio (OR) 1.34, 95% confidence interval (CI) 1.28-2.22; P < 0.01], female gender (OR 1.63, 95% CI 1.52-2.11; P < 0.01), residence >20 km from UNTH (OR 0.65, 95% CI 0.38-0.89; P = 0.0212), individual-level deprivation (OR 0.69, 95% CI 0.55-0.92; P = 0.0324) and subnormal visual acuity at presentation (OR 1.32, 95% CI 1.05-1.76; P = 0.0353). At UNTH, most new adult ophthalmic outpatients present >3 months after onset of their current eye disease. Measures to overcome age-, gender- and distance-related causes of late presentation, grassroots economic empowerment of the feeder population and public education about eye health are required.


Bioavailability study of paracetamol tablets in saliva and urine.
A bioavailability study of two lots of paracetamol tablets was carried out in 5 healthy volunteers, using a crossover aleatory design, and drug monitoring in urine and saliva by high performance liquid chromatography (HPLC). Results were correlated with those obtained in an in vitro dissolution study. Statistical evaluation of bioavailability parameters indicates that the two formulations may be considered bioequivalent, in spite of differences found during early stages of the absorption process, which were preventable according to an in vitro dissolution study.


Tics and Tourette's syndrome in childhood.
Childhood tics are multidimensional in nature. The dimensions run along various continuums, including duration of symptoms (from fewer than 1 year to lifelong), intensity of symptoms (from mild to severe), frequency of symptoms (from rare to constant), variety of symptoms (from single motor groups/single phonic tic to multiple occurrences of both types), complexity of tics (from simple motor/phonic tic to multiple motor groups or the production of multiple sounds, including involuntary phrases), response to treatment (from good to minimal or no response), and comorbid psychiatric disorders (from none to multiple). This review describes these dimensions and their relationships to the current diagnostic scheme for tic disorders.


A comparison of American student and faculty experiences in mathematics courses during the COVID-19 pandemic.
This study examined the experiences of mathematics students (n = 2867) and faculty (n = 81) at California State University, Fullerton during the fall 2020 semester during which all mathematics classes were taught in a synchronous virtual setting as a result of the COVID-19 pandemic. Survey results showed that faculty concerns centered around student participation, communication, and academic integrity, while student concerns focused on understanding the material, performance in the course, and commuting to campus. For both students and faculty, appreciation for increased time flexibility was accompanied by feelings of disconnectedness from the course. While student course outcomes did not affect student preference for virtual courses, there was evidence that faculty and students may have experienced virtual learning very differently. As educational institutions move forward there will need to be substantive discussions involving both faculty and students that address the role that academic departments can take to ensure equitable learning for all.


The Importance of Patency of Tibial Run Off Arteries on Clinical Outcomes After Stenting for Chronic Total Occlusions in the Superficial Femoro-popliteal Artery.
The aim was to evaluate the impact of patent tibial arteries on stenting for chronic total occlusions (CTO) in superficial femoropopliteal artery (SFA) lesions. Additionally, the efficacy of additive tibial percutaneous transluminal angioplasty (PTA) was evaluated. A total of 238 limbs in 199 patients with de novo SFA CTO lesions treated with bare nitinol stents between 2009 and 2015 were retrospectively identified. These limbs were divided into two groups (group A [number of patent tibial arteries at baseline angiogram ≥ 2, 127 limbs in 104 patients] vs. group B [number of patent tibial arteries at baseline angiogram ≤ 1, 111 limbs in 95 patients]). Furthermore, the efficacy of additive tibial PTA on stenting for SFA CTO lesions was evaluated by comparing subgroups (group B with tibial PTA vs. without tibial PTA). The primary end point was freedom from major adverse limb events (MALE) two years after PTA, defined as a composite of ischaemic driven target lesion revascularisation (TLR) and major amputation. Group A had a significantly higher MALE free survival rate two years after PTA compared with group B (80.9% vs. 43.5%; p < .001), which was mainly driven by higher TLR free survival rates (80.9% vs. 45.9%; p < .001). In subgroup analysis, patients in group B with tibial PTA had significantly higher MALE free survival rate at two years compared with those without tibial PTA (65.5% vs. 26.2%; p = .001). The presence of patent tibial arteries was an important predictor of MALE after PTA for SFA CTO lesions. Furthermore, additional tibial PTA on SFA CTO stenting might be beneficial for clinical outcomes.


Cilostazol administration for subarachnoid hemorrhage: A meta-analysis of randomized controlled trials.
The efficacy of cilostazol administration to treat subarachnoid hemorrhage remains controversial. We conduct a systematic review and meta-analysis to explore the influence of cilostazol administration on treatment efficacy for subarachnoid hemorrhage. We have searched PubMed, EMbase, Web of science, EBSCO, and Cochrane library databases through July 2020 for randomized controlled trials (RCTs) assessing the effect of cilostazol administration in patients with subarachnoid hemorrhage. This meta-analysis is performed using the random-effect model. Four RCTs involving 405 patients were included in the meta-analysis. Overall, compared with control group for subarachnoid hemorrhage, cilostazol intervention can significantly reduce symptomatic vasospasm (OR = 0.35; 95% CI = 0.21 to 0.60; P = 0.0001) and cerebral infarction (OR = 0.40; 95% CI = 0.22 to 0.73; P = 0.003), as well as improve no or mild angiographic vasospasm (OR = 2.01; 95% CI = 1.19 to 3.42; P = 0.01) and mRS score ≤ 2 (OR = 2.70; 95% CI = 1.09 to 6.71; P = 0.03), but revealed no obvious influence on severe angiographic vasospasm (OR = 0.53; 95% CI = 0.27 to 1.02; P = 0.06). There were no increase in adverse events (OR = 1.17; 95% CI = 0.54 to 2.52; P = 0.69), hemorrhagic events (OR = 0.62; 95% CI = 0.06 to 6.27; P = 0.69) and cardiac events (OR = 2.14; 95% CI = 0.44 to 10.27; P = 0.34) after the cilostazol intervention than control intervention. Cilostazol treatment may be effective to treat subarachnoid hemorrhage in the terms of symptomatic vasospasm, cerebral infarction, no or mild angiographic vasospasm and mRS score ≤ 2.


Multidisciplinary team approach for Merkel cell carcinoma: the European Institute of Oncology experience with focus on radiotherapy.
To review the therapeutic strategy in Merkel cell carcinoma (MCC) treated with radiotherapy (RT) discussed in a multidisciplinary tumour board. Clinical records of patients with a diagnosis of MCC and with an indication to undergo RT at the European Institute of Oncology between 2003 and 2018 were reviewed retrospectively. Twenty-six patients were included in the analysis (median age 65 years, range 42-87). Nineteen received adjuvant RT, 4 exclusive RT, and the remainder palliative RT. Intensity-modulated RT was used in 13 cases, a 3D conformal technique in 11 cases, and stereotactic RT in 2 cases. No major toxicities were recorded. The median relapse-free survival (RFS) after adjuvant RT was 20.5 months, while for unknown primary MCC, it was 23 months. In the adjuvant setting, median polyomavirus-positive RFS was 21.5 months (range 1-49) and median polyomavirus-negative RFS was only 14 months (range 4-45). Overall, RFS of polyomavirus-positive and polyomavirus-negative patients was 10.5 and 8 months, respectively. After adjuvant RT, only 1 out of 10 patients had a recurrence in the RT field. At the time of data collection, 16 patients were alive with no evidence of disease, 1 patient was alive with advanced status of disease, 8 patients died of disease progression, and 1 patient died of other causes. The management of unknown primary and polyomavirus-positive cases, which had a better prognosis in our series, may benefit from a multidisciplinary approach, given the limited data available regarding optimal treatment.


Legionella in water samples: how can you interpret the results obtained by quantitative PCR?
Evaluation of the potential risk associated with Legionella has traditionally been determined from culture-based methods. Quantitative polymerase chain reaction (qPCR) is an alternative tool that offers rapid, sensitive and specific detection of Legionella in environmental water samples. In this study we compare the results obtained by conventional qPCR (iQ-Check™ Quanti Legionella spp.; Bio-Rad) and by culture method on artificial samples prepared in Page's saline by addiction of Legionella pneumophila serogroup 1 (ATCC 33152) and we analyse the selective quantification of viable Legionella cells by the qPCR-PMA method. The amount of Legionella DNA (GU) determined by qPCR was 28-fold higher than the load detected by culture (CFU). Applying the qPCR combined with PMA treatment we obtained a reduction of 98.5% of the qPCR signal from dead cells. We observed a dissimilarity in the ability of PMA to suppress the PCR signal in samples with different amounts of bacteria: the effective elimination of detection signals by PMA depended on the concentration of GU and increasing amounts of cells resulted in higher values of reduction. Using the results from this study we created an algorithm to facilitate the interpretation of viable cell level estimation with qPCR-PMA.


Protective activity of 30kDa phytoglycoprotein from glucose/glucose oxidase-induced cell death in primary cultured mouse thymocytes.
Dioscorea batatas Decne (DBD) has been traditionally used as herbal agent in folk medicine. DBD glycoprotein with a molecular weight of 30kDa consists of carbohydrate (83.75%) and protein (16.25%), and has a strong anti-oxidative activity. To understand the protection from thymocytes death, we evaluated the activity changes of pro-apoptotic factors [cytochrome c, caspase 3, poly(ADP-ribose) polymerase (PARP), AP-1, NF-κB and nitric oxide (NO)] by DBD glycoprotein from glucose/glucose oxidase (G/GO)-induced cell death in primary cultured mouse thymocytes. In the activity of the apoptotic related proteins [cytochrome c, caspase 3 and PARP], the results showed that DBD glycoprotein (200μg/ml) has an inhibitory effect on cytochrome c release into cytosol, caspase 3 activation and PARP cleavage in thymocytes. In the transcription factors (AP-1 and NF-κB) activity and NO production, the activities of NF-κB and NO production significantly decreased after DBD glycoprotein (200μg/ml) treatment for 4h in G/GO-induced thymocytes, compared with the control. Therefore, we speculate that DBD glycoprotein is one of the natural compounds for the protection of thymocytes that can produce cytokines.


Patterned membranes for improving hydrodynamic properties and mitigating membrane fouling in water treatment: A review.
Membrane technologies have been widely applied in water treatment over the past few decades. However, membrane fouling remains a hinderance for the widespread use of membrane processes because it decreases effluent quality and increases operating costs. To mitigate membrane fouling, researchers have been exploring effective anti-fouling strategies. Recently, patterned membranes are gaining attention as a novel non-chemical membrane modification for membrane fouling control. In this paper, we review the research on patterned membranes used in water treatment over the past 20 years. In general, patterned membranes show superior anti-fouling performances, which mainly results from two aspects: hydrodynamic effects and interaction effects. Due to the introduction of diversified topographies onto the membrane surface, patterned membranes yield dramatic improvements on hydrodynamic properties, e.g., shear stress, velocity field and local turbulence, restraining concentration polarization and foulants' deposition on the membrane surface. Besides, the membrane-foulant and foulant-foulant interactions play an important role in the mitigation of membrane fouling. Due to the existence of surface patterns, the hydrodynamic boundary layer is destroyed and the interaction force as well as the contact area between foulants and surface are decreased, which contributes to the fouling suppression. However, there are still some limitations in the research and application of patterned membranes. Future research is suggested to focus on the development of patterned membranes appropriate for different water treatment scenarios, the insights into the interaction forces affected by surface patterns, and the pilot-scale and long-term studies to verify the anti-fouling performances of patterned membranes in practical applications.


Sustaining aviation workforce after the pandemic: Evidence from Hong Kong aviation students toward skills, specialised training, and career prospects through a mixed-method approach.
The aviation industry is in a recession with the rapid and immense outbreak of COVID-19 under globalisation. The future young aviation professionals might suffer from a 'career shock'. This study analysed the post-pandemic career prospects for Hong Kong aviation students using mixed-method research considering specialised and licensed training. We conducted a survey (N = 101) and focus group interviews (N = 6) to investigate students' perceived impediments and potential support from the institutions. Matt-Whitney U test is used to compare the perceptual difference in the impediments, career prospects, skills required, and institutional supports between (non-)specialised training students, (non-)engineering-related students, and (non-)final-year students. The results demonstrated no significant difference between students with and without specialised training. While final-year students perceive themselves as lacking more in terms of non-technical skills than non-final-year students, students are interested in broadening their career options to include airline operations, aircraft engineering and maintenance via acquiring a variety of emerging knowledge and technical skills. Given most studies focus on the recovery pattern of the aviation industry, this study is original in considering Hong Kong aviation students' career impediments and prospects using a mixed-method approach to provide policy insights.


Risk-based caries prevention may be more effective in children.
Randomised control trial in six-year-old children. The control group received dental check-ups twice a year, including professional fluoride gel applications and fissure sealants. The increased professional fluoride application (IPFA) group has the same care as in the control group plus two additional fluoride gel application per year. The non-operative caries treatment and prevention (NOCTP) had individualised recall intervals following the Nexø protocol.(1) Data on time and resource use as well as data on effectiveness were collected for three years. The primary outcome measure was the incremental cost effectiveness ratio of methods of caries prevention. Other outcomes included societal and health perspective cost effectiveness of the caries prevention methods and overall effectiveness (number of prevented DMFS) of the methods. Two hundred and thirty children participated in the trial, with a 32% drop out in the NOCTP group, 20% in the IPFA group and 15% in the control group. The resources use and total costs in Euros over three years are shown in the table below. The NOCTP regimen was more effective and more costly than regular dental care. Based on the limited available amount of evidence regarding the willingness to pay for dental care, the benefits seem to outweigh the additional costs, implying that this is a cost-effective strategy. Increasing the number of professional fluoride applications resulted in a slight reduction of caries increment, but at higher costs than the NOCTP strategy. The results of this study confirm the findings in previous research. Therefore, implementing NOCTP on a larger scale should be considered.


General mutagenesis/gene expression procedure for the construction of variant immunoglobulin domains in Escherichia coli. Production of the Bence-Jones protein REIv via fusion to beta-lactamase.
A novel mutagenesis/gene expression and protein purification scheme was established for ready construction and purification of variant immunoglobulin domains in Escherichia coli. This procedure, which has been applied to the production of the VK domain of the Bence-Jones protein REI and structural variants of it, rests on the synthesis of chimeric proteins with beta-lactamase as the amino-terminal fusion partner. The beta-lactamase not only guides the fusion protein to the periplasmic space, but also allows affinity chromatography on phenylboronate-Sepharose as an efficient and general purification procedure, independent of hypervariable loop structure. The REIv protein was released from the purified fusion protein by site-specific proteolytic cleavage. After a second passage through the same affinity column, up to 2 mg of pure REIv was obtained starting from one liter of bacterial liquid culture. A scheme of oligonucleotide-directed mutagenesis was introduced for replacement of DNA stretches encoding hypervariable loops. It exploits a colony color genetic screen and can be applied to any DNA sequence replacement. Mutations can be constructed by simple co-transformation with single-stranded template DNA and mutagenic oligonucleotide.


Genome-wide methylation analyses identifies Non-coding RNA genes dysregulated in breast tumours that metastasise to the brain.
Brain metastases comprise 40% of all metastatic tumours and breast tumours are among the tumours that most commonly metastasise to the brain, the role that epigenetic gene dysregulation plays in this process is not well understood. We carried out 450 K methylation array analysis to investigate epigenetically dysregulated genes in breast to brain metastases (BBM) compared to normal breast tissues (BN) and primary breast tumours (BP). For this, we referenced 450 K methylation data for BBM tumours prepared in our laboratory with BN and BP from The Cancer Genome Atlas. Experimental validation on our initially identified genes, in an independent cohort of BP and in BBM and their originating primary breast tumours using Combined Bisulphite and Restriction Analysis (CoBRA) and Methylation Specific PCR identified three genes (RP11-713P17.4, MIR124-2, NUS1P3) that are hypermethylated and three genes (MIR3193, CTD-2023M8.1 and MTND6P4) that are hypomethylated in breast to brain metastases. In addition, methylation differences in candidate genes between BBM tumours and originating primary tumours shows dysregulation of DNA methylation occurs either at an early stage of tumour evolution (in the primary tumour) or at a later evolutionary stage (where the epigenetic change is only observed in the brain metastasis). Epigentic changes identified could also be found when analysing tumour free circulating DNA (tfcDNA) in patient's serum taken during BBM biopsies. Epigenetic dysregulation of RP11-713P17.4, MIR3193, MTND6P4 are early events suggesting a potential use for these genes as prognostic markers.


Up-to-date monitoring data of wastewater and stormwater quality in Germany.
A comprehensive dataset of pollutant concentrations in German urban wastewater systems is available from recently completed monitoring projects. It contains up to 1000 concentration values for each of 79 substances in wastewater treatment plant (WWTP) effluents from 49 sites, and up to 157 values for each of 95 substances in combined sewer overflows (CSOs) from 12 sites. WWTP influents and stormwater outfalls were sampled to a lesser extent. All sampling methods were harmonised and aimed at collecting event or multi-day composite samples over periods of ≥1 year. Among the substances analysed were biocides and pesticides, polycyclic aromatic hydrocarbons, perfluorinated alkyl substances, metals, pharmaceuticals, benzotriazoles, phenols, acesulfame, di-(2-ethylhexyl)phthalate, and hexabromocyclododecanes. Occurrence, concentration ranges, and removal rates of selected WWTPs are presented. CSOs can be confirmed as an important pathway of metals and PAH to receiving waters when compared to WWTPs on the basis of annual per capita loads. The derived volume-weighted site mean concentrations are qualified to be used as representative input data for estimation of average substance emissions in large areas, e.g. on river basin scale, if no site-specific data are available. As such, they will contribute to the development of strategies to reduce substance emissions, taking into account not only WWTPs but also stormwater-related discharges.


Therapeutic and kinetic properties of ceftazidime in animals.
The pharmacokinetic properties of ceftazidime were evaluated in laboratory animals. Peak serum concentrations following subcutaneous or intramuscular dosing of 25 mg/kg occurred 15-30 min after injection and ranged from 26 mg/l in mice to 63 mg/l in rabbits. Serum half-life values were 21 min in mice, 23 min in rats, 48 min in rabbits, 60 min in beagle dogs and 58 min in cynomolgus monkeys. Ceftazidime was not absorbed following oral dosing. Large amounts of unchanged ceftazidime were excreted in urine. Low biliary excretion, i.e. 1.2%, of subcutaneously administered ceftazidime was found in rats. This contrasted to high biliary excretion of cefmenoxime (20%), cefotiam (37.5%), moxalactam (40%) and cefoperazone (52%). The high intrinsic antibacterial activity of ceftazidime combined with good pharmacokinetics was reflected in excellent therapeutic effects in experimental infections. Ceftazidime was the most active of the newer beta-lactam antibiotics tested and only the aminoglycoside antibiotic gentamicin achieved the same level of activity. Ceftazidime, which is currently being assessed clinically, is a promising potential alternative to aminoglycoside antibiotics.


Large-scale validation of the prediction model risk of bias assessment Tool (PROBAST) using a short form: high risk of bias models show poorer discrimination.
To assess whether the Prediction model Risk Of Bias ASsessment Tool (PROBAST) and a shorter version of this tool can identify clinical prediction models (CPMs) that perform poorly at external validation. We evaluated risk of bias (ROB) on 102 CPMs from the Tufts CPM Registry, comparing PROBAST to a short form consisting of six PROBAST items anticipated to best identify high ROB. We then applied the short form to all CPMs in the Registry with at least 1 validation (n=556) and assessed the change in discrimination (dAUC) in external validation cohorts (n=1,147). PROBAST classified 98/102 CPMS as high ROB. The short form identified 96 of these 98 as high ROB (98% sensitivity), with perfect specificity. In the full CPM registry, 527 of 556 CPMs (95%) were classified as high ROB, 20 (3.6%) low ROB, and 9 (1.6%) unclear ROB. Only one model with unclear ROB was reclassified to high ROB after full PROBAST assessment of all low and unclear ROB models. Median change in discrimination was significantly smaller in low ROB models (dAUC -0.9%, IQR -6.2-4.2%) compared to high ROB models (dAUC -11.7%, IQR -33.3-2.6%; P<0.001). High ROB is pervasive among published CPMs. It is associated with poor discriminative performance at validation, supporting the application of PROBAST or a shorter version in CPM reviews.


Non-species-specific pollen transfer and double-reward production in euglossine-pollinated Vanilla.
Commonly attributed to orchids, the pollen movement in Vanilla has been associated with food deception and specific plant-pollinator relationships. This study investigated the role of flower rewards and pollinator specificity in the pollen transfer of a widely distributed member to the euglossinophilous Vanilla clade, V. pompona Schiede using data collected from Brazilian populations. These included investigations on morphology, light microscopy and histochemistry, and analysis of flowers scent using GC-MS. The pollinators and the mechanisms of pollination were recorded through focal observations. The yellow flowers of V. pompona are fragrant and offer nectar as reward. The major volatile compound of the V. pompona scent, carvone oxide, shows convergent evolution in Eulaema-pollinated Angiosperms. The pollination system of V. pompona is not species-specific, but its flowers are strongly adapted to pollination by large Eulaema males. Pollination mechanism is based in a combination of perfume collection and nectar seeking. The dogma of a species-specific pollination system based on food deception in Vanilla has been broken with the increase in studies on this Pantropical orchid genus. Here, least three bee species and dual reward-offering are involved in pollen transfer in V. pompona. Visitation frequency of bees collecting perfumes, used in courtship by male euglossines, is higher than in searching for food, as short-lived young euglossine males seem to be more interested in sex than food. A pollination system based on offering both nectar and perfumes as resources is described for the first time in orchids.


Three year longitudinal study for out-of-hospital cardiac arrest in Osaka Prefecture.
To analyze the longitudinal changes in the treatment of out-of-hospital cardiac arrests. These analyses have focused on the time interval from the receipt of call until defibrillation of patients with ventricular fibrillation. Population-based, prospective longitudinal study according to the Utstein style. Osaka Prefecture (population 8, 800, 000), served by 36 municipal fire and emergency departments. Consecutive, out-of-hospital cardiac arrests occurring between May 1998 and April 2001. Change in the interval to defibrillation, and one-year survival from cardiac arrest. Of the 15,211 cases of confirmed cardiac arrests during the three years, resuscitation was attempted in 14,609 subjects. Of the 2957 cases of cardiac origin and witnessed by bystanders, 90 cases (3.0%) were alive 1 year following the episode. In 383 cases of defibrillation, the interval from receipt of call to defibrillation was evaluated annually. This interval decreased significantly during the three year course (14.5, 13.0, and 11.5 min expressed by the median), suggesting that this project to report the data of out-of-hospital arrests was an effective campaign for EMT. However, the outcome did not improve significantly during this period (3.0%, 2.6%, and 3.6% alive 1 year in witnessed arrests with cardiac etiology). This may be because the third year median duration of 11.5 min, is still insufficient to indicate a significant improvement in the outcome. This project to report the data of out-of-hospital cardiac arrest might have contributed to the reduction of the interval for defibrillation, as a campaign for the EMTs; although the decrease in this interval was still insufficient to result in a significant increase in the number of cases who are alive one year later.


Effect of autonomic influences to induce triggered activity in muscular sleeves extending into the coronary sinus of the canine heart and its suppression by ranolazine.
Extrasystoles arising from the muscular sleeves associated with the pulmonary veins (PV), superior vena cava (SVC), and coronary sinus (CS) are known to precipitate atrial fibrillation (AF). The late sodium channel current (INa ) inhibitor ranolazine has been reported to exert antiarrhythmic effects in canine PV and SVC sleeves by suppressing late phase 3 early and delayed after depolarization (EAD and DAD)-induced triggered activity induced by parasympathetic and/or sympathetic stimulation. The current study was designed to extend our existing knowledge of the electrophysiological and pharmacologic properties of canine CS preparations and assess their response to inhibition of late INa following autonomic stimulation. Transmembrane action potentials were recorded from canine superfused CS using standard microelectrode techniques. Acetylcholine (ACh, 1 µM), isoproterenol (Iso, 1 µM), high calcium ([Ca2+ ]o = 5.4 mM), or a combination were used to induce EADs, DADs, and triggered activity. Action potentials (AP) recorded from the CS displayed short and long AP durations (APD), with and without phase 4 depolarization (n = 19). Iso induced DAD-mediated triggered activity. The combination of sympathetic and parasympathetic agonists resulted in late phase 3 EAD-induced triggered activity in all CS preparations. Ranolazine (5-10 µM) suppressed late phase 3 EAD- and DAD-induced triggered activity in 8 of 8 preparations. Subthreshold stimulation induced a prominent hyperpolarization that could be suppressed by atropine. Our results suggest the important role of parasympathetic innervation in the activity of the CS. Autonomic influences promote DAD- and late phase-3-EAD-mediated triggered activity in canine CS, thus generating extrasystolic activity capable of initiating atrial arrhythmias. Ranolazine effectively suppresses these triggers.


Suppression of Inflammasome Activation by IRF8 and IRF4 in cDCs Is Critical for T Cell Priming.
Inflammasome activation leads to pyroptotic cell death, thereby eliminating the replicative niche of virulent pathogens. Although inflammasome-associated cytokines IL-1β and IL-18 have an established role in T cell function, whether inflammasome activation in dendritic cells (DCs) is critical for T cell priming is not clear. Here, we find that conventional DCs (cDCs) suppress inflammasome activation to prevent pyroptotic cell death, thus preserving their ability to prime both CD4 and CD8 T cells. Transcription factors IRF8 and IRF4, in cDC1s and cDC2s, respectively, mediate suppression of inflammasome activation by limiting the expression of inflammasome-associated genes. Overexpression of IRF4 or IRF8 inhibits inflammasome activation in macrophages, while reduced expression of IRF8 leads to aberrant inflammasome activation in cDC1s and hampers their ability to prime CD8 T cells. Thus, activation of inflammasome in DCs is detrimental to adaptive immunity, and our results reveal that cDCs use IRF4 and IRF8 to suppress this response.


Enhancing the recombinant protein productivity of Yarrowia lipolytica using insitu fibrous bed bioreactor.
In this study, the ability of Yarrowia lipolytica to produce the recombinant lipase CalB from Candida antarctica, used as a model protein has been compared across different bioreactor processes using glycerol, a byproduct from the biodiesel industry as the main carbon source. Batch, pulsed fed-batch (PFB), and continuous fed-batch (CFB) strategies were first compared using classical stirred tank (STR) bioreactors in terms of biomass production, carbon source uptake, and lipase production. Additionally, an in situ fibrous bed bioreactor (isFBB) was developed using sugarcane bagasse as a cell immobilization support. The maximum lipase titer achieved using the isFBB culture mode was 38%, 33%, and 49% higher than those obtained using the batch, PFB, and CFB cultures, respectively. The lipase productivity in isFBB mode (142U/mL/h) was 1.4-fold higher than that obtained using batch free cell cultures. These results highlight that isFBB is an efficient technology for the production of recombinant enzymes.


Lithium inhibits the modulatory effects of morphine on susceptibility to pentylenetetrazole-induced clonic seizure in mice: involvement of a nitric oxide pathway.
Lithium has been reported to inhibit opioid-induced properties. The present study examined the effect of acute and chronic administration of lithium chloride (LiCl) on morphine's biphasic modulation of susceptibility to pentylenetetrazole (PTZ)-induced clonic seizure in mice. We also examined the possible involvement of nitric oxide (NO) pathway in lithium effect. Both acute (0.1 and 1 mg/kg) and chronic (same doses, 21 consecutive days) administration of LiCl completely inhibited the anticonvulsant and proconvulsant effects of morphine (at doses 1 and 30 mg/kg, respectively). A very low and per se noneffective dose of LiCl (0.05 mg/kg) significantly inhibited both phases of morphine effect when administered concomitant with a noneffective low dose of naloxone (0.1 mg/kg). The NO synthase inhibitor N(G)-nitro-l-arginine methyl ester (L-NAME) at a per se noneffective dose of 0.3 mg/kg potentiated the inhibitory effects of low doses of LiCl (0.01 and 0.05 mg/kg) on both phases of morphine effect. l-arginine, a NO synthase substrate, at a per se noneffective dose of 30 mg/kg reversed the inhibitory effects of lithium (1 mg/kg). Lithium is capable of antagonizing both modulatory effects of morphine on seizure susceptibility even at relatively low doses. These inhibitory effects of lithium may also involve NO synthesis.


Green catalytic process for in situ oxidation of Arsenic(III) in concentrated streams using activated carbon and oxygen gas.
Arsenic(III) oxidation is a critical pre-treatment step for overall arsenic immobilization in concentrated industrial arsenic streams. Activated carbon (AC) catalysis is a green, economical and efficient method to oxidize As(III) from waters with high arsenic concentration prior to its removal through precipitation or adsorption. This research investigates AC-catalyzed oxidation process for oxidizing aqueous solutions of As(III) and proposed the possible reaction pathway. Batch tests were performed and efficient oxidation of 2.0 g/L acidic As(III) solution have been induced on AC surfaces in the presence of oxygen. The in-situ formation of reactive oxygen species on carbon surfaces and arsenic adsorption onto AC play important roles in As(III) oxidation. The kinetics of adsorption and catalyzed oxidation has been studied and the samples were characterized using ICP-OES, Zeta potential, TEM coupled with EDX and XPS techniques. A systematic reaction pathway was proposed, and reusability of AC has confirmed the economic viability of the proposed green process. This study offers a promising and facile solution for As(III) oxidation from waste water, mining and metal industrial waste streams under ambient conditions for arsenic immobilization.


Randomised controlled trial of the Lidcombe programme of early stuttering intervention.
To evaluate the efficacy of the Lidcombe programme of early stuttering intervention by comparison to a control group. A pragmatic, open plan, parallel group, randomised controlled trial with blinded outcome assessment. Two public speech clinics in New Zealand. Stuttering preschool children who presented to the speech clinics for treatment. Inclusion criteria were age 3-6 years and frequency of stuttering of at least 2% syllables stuttered. Exclusion criteria were onset of stuttering during the six months before recruitment and treatment for stuttering during the previous 12 months. 54 participants were randomised: 29 to the Lidcombe programme arm and 25 to the control arm. 12 of the participants were girls. Lidcombe programme of early stuttering intervention. Frequency of stuttering was measured as the proportion of syllables stuttered, from audiotaped recordings of participants' conversational speech outside the clinic. Parents in both arms of the trial collected speech samples in three different speaking situations before randomisation and at three, six, and nine months after randomisation. Analysis showed a highly significant difference (P = 0.003) at nine months after randomisation. The mean proportion of syllables stuttered at nine months after randomisation was 1.5% (SD 1.4) for the treatment arm and 3.9% (SD 3.5) for the control arm, giving an effect size of 2.3% of syllables stuttered (95% confidence interval 0.8 to 3.9). This effect size was more than double the minimum clinically worthwhile difference specified in the trial protocol. The results provide evidence from a randomised controlled trial to support early intervention for stuttering. The Lidcombe programme is an efficacious treatment for stuttering in children of preschool age.


A photograph of the researcher on the invitation letter did not affect the participation rate of a postal survey: a randomized study within a trial (SWAT).
Participant recruitment is one of the main challenges in research. It is suggested that including researcher photographs might increase participation rates, but empirical evidence is lacking. This study within a trial (SWAT) aims to assess whether invitation letters including researcher photographs increase the participation rate in the context of a survey on medical second opinions. Through 25 local register offices in Berlin and Brandenburg (Germany), we identified a random sample of 9990 persons. We randomly assigned our sample to the intervention group (IG) receiving an invitation letter with researcher photographs and control group (CG) receiving an invitation letter without photographs in a 1:1 ratio. Our primary outcome was the participation rate. Furthermore, we compared participants to non-participants' characteristics. Of 9990 invitations, 9797 could be delivered (IG: 4890, CG: 4907). Of these, 1349 (13.8%) participated. There were 682/4890 (13.9%) participants in the IG and 662/4907 (13.5%) in the CG with an odds ratio of 1.030 (95% confidence interval: 0.918-1.156). Additional analyses on non-participant characteristics did not show any differences. We could not find any difference in the participation rates. Our study does not confirm the results of previous studies. The length of our questionnaire may have affected our results. Queens University Belfast - SWAT Store, SWAT 104.


Dynamic items delivery network: prediction and clustering.
Items delivery companies generally use a model to minimize delivery costs. From a mathematical perspective, the model is an objective function that involves constraints. Meanwhile, from a practical point of view, these constraints include aspects that affect item delivery, for example, delivery zones, number of delivery vehicles, vehicle capacity, trip routes, etc. However, the models built so far have not paid attention to changes in road density. This aspect can result in a nonoptimal delivery model, which results in not a minimum delivery cost. For this reason, this paper discusses how to divide zones using the clustering method and predict changes in the shipping zone of a dynamic network using predictive distribution. So, the model can work optimally if the delivery zones and delivery strategies are suitable.


Salivary fluoride concentration and retention after rinsing with 0.05 and 0.2% sodium fluoride (NaF) compared with a new high F rinse containing 0.32% NaF.
To compare salivary fluoride (F) concentration and F retention after rinsing with a new 0.32% sodium fluoride (NaF) rinse and conventional 0.05 and 0.2% NaF rinses. Seventeen subjects (aged 22-26 years), with normal salivary secretion rates, participated in a double blind, cross-over study. In three separate sessions with a minimum washout period of 48 h, they rinsed for 1 min with 10 ml of 0.05, 0.2 or 0.32% NaF mouthrinse. Unstimulated whole saliva was collected before (baseline: 0 min) and after 1, 3, 5, 10, 20, 30, 45 and 60 min. The F concentration was plotted against time, and the area under the curve (AUC) calculated. Salivary F concentration and F retention for the three mouthrinses were compared by a randomized block test, followed by Tukey's test and a paired 2-tailed test. There was a clear dose-response for AUC 3-60 min; 0.32% > 0.2% > 0.05% (p < .05). The mean F retention was 0.25 mg for 0.05% NaF, 0.86 mg F for 0.2% Na and 1.31 mg F for 0.32% NaF, (p < .05). The higher salivary F concentration over time and the higher F retention after rinsing with an 0.32% NaF solution suggests a potential application in prevention of caries and dental erosion.


Association of toll-like receptor polymorphisms with acquisition of HIV infection and clinical findings: A protocol for systematic review and meta-analysis.
To find the relationship between toll-like receptor (TLR) gene variants and human immunodeficiency virus (HIV) infection and clinical findings, which could inform clinical decisions and vaccination strategies. Four databases were searched for articles that were published on or before Jul.1, 2020. Review Manager 5.3 software was applied to perform meta-analysis to explore. A total of 10 studies involving 20 genes, 3697 cases, and 6498 controls were included in this systematic review. TLR2 -196 to -174 Ins/Del (odds ratio [OR] = 1.562; P = .002), TLR4 rs4986790 (OR = 2.05; P = .002), TLR3 rs3775291 (OR = 0.25; P = .03), TLR7 rs179008 (P = .002), TLR7 rs2074109 (OR = 0.27, P = .019) were found associated with HIV infection. TLR2 -196 to -174, TLR4 rs4986790, TLR7 rs179008, TLR8 rs3764880, TLR9 rs352140 were found associated with clinical findings of HIV infection. We identified 5 case-control studies in meta-analysis, involving 695 cases and 729 controls on TLR7 rs179008 polymorphism, totaling 652 cases and 614 controls on TLR9 rs352140 polymorphism. In meta-analysis, we employed various genetic models. The T allele of TLR7 rs179008 was conferred the risk of HIV infection (T vs A: OR = 1.25, PA = .02). An increased risk of HIV infection was found for individuals with the TLR9 rs352140 GG genotype (GG vs AA: OR = 1.50, PA = .04). The systematic review indicated that TLR7 rs179008 T allele provides risk effects for HIV infection. TLR9 rs352140 GG genotype may associate with HIV infection.


Effects of multiple climate change stressors on gene expression in blue rockfish (Sebastes mystinus).
Global climate change is predicted to increase the co-occurrence of high pCO2 and hypoxia in coastal upwelling zones worldwide. Yet, few studies have examined the effects of these stressors on economically and ecologically important fishes. Here, we investigated short-term responses of juvenile blue rockfish (Sebastes mystinus) to independent and combined high pCO2 and hypoxia at the molecular level, using changes in gene expression and metabolic enzymatic activity to investigate potential shifts in energy metabolism. Fish were experimentally exposed to conditions associated with intensified upwelling under climate change: high pCO2 (1200 μatm, pH~7.6), hypoxia (4.0 mg O2/L), and a combined high pCO2/hypoxia treatment for 12 h, 24 h, or two weeks. Muscle transcriptome profiles varied significantly among the three treatments, with limited overlap among genes responsive to the single and combined stressors. Under elevated pCO2, blue rockfish increased expression of genes encoding proteins involved in the electron transport chain and muscle contraction. Under hypoxia, blue rockfish up-regulated genes involved in oxygen and ion transport and down-regulated transcriptional machinery. Under combined stressors, blue rockfish induced a unique set of ionoregulatory and hypoxia-responsive genes not expressed under the single stressors. Thus, high pCO2 and hypoxia exposure appears to induce a non-additive transcriptomic response that cannot be predicted from single stressor exposures alone, further highlighting the need for multiple stressor studies at the molecular level. Overall, lack of a shift towards anaerobic metabolism or induction of a cellular stress response under multiple stressors suggests that blue rockfish may be relatively resistant to intensified upwelling conditions in the short term.


High selectivity and adsorption proficiency of surfactant-coated selenium nanoparticles for dye removal application.
The rate of environmental pollution augmenting at an alarming rate due to the continuous disposal of toxic dyes directly into the environment and water streams. The direct contact of dyes with water resources directly affects the living beings. The identification of superior methods for the treatment of water pollution caused due to effluent dyes needs higher consideration among researchers for the well-being of living flora and fauna. The available methods for controlling the decontamination of water through toxic dyes have various drawbacks. So, it is highly significant to develop such materials which can easily adsorb the dyes without causing any toxic effect on the environment and living beings. While keeping all the facts in mind, the current work highlights the comparative enhancement in adsorption capacity and selectivity of Brij-58-coated selenium nanoparticles (Brij-58@Se NPs) towards the removal of bromophenol blue (BB) dye from series of chosen dyes in aqueous media. The fabricated Se NPs were methodically characterized and the adsorption behaviour displayed fast adsorption efficiency (98% within 6 min) for BB dye out of series of chosen dyes. The optimization studies were carried out to verify the influence of working variables such as pH (2.0-12.0), response time (1-10 min), dosage amount (0.1-80 mg/l) and concentration of BB dye (1-70 ppm). The adsorption process found to be best fitted for Freundlich adsorption isotherm and pseudo first-order kinetic model. The interference studies of different cationic, anionic species including dyes or metal ions suggested the higher efficiency of Brij-58@Se NPs for adsorptive removal of BB dye from aqueous media. The efficacy of the adsorbent was further tested in six different water resources and displayed 95% adsorption efficiency for BB dye in different wastewater samples. Therefore, Brij-58@Se NP is expected as a potential adsorbent for the adsorption of organic dyes from wastewater samples.


Detoxification of Aflatoxin B1 and Ochratoxin A Using Salvia farinacea and Azadirachta indica Water Extract and Application in Meat Products.
Seventy-five samples of selected meat products, including luncheon, beef burger, sausage, basterma, and kofta, were collected from Alexandria and New Borg El-Arab cities (Egypt). The samples were subjected to mycological examination as well as for detection of aflatoxin B1 (AFB1) and ochratoxin A (OTA) residues. Besides, the study evaluated the effect of aqueous leaf extracts from mealycup sage (Salvia farinacea) and neem (Azadirachta indica), individually and in combination, on the growth of human pathogens Aspergillus parasiticus and Aspergillus flavus producing AFB1, as well as Aspergillus ochraceus and Aspergillus niger which produce OTA. The obtained results revealed that sausage samples had the highest mould count with a mean value of 13.20×102/g, followed by basterma samples 12.05×102/g, then beef burger 7.39×102/g. In contrast, luncheon and kofta samples had the lowest count with a mean value of 5.51×102/g and 2.82×102/g. The findings revealed the antifungal potential of tested extracts. The total inhibition of A. parasitcus and A. niger growth was observed at 2 mg/mL of the combined extract. Salvia farinacea extract had the highest total phenolic content and total flavonoid content with a value of 174.1 and 52.6 mg g-1, respectively. Rutin was the major phenolic component in neem and combined extracts, accounting for 19123 and 8882 μg/g, respectively. Besides, the study investigated detoxification of AFB1 and OTA using combined extract in albino rats. The results confirmed the convenient and safe use of Salvia farinacea and Azadirachta indica extract and their combination as natural antifungal and antioxidant agents. The combined extract could be used as a natural preservative in food processing to control or prevent contamination.


Nanoconfinement of microvilli alters gene expression and boosts T cell activation.
T cells sense and respond to their local environment at the nanoscale by forming small actin-rich protrusions, called microvilli, which play critical roles in signaling and antigen recognition, particularly at the interface with the antigen presenting cells. However, the mechanism by which microvilli contribute to cell signaling and activation is largely unknown. Here, we present a tunable engineered system that promotes microvilli formation and T cell signaling via physical stimuli. We discovered that nanoporous surfaces favored microvilli formation and markedly altered gene expression in T cells and promoted their activation. Mechanistically, confinement of microvilli inside of nanopores leads to size-dependent sorting of membrane-anchored proteins, specifically segregating CD45 phosphatases and T cell receptors (TCR) from the tip of the protrusions when microvilli are confined in 200-nm pores but not in 400-nm pores. Consequently, formation of TCR nanoclustered hotspots within 200-nm pores allows sustained and augmented signaling that prompts T cell activation even in the absence of TCR agonists. The synergistic combination of mechanical and biochemical signals on porous surfaces presents a straightforward strategy to investigate the role of microvilli in T cell signaling as well as to boost T cell activation and expansion for application in the growing field of adoptive immunotherapy.


A model of electrical activity and cytosolic calcium dynamics in vascular endothelial cells in response to fluid shear stress.
A mathematical model is proposed to describe the intracellular Ca2+ (Cai) transient and electrical activity of vascular endothelial cells (VEC) elicited by fluid shear stress (tau). The intracellular Ca2+ store of the model VEC is comprised of a Cai-sensitive (sc) and an inositol (1,4,5)-trisphosphate (IP3)-sensitive compartment (dc). The dc [Ca2+] is refilled by the sc whose [Ca2+] is the same as extracellular [Ca2+]. IP3 produced by the tau-deformed mechanoreceptors discharges the dc Ca2+ into the cytosol. The increase of cytosolic [Ca2+] induces Ca2+ release (CICR) from the sc. The raised Cai activates a Cai-activated K+ current (IK,Ca) and inhibits IP3 production. The cell membrane potential is determined by IK,Ca, voltage-dependent Na+ and K+ currents. Steady tau > 0.1 dyne/cm2 elicits a Cai transient which reaches peak value at 19-54 sec. The peak Cai varies sigmoidally with Log10(tau) with a maximal peak Cai of 150 nM at tau = 4 dynes/cm2. Step increases of tau fail to elicit a Ca2+ response in cells previously stimulated by a lower shear. The Ca2+ response gradually decreases with repetitive tau stimuli. Pulsatile shear elicits two to three times higher Cai and hyperpolarizes the cell more than steady shear of the same magnitude. The simulated Ca2+ responses to tau are quantitatively and qualitatively similar to those observed in cultured VEC. The model provides a possible explanation of why the vasodilating stimulus is greater for pulsatile flow than for nonpulsatile flow.


Patterns of occurrence of second primary non-mammary malignancies in breast cancer patients: results from 1382 consecutive autopsies.
An autopsy series on the patterns of occurrence of second primary non-mammary malignancies (SPNM) in breast cancer patients is presented. SPNM occurred in 11.4% of breast cancer patients at a mean interval of 83.9 months. Seventy-five per cent of them occurred by the first decade following breast cancer. The most common system of SPNM occurrence was the female genital system, followed by the gastrointestinal system. The single organs most commonly involved were the colon and rectum, ovary and uterine cervix. There was no evident association between administration of radiotherapy or chemotherapy for the breast cancer and the risk for SPNM development except in the case of post-radiation sarcomas at or near the site of post-mastectomy radiotherapy. Death was caused by the breast cancer in 28.7% of patients and by the SPNM in 53.5%. In 10.6% of the cases the SPNM was clinically interpreted as metastatic breast cancer until autopsy.


Genetic Parameters of Bovine Milk Fatty Acid Profile, Yield, Composition, Total and Differential Somatic Cell Count.
The growing interest of consumers for milk and dairy products of high nutritional value has pushed researchers to evaluate the feasibility of including fatty acids (FA) in selection programs to modify milk fat profile and improve its nutritional quality. Therefore, the aim of this study was to estimate genetic parameters of FA profile predicted by mid-infrared spectroscopy, milk yield, composition, and total and differential somatic cell count. Edited data included 35,331 test-day records of 25,407 Italian Holstein cows from 652 herds. Variance components and heritability were estimated using single-trait repeatability animal models, whereas bivariate repeatability animal models were used to estimate genetic and phenotypic correlations between traits, including the fixed effects of stage of lactation, parity, and herd-test-date, and the random effects of additive genetic animal, cow permanent environment and the residual. Heritabilities and genetic correlations obtained in the present study reflected both the origins of FA (extracted from the blood or synthesized de novo by the mammary gland) and their grouping according to saturation or chain length. In addition, correlations among FA groups were in line with correlation among individual FA. Moderate negative genetic correlations between FA and milk yield and moderate to strong positive correlations with fat, protein, and casein percentages suggest that actual selection programs are currently affecting all FA groups, not only the desired ones (e.g., polyunsaturated FA). The absence of association with differential somatic cell count and the weak association with somatic cell score indicate that selection on FA profile would not affect selection on resistance to mastitis and vice versa. In conclusion, our findings suggest that genetic selection on FA content is feasible, as FA are variable and moderately heritable. Nevertheless, in the light of correlations with other milk traits estimated in this study, a clear breeding goal should first be established.