Malaria pharmacovigilance in Africa: lessons from a pilot project in Mpumalanga Province, South Africa.
Prior to the introduction of artemisinin-based combination antimalarial therapy in Mpumalanga province, South Africa, a pharmacovigilance strategy was developed to pilot locally relevant surveillance methods for detecting serious adverse drug reactions (ADRs) and signals related to artesunate plus sulfadoxine/pyrimethamine. From 1 March 2002 to 30 June 2004, five methods for detecting ADRs in patients receiving antimalarials were piloted in the rural communities of Mpumalanga province in South Africa: (i) home follow-up of patients by malaria control staff; (ii) enhanced spontaneous reporting of suspected ADRs by health professionals at clinics and hospitals; (iii) active hospital surveillance for malaria-related admissions and patients recently treated for malaria; (iv) a confidential enquiry into malaria-related deaths; and (v) adverse events monitoring during two therapeutic efficacy studies conducted in 2002 and 2004. During the study period, the malaria control programme was notified of 4778 cases of malaria while sulfadoxine/pyrimethamine monotherapy was the recommended treatment and 7692 cases after the introduction of artesunate plus sulfadoxine/pyrimethamine in January 2003. Of 2393 home follow-up visits of reported cases of malaria, three fatal adverse events were identified where recent use of artesunate plus sulfadoxine/pyrimethamine treatment was reported. Two cases were attributed to poor response to treatment, while one case was considered possibly related to artesunate plus sulfadoxine/pyrimethamine treatment. Clinic and hospital surveillance reported six ADRs in association with sulfadoxine/pyrimethamine treatment, five being treatment failures and one being a non-serious rash. During active hospital surveillance, 38 inpatients exposed to sulfadoxine/pyrimethamine were identified, including one child who experienced pancytopenia following treatment with sulfadoxine/pyrimethamine 11 days before admission; this adverse effect was considered to be possibly due to sulfadoxine/pyrimethamine treatment. The confidential enquiry into malaria-related deaths identified three adverse events, including a death where the contribution of treatment could not be excluded. A therapeutic efficacy study of 95 patients followed over 42 days identified one case of repeated vomiting possibly associated with artesunate plus sulfadoxine/pyrimethamine. Multifaceted monitoring throughout the malaria patient journey is necessary in developing countries implementing new treatments to safeguard against missing serious complications associated with malaria treatment.


Circularly Polarized Phosphorescence of Benzils Achieved by Chiral Supramolecular Polymerization.
In current approaches for circularly polarized phosphorescent materials, the crystallization of chiral phosphors suffers from poor processability, while integrating them into an amorphous polymer matrix results in unsatisfactory chiroptical signals due to the absence of chirality communication. Here, we have developed an innovative strategy through chiral supramolecular polymerization of benzil phosphors facilitated by intermolecular hydrogen bonds. The inherent film-forming capabilities of non-covalent supramolecular polymers obviate the need for an external polymer matrix. The pronounced helical asymmetry of benzil phosphors resulting from chiral supramolecular polymerization leads to enhanced circularly polarized phosphorescence compared to their non-hydrogen-bonded counterparts. The circularly polarized phosphorescent signals can be further modulated by varying the location of stereogenic centers or introducing halogen bonding to benzils. Incorporation of platinum(II) phosphor into the benzil supramolecular polymers induces both chirality and triplet-to-triplet energy transfer, leading to a change in circularly polarized phosphorescent color from yellow to red. In summary, chiral supramolecular polymerization of phosphors represents a novel and effective approach to circularly polarized phosphorescent materials.


Stress-related alterations of acyl and desacyl ghrelin circulating levels: mechanisms and functional implications.
Ghrelin is the only known peripherally produced and centrally acting peptide hormone that stimulates food intake and digestive functions. Ghrelin circulates as acylated and desacylated forms and recently the acylating enzyme, ghrelin-O-acyltransferase (GOAT) and the de-acylating enzyme, thioesterase 1/lysophospholipase 1 have been identified adding new layers of complexity to the regulation of ghrelin. Stress is known to alter gastrointestinal motility and food intake and was recently shown to modify circulating ghrelin and GOAT levels with differential responses related to the type of stressors including a reduction induced by physical stressors (abdominal surgery and immunological/endotoxin injection, exercise) and elevation by metabolic (cold exposure, acute fasting and caloric restriction) and psychological stressors. However, the pathways underlying the alterations of ghrelin under these various stress conditions are still largely to be defined and may relate to stress-associated autonomic changes. There is evidence that alterations of circulating ghrelin may contribute to the neuroendocrine and behavioral responses along with sustaining the energetic requirement needed upon repeated exposure to stressors. A better understanding of these mechanisms will allow targeting components of ghrelin signaling that may improve food intake and gastric motility alterations induced by stress.


Low genetic differentiation in a sedentary bird: house sparrow population genetics in a contiguous landscape.
The house sparrow Passer domesticus has been declining in abundance in many localities, including Finland. We studied the genetic diversity and differentiation of the house sparrow populations across Finland in the 1980s, at the onset of the species' decline in abundance. We genotyped 472 adult males (the less dispersive sex) from 13 locations in Finland (covering a range of 400 × 800 km) and one in Sweden (Stockholm) for 13 polymorphic microsatellite markers. Our analysis of Finnish ringing records showed that natal dispersal distances are limited (90% <16 km), which confirmed earlier finding from other countries. The Finnish populations were panmictic, and genetically very homogeneous and the limited dispersal was sufficiently large to maintain their connectivity. However, all Finnish populations differed significantly from the Stockholm population, even though direct geographical distance to it was often smaller than among Finnish populations. Hence, the open sea between Finland and Sweden appears to form a dispersal barrier for this species, whereas dispersal is much less constrained across the Finnish mainland (which lacks geographical barriers). Our findings provide a benchmark for conservation biologists and emphasize the influence of landscape structure on gene flow.


Relative and absolute stability in perceived parenting behaviour: a longitudinal study with children and adolescents.
Patterns of relative and absolute stability in parental behaviour with children and adolescents are reported. The sample comprised 523 youth (58.7% girls). Data were collected at three time periods: T1 (M age = 11.1 yr.), T2 (M age = 12.2 yr.), and T3 (M age = 13.2 yr.), each separated by one year. According to children's reports, relative consistency was moderate in both mothers and fathers, particularly as regards communication and strict control. In contrast, as children got older, parental rearing practices related to strict control and hostility decreased. There was a similarity between fathers and mothers in terms of relative and absolute stability. Relative stability was affected by the child's sex, the parenting variable, and the time period; however, the patterns of absolute stability reveal no differences by sex.


Hollow-Fiber Membrane Contactor for Biogas Recovery from Real Anaerobic Membrane Bioreactor Permeate.
This study demonstrates the application of hollow-fiber membrane contactors (HFMCs) for the recovery of biogas from the ultrafiltration permeate of an anaerobic membrane bioreactor (AnMBR) and synthetic effluents of pure and mixed CH4 and CO2. The developed membrane degassing setup was coupled with a pilot-scale AnMBR fed with synthetic domestic effluent working at 25 °C. The membrane degassing unit was able to recover 93% of the total dissolved CH4 and 83% of the dissolved CO2 in the first two hours of permeate recirculation. The initial recovery rates were very high (0.21 mg CH4 L-1 min-1 and 8.43 mg CO2 L-1 min-1) and the membrane was able to achieve a degassing efficiency of 95.7% for CH4 and 76.2% for CO2, at a gas to liquid ratio of 1. A higher mass transfer coefficient of CH4 was found in all experimental and theoretical evaluations compared to CO2. This could also be confirmed from the higher transmembrane mass transport resistance to CO2 rather than CH4 found in this work. A strong dependency of the selective gas transport on the gas and liquid side hydrodynamics was observed. An increase in the liquid flow rate and gas flow rate favored CH4 transport and CO2 transport, respectively, over each component. The results confirmed the effectiveness of the collective AnMBR and membrane degassing setup for biogas recovery. Still, additional work is required to improve the membrane contactor's performance for biogas recovery during long-term operation.


Relations between on-off phenomena and cognitive functions in Parkinson disease.
10 patients with Parkinson disease on long term levodopa therapy and with fluctuations in motor performance unrelated to drug administration (on-off phenomena) were assessed on the following neuropsychological tests during the on and off phases: tests of attention (Toulouse-Pieron), memory (Digit Span, Rey forms 1 and 2), psychomotor capacity (maze test, single and multiple choice reaction times) and mood (Maudley Adjective Check List). The extrapyramidal symptoms were assessed on the Webster Rating Scale. We found no significant differences in attention, cognitive performance or mood between the on and off phases despite large fluctuations in motor performance.


A nomogram for predicting cancer-specific survival in patients with osteosarcoma as secondary malignancy.
The prognostic factors for survival among patients with secondary osteosarcoma remain unclear. The aim of this study was to develop a practical nomogram for predicting cancer-specific survival (CSS) in patients with osteosarcoma as a secondary malignancy. The surveillance, epidemiology, and end results database was used for the identification of osteosarcoma cases. The total sample comprised 5860 cases of primary osteosarcoma and 268 cases of secondary osteosarcoma during the period from 1973 to 2015. The CSS and overall survival (OS) of primary and secondary osteosarcomas were analyzed. The predictors of CSS for secondary osteosarcoma were identified and integrated to build a nomogram. Validation of the nomogram was performed using concordance index (C-index) and calibration plots. The results indicated that patients with secondary osteosarcoma had poorer CSS and OS than patients with primary osteosarcoma. The nomogram model exhibited high discriminative accuracy in the training cohort (C-index = 0.826), which was confirmed in the internal validation cohort (C-index = 0.791). In addition, the calibration plots confirmed good concordance for prediction of CSS at 3, 5, and 10 years. In conclusion, we developed a practical nomogram that provided individual predictions of CSS for patients with secondary osteosarcoma. This nomogram may help clinicians with prognostic evaluations and with the development of individualized therapies for this aggressive disease.


[The immune status characteristics of pregnant women with iron-deficiency anemia after combined treatment using reflex acupuncture therapy].
Results are submitted of clinical and immunological investigation conducted in 30 pregnant women whose therapeutic programme incorporated acupuncture procedures apart from a complex of conventional antianemic measures. There have been examined pregnant women with varying degree anemia over different time periods of their pregnancy course. Antianemic treatment using acupuncture procedures in pregnant women with iron deficiency anemia was found to significantly activate the state of both cell-mediated and humoral immunity, mobilizing defensive and adaptive bodily reactions, being an efficient option designed to preserve the pregnant women's immunologic tolerance in the system mother-fetus.


Studies on the minimum reproducible unit of staphylococcal L-forms.
The minimum size of a reproducible unit of staphylococcal L-forms was determined by filtration and electron microscopic methods. Ultrathin sections of an induced strain of Staphylococcal L-forms (STA-EMT-1) in liquid medium revealed several types of structures, all of which were bound by a single membrane and most of which possessed ribosome-like granules. Many of the small granules were less than 0.3 micron and were attached to the membrane of the large bodies. Using a serial filtration method, it was observed that viable L-forms were still detected in 0.22 micron filtrate, but the viable cell count of L-forms decreased in number with the decrease in pore size of membrane filters. A fractionation technique, using L-forms filtered through a membrane filter with a 0.45 micron pore size, revealed that there were three classes of small bodies but only the first class with ribosome-like granules over approximately 0.2 micron in diameter seems to be able to reproduce.


'Help, educate, encourage?': Geographical variations in the provision and utilisation of diabetes education in New Zealand.
In New Zealand, as elsewhere, it is argued that a diabetes epidemic is underway. With careful management from individuals and professionals and appropriate levels of education, it is possible to prevent many complications of diabetes. The overall objective of the paper is to evaluate the role and impact of Diabetes New Zealand (DNZ), the key voluntary sector provider of diabetes education and support services, with respect to four criteria: (i) the extent to which DNZ is reaching groups most at risk of diabetes; (ii) the degree to which it has encouraged levels of member involvement; (iii) whether voluntary group provision of education is that most preferred by members; and (iv) the extent to which members see the voluntary sector model as being effective in combating the growth of diabetes. A survey of members of six of the 41 affiliated societies of DNZ suggests that such organisations, although having a high proportion of older members, have generally failed to target more deprived groups. While the societies generally score more positively in encouraging member involvement and being perceived as effective by their members, they do not always utilise the preferred form of educational provision. However, there are significant contextual variations by urban-rural location and according to the organisational structure of the societies. Rural societies and those with decentralised organisational structures generally score highest on the above criteria. The results pose a problem for DNZ which, like many other voluntary sector organisations, is facing pressures of increased corporatisation and centralisation. We see this as an important challenge that DNZ needs to address if New Zealand is going to better cope with the emerging diabetes epidemic.


Discordance Between Oncology Clinician-Perceived and Radiologist-Intended Meaning of the Postradiotherapy Positron Emission Tomography/Computed Tomography Freeform Report for Head and Neck Cancer.
Assessment of response after radiotherapy (RT) using 18F-fluorodeoxyglucose positron emission tomography (PET) with computed tomography (CT) is routine in managing head and neck squamous cell carcinoma (HNSCC). Freeform reporting may contribute to a clinician's misunderstanding of the nuclear medicine (NM) physician's image interpretation, with important clinical implications. To assess clinician-perceived freeform report meaning and discordance with NM interpretation using the modified Deauville score (MDS). In this retrospective cohort study that was conducted at an academic referral center and National Cancer Institute-designated Comprehensive Cancer Center and included patients with HNSCC treated with RT between January 2014 and December 2019 with a posttreatment PET/CT and 1 year or longer of follow-up, 4 masked clinicians independently reviewed freeform PET/CT reports and assigned perceived MDS responses. Interrater reliability was determined. Clinician consensus-perceived MDS was then compared with the criterion standard NM MDS response derived from image review. Data analysis was conducted between December 2021 and February 2022. Patients were treated with RT in either the definitive or adjuvant setting, with or without concurrent chemotherapy. They then underwent posttreatment PET/CT response assessment. Clinician-perceived (based on the freeform PET/CT report) and NM-defined response categories were assigned according to MDS. Clinical outcomes included locoregional control, progression-free survival, and overall survival. A total of 171 patients were included (45 women [26.3%]; median [IQR] age, 61 [54-65] years), with 149 (87%) with stage III to IV disease. Of these patients, 52 (30%) received postoperative RT and 153 (89%) received concurrent chemotherapy. Interrater reliability was moderate (κ = 0.68) among oncology clinicians and minimal (κ = 0.36) between clinician consensus and NM. Exact agreement between clinician consensus and the NM was 64%. The NM-rated MDS was significantly associated with locoregional control, progression-free survival, and overall survival. The results of this cohort study suggest that considerable variation in perceived meaning exists among oncology clinicians reading freeform HNSCC post-RT PET/CT reports, with only minimal agreement between MDS derived from clinician perception and NM image interpretation. The NM use of a standardized reporting system, such as MDS, may improve clinician-NM communication and increase the value of HNSCC post-RT PET/CT reports.


Use of surgery in patients with native valve infective endocarditis: results from the International Collaboration on Endocarditis Merged Database.
Early surgery has been shown to be beneficial for patients with infective endocarditis (IE), yet surgery is not used in most patients. Evidence of the uncertainty around the use of surgery can be found in the wide variations in the use of cardiac surgery in IE with few precise indications for cardiac surgery yet defined. The aim of the study was to characterize patients with native valve IE relative to surgery and to determine if patients who benefit from an early surgical intervention can be identified. The International Collaboration on Endocarditis Merged Database was used to quantify the differences between patients with IE receiving medical and surgical intervention in 1516 patients with definite native valve IE. Propensity models were built to identify a group of patients that benefit from early surgery. Patients in the early surgical group were more likely to be male, younger, and with less comorbidities compared with the early medical group (P < .001 for all) and were less likely to have infection with Staphylococcus aureus or viridans group streptococci (P < .05 for all). Intracardiac abscess and heart failure were much more common in the surgical group (P < .001 for all). In an unadjusted comparison, there was no statistically significant survival advantage in the surgical group. However, in the propensity analysis, in the subgroup of patients with the most indications for surgery, there was a significant decrease in mortality associated with early surgery (11.2% vs 38.0%, P < .001). The benefits of surgery are not seen uniformly in all patients with native valve IE, but are most realized in a targeted population. This observation requires confirmation in other populations of patients with definite IE.


Clinical features of thyroid cancer in paediatric age. Experience of a tertiary centre in the 2000-2020 period.
To describe the clinical features of a paediatric cohort affected by differentiated thyroid cancer (DTC) followed in a tertiary Department of Paediatric Endocrinology. Clinical data of 41 patients affected by DTC in the 2000-2020 period were reviewed. The main risk factor was autoimmune thyroiditis (39%). Cytological categories were TIR3b in 39%, TIR4 in 9.8%, TIR5 in 51.2%. After total thyroidectomy, radioiodine treatment was performed in 38 subjects (92.7%). ATA low-risk category was assigned in 11 (30.5%), intermediate-risk category in 15 (41.7%), and high-risk category in 10 patients (27.8%). Age at diagnosis was 15.1 ± 0.92 years in low-risk category, 14.7 ± 0.59 in intermediate-risk category, 11.7 ± 0.89 years in high-risk category (p = 0.01). TIR3b was manly observed in low-risk class (63.6%), while TIR5 was mainly reported in intermediate and high-risk class (60 and 80% respectively) (p = 0.04). Post-surgery stimulated thyroglobulin was increased in high-risk class (407.8 ± 307.1 ng/ml) [p = 0.04]. Tumour size was larger in high-risk category (42.6 ± 2.6 mm), than in low and intermediate-risk categories (19.4 ± 3.5 mm and 28.5 ± 3.9 mm, respectively) (p = 0.008). Patients in intermediate and high-risk categories displayed more tumour multifocality (60 and 90% respectively) (p < 0.005). Disease relapse was mainly observed in high risk category (40%, p = 0.04). DTC in childhood is more aggressive than in adults, but the overall survival rate is excellent. The therapeutic approach is still heterogeneous, especially in low-risk category. Further studies are needed to standardise management and reduce disease persistence in childhood.


Effects of manganese (II) on Bacillus licheniformis ATCC 9945A physiology and gamma-poly(glutamic acid) formation.
Bacillus licheniformis ATCC 9945A was cultivated in shake flasks using citrate (12 gl-1), glutamate (20 gl-1) and glycerol (80 gl-1) as carbon sources for cell growth and gamma-poly(glutamic acid) (gamma-PGA) production. The effect of the MnSO4 concentration in the medium over a range from 0.0 to 615 microns was studied. The number of viable cells increased for all concentrations of MnSO4 from approximately 10(5) to 10(9) colony-forming units (cfu) ml-1 by the early stationary phase (24 h). However, after 50 h, the cell viability decreased rapidly for relatively lower MnSO4 concentrations (0.615 and 0 microns). The utilization of carbon sources by B. licheniformis was greater for cultures containing 33.8 and 615 microns MnSO4 relative to cultures with no added MnSO4. For example, cultures with 615 microns MnSO4 utilized 37, 54 and 93% and cultures with no added MnSO4 utilized 19, 10 and 17% of glutamate, glycerol and citrate, respectively. The gamma-PGA volumetric yield increased from approximately 5 to 17 gl-1 for corresponding increases in MnSO4 concentration from 0 to 33.8 microns and then decreased at higher MnSO4 concentrations. The stereochemical content of gamma-PGA was found to vary inversely with MnSO4 concentration, and ranged from 59 to 10% L-glutamate units for MnSO4 concentrations of 0 and 615 microns, respectively. For all of the MnSO4 concentrations investigated, the gamma-PGA molecular weights decreased rapidly as the gamma-PGA volumetric yield simultaneously increased for cultivation times from 24 to approximately 50 h. Mw and Mn values after approximately 50 h cultivation times, determined by gel permeation chromatography (GPC), were 1.3 to 1.6 and 0.5 to 0.8 million g mol-1, respectively. A complex gamma-PGA molecular weight distribution that appeared bimodal by GPC analysis due to the presence of a low-molecular-weight product fraction was observed in cultures containing 33.8 and 61.5 microns MnSO4 at extended cultivation times. A high-molecular-weight fraction and the unfractionated gamma-PGA sample from the 33.8 microns MnSO4 culture contained 13 +/- 4 and 30 +/- 1% L-repeat units, respectively. A relationship between the product molecular weight and its stereochemical composition was thus established.


Identification of Neisseria gonorrhoeae with the ORTHOProbe DNA probe test.
We evaluated and compared the ORTHOProbe DNA hybridization test (Ortho Diagnostic Systems, Inc., Raritan, NJ) with conventional carbohydrate fermentation and commercial rapid tests for identifying gonococci (GC). The ORTHOProbe system employs a biotinylated DNA probe that hybridizes specifically with chromosomal target sequences of GC. Hybridization is detectable visually following the addition of a streptavidin-peroxidase conjugate in a rapid 10-min. assay. A total of 200 clinical isolates resembling Neisseria (gram-negative, oxidase-positive diplococci) cultured from various sites were tested. The ORTHOProbe test reacted strongly with all GC (94) and not with nongonococcal organisms (106), yielding a sensitivity and specificity of 100%. The ORTHOProbe system provides a convenient and reliable test for identifying Neisseria gonorrhoeae.


The miR-100-mediated pathway regulates apoptosis against virus infection in shrimp.
The process of programmed cell death process or apoptosis can be regulated by microRNAs, 21-25 nt short non-coding RNAs. However, a comprehensive view of apoptosis-associated miRNAs has not been intensively characterized. In this study, the shrimp miRNA microarray data showed that 199 miRNAs were involved in the regulation of apoptosis, among which 8 miRNAs were evolutionarily conserved in animals. The loss-of-function experiments in vivo in shrimp revealed that miR-100 was served as an anti-apoptosis miRNA through targeting the mRNA of trypsin gene. The results indicated that the silencing of miR-100 expression resulted in the increase of apoptotic activity of shrimp hemocytes and further led to the decreases of virus genome copies in shrimp and virus-infected shrimp mortality compared with the controls. The findings showed that miR-100-trypsin signaling pathway played an important role in the antiviral immunity by regulating apoptosis. Therefore, our study presented a novel miR-100-mediated pathway in the regulation of apoptosis.


A method for non-destructive determination of cocoa bean fermentation levels based on terahertz hyperspectral imaging.
Fermentation of cocoa is a key process to obtain aromatic chocolate products from raw cocoa beans. Hitherto, the levels of fermentation in cocoa are determined using destructive techniques, for example by a cut-test to manually observe the colour inside the beans, or by quantifying ammonia nitrogen (NH3) in the cocoa powder. In this paper, we present the use of Terahertz hyperspectral imaging as a new way to non-destructively analyse and detect fermented cocoa beans. The study analysed two sets of twenty-two cocoa bean samples with different levels of fermentation from two producers in Brazil. A correlation between fermentation conditions and the outcome results of their THz measurements was observed.


A meta-analysis evaluating risk factors for compound free flaps for upper extremity defect reconstruction comparing complications and functional outcomes of compound free flaps with and without bone components.
Compound flaps offer the advantage of one stage defect reconstruction respecting all relevant tissues and early functional recovery by optimal vascularity of all components. Due to its specific vascular anatomy and the three-dimensional donor site, compound flaps with bone components may result in higher complication rates compared to soft tissue compound flaps. The meta-analysis summarizes the available evidence and evaluates whether bone components are a risk factor for periprocedural complications in upper extremity multidimensional defect reconstruction. PubMed and Embase were searched for all publications addressing compound free flaps for upper extremity defect reconstruction with bone or soft tissue components published between January 1988 and May 2018. The methodological quality was assessed with the American Society of Plastic Surgeons Evidence Rating Scale for Therapeutic Studies. Flap loss, thrombosis rate, early infection, hematoma, seroma, as well as donor site complications were extracted and analyzed. Twelve out of 1157 potentially eligible studies (evidence-III) comprising 159 patients were finally included with publication bias for all summarized complication rates. Complication rates for flaps with/ without bone components were: total flap loss 5%, 95% CI = 3%-10% (6%/5%); partial flap loss 8%, 95% CI = 5%-15%, (9%/8%); arterial/venous thrombosis 7%, 95% CI = 4%-12%, (8%/5%)/14%, 95% CI = 9%-21% (16%/6%, P < .05) with higher risk for flaps with bone components; infection 6%, 95% CI = 3%-12% (6%/6%); hematoma 6%, 95% CI = 3%-11% (6%/5%); seroma 5%, 95% CI = 3%-10% (5%/5%); dehiscence 10%, 95% CI = 6%-17% (11%/9%). Compound flaps for upper extremity defect reconstruction including bone components have a higher venous thrombosis rate compared to compound soft-tissue flaps.


Metabolic engineering of Escherichia coli for efficient biosynthesis of butyl acetate.
Butyl acetate is a versatile compound that is widely used in the chemical and food industry. The conventional butyl acetate synthesis via Fischer esterification of butanol and acetic acid using catalytic strong acids under high temperature is not environmentally benign. Alternative lipase-catalyzed ester formation requires a significant amount of organic solvent which also presents another environmental challenge. Therefore, a microbial cell factory capable of producing butyl acetate through fermentation of renewable resources would provide a greener approach to butyl acetate production. Here, we developed a metabolically engineered strain of Escherichia coli that efficiently converts glucose to butyl acetate. A modified Clostridium CoA-dependent butanol production pathway was used to synthesize butanol which was then condensed with acetyl-CoA through an alcohol acetyltransferase. Optimization of alcohol acetyltransferase expression and redox balance with auto-inducible fermentative controlled gene expression led to an effective titer of 22.8 ± 1.8 g/L butyl acetate produced in a bench-top bioreactor. Building on the well-developed Clostridium CoA-dependent butanol biosynthetic pathway, expression of an alcohol acetyltransferase converts the butanol produced into butyl acetate. The results from this study provided a strain of E. coli capable of directly producing butyl acetate from renewable resources at ambient conditions.


Intrauterine left chamber myocardial infarction of the heart and hydrops fetalis in the recipient fetus due to twin-to-twin transfusion syndrome.
A rare complication of twin-to-twin transfusion syndrome (TTTS) is described: myocardial infarction of the recipient fetus. Myocardial infarction and hydrops are considered to be consequences of hypertension in the recipient. No other organs were affected. Pathological signs of intrauterine hypertension were estimated by the thickness of vessel walls and signs of hypertrophied myocardial cells. In the heart of the recipient fetus there was a chronic myocardial infarction near the apex cordis on the anterior wall with an aneurysm 4x5 mm in diameter. Diagnosis was based on light microscopic examination. The poor myocardial systolic function resulted in hydrops. Since the mother was administered beta sympathomimetics in therapeutic doses the contribution of the drug to the myocardial infarction is uncertain, but we would like to suggest this as a possible adverse effect in TTTS. The present case is the first reported myocardial infarction in connection with the syndrome.


Eight-year dry deposition of atmospheric mercury to a tropical high mountain background site downwind of the East Asian continent.
Atmospheric deposition, either dry or wet, has been identified as an important pathway of mercury (Hg) input to terrestrial and aquatic systems. Although East Asia is the major atmospheric Hg emission source region, very few studies have been conducted to quantify atmospheric Hg deposition in its downwind region. In this study, 8-year (2009-2016) atmospheric Hg dry deposition was reported at the Lulin Atmospheric Background Station (LABS), a high mountain forest site in central Taiwan. Dry deposition of speciated Hg was estimated using a bi-directional air-surface flux exchange model for gaseous elemental mercury (GEM) and dry deposition models for gaseous oxidized mercury (GOM) and particulate-bound mercury (PBM), making use of the monitored speciated atmospheric Hg concentrations. Annual total Hg dry deposition ranged from 51.9 to 84.9 μg m-2 yr-1, with a multi-year average of 66.1 μg m-2 yr-1. Among the three forms of atmospheric Hg, GEM was the main contributor to the total dry deposition, contributing about 77.8% to the total, due to the high density of forest canopy as well as the much higher concentration of GEM than GOM and PBM at LABS. Mercury dry deposition is higher in winter and spring than in summer and fall, partly due to the elevated Hg concentrations associated with air masses from East and Southeast Asia where with high atmospheric Hg emissions. The mean annual dry/wet deposition ratio of 2.8 at LABS indicated that Hg deposition to forest landscape was governed by dry rather than wet deposition.


The effect of intraperitoneal administration of BromAc on blood parameters: phase 1 study.
Intraperitoneal administration of BromAc (bromelain + acetylcysteine) is currently undergoing a phase 1 clinical trial for pseudomyxoma peritonei at our institution. This study reports on analysis of routine blood parameters before and after treatment for a series of 25 patients in this trial. Blood parameters assessed included full blood count, electrolytes, urea, and creatinine, liver function tests, coagulation studies, as well as inflammatory markers (CRP). Certain parameters such as CRP, and white cell count, were significantly elevated after treatment whilst serum albumin level was reduced indicating an inflammatory reaction. However, liver enzymes, coagulation studies, and other parameters were not affected. Therefore, there are no additional safety signals evident upon analysis of routine blood parameter testing.


Cefetamet pivoxil treatment causes loss of carnitine reserves that can be prevented by exogenous carnitine administration.
Two groups of pediatric patients receiving cefetamet pivoxil treatment (3 x 500 mg daily) for 7 days were studied. In the first group (Group A) the drug was administered alone; in the second group (Group B) the drug was given in combination with a molar excess of carnitine (3 x 1 g). Medication with cefetamet pivoxil alone was associated with a large urinary excretion of pivaloylcarnitine: Approximately 71% of the daily pivalate intake could be eliminated as carnitine ester in the urine. In this group, the plasma level and the urinary output of free carnitine decreased. By contrast, in Group B, the administration of molar excess of carnitine aided stochiometric elimination of pivalate as carnitine ester, and the plasma levels and carnitine-free urinary output were unchanged. The data show that medication of cefetamet pivoxil results in the formation of pivaloylcarnitine in children; the sustained loss of carnitine esters can ultimately lead to carnitine deficiency. Molar excess of exogenous carnitine aids in the elimination of pivalate derived from cefetamet pivoxil therapy and helps to maintain the carnitine reserves.


Disease Course, Management and Outcomes in Kidney Transplant Recipients with SARS-CoV-2 Infection during the Omicron-Variant Wave: A Single-Center Experience.
Since December 2019, kidney transplant recipients (KTRs) have experienced a great impact of the coronavirus disease 2019 (COVID-19) pandemic, with a higher risk of morbidity and mortality compared to the general population. Preliminary data in KTRs suggest that the Omicron variant, which has been dominant since December 2021, is more infectious than the previous ones but is associated with reduced risk of severity and low lethality rates. The purpose of our study was to assess the disease course and outcomes of the SARS-CoV-2 infection in KTRs during the Omicron-surge. This retrospective study included 451 KTRs diagnosed with SARS-CoV-2 infection between 1 December 2021 and 30 September 2022. Demographic and clinical characteristics at the time of infection, vaccination data, treatment, clinical course, and outcomes were recorded and analyzed. Mean age was 51.8 ± 13.7 years with a male predominance (61.2%). The majority (76.1%) were vaccinated with at least three doses of the available mRNA vaccines, although serology revealed low anti-SARS-CoV-2 antibody titers before infection (33 [3.3-1205] AU/mL). Only 6% of the patients experienced moderate-severe disease. Accordingly, there was low prevalence of adverse outcomes, such as SARS-CoV-2-related hospitalization (11.3%) and death (0.9%). Multivariate analysis revealed that only age significantly increased the risk of SARS-CoV-2-related hospitalization. During the Omicron wave, the clinical course of the SARS-CoV-2 infection in KTRs has substantially changed, with lower rates of moderate and severe disease and a low prevalence of adverse outcomes. Prospective clinical trials are warranted to further elucidate the evolving pathogenesis, management, and long-term outcomes of COVID-19 in such high-risk populations.


Influence of chemical signals on the topographic orientation of the cave fish Caecobarbus geertsi Boulenger (Pisces, Cyprinidae).
Adult individuals of the cave cyprinid Caecobarbus geertsi Boulenger, when placed in a choice-apparatus, show a significant tendency to orient towards the zone in which water from a tank occupied by known conspecifics is introduced. The phenomenon is briefly discussed in relation to physical features of the subterranean biotopes.


The LAM-SAFE Study: lamotrigine versus carbamazepine or valproic acid in newly diagnosed focal and generalised epilepsies in adolescents and adults.
To investigate efficacy and safety of lamotrigine (LTG) versus carbamazepine (CBZ) or valproic acid (VPA) in newly diagnosed focal (FE) and idiopathic generalised (GE) epilepsies in adolescents and adults. Open-label randomised comparative multicentre 24-week monotherapy trial in newly diagnosed epilepsy patients of >or=12 years of age. Patients with FE were treated with LTG or CBZ, those with GE received LTG or VPA. The primary efficacy variable was the number of seizure-free patients during study weeks 17 and 24. Two hundred and thirty-nine patients were included. One hundred and seventy-six patients suffered from FE and 63 from GE. In the FE group, 88 patients each were treated with CBZ or LTG. Ninety-four percent of the CBZ patients and 89% of the LTG patients became seizure-free according to an intent-to-treat analysis (not statistically different). The rate of patients discontinuing treatment due to adverse events or a lack of efficacy was 19% with CBZ compared to 9% with LTG (not statistically different). In the GE group, 30 patients received VPA and 33 LTG. During study weeks 17 and 24, 61% of the LTG patients and 84% of the VPA patients had become seizure-free (not statistically significant). The drop-out rate due to lack of efficacy or adverse events was 12% with LTG and 3% with VPA (not statistically different). This study indicates that the effectiveness of LTG in focal and generalised epilepsy syndromes as initial monotherapy in patients >or=12 years is in the range of standard first-line antiepileptic drugs.


Optimization of a capillary zone electrophoresis method by using a central composite factorial design for the determination of codeine and paracetamol in pharmaceuticals.
Capillary zone electrophoresis was optimized to quantitatively determine codeine and paracetamol via central composite factorial design. Critical parameters (concentration, buffer, pH, voltage) assessed effects on resolution, analysis time and efficiencies. Optimum separation conditions were achieved using phosphate buffer 20 mM (pH 6.8) and voltage (15 kV). The optimized procedure easily determined codeine and paracetamol with separation in less than 3 min. Calibration curves (R > 0.999) were prepared, with LODs of 13.5 and 340 ng mL(-1) for codeine and paracetamol, respectively, and a good R.S.D.% (<3%). This method was applied to determine codeine and paracetamol in pharmaceutical formulations; recoveries coincided with stated contents.


Superoxide anion, superoxide dismutase and lipid peroxidation in the murine macrophage cell line C4M phi.
A remarkable increase in the production of superoxide radicals and SOD activity was measured in suspension of the murine macrophage cell line C4M phi treated with Lentinan (4-10 X 10(3) micrograms/5 X 10(6) cells). In activated macrophages the decrease of lipid peroxidation could be interpreted as a consequence of enhanced SOD activity.


Functionally important arginine residues of aspartate transcarbamylase.
The reaction of phenylglyoxal with aspartate transcarbamylase and its isolated catalytic subunit results in complete loss of enzymatic activity (Kantrowitz, E. R., and Lipscomb, W. N. (1976) J. Biol. Chem. 251, 2688-2695). If N-(phosphonacetyl)-L-aspartate is used to protect the active site, we find that phenylglyoxal causes destruction of the enzyme's susceptibility to activation by ATP and inhibition by CTP. Furthermore, CTP only minimally protects the regulatory site from reaction with this reagent. The modified enzyme still binds CTP although with reduced affinity. After reaction with phenylglyoxal, the native enzyme shows reduced cooperativity. The hybrid with modified regulatory subunits and native catalytic subunits exhibits slight heterotropic or homotropic properties, while the reverse hybrid, with modified catalytic subunits and native regulatory subunits, shows much reduced homotropic properties but practically normal heterotropic interactions. The decrease in the ability of CTP to inhibit the enzyme correlates with the loss of 2 arginine residues/regulatory chain (Mr = 17,000). Under these reaction conditions, 1 arginine residue is also modified on each catalytic chain (Mr = 33,000). Reaction rate studies of p-hydroxymercuribenzoate, with the liganded and unliganded modified enzyme suggest that the reaction with phenylglyoxal locks the enzyme into the liganded conformation. The conformational state of the regulatory subunit is implicated as having a critical role in the expression of the enzyme's heterotropic and homotropic properties.


Cerebral chronic hypoperfusion in mice causes premature aging of the cerebrovasculature.
Chronic cerebral hypoperfusion (CCH) is the main characteristic of an aged brain showing cerebrovascular alterations. Our previous study that the morphological changes in the pial arteries accompany a decrease in the cerebral blood flow in aged mouse brains, and it raises the question of whether artificial CCH can induce the same changes in brain vessel morphology. Here, we examined the effect of CCH on cerebrovascular morphology. Using a microcoil-induced chronic cerebral hypoperfusion (MCH) model, we induced CCH for 8 and 12 weeks. The cerebrovasculature morphology was evaluated using three-dimensional vessel analysis and compared with that of aging mice. We found the morphological changes in brain vessels of MCH mice, indicating that the CCH can induce cerebrovascular alteration. However, the changes in brain vessel morphology in the MCH mice were different in detail from those in the aging mice. Aging mice showed an increase in vessel tortuosity and thinned string vessels; MCH mice mainly showed thinned string vessels. This suggests that CCH may be a cause of age-related cerebrovascular alterations.


Herpes zoster: a possible early clinical sign for development of acquired immunodeficiency syndrome in high-risk individuals.
Zoster is uncommon before the age of 50 years in immunologically normal individuals, but it occurs with increased frequency in people who are immunosuppressed. A retrospective review of 300 patients with acquired immunodeficiency syndrome associated with Kaposi's sarcoma, revealed that 8% had prior zoster, a rate that is sevenfold greater than historic controls of the same age. We prospectively examined forty-eight patients, with no known immunodeficiency or signs of AIDS or AIDS related complex (ARC), who presented with zoster localized to the thoracic region. Forty-one patients had known risk factors for AIDS and thirty-five had antibody to the AIDS-associated virus (AAV) at the time of presentation. One seropositive subject had no known risk factors. Absolute lymphocyte counts, lymphocyte OKT4/OKT8 ratios, and lymphocyte mitogen responses were all depressed in subjects with antibody to AAV when compared with seronegative individuals. Seven of thirty-three AAV antibody-positive subjects, who could be followed longitudinally, developed AIDS from 1 to 28 months (mean = 13) after zoster. One antibody-negative subject seroconverted to become AAV seropositive 16 months after zoster and developed Kaposi's sarcoma 1 month later. These eight subjects had persistently low lymphocyte OKT4/OKT8 ratios and elevated beta-2 microglobulin. In patients at risk for AIDS, the occurrence of zoster may be one sign that heralds the marked depression of cellular immunity associated with AIDS or ARC.


Transforming Access to Specialist Care for Inflammatory Bowel Disease: The PACE Telemedicine Program.
There are significant geographic disparities in the delivery of IBD healthcare in Ontario which may ultimately impact health outcomes. Telemedicine-based health services may potentially bridge gaps in access to gastroenterologists in remote and underserved areas. We conducted a needs assessment for IBD specialist care in Ontario using health administrative data. As part of a separate initiative to address geographic disparities in access to care, we described the development and implementation of our Promoting Access and Care through Centres of Excellence (PACE) Telemedicine Program. Over the first 18 months, we measured wait times and potential cost savings. We found substantial deficiencies in specialist care early in the course of IBD and continuous IBD care in regions where the number of gastroenterologists per capita were low. The PACE Telemedicine Program enabled new IBD consultations within a median time of 17 days (interquartile range [IQR], 7-32 days) and visits for active IBD symptoms with a median time of 8.5 days (IQR, 4-14 days). Forty-five percent of new consultations and 83% of patients with active IBD symptoms were seen within the target wait time of two weeks. Telemedicine services resulted in an estimated cost savings of $47,565 among individuals who qualified for Ontario's Northern Travel Grant. The implementation of telemedicine services for IBD is highly feasible and can reduce wait times to see gastroenterologists that meet nationally recommended targets and can lead to cost savings.


Persistent pain at multiple sites--connection to glucose derangement.
The aim of this study was to analyse the prevalence of prediabetes and diabetes among subjects with daily chronic widespread pain (DCWP). In the multivariate analysis, DCWP was significantly associated with prediabetes and diabetes. Persistent chronic pain at multiple sites may be an additional symptom of prediabetes and diabetes.


Inhibition of nuclear factor kappa B inducing kinase suppresses inflammatory responses and the symptoms of chronic periodontitis in a mouse model.
Chronic periodontitis is an inflammatory disease that represents a major public health issue nowadays. Here, we investigated the protective role of nuclear factor kappa B (NF-κB) inducing kinase (NIK)-inhibitor on chronic periodontitis and revealed the underlying molecular mechanism. NIK-inhibitor was synthesized, and its functions were examined in primary osteoclasts and wild-type (WT) and NIK-/- chronic periodontitis mouse model. Lipopolysaccharides (LPS) or activator of NF-κB was applied to stimulate inflammatory response of osteoclasts. The qRT-PCR, ELISA and Western blot were used to measure the expression of pro-inflammatory and osteoclast-related genes, and the activation of NF-κB signaling. Osteoclastogenesis and bone damage were detected by TRAP staining and micro-CT. NIK knockdown mice had lower expression of osteoclast-related genes and improved CEJ-ABC damage. Similarly, NIK-inhibitor administration inhibited inflammatory responses and CEJ-ABC damage in chronic periodontitis models. NIK-inhibitor suppressed osteoclastogenesis and osteoclast-related genes expression through inhibiting the non-canonical NF-κB signaling. NIK plays important role in bone destruction of chronic periodontitis and NIK-inhibitor represents a promising therapeutic strategy for this disease.


Hypertension and cerebrovascular disease.
Although hypertension is the greatest risk factor for stroke, its control with antihypertensive drugs improves survival and decreases the incidence of stroke. If a stroke should occur, careful antihypertensive therapy has not been harmful. Sodium nitroprusside is the initial drug of choice in acute crises.


Efficient transfer of highly resolved small DNA fragments from polyacrylamide gels to DBM paper.
A procedure is described that combines high resolution of small DNA molecules (10 to 250 bases) with high transfer efficiency from polyacrylamide gels to diazobenzyloxymethyl (DBM) paper. The DNA fragments are separated electrophoretically in denaturing or nondenaturing step gels. These consist of a short gel of relatively high polyacrylamide concentration (8%) above a long gel of relatively low polyacrylamide concentration (4%). Step gels permit a high resolution of small DNA fragments in gels of sufficiently low polyacrylamide concentration from which efficient transfer to DBM paper is feasible. The combination of the step gel with a short treatment of the gel before transfer ensures a high transfer efficiency. As much as 30% and 50% of the DNA applied to nondenaturing and denaturing gels, respectively, are bound covalently to the DBM-paper. Optimal conditions for hybridization to DBM-linked DNA molecules of 30 to 250 base length are described.


Intraoral distraction osteogenesis to lengthen the ascending ramus. Experience with seven patients.
Seven children with facial asymmetry, mean age 12 years (range 11-14.5) were treated by intraoral distraction osteogenesis to lengthen the hypoplastic ramus. We achieved a mean increase in length of the ramus of 13mm (range 10-16). In only one patient did we achieve a posterior open bite on the distraction side. All patients ended with a symmetrical chin. It was helpful to place an orthodontic bite block on the opposite side either preoperatively or postoperatively to cant the plane of occlusion. The duration of follow-up was too short to allow conclusions to be drawn about the future requirement for bimaxillary osteotomies.


Circulating miRNA-202-3p is a potential novel biomarker for diagnosis of type 1 gastric neuroendocrine neoplasms.
Currently, there are no circulating diagnostic biomarkers for gastric neuroendocrine neoplasms (g-NENs). In previous studies, we found that miRNA-202-3p is overexpressed in the tumour tissue of type 1 g-NEN. We speculated that miRNA-202-3p is also likely to be highly expressed in circulating blood. A total of 27 patients with type 1 g-NEN and 27 age- and sex-matched control participants were enrolled in this study. The miRNA-202-3p levels in serum obtained from the participants were measured by qRT-PCR. The expression level of miRNA-202-3p in the samples was calculated by comparison with a standard curve. The clinical characteristics of the patients were similar to those of the patient samples in previous reports. Expression of miRNA-202-3p was significantly higher in the patient group (3.84 × 107 copies/nl) than in the control group (0.635 × 107 copies/nl). The area under the ROC curve (AUC) was 0.878 (95% CI: 0.788-0.968), and the optimal cut-off point was approximately 1.12 × 107 copies/nl. The sensitivity and specificity were 88.9% and 77.8%, respectively. This study suggests that miRNA-202-3p is potentially useful as a biomarker of type 1 g-NEN; further investigation and verification should be performed in future research.


Characterization of water-soluble brown carbon in atmospheric fine particles over Xi'an, China: Implication of aqueous brown carbon formation from biomass burning.
Brown carbon (BrC) aerosols can affect not only the climate but also human health, however, the light absorption, chemical compositions, and formation mechanisms of BrC are still uncertain, which leads to uncertainties in the accurate estimation of its climate and health impacts. In this study, highly time - resolved brown carbon (BrC) in fine particles was investigated in Xi'an using offline aerosol mass spectrometer analysis. The light absorption coefficient (babs365) and mass absorption efficiency (MAE365) at 365 nm of water-soluble organic aerosol (WSOA) generally increased with oxygen-to-carbon (O/C) ratios, indicating that oxidized OA could have more impacts on BrC light absorption. Meanwhile, the light absorption appeared to increase generally with the increases of nitrogen-to-carbon (N/C) ratios and water-soluble organic nitrogen; strong correlations (R of 0.76 for CxHyNp+ and R of 0.78 for CxHyOzNp+) between babs365 and the N - containing organic ion families were observed, suggesting that the N - containing compounds are the effective BrC chromophores. babs365 correlated relatively well with BBOA (r of 0.74) and OOA (R of 0.57), but weakly correlated with CCOA (R of 0.33), indicating that BrC in Xi'an was likely to be associated with biomass burning and secondary sources. A multiple linear regression model was applied to apportion babs365 to contributions of different factors resolved from positive matrix factorization on water-soluble organic aerosols (OA) and obtained MAE365 values of different OA factors. We found that biomass-burning organic aerosol (BBOA) dominated the babs365 (48.3 %), followed by oxidized organic aerosol (OOA, 33.6 %) and coal combustion organic aerosol (CCOA, 18.1 %). We further observed that nitrogen-containing organic matter (i.e., CxHyNp+ and CxHyOzNp+) increased with the increase of OOA/WSOA and the decrease of BBOA/WSOA, especially under high ALWC conditions. Our work offered proper observation evidence that BBOA is oxidized through the aqueous formation to produce BrC in Xi'an, China.


Characterization of Feeding, Sport Management, and Routine Care of the Chilean Corralero Horse during Rodeo Season.
The aim of this study was to characterize the routine care, training, feeding, and nutritional management of Chilean corralero horses that participated in the rodeos of the Chilean Rodeo Federation. Forty-nine horse farms between the Metropolitan (33°26'16″ south (S) 70°39'01″ west (W)) and Los Lagos Regions (41°28'18″ S 72°56'12″ W), were visited and a survey was conducted on the management and feeding of the Chilean horse. Of the horses which participated in at least one official rodeo in the 2014-2015 season, 275 horses were included in the study. The survey consisted of five questions about general data on the property and the respondent, four questions on the animal characteristics, five questions about where the horses were kept during the day, seven questions to characterize the amount of exercise done by the horse, and 18 questions about feeding practices; additionally, the amount of feed offered was weighed. All horses in this study were in training and kept in their stall for at least 12 h and remained tied or loose for the rest of the day. The intensity of daily exercise of the rodeo Chilean horse could be classified as moderate to heavy and consisted of being worked six days/week and participating in two rodeos/month. Ninety-eight percent of respondents had watering devices in the stables. The diet of the Chilean corralero horse during the training season is based on forages, mainly alfalfa hay, plus oats as an additional energy source. Protein supplements such as oil seed by-products are used less frequently. A wide variation was observed in the diets and quantities of feed offered, which suggests that the feeding management of these individuals is not formulated according to their requirements.


Conserved KIR allele-level haplotypes are altered by microvariation in individuals with European ancestry.
NK cell immunoglobulin-like receptor (KIR) haplotype-specific DNA fragments were sequenced to identify centromeric and telomeric allele-level haplotype structures and their frequencies from 76 unrelated individuals with European ancestry. Analysis was simplified by redefining the 5' boundary of the centromeric KIR gene cluster to include only exons 7-9 of KIR3DL3. Three consensus allele-level haplotypes were identified for a centromeric gene presence/absence structure designated as Cen-A1. KIR3DL3*00201 (exons 7-9)∼KIR2DL3*001∼KIR2DL1*00302 was the most frequent (37.5%) centromeric structure. Single consensus haplotypes were observed for haplotype structures Cen-B1 and Cen-B2. Six Tel-A1 and two Tel-B1 consensus haplotypes were observed; the most prevalent (23.0%) was KIR2DL4*00102∼KIR3DL1*002∼KIR2DS4*00101∼KIR3DL2*002. A small number of nucleotide substitutions (≤3) in the coding regions of the functional KIR genes created microvariants of the consensus haplotypes. Eight less common haplotype structures were also detected. Four carried hybrid genes formed during gene deletion events, two carried an insertion with a 2DL5/3DP1 fusion gene and two included a very large insertion. These data show that the KIR gene complex is composed of a limited number of conserved allele-level centromeric and telomeric haplotypes that have diversified by mutation, recombination within a locus and unequal crossing over.


Heavy metal(loid)s contamination in water and sediments in a mining area in Ecuador: a comprehensive assessment for drinking water quality and human health risk.
Elevated heavy metal(loid)s concentrations in water lower its quality posing a threat to consumers. This study aims to assess the human health risk caused by heavy metal(loid)s in tap water in Santa Rosa city, Ecuador, and the ecological risk of stream water and sediments in the Santa Rosa River. Concentrations of As, Cd, Cr, Cu, Ni, Pb, and Zn were evaluated in tap waters, stream waters, and sediment samples during the rainy and dry seasons. The Metal Index (MI), Geo-accumulation Index (Igeo), Potential Ecological Risk Index (PERI), and the levels of carcinogenic (CR) and non-carcinogenic risk (HQ) were determined. The results revealed severe pollution levels, mainly in Los Gringos and El Panteon streams, both tributaries of the Santa Rosa River, the primary water source for Santa Rosa inhabitants. More than 20% of the surface water samples showed severe contamination (MI > 6), and 90% of the tap water samples presented a MI value between 1 and 4, which indicates slight to moderate pollution. Drinking water displayed high levels of As, with 83% of the tap water samples collected from households in the dry season above the recommended concentration set by the World Health Organization and Ecuadorian legislation. The Igeo-Cd in the sediment samples was significantly high (Igeo > 3), and the PERI showed very high ecological risk (PERI > 600), with Cd as the main pollutant. HQ and CR were above the safe exposure threshold, suggesting that residents are at risk from tap water consumption, with As being the primary concern.


Mental health and risk behaviors among secondary school students: A study on ethnic minorities.
Mental health disorders are highly correlated with risk behaviors. The objective of the present study is to examine the relationship between risk behaviors and mental health among school-going students with a focus on ethnic minorities. The National Health and Morbidity Survey (NHMS) 2017 (n = 8230) was used for analyses. It was a nationwide survey conducted in Malaysia. The dependent variables were measured by three risk behaviors (cigarette smoking, alcohol drinking and use of illicit drugs). Probit regressions were utilized to examine the effect of mental health on the probability of smoking, drinking and using illicit drugs. Demographic and lifestyle factors were used as the control variables. Truancy was identified as a mediating variable. Anxiety, depression and suicidal ideation affected cigarette smoking, alcohol drinking and use of illicit drugs through mediation of truancy. After controlling for demographic and lifestyle factors, students with anxiety, depression and suicidal ideation were more likely to smoke, drink and use illicit drugs compared with their peers without any mental health disorders. Furthermore, the likelihood of consuming cigarettes, alcohol and illicit drugs was found to be higher among students who played truant than those who did not. Mental health plays an important role in determining participation in risk behaviors among ethnic minority students in Malaysia. Public health administrators and schools have to be aware that students who suffer from mental health disorders are likely to indulge in risk behaviors.


Preliminary evaluation of a candidate international reference for Epstein-Barr virus capsid antigen immunoglobulin A in China.
The detection of the Epstein-Barr capsid antigen (VCA) immunoglobulin A (IgA) is widely used in the diagnosis of nasopharyngeal carcinoma (NPC), but a reference standard for evaluating the presence of VCA-IgA is not yet available. Therefore, a reference standard is urgently needed for a uniform and quantitative detection of VCA-IgA. A mixed reference serum from three NPC patients diluted with healthy subject serum was made as a potential first international standard for VCA-IgA. VCA-IgA was detected in twenty NPC patients by four ELISA kits and two chemiluminescent immunoassays kits using the reference as a calibration curve. The performance of these six kits was evaluated, and the quantitative results were compared. Our results showed a good linearity of the reference in different kits. Without reference, the difference of the total coefficient of variation (from 3.98 to 43.11%) and Within-run coefficient of variation (from 2.47 to 19.66%) was large in the 6 kits. The positive and negative coincidence rate between the 6 kits and indirect immunofluorescence for NPC diagnosis was 75% overall agreement, but a difference among the six kits was found, ranging from 55 to 90%. The concentration of VCA-IgA in the 20 NPC samples led in the division into three categories such as negative, low, or medium/high positive, but these concentrations were significantly different within these three categories depending on the kit used of the 6 considered. However,a good correlation (R2 = 0.986) was observed between Antu and Beier ELISA kits. The reference serum mightbe used as a reference standard for a better comparison of the results from different kits/laboratories. However, the quantitative results of some kits are still inconsistent due to the diversity of VCA antigens.


[Wife against advance directive: a case-inspired legal and ethical clarification].
Advance directives and durable powers of attorney are two increasingly used tools for patients' precedent autonomy; however, their combined use, as recommended by major institutions in Germany, might in reality result in various discrepancies between the wording and interpretation of the directive and the surrogate's understanding of the patient's relevant will. In one of the possible conflict constellations, the surrogate wants to overrule a relevant and unambiguous advance directive by reference to a privileged access to the patient's "real" treatment preferences or the presumed will of the patient. Such cases, which must be strictly distinguished from cases with real or alleged leeway for interpretation in the advance directive, can lead to normative uncertainty as well as to substantial psychological distress for all persons involved. Based on an exemplary real clinical case from 2015 (which did not go to court) legal, ethical and pragmatic aspects of the described constellation are discussed. Ethically, caution should be exercised against a relapse into a masked treatment paternalism, which currently seems to be partly caused by judicial exegesis.


Immunological reactivity and passive protective activity of monoclonal antibodies against protective antigen (PAg) of Leptospira interrogans serovar lai.
Monoclonal antibody (MAb) AG1 against the protective antigen (PAg) was produced and characterized. It had been extracted from Leptospira interrogans serovar lai by the chloroform-methanol-water method and was of glycolipid nature (23-30Kd). The fact that the PAg was a serogroup-specific antigen was shown by MAb AG1, because MAb AG1 agglutinated serovars of serogroup Icterohaemorrhagiae. Purified MAb LW2 and LW3 which are agglutinating antibodies of serovar lai and AG1 passively protected hamsters from leptospiral infection. Induction of the reactive oxygen intermediates by MAbs from peritoneal exudate macrophages of mice were observed in the chemical luminescence assay and the MAbs reacted with the PAg in the dot enzyme-linked immunosorbent assay. However, MAb LW4a against the genus-specific antigen present in the sub-surface of leptospiral cells did not show protective and reactive-oxygen-inducing activities; they reacted with the non-protective glycolipid antigen of low molecular weight (Fr I, 10-15Kd) in the dot enzyme-linked immunosorbent assay. These results indicated that anti-PAg antibody exhibited opsonic activity against Leptospira and the production of reactive oxygens by macrophages led to leptospiricidal action as one of the defence mechanisms of the host against leptospiral infection. However, the antibody against the genus-specific glycolipid antigen may not be important for protection against leptospiral infection.


The differences of susceptibility of the target thyroid gland to autoimmune thyroiditis and of antigenicity of thyroid gland for induction of experimental autoimmune thyroiditis.
By using a recently developed method for producing thyroiditis in mice consisting of implantation of a fresh thyroid gland into the peritoneal cavity or under the capsule of the kidney with subsequent injection of lipopolysaccharide, differences were shown in susceptibility of the target thyroid gland to autoimmune destruction and in antigenicity of the thyroid gland for induction of experimental autoimmune thyroiditis. Using recombinant congenic mice, the H-2 haplotypes of the target thyroid gland were found to be as important as those of the immune system in development of autoimmune thyroiditis. On the other hand, the H-2 haplotypes of the thyroid gland are unimportant for induction of autoimmune thyroiditis.


Long-Term Outcomes of Patients With Early Stage Nonbulky Hodgkin Lymphoma Treated With Combined Modality Therapy in the Stanford V Trials (the G4 and G5 Studies).
Combined modality therapy (CMT) is standard therapy for early-stage Hodgkin lymphoma (ESHL). We previously reported excellent outcomes with the abbreviated Stanford V regimen. Herein we report updated results with median follow-up >10 years on survival, therapy-related late effects, and impact of disease risk factors on patient outcomes. The G4 and G5 studies enrolled patients with stage I-IIA nonbulky ESHL. Patients received 8 weeks of Stanford V chemotherapy followed by 30 Gy modified involved-field radiation therapy (mIFRT) (G4) or Stanford V-C + 20 Gy mIFRT (G5). Patients were categorized as favorable or unfavorable risk per German Hodgkin Study Group (GHSG) criteria and outcomes between groups compared. A total of 129 patients were enrolled (68 favorable and 61 unfavorable risk). In the G4 study (n = 87), at median follow-up of 19.7 years, 5-, 10-, and 15-year progression-free survival (PFS) and overall survival (OS) were 95.4%/97.7%, 91.8%/96.5%, and 91.8%/95.3%, respectively. In the G5 study (n = 42), at median follow-up of 13.5 years, the 5-, 10-, and 15-year PFS and OS were 92.9%/100%, 92.9%/100%, and 88.4%/91.9%, respectively. PFS (P = .86) and OS (P = .86) were not significantly different between studies. There were also no significant differences between studies in patients with favorable or unfavorable risk for PFS (F: P = .53; U: P = .96), OS (F: P = .99; U: P = .78), secondary malignancies (F: P = .74; U: P = 1.0), and cardiovascular complications (F: no cases; U: P = 1.0). The G4 and G5 studies achieve high rates of durable remission; 20 versus 30 Gy mIFRT and cyclophosphamide substituted for mechlorethamine did not compromise nodal control, PFS, or OS in both favorable and unfavorable risk disease. These results support the efficacy of CMT in early-stage disease and lower-dose radiation therapy in patients with favorable and nonbulky unfavorable ESHL.


Improved AP-3 production through combined ARTP mutagenesis, fermentation optimization, and subsequent genome shuffling.
Ansamitocin (AP-3) is an ansamycins antibiotic isolated from Actinosynnema pretiosum and demonstrating high anti-tumor activity. To improve AP-3 production, the A. pretiosum ATCC 31565 strain was treated with atmospheric and room temperature plasma (ARTP). Four stable mutants were obtained by ARTP, of which the A. pretiosum L-40 mutant produced 242.9 mg/L AP-3, representing a 22.5% increase compared to the original wild type strain. With seed medium optimization, AP-3 production of mutant L-40 reached 307.8 mg/L; qRT-PCR analysis revealed that AP-3 biosynthesis-related gene expression was significantly up-regulated under optimized conditions. To further improve the AP-3 production, genome shuffling (GS) technology was used on the four A. pretiosum mutants by ARTP. After three rounds of GS combined with high-throughput screening, the genetically stable recombinant strain G3-96 was obtained. The production of AP-3 in the G3-96 strain was 410.1 mg/L in shake flask cultures, which was 44.5% higher than the L-40 production from the parental strain, and AP-3 was increased by 93.8% compared to the wild-type A. pretiosum. These results suggest that the combination of mutagenesis, seed medium optimization, and GS technology can effectively improve the AP-3 production capacity of A. pretiosum and provide an enabling methodology for AP-3 industrial production.


Peanut skin in diet alters average daily gain, ruminal and blood metabolites, and carcass traits associated with Haemonchus contortus infection in meat goats.
The aim of this study was to determine the effects of tannin-rich peanut skin (PS) supplementation on growth performance, ruminal and blood metabolites, and carcass traits associated with internal parasite infection in meat goats under confined conditions. Twenty-one Kiko crossbred male goats were blocked by body weight (BW) and randomly assigned to one of 3 treatment groups. Experimental diets contained different levels of peanut (Arachis hypogaea) skin replacing alfalfa (Medicago sativa) pellets (ALP) in a control diet. Experimental treatments included: 30% ALP (control), 15% PS and 15% ALP, and 30% PS. Peanut skin was incorporated in the grain mix portion of the diets. Animals were fed once daily, and the intake was adjusted every 3 to 4 d. Each animal was each artificially infected with 5,000 larvae of the 3rd stage of barber's pole worm (Haemonchus contortus). Body weights, dry matter intake (DMI), and fecal samples for fecal egg counts (FEC) were taken at d 0, 12, 23, and 41. Rumen fluid and blood samples were collected at d 45. The performance period lasted 45 d and at the completion of the study, goats were harvested, and carcass characteristics, abomasal worm counts were measured. The results showed that DMI, BW, carcass traits, and meat color were not affected by PS supplementation, whereas average daily gain (ADG, P < 0.01), blood glucose (P < 0.001), phosphorus (P < 0.05), and cholesterol levels (P < 0.001) significantly increased with increasing levels of PS supplementation. There was a linear (P < 0.01) reduction in rumen acetate to propionate ratio, ammonia-nitrogen, FEC, and H. contortus worm counts, with increasing levels of PS supplementation. This study shows that PS supplementation up to 30% of the diet can improve ADG and rumen fermentation while reducing gastrointestinal parasite infection in meat goats.


Photochemically-activated electrodes: application in design of reversible immunosensors and antibody patterned interfaces.
Antigen monolayers assembled onto Au electrodes associated with a quartz crystal act as electrochemical or microgravimetric quartz-crystal-microbalance (QCM) sensing interfaces for the complementary antibody. Electrochemical analysis of the antibody (Ab) is based on the insulation of the antigen monolayer electrode by the associated Ab towards a redox probe in the electrolyte solution. Ferrocene-modified glucose oxidase (Fc-GOx) and glucose are employed as redox probes for the amperometric transduction of the Ab association to the electrode. Bioelectrocatalyzed oxidation of glucose provides an electrochemical route to amplify the antigen-Ab complex formation. Electrochemical analysis of the dinitrophenyl antibody, DNP-Ab, by a dinitrophenyl-lysine monolayer electrode is presented. QCM analysis of the Ab is based on the frequency changes of the quartz crystal resulting from the association of the Ab to the crystal assembly. This method is discussed with the analysis of the fluorescein antibody, Flc-Ab, using a fluorescein monolayer-modified quartz crystal. A novel method to tailor reversible immunosensor devices by the application of photoisomerizable antigen monolayers on electrodes is presented. The antigen is modified by photoactive units exhibiting reversible photoisomerizable properties. In one photoisomer state, the antigen exhibits affinity for the Ab and enables its electrochemical or QCM analysis. Photoisomerization to the complementary state perturbs the antigen structure and the monolayer lacks affinity for the Ab. This enables the washing-off of the Ab and the regeneration of the actively sensing interface by a second illumination process that restores the antigen monolayer-modified surface. This method is exemplified by the development of a reversible DNP-Ab sensing electrode. N-Mercaptobutyl dinitrospiropyran was assembled as a photoisomerizable monolayer on a Au electrode. The dinitrospiropyran monolayer, SP-state, exhibits affinity for the DNP-Ab and enables the amperometric detection of the Ab using Fc-GOx and glucose as redox probe. The complementary photoisomerized protonated dinitromerocyanine monolayer, MRH(+)-state, lacks affinity for the DNP-Ab. By photoisomerization of the DNP-Ab associated with the SP-monolayer electrode to the MRH(+)-monolayer state, the DNP-Ab is washed-off, and by a second illumination process, the MRH(+)-monolayer is re-isomerized to the SP-monolayer assembly, which is the active interface for further analysis of the DNP-Ab. Cyclic amperometric detection of the DNP-Ab by the photoisomerizable dinitrospiropyran monolayer is demonstrated. The association of the DNP-Ab to the SP-monolayer electrode and the dissociation of the Ab from the MRH(+)-monolayer electrode are confirmed by QCM experiments using a dinitrospiropyran monolayer-modified quartz crystal. The insulating features of an antigen-Ab complex on a conductive surface and the photochemically controlled association of an antibody to a photoisomerizable monolayer assembled onto the surface were used to develop means for micropatterning of surfaces by the antibody. A dinitrospiropyran antigen monolayer was assembled onto conductive ITO glass. A DNP-Ab solution was used as 'ink solution' to pattern the surface. The Ab-pattern was imaged by electrochemical copper deposition onto the Ab-lacking surface domains. The dinitrospiropyran monolayer assembled onto ITO or Pyrex glass surfaces was employed as an active interface for the photolithographic patterning of the surface with the DNP-Ab. (ABSTRACT TRUNCATED)


Silver nanoparticles induce cell death of colon cancer cells through impairing cytoskeleton and membrane nanostructure.
Globally, colon cancer is a predominant cause of increased morbidity and mortality annually; therefore, in addition to traditional treatments, new protocols are under continuous investigation. Nanotechnology-based cancer therapy is a new strategy and considered one of the most promising research directions for colon cancer. In this study, we used a silver nanoparticle (AgNP)-based methodology to treat colon cancer cells, and single cell approaches to examine how AgNPs exerted inhibiting effects on cells. We found that AgNPs could apparently destroy cytoskeleton and topography structures, alter cell membrane nanostructures, and thus increase membrane roughness, and depress cell membrane adhesion properties and cell stiffness. We also found that AgNPs caused mitochondrial dysfunctions including hyperpolarization of membrane potential and reactive oxygen species (ROS) accumulation. Notably, AgNPs altered all phenotypes or functions of cells in a dose-dependent manner. Therefore, our research provided a new paradigm for revealing killing mechanisms of AgNPs against colon cancer cells from single cell biophysical aspects, which could advance AgNP-based nanotechnology cancer therapy.


"Doing Things Together Is What It's About": An Interpretative Phenomenological Analysis of the Experience of Group Therapeutic Songwriting From the Perspectives of People With Dementia and Their Family Caregivers.
The wellbeing of people living with dementia and their family caregivers may be impacted by stigma, changing roles, and limited access to meaningful opportunities as a dyad. Group therapeutic songwriting (TSW) and qualitative interviews have been utilized in music therapy research to promote the voices of people with dementia and family caregivers participating in separate songwriting groups but not together as dyads. This study aimed to explore how ten people with dementia/family caregiver dyads experienced a 6-week group TSW program. Dyads participated in homogenous TSW groups involving 2-4 dyads who were either living together in the community (2 spousal groups) or living separately because the person with dementia resided in a care home (1 family group, 1 spousal group). The TSW program, informed by personhood, couplehood, family centered and group process frameworks, involved creating original lyrics through song parody and song collage. Qualified Music Therapists facilitated sessions and interviewed each dyad separately. Interviews were analyzed using interpretative phenomenological analysis. Five recurrent group themes were developed, indicating group TSW: (1) was a positive shared experience, benefiting both members of the dyad and motivating further engagement with music; (2) stimulated mental processes and reignited participants' interests and skills; (3) provided meaningful opportunities for reflection and connection with memories and life experiences; and (4) prompted interaction and collaboration, leading to social connections, empathic relationships and experiences of inclusion. Participants also highlighted how: (5) the facilitated process supported engagement, highlighting abilities and challenging doubts. Dyads identified group TSW as an opportunity to recognize strengths, voice ideas and opinions, share meaningful experiences, and do "more with music." Participants valued TSW as a new, creative and stimulating experience that enabled connection with self and others and led to feelings of pride and achievement. Our findings further recognize how therapeutic intention and approach were reflected in participants' engagement and responses regardless of dementia stage and type, dyad relationship, or musical background. This research may broaden perspectives and expand understanding about how people with dementia and their family caregivers access and engage in music therapy.


Evaluation of a new assay for antibodies to LAV/HTLV III.
The sensitivity, specificity and reproducibility of an enzyme-linked immunosorbent assay (ELISA) for the detection of antibodies to LAV/HTLV III produced by Genetic Systems was assessed with the identical panel of sera used in previous evaluations of anti-HTLV III ELISAs. The results from this study show that the Genetic Systems anti-LAV/HTLV III ELISA proved to be of equivalent sensitivity and to have higher specificity than assays currently used in Australia for screening purposes while maintaining high levels of intra- and inter-laboratory reproducibility.


A composite somatotroph-corticotroph pituitary adenoma.
A 76-year-old woman presented with enlargement and weakness of her hands and feet coarsening of facial features, proximal muscle weakness, and worsening of her noninsulindependent diabetes mellitus. Serum growth hormone, somatomedin-C, and prolactin levels were elevated. Thyroid function test results and serum cortisol and adrenocorticotropic hormone levels were within normal limits. Luteinizing and follicle-stimulating hormone levels were both low, suggesting possible partial hypopituitarism. Magnetic resonance imaging of the sella demonstrated a pituitary lesion that measured 2.2 x 1 x 0.5 cm; it partially obliterated the suprasellar cistern and it distorted the optic chiasm. Light microscopic and ultrastructural examination of the trans-sphenoidally resected tissues identified characteristic features of 2 discrete pituitary adenomas that were in close apposition, but they were sharply demarcated. The 2 components were a corticotroph adenoma and a sparsely granulated somatotroph adenoma. Multiple adenomas of the pituitary are not rare; however, the majority are endocrinologically "nonfunctional." We report a patient with clinical features of acromegaly whose tumor was a composite lesion: one area exhibited morphological characteristics of a corticotroph adenoma and another distinct area exhibited features of a somatotroph adenoma. The possible histogenesis is discussed.


Limited factor VIIa surface localization requirement of the factor VIIa-induced overall thrombin generation in platelet-rich hemophilia A plasma.
Thrombin generation assay (TGA) and thrombelastography (TEG) are increasingly employed, global, in vitro methods for assessment of the procoagulant potential of plasma/blood and possibly ideally suited tools to monitor, for example, therapy with recombinant factor VIIa (FVIIa). It remains controversial to what extent results obtained with spiked and postinfusion samples reflect the outcome in patients. To characterize the TGA response to FVIIa in hemophilic plasma and compare with TEG data. Hemophilia A (HA) was induced in platelet-rich plasma (PRP) from healthy volunteers, followed by spiking with FVIIa, γ-carboxyglutamic acid (Gla)-domainless FVIIa or V158D/E296V/M298Q-FVIIa (FVIIaDVQ). Samples were triggered with tissue factor and analyzed by TGA and TEG in parallel. Addition of 25 nmol L-1 FVIIa to HA PRP normalized TEG parameters angle and R time, as well as TGA lag time, but had poor effects on the thrombin peak height and velocity index. All parameters (at least) returned to normal levels either upon adding a much higher concentration of FVIIa (~1500 nmol L-1) or by using the superactive variant FVIIaDVQ. Surprisingly, Gla-domainless derivatives of FVIIa and FVIIaDVQ also yielded considerable effects in HA PRP. The good general responses to clinically effective concentrations of FVIIa (25 and 75 nmol L-1) seen in TEG analyses, as well as for TGA lag time, were accompanied by far-from-normal thrombin peaks. A near-normal thrombin peak response required the presence of considerably higher FVIIa activity but, intriguingly, relied only marginally on a functional Gla domain (ie, on platelet surface localization).


Lower maximum forces on oral structures when using gum-elastic bougie than when using endotracheal tube and stylet during both direct and indirect laryngoscopy by novices: a crossover study using a high-fidelity simulator.
Applying excessive force during endotracheal intubation (ETI) is associated with several complications, including dental trauma and hemodynamic alterations. A gum-elastic bougie (GEB), a type of tracheal tube introducer, is a useful airway adjunct for patients with poor laryngoscopic views. However, how the use of a GEB affects the force applied during laryngoscopy is unclear. We compared the force applied on the oral structures during ETI performed by novices using the GEB versus an endotracheal tube + stylet. This prospective crossover study was conducted from April 2017 to March 2019 in a public medical university in Japan. In total, 209 medical students (4th and 5th grade, mean age of 23.7 ± 2.0 years) without clinical ETI experience were recruited. The participants used either a Macintosh direct laryngoscope (DL) or C-MAC video laryngoscope (VL) in combination with a GEB or stylet to perform ETI on a high-fidelity airway management simulator. The order of the first ETI method was randomized to minimize the learning curve effect. The outcomes of interest were the maximum forces applied on the maxillary incisors and tongue during laryngoscopy. The implanted sensors in the simulator quantified these forces automatically. The maximum force applied on the maxillary incisors was significantly lower when using a GEB than when using an endotracheal tube + stylet both with the Macintosh DL (39.0 ± 23.3 vs. 47.4 ± 32.6 N, P < 0.001) and C-MAC VL (38.9 ± 18.6 vs. 42.0 ± 22.1 N, P < 0.001). Similarly, the force applied on the tongue was significantly lower when using a GEB than when using an endotracheal tube + stylet both with the Macintosh DL (31.9 ± 20.8 vs. 37.8 ± 22.2 N, P < 0.001) and C-MAC VL (35.2 ± 17.5 vs. 38.4 ± 17.5 N, P < 0.001). Compared with the use of an endotracheal tube + stylet, the use of a GEB was associated with lower maximum forces on the oral structures during both direct and indirect laryngoscopy performed by novices. Our results suggest the expanded role of a GEB beyond an airway adjunct for difficult airways.


Nanostructured DNA for the delivery of therapeutic agents.
DNA and RNA, the nucleic acids found in every living organism, are quite crucial, because not only do they store the genetic information, but also they are used as signals through interaction with various molecules within the body. The nature of nucleic acids, especially DNA, to form double-helix makes it possible to design nucleic acid-based nanostructures with various shapes. Because the shapes as well as the physicochemical properties determine their interaction with proteins or cells, nanostructured DNAs will have different features in the interaction compared with single- or double-stranded DNA. Some of these unique features of nanostructured DNA make ways for efficient delivery of therapeutic agents to specific targets. In this review, we begin with the factors affecting the properties of nanostructured DNA, followed by summarizing the methods for the development of nanostructured DNA. Further, we discuss the characteristics of nanostructured DNA and their applications for the delivery of bioactive compounds.


Analysis of the Trend Over Time of High-Urgency Liver Transplantation Requests in Italy in the 4-Year Period 2014-2017.
The national protocol for the handling of high-urgency (HU) liver organ procurement for transplant is administered by the Italian National Transplant Center. In recent years, we have witnessed a change in requests to access the program. We have therefore evaluated their temporal trend, the need to change the access criteria, the percentage of transplants performed, the time of request satisfaction, and the follow-up. We analyzed all the liver requests for the HU program received during the 4-year period of 2014 to 2017 for adult recipients (≥18 years of age): all the variables linked to the recipient or to the donor and the organ transplants are registered in the Informative Transplant System as established by the law 91/99. In addition, intention to treat (ITT) survival rates were compared among 4 different groups: (1) patients on standard waiting lists vs (2) patients on urgency waiting lists, and (3) patients with a history of transplant in urgency vs (4) patients with a history of transplant not in urgency. Out of the 370 requests included in the study, 291 (78.7%) were satisfied with liver transplantation. Seventy-nine requests (21.3%) have not been processed, but if we consider only the real failures, this percentage falls to 13.1% and the percentage of satisfied requests rises to 86.9%. The average waiting period for liver transplantation (LT) is 1.7 days and most requests (74%) are met in less than 24 hours, if we consider the hours between the registration of the request and the donor reporting . The percentage of late retransplantations is 2.1%. The clinical indication for HU-LT that appears to improve over time is hepatic artery thrombosis (82.5%). The overall 1-year patient survival is 68.3%. The overall 1-year graft survival, performed on all the patients, is 89% and all the indications for HU-LT appear to go well over time with an average survival rate greater than 85%. The indications for HU-LT are changing according to the changes in the hepatologic field in recent years. The centralized management of requests has proven to be successful in optimizing responses. Urgent LT is confirmed to be lifesaving in its timeliness.


Visual perceptive skills account for very preterm children's mathematical difficulties in preschool.
Already in preschool, very preterm (VP) children perform worse than term born-children on preschool mathematical skills tests. Strong associations have been found between preschool mathematical skills, cognition and visual-motor integration. To compare VP children and their term-born peers on preschool mathematical achievement at the corrected age of five years, and determine whether cognitive, visual-perceptive, visual-motor, and motor-coordination skills, account for any significant differences observed. Single-center, consecutive cohort study with a term-born comparison group. 54 five-year-old VP children and 28 term-born comparison children. Standardized test for preschool mathematical skills (Dutch pupil monitoring system), cognitive skills (Wechsler Preschool and Primary Scale for Intelligence - third edition), visual-perception, visual-motor integration, and motor-coordination (Beery Visual-Motor Integration test - sixth edition). Group differences were analyzed with ANCOVAs, adjusting for maternal education, preschool grade, and time of assessment. Sobel's mediation analyses tested for possible mediation effects. Preschool mathematical skills and visual perceptive skills were significantly lower in VP children than in term-born children (Cohen's d = 0.63, p = 0.01; Cohen's d = 0.84, p < 0.01, respectively). Sobel's test indicated a significant mediating effect of visual perceptive skills on the association between VP birth and preschool mathematical skills. At preschool age, VP children have poorer preschool mathematical skills compared to term-born peers; deficits that were fully accounted for by poor visual perceptive skills. Our findings indicate the relevance of screening visual perceptive skills at preschool age, enabling timely identification of children at risk for mathematical difficulties.


The stroke in an emergency: the grey areas.
In spite of the development of advanced technologies, diagnosis and therapy for an ictus in emergency still pose difficulties in a significant percentage of cases. Diagnostic problems are encountered both when faced with focal symptoms and in the presence of disturbances to consciousness, confusional states, vertigo or cephalea. The most significant therapeutic problems, on the other hand, are encountered in the case of extended cardioembolic ischaemias, haemorrhages from venous thrombosis and intradural arterial dissections (eventual antithrombotic treatment), when faced with a large cerebral oedema (eventual medical and/or surgical treatment), or in indicating surgery for intraparenchymal haemorrhages or symptomatic stenotic carotids.


Arsenic triggered nano-sized uranyl arsenate precipitation on the surface of Kocuria rosea.
Arsenic (As) and uranium (U) frequently occur together naturally and, in consequence, transform into cocontaminants at sites of uranium mining and processing, yet the simultaneous interaction process of arsenic and uranium has not been well documented. In the present contribution, the influence of arsenate on the removal and reduction of uranyl by the indigenous microorganism Kocuria rosea was characterized using batch experiments combined with species distribution calculation, SEM-EDS, FTIR, XRD and XPS. The results showed that the coexistence of arsenic plays an active role in Kocuria rosea growth and the removal of uranium under neutral and slightly acidic conditions. U-As complex species of UO2HAsO4 (aq) had a positive effect on uranium removal, while Kocuria rosea cells appeared to have a large specific surface area serving as attachment sites. Furthermore, a large number of nano-sized flaky precipitates, constituted by uranium and arsenic, attached to the surface of Kocuria rosea cells at pH 5 through P=O, COO-, and C=O groups in phospholipids, polysaccharides, and proteins. The biological reduction of U(VI) and As(V) took place in a successive way, and the formation of a chadwickite-like uranyl arsenate precipitate further inhibited U(VI) reduction. The results will help to design more effective bioremediation strategies for arsenic-uranium cocontamination.


CCD Camera Detection of HIV Infection.
Rapid and precise quantification of the infectivity of HIV is important for molecular virologic studies, as well as for measuring the activities of antiviral drugs and neutralizing antibodies. An indicator cell line, a CCD camera, and image-analysis software are used to quantify HIV infectivity. The cells of the P4R5 line, which express the receptors for HIV infection as well as β-galactosidase under the control of the HIV-1 long terminal repeat, are infected with HIV and then incubated 2 days later with X-gal to stain the infected cells blue. Digital images of monolayers of the infected cells are captured using a high resolution CCD video camera and a macro video zoom lens. A software program is developed to process the images and to count the blue-stained foci of infection. The described method allows for the rapid quantification of the infected cells over a wide range of viral inocula with reproducibility, accuracy and at relatively low cost.


Successful restoration of knee extension after transferring of the anterior branch of the obturator nerve: a case study.
Objective: Femoral nerve palsy occurs after trauma, surgical procedures and tumors and leads to loss of quadriceps functions, disability and decreased quality of life. The aim of this report was to describe a successful restoration of knee extension by transferring the anterior branch of the obturator nerve to selective branches of the femoral nerve at the thigh level.Methods: We describe a 27-year-old male who had quadriceps femoris muscle paralysis after surgical evacuation for retroperitoneal hematoma five months ago. Since proximal stump of femoral nerve was not accessible, we transferred anterior branch of obturator nerve to selective branches of femoral nerve for reconstruction of quadriceps femoris muscle.Results: After four months, he regained quadriceps muscle strength M3 and began to walk. He achieved full muscle strength (M5) nine months after surgery and was able to walk up-stairs easily 14 months after surgery and atrophy of the quadriceps was improved.Conclusion: The anterior branch of the obturator nerve is an available donor nerve with an excellent functional recovery for the reconstruction of knee extension when proximal stump of femoral nerve is not reachable or the repair needs a long graft.


Clinical Importance of Main Portal Vein and Right Portal Vein Variations: A Prevalence Study With 128-Slice Multidetector Computed Tomography.
The portal vein variation type significantly affects the outcome of transplant surgery, hepatectomies, and interventional radiological procedures. To reveal variation types, especially rare types, we used high-technology multidetector computed tomography. We evaluated multiphase abdominal multidetector computed tomography scans of 278 consecutive patients. Multidetector computed tomography scans were processed for axial, coronal, and axial-oblique multiplane reformation and for maximum intensity projection. Variations of the main portal vein and right portal vein were simulta-neously analyzed by 2 radiologists. Prevalence of each variation and differences in sexes were investigated. Variant anatomy was detected in 29.5% of main portal veins and 20.9% of right portal veins. There was no statistical difference between sexes. Type 3 was reported as the most frequent variant of main portal vein, whereas type 4 was the most frequent variant of right portal vein. Some miscellaneous types were also ascertained. Different types of anatomic variations may adversely affect the course of surgery and interventional radiological procedures. Fortunately, radiologists can now discover the critical types by using the new generation multidetector computed tomography with 3-dimensional reconstruction techniques. This information should be included in the radiology reports of patients who are scheduled for major surgery.


DNA repair pathways and their roles in drug resistance for lung adenocarcinoma.
Lung cancer is the leading cancer type of death rate. The lung adenocarcinoma subtype is responsible for almost half of the total lung cancer deaths. Despite the improvements in cancer treatment in recent years, lung adenocarcinoma patients' overall survival rate remains poor. Immunetherapy and chemotherapy are two of the most widely used options for the treatment of cancer. Although many cancer types initially respond to these treatments, the development of resistance is inevitable. The rapid development of drug resistance mainly characterizes lung adenocarcinoma. Despite being the subject of many studies in recent years, the resistance initiation and progression mechanism is still unclear. In this review, we have examined the role of the primary DNA repair pathways (non-homologous end joining (NHEJ) pathway, homologous-recombinant repair (HR) pathway, base excision repair (BER) pathway, and nucleotide excision repair (NER) pathway and transactivation mechanisms of tumor protein 53 (TP53) in drug resistance development. This review suggests that mentioned pathways have essential roles in developing the resistance against chemotherapy and immunotherapy in lung adenocarcinoma patients.