Triiodothyroacetic acid-induced reversal of learned helplessness in rats.
Triiodothyronine (T3), successfully used as therapeutic agent in euthyroid depressive states, has been found to exert an antidepressant-like effect in various psychopharmacological tests in rodents. Therefore the possible antidepressant-like activity of triiodothyroacetic acid (TA3), a natural metabolite of T3, was investigated in rats subjected to helplessness training. The animals were first exposed to inescapable shock pretreatment (60 shocks, 15 s duration, 0.8 mA every min +/- 15 s) and 48 h later, shuttle-box training (30 trials/day, ITI: 30 s) was performed on 3 consecutive days in order to assess escape deficits. As compared to control rats (no shock pretreatment), the rats exposed to inescapable shocks exhibited escape deficits when tested for subsequent responding in the shuttle-box. Daily i.p. injections of TA3 (0.5 mg/kg) prevented escape deficits as did daily injections of tricyclic antidepressants. These data are in agreement with previous results bearing on the similarity of action of TA3 and tricyclic antidepressants and extend to the thyroid axis the neuroendocrine systems that can be affected by exposure to uncontrollable stressors.


Non-invasive detection of haemoglobin, platelets, and total bilirubin using hyperspectral cameras.
Hyperspectral imaging has emerged as a promising high-resolution and real-time imaging technology with potential applications in medical diagnostics and surgical guidance. In this study, we developed a high-speed hyperspectral camera by integrating a Fabry-Perot cavity filter on each CMOS pixel. We used it to non-invasively detect three blood components (haemoglobin, platelet, and total bilirubin). Specifically, we acquired transmission images of the subject's fingers, extracted spectral signals at each wavelength, and used dynamic spectroscopy to obtain non-invasive blood absorption spectra. The prediction models were established using the PLSR method and were modelled and validated based on the standard clinical-biochemical test values. The experimental results demonstrated excellent performance. The best predictions were obtained for haemoglobin, with a high related coefficient (R) of 0.85 or more in both the calibration and prediction sets and a mean absolute percentage error (MAPE) of only 5.7%. The results for total bilirubin were also ideal, with R values exceeding 0.8 in both sets and a MAPE of 10.6%. Although the prediction results for platelets were slightly less satisfactory, the error was still less than 15%, indicating that the results were also acceptable. Overall, our study highlights the potential of hyperspectral imaging technology for the development of portable and affordable devices for blood analysis, which can be used in various settings.


Radioimmunoassay for human pancreatic amylase: comparison of human serum amylase by measurement of enzymatic activity and by radioimmunoassay.
A radioimmunoassay (RIA) for human pancreatic amylase has been developed for the determination of human serum amylase content. The assay was shown to be sensitive (7 ng/ml), reproducible and specific, but human pancreatic amylase and salivary amylase could not be distinguished by the antiserum used. In normal subjects, the mean concentration of amylase determined by the RIA was found to be 122.1 ng/ml (range: 55--250 ng/ml). A good correlation was observed between the concentration of amylase and its enzymatic activity in normal subjects. In some instances with high amylase activity, however, the rise in enzymatic activity was not accompanied by increasing amount of amylase content.


Laparoscopic repair of vesicouterine fistula--a case report.
We report the technique of laparoscopic repair of vesicouterine fistula. A 30 year old lady presented with incapacitating cyclical pain for one and a half years. She had undergone cesarean section 18 months ago. She was evaluated by a CT scan of abdomen and pelvis followed by a cystoscopy and diagnosed to have a vesicouterine fistula. This was managed laparoscopically (laparoscopic disconnection of fistula; closure of bladder and uterine rent; and omental interposition). There were no intraoperative or postoperative complications. Follow up CT scan of abdomen and cystoscopy revealed good healing of the repaired area. Laparoscopic repair of vesicouterine fistula is a feasible procedure.


In Vitro and In Vivo Pretreatment with Selenium Mitigates Tetrahydrocannabinol-Induced Testicular Cell Apoptosis: the Role of AKT and p53 Pathways.
Exocannabinoids such as tetrahydrocannabinol (THC) may alter the physiological function of endocannabinoids in male reproduction and thus affect male fertility. This study aimed to investigate the apoptotic effects of THC via mechanisms related to p53 and AKT signaling pathways on Sertoli cells and seminiferous germinal cells, as well as the possible protective role of selenium pretreatment in both in vitro and in vivo models. The Mus musculus Sertoli cell line, TM4, was used for in vitro experiments. The TM4 cells were cultured and exposed to selenium (2 μM, 48 h) and THC (470 μM, 24 h). The MTT test was performed to evaluate cell viability. Fifteen male Wistar rats (220 ± 20 g) were used for in vivo experiments and divided into three groups: (1) control, (2) tetrahydrocannabinol (THC, 5 mg/kg, dissolved in DMSO 5%, i.p., for 21 consecutive days), and (3) THC + selenium (selenium, 0.5 mg/kg per day, i.p.). At the end of the experiments, Sertoli cells and testis tissue samples were collected for biochemical (AKT, P53), cell apoptosis, and histological analyses. The results of the in vitro study revealed that THC significantly decreases the cell viability (p < 0.001) and expression of the p-AKt protein (p < 0.05) and increases Sertoli cells' apoptosis (p < 0.001) and p53 protein expression (p < 0.001). The in vivo effects of THC were in line with the in vitro results. Pretreatment with selenium (as sodium selenite) significantly decreased the THC-induced Sertoli cell and testicular tissue damages in the rats. Pathological changes were significantly alleviated in the selenium-pretreated rats. Collectively, these data suggest that pretreatment with selenium is able to protect against THC-induced testicular cell damage. The attenuating effect of selenium may be due to its anti-apoptotic activity through the p53 and AKT modulation.


Polar lipid composition of mammalian hair.
The types and amounts of polar lipids from the hair of monkey (Macacca fascicularis), dog (Canis familiaris), pig (Sus scrofa) and porcupine (Erethizon dorsatum) have been determined by quantitative thin-layer chromatography. The polar lipid content of the hair samples ranged from 0.6 to 1.6 wt%. Lipid compositions included ceramides (57-63% of the polar lipid by weight), glycosphingolipids (7-9%) and cholesteryl sulfate (22-29%). Several minor components (4-7%) remain unidentified. The results suggest that cholesteryl sulfate may be an important determinant of the cohesiveness of hair.


A novel nomogram to predict mortality in patients with stroke: a survival analysis based on the MIMIC-III clinical database.
Stroke is a disease characterized by sudden cerebral ischemia and is the second leading cause of death worldwide. We aimed to develop and validate a nomogram model to predict mortality in intensive care unit patients with stroke. All data involved in this study were extracted from the Medical Information Mart for Intensive Care III database (MIMIC-III). The data were analyzed using multivariate Cox regression, and the performance of the novel nomogram, which assessed the patient's overall survival at 30, 180, and 360 days after stroke, was evaluated using Harrell's concordance index (C-index) and the area under the receiver operating characteristic curve. A calibration curve and decision curve were introduced to test the clinical value and effectiveness of our prediction model. A total of 767 patients with stroke were randomly divided into derivation (n = 536) and validation (n = 231) cohorts at a 7:3 ratio. Multivariate Cox regression showed that 12 independent predictors, including age, weight, ventilation, cardiac arrhythmia, metastatic cancer, explicit sepsis, Oxford Acute Severity of Illness Score or OASIS score, diastolic blood pressure, bicarbonate, chloride, red blood cell and white blood cell counts, played a significant role in the survival of individuals with stroke. The nomogram model was validated based on the C-indices, calibration plots, and decision curve analysis results. The plotted nomogram accurately predicted stroke outcomes and, thus may contribute to clinical decision-making and treatment as well as consultation services for patients.


What can be learned from the literature about intervals and strategies for paediatric CPR retraining of healthcare professionals? A scoping review of literature.
Effective training and retraining may be key to good quality paediatric cardiopulmonary resuscitation (pCPR). PCPR skills decay within months after training, making the current retraining intervals ineffective. Establishing an effective retraining strategy is fundamental to improve quality of performance and potentially enhance patient outcomes. To investigate the intervals and strategies of formal paediatric resuscitation retraining provided to healthcare professionals, and the associated outcomes including patient outcomes, quality of performance, retention of knowledge and skills and rescuer's confidence. This review was drafted and reported using the Preferred Reporting Items for Systematic Reviews and Meta-analysis extension for Scoping Reviews (PRISMA-ScR). PubMed, Medline, Cochrane, Embase, CINAHL Complete, ERIC and Web of Science were searched and studies addressing the PICOST question were selected. The results indicate complex data due to significant heterogeneity among study findings in relation to study design, retraining strategies, outcome measures and length of intervention. Out of 4706 studies identified, 21 were included with most of them opting for monthly or more frequent retraining sessions. The length of intervention ranged from 2-minutes up to 3.5 hours, with most studies selecting shorter durations (<1h). All studies pointed to the importance of regular retraining sessions for acquisition and retention of pCPR skills. Brief and frequent pCPR retraining may result in more successful skill retention and consequent higher-quality performance. There is no strong evidence regarding the ideal retraining schedule however, with as little as two minutes of refresher training every month, there is the potential to increase pCPR performance and retain the skills for longer.


Tumor-induced osteomalacia: long-term follow-up of two patients cured by removal of their tumors.
Two patients with mesenchymal tumors had osteomalacia associated with marked hypophosphatemia and renal phosphate wasting. Their serum calcium and parathyroid hormone levels were normal. The first patient also had aminoaciduria and glucosuria in addition to phosphaturia. Both patients were treated with very large doses of vitamin D2 and phosphate without improvement in the osteomalacia or normalization of the serum phosphate. Complete removal of a low-grade fibrosarcoma in the second patient and removal of an ossifying fibroma in the first patient resulted in a cure in both patients despite no further therapy with vitamin D or phosphate. The excessive aminoaciduria and glucosuria of the first patient also remitted. During a 14-year follow-up period, there has been no evidence of tumor recurrence, hypophosphatemia, or osteomalacia in either patient. The levels of 1,25-dihydroxycholecalciferol remain within the normal range in both patients.


Infliximab Rescue Therapy in Pediatric Severe Colitis.
Clinical remission has been achieved with infliximab in patients with refractory ulcerative colitis (UC). However, there is conflicting data regarding its effectiveness as rescue therapy in adult acute severe colitis. Furthermore, pediatric inflammatory bowel disease (IBD) is associated with more severe disease that may be less amenable to attempted rescue. We reviewed our experience and outcomes with pediatric severe colitis after attempted inpatient rescue with infliximab. A single-institution, retrospective review was conducted of pediatric patients with UC or indeterminate colitis who received inpatient rescue infliximab therapy from 1/2000 to 1/2019. Rescue infliximab therapy was considered if a child failed non-biologic therapy or progressed to fulminant or toxic colitis. Primary outcome was failed therapy resulting in colectomy. A p-value of <0.05 determined significance. Thirty patients met inclusion criteria. The median age at administration of rescue infliximab treatment was 14 years [IQR 13,17]. Rescue therapy with infliximab was successful in 33% (n = 10), while 67% (n = 20) underwent colectomy. Children on maintenance steroids were less likely to be successfully rescued with infliximab and require colectomy (p = 0.03). Children requiring colectomy had a longer hospital stay (p = 0.03), more abdominal radiographs (p = 0.01), and were on a longer duration of antibiotics (p = <0.01) compared to children who were successfully rescued with infliximab. There was no difference in baseline vital signs or laboratory abnormalities between the two groups. In severe acute ulcerative or indeterminate colitis cases where infliximab has not been previously used, rescue infliximab can be used to avoid colectomy but has a high failure rate. IV. Retrospective study.


Very rapid amyloid fibril formation by a bacterial lipase in the absence of a detectable lag phase.
The conversion of proteins from their soluble states into well-organized amyloid fibrils has received abundant attention. This process typically consists of three stages: lag, growth and plateau phases. In this study, the process of amyloid fibril formation by lipase from Pseudomonas sp. after diluting out urea was examined by Thioflavin T (ThT) fluorescence, Congo red (CR) binding, 8-anilinonaphthalene-1-sulfonic acid (ANS) binding, dynamic light scattering (DLS), circular dichroism (CD) and Fourier transform infrared (FTIR) spectroscopies, X-ray diffraction (XRD) and transmission electron microscopy (TEM). To exclude the presence of preformed aggregates in the pure lipase sample, aforementioned assays were also performed for the protein unfolded in urea before dilution. The aggregates formed immediately after dilution were found to bind to ThT and CR and contain a significant amount of β-sheet structure, as determined by far-UV CD and FTIR spectroscopies, as well as XRD analysis. Moreover, these aggregates present, at least in part, a fibrillar morphology, as deduced with TEM. This examination showed that lipase fibril formation proceeds quickly after dilution, within a few seconds, without a detectable lag phase. We also investigated bacterial inclusion bodies formed after expression of lipase in E. coli, providing evidence for the existence of rapidly formed amyloid-like structural and tinctorial properties in the lipase-containing inclusion bodies.


Treatment of the elderly brain-injured patient. Experience in a traumatic brain injury unit.
Recovery from traumatic brain injury in the elderly is a subject rarely discussed in the medical literature, and existing data is conflicting. The Traumatic Brain Injury Unit at Gaylord Hospital routinely admits patients over 50 years of age for rehabilitation after significant closed head injury. Of the 26 elderly head-injured patients reviewed over a four-year period for this study, 85% eventually returned to a home setting, with more than half independent in activities of daily living. Based on this encouraging data, it is suggested that the older head-injured patient can recover from severe closed head injury.


Changing Fields-Diabetes Medications Invading the Cardiovascular Space.
Cardiovascular disease (CVD) remains the leading cause of mortality in patients with type 2 diabetes, and treatment strategies that impact cardiovascular (CV) outcomes in this population is an area of growing interest. Pharmacologic agents that reduce CVD risk have been developed, and data supporting their use have grown extensively. Glucagon-like peptide 1 agonists and sodium-glucose cotransporter 2 inhibitors when added to metformin therapy provide the most CV benefit and should be considered in most patients. Data available suggest that sulfonylureas should be avoided in patients at risk for CVD and if a thiazolidinedione is utilized, pioglitazone may be preferred. When selecting an agent, the potential benefit, risk, and cost of each agent should be considered prior to initiation. The purpose of this review is to summarize the literature surrounding the CV effects of antidiabetic agents and to provide practical guidance on their use in patients with type 2 diabetes and CVD.


Enrichment of AOB and NOB Population by Applying a BABE Reactor in an Activated Sludge Pilot Plant.
This paper deals with the effect of a bioaugmentation batch enhanced (BABE) reactor implementation in a biological nutrient removal pilot plant on the populations of ammonia-oxidizing bacteria (AOB) and nitrite-oxidizing bacteria (NOB). The results of fluorescence in situ hybridization (FISH) technique showed that AOB and NOB populations were significantly enhanced, from 4 to 8% and from 2 to 9%, respectively, as a result of the BABE reactor implementation. Regarding AOB, the percentage of Nitrosomonas oligotropha was mainly increased (3 to 6%). Regarding NOB, Nitrospirae spp was greatly enhanced (1 to 7%). Both species are considered K-strategist (high affinity to the substrate, low maximum growth rates) and they usually predominate in reactors with low ammonium and nitrite concentrations, respectively.


Differentiation of angiogenic burden in human cancer xenografts using a perfusion-type optical contrast agent (SIDAG).
Use of fluorescence imaging in oncology is evolving rapidly, and nontargeted fluorochromes are currently being investigated for clinical application. Here, we investigated whether the degree of tumour angiogenesis can be assessed in vivo by planar and tomographic methods using the perfusion-type cyanine dye SIDAG (1,1'-bis- [4-sulfobutyl]indotricarbocyanine-5,5'-dicarboxylic acid diglucamide monosodium). Mice were xenografted with moderately (MCF7, DU4475) or highly vascularized (HT1080, MDA-MB435) tumours and scanned up to 24 hours after intravenous SIDAG injection using fluorescence reflectance imaging. Contrast-to-noise ratio was calculated for all tumours, and fluorochrome accumulation was quantified using fluorescence-mediated tomography. The vascular volume fraction of the xenografts, serving as a surrogate marker for angiogenesis, was measured using magnetic resonance imaging, and blood vessel profile (BVP) density and vascular endothelial growth factor expression were determined. SIDAG accumulation correlated well with angiogenic burden, with maximum contrast to noise ratio for MDA-MB435 (P < 0.0001), followed by HT1080, MCF7 and DU4475 tumours. Fluorescence-mediated tomography revealed 4.6-fold higher fluorochrome concentrations in MDA-MB435 than in DU4475 tumours (229 +/- 90 nmol/l versus 49 +/- 22 nmol/l; P < 0.05). The vascular volume fraction was 4.5-fold (3.58 +/- 0.9% versus 0.8 +/- 0.53%; P < 0.01), blood vessel profile density 5-fold (399 +/- 36 BVPs/mm2 versus 78 +/- 16 BVPs/mm2) and vascular endothelial growth factor expression 4-fold higher for MDA-MB435 than for DU4475 tumours. Our data suggest that perfusion-type cyanine dyes allow assessment of angiogenesis in vivo using planar or tomographic imaging technology. They may thus facilitate characterization of solid tumours.


Regulation of abalone sperm cyclic AMP concentrations and the acrosome reaction by calcium and methylxanthines.
When Ca2+ is added to abalone sperm (Haliotis rufescens) in Ca2+-free artificial seawater (CaFASW) to a final concentration of 9.6 mM a 4-fold elevation in sperm cAMP occurs within 15-30 sec. The methylxanthines, theophylline and 1-methyl-3-isobutylxanthine (MIX), also elevate sperm cAMP concentrations. In CaFASW, either compound causes up to a 3-fold increase in cAMP within 15-30 sec. MIX (150 microM), added to sperm in the presence of 9.6 mM Ca2+, elevates sperm cAMP 100-fold within 15-30 sec and also triggers the acrosome reaction (AR) in the same period. Under identical conditions theophylline (1.67 mM) is much less potent at elevating cAMP and inducing the AR. The effects of methylxanthines on cAMP of sperm incubated in the presence of Ca2+ appear to represent a potentiation by these compounds of the action of Ca2+. Neither compound induces the AR in the absence of Ca2+. All of the observed effects on sperm cAMP and the AR are dependent on Ca2+ and methylxanthine concentrations. Added cyclic nucleotides or their derivatives do not induce the AR in either the absence or presence of Ca2+. Experiments with isolated sperm heads and flagella indicate that the dramatic stimulatory response of sperm cAMP to Ca2+ plus MIX is present in the head region (acrosome, nucleus, midpiece) of the cell. The data suggest that the dramatic elevation of cAMP by MIX in the presence of Ca2+ may occur directly by an inhibition of phosphodiesterase activity and indirectly by an increase in cellular Ca2+. A strong temporal correlation between the cAMP elevation and the abalone AR exists, although cAMP elevation by itself does not act as the primary mediator of this exocytotic event.


Nursing resource team capacity planning using forecasting and optimization methods: A case study.
To estimate the cost-minimizing size and skill mix of a nursing resource team (NRT). Nurse absences can be filled by an NRT at lower hourly cost than staffing agencies or nurses working overtime, but an NRT must be appropriately sized to minimize total cost. Using all registered nurse (RN) absences at an academic teaching hospital from 1 October 2014 to 31 March 2018, we developed a generalized additive model (GAM) to forecast the weekly frequency of each of ten types of absence over 52 weeks. We used the forecasts in an optimization model to determine the cost-minimizing NRT composition. The median weekly frequencies for the ten absence types ranged between 12 and 65.5. The root mean squared errors of the GAMs ranged between 4.55 and 9.07 on test data. The NRT dimensioned by the optimization model yields an estimated annual cost reduction of $277,683 (Canadian dollars) (7%). The frequency of RN absences in a hospital can be forecasted with high accuracy, and the use of forecasting and optimization to dimension an NRT can substantially reduce the cost of filling RN absences. This methodology can be adapted by any hospital to optimize nurse staffing.


Sarcopenia is as common in older patients with dementia with Lewy bodies as it is in those with Alzheimer's disease.
Alzheimer's disease (AD) and dementia with Lewy body (DLB) constitute the most common types of dementia, and are two common geriatric syndromes; however, sarcopenia has not been elaborately evaluated in DLB so far. Therefore, this study aimed to investigate the relationship between sarcopenia and DLB in older adults. In this retrospective and cross-sectional study, 662 participants, who were followed in a memory clinic at the Geriatrics department of a university hospital, were included. Comprehensive Geriatric Assessment, including the activities of daily living, malnutrition and malnutrition risk, frailty, cognition, and sarcopenia were assessed. Sarcopenia was defined according to the revised European Working Group on Sarcopenia in Older People-2 criteria. A total of 662 participants (461 healthy controls, 133 with AD and 68 with DLB) with a mean age of 73.60 ± 7.50 years were included. The prevalence of probable sarcopenia and sarcopenia was 53.4% and 19.5%, respectively, in patients with AD, whereas it was 55.9% and 19.1%, respectively, in patients with DLB. After adjustment analyses, probable sarcopenia, sarcopenia and low muscle mass were related to AD (P < 0.001, P = 0.001, P < 0.001, respectively). Probable sarcopenia and slow gait speed were associated with DLB (P < 0.01, P < 0.001, respectively). Sarcopenia is common in patients with DLB and in those with AD, and seems to be closely related to low muscle strength and slow gait speed in DLB patients. Considering sarcopenia-related negative health outcomes in older adults, the evaluation of sarcopenia, therefore, should also be among the follow-up and treatment goals of DLB patients. Geriatr Gerontol Int 2022; 22: 418-424.


Improving Patients' Life Quality after Radiotherapy Treatment by Predicting Late Toxicities.
Personalized treatment and precision medicine have become the new standard of care in oncology and radiotherapy. Because treatment outcomes have considerably improved over the last few years, permanent side-effects are becoming an increasingly significant issue for cancer survivors. Five to ten percent of patients will develop severe late toxicity after radiotherapy. Identifying these patients before treatment start would allow for treatment adaptation to minimize definitive side effects that could impair their long-term quality of life. Over the last decades, several tests and biomarkers have been developed to identify these patients. However, out of these, only the Radiation-Induced Lymphocyte Apoptosis (RILA) assay has been prospectively validated in multi-center cohorts. This test, based on a simple blood draught, has been shown to be correlated with late radiation-induced toxicity in breast, prostate, cervical and head and neck cancer. It could therefore greatly improve decision making in precision radiation oncology. This literature review summarizes the development and bases of this assay, as well as its clinical results and compares its results to the other available assays.


Cell culture purity issues and DFAT cells.
Dedifferentiation of mature adipocytes, in vitro, has been pursued/documented for over forty years. The subsequent progeny cells are named dedifferentiated adipocyte-derived progeny cells (DFAT cells). DFAT cells are proliferative and likely to possess mutilineage potential. As a consequence, DFAT cells and their progeny/daughter cells may be useful as a potential tool for various aspects of tissue engineering and as potential vectors for the alleviation of several disease states. Publications in this area have been increasing annually, but the purity of the initial culture of mature adipocytes has seldom been documented. Consequently, it is not always clear whether DFAT cells are derived from dedifferentiated mature (lipid filled) adipocytes or from contaminating cells that reside in an impure culture.


Free surface entrainment of oxide particles and their role in ultrasonic treatment performance of aluminum alloys.
Although the ultrasonic treatment of molten aluminum has been studied for long period, there is still much to be revealed for this process. Many studies have focused on the investigation of acoustic cavitation and streaming under the horn tip and their effects on the treatment efficiency. However, to the best of our knowledge, no attempt has been done to explain phenomena occurring near or on the melt free surface. Thus, the goal of this study is to investigate phenomena occurring at the free surface during ultrasound irradiation and clarify their possible influence on the ultrasound treatment performance. The results of high temperature and water model experiments reveal that ultrasound irradiation significantly promotes the formation of alumina particles on the melt free surface around sonotrode, and part of these particles can be entrained into aluminum melts. Furthermore, TEM observation results suggested that the entrained alumina inclusions can serve as nucleation sites for the primary Al3Zr compounds. Most importantly, the oxidation and entrainment of particles from free surface are likely to be controllable by the immersion depth of sonotrode into molten aluminum.


Secretory phospholipase A2 inhibitors and calmodulin antagonists as inhibitors of cytosolic phospholipase A2.
Human cytosolic phospholipase A2 (cPLA2, 85 kDa) appears to be pharmacologically distinct from human secretory phospholipase A2 (sPLA2, 14 kDa). Marine natural products and PLA2 substrate and product analogs were potent inhibitors of human recombinant sPLA2 (r-sPLA2), whereas these compounds stimulated, weakly inhibited, or had no effect on cPLA2 activity from the human monocytic cell line U937. In contrast, within a series of seven reported calmodulin (CaM) antagonists tested, significant correlations among the rank order of potencies of these compounds as inhibitors of cPLA2, r-sPLA2, and a CaM-dependent phosphodiesterase were observed. The correlated inhibitory effects of the hydrophobic CaM antagonists on cPLA2 and sPLA2 may reflect a common feature (possibly a hydrophobic domain) shared by these two types of enzymes.


ALIMUS-We are feeding! Study protocol of a multi-center, cluster-randomized controlled trial on the effects of a home garden and nutrition counseling intervention to reduce child undernutrition in rural Burkina Faso and Kenya.
Climate change heavily affects child nutritional status in sub-Saharan Africa. Agricultural and dietary diversification are promising tools to balance agricultural yield losses and nutrient deficits in crops. However, rigorous impact evaluation of such adaptation strategies is lacking. This project will determine the potential of an integrated home gardening and nutrition counseling program as one possible climate change adaptation strategy to improve child health in rural Burkina Faso and Kenya. Based on careful co-design with stakeholders and beneficiaries, we conduct a multi-center, cluster-randomized controlled trial with 2 × 600 households in North-Western Burkina Faso and in South-Eastern Kenya. We recruit households with children at the age of complementary feed introduction (6-24 months) and with access to water sources. The intervention comprises the bio-diversification of horticultural home gardens and nutritional health counseling, using the 7 Essential Nutrition Action messages by the World Health Organization. After 12-months of follow-up, we will determine the intervention effect on the primary health outcome height-for-age z-score, using multi-level mixed models in an intention-to-treat approach. Secondary outcomes comprise other anthropometric indices, iron and zinc status, dietary behavior, malaria indicators, and household socioeconomic status. This project will establish the potential of a home gardening and nutrition counseling program to counteract climate change-related quantitative and qualitative agricultural losses, thereby improving the nutritional status among young children in rural sub-Saharan Africa. German Clinical Trials Register (DRKS) DRKS00019076 . Registered on 27 July 2021.


Application of Bacillus mucilaginosus in the carbonation of steel slag.
The stacking of steel slag has detrimental effects mainly for the waste of resources and the pollution of environment. In this study, a novel method based on microbially induced calcium precipitation (MICP) was proposed by utilizing a type of microorganism named Bacillus mucilaginosus, which could secrete carbonic anhydrase (CA) through the metabolism process, accelerating the hydration of carbon dioxide (CO2) and thus facilitating the formation of carbonate ions (CO32-). First, comparing the biologically deposited calcium carbonate with the chemically deposited one, it was found that the crystallinity and crystal size of the biological deposition was lower, leading to its cementitious properties. Under the condition of 1 wt. (weight) % dosage, the carbonation degree increased from 66.34 to 86.25% and the compressive strength improved greatly from 7.4 to 11.2 MPa as well. The weight gain rate of biologically carbonated specimens was also twice as much as the directly carbonated ones. This work strongly demonstrated that biological carbonation technology could not only improve the CO2 sequestration potential of steel slag but also enhance the mechanical properties and durability of steel slag products. KEY POINTS: • Bacillus mucilaginosus could resuscitate and proliferate in the steel slag environment. • B. mucilaginosus secreted carbon anhydrase, which could accelerate the hydration of CO2 and facilitate the precipitation of calcium carbonate. • Biologically carbonated steel slag had greater mechanical performance than directly carbonated one.


Indicators for lack of systemic availability of organic pigments.
Experimental data of all 143 organic pigments registered with the European Chemicals Agency, of which 88 were listed in a nanomaterial inventory, was retrieved from the registered substance fact sheets. Availability of the data was 93% for solubility, 82% for bacterial mutagenicity, 79% for acute oral toxicity, 75% for irritation, 59% for skin sensitisation, 36% for repeated dose toxicity and 34% for each clastogenicity and mutagenicity in mammalian cells and 23% for toxicity to reproduction. Pigments mostly had a water and octanol solubility of significantly below 0.1 mg/L, but fourteen were found to be of higher solubility. None were irritating to skin and eyes. Except for the metal salt and the β-naphthol pigments, none of the insoluble pigments showed adverse effects up to limit doses indicating that poor solubility prevents systemic uptake of toxicologically relevant amounts. The few available toxicokinetic data shows absence of metabolism or significant uptake and is in support of this. Occasional effects observed on bacterial mutagenicity and skin sensitisation are attributed to impurities. There is no indication that for organic pigments other particle characteristics such as surface area or morphology have an impact on the investigated toxicological endpoints.


Physiological responses of Uroleucon jaceae (L.) to seasonal changes in the quality of its host plant Centaurea jacea L.: multilevel control of adaptations to the life cycle of the host.
Exploiters of short-lived plants have evolved strategies in response to physiological changes that occur during the development of their hosts. The ability to adapt to host quality changes is necessary particularly if the mobility of an animal is poor or risk-constrained. In the plant-aphid system Centaurea jaceae-Uroleucon jaceae, the responses of the aphid to the seasonal changes in its host plant grown in poor and good quality soil were investigated. Coarse- and fine-tuned physiological reactions were observed in discrete aphid generations which were reared on plants grown either in a growth chamber or in a greenhouse. The number of ovarioles and developmental time depended on extrinsic factors (length of photoperiod) not directly related to plant quality. The reproductive investment of the aphids was also independent of their total dry weight. However, within the gonadal system high correlations were found at the embryonic level (e.g. the number of sclerotized embryos or the length of the oldest embryos per ovariole were highly correlated with gonadal dry weight). Aphids which were living on the 4-leaf stage of high-quality host plants showed a significantly higher investment in their gonads than aphids feeding on senescenting hosts. Factor analysis corroborated that aphids reared on poor-quality hosts revealed no grouping of variables measured, whereas those which were reared on high-quality plants showed clustering in respect of somatic (tibia length, dry weight of soma) and gonadal (number of sclerotized and unsclerotized embryos, length of the oldest embryos, ovariole number, gonad dry weight) factors. Three different levels of adaptive response to plant quality are distinguished: individual response to host quality, maternal influences on offspring and response to changes not specific to habitat (photoperiod). These different levels of regulation are thought to enable the aphids to adapt to a host of a given nutritional quality and anticipate deteriorating habitat quality simultaneously. It is concluded that physiological constraints in aphids are only revealed when aphids are exposed to severe nutritional stress for several generations.


A phase response curve for the locomotor activity rhythm of the rat.
A phase response curve was obtained for the locomotor activity rhythm of the rat. Mus norvegicus albicus, by interrupting a free-running rhythm with light signals of short duration. The response curve obtained was continuous and had the switch-over point at the position of 2 h before the acrophase, followed by the portion of advancing phase shift. The pattern of the curve was typical for the nocturnal rodent.


Eosinophilic fungal rhinosinusitis (EFRS): a distinct CT/MRI-entity? A European experience.
To determine the value of radiological features in the diagnosis of Eosinophilic Fungal Rhinosinusitis (EFRS). Retrospective review of the radiological materials of 65 patients with documented Eosinophilic Fungal Rhinosinusitis treated at the same institution. Evaluation by the ENT surgeon and the head and neck radiologist. EFRS was more common in female patients in this series. Fifty-four (83%) patients were above 30 years of age, with a peak of 18 patients (27.7%) in the seventh decade. All the patients except one (98.5%) showed bilateral mucosal thickening on unenhanced CT scans. Thirty-eight patients (58%) showed increased intrasinus attenuation on unenhanced CT scans. Thirty-seven patients (57%) showed opacification of at least one sinus; 25 (38%) showed osteitis; 11 (17%) had erosion of the sinus wall and only one patient showed minor expansion of an involved sinus. In 6 patients, typical hyperattenuation patterns on CT scans, together with distinctive MRI images, were highly suggestive of EFRS. Our data show that hyperattenuation on CT images with bone window settings suggests the presence of EFRS. This hyperattenuation is more clearly seen with soft-tissue window settings. When necessary, adjunctive MRI can provide information which might be highly predictive for the diagnosis of EFRS. However, non-specific imaging findings of chronic rhinosinusitis (CRS) should also be seen as possible EFRS pathology.


Exploration of the parameters affecting the radioactive europium removal from aqueous solutions by activated carbon-epoxy composite.
Adsorption of radioactive europium from aqueous solution was achieved using activated carbon - epoxy composite. The preparation of activated carbon - epoxy composite was reported using gamma radiation. The ratio of the activated carbon: epoxy was 50:50 Wt %. Irradiation of the mixture by the dose 20 KGy in gamma cell was performed. The physicochemical properties of the prepared composite were investigated by using different analytical techniques. The obtained results were analyzed using different kinetic models. The sorption kinetic process fitted with the pseudo-second-order model preferably than the pseudo-first-order model. The sorption mechanism was achieved by multi-diffusion steps comprising both film and intra-particle diffusion. The monolayer capacity of the composite was 297.62 mg/g. The thermodynamic parameters were studied. The negative value of ΔG0 and the positive value of ΔH0 revealed the spontaneous and endothermic nature of the sorption process.


Selective transport of copper(II) ions across a liquid membrane mediated by Piroxicam.
Piroxicam was found to be a highly selective carrier for uphill transport of Cu2+ ions through a chloroform liquid membrane. The transport occurs via a counterflow of protons from the receiving phase to the source phase. The effects of several parameters on the transport of Cu2+ ions, such as the carrier concentration, pH of the source phase, composition of the receiving phase, and duration are described. A high transport efficiency (98+/-2%) was provided by the carrier for Cu2+ ions in a receiving phase of 0.01 mol l(-1) sulfuric acid after 4 h. Different metal ion transport experiments showed that Cu2+ ions were selectively transported over other ions, such as Co2+, Ni2+, Cd2+, Pb2+, Zn2+, UO2(2+) and ZrO2(2+) . In the presence of fluoride ions (used as a suitable masking agent in the source phase), the interfering effects of UO2(2+) and ZrO2(2+) ions were eliminated. The applicability of the method was tested on a real sample, and the results obtained show that it is potentially useful for solvent extraction of copper.


Artificial hand illusions dynamics: Onset and fading of static rubber and virtual moving hand illusions.
The aim of this study was to investigate the temporal dynamics of two multisensory body illusions: a static rubber hand illusion (RHI) and a moving virtual hand illusion (VHI). We explored the onset and fading of these illusions. A sense of ownership questionnaire and proprioceptive drift were used for illusion estimation. Novel kinematic analysis was applied for the VHI. Positive dynamics of ownership were found in the RHI but not in the VHI. The general dynamics of proprioceptive drift were similar in both illusions: during the onset phase of artificial hand representation proprioceptive drift gradually increased, and during the fading phase - it gradually decreased. Kinematic analysis of the VHI revealed several motion features (such as jerk, smoothness, velocity), predicted illusion measures, and probably reflected that participants with higher motor abilities and better adaptation to new sensory conditions may have better multisensory integration mechanisms that are responsible for the ownership illusion.


Vascular endothelial growth factor (VEGF-a) in Fabry disease: association with cutaneous and systemic manifestations with vascular involvement.
Fabry disease is an X-linked inherited metabolic disorder characterized by the deficiency of lysosomal α-galactosidase A enzyme. This leads to the accumulation, into lysosomes through the body, of glycosphingolipids, mainly Gb3. Skin involvement and progressive multi-organ failure are usually observed. Endothelium is the preferential target of the Gb3 storage that determines endothelial dysfunction and vasculopathy leading to the clinical manifestations of the disease. The serum levels of Vascular Endothelial Growth Factor-A (VEGF-A), a specific endothelial cell mitogen, were analyzed in Fabry patients to explore a possible association to the clinical manifestations with vascular involvement. Thirty-five patients with a biochemical and genetic diagnosis of Fabry disease, along with an age-gender-matched healthy control group, were enrolled. Serum samples were collected and analyzed by ELISA. The genetic mutations, the specific organ dysfunction, and the cardiovascular risk factors such as dyslipidaemia, diabetes, smoking habits and hypertension were evaluated in Fabry patients. The mean serum level of VEGF-A in Fabry patients group was significantly higher than in the control group (P=0.006). A statistical significant association, between VEGF-A levels and the skin manifestation including angiokeratomas, sweating abnormalities and Fabry Facies was found. An association was also found between high VEGF-A and specific GLA mutations, the male gender, the renal and neurological manifestations, the presence of eye vessels tortuosity, smoking habit and hypertension. We detected increased VEGF-A levels in patients with Fabry disease compared to the controls, and we hypothesized that this could be a response to the vascular damage characterising this lysosomal disorder. However, further studies are necessary to clarify the role of VEGF-A in Fabry.


Influence of feeding on metabolite excretion evidenced by urine 1H NMR spectral profiles: a comparison between subjects living in Rome and subjects living at arctic latitudes (Svaldbard).
Urines from 25 normal subjects living in Rome and 25 normal subjects living in Ny-Alesund (Svaldbard) were analysed by 1HNMR spectroscopy. The observed differences in the concentration of the major metabolites were correlated to the composition of the diet. It was found that a diet rich of carbohydrates, such as the Italian diet, is responsible for an increased excretion of citrate, lactate, alanine, and glycine. Thus, a correct diagnostical interpretation of urinary metabolites needs to consider feeding habits.


Resectability of Pancreatic Cancer Is in the Eye of the Observer: A Multicenter, Blinded, Prospective Assessment of Interobserver Agreement on NCCN Resectability Status Criteria.
To determine the reproducibility of the National Comprehensive Cancer Network (NCCN) resectability status classification for pancreatic cancer. The NCCN classification defines 3 resectability classes (resectable, borderline resectable, locally advanced), according to vascular invasion. It is used to recommend different approaches and stratify patients during clinical trials. Prospective, multicenter, observational study (trial ID: NCT03673423). Main outcome measure was the interobserver agreement of tumor assignment to different resectability classes and quantification of vascular invasion degrees. Agreement was measured by Fleiss' k (k = 1 perfect agreement; k = 0 agreement by chance). Sixty-nine computed tomography (CT) scans of pathologically confirmed pancreatic adenocarcinoma were independently reviewed in a blinded fashion by 22 observers from 11 hospitals (11 surgeons and 11 radiologists). Rating differences between surgeons or radiologists and between hospitals with different volumes (≥60 or <60 resections/year) were assessed. Complete agreement among 22 observers was recorded in 5 CT scans (7.2%), whereas 25 CT scans (36.2%) were variously assigned to all 3 resectability classes. Interobserver agreement varied from fair to moderate (Fleiss' k range: 0.282-0.555), with the lowest agreement for borderline resectable tumors. Assessing vascular contact ≤180° had the lowest agreement for all vessels (k range: 0.196-0.362). The highest concordance was recorded for venous invasion >180° (k range: 0.619-0.756). Neither reviewers' specialty nor hospital volume influenced the agreement. There is high variability in the assignment to resectability categories, which may compromise the reliability of treatments recommendations and the evidence of trials stratifying patients in resectability classes. Criteria should be revised to allow a reproducible classification.


Germ cell apoptosis control during spermatogenesis.
The aim of the present study was to investigate the expression and role of c-Flip long isoform (c-FlipL), a known anti-apoptotic protein. No data are currently available on c-FlipL in male gonad before puberty; therefore, this study was carried out in prepuberal mouse testis. We investigated pachytene spermatocytes and spermatogonia by immunostaining of testis sections and found a strong and specific expression of c-FlipL in pachytene spermatocytes, while spermatogonia expressed very low levels of c-FlipL. This finding inversely correlated with the caspases activity, which was higher in spermatogonia as compared to pachytene spermatocytes. Other experiments carried out in an organ-culture model revealed that Fas-induced apoptosis was higher in spermatogonia as compared to pachytene spermatocytes. These data suggest that c-FlipL may play a role as an anti-apoptotic molecule in the prepuberal mouse testis and open new perspectives in the comprehension of the mechanisms controlling germ cells apoptosis.


Pupillary peaking with exposure of an intraocular lens positioning hole corrected by Nd:YAG laser treatment.
After posterior chamber intraocular lens insertion, a patient complained of "glare" and of seeing an "extra line." The pupil was seen to be "peaked" at the 10-o'clock meridian, exposing a lens positioning hole. Following dilation, adhesions between the anterior capsule remnants and the posterior iris surface were seen. These adhesions were severed with a Nd:YAG laser, restoring the normal pupillary shape and eliminating the patient's optical aberrations.


The serotonergic hypothesis for depression in Parkinson's disease: an experimental approach.
The serotonergic hypothesis for depression in Parkinson's disease (PD) states that the reduced cerebral serotonergic activity that occurs in PD constitutes a biological risk factor for depression. The aim of our study was to assess the serotonergic hypothesis of depression in PD patients using an experimental approach. In a double-blind, randomized order, placebo-controlled crossover design, the response on the Profile of Mood States (POMS) questionnaire to acute tryptophan depletion (ATD) was studied in 15 PD nondepressed patients and 15 control subjects, without a prior personal or family history of depression. PD patients had lower (worse) baseline scores on the sadness, fatigue and vigor subscales of the POMS, in both ATD and the placebo condition, but not on the tension and anger subscales. There was however neither a significance between group effect, nor significance within-group effect due to ATD. We could find no evidence of a specific serotonergic vulnerability of PD patients for depression. Therefore, our results do not support the serotonergic hypothesis for depression in PD.


Burning mouth syndrome: recognition, understanding, and management.
Burning mouth syndrome (BMS) can be a frustrating condition to the patient and the practitioner because the patient often experiences a continuous burning pain in the mouth without any apparent clinical signs, but the practitioner is unable to definitively diagnose symptoms even with the use of diagnostic testing or imaging. To overcome this dilemma, it is important for the practitioner to recognize and understand the complexities of BMS. The practitioner can then develop a sound approach to management of this condition and patients can be educated and reassured regarding BMS.


Localized dystrophic amyloidosis of heart valves.
A survey of 152 surgically resected heart valves (90 aortic, 60 mitral, two pulmonic) from a consecutive series of 142 adult patients revealed congophilic, green birefringent, amyloid deposits in 81 valves (59 aortic, 22 mitral) from 77 patients from 41 to 79 years of age. Amyloid was found in 50 (82 per cent) of 61 valves showing degenerative calcific sclerosis and in 31 (53 per cent) of 58 valves showing post-rheumatic sclerosis but in none of 33 valves showing more acute disease processes (myxoid transformation, "stretch lesions," healed bacterial endocarditis). All the amyloidotic valves showed some calcification, and amyloid deposits frequently occurred around the calcified foci. Histochemically, the valvular amyloid was distinguishable from other major forms of amyloid by its largely negative alcian blue and periodic acid-Schiff staining and by its pepsin-resistant iodine staining. The localized, dystrophic nature and unusual histochemical properties of this valvular amyloidosis clearly distinguish it from other forms of cardiac amyloidosis.


Neuromuscular and mitochondrial disorders: what is relevant to the anaesthesiologist?
The review provides an up-to-date information to the anaesthesiologist about the more frequent and important neuromuscular disorders for which new basic insights or clinical implications have been reported. The findings include the mechanisms of the hyperkalemia after succinylcholine in patients with upregulation of acetylcholine receptors. New insights into the mechanism of malignant hyperthermia-like reactions such as rhabdomyolysis during anaesthesia in patients with Duchenne muscular dystrophy have been published. The importance of mitochondrial defects and the effect of agents used in anaesthesia on mitochondrial function are also highlighted. The increased understanding of the genetics and pathophysiology of common muscle disorders may lead to a decrease in life-threatening complications related to surgery and anaesthesia. However, there is still a lack of prospective clinical studies to determine which is the safest anaesthetic technique for these patients.


Blood pressure decrease correlates with tau pathology and memory decline in hypertensive elderly.
In hypertension (HTN), cerebral blood flow regulation limits are changed, and the threshold for blood pressure (BP) at which perfusion is safely maintained is higher. This shift may increase the brain's vulnerability to lower BP in subjects with vascular disease. We investigated whether longitudinal reduction in mean arterial pressure (MAP) was related to changes in cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease in a group of cognitively healthy elderly with and without HTN. The relationships among MAP, memory decline, and hippocampal atrophy were also examined. Seventy-seven subjects (age 63.4 ± 9.4, range 44-86 years; education 16.9 ± 2.1, range 10-22 years; 60% women) were assessed twice, 2 ± 0.5 years apart. At both time points, all subjects underwent full medical and neuropsychological evaluations, lumbar punctures, and magnetic resonance imaging examinations. Twenty-five subjects had HTN. Hyper- and normotensive subjects did not differ in their CSF biomarkers, hippocampal volumes (HipVs), or memory scores at baseline. In the entire study group, the increase in tau phosphorylated at threonine 181 (p-tau(181)) was associated with a decline in verbal episodic memory (β = -0.30, p = 0.01) and HipV reduction (β = -0.27, p = 0.02). However, longitudinal decrease in MAP was related to memory decline (β = 0.50, p = 0.01) and an increase in p-tau(181) (β = -0.50, p = 0.01) only in subjects with HTN. Our findings suggest that the hypertensive group may be sensitive to BP reductions.


Barriers and facilitators to discussing HPV with head and neck cancer patients: A qualitative study using the theoretical domains framework.
The incidence of human papillomavirus-associated head and neck cancers (HPV-HNC) is increasing worldwide. Research in other clinical contexts has shown that healthcare professionals (HCPs) can find discussing HPV with patients challenging. However, limited research has been conducted in HNC. This study aimed to investigate barriers and facilitators to, discussing HPV among HCPs caring for patients with HNC in Ireland. Semi-structured telephone/face-to-face interviews were conducted with HCPs. Barriers and facilitators to discussing HPV with patients were identified using the Theoretical Domains Framework (TDF). 20 HCPs (8 clinicians, 3 nurses, 9 allied healthcare professionals) were interviewed. Barriers to discussing HPV included professionals' lack of HPV knowledge, difficulties in talking about sexual issues with patients and lack of privacy to discuss HPV in busy clinic settings. Facilitators included increasing public and patient awareness of the link between HPV and HNC and professional education and skills development. This is the first theoretically informed study to identify barriers and facilitators to discussing HPV with HNC patients. HCPs consider HPV discussions to be an essential part of HNC patient care. Understanding the issues associated with patient-provider HPV communication will help develop effective interventions to support HCPs in their HPV discussions.


Use of simian immunodeficiency virus vectors for simian embryonic stem cells.
The ability to stably introduce genetic material into primate embryonic stem (ES) cells could allow broader application. In this chapter, we describe a method of gene transfer into simian (cynomolgus macaque) ES cells using a simian immunodeficiency virus-based lentivirus vector. When cynomolgus ES cells are transduced with a simian immunodeficiency virus vector encoding the green fluorescent protein (GFP) gene, a large fraction of cells (greater than 50%) fluoresce, and high levels of GFP expression persist for months as assessed by flow cytometry and real-time polymerase chain reaction. Thus, the use of GFP as a reporter gene allows direct and simple detection of successfully transduced ES cells and facilitates monitoring of ES cell proliferation and differentiation both in vitro and in vivo. In addition, this highly efficient gene transfer method allows faithful gene delivery to primate ES cells with potential for both research and therapeutic applications.


Ventricular tachycardia ablation in structural heart disease: Impact of ablation strategy and non-inducibility as an end-point on long term outcome.
To investigate the long term outcomes after catheter ablation (CA) of ventricular tachycardia (VT) in the context of structural heart disease in a multicenter cohort. The impact of different ablation strategies (substrate ablation versus activation guided versus combined) and non-inducibility as an end-point was evaluated. Data was pooled from prospective registries at 5 centres over a 5 year period. Success was defined as survival free from recurrent ventricular arrhythmias (VA). Multivariate analysis of factors predicting survival free from VA was analysed by Cox regression. Five hundred sixty-six patients underwent CA for VT. Patients were 64 ± 15 years. Left ventricular ejection fraction was 35 ± 15% and 66% had ischaemic heart disease. At 2.3 (IQR 1.0-4.2) years, success was achieved in 44% after a single procedure, rising to 60% after repeat procedures. Mortality at final follow up was 22%. Multivariate analysis showed that higher left ventricular ejection fraction, younger age, ischaemic heart disease, and non-inducibility of VA predicted long term survival free from VA (all p < 0.05). There was no impact of the approach to ablation. CA eliminates VT in a large proportion of patients long term. Ablation strategy did not impact outcome and hence substrate ablation is a reasonable initial strategy. Non-inducibility of VA predicted survival free from VA and may be worth pursuing as a procedural end-point.


Heteropagus twins: six cases with systematic review and embryological insights.
Heteropagus twinning (HT) is a rare anomaly. Six new cases along with a systematic review are described. Six cases of HT managed at two tertiary care teaching hospitals over the last 26 years are described. A PubMed search with words: Heteropagus AND/ OR parasitic twins from 2001 to 2021 hit 183 articles. 36 were added from non-PubMed sources. Finally, 120 cases including 114 from 69 articles and 6 new cases were analysed. Of the new cases, 2/6 had an antenatal diagnosis. Five were males. 4 autosites had omphaloceles. Split notochord and 2 parasites attached to a single autosite were encountered. 5/6 autosites survived. On systematic review, the most frequent variant seen was rachipagus (n = 50) followed by omphalopagus (n = 46). Limbs were reported in 75 cases. Congenital heart disease was seen in 17/120(14.2%) autosites. Omphalocele and meningomyelocele were the most common extracardiac anomalies in autosites. Weight along with the anatomy and position of heteropagus twins was a better determinant of the mode of delivery than weight alone. Mortality was reported in 12 cases. Autosites in HT generally carry a good prognosis, however, final outcome depends mainly on associated major cardiac anomalies. Meticulous antenatal assessment and preoperative planning are of paramount importance. IV.


Prevalence, Knowledge and Perceptions of Smoking and Tobacco Products and Vape Among SEPAR Members.
The professional dedicated to respiratory health has an exemplary role in tobacco control, promoting smoking cessation in their patients. However, multiple circumstances cause a low implementation. Therefore, the objective of the study is to identify the consumption, knowledge and perception of tobacco and its emerging products in a representative sample of professionals involved in the treatment of respiratory patients integrated into the Spanish Society of Pneumology and Thoracic Surgery (SEPAR). Descriptive analysis of a structured online interview addressed to 5340 SEPAR members. In a sample of 802 respondents, more than 33% have smoked at some time and 6.6% continue to smoke. More than 66% consider smoking as a chronic disease. More than 90% consider their role model important and advise their patients to quit smoking, but less than half carry out a smoking intervention. Only 35% of them believe that the ban on smoking in health centers is always complied. More than 75% do not consider nicotine delivery devices an option for smoking cessation or harm reduction. 22% are unaware of water pipes and 29% of heated tobacco. Professionals specialized in respiratory diseases are highly sensitized to smoking. Despite this, there are still weak points such as the insufficient implementation of smoking cessation interventions or the scant training in smoking and in new emerging products.


Role of serotonin on cocaine-mediated effects on prodynorphin gene expression in the rat brain.
The effect of the selective serotonin uptake inhibitor fluoxetine was examined on prodynorphin gene expression. Fluoxetine or vehicle was infused continuously for 7 d via osmotic minipumps into male rats. Northern blot analysis showed significant increases in prodynorphin gene expression in the hypothalamus (171% of controls) and significant decreases in the caudate putamen and nucleus accumbens (62% and 70% of controls, respectively). There were no significant changes in the hippocampus. Thus, chronic inhibition of serotonin uptake can regulate prodynorphin gene expression in the hypothalamus, caudate putamen, and nucleus accumbens. Fluoxetine effects were also evaluated in rats treated with p-chloroamphetamine (PCA), a neurotoxin that depletes serotonin. Because we previously reported that continuous infusion of cocaine for 7 d (which inhibits dopamine, serotonin, and norepinephrine uptake), or GBR 12909 (a selective dopamine uptake inhibitor), produced significant decreases in the hypothalamus and cocaine also produced a significant increase in prodynorphin gene expression in caudate putamen, regulation of prodynorphin gene expression by fluoxetine is suggested to be different from that by cocaine. Because neither a selective dopamine uptake inhibitor nor a selective serotonin uptake inhibitor produced the same effect as cocaine in the caudate putamen, this effect is likely regulated by the inhibition of norepinephrine uptake, by a combination of effects on two or three neurotransmitter transporters, or by a mechanism unrelated to transporter inhibition.


In the quest for the ideal sweetener: Aspartame exacerbates selected biomarkers in the fruit fly (Drosophila melanogaster) model of Alzheimer's disease more than sucrose.
This study evaluated the effect of dietary inclusions of aspartame and sucrose on some selected behavioral and biochemical indices linked with Alzheimer's disease in a transgenic fruit fly (Drosophila melanogaster) model expressing human amyloid precursor protein and secretase. Flies were raised on a diet supplemented with sucrose and aspartame for 14 days. Thereafter, the flies were assessed for their survival rate, learning and memory, as well as locomotor performance, 14 days post-treatment. This was followed by homogenising the fly heads, and the homogenates were assayed for acetylcholinesterase and monoamine oxidase activities, as well as levels of lipid peroxidation, reactive oxygen species, and total thiol. The results showed aspartame at all levels of dietary intake and a high proportion of sucrose significantly aggravated the mortality rate, locomotor deficiency, and impaired biomarkers of oxidative stress and antioxidant status in the transgenic flies, while no significant effect was found on acetylcholinesterase activity or memory function. These findings therefore suggest that while low dietary inclusions of sucrose are tolerable under AD-like phenotypes in the flies, high inclusions of sucrose and all proportions of aspartame tested aggravated mortality rate, locomotion and oxidative stress in the flies.


Solid-state NMR and the thermal polymerization of 2,4-hexadiyne-1,6-diol bis-(p-toluenesulfonate).
The solid-state thermal polymerization of crystalline 2,4-hexadiyne-1,6-diol bis-(p-toluenesulfonate) (PTS) was investigated by solid-state 13C NMR, the first application of this technique to such a process. The kinetics of the thermal process was examined at temperatures of 40.5, 51.0, and 59.5 degrees C, with a magic angle spinning (MAS) rate of 5 kHz. The first-order rate constants associated with the induction (k0) and autocatalytic (k max) periods were calculated by monitoring signal intensities (conversion) throughout the course of the thermal polymerization. While estimations of the activation energy (E(a) approximately 20 kcal/mol) from the NMR experiments are similar to values obtained by other analytical techniques, estimations of the autocatalytic effect (k max/k0 approximately 22) were significantly lower. Likely causes for the unusually small autocatalytic effect are discussed.


Mannose: Good player and assister in pharmacotherapy.
Mannose is a monosaccharide widely distributed in body fluids and tissues, especially in the nerve, skin, testicles, retina, liver and intestines. It is used to synthesize glycoproteins and participate in immune regulation. In recent years, mannose has been applied more and more widely in the biomedical context as people have a deeper understanding of its biological effects. This review introduces the use of mannose in treating various diseases (including cancer, urinary tract infections, type 1 diabetes, and diabetic wounds), preventing pancreatic fistula, and improving magnetic resonance imaging for acute pancreatitis. We also demonstrate that mannose has the potential for clinical applications.


Comparison of therapeutic outcomes of sorafenib and lenvatinib as primary treatments for hepatocellular carcinoma with a focus on molecular-targeted agent sequential therapy: A propensity score-matched analysis.
The optimal choice between sorafenib (SOR) or lenvatinib (LEN) as the first-line treatment for unresectable hepatocellular carcinoma (u-HCC) remains debatable. Using propensity score matching, this study compares the outcomes of SOR and LEN in the molecular-targeted agent (MTA) sequential treatment of u-HCC patients. This retrospective, multicenter, observational study recruited 137 u-HCC patients who underwent primary treatment with LEN (n = 52) or SOR (n = 85) between June 2017 and June 2020 after regorafenib was approved as the secondary treatment for u-HCC. Propensity score matching was used to reduce confounding, resulting in the selection of 104 patients (n = 52 for the SOR and LEN cohorts). The median overall survival was 21.8 months for LEN and 20.4 months for SOR. LEN exhibited significantly greater therapeutic efficacy as compared to SOR (objective response rate: 3.8% [SOR] vs. 42.3% [LEN], p < 0.01; progression-free survival: 10 months [LEN] vs. 5.1 months [SOR], p < 0.01). No significant intergroup differences were noted in the rate of transition to secondary MTA treatments (SOR: 58.7%; LEN: 48.4%), adverse events (SOR: 86%; LEN: 95%), and maintenance of the Child-Pugh (CP) score during treatment. Compared to non-MTA treatments, secondary MTA treatment achieved a greater improvement in survival (4.3 vs. 2.8 months, p = 0.0047). Multivariate analysis demonstrated that the CP score (p < 0.01) and alpha-fetoprotein level (p < 0.01) were independent prognostic factors. Both SOR and LEN treatments showed a clinically comparable therapeutic efficacy as the first-line treatments for u-HCC patients in an MTA sequential therapy.


Fingerprinting of complex mixtures with the use of high performance liquid chromatography, inductively coupled plasma atomic emission spectroscopy and chemometrics.
The molecular and metal profile fingerprints were obtained from a complex substance, Atractylis chinensis DC-a traditional Chinese medicine (TCM), with the use of the high performance liquid chromatography (HPLC) and inductively coupled plasma atomic emission spectroscopy (ICP-AES) techniques. This substance was used in this work as an example of a complex biological material, which has found application as a TCM. Such TCM samples are traditionally processed by the Bran, Cut, Fried and Swill methods, and were collected from five provinces in China. The data matrices obtained from the two types of analysis produced two principal component biplots, which showed that the HPLC fingerprint data were discriminated on the basis of the methods for processing the raw TCM, while the metal analysis grouped according to the geographical origin. When the two data matrices were combined into a one two-way matrix, the resulting biplot showed a clear separation on the basis of the HPLC fingerprints. Importantly, within each different grouping the objects separated according to their geographical origin, and they ranked approximately in the same order in each group. This result suggested that by using such an approach, it is possible to derive improved characterisation of the complex TCM materials on the basis of the two kinds of analytical data. In addition, two supervised pattern recognition methods, K-nearest neighbors (KNNs) method, and linear discriminant analysis (LDA), were successfully applied to the individual data matrices-thus, supporting the PCA approach.


Experiences of nurses practising home-based palliative care in a rural South African setting.
Home-based care is necessary in rural South Africa owing to the impact of the HIV/AIDS epidemic, inaccessible health-care institutions, and overcrowding in hospitals. Palliative care has been introduced as part of home-based care and there is a call for research to inform practice, training, and support of caregivers. This exploratory paper reports on four nurses' experiences of providing home-based palliative care (HBPC) in rural KwaZulu-Natal. The study employed the qualitative method of photo-elicitation, which was used as a launching point for individual one-to-one interviews with the participants. HBPC increases access to care and provides a means of humanizing care and supporting patients in familiar community structures. It also enables nurses to practise independently and facilitates practise of traditional customs and use of traditional medicines. Challenges include patients' understanding of palliative care and nurses being placed at risk. The study uncovered several benefits to HBPC for patients and nurses, but also highlighted various challenges in its implementation. Further research is needed before any recommendations for practice, training, and support can be made.


Joint Engagement in Mother-Child Dyads of Autistic and Non-Autistic Children Among Asian Indian Tamil Speaking Families.
This study profiled various levels of engagement and related communication behaviours among 50 Asian Indian Tamil autistic children (AUT) and their mothers. The interaction was compared with two groups of mother-child dyads of non-autistic (NA) children, 50 in each group, matched for chronological age (CA), and for language level (LL). Results indicated that despite mother's efforts to engage with their children, autistic children were often 'engaged with objects' or remained 'unengaged' due to children's preference for solitary play, while NA children were often engaged in 'co-ordinated' and 'people engagement'. Across the three groups, mothers predominantly took the lead and dominated the interaction, irrespective of children's language levels. These initiations by the mothers were often to provide instructions and to ask 'What' questions. Autistic children initiated communication predominantly to ask for an object and responded often in the form of negations and protests with limited verbal output or non-verbally. Most of the communication behaviours of both children and mothers in AUT group was quantitatively and qualitatively different when compared to those in both the NA groups, indicating unique nature of interactions despite matching for CA or LL. The observations from the study highlights the need for considering adult's contingent behaviours also, while assessing communication skills of autistic children in order to provide effective intervention.


The role of Phe150 in human voltage-gated proton channel.
The voltage-gated proton channel Hv1 is a member of voltage-gated ion channels containing voltage-sensing domains (VSDs). The VSDs are made of four membrane-spanning segments (S1 through S4), and their function is to detect changes in membrane potential in the cells. A highly conserved phenylalanine 150 (F150) is located in the S2 segment of human voltage-gated proton channels. We previously discovered that the F150 is a binding site for the open channel blocker 2GBI. Here, we show that the Hv1 VSD voltage-dependent activation requires a hydrophobic group at position F150. We perform double-mutant cycle analysis to probe interactions between F150 and positively charged arginines in the S4 segment of the channel. Our results indicate that F150 interacts with two arginines (R2 and R3) in the S4 segment and catalyzes the transfer of the S4 arginines in the process of voltage-dependent activation.


Occurrence of singlet oxygen oxygenation of oleic acid and linoleic acid in the skin of live mice.
To assess the contribution of singlet molecular oxygen [O(2) ((1)Delta(g))] to lipid peroxidation in vivo, this study combined gas chromatography-mass spectrometry with thin layer chromatography to analyse peroxidized lipids in the skin of hairless mice. Hydroxyoctadecenoate isomers and unconjugated hydroxyoctadecadienoate isomers derived from peroxidized oleic acid and linoleic acid, respectively, which are specific to O(2) ((1)Delta(g))-dependent oxygenation, were detected in the skin of live mice under ordinary feeding conditions. Short-term ultraviolet A (UVA)-irradiation of the skin in vivo elevated levels of the unconjugated hydroxyoctadecadienoate isomers significantly, whereas the irradiation of skin homogenate in vitro increased levels of all isomers derived from both O(2) ((1)Delta(g)) and free radical-dependent oxygenation to a much greater extent. This is the first report to demonstrate the occurrence of O(2) ((1)Delta(g))-specific oxygenation of unsaturated fatty acids in living animals.


Anuran Traits of the United States (ATraiU): a database for anuran traits-based conservation, management, and research.
The United States is home to many anuran species, each with traits that set them apart from one another. Understanding trait variation within and between anurans is key to many successful conservation, management, and research efforts. However, compiling trait data is intensive and time consuming. Trait databases can meet this need, but currently there is no detailed database that collates trait data for anurans of the contiguous United States. into a single location with transparency regarding original data sources. Furthermore, many currently available trait databases rarely report multiple data points for a given species' trait, frequently reporting a single averaged value. We present an anuran traits database for the contiguous United States that includes trait data from 411 unique references. We collated trait values for 106 native and nonnative species using a tiered search protocol. First, we digitized trait data from 33 state guide books for 12 ecological, morphological, and life history traits commonly reported in the literature. We then performed a targeted search of the primary literature to address data gaps, ultimately identifying an additional 356 peer-reviewed publications, theses, and agency reports with data fitting our criteria. Finally, we digitized trait data from 22 national and regional guidebooks. Following data compilation, we conducted an intensive data quality check procedure that included both manual and statistical analyses. For full transparency, all trait values are traceable to their original reference with additional metrics (e.g., reference count, data tier) to allow users to easily filter the full data set to fit the user's needs. Overall, we report 89% of included species with trait values for at least half of the 12 traits included, providing high coverage for interspecific analyses. With a high degree of transparency, inclusion of all original data sources, and a tiered system for cataloguing data source type, ATraiU can uniquely contribute to anuran ecology and conservation in the United States. Please cite this data paper when using the data. If using a specific trait value or values, please cite the original reference(s).


Highly Dense Packing of Chromophoric Linkers Achievable in a Pyrene-Based Metal-Organic Framework for Photoelectric Response.
Highly dense packing of chromophoric linkers is achieved in a novel pyrene-based metal-organic framework (MOF), [Zn(TBAPy)1/2(H2O)2], induced by an ionic liquid. This MOF displays a quick response to visible-light irradiation (photocurrent density of up to 4.492 μA cm-2) and is capable of repetitive on-off photocurrent switching with a large on-off ratio (37.55).


The effect of semantic plausibility on sentence comprehension in aphasia.
Tested were 50 aphasic patients (16 Broca's, 15 Wernicke's, 10 global, and 9 amnesic), 13 nonaphasic brain damaged patients, and 13 normal adults to evaluate the effect of semantic plausibility on sentence comprehension in active affirmative declarative sentences with a sentence-picture matching task. A plate of two pictures was provided for each stimulus sentence, and the subject was required to choose the picture corresponding to the sentence presented auditorily. Two types of sentences in terms of plausibility were prepared, i.e., probable sentences (P) describing common events in our daily life and improbable sentences (I) describing rare events. There were four kinds of combinations of a picture with the other to make a correct/(distractor) set, i.e., P/(P), P/(I), I/(P), and I/(I) constructions. The results indicated that probable sentences were more comprehensible than improbable sentences, and that the effect of semantic plausibility did not differ among aphasic types.


Long noncoding RNA lncTCF7, induced by IL-6/STAT3 transactivation, promotes hepatocellular carcinoma aggressiveness through epithelial-mesenchymal transition.
Accumulating evidence suggests the pro-inflammatory cytokine interleukin-6 (IL-6) in tumor microenvironment may promote the development of hepatocellular carcinoma (HCC). However, the underlying mechanism remains largely unknown. The expression and promoter activity of lncTCF7 were measured by quantitative real-time polymerase chain reaction (qRT-PCR) and luciferase reporter assay. The function of the STAT3 binding site in the lncTCF7 promoter region was tested by luciferase reporter assay with nucleotide substitutions. The binding of STAT3 to the lncTCF7 promoter was confirmed by chromatin immunoprecipitation assay (CHIP) in vivo. The effects of decreasing STAT3 with small interference RNA and inhibiting STAT3 activation by small molecular inhibitor on lncTCF7 expression were also determined. We demonstrate that IL-6 could induce lncTCF7 expression in a time- and dose-dependent manner, and we showed that IL-6 transcriptionally activated the expression of lncTCF7 in HCC cells by activating STAT3, a transcription activator which binds to promoter regions of lncTCF7. Furthermore, knocking-down STAT3 and inhibiting STAT3 activation reduced lncTCF7 expression. Importantly, RNA interference-based attenuation of lncTCF7 prevented IL-6-induced EMT and cell invasion. Thus, these data provides evidence to the existence of an aberrant IL-6/STAT3/ lncTCF7 signaling axis that leads to HCC aggressiveness through EMT induction, which could be novel therapeutic targets in malignancies.


Prediction of long-term mortality following hip fracture surgery: evaluation of three risk models.
Several prognostic models have been developed for mortality in hip fracture patients, but their accuracy for long-term prediction is unclear. This study evaluates the performance of three models assessing 30-day, 1-year and 8-year mortality after hip fracture surgery: the Nottingham Hip Fracture Score (NHFS), the model developed by Holt et al. and the Hip fracture Estimator of Mortality Amsterdam (HEMA). Patients admitted with a fractured hip between January 2012 and June 2013 were included in this retrospective cohort study. Relevant variables used by the three models were collected, as were mortality data. Predictive performance was assessed in terms of discrimination with the area under the receiver operating characteristic curve and calibration with the Hosmer-Lemeshow goodness-of-fit test. Clinical usefulness was evaluated by determining risk groups for each model, comparing differences in mortality using Kaplan-Meier curves, and by assessing positive and negative predictive values. A total of 344 patients were included for analysis. Observed mortality rates were 6.1% after 30 days, 19.1% after 1 year and 68.6% after 8 years. The NHFS and the model by Holt et al. demonstrated good to excellent discrimination and adequate calibration for both short- and long-term mortality prediction, with similar clinical usefulness measures. The HEMA demonstrated inferior prediction of 30-day and 8-year mortality, with worse discriminative abilities and a significant lack of fit. The NHFS and the model by Holt et al. allowed for accurate identification of low- and high-risk patients for both short- and long-term mortality after a fracture of the hip. The HEMA performed poorly. When considering predictive performance and ease of use, the NHFS seems most suitable for implementation in daily clinical practice.


Enhanced antibacterial activity of the gentamicin against multidrug-resistant strains when complexed with Canavalia ensiformis lectin.
The lectins are carbohydrate-binding proteins that are highly specific to sugar groups associated to other molecules. In addition to interacting with carbohydrates, a number of studies have reported the ability of these proteins to modulate the activity of several antibiotics against multidrug-resistant (MDR) strains. In this study, we report the enhanced antibacterial activity of the gentamicin against MDR strains when complexed with a lectin from Canavalia ensiformis seeds (ConA). Hemagglutination activity test and intrinsic fluorescence spectroscopy revealed that the gentamicin can interact with ConA most likely via the carbohydrate recognition domain (CRD) with binding constant (Kb) value estimated of (0.44 ± 0.04) x 104 M-1. Furthermore, the minimum inhibitory concentrations (MIC) obtained for ConA against all strains studied were not clinically relevant (MIC ≥ 1024 μg/mL). However, when ConA was combined with gentamicin, a significant increase in antibiotic activity was observed against Staphylococcus aureus and Escherichia coli. The present study showed that ConA has an affinity for gentamicin and modulates its activity against MDR strains. These results indicate that ConA improves gentamicin performance and is a promising candidate for structure/function analyses.


Coronary blood flow changes during atrioventricular sequential pacing with different atrioventricular delays in normal individuals.
This study examined the effects of different atrioventricular (AV) intervals, during AV sequential pacing, on hemodynamics and coronary blood flow in individuals with normal hearts. Left anterior descending artery blood flow velocity was measured, using intracoronary Doppler, in 17 normal individuals. Five pacing tests were applied in random order for 5 min, at 15 beats/min above the sinus rate. Four tests using AV sequential pacing with AV intervals of 175, 150, 100, and 50 ms, and one using atrial pacing were applied. Mean flow velocity was 21 +/- 9 cm/s, 20 +/- 9 cm/s, 17 +/- 7 cm/s, 17 +/- 7 cm/s, and 22 +/- 10 cm/s, respectively (F = 8.87, p = .00001). The hemodynamic effects of these 5 pacing tests were assessed in 8 different normal subjects. Isovolumic relaxation time constant and left ventricular systolic pressure decreased, whereas right atrial pressure increased during AV sequential pacing with short AV intervals. Thus, during short-term AV sequential pacing at rest, coronary blood flow in a normal left anterior descending artery decreases with short AV intervals.


Abstinence promotion under PEPFAR: the shifting focus of HIV prevention for youth.
Abstinence-until-marriage (AUM) - strongly supported by religious conservatives in the USA - became a key element of initial human immunodeficiency virus (HIV) prevention efforts under the President's Emergency Plan for AIDS Relief (PEPFAR). AUM programmes have demonstrated limited efficacy in changing behaviours, promoted medically inaccurate information and withheld life-saving information about risk reduction. A focus on AUM also undermined national efforts in Africa to create integrated youth HIV prevention programmes. PEPFAR prevention efforts after 2008 shifted to science-based programming, however, vestiges of AUM remain. Primary prevention programmes within PEPFAR are essential and nations must be able to design HIV prevention based on local needs and prevention science.


Cellular retinoic acid binding protein type II was preferentially localized in medium and posterior parts of the progress zone of the chick limb bud.
The expression and distribution of cellular retinoic acid binding protein II (CRABP II) was examined in chick limb buds. CRABP II was detected in the limb buds at Hamburger and Hamilton (1) stage 21 and the amount of CRABP II was gradually increased during stages 21-27 and thereafter decreased. CRABP II was mainly located in the progress zone, and the dorsal and ventral premuscular mass in the proximal region of the limb buds at stage 23. CRABP II was preferentially localized in the medium and posterior parts rather than the anterior part of the progress zone; The content of CRABP II in the medium and posterior parts was 8-9 times more than that in the anterior part.


Large-scale synthesis of a persistent trityl radical for use in biomedical EPR applications and imaging.
Tetrathiatriarylmethyl radicals are ideal spin probes for biological electron paramagnetic resonance (EPR) spectroscopy and imaging. The wide application of trityl radicals as biosensors of oxygen or other biological radicals was hampered by the lack of affordable large-scale syntheses. We report the large-scale synthesis of the Finland trityl radical using an improved addition protocol of the aryl lithium monomer to methylchloroformate. A new reaction for the formal one-electron reduction of trityl alcohols to trityl radicals using neat trifluoroacetic acid is reported as well. Initial applications show that the compound is very sensitive to molecular oxygen. It has already provided high-resolution EPR images on large aqueous samples and should be suitable for a broad range of in vivo applications.


Platelets, endothelium and blood vessel wall.
Aggregating platelets cause contraction of vascular smooth muscle, because they release serotonin and thromboxane A2. If the platelets aggregate in a blood vessel with intact intima, the platelet-products cause endothelium-dependent relaxation of the underlying smooth muscle. Hence, the presence of an intact intima considerably reduces the vasospastic response to platelet-aggregation. The major platelet products which trigger endothelium-dependent relaxations are the adenine nucleotides and serotonin. The ability of the endothelium to prevent platelet-induced vasospasm is augmented after chronic intake of cod liver oil, but is reduced after previous intimal injury.


Evolution of plastid genomes of Holcoglossum (Orchidaceae) with recent radiation.
The plastid is a semiautonomous organelle with its own genome. Plastid genomes have been widely used as models for studying phylogeny, speciation and adaptive evolution. However, most studies focus on comparisons of plastid genome evolution at high taxonomic levels, and comparative studies of the process of plastome evolution at the infrageneric or intraspecific level remain elusive. Holcoglossum is a small genus of Orchidaceae, consisting of approximately 20 species of recent radiation. This made it an ideal group to explore the plastome mutation mode at the infrageneric or intraspecific level. In this paper, we reported 15 complete plastid genomes from 12 species of Holcoglossum and 1 species of Vanda. The plastid genomes of Holcoglossum have a total length range between 145 kb and 148 kb, encoding a set of 102 genes. The whole set of ndh-gene families in Holcoglossum have been truncated or pseudogenized. Hairpin inversion in the coding region of the plastid gene ycf2 has been found. Using a comprehensive comparative plastome analysis, we found that all the indels between different individuals of the same species resulted from the copy number variation of the short repeat sequence, which may be caused by replication slippage. Annotation of tandem repeats shows that the variation introduced by tandem repeats is widespread in plastid genomes. The hairpin inversion found in the plastid gene ycf2 occurred randomly in the Orchidaceae.


Safety and efficacy of long-term emicizumab prophylaxis in hemophilia A with factor VIII inhibitors: A phase 3b, multicenter, single-arm study (STASEY).
The bispecific monoclonal antibody emicizumab bridges activated factor IX and factor X, mimicking the cofactor function of activated factor VIII (FVIII), restoring hemostasis. The Phase 3b STASEY study was designed to assess the safety of emicizumab prophylaxis in people with hemophilia A (HA) with FVIII inhibitors. People with HA received 3 mg/kg emicizumab once weekly (QW) for 4 weeks followed by 1.5 mg/kg QW for 2 years. The primary objective was the safety of emicizumab prophylaxis, including incidence and severity of adverse events (AEs) and AEs of special interest (thrombotic events [TEs] and thrombotic microangiopathies). Secondary objectives included efficacy (annualized bleed rates [ABRs]). Overall, 195 participants were enrolled; 193 received emicizumab. The median (range) duration of exposure was 103.1 (1.1-108.3) weeks. Seven (3.6%) participants discontinued emicizumab. The most common AEs were arthralgia (n = 33, 17.1%) and nasopharyngitis (n = 30, 15.5%). The most common treatment-related AE was injection-site reaction (n = 19, 9.8%). Two fatalities were reported (polytrauma with fatal head injuries and abdominal compartment syndrome); both were deemed unrelated to emicizumab by study investigators. Two TEs occurred (myocardial infarction and localized clot following tooth extraction), also deemed unrelated to emicizumab. The negative binomial regression model-based ABR (95% confidence interval) for treated bleeds was 0.5 (0.27-0.89). Overall, 161 participants (82.6%) had zero treated bleeds. The safety profile of emicizumab prophylaxis was confirmed in a large population of people with HA with FVIII inhibitors and no new safety signals occurred. The majority of participants had zero treated bleeds.


Comparison of Continuation of Low-Molecular-Weight Heparin versus Switching to Unfractionated Heparin in the Peripartum.
This study aimed to determine whether switching from low-molecular-weight heparin (LMWH) to unfractionated heparin (UFH) or its continuation in the peripartum affected anesthesia choice or bleeding complications. A retrospective cohort study of 189 anticoagulated pregnant women who delivered at the University of Illinois at Chicago Hospital and Health Science System from 2005 to 2016. Demography, anesthesia choice, and bleeding complications were compared between the two groups. There were 138 (73%) women on LMWH versus 51 (27%) who switched from LMWH to UFH during the peripartum. The demographics were similar, 123 women were on prophylactic: 81 (66%) were on LMWH and 42 (34%) switched to UFH. Of the 66 women on therapeutic anticoagulation, 57 (86%) continued on LMWH, while 9 (14%) switched to UFH. No difference in neuraxial anesthesia type received: 42 (82.4%) versus 108 (79.7%) women (odds ratio: 1.20, 95% confidence interval [CI]: 0.52-2.73, p = 0.837). Bleeding complications more than 1,000 mL, 6 versus 10% (relative risk [RR]: 0.58, 95% CI: 0.17-1.94, p = 0.380) and relaparotomy due to hemoperitoneum, 2% in either group (RR: 0.9, 95% CI: 0.10-8.48, p = 0.930) were similar in the two groups regardless of time of last injection. Anesthesia type and rate of bleeding complications were similar between women on LMWH and UFH during the peripartum.


Genetic polymorphism of 12 Y-chromosomal STR loci in the Minnan Han Chinese in Southeast China.
The 12Y-chromosomal short tandem repeat (STR) loci DYS19, DYS389I and II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439, DYS385a and b were analyzed in a sample of 109 unrelated male individuals from mountainous areas of Minnan, Southeast China. A total of 95 haplotypes were identified. The allele diversity values for each locus ranged from 0.3205 (DYS391) to 0.9553 (DYS385), the haplotype diversity was 0.9863, and the discrimination capacity 0.8716.


Stoichiometry of 4-methyl sterol oxidase of rat liver microsomes.
The stoichiometry of 4-methyl sterol oxidase has been investigated by concurrent assays of rates of oxygen consumption, oxidation of reduced pyridine nucleotide, and formation of steroid 4alpha-oic acid, which is the oxidized product of attack of 4-methyl sterol precursors of cholesterol. The basal, steroid-independent rates of oxidation of alpha-NADH and alpha-NADH-dependent oxygen consumption by rat liver microsomes are about 10 to 15% of the rates observed with beta-NADH. Thus, alpha-NADH is substituted for beta-NADH; alpha-NADH oxidation is observed spectrophotometrically. The slow rate of oxygen consumption is measured accurately with a galvanic oxygen electrode that is attached to an offset amplifier. For maximal velocity, 4alpha-hydroxymethyl-5alpha-cholest-7-en-3beta-ol is the steroid substrate, and oxidase activity is induced 2-fold with a dietary bile acid sequestrant. Under these conditions, accurate measurements are obtained for substrate-dependent increments, which are equal to or greater than basal, substrate-independent rates. For each equivalent of hydroxymethyl group oxidized to carboxylic acid, 2 eq each of oxygen and alpha-NADH are consumed. Thus, the stoichiometry is consistent with that expected for two sequential attacks of the 4alpha-hydroxymethyl group by an external mixed function oxidase. In addition to establishing the stoichiometry of the 4-methyl sterol oxidase, the results further demonstrate that the steroidal 4alpha-carboxylic acid is formed from the hydroxymethyl intermediate by catalysis of a mixed function oxidase rather than dehydrogenases.


[A model of a rat cage for the collection of urine free of fecal matter].
A cage for total separation of feces and urine in the awake rat is presented. Construction and function are described in detail. Two important indications (investigation of the urinary enzyme activity, and determination of the endogenous creatinine clearance) are denominated.


Closed-loop vagus nerve stimulation for heart rate control evaluated in the Langendorff-perfused rabbit heart.
Persistent sinus tachycardia substantially increases the risk of cardiac death. Vagus nerve stimulation (VNS) is known to reduce the heart rate, and hence may be a non-pharmacological alternative for the management of persistent sinus tachycardia. To precisely regulate the heart rate using VNS, closed-loop control strategies are needed. Therefore, in this work, we developed two closed-loop VNS strategies using an in-silico model of the cardiovascular system. Both strategies employ a proportional-integral controller that operates on the current amplitude. While one control strategy continuously delivers stimulation pulses to the vagus nerve, the other applies bursts of stimuli in synchronization with the cardiac cycle. Both were evaluated in Langendorff-perfused rabbit hearts (n = 6) with intact vagal innervation. The controller performance was quantified by rise time (Tr), steady-state error (SSE), and percentual overshoot amplitude (%OS). In the ex-vivo setting, the cardiac-synchronized variant resulted in Tr = 10.7 ± 4.5 s, SSE = 12.7 ± 9.9 bpm and %OS = 5.1 ± 3.6% while continuous stimulation led to Tr = 10.2 ± 5.6 s, SSE = 10 ± 6.7 bpm and %OS = 3.2 ± 1.9%. Overall, both strategies produced a satisfying and reproducible performance, highlighting their potential use in persistent sinus tachycardia.


Dimethylsiloxanes in dust from nine indoor microenvironments of Henan Province: Occurrence and human exposure assessment.
Dimethylsiloxanes (MSs) are widely used in daily life and industry, with indoors being the main release site. Detecting the levels of MSs in indoor dust is essential for assessing the risks of human exposure. In this study, the content of MSs (D3-D8 and L3-L16) was quantified in indoor dust samples from nine microenvironments of Henan Province. The detection frequency of the targets ranged from 5.00 % to 100 %. The sum concentration of dimethylsiloxanes (TSi) was in a range of 463-3.32 × 104 ng·g-1 (median: 1.92 × 103 ng·g-1). The sum concentration of linear dimethylsiloxanes (TLSi) from all microenvironments was higher than the sum concentration of cyclic dimethylsiloxanes (TCSi), which was consistent with previously reported results. D7 and D8 were the main cyclic dimethylsiloxane, which had similar sources based on Spearman correlation analysis (p < 0.001). Moreover, D8 was detected with high levels in indoor dust for the first time, which warrants further exploration. L8-L16 were the main linear dimethylsiloxanes, which may have been due to their widespread use in electronic equipment and office equipment. The Spearman analysis found that total organic carbon (TOC) in indoor dust had weak effect on MSs. Additionally, relatively high MS levels were recorded in high people-flow working microenvironments. Accordingly, the exposure doses of MSs via indoor dust intake were estimated for different age groups using the model of worst-case exposure and median concentration. Toddlers had the highest EDIs (95th percentile concentration, 90.7 ng·kg-1-bw·d-1) to MSs.


Human milk and formulae: neurotrophic and new biological factors.
Mother milk is widely accepted to be a unique product believed to contain biological factors involved in the regulation of newborn optimal growth including brain when compared to milk-formula milks. In this setting, there is growing evidence that in milk-formula neuro-oxidative stress biomarkers, neurotrophic proteins and calcium binding proteins, known to be involved in a cascade of events leading to brain, cardiac and vascular development/damage, are to date lacking or at a lower concentration than breast milk. Therefore, this review is aimed at offering additional insights to the role in human milk of some selected biomarkers such as: i) neurotrophic factors such as Activin A; ii) Calcium binding protein such as S100B and, iii) heat shock protein known to be involved in oxidative stress response (namely hemeoxygenase-1, HO-1 or Heat shock Protein 32, HSP32).