The utility of inpatient anemia workup in hemoglobin < 10 g/dL diagnosed randomly in the third trimester: a retrospective study.
About 40% of pregnant women are anemic and at an increased risk for complications. We examined the efficacy of inpatient anemia workup and treatment in pregnant women diagnosed with moderate-severe anemia (hemoglobin < 10 mg/dL), during hospitalization in the late second-trimester and third-trimester. This retrospective study, conducted between March 2020 and November 2022, included women at ≥ 24 gestational weeks who were hospitalized due to various indications and diagnosed with anemia (hemoglobin < 10 mg/dL). The study group comprised women who underwent an inpatient anemia workup and initiation of anemia treatment. The comparison group comprised women who did not undergo an inpatient anemia investigation. The primary outcome was the rate of pre-delivery hemoglobin > 11 g/dL. The most frequent etiology of anemia in the study group (n = 188) was iron-deficiency anemia (30.2%), followed by mixed anemia of iron, folate and vitamin-B12 deficiencies (20.7%). In the study vs. the comparison group (n = 179), the rate of pre-delivery hemoglobin > 11 g/dL was higher, and the increase in hemoglobin from intervention to delivery was greater. The ideal timing for anemia intervention for maximizing the increase in pre-delivery hemoglobin was 6-weeks or more prior to delivery. The rates of postpartum hemorrhage and blood transfusions were similar. The rate of postpartum hemoglobin < 10 g/dL was lower in the study than the comparison group. Inpatient anemia investigation and treatment resulted in higher peri-delivery hemoglobin. In women randomly diagnosed with anemia at hospitalization, the rate of pre-delivery hemoglobin > 11 g/dL was increased among those who underwent a simple anemia investigation and treatment initiation.


Commutability of serum protein values: persisting bias among manufacturers using values assigned from the certified reference material 470 (CRM 470) in the United States.
Significant among-manufacturer differences in values for serum proteins persist 7 years after the introduction of the international reference material (Certified Reference Material 470; Reference Preparation for Proteins in Human Serum). In some cases, such as transthyretin and C4, the biases actually continue to increase. Further efforts at standardization are needed in order to improve commutability of results among laboratories and are essential if universal reference intervals are to be developed.


Upgrading Common Wheat Pasta by Fiber-Rich Fraction of Potato Peel Byproduct at Different Particle Sizes: Effects on Physicochemical, Thermal, and Sensory Properties.
Fiber-enriched food has numerous health benefits. This study develops functional fiber-enriched pasta (FEP) by partially substituting wheat flour for alcohol-insoluble residue prepared from potato processing byproducts (AIR-PPB) at various particle sizes (PS). The independent variables' effects, AIR-PPB at 2-15% substitution levels, and PS 40-250 µm were investigated in terms of chemical, cooking, thermal, and sensory properties. AIR-PPB is rich in total dietary fibers (TDF) (83%), exhibiting high water-holding capacity (WHC) and vibrant colors. Different concentrations of AIR-PPB increase TDF content in FEPs by 7-21 times compared to the control pasta (CP). Although the optimal cooking time (OCT) decreases by 15-18% compared to CP, where a lower OCT should reduce cooking time and save energy, cooking loss (Cl) increases slightly but remains within an acceptable range of 8%. Additionally, AIR-PPB altered the texture properties of FEP, with a moderate decrease in mass increase index (MII), firmness, and stickiness. AIR-PPB impairs the gluten network's structure in pasta due to AIR-PPB's WHC, which competes with starch for water binding, increasing the starch gelatinization temperature. FEPs show an increased lightness and yellowness and improved sensory properties. Highly acceptable FEPs were obtained for the following substitution levels: FEP11 (AIR-PPB at 2% and PS of 145 µm), FEP9 (AIR-PPB 4% level with PS of 70 µm), FEP6 (AIR-PPB of 4% level with 219 µm PS), and FEP1 (AIR-PPB = 8.5% with 40 µm PS), as compared to other FEPs.


Relationship of perioperative hyperglycemia and postoperative infections in patients who undergo general and vascular surgery.
Evaluate the association of perioperative hyperglycemia and postoperative infections (POI) in patients who had undergone general surgery. Intensive glucose control leads to less postoperative infections (POI) in critically ill surgical patients, but the relationship of hyperglycemia and POI in a general surgical population remains unknown. A retrospective study of 995 patients who had undergone general and vascular surgery investigated the association of perioperative acute hyperglycemia and risk of 30-day POI over an 18-month period. The primary predictor of interest was postoperative glucose (POG). Bivariate analyses determined the association of each independent variable with POI. Factors significant at P < 0.05 were used in multivariable logistic regression models. In bivariate analyses, preoperative blood glucose (P = 0.012), POG (P = 0.009), age (P = 0.002), diabetes (P = 0.04), American Society of Anesthesia Classification (ASAC) (P < 0.0001), operation length (P = 0.02), and blood transfusions (P = 0.02) were significant predictors of POI. In multivariate analyses, only POG (OR = 1.3, (1.03-1.64)), ASAC (OR = 1.9, (1.31-2.83)), and emergency status (OR = 2.2, (1.21-3.80)) remained significant predictors of POI. Postoperative hyperglycemia increased the risk of POI by 30% with every 40-point increase from normoglycemia (<110 mg/dL). Longer hospitalization was also observed for patients with POG from 110 to 200 mg/dL (OR = 1.4, (1.1-1.7)) and >200 mg/dL (OR = 1.8, (1.4-2.5)). The increased risk of POI and length of hospitalization posed by postoperative hyperglycemia is independent of diabetic status and needs further evaluation to assess for possible benefits of postoperative glycemic control in patients who have undergone general surgery.


Geographic access to assisted reproductive technology health care in the United States: a population-based cross-sectional study.
To evaluate the geographic distribution of assisted reproductive technology (ART) clinics and the number of ART clinics within U.S. Census metropolitan areas and to estimate the number of reproductive-age women who have geographic access to ART services in the United States. A population-based cross-sectional study. Not applicable. None. None. Number of U.S. reproductive-age women living in areas with no ART clinic, a single ART clinic, or more than one ART clinic. There were 510 ART clinics in the United States in 2009-2013. Multiple ART clinics were present in 76 metropolitan areas (median population of 1.45 million people), where a total of 442 clinics were located. A single ART clinic was present in 68 metropolitan areas (median population of 454,000 people). Among U.S. reproductive-age women in 2010, 38.1 million (60.4% of the U.S. population) lived in an area with multiple ART clinics, 6.8 million (10.8% of the U.S. population) lived in an area with a single clinic, and 18.2 million (28.8% of the U.S. population) lived in an area (metropolitan and nonmetropolitan) with no ART clinics. Nearby geographic access to ART services is limited or absent for more than 25 million reproductive-age women (39.6% of the U.S. population) in the United States. This population estimate should spur continued policy and technological progress to increase access to ART services.


Response of sensory neurites and growth cones to patterned substrata of laminin and fibronectin in vitro.
During neurite elongation in the developing peripheral nervous system, the distribution of laminin and fibronectin may provide preferred substrates for neurite elongation. In this study, the response of sensory neurites and growth cones to patterns of laminin or fibronectin applied to a background substrate of Type IV collagen was studied to determine any possible substrate preference. Neurites exhibited elongation restricted to a laminin pattern, but not a fibronectin pattern, indicating that sensory neurites prefer to elongate on laminin compared to Type IV collagen. When polylysine is included in the background substrate, neurite preference for laminin is decreased. Laminin also enhances neurite elongation and defasciculation and stabilizes growth cone protrusions. These results suggest an adhesive as well as a cytoskeletal involvement in the response to laminin, but direct adhesion estimates indicate that laminin decreases overall adhesion, arguing against an adhesive involvement. Regardless of the mechanism involved, the observed neurite preference for laminin is consistent with the hypothesis that spatial and temporal laminin distributions provide preferred pathways for peripheral neurite elongation.


Feeding patterns in eastern tropical Pacific blennioid fishes (Teleostei: Tripterygiidae, Labrisomidae, Chaenopsidae, Blenniidae).
In terms of species number (47) and numerical abundance, blennioids are the most important primary resident rocky reef fishes in the Gulf of California, Mexico. We present the feeding patterns of the 34 most abundant species of blennioid fishes, 8 of which are Gulf endemics. A total of 2,144 specimens were sampled at 51 anaesthetic stations in 9 areas throughout the Gulf. Four feeding guilds were distinguished: 1) The majority (29 of 34 species) are microcarnivores exhibiting a number of different feeding strategies (ambush and stalking predators, active foragers, pickers, etc.). The more important prey categories were mobile invertebrates, and to some extent also sedentary fauna. Algae were of no importance for most of the latter species. 2) Hypsoblennius brevipinnis and H. gentilis are two omnivorous species, browsing mainly on sessile items including 52% and 13% (Vol.) algae in their diets. 3) Entomacrodus chiostictus and Ophioblennius steindachneri are herbivores, grazing on fine algae. 4) Plagiotremus azaleus specializes in cropping mucus and scales from the body surface of other fishes.Crustaceans account for 58.6% of the total volume of prey items in the 34 species investigated. Benthic amphipods were most important and made up 26% of the total volume of all prey items.Cluster analysis of percentage volumetric data using Squared Euclidian Distance and Horn's Index of Overlap produced distinct subgroups which coarsely reflected taxonomic grouping.The species are separated either by their geographic ranges, habitat and microhabitat preferences, feeding, or a combination thereof. Only rarely do sympatric species significantly overlap in diet.Trophic diversity as measured by the Shannon-index provides a tool for distinguishing: 1) specialists (6 species) from 2) low diversity feeders (18 species) and 3) high diversity generalists (10 species). Two different types of specialists can be distinguished: those which feed on the same items as the generalists but utilize only a very restricted prey spectrum (Stathmonotus sinuscalifornici and the chaenopsids Chaenopsis alepidota and Emblemaria hypacanthus). A second group of specialists (Entomacrodus chiostictus and Ophioblennius steindachneri as well as Plagiotremus azaleus) feed on items not utilized by any of the generalists.There is some evidence that high diversity generalists are numerically more abundant than the other trophic groups.In the labrisomids and blenniids a phylogenetic trend from microcarnivory towards feeding on sessile items appears to be expressed.


Evaluation of serum estrogen-DNA adducts as potential biomarkers for breast cancer risk.
This study was conducted to determine whether the ratio of estrogen-DNA adducts to their respective metabolites and conjugates in serum differed between women with early-onset breast cancer and those with average or high risk of developing breast cancer. Serum samples from women at average risk (n=63) or high risk (n=80) for breast cancer (using Gail model) and women newly diagnosed with early breast cancer (n=79) were analyzed using UPLC-MS/MS. Adduct ratios were statistically compared among the three groups, and the Area Under the Receiver Operating Characteristic Curve (AUC) was used to identify a diagnostic cut-off point. The median adduct ratio in the average-risk group was significantly lower than that of both the high-risk group and the breast cancer group (p values<0.0001), and provided good discrimination between those at average versus high risk of breast cancer (AUC=0.84, 95% CI 0.77-0.90). Sensitivity and specificity were maximized at an adduct ratio of 77. For women in the same age and BMI group, the odds of being at high risk for breast cancer was 8.03 (95% CI 3.46-18.7) times higher for those with a ratio of at least 77 compared to those with a ratio less than 77. The likelihood of being at high risk for breast cancer was significantly increased for those with a high adduct ratio relative to those with a low adduct ratio. These findings suggest that estrogen-DNA adducts deserve further study as potential biomarkers for risk of developing breast cancer.


Capecitabine and oxaliplatin in advanced colorectal cancer: a dose-finding study.
Capecitabine and oxaliplatin are both active anticancer agents in the treatment of patients with advanced colorectal cancer (ACRC). The aim of this dose-finding trial was to determine the maximum-tolerated dose (MTD), the dose-limiting toxicities (DLTs) and the activity of the combination in patients with advanced colorectal cancer. Twenty-five chemotherapy-pretreated patients received the combination of capecitabine and oxaliplatin. Capecitabine was administered orally twice a day continuously for 14 days in doses ranging from 1,650 to 2,500 mg/m2/d, and oxaliplatin was administered as a two-hour infusion on day 1 using dose, ranges from 100 to 130 mg/m2 repeated every three weeks. Twenty-five patients were assessable for toxicity, and DLTs were diarrhea (grade > or = 3: 27%) and stomatitis (grade > or = 3: 9%) at dose level VI. Dose level V (capecitabine 2500 mg/m2 and oxaliplatin 120 mg/m2) was found to be the MTD. Hematological toxicity was minimal, overall neurotoxicity (grade 1-4) was 27% with 1% grade 3-4. A global response rate was 17% (95% confidence interval (95% CI): 2%-32%) and the median overall survival was 12 months. The recommended dose for further phase II studies is capecitabine 2,500 mg/m2/d with intermittent schedule and oxaliplatin 120 mg/m2 every three weeks. The toxicities were mainly gastrointestinal: diarrhea, stomatitis and vomiting. This combination should be studied in phase II trials in advanced colorectal.


Osteoclast differentiation by human osteoblastic cell line SaOS-2 primed with bacterial lipid A.
We examined the responses of human osteoblastic cell line SaOS-2 to bacterial lipid A, a bioactive center of lipopolysaccharide, during osteoclast differentiation of human peripheral blood mononuclear cells (PBMC). SaOS-2 cells expressed mRNA for Toll-like receptor (TLR) 4, MD-2, CD14, and myeloid differentiation factor 88, whereas they failed to express mRNA for TLR2. Escherichia coli-type synthetic lipid A (compound 506) induced cytokine mRNA expression and nuclear factor (NF)-kappaB activation in SaOS-2 cells. Compound 506 also increased the expression of receptor activator of NF-kappaB ligand. Further, cells primed with compound 506 augmented the differentiation of PBMC into osteoclastic cells, and the effect was inhibited by anti-TLR4 monoclonal antibody. These findings suggest that the TLR signaling cascade in osteoblastic cells is involved in regulating the function of osteoclastogenesis.


High-salt stabilization of Laponite clay particles.
Colloidal radioactive transuranic wastes are currently buried in large tanks in the form of dense colloids in high salt, high pH aqueous media. These facilities are beginning to fail, so it is necessary to transport and "package" them for more permanent disposal, processes requiring understanding of the microstructure that develops under such conditions. Laponite RD clay is believed to be a good simulant for the colloids in the waste tanks, and the present study addresses their behavior under high salt conditions, where previous studies have frequently observed the phenomenon of "restabilization," i.e., the attainment of aggregation stability at high electrolyte conditions. Specifically, the aggregation kinetics and the resulting cluster structure (fractal dimension) of Laponite RD clay colloids at high concentrations of BaCl2 (an electrolyte previously shown to lead to restabilization) are investigated. At low-to-intermediate electrolyte concentrations, the clay is found to behave in accord with DLVO theory, i.e., low salt conditions yield slow aggregation into densely-packed aggregates, whereas intermediate salt concentrations, sufficient to cause double layer collapse, produce rapid aggregation into open aggregates. High salt concentrations, however, show slow rates of aggregation. The aggregate structure under these conditions is found to mimic that found for very low electrolyte concentrations, i.e., high fractal dimension. Further experiments show that a sudden increase in salt concentration in a system containing young open aggregates produced under intermediate salt concentrations causes them to reform into more compact structures.


Inflammation-Enhanced Drug-Induced Liver Injury.
Drug-induced liver injury is a major concern in clinical studies as well as in post-marketing surveillance. Previous evidence suggests that drug exposure during periods of inflammation can increase an individual's susceptibility to toxicity. Inflammation caused by infections or endotoxin markedly activates NADPH oxidase that generates superoxide radicals by transferring electrons from NADPH. In the phagosome, superoxide radicals spontaneously form hydrogen peroxide (H2O2) and other reactive oxygen species. Neutrophils or Kupffer cells also release myeloperoxidase on activation. The aim of this study was to develop and validate an in vitro oxidative stress inflammation model to identify compounds that may increase hepatotoxicity during inflammation. When a non-toxic H2O2 generating system (glucose/glucose oxidase) with peroxidase or Fe(II) (to simulate in vivo inflammation) were added to the freshly isolated rat hepatocytes prior to the addition of the investigated drug which increased drug-induced cytotoxicity and ROS formation. This was reversed by 6-N-propyl-2-thiouracil (a peroxidase inhibitor) or desferoxamine (an Fe(II) chelator), respectively. Flutamide, nilutamide, nimesulide, methotrexate, and 6-mercaptopurine were found to form pro-oxidant radicals leading to oxidative stress and mitochondrial injury whereas azathioprine did not form any radicals with this inflammation system. Electron spin resonance spectrometry spin trapping studies of 6-mercaptopurine metabolism by HRP (horseradish peroxidase)/H2O2 was also investigated. A mixture of two radicals were trapped using DMPO (5,5-dimethyl-1-pyrroline-N-oxide) which were previously reported as purine-6-thiyl and superoxide radicals. This system may provide a more robust in vitro pre-clinical tool for screening of drugs for potential hepatotoxicity associated with inflammation.


Same-day antiretroviral therapy initiation hub model at the Thai Red Cross Anonymous Clinic in Bangkok, Thailand: an observational cohort study.
WHO has recommended rapid antiretroviral therapy (ART) initiation, including same-day ART (SDART). However, data on the feasibility in real-world settings are limited. We implemented a cohort study at a stand-alone HIV testing centre to examine its applicability and effectiveness. Data were collected from the Thai Red Cross Anonymous Clinic in Bangkok, Thailand, between July 2017 and July 2018 from clients who were ART-naïve and could return for follow-up visits. Baseline laboratory tests and chest X-ray were performed according to national guidelines, and clinical eligibility was determined based on physical examination and chest X-ray findings. Primary outcomes were retention in care and viral load suppression at 3, 6 and 12 months. During the study period, 2427 people tested HIV positive. Of these, 2107 (2207/2427, 86.8%) met logistical criteria, and 1904 (1904/2427, 78.5%) agreed to SDART. One thousand seven hundred and twenty-nine (1729/2427, 71.2%) were placed on ART, with 1257 received same-day initiation and 1576 initiated ART within 7 days; 1198 clients were successfully referred to free, sustained ART sites. Retention among eligible clients who accepted SDART service at months 3, 6 and 12 was 79.8%, 75.2% and 75.3%, respectively. Same-day ART initiation hub model at a stand-alone HIV testing centre in an urban setting in Bangkok, Thailand, is highly feasible and has a potential for scaling up. NCT04032028.


Metabolic activity of osteoblasts retrieved from osteoarthritic patients after stimulation with mediators involved in periprosthetic loosening.
To compare the effects of polymethylmetacrylate (PMMA), interleukin-1beta (IL-1beta), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) on osteoarthritic (OA) human osteoblasts (Ob). Ob cell cultures were prepared from metaphyseal trabecular bone of OA patients (n=9). Their cellular metabolic activity was characterized by measuring alkaline phosphatase (ALPase), osteocalcin (Oc), osteoprotegerin (OPG), prostaglandin E2 (PGE2), IL-6, macrophage colony-stimulating factor (M-CSF) and soluble receptor activator of NF-kappaB ligand (sRANKL) in supernatants after Ob stimulation with PMMA, IL-1beta, IL-6 or TNF-alpha. IL-6 and PGE2 production by Ob was significantly increased by all mediators used. PMMA and TNF-alpha both stimulated M-CSF and sRANKL production whereas PMMA decreased and TNF-alpha augmented OPG release by Ob. The ratio sRANKL/OPG was significantly increased with PMMA and TNF-alpha, and treatment with anti-IL-6 antibodies did not alter this ratio. ALPase levels remained constant while only PMMA affected Oc production. Subclassification of patients into high or low endogenous producers of IL-6 and PGE2 before stimulation of Ob indicated that the two subgroups maintained similar responses to stimulation by all mediators. PMMA and TNF-alpha have comparable dual action on Ob, lowering their anabolic capacity and favoring production of bone resorption activators, an action not mediated by IL-6. This study confirms the important role of PMMA in implant loosening. However, the pertinence of high and low metabolic activities in OA Ob remains unclear, but could be involved in the pathophysiology of bone disease and aseptic loosening.


Can counter-advertising diminish persuasive effects of conventional and pseudo-healthy unhealthy food product advertising on parents?: an experimental study.
To help address rising rates of obesity in children, evidence is needed concerning impacts of common forms of marketing for unhealthy child-oriented food products and the efficacy of educational interventions in counteracting any detrimental impacts of such marketing. This study aims to explore parents' responses to advertising for unhealthy children's food products that employ different types of persuasive appeals and test whether a counter-advertising intervention exposing industry motives and marketing strategies can bolster parents' resistance to influence by unhealthy product advertising. N = 1613 Australian parents were randomly assigned to view online either a: (A) non-food ad (control); (B) conventional confectionery ad (highlighting sensory benefits of the product); (C) pseudo-healthy confectionery ad (promoting sensory benefits and health attributes of the product); (D) conventional confectionery ad + counter-ad (employing inoculation-style messaging and narrative communication elements); (E) pseudo-healthy confectionery ad + counter-ad. Parents then viewed various snacks, including those promoted in the food ads and counter-ad. Parents nominated their preferred product, then rated the products. Exposure to the conventional confectionery ad increased parents' preference for the advertised product, enhanced perceptions of the product's healthiness and reduced sugar content and boosted brand attitude. Exposure to the pseudo-healthy confectionery ad increased parents' preference for the advertised product, and enhanced perceptions of healthiness, fibre content and lower sugar content. The counter-ad diminished, but did not eliminate, product ad effects on parents' purchasing preference, product perceptions and brand attitudes. The counter-ad also prompted parents to perceive processed foods as less healthy, higher in sugar and lower in fibre and may have increased support for advertising regulation. Exposure to unhealthy product advertising promoted favourable perceptions of products and increased preferences for advertised products among parents. Counter-advertising interventions may bolster parents' resistance to persuasion by unhealthy product advertising and empower parents to more accurately evaluate advertised food products.


Quality of life after bariatric surgery--a comparative study of laparoscopic banding vs. bypass.
Laparoscopic gastric banding and Roux-en-Y gastric bypass are widely used for the treatment of morbid obesity. The impact of these two procedures on health-related quality of life has not been analyzed in comparative studies. A matched-pair analysis of a prospectively collected database was performed. Fifty-two consecutive patients with laparoscopic gastric bypass were randomly matched to fifty-two patients with laparoscopic gastric banding according to age, BMI, and gender. Quality of life was assessed using two standardized questionnaires (SF 36 and Moorehead-Ardelt II). Mean preoperative BMI was 45.7 kg/m(2) for the bypass patients and 45.3 kg/m(2) for the banding patients. Mean BMI after 3 years follow-up of was 30.4 kg/m(2) and 33.1 kg/m(2) (p=0.036). In the SF 36 questionnaire, gastric bypass patients yielded a mean total score of 613 versus 607 points in the gastric banding group (p=0.543), which is comparable to the normal population in Europe. In the Moorhead-Ardelt II questionnaire, the gastric bypass patients scored a mean total of 1.35 points and the gastric banding patients 1.28 points (p=0.747). Of the patients, 97% with a gastric bypass and 83% with a gastric banding were satisfied with the result of the operation (p=0.145). The patients after laparoscopic gastric bypass and laparoscopic gastric banding have a high level of satisfaction 3 years after the operation and have similar quality of life scores compared to the normal population. Quality of life indexes were not different between the two procedures and were independent of weight loss in successfully operated patients.


Dementia from the ABCD1 mutation c.1415-1416delAG in a female carrier.
Progressive dementia is a rare phenotypic feature of female X-ALD carriers. Even rarer is the additional presence of further risk factors for dementia, such as diabetes, hypothyroidism, and hepatopathy. We report a unique female X-ALD carrier presenting with severe, progressive dementia, paraspasticity, sphincteric dysfunction, and multisystem disease. A 79 years-old female with a history of strumectomy, diabetes, hepatopathy, hypothyroidism, arterial hypertension, hiatal hernia, left retinal ablation, ovariectomy, hysterectomy, osteoporosis, bilateral hip endoprosthesis, and neurogenic bladder dysfunction developed slowly progressive cognitive decline since age of 77 years. She had been identified as a female carrier of X-ALD in 12/2010 upon a family screening. At age of 79 years she presented with severe dementia, anxiety, unsteadiness, helplessness, hypertelorism, exaggerated patella tendon reflexes, reduced Achilles tendon reflexes, club feet, contractures of the ankles, the knees, and the hips, and the inability to stay or walk. Cerebral CT showed diffuse atrophy, demyelination periventricularly, small lacunas in the basal ganglia, and small calcifications of the basal ganglia and the temporal lobe on the right side. Differential diagnoses of dementia were considered but were all excluded upon the clinical presentation, blood chemical investigations, imaging studies, and the pattern of neuropsychological deficits. With progression of the disease manifesting X-ALD carriers may develop progressive severe dementia, severe paraspasticity, and sphincteric dysfunction. Female carriership of X-ALD can be a differential diagnosis of dementia.


After daily bingeing on a sucrose solution, food deprivation induces anxiety and accumbens dopamine/acetylcholine imbalance.
Bingeing on sugar may activate neural pathways in a manner similar to taking drugs of abuse, resulting in related signs of dependence. The present experiments test whether rats that have been bingeing on sucrose and then fasted demonstrate signs of opiate-like withdrawal. Rats were maintained on 12-h deprivation followed by 12-h access to a 10% sucrose solution and chow for 28 days, then fasted for 36 h. These animals spent less time on the exposed arm of an elevated plus-maze compared with a similarly deprived ad libitum chow group, suggesting anxiety. Microdialysis revealed a concomitant increase in extracellular acetylcholine and decrease in dopamine release in the nucleus accumbens shell. These results did not appear to be due to hypoglycemia. The findings suggest that a diet of bingeing on sucrose and chow followed by fasting creates a state that involves anxiety and altered accumbens dopamine and acetylcholine balance. This is similar to the effects of naloxone, suggesting opiate-like withdrawal. This may be a factor in some eating disorders.


Boosting lung accumulation of gallium with inhalable nano-embedded microparticles for the treatment of bacterial pneumonia.
The potential of intra-venous gallium nitrate (GaN) administration against Pseudomonas aeruginosa pneumonia was recently demonstrated in mice and in cystic fibrosis (CF) patients. Likewise, the added value of direct lung delivery of Ga(III) has been shown in rats. Therefore, the design of a drug delivery system specifically engineered for Ga(III) inhalation is imperative to improve its accumulation in lungs. To this purpose, Ga(III) was efficiently encapsulated into hyaluronic acid/chitosan nanoparticles (Ga_HA/CS NPs), whose features were tuned to facilitate access to the target by overcoming mucus and biofilm surrounding bacteria. Then, to improve in vivo lung deposition, Ga_HA/CS NPs were engineered into mannitol-based NEM (Ga_Man NEM). The powders showed optimal in vitro aerosol performance, and sustained release kinetics in lung lining fluids. Moreover, good tolerability and antimicrobial properties were shown in vitro. Intratracheal insufflation of Ga_Man NEM in rats resulted in a significant improvement of Ga(III) persistence in the lungs coupled to a lower Ga(III) concentration in plasma and urine, compared to GaN solution. Noteworthy, the developed formulation significantly modifies the unfavorable Ga(III) kinetic increasing the Ga(III) to the lung and preventing Ga(III) accumulation in the kidney, key responsible for adverse effects, conclusively demonstrating the benefit of Ga_Man NEM to exploit the therapeutic effect of Ga(III) via inhalation route.


Breast cancer and oral contraceptives: patterns of risk among parous and nulliparous women--further analysis of the Swedish-Norwegian material.
A Swedish-Norwegian case-control study comprising 473 women less than 45 years old with newly diagnosed invasive breast cancer diagnosed in 1984-85, and 722 age-matched control women, was reanalyzed to evaluate if nulliparous women who had used oral contraceptives (OCs) were at particular risk for breast cancer. The relative risk for nulliparous women who had used OCs for eight years or more was 4.3 (95% confidence interval, 1.4-13.1), and parous women with the same duration of use had relative risk 1.7 (0.7-4.2) as compared to nulliparous and parous women, respectively, who had never used OCs. Parous women who had used OCs for twelve years or more after their first full-term pregnancy had a relative risk of 3.0 (1.3-7.4). The findings from the study suggest that nulliparous women may be particularly susceptible to the risk for breast cancer with long-term OC use.


Potential feature exploration and model development based on 18F-FDG PET/CT images for differentiating benign and malignant lung lesions.
The study is to explore potential features and develop classification models for distinguishing benign and malignant lung lesions based on CT-radiomics features and PET metabolic parameters extracted from PET/CT images. A retrospective study was conducted in baseline 18 F-flurodeoxyglucose positron emission tomography/ computed tomography (18 F-FDG PET/CT) images of 135 patients. The dataset was utilized for feature extraction of CT-radiomics features and PET metabolic parameters based on volume of interest, then went through feature selection and model development with strategy of five-fold cross-validation. Specifically, model development used support vector machine, PET metabolic parameters selection used Akaike's information criterion, and CT-radiomics were reduced by the least absolute shrinkage and selection operator method then forward selection approach. The diagnostic performances of CT-radiomics, PET metabolic parameters and combination of both were illustrated by receiver operating characteristic (ROC) curves, and compared by Delong test. Five groups of selected PET metabolic parameters and CT-radiomics were counted, and potential features were found and analyzed with Mann-Whitney U test. The CT-radiomics, PET metabolic parameters, and combination of both among five subsets showed mean area under the curve (AUC) of 0.820 ± 0.053, 0.874 ± 0.081, and 0.887 ± 0.046, respectively. No significant differences in ROC among models were observed through pairwise comparison in each fold (P-value from 0.09 to 0.81, Delong test). The potential features were found to be SurfaceVolumeRatio and SUVpeak (P < 0.001 of both, U test). The classification models developed by CT-radiomics features and PET metabolic parameters based on PET/CT images have substantial diagnostic capacity on lung lesions.


[Increase of prilocaine-induced methemoglobinemia following anesthesia induction].
Although the local anaesthetic prilocaine is less cardio- and neurotoxic than lidocaine, it bears the disadvantage of the formation of methaemoglobin by the metabolite o-toluidine. Prilocaine is often successfully used, especially for the blockade of the brachial plexus, but one problem of this technique is the failure rate of 3-10%, with the consequence that general anaesthesia after administration of prilocaine is frequently necessary. Methaemoglobin formation after prilocaine administration has been thoroughly investigated. Nothing is known, however, about the interactions of prilocaine and the induction of general anaesthesia relative to methaemoglobinaemia. CASE REPORT. Two patients (47 and 52 years old) each received 500 mg prilocaine for the axillary blockade of the brachial plexus. After 100 and 120 min respectively, it was necessary to induce general anaesthesia, for which 350 mg thiopental, 1 mg alfentanil and 45 mg atracurium were used. At 15 min after induction, methaemoglobin levels had increased by 70% and 25%, respectively, from baseline before general anaesthesia. CONCLUSION. It is not possible to explain these findings conclusively with the present method. To check whether displacement of o-toluidine from the plasma protein binding might have been responsible, we provoked methaemoglobinaemia in vitro by adding o-toluidine to heparinised blood. Thiopental was then added to half the specimens. Subsequently, methaemoglobin levels were lower in the samples with thiopental. Three explanations seem plausible: (1) Thiopental blocks the hydroxylase of the endoplasmic reticulum, with the result that o-toluidine cannot be further metabolised, leading to higher o-toluidine and methaemoglobin levels. (2) Isoflurane improves the blood supply of the liver. This results in increased metabolism of prilocaine to o-toluidine. (3) The results were accidental. To clarify which of these explanations is correct, further investigation is necessary.


Beyond the Burke-Fahn-Marsden Dystonia Rating Scale: deep brain stimulation in childhood secondary dystonia.
Deep brain stimulation is now widely accepted as an effective treatment for children with primary generalized dystonia. More variable results are reported in secondary dystonias and its efficacy in this heterogeneous group has not been fully elucidated. Deep brain stimulation outcomes are typically reported using impairment-focused measures, such as the Burke-Fahn-Marsden Dystonia Rating Scale, which provide little information about function and participation outcomes or changes in non-motor areas. The aim is to demonstrate that in some cases of secondary dystonia, the sole use of impairment level measures, such as the Burke-Fahn-Marsden Dystonia Rating Scale, may be insufficient to fully evaluate outcome following deep brain stimulation. Six paediatric cases who underwent deep brain stimulation surgery with a minimum of one year follow up were selected on the basis of apparent non-response to deep brain stimulation, defined as a clinically insignificant change in the Burke-Fahn-Marsden Dystonia Movement Scale (<20%), but where other evaluation measures demonstrated clinical efficacy across several domains. Despite no significant change in Burke-Fahn-Marsden Dystonia Rating Scale scores following deep brain stimulation, parallel outcome measures demonstrated significant benefit in a range of child and family-centred goal areas including: pain and comfort, school attendance, seating tolerance, access to assistive technology and in some cases carer burden. Sole use of impairment-focused measures, are limited in scope to evaluate outcome following deep brain stimulation, particularly in secondary dystonias. Systematic study of effects across multiple dimensions of disability is needed to determine what deep brain stimulation offers patients in terms of function, participation, care, comfort and quality of life. Deep brain stimulation may offer meaningful change across multiple domains of functioning, disability and health even in the absence of significant change in dystonia rating scales.


Fate in the environment and long-range atmospheric transport of the organophosphorus insecticide, chlorpyrifos and its oxon.
The fate and movement of the organophosphorus insecticide chlorpyrifos (CPY;CAS No.2921-88-2) and its metabolite chlorpyrifos-oxon (CPYO; CASNo.5598-15-2) determine exposures in terrestrial and aquatic environments.Detectable concentrations of the organophosphorus insecticide CPY in air, rain,snow and other environmental media have been measured in North America and other locations at considerable distances from likely agricultural sources, which indicates the potential for long range transport (LRT) in the atmosphere. This issue was addressed by first compiling monitoring results for CPY in all relevant environmental media. As a contribution to the risk assessment of CPY in remote regions, a simple mass balance model was developed to quantify likely concentrations at locations ranging from local sites of application to more remote locationsup to hundreds of km distant. Physical-chemical properties of CPY were reviewed and a set of consistent values for those properties that determine partitioning and reactivity were compiled and evaluated for use in the model. The model quantifies transformation and deposition processes and includes a tentative treatment of dispersion to lesser atmospheric concentrations. The model also addressed formation and fate of CPYO, which is the major transformation product of CPY. The Characteristic Travel Distance (CTD) at which 63% of the original mass of volatilized CPY is degraded or deposited-based on a conservative concentration of •OHradicals of 0.7 x 106 molecules cm-3 and a half-life of 3 h, was estimated to be 62 km. At lesser concentrations of •OH radical, such as occurs at night and at lesser temperatures, the CTD is proportionally greater. By including monitoring data from a variety of media, including air, rain, snow and biota, all monitored concentrations can be converted to the equilibrium criterion of fugacity, thus providing asynoptic assessment of concentrations of CPY and CPYO in multiple media. The calculated fugacities of CPY in air and other media decrease proportionally with increasing distance from sources, which can provide an approximate prediction of downwind concentrations and fugacities in media and can contribute to improved risk assessments for CPY and especially CPYO at locations remote from points of application, but still subject to LRT. The model yielded estimated concentrations that are generally consistent with concentrations measured, which suggests that the canonical fate and transport processes were included in the simulation model. The equations included in the model enable both masses and concentrations of CPY and CPYO to be estimated as a function of distance downwind following application.While the analysis provided here is useful and an improvement over previous estimates of LRT of CPY and CPYO, there is still need for improved estimates of the chemical-physical properties of CPYO.Based on the persistence in water, soils, and sediments, its bioconcentration and biomagnification in organisms, and its potential for long-range transport, CPY and CPYO do not trigger the criteria for classification as a POP under the Stockholm convention or a PB chemical under EC 1107/2009. Nonetheless, CPY is toxic at concentrations less than the trigger for classification as T under EC 11 07 /2009; however,this simple trigger needs to be placed in the context of low risks to non-target organisms close to the areas of use. Overall, CPY and CPYO are judged to not trigger the PBT criteria of EC 1107/2009.


Suicide in urban New South Wales, Australia 1985-1994: socio-economic and migrant interactions.
Variation of suicide with socio-economic status (SES) in urban NSW (Australia) during 1985-1994, by sex and country or region of birth, was examined using Poisson regression analysis of vital statistics and population data (age >¿ approximately 15 yr). Quintiles of SES were defined by municipality of residence and comparisons of suicide by SES were adjusted for age and country (or region) of birth (COB), and examined by COB. Risk of suicide in females was 28% that of males for all adults and 21% for youth (age 15-24 yr). Suicide risk was lower in males from southern Europe, Middle East and Asia, and higher in northern and eastern European males, compared to the Australian-born. Risks for suicide increased significantly with decreasing SES in males, but not in females. The relationship of male suicide and SES was stronger when controlled for COB. For males, the relative risk of suicide, adjusted for age and COB, was 66% higher in the lowest SES quintile compared to the highest quintile. and 39% higher for youth (age 15-24 yr). For male suicide, the population attributable fraction for SES (less than the highest quintile) was 27%. Analysis of SES differentials in male suicide according to COB indicated a significant inverse suicide gradient in relation to SES for the Australian-born and those born in New Zealand and the United Kingdom or Eire, but not in non-English speaking COB groups, except for Asia. For Australian-born males, suicide risk was 71% higher in the lowest SES group (compared to the highest), adjusted for age. These findings indicate that SES plays an important role in male suicide rates among the Australian-born and migrants from English-speaking countries and Asia, and among youth; but not in female suicide, nor suicide in most non-English speaking migrant groups. Reduction in SES differentials through economic and social policies may reduce male suicide in lower SES groups and should be seen to be at least as important as individual level interventions.


Cloning and sequencing of porcine moesin and radixin cDNA and identification of highly conserved domains.
The full length cDNA of porcine moesin and radixin have been cloned and sequenced. Comparison of the closely related sequences of human, murine and porcine moesin, ezrin and radixin with a protein from Echinococcus multilocularis, an evolutionarily quite distant human parasite, reveals several highly invariant domains in the aminoterminal and carboxyterminal regions. Most of these conserved domains are clustered around tyrosine residues that are putative phosphorylation sites for tyrosine phosphokinases.


[Partial delegation to radiation therapists of the control by onboard imaging of patient positioning].
Daily set up of patients with prostate cancer using orthogonal kV/kV imaging and weekly set up control require 1h to 1h30 of off line revision by a radio-oncologist per day and per accelerator. The aim of this study was to evaluate the possibility to delegate this control to radiation therapists. The files of 33 patients (including 13 with prostate cancer) treated from November 2010 to February 2011 on a Varian™ Clinac IX accelerator with an OBI™ system were evaluated. Radiation therapists made the daily kV/kV imaging. Radiation therapists made the online control by kV/kV for patient repositioning and radio-oncologists made the offline reviews; the results were compared and analysed (seven radiation therapists and seven radio-oncologists). For an isocentre displacement of 5mm, the radiation therapist had to call the radio-oncologist to make a medical decision (treatment or patient displacement). The difference of measures and the concordance of decisions between radiation therapists and radio-oncologists were calculated. Five hundred and fifty-six measures were made for 33 treatments, including 226 measures for prostate cancer treatment. The difference of measures between radiation therapists and radio-oncologists was 3mm or less in 93.7% for all treatments and 96.2% for prostate cancer treatment. The concordance of decision between radiation therapists and radio-oncologists for measures up to 4mm was 97% (CI95±2%) vs. 57% (CI95±10%) for measures equal to or higher than 5mm (P<0.0001). Radiation therapists are able to do daily set up using kV/kV on the bony structures of patients with prostate cancer, with a risk of disagreement higher than 3mm less than 4%. The weekly set up controls (different primaries) can be delegated to the radiation therapists, subject to an accurate procedure using a medical alert for a given threshold. Training and competence certification are required to secure the process.


New norsesquiterpenoids from Cucubalus baccifer.
The chemical investigation of Cucubalus baccifer L. afforded three new norsesquiterpenoids, cucubalol, cucubalactone and drummondol-11-O-beta-D-glucopyranoside together with two known related compounds, drummondol and 5,7[E]-megastigmadiene-3 beta,4 alpha,9 xi-triol. Their structures were established based on spectral and chemical evidence. No activity was observed in anti-cancer (CDC25), antibacterial (PEPT) and antifungal (YNG) assays.


Real-time reverse transcription-PCR assay for differentiating the Pandemic H1N1 2009 influenza virus from swine influenza viruses.
Since the Pandemic H1N1 2009 (H1N1pdm) influenza virus emerged in human in 2009, H1N1pdm, classical swine H1, Eurasian avian-like H1, human-like H1 and human-like H3 swine influenza viruses have circulated in pig populations, and avian H9N2 viruses have been isolated in pigs as well. In this study, TaqMan single-step real-time reverse transcription-PCR (rtRT-PCR) assays targeting the hemagglutinin gene were developed to differentiate H1N1pdm from other genetic lineages of the H1 subtype and other subtypes of influenza viruses circulating in human and pig populations for veterinary use. H1N1pdm rtRT-PCR detected H1N1pdm RNA and did not cross-react with classical swine H1, Eurasian avian-like H1, human-like H1, human-like H3 swine and avian H9 influenza viruses RNA. Classical swine H1, Eurasian avian-like H1, human-like H1 and H3 and avian H9 rtRT-PCR were reacted exclusively with viral RNA of their respective lineages and subtypes. The results demonstrate that these assays are useful for the diagnosis of the H1N1pdm virus in both human- and animal-health-related fields.


Effectiveness of myofascial release in the management of lateral epicondylitis in computer professionals.
To investigate whether myofascial release (MFR) reduces the pain and functional disability of lateral epicondylitis (LE) in comparison with a control group receiving sham ultrasound therapy in computer professionals. Randomized, controlled, single blinded trial. Nonprofit research foundation clinic in Kerala, India. Computer professionals (N=68) with LE. MFR group or control group. The techniques were administered by certified MFR practitioners and consisted of 12 sessions per client over 4 weeks. The Patient-Rated Tennis Elbow Evaluation (PRTEE) scale was used to assess pain severity and functional disability. The primary outcome measure was the difference in PRTEE scale scores between week 1 (pretest score), week 4 (posttest score), and follow-up at week 12 after randomization. The simple main effects analysis showed that the MFR group performed better than the control group in weeks 4 and 12 (P<.005). Patients in the MFR and control groups reported a 78.7% and 6.8% reduction, respectively, in their pain and functional disability in week 4 compared with that in week 1, which persisted as 63.1% in the follow-up at week 12 in the MFR group. This study provides evidence that MFR is more effective than a control intervention for LE in computer professionals.


Dynamic subcortical modulators of human default mode network function.
The brain's "default mode network" (DMN) enables flexible switching between internally and externally focused cognition. Precisely how this modulation occurs is not well understood, although it may involve key subcortical mechanisms, including hypothesized influences from the basal forebrain (BF) and mediodorsal thalamus (MD). Here, we used ultra-high field (7 T) functional magnetic resonance imaging to examine the involvement of the BF and MD across states of task-induced DMN activity modulation. Specifically, we mapped DMN activity suppression ("deactivation") when participants transitioned between rest and externally focused task performance, as well as DMN activity engagement ("activation") when task performance was internally (i.e., self) focused. Consistent with recent rodent studies, the BF showed overall activity suppression with DMN cortical regions when comparing the rest to external task conditions. Further analyses, including dynamic causal modeling, confirmed that the BF drove changes in DMN cortical activity during these rest-to-task transitions. The MD, by comparison, was specifically engaged during internally focused cognition and demonstrated a broad excitatory influence on DMN cortical activation. These results provide the first direct evidence in humans of distinct BF and thalamic circuit influences on the control of DMN function and suggest novel mechanistic avenues for ongoing translational research.


Determination of LC50 and sub-chronic neurotoxicity of diesel exhaust nanoparticles.
Air pollution is a major problem faced globally and is seen associated with central nervous system (CNS) disorders like neuropathology and neuro-inflammation. Here, we investigated the CNS disorders as a result of sub-chronic exposure (90 days) to diesel exhaust nanoparticles (DENPs) and explored the minimal levels of DENPs needed to exhibit the early mediators of neuro-inflammation and neuropathology. Male and female wistar rats (6 rats per group) were exposed to DENPs (1/5th, 1/10th and 1/15th LC50) by inhalation for 4h per day, 5 days per week over 90 days and neurotoxicity end-points were analyzed. DENP exposure caused elevation in levels of pro-inflammatory cytokines, amyloid beta 42 (Aβ 42), reactive oxygen species (ROS), hydrogen peroxide (H2O2), nitrate (NO3(-)), nitrite (NO2(-)) and apurinic/apyrimidinic sites (AP) at varying degrees at different sections of rat brain. Hence, exposure to DENPs resulted in dose-dependent toxicity and was closely correlated to increased inflammation, DNA damage and oxidative stress.


Antioxidant defense enzymes in multiple sclerosis: A 5-year follow-up study.
Oxidative stress biomarkers are increased in multiple sclerosis (MS) lesions. Antioxidant defense enzymes regulate reactive oxygen species that can cause tissue injury in MS. The study of 91 subjects included 64 relapsing-remitting MS (RR-MS; 72% female, baseline age ± SD = 44.6 ± 11 years, disease duration = 13.3 ± 8.8 years, median Expanded Disability Status Scale [EDSS] = 2.0, interquartile range = 1.8) and 27 healthy controls (HC) at baseline and 5-year follow-up (5YFU). Serum glutathione peroxidase (GPX), glutathione-S-transferase (GST), glutathione reductase (GSHR), superoxide dismutase, and paraoxonase-1 (PON1) arylesterase and paraoxonase activities were measured using kinetic enzyme assays. Total cholesterol (TC), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol (LDL-C), and an apolipoprotein (Apo) panel with ApoA-I, ApoA-II, ApoB, ApoC-II, and ApoE were obtained. Serum neurofilament (sNfL) was used to assess axonal injury. Disability was measured on the EDSS. GSHR activity was lower in HC compared to RR-MS at baseline and 5YFU. GPX (p = 0.008) and PON1 arylesterase and paraoxonase activities (both p = 0.05) increased between baseline and 5YFU in HC but did not increase in RR-MS. At baseline and 5YFU, GPX and GST were associated with TC, LDL-C, and ApoA-II; GSHR was associated with ApoA-II and ApoC-II. Antioxidant enzymes were not associated with sNfL or EDSS in RR-MS. RR-MS patients did not exhibit the changes in antioxidant enzyme activities over 5YFU found in HC; however, the differences were modest. Antioxidant enzyme activities are not associated with disability.


Preprocedural Imaging : A Review of Different Radiological Factors Affecting the Outcome of Thrombectomy.
Endovascular treatment (EVT) has strong evidence for its effectiveness in treatment of acute ischemic stroke (AIS); however, up to half of the patients who undergo EVT still do not have good functional outcomes. Various prethrombectomy radiological factors have been shown to be associated with good clinical outcomes and may be the key to better functional outcomes, reduced complications, and reduced mortality. In this paper, we reviewed the current literature on these imaging parameters so they can be employed to better estimate the probability of procedural success, therefore allowing for more effective preprocedural planning of EVT strategies. We reviewed articles in the literature related to imaging factors which have been shown to be associated with EVT success. The factors which are reviewed in this paper included: anatomical factors such as 1) the type of aortic arch and its characteristics, 2) the characteristics of the thrombus such as length, clot burden, permeability, location, 3) the middle cerebral artery features including the tortuosity and underlying intracranial stenosis, 4) perfusion scans estimating the volume of infarct and the penumbra and 5) the effect of collaterals on the procedure. The prognostic effect of each factor on the successful outcome of EVT is described. The identification of preprocedural thrombectomy imaging factors can help to improve the chances of recanalization, functional outcomes, and mortality. It allows the interventionist to make time-sensitive decisions in the treatment of acute ischemic stroke.


Body Composition and Biochemical Markers of Nutrition in Non-dialysis-Dependent Chronic Kidney Disease Patients.
The aim of this study was to examine the body composition in stages 3b to 5 of chronic kidney disease. There were 149 patients included in the study, with the mean age of 65.5 ± 16.5 years, body mass index (BMI) of 29.4 ± 5.6 kg/m2, and estimated glomerular filtration rate (eGFR) of 23.2 ± 9.3/min/1.73m2. They remained with dialysis. Body composition was measured using bioimpedance spectroscopy, and handgrip strength was measured with a hydraulic dynamometer. The main biochemical markers assessed consisted of serum protein, albumin, prealbumin, high-sensitivity C-reactive protein (hsCRP), and interleukin (IL)-6 content. We found that 39% of patients were overweight and 41% were obese. Obesity was more prevalent in stage 3b of chronic kidney disease than in stages 4-5 in women and in patients older than 60 years of age. Thirty-eight percent of the study population were sarcopenic, of whom 20% presented a sarcopenic obesity phenotype. There were significant associations between lean tissue index (LTI) and serum prealbumin content and handgrip strength. Fat tissue index (FTI) was associated and hsCRP, serum protein, body mass index (BMI), waist-hip ratio, and waist-to-height ratio. There were inverse associations between FTI-LTI and LTI-age. We conclude that the prevalence of obesity in non-dialysis-dependent patients with chronic kidney disease is higher than that in the general population. Earlier stages of chronic kidney disease are associated with a higher prevalence of obesity.


Systematic review and meta-analysis comparing educational and reminder digital interventions for promoting HPV vaccination uptake.
Global Human papillomavirus (HPV) vaccination rates remain low despite available WHO-approved vaccines. Digital interventions for promoting vaccination uptake offer a scalable and accessible solution to this issue. Here we report a systematic review and meta-analysis examining the efficacy of digital interventions, comparing educational and reminder approaches, for promoting HPV vaccination uptake (HVU). This study also identifies factors influencing the effectiveness of these interventions. We searched PubMed, PsycInfo, Web of Science, and the Cochrane Library from each database's inception to January 2023. Three raters independently evaluate the studies using a systematic and blinded method for resolving disagreements. From 1929 references, 34 unique studies (281,280 unique participants) have sufficient data. Client reminder (OR, 1.41; 95% CI, 1.23-1.63; P < 0.001), provider reminder (OR, 1.39; 95% CI, 1.11-1.75; P = 0.005), provider education (OR, 1.18; 95% CI, 1.05-1.34; P = 0.007), and client education plus reminder interventions (OR, 1.29; 95% CI, 1.04-1.59; P = 0.007) increase HVU, whereas client education interventions do not (OR, 1.08; 95% CI, 0.92-1.28; P = 0.35). Digital intervention effectiveness varies based on participants' gender and the digital platform used. Interventions targeting male or mixed-gender participants demonstrate greater benefit, and reminder platforms (SMS, preference reminders, or electronic health record alerts) are more effective in increasing HVU. Digital interventions, particularly client and provider reminders, along with provider education, prove significantly more effective than client education alone. Incorporating digital interventions into healthcare systems can effectively promote HPV vaccination uptake. Reminder interventions should be prioritized for promoting HVU.


Functional redundancy of structural proteins of the peritrophic membrane in Trichoplusia ni.
The peritrophic membrane (or peritrophic matrix) (PM) in insects is formed by binding of PM proteins with multiple chitin binding domains (CBDs) to chitin fibrils. Multi-CBD chitin binding proteins (CBPs) and the insect intestinal mucin (IIM) are major PM structural proteins. To understand the biochemical and physiological role of IIM in structural formation and physiological function of the PM, Trichoplusia ni mutant strains lacking IIM were generated by CRISPR/Cas9 mutagenesis. The mutant T. ni larvae were confirmed to lack IIM, but PM formation was observed as in wild type larvae and lacking IIM in the PM did not result in changes of protease activities in the larval midgut. Larval growth and development of the mutant strains were similar to the wild type strain on artificial diet and cabbage leaves, but had a decreased survival in the 5th instar. The larvae of the mutant strains with the PM formed without IIM did not have a change of susceptibility to the infection of the baculovirus AcMNPV and the Bacillus thuringiensis (Bt) formulation Dipel, to the toxicity of the Bt toxins Cry1Ac and Cry2Ab and the chemical insecticide sodium aluminofluoride. Treatment of the mutant T. ni larvae with Calcofluor reduced the larval susceptibility to the toxicity of Bt Cry1Ac, as similarly observed in the wild type larvae. Overall, in the mutant T. ni larvae, the PM was formed without IIM and the lacking of IIM in the PM did not drastically impact the performance of larvae on diet or cabbage leaves under the laboratory conditions.


Association between glucose variation and lower extremity amputation incidence in individuals with type 2 diabetes: a nationwide retrospective cohort study.
Elevated glucose level is one of the risk factors for lower extremity amputation (LEA), but whether glycaemic variability confers independent risks of LEA remains to be elucidated. This study aimed to investigate the association between visit-to-visit glycaemic variability and minor and major LEA risks during 8 years of follow-up in type 2 diabetic individuals aged 50 years and older. This retrospective cohort study included 27,574 ethnic Chinese type 2 diabetic individuals aged ≥50 years from the National Diabetes Care Management Program in Taiwan. Glycaemic variability measures were presented as the CVs of fasting plasma glucose (FPG-CV) and of HbA1c (A1c-CV). The effect of glycaemic variability on the incidence of LEA events was analysed using Cox proportional hazards models. After a median follow-up of 8.9 years, 541 incident cases of LEA with a crude incidence density rate of 2.4 per 1000 person-years were observed. After multivariate adjustment, FPG-CV and A1c-CV were found to be significantly associated with minor LEA, with corresponding HRs of 1.53 (95% CI 1.15, 2.04) and 1.34 (95% CI 1.02, 1.77) for the third tertiles of FPG-CV and A1c-CV, respectively. In addition, these associations were stronger amongst older adults with longer diabetes duration (≥3 years) than amongst those with shorter duration (<3 years) (pinteraction < 0.01). Our study suggests that visit-to-visit variations in HbA1c and FPG are important predictors of minor LEA amongst older adults with type 2 diabetes, particularly for those with more than 3 years of diabetes duration.


Polycyclic aromatic hydrocarbons (PAHs) in agricultural soils from Ningde, China: levels, sources, and human health risk assessment.
Soil-bound polycyclic aromatic hydrocarbons (PAHs) in farmland are critical to human health. The level, composition, source, and cancer risk of sixteen PAHs in agricultural soil from Ningde, China, were investigated. The results indicated that the total concentrations of 16 PAHs ranged from 77.3 to 1188 ng g-1, with a mean value of 406 ng g-1. Five-ring PAHs were found to have the highest concentrations (148 ± 133 ng g-1), followed by four-ring (120 ± 101 ng g-1), three-ring (61.9 ± 54.2 ng g-1), six-ring (44.6 ± 61.0 ng g-1), and two-ring (31.3 ± 31.0 ng g-1). Employing positive matrix factorization (PMF), four PAH sources including biomass burning (36.3%), coal combustion (35.5%), traffic emissions (16.4%), and coke source (11.8%) were identified. Incremental lifetime cancer risk (ILCR) results showed that ILCR values ranged from 7.1 × 10-4 to 1.1 × 10-3, which will cause moderate-to-high cancer risk to human health mainly via the soil ingestion and dermal contact exposure pathways. The source-oriented results indicated that coal combustion (32.7%), traffic emission (34.3%), and biomass burning (32.4%) had similar contributions to the total cancer risk. Therefore, more attention should be paid to these pyrolysis-originated sources to protect humanity from the health risk of PAHs.


Single multiplex PCR assay to identify simultaneously the six categories of diarrheagenic Escherichia coli associated with enteric infections.
We designed a multiplex PCR for the detection of all categories of diarrheagenic Escherichia coli. This method proved to be specific and rapid in detecting virulence genes from Shiga toxin-producing (stx(1), stx(2), and eae), enteropathogenic (eae and bfp), enterotoxigenic (st II and lt), enteroinvasive (vir F and ipa H), entero-aggregative (aaf II), and diffuse adherent (daa E) Escherichia coli in stool samples.


Conventional and spectral EEG analysis in children treated with cytotoxic agents.
One hundred and six EEG investigations were carried out in 17 children with various types of neoplastic disease without cerebral involvement during one or more courses of treatment with cytotoxic agents EEGs were recorded before and 24 hr after administration of the drugs. The EEGs were evaluated visually and by spectral analysis. A transient slowing of the dominant frequency in the alpha band by about 1 Hz and a decrease in the relative power of alpha activity by 20-30% was observed in only 4 patients. These children did not show any clinical or biochemical signs of neurotoxicity. The children did not receive the same antineoplastic treatment. One patient received very high dose methotrexate, 2 patients received vincristine combined with other cytotoxic agents and the other patient received L-asparaginase. It is suggested that EEG changes in patients receiving intravenous cytotoxic treatment usually occur only where there is pre-existing impairment of the blood--cerebrospinal fluid barrier or blood-brain barrier. No clinical signs of epilepsy, new epileptiform waves in the EEG or long-term changes in the background activity of the EEG were observed in this pilot study.


Temporal patterns of odorant receptor gene expression in adult and aged mice.
In the mouse, the sense of smell relies predominantly on the expression of ~1200 odorant receptor (OR) genes in the main olfactory epithelium (MOE). Each mature olfactory sensory neuron (OSN) in the MOE is thought to express just one of these OR genes; conversely, an OR gene is expressed in thousands to tens of thousands of OSNs per mouse. Here, we have characterized temporal patterns of OR gene expression in a cohort of inbred C57BL6/N mice from the Aged Rodent Colonies of the National Institute on Aging. We applied the NanoString multiplex platform to quantify RNA abundance for 531 OR genes in whole olfactory mucosa (WOM) tissue samples. The five study groups were females aged 2, 6, 12, 18, and 31 months (mo). We classified the 531 temporal patterns using a step-down quadratic regression method for time course analysis. The majority of OR genes (58.4%) are classified as flat: there is no significant difference from a horizontal line within this time window. There are 32.8% of OR genes with a downward profile, 7.2% with an upward profile, and 1.7% with a convex or concave profile. But the magnitude of these decreases and increases tends to be small: only 4.3% of OR genes are differentially expressed (DE) at 31 mo compared to 2 mo. Interestingly, the variances of NanoString counts for individual OR genes are homogeneous among the age groups. Our analyses of these 15,930 OR gene expression data of C57BL6/N mice that were raised and housed under well-controlled conditions indicate that OR gene expression at the MOE level is intrinsically stable.


Heart valve calcifications, survival, and cardiovascular risk in hemodialysis patients.
Cardiovascular (CV) calcifications constitute a strong risk marker, and recent studies in continuous ambulatory peritoneal dialysis patients have associated valvular calcifications to inflammation, mortality, and CV events. The prognostic value of cardiac valve calcifications and their relationship with left ventricular hypertrophy and background cardiovascular risk in hemodialysis patients is still unknown. The prognostic value of heart valve calcifications (detected by echocardiography) for all-cause and CV death was tested in a cohort of 202 hemodialysis (HD) patients. Forty-seven patients had 1 or more calcified valves. Background CV complications were more frequent (P = 0.001) and left ventricular hypertrophy was more severe (P < 0.001) in patients with calcified valves than in those without this alteration. During the follow-up period (44 +/- 23 months), 96 patients died, 66 patients (69%) of CV causes. Valve calcifications were significantly associated with all-cause (P = 0.02) and CV mortality (P < or = 0.001). However, in statistical models adjusting for traditional and nontraditional CV risk factors and background CV complications and left ventricular mass index (LVMI), the relationship between calcified valves and incident all-cause and CV mortality was not significant. In HD patients, cardiac valve calcifications predict all-cause and CV mortality in unadjusted analyses, but these associations are not evident in models adjusting for background CV complications, LVMI, and other risk factors. Cardiac valve calcifications do not provide an independent contribution in the prediction of death and CV mortality.


Short-term exposure to air pollution (PM2.5) induces hypothalamic inflammation, and long-term leads to leptin resistance and obesity via Tlr4/Ikbke in mice.
A previous study demonstrated that a high-fat diet (HFD), administered for one-three-days, induces hypothalamic inflammation before obesity's established, and the long term affects leptin signaling/action due to inflammation. We investigate whether exposure to particulate matter of a diameter of ≤2.5 μm (PM2.5) in mice fed with a chow diet leads to similar metabolic effects caused by high-fat feeding. Compared to the filtered air group (FA), one-day-exposure-PM2.5 did not affect adiposity. However, five-days-exposure-PM2.5 increased hypothalamic microglia density, toll-like-receptor-4 (Tlr4), and the inhibitor-NF-kappa-B-kinase-epsilon (Ikbke) expression. Concurrently, fat mass, food intake (FI), and ucp1 expression in brown adipose tissue were also increased. Besides, decreased hypothalamic STAT3-phosphorylation and Pomc expression were found after twelve-weeks-exposure-PM2.5. These were accompanied by increased FI and lower energy expenditure (EE), leading to obesity, along with increased leptin and insulin levels and HOMA. Mechanistically, the deletion of Tlr4 or knockdown of the Ikbke gene in the hypothalamus was sufficient to reverse the metabolic outcomes of twelve-weeks-exposure-PM2.5. These data demonstrated that short-term exposure-PM2.5 increases hypothalamic inflammation, similar to a HFD. Long-term exposure-PM2.5 is even worse, leading to leptin resistance, hyperphagia, and decreased EE. These effects are most likely due to chronic hypothalamic inflammation, which is regulated by Tlr4 and Ikbke signaling.


Exhaled Nitric Oxide (FeNO) in Patients Hospitalized for an Exacerbation of Bronchiectasis and/or COPD : FeNO Levels in COPD and Bronchiectasis.
Exhaled nitric oxide (FeNO) represents an important marker of airway inflammation, yet its role in chronic obstructive pulmonary disease (COPD) and/or bronchiectasis is not well studied. We aimed to measure FeNO in patients with COPD, bronchiectasis, and combination of COPD/bronchiectasis during an acute exacerbation (AE) of the underlying disease as well as to describe the characteristics of patients with COPD/bronchiectasis overlap in patients hospitalized for an acute exacerbation (AE). Seventy-nine patients were enrolled in the study as follows: COPD n = 45, bronchiectasis n = 18, and COPD and bronchiectasis n = 16. FeNO was measured with a commercially available analyzer within 24 hours of admission and at discharge. FeNO differed significantly on admission when compared at discharge in the whole group (16.91 ± 16.14 vs 12.48 ± 10.67, p = 0.008, respectively). On admission, FeNO was 17.80 ± 18.77 ppb in COPD patients, 17.12 ± 6.59 in bronchiectasis patients, and 11.55 ± 2.42 in patients with COPD/bronchiectasis overlap. At discharge, FeNO was 12.40 ± 12.11 ppb in COPD patients, 15.50 ± 6.39 in bronchiectasis patients, and 9.00 ± 3.22 in patients with combination. FeNO differed significantly in bronchiectasis patients versus patients with COPD/bronchiectasis overlap at admission (p = 0.043) and at discharge (p = 0.020) and versus COPD patients at discharge (p = 0.043). FeNO decreased significantly during the AE in all groups (p = 0.001 for COPD, p = 0.021 for bronchiectasis, and p = 0.026 for combination). FeNO levels in patients with COPD and/or bronchiectasis exacerbation are possibly increased at admission and decrease at discharge. The differences in FeNO levels between groups may reflect different underlying inflammatory mechanisms.


Community Advocacy in Pediatric Practice: Perspectives from the Field.
Pediatrics is a specialty that is grounded in advocacy, possibly more than any other field of medicine. Infants, children, and adolescents depend on others to cover their basic needs including food, shelter, and education and rely on proxy voices to speak out on their behalf. In this article, we describe the importance of community advocacy in pediatrics, best practices for training pediatricians in community advocacy, and case studies to highlight trainee experiences and demonstrate how community advocacy and community-based participatory research can be incorporated in the career of a pediatrician.


Buccal mucosal cell immunohistochemistry: a simple method of determining the ABH phenotype of baboons, monkeys, and pigs.
Baboons and monkeys fail to express ABH antigens on red blood cells (RBCs), and the A or H antigens are expressed only weakly on the surface of pig RBCs. Baboons and monkeys have been previously blood typed by detection of ABH antigens in the saliva after administration of pilocarpine. A reliable method to ABH type pigs is by immunohistochemical staining of renal distal tubules in kidney biopsies. We describe a simple and efficient method to blood type baboons, monkeys, and pigs. Baboons (n = 14) and cynomolgus monkeys (n = 8) were blood typed by staining of buccal mucosal smears and by determining the presence of serum anti-A or B antibodies following human type O adsorption. Pigs (n = 11) were tested for ABH type by immunohistochemistry for the presence of A, B, and H antigens using monoclonal antibodies on (i) renal biopsies, (ii) RBCs, and (iii) buccal mucosal smears, without pilocarpine administration, in addition, (iv) after adsorption on human type O RBCs to remove anti-human antibodies, the pig sera were typed by hemagglutination assay for the presence of anti-A or B antibodies using human A and B RBCs. There was complete consistency among the results obtained using all of the above methods, except that no determination could be made from staining of RBCs in one pig. Staining of buccal mucosal cells proved to be the preferred method in all three species because: (i) expression of A or H antigen is weak on pig RBCs, making an accurate blood type determination difficult, and A, B, and H expression is non-existent on baboon and monkey RBCs, (ii) neither venepuncture nor organ biopsy is necessary, (iii) time-consuming adsorption of anti-human antibodies from the sera of the test animal is not required, and (iv) it proved a quick method of evaluation.


Correction: Solution-processed Cu2XSnS4 (X = Fe, Co, Ni) photo-electrochemical and thin film solar cells on vertically grown ZnO nanorod arrays.
[This corrects the article DOI: 10.1039/C6RA24149B.].


Traumatic spinal cord injury in rabbits decreases intracellular free magnesium concentration as measured by 31P MRS.
The mechanisms by which traumatic injury to the central nervous system cause irreversible tissue damage remain speculative. Recent reports suggest that a decrease in tissue total and free Mg2+ concentration may be an important factor in the development of such injury after experimental brain trauma. Although total Mg changes have been reported following spinal cord trauma, no studies have examined spinal cord-free Mg2+. In the present study, we have used phosphorus magnetic resonance spectroscopy to determine intracellular free Mg2+ concentration and atomic absorption spectrophotometry to measure total tissue Mg concentration in rabbit spinal cord prior to and following impact trauma. We report that intracellular free Mg2+ concentration decreases from a pre-injury value of 0.80 +/- 0.12 mM (mean +/- S.E.M.) to 0.31 +/- 0.05 mM at 2 h post-trauma. Following injury there was an associated decrease in total tissue Mg and K concentration, but no alterations in tissue Na or water content.


Liquid chromatographic-tandem mass spectrometric method for the plant lignan 7-hydroxymatairesinol and its potential metabolites in human plasma.
A HPLC-MS-MS method was developed for the determination of the plant lignan 7-hydroxymatairesinol and its potential metabolites matairesinol, oxomatairesinol, alpha-conidendrin, 7-hydroxyenterolactone, enterodiol, and enterolactone in human plasma. The method included sample cleanup by solid-phase extraction (SPE) and analysis using a PE Sciex API3000 triple quadrupole mass spectrometer with electrospray ionisation. The lignans were quantified using two deuterated internal standards. They showed good chromatographic linearity, analysis repeatability, and SPE recovery in the presence of plasma. In pooled plasma and in plasma samples collected from two individual subjects lignan glucuronides and sulfates were enzymatically hydrolysed to free lignans and then analysed. All the lignans could be detected in the samples.


Pediatric displaced radial neck fractures: retrospective results of a modified Metaizeau technique.
Treatment of displaced radial neck fractures is challenging and controversial, as the risk of unsatisfactory outcome increases after operative as well non-operative treatment. Between 2004 and 2012, we treated 14 children with type IV fracture of radial neck with mean angulation of 72.8°, using the modified Metaizeau technique. The average follow-up was 39 months. Heterotrophic ossification and transient posterior interosseous nerve palsy were the only complication seen in two patients who had to undergo open reduction. We feel that the inability to achieve closed reduction can be attributed to loss of periosteal hinge. We obtained 100 % excellent clinical outcome and 79 % excellent radiological outcome at final follow-up. The modified closed intramedullary pin reduction technique proved to be minimal invasive technique for displaced radial neck fractures by allowing stable anatomic reconstruction while avoiding all the complications of classical Metaizeau technique.


Prednimustine in combination with methotrexate and 5-fluorouracil in advanced breast cancer: a phase I-II study.
Forty-seven patients with advanced breast cancer were treated with a combination of prednimustine (P), methotrexate (M), 5-fluorouracil (F), and tamoxifen (TAM). Twenty-six patients received P, 80 mg/m2 day 1-5 (series I) and 21 patients received P, 100 mg/m2 day 1-5 (series II). Both series of patients received M, 40 mg/m2 day 1 and 8 and F, 600 mg/m2 day 1 and 8 with a cycle duration of 4 weeks. All patients received TAM 20 mg twice daily. As concerns the haematologic toxicity, WBC were depressed significantly more often than platelet counts, and during the first 3 cycles 70% of the patients had a WBC nadir corresponding to toxicity grade II or more. No signs of cumulative haematologic toxicity were observed. Nausea and vomiting were registered in 40 out of 47 patients but in 35 of these only of grade I-II. Only one patient developed alopecia requiring a wig. The response to treatment could be evaluated in 28 patients, 21 of whom experienced response (CR or PR) of a median duration of 13 months. In conclusion, it seems that prednimustine can be safely used in combination with methotrexate and 5-fluorouracil. The frequency of alopecia is definitely lower than with CMF. Whether this relates also to subjective side effects will require a randomized study, as will a final conclusion concerning the efficacy compared to that of CMF.


The Quality of Health Information Available on the Internet for Patients With Fecal Incontinence.
The aim of this study was to assess the quality of information available through the Internet for a variety of search terms for fecal incontinence (FI). Using the Google search engine, searches were performed for 4 terms: "bowel control problem," "accidental bowel leakage," "fecal incontinence," and "leaking stool." The DISCERN quality analysis tool and JAMA benchmark criteria were implemented by 2 independent reviewers to evaluate the first 20 search results for each term. To determine if 1 term provided higher-quality information, mean DISCERN and JAMA criteria scores as well as Web site category were compared using analysis of variance and Pearson χ tests. Mean DISCERN scores for all terms fell in the middle range of possible scores. DISCERN questions addressing risks of treatment options, effects of treatment on quality of life, and gaps in knowledge/differences in expert opinion had the lowest scores across all search terms (range of scores, 1.1-1.7/5). JAMA criteria on authorship and attribution were most frequently missing on average in 48 of 80 and 42 of 80 Web sites, respectively. There were significant differences in mean DISCERN scores among the terms, with "fecal incontinence" yielding the highest mean score. The term "accidental bowel leakage" yielded the highest number of marketing Web sites, whereas "leaking stool" had the highest proportion of social Web sites. The quality of available information about FI on the Internet is variable, and key components are often missing. The term "fecal incontinence" yielded the highest quality information of all search terms.


Structural Characterization of a Cyclodextrin/l-menthol Inclusion Complex in the Solid-state by Solid-state NMR and Vibrational Circular Dichroism.
Hydrophobic and volatile flavor molecules can be encapsulated inside cyclodextrins (CyDs). Inclusion complexes are frequently used in solid or dispersed states in preserved food and cosmetics. In this study, the solid-state structures of spray-dried inclusion complexes of l-menthol in α-CyD and β-CyD were analyzed using 13C solid-state NMR and vibrational circular dichroism (VCD). The NMR signals of l-menthol and CyDs were identified in the physical mixture and the l-menthol inclusion complex of α- and β-CyD. The NMR signal of the isopropyl-methyl group of menthol in the α-CyD inclusion complex exhibited a large low-field shift, which suggested a steric hindrance between menthol and α-CyD. VCD exhibited specific changes in the intensity of bands corresponding to C-C vibrations in α-CyD and O-C stretching vibrations in l-menthol. Our results indicated that l-menthol specifically fitted the narrow space within α-CyD. The combined solid-state NMR and VCD analysis provided structural insights into the flavor inclusion complex in the solid-state.


3D printing in designing of anatomical posterior column plate.
Acetabulum has a complex anatomy due to which anatomical acetabular plates are still under developmental phase. Although intra-operative contouring of reconstruction plate is done as a standard practice, it is associated with increased operative time and morbidity of patient. We have designed an acetabular plate for posterior fixation from experience of previous studies performed in our institute on acetabular fracture fixation which should be appropriate for most of the patient of Indian origin. Apart from avoiding intra-operative contouring of acetabular plates it also helps in preventing intra articular screw penetration. We selected five consecutive patients with acetabular fracture needed to be operated from posterior approach and designed patient specific plate template from virtual surgical planning and 3D printing. These plate templates were then matched with our acetabular plate design and were used intra-operatively. Many parameters were assessed to evaluate accuracy of our plate design in those five patients. All the plate templates appear to match our designed plate and no intra-operative contouring was required with our plate design. This was a pilot study and we need a large sample size to study accuracy of our acetabular plate design which might avoid intra-operative contouring, decreasing morbidity of patient and prevent wastage of resources in pre-operative planning and computer designing.


Oxidative and antioxidative status in pregnant women with either gestational or type 1 diabetes.
To evaluate oxidative and antioxidative status in pregnant diabetic women between 26 and 32 weeks of gestation. Free and total malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPX), and vitamins A and E were determined in plasma and erythrocytes of 54 pregnant women. Among these, 27 were diabetics with either gestational diabetes mellitus (GDM), sub-group I, or previous insulin-dependent diabetes mellitus (type 1 diabetes), sub-group II. The other 27 patients were controls. Fasting plasma glucose and HbA(1c) levels were determined in all women. HbA(1c) levels, plasma-, and erythrocyte-free MDA levels were significantly higher in all diabetic women and in both sub-groups than in controls. Plasma vitamin E and erythrocyte vitamin A levels were significantly lower in all diabetic women than in controls. Moreover, GPX and SOD activities were significantly reduced in all diabetic women, GPX in both sub-groups and SOD only in type 1 diabetes. The increased oxidative stress we demonstrated in pregnant women with previous type 1 diabetes or with GDM should be monitored by strictly controlling blood glucose during pregnancy with stringent recommendations and perhaps antioxidant supplementation.


Fluorine in metal-catalyzed asymmetric transformations: the lightest halogen causing a massive effect.
This review aims at providing an overview of the most significant applications of fluorine-containing ligands reported in the literature starting from 2001 until mid-2021. The ligands are classified according to the nature of the donor atoms involved. This review highlights both metal-ligand interactions and the structure-reactivity relationships resulting from the presence of the fluorine atom or fluorine-containing substituents on chiral catalysts.


Difficult life events affect lower extremity illness.
Given the relationship between psychological distress and activity tolerance (capability), a stressful life event might diminish accommodation, increase symptoms, and induce a person to seek specialty care. As a first step to investigate this possibility, this study addressed whether difficult life events are associated with greater activity intolerance and pain intensity. A cohort of 127 patients seeking specialty care for lower extremity symptoms completed questionnaires that inquired about difficult life events within the last 12 months as derived from the Holmes Rahe Life Stress Inventory, and recorded pain intensity on an 11-point ordinal scale, activity tolerance [Patient Reported Outcomes Measurement Information System Physical Function Computer Adaptive Test (CAT)], symptoms of anxiety (GAD-2; 2 item version of the Generalized Anxiety Disorder questionnaire), symptoms of depression (PROMIS Depression CAT), self-efficacy when in pain (Pain Self-Efficacy Questionnaire, 2 question version), and demographics. The treating clinician indicated if the disease was established (e.g. arthritis) or relatively new (e.g. sprain/strain). Bivariate and multivariable analyses sought factors associated with activity intolerance and pain intensity. Greater activity intolerance was associated with difficult life events in bivariate analyses (t = 2.13, MD = 3.18, 95% C.I. = 0.22-6.13, p = 0.04) and in multivariable analyses that excluded symptoms of depression. Greater pain intensity was not associated with difficult life events, but was associated with surgeon rating of established disease (β = 1.20, 95% C.I. = 0.33-2.08, p < 0.01), greater symptoms of anxiety (MD = 3.35, s = 1.72; ρ = 0.30, p < 0.01), and less education (β = - 1.06, 95% C.I. = - 1.94- - 0.18, p = 0.02) (no college degree). When a musculoskeletal specialist identifies less activity tolerance (less capability) than anticipated for a given injury or pathology, they can anticipate a potential difficult life event, and expect alleviation of symptoms and improved capability as the stress is ameliorated with time and support. Specialists can be prepared to direct people to community or professional support if requested.


Transcutaneous Carbon Dioxide Measurement in Adult Patients with Neuromuscular Disorders: A quality Level Assessment.
Carbon dioxide tension (PCO2) monitoring during sleep, is crucial to identify respiratory failure in patients with neuromuscular disorders (NMD). Transcutaneous PCO2 monitoring is an available technique to measure PCO2. To assess the quality level of transcutaneous blood gas measurements via SenTec monitor. A 12-month analysis of SenTec measurements was conducted in a Belgian Centre for Home Mechanical Ventilation (HMV). Over two consecutive nights; SpO2 and PCO2 measurements, the presence of PCO2 drift and drift correction with SenTec, were reviewed and scores (0, 1, 2 for poor, medium and high level) were assigned to estimate the quality of measurements. Sixty-nine NMD patients met the inclusion criteria, of which 48/69 used HMV. PCO2 drift and drift correction were present in 15% and 68% of the 138 recordings, respectively. The quality level of measurements throughout night 1, scored 1.55 (0-2). The relevance of our clinical findings from SenTec scoring 1.94 (1-2); was considered highly satisfactory. HMV was ineffective in 24/48 patients. Among 12 patients with hypercapnia, 8 patients improved PCO2 between night 1 and 2. Among 12 patients with hypocapnia, PCO2 improved in 4/12 patients, who reached the range of normal PCO2 (35-47 mmHg). The quality of SenTec measurements was acceptable in the majority of recordings and clinical findings were deemed satisfactory in all cases. A single SenTec measurement was sufficient to determine the need for NIV. However, two SenTec registrations were insufficient to both improve NIV effectiveness in 50% of cases, and, to ensure follow-up of our interventions.


Eosinophils from patients with type 1 diabetes mellitus express high level of myeloid alpha-defensins and myeloperoxidase.
Type 1 diabetes (T1D) is an autoimmune disease caused by T-cell mediated destruction of pancreatic beta cells. Recently, small cationic α-defensin molecules have been implicated in the pathogenesis of certain inflammatory and autoimmune diseases. The purpose of this study was to assess the α-defensin expression in patients with T1D and elucidate the cellular source of their production. Our results show that 30% of patients exhibit increased levels of α-defensin mRNAs in their capillary blood. Quantitative RT-PCR performed on FACS-sorted granulocytes identified CD15(dull)/CD14(weak) population as the cellular source of α-defensins. Surprisingly, this granulocyte subpopulation displayed augmentation of α-defensin expression in all T1D patients tested. The determination of cell surface markers, expression of cell-specific genes and confocal microscopy identified CD15(dull)/CD14(weak) cells as eosinophils. The presence of transcriptionally active eosinophils in diabetic patients suggests that eosinophils could be a part of an intricate innate immune cellular network involved in the development of diabetes.


BRCA1 point mutations in premenopausal breast cancer patients from Central Sudan.
Premenopausal breast cancer (BC) is one of the most common cancers of women in rural Africa and part of the disease load may be related to hereditary predisposition, including mutations in the BRCA1 gene. However, the BRCA1 mutations associated with BC in Africa are scarcely characterized. We report here 33 BRCA1 point mutations, among which 2 novel missense variants, found in 59 Central Sudanese premenopausal BC patients. The high fractions of mutations with intercontinental and uniquely African distribution (17/33, 51.5 % and 14/33, 42.4 %, respectively) are in agreement with the high genetic diversity expected in an African population. Overall 24/33 variants (72.7 %) resulted neutral; 8/33 of unknown significance (24.3 %, including the 2 novel missense mutations); 1 (3.0 %) overtly deleterious. Notably, in silico studies predict that the novel C-terminal missense variant c.5090G>A (p.Cys1697Tyr) affects phosphopeptide recognition by the BRCA1 BRCT1 domain and may have a pathogenic impact. Genetic variation and frequency of unique or rare mutations of uncertain clinical relevance pose significant challenges to BRCA1 testing in Sudan, as it might happen in other low-resource rural African contexts.


Rheological and mechanical properties and interfacial stress development of composite cements modified with thio-urethane oligomers.
Thio-urethane oligomers have been shown to reduce stress and increase toughness in highly filled composite materials. This study evaluated the influence of thio-urethane backbone structure on rheological and mechanical properties of resin cements modified with a fixed concentration of the oligomers. Thio-urethane oligomers (TU) were synthesized by combining thiols - pentaerythritol tetra-3-mercaptopropionate (PETMP) or trimethylol-tris-3-mercaptopropionate (TMP) - with isocyanates - 1,6-hexanediol-diissocyante (HDDI) (aliphatic) or 1,3-bis(1-isocyanato-1-methylethyl)benzene (BDI) (aromatic) or dicyclohexylmethane 4,4'-diisocyanate (HMDI) (cyclic), at 1:2 isocyanate:thiol, leaving pendant thiols. 20wt% TU were added to BisGMA-UDMA-TEGDMA (5:3:2). 60wt% silanated inorganic fillers were added. Near-IR was used to follow methacrylate conversion and rate of polymerization ( [Formula: see text] ). Mechanical properties were evaluated in three-point bending (ISO 4049) for flexural strength/modulus (FS/FM, and toughness), and notched specimens (ASTM Standard E399-90) for fracture toughness (KIC). PS was measured on the Bioman. Viscosity (V) and gel-points (defined as the crossover between storage and loss shear moduli (G'/G″)) were obtained with rheometry. Glass transition temperature (Tg), cross-link density and homogeneity of the network were obtained with dynamic mechanical analysis. Film-thickness was evaluated according to ISO 4049. DC and mechanical properties increased and [Formula: see text] and PS decreased with the addition of TUs. Gelation (G'/G″) was delayed and DC at G'/G″ increased in TU groups. Tg and cross-link density dropped in TU groups, while oligomers let to more homogenous networks. An increase in V was observed, with no effect on film-thickness. Significant reductions in PS were achieved at the same time conversion and mechanical properties increased. The addition of thio-urethane oligomers proved successful in improving several key properties of resin cements, without disrupting the procedures dentists use to polymerize the material. This approach has potential to be translated to commercial materials very readily.


The Antirrhinum AmDEL gene enhances flavonoids accumulation and salt and drought tolerance in transgenic Arabidopsis.
A basic helix-loop-helix (bHLH) transcription factor gene from Antirrhinum, AmDEL , increases flavonoids accumulation and enhances salt and drought tolerance via up-regulating flavonoid biosynthesis, proline biosynthesis and ROS scavenging genes in transgenic Arabidopsis. In plants, transcriptional regulation is the most important tools for increasing flavonoid biosynthesis. The AmDEL gene, as a basic helix-loop-helix transcription factor gene from Antirrhinum, has been shown to increase flavonoids accumulation in tomato. However, its role in tolerance to abiotic stresses has not yet been investigated. In this study, the codon-optimized AmDEL gene was chemically synthesized. Subcellular localization analysis in onion epidermal cells indicated that AmDEL protein was localized to the nucleus. Expression analysis in yeast showed that the full length of AmDEL exhibited transcriptional activation. Overexpression of AmDEL significantly increased flavonoids accumulation and enhanced salt and drought tolerance in transgenic Arabidopsis plants. Real-time quantitative PCR analysis showed that overexpression of AmDEL resulted in the up-regulation of genes involved in flavonoid biosynthesis, proline biosynthesis and ROS scavenging under salt and drought stresses. Meanwhile, Western blot and enzymatic analyses showed that the activities of phenylalanine ammonia lyase, chalcone isomerase, dihydroflavonol reductase, pyrroline-5-carboxylate synthase, superoxide dismutase and peroxidase were also increased. Further components analyses indicated that the significant increase of proline and relative water content and the significant reduction of H2O2 and malonaldehyde content were observed under salt and drought stresses. In addition, the rates of electrolyte leakage and water loss were reduced in transgenic plants. These findings imply functions of AmDEL in accumulation of flavonoids and tolerance to salt and drought stresses. The AmDEL gene has the potential to be used to increase the content of valuable flavonoids and improve tolerance to abiotic stresses in plants.


Levels of organochlorine pesticides in human milk in Ahmedabad, India.
Concentrations of organochlorine compounds, i.e., alpha HCH, gamma HCH, beta HCH, p,p'-DDE, p,p'-DDT, o,p'-DDT, p,p'-DDD and PCBs were determined in 50 human milk samples collected in Ahmedabad, India during 1981-1982. The mothers' ages ranged from 18 to 30 years (mean 24 years), and they were nursing their first or second child. All 50 samples contained alpha-HCH, gamma HCH, beta HCH, p,p'-DDE, and p,p'-DDT in a concentration of 17.51, 1.62, 205.48, 244.71, and 53.43, respectively (median micrograms/kg: whole-milk basis). o,p'-DDT was found in 48 samples whereas p,p'-DDD was detected in 44 samples. The concentration of o,p'-DDT and p,p'-DDD was 53.43 and 5.13 micrograms/kg (median), expressed on a whole-milk basis. PCBs were absent in all samples.


Unilateral hyperplasia of lamina and spinous process of C6 vertebra: case report.
We report a 20-year-old male patient who was admitted to our emergency clinic after a traffic accident and who suffered from neck pain. Radiographic examination of the cervical spine showed hypertrophy of the left lamina and hypertrophy and elongation of the left spinous process of the sixth cervical vertebra (C6). A computed tomography scan revealed the associated schisis of the spinous process at the same level. Magnetic resonance imaging scan demonstrated no abnormality of the neural elements. The patient underwent a surgical operation due to persistent neck pain and the local aesthetic abnormality.