Communication between community mental health services and primary care.
This study aims to assess the rate of six monthly communications between specialised psychiatric services and primary care and to determine factors which predict such communication. A retrospective review of the clinical records of all patients attending the relevant local psychiatric outpatient clinic was carried out by all members of the multidisciplinary team to identify patient demographic and clinical variables as well as to determine if there has been documentation of communication with primary care in the preceding six months. Letters were sent to the relevant primary care teams regarding progress on their patients in cases where it was identified that no communication had occurred in the preceding six months. A total of 145 patients' charts were reviewed. Of these, 53.3% of the patients were females and 46.7% were males. The mean age was 47.9 years (SD = 14). Patients' diagnoses included; depression (41%), bipolar affective disorder (6.7%), schizophrenia/schizoaffective disorder (27.6%), anxiety disorders (6.7%), alcohol dependency syndrome (11%) and other disorders (7%). Overall, only 36% of patients' charts had a record of communication with primary care in the last six months. Only one variable, 'changes made to the patents medication in the last six months' was significantly associated with the likelihood that there had been communication with primary care with an odds ratio of 15 and a p-value of 0.00. A six monthly review has a potential to improve the level of communication between specialised psychiatric services and primary care.


Quality assurance and improvement in oncology using guideline-derived quality indicators - results of gynaecological cancer centres certified by the German cancer society (DKG).
Based on the example of Gynaecological Cancer Centres (GCCs) certified by the German Cancer Society, this study evaluates the results of medical-guideline-derived quality indicators (QIs) for cervical cancer (CC) and ovarian cancer (OC), examines the development of indicator implementation over time as well as the status of guideline-compliant care and identifies improvement measures. QI results for patients with CC and OC treated in GCCs between 2015 and 2019 are analysed. The median, overall proportion and standard deviation of each QI were calculated. Two-sided Cochran-Armitage tests were applied. QIs are divided into two categories: process-organization (PO-QIs) and treatment-procedures (TP-QIs), to allow a differentiated analysis for identifying improvement measures. PO-QIs that reflect the implementation of processes and structures show a high degree of application. PO-QIs have a tremendous influence on the quality of care and are easy to implement through SOPs. TP-QIs report on treatments that are performed in the GCC. TP-QIs that report on systemic therapies reach a plateau where the guideline is known, but patient-related-factors meaningfully prevent further increase. TP-QIs that report on surgical interventions fluctuate. The most relevant factors are practitioners' personal skills. Besides the discussion of results amongst peers during the audit, improvement measures could include surgical courses or coaching. The analysis shows that a combination of different measures is necessary to anchor quality sustainably in health care and thus improve it.


Acamprosate effect on neuropathic pain in rats: With emphasis on the role of ERK/MAPK pathway and SCN9A sodium channel.
Neuropathic pain is a chronic pain owing to nerve damage or diseases of the central nervous system (CNS). The expression of SCN9A, which encodes the Nav1.7 voltage-gated sodium channel and ERK have been found to change significantly in many cases of neuropathic pain. Here, we investigated effects of acamprosate on neuropathic pain, taking into account the crucial roles of SCN9A, the ERK signaling pathway, and inflammatory markers in a rat model of chronic constriction injury (CCI). Acamprosate (300 mg/kg) was injected intraperitoneally (i.p.) for 14 days. The tail-immersion, acetone, and formalin tests were used to determine behavioral tests such as heat allodynia, cold allodynia, and chemical hyperalgesia, respectively. Lumbar spinal cord was extracted and processed for Nissl staining. The amount of spinal SCN9A expression and ERK phosphorylation were examined using ELISA assay. The expression of SCN9A, ERK, inflammatory cytokines (IL-6 and TNF-α), allodynia and hyperalgesia significantly increased on days 7 and 14 following CCI. The treatment not only reduced neuropathic pain but also blocked CCI's effects on SCN9A upregulation and ERK phosphorylation. This research demonstrated that acamprosate reduces the neuropathic pain induced by CCI of the sciatic nerve in rats by preventing cell loss, inhibiting spinal SCN9A expression, ERK phosphorylation, and inflammatory cytokines, suggesting potential therapeutic implications of acamprosate administration for the treatment of neuropathic pain.


Psychological morbidity of celiac disease: A review of the literature.
Celiac disease has been linked to decreased quality of life and certain mood disorders. The effect of the gluten free diet on these psychological aspects of the disease is still unclear. The objective of this article is to review the literature on psychological morbidity of celiac disease. We performed a PubMed search for the time period from 1900 until June 1, 2014, to identify papers on psychological aspects of celiac disease looking specifically at quality of life, anxiety, depression and fatigue. Anxiety, depression and fatigue are common complaints in patients with untreated celiac disease and contribute to lower quality of life. While aspects of these conditions may improve within a few months after starting a gluten-free diet, some patients continue to suffer from significant psychological morbidity. Psychological symptoms may affect the quality of life and the dietary adherence. Health care professionals need to be aware of the ongoing psychological burden of celiac disease in order to support patients with this disease.


Aromatic Schiff bases confer inhibitory efficacy against New Delhi metallo-β-lactamase-1 (NDM-1).
The irregular use of antibiotics has created a natural selection pressure for bacteria to adapt resistance. Bacterial resistance caused by metallo-β-lactamases (MβLs) has been the most prevalent in terms of posing a threat to human health. The New Delhi metallo-β-lactamase-1 (NDM-1) has been shown to be capable of hydrolyzing almost all β-lactams. In this work, eight aromatic Schiff bases 1-8 were prepared and identified by enzyme kinetic assays to be the potent inhibitors of NDM-1 (except 4). These molecules exhibited a more than 95 % inhibition, and an IC50 value in the range of 0.13-19 μM on the target enzyme, and 3 was found to be the most effective inhibitor (IC50 = 130 nM). Analysis of structure-activity relationship revealed that the o-hydroxy phenyl improved the inhibitory activity of Schiff bases on NDM-1. The inhibition mode assays including isothermal titration calorimetry (ITC) disclosed that both compounds 3 and 5 exhibited a reversibly mixed inhibition on NDM-1, with a Ki value of 1.9 and 10.8 μM, respectively. Antibacterial activity tests indicated that a dose of 64 μg·mL-1 Schiff bases resulted in 2-128-fold reduction in MICs of cefazolin on E. coli producing NDM-1 (except 4). Cytotoxicity assays showed that both Schiff bases 3 and 5 have low cytotoxicity on the mouse fibroblast (L929) cells at a concentration of up to 400 μM. Docking studies suggested that the hydroxyl group interacts with Gln123 and Glu152 of NDM-1, and the amino groups interact with the backbone amide groups of Glu152 and Asp223. This study provided a novel scaffold for the development of NDM-1 inhibitors.


Exiting the tunnel of uncertainty: crystal soak to validated hit.
Crystallographic fragment screens provide an efficient and effective way to identify small-molecule ligands of a crystallized protein. Due to their low molecular weight, such hits tend to have low, often unquantifiable, affinity for their target, complicating the twin challenges of validating the hits as authentic solution-phase ligands of the target and identifying the `best' hit(s) for further elaboration. In this article, approaches that address these challenges are assessed. Using retrospective analysis of a recent ATAD2 hit-identification campaign, alongside other examples of successful fragment-screening campaigns, it is suggested that hit validation and prioritization are best achieved by a `triangulation' approach in which the results of multiple available biochemical and biophysical techniques are correlated to develop qualitative structure-activity relationships (SARs). Such qualitative SARs may indeed be the only means by which to navigate a project through the tunnel of uncertainty that prevails before on-scale biophysical, biochemical and/or biological measurements become possible.


Effect of induction chemotherapy on estimated risk of radiation pneumonitis in bulky non-small cell lung cancer.
Patients with bulky non-small cell lung cancer (NSCLC) may be at a high risk for radiation pneumonitis (RP) if treated with up-front concurrent chemoradiation. There is limited information about the effect of induction chemotherapy on the volume of normal lung subsequently irradiated. This study aims to estimate the reduction in risk of RP in patients with NSCLC after receiving induction chemotherapy. Between 2004 and 2009, 25 patients with Stage IV NSCLC were treated with chemotherapy alone (no surgery or radiation therapy [RT]) and had computed tomography (CT) scans before and after 2 cycles of chemotherapy. Simulated RT plans were created for the prechemotherapy and postchemotherapy scans so as to deliver 60Gy to the thoracic disease in patients who had either a >20% volumetric increase or decrease in gross tumor volume (GTV) from chemotherapy. The prechemotherapy and postchemotherapy scans were analyzed to compare the percentage of lung volume receiving≥20Gy (V20), mean lung dose (MLD), and normal tissue complication probability (NTCP). Eight patients (32%) had a GTV reduction >20%, 2 (8%) had GTV increase >20%, and 15 (60%) had stable GTV. In the 8 responders, there was an absolute median GTV decrease of 88.1cc (7.3 to 351.6cc) or a 48% (20% to 62%) relative reduction in tumor burden. One had >20% tumor progression during chemotherapy, yet had an improvement in dosimetric parameters postchemotherapy. Among these 9 patients, the median decrease in V20, MLD, and NTCP was 2.6% (p<0.01), 2.1Gy (p<0.01), and 5.6% (p<0.01), respectively. Less than one-third of patients with NSCLC obtain >20% volumetric tumor reduction from chemotherapy alone. Even with that amount of volumetric reduction, the 5% reduced risk of RP was only modest and did not convert previously ineligible patients to safely receive definitive thoracic RT.


Severity of oxygen free radical effects after ischemia and reperfusion in intestinal tissue and the influence of different drugs.
The influence of different drugs on ischemia induced oxygen free radical damage was examined in intestinal tissue of rats by determination of thiobarbituric acid reactive substances (TBARS). Some methodical aspects of this method were considered. Experiments were done with and without the use of polymerized stromafree hemoglobin (PHb) as an additional oxygen carrier. Reversible total occlusion of the superior mesenteric artery was performed for 90 min, reperfusion time was 2.5 hours. Despite higher O2 availability PHb did not increase the TBARS level any further. Superoxide dismutase with catalase; allopurinol; ciprofloxacin; and deferoxamine produced a highly significant reduction of TBARS, even if used together with PHb.


Lower levels of F2-isoprostanes in serum and livers of long-lived Ames dwarf mice.
F2-isoprostanes (IsoPs), lipid peroxidation products, are markers that quantitatively measure levels of oxidative stress. IsoP levels increase in tissues and serum of aging animals suggesting an increase in oxidative stress. This supports the Free Radical Theory of Aging, which proposes that elevated levels of reactive oxygen species (ROS) cause macromolecular damage, and is a factor in the age-associated decline in tissue function. Numerous studies have shown that the longevity of long-lived mutant mice correlates with their resistance to oxidative stress. However, although the Ames dwarf (DW) mice show resistance to oxidative stress, it has not been shown that these mice have inherently lower levels of ROS. Our results show that the serum and liver IsoP levels in DW mice are lower at all ages suggesting that the lower levels of endogenous ROS production in DW mice may be a factor in their resistance to oxidative stress and longevity.


Multicenter clinical trial of a home-use nonablative fractional laser device for wrinkle reduction.
Until now, nonablative fractional treatments could only be delivered in an office setting by trained professionals. The goal of this work was to perform clinical testing of a nonablative fractional laser device designed for home-use. This multicenter trial consisted of two clinical studies with slightly varying treatment protocols in which subjects performed at-home treatments of periorbital wrinkles using a handheld nonablative fractional laser. Both studies included an active treatment phase (daily treatments) and a maintenance phase (twice-weekly treatments). In all, 36 subjects were followed up for as long as 5 months after completion of the maintenance phase and 90 subjects were followed up until the completion of the maintenance phase. Evaluations included in-person investigator assessment, independent blinded review of high-resolution images using the Fitzpatrick Wrinkle Scale, and subject self-assessment. All 124 subjects who completed the study were able to use the device following written instructions for use. Treatments were well tolerated with good protocol compliance. Independent blinded evaluations by a panel of physicians showed Fitzpatrick Wrinkle Scale score improvement by one or more grades in 90% of subjects at the completion of the active phase and in 79% of subjects at the completion of the maintenance phase. The most prevalent side effect was transient posttreatment erythema. Lack of a control group and single-blinded study groups were limitations. Safety testing with self-applications by users demonstrated the utility of the device for home use. Independent blinded review of clinical images confirmed the device's proficiency for improving periorbital wrinkles.


Monoclonal antibodies to human trophoblast and sperm antigens: report of two WHO-sponsored workshops, June 30, 1986--Toronto, Canada.
Two WHO-sponsored workshops were recently held to obtain a consensus view from researchers active in the field of reproductive immunology on the current status of the application of monoclonal antibodies to studies of molecular events underlying reproduction and to determine the feasibility of using this approach to identify trophoblast- or sperm-specific antigens that might represent suitable candidates for the development of antifertility vaccines. A total of 66 mouse monoclonal antibodies reacting with human sperm and 45 monoclonal antibodies reacting with human trophoblast membrane components were submitted by 29 laboratories. These were evaluated in coded form by 42 laboratories with the appropriate expertise in biochemistry, immunohistology and tests of reproductive cell function. The majority of both anti-sperm and anti-trophoblast monoclonal antibodies cross-reacted with cellular elements in non-reproductive tissues. However, at least five monoclonal antibodies (two anti-trophoblast and three anti-sperm) appeared to demonstrate sufficient specificity to warrant further investigation as reagents for the identification of antifertility vaccine candidates.


Impact of attenuation correction on clinical [(18)F]FDG brain PET in combined PET/MRI.
In PET/MRI, linear photon attenuation coefficients for attenuation correction (AC) cannot be directly derived, and cortical bone is, so far, usually not considered. This results in an underestimation of the average PET signal in PET/MRI. Recently introduced MR-AC methods predicting bone information from anatomic MRI or proton density-weighted zero-time imaging may solve this problem in the future. However, there is an ongoing debate if the current error is acceptable for clinical use and/or research. We examined this feature for [(18)F] fluorodeoxyglucose (FDG) brain PET in 13 patients with clinical signs of dementia or movement disorders who subsequently underwent PET/CT and PET/MRI on the same day. Multiple MR-AC approaches including a CT-derived AC were applied. The resulting PET data was compared to the CT-derived standard regarding the quantification error and its clinical impact. On a quantitative level, -11.9 to +2 % deviations from the CT-AC standard were found. These deviations, however, did not translate into a systematic diagnostic error. This, as overall patterns of hypometabolism (which are decisive for clinical diagnostics), remained largely unchanged. Despite a quantitative error by the omission of bone in MR-AC, clinical quality of brain [(18)F]FDG is not relevantly affected. Thus, brain [(18)F]FDG PET can already, even now with suboptimal MR-AC, be utilized for clinical routine purposes, even though the MR-AC warrants improvement.


Diffuse basal ganglia or thalamus hyperechogenicity in preterm infants.
To determine the incidence and factors associated with diffuse basal ganglia or thalamus hyperechogenicity (BGTH) in preterm infants. (1) Review of serial neurosonograms among neonates with gestational age (GA) <34 weeks born at Weiler Hospital during a 21-month period; (2) Color Doppler flow imaging; (3) Case-control study using GA group-matched controls; and (4) Blind reading of CT scans or MRIs in patients with BGTH. Among 289 infants, 24 (8.3%) had diffuse BGTH. Color Doppler flow imaging was normal in nine patients. The incidence of diffuse BGTH was inversely related to GA (P<0.01). Logistic regression (n=96) showed that diffuse BGTH was significantly associated with requirement of high-frequency oscillation (HFO) (P=0.031), severe intraventricular hemorrhage (IVH) (P=0.004), hypotension requiring vasopressors (P=0.040), hypoglycemia (P=0.031) and male gender (P=0.014). Most patients with diffuse BGTH had normal basal ganglia and thalamus on CT/MRI, one had a hemorrhage, and one had an ischemic infarction. In our series, diffuse BGTH occurred in 8.3%, and was associated with factors similar to those previously reported. In contrast, several series have reported almost exclusively linear or punctuate hyperechoic foci, corresponding to hyperechogenicity of the lenticulostriate vessels. Our data provide further evidence to suggest that diffuse BGTH and hyperechogenicity of the lenticulostriate vessels are two different entities. Additional studies are required to determine the long-term significance of diffuse BGTH.


Making and sharing decisions about management with patients: the views and experiences of pre-registration house officers in general practice and hospital.
To explore the views and experiences of pre-registration house officers (PRHOs) in general practice and hospital settings regarding the concept of patient partnership and their experience of involving patients in management decisions. The 12 PRHOs who had graduated from British universities and who were working within the Yorkshire Deanery were interviewed towards the end of their four-month general practice attachments. The interviews were semi-structured and analysed qualitatively. Three major themes emerged. The PRHOs perceived differences in approach between consultations carried out in hospital and primary care settings, with general practitioners being more likely to share information and decisions with patients. As medical students, the PRHOs had little opportunity to practise sharing information and management decisions with patients, and variable experience of this after graduation. On the whole they were favourable to the concept of patient partnership. Medical students and PRHOs lack training and opportunities to decide on management and discuss this with patients and yet, particularly in general practice settings, they have to practise these skills. The PRHOs had begun to develop strategies to decide how much information to give to patients and to what extent to involve patients in management decisions. This is an area that needs further consideration when planning both undergraduate and postgraduate medical education.


Persistent decreases in blood plasmacytoid dendritic cell number and function despite effective highly active antiretroviral therapy and increased blood myeloid dendritic cells in HIV-infected individuals.
Dendritic cells (DC) have an instrumental role in the activation and function of both innate and adaptive immune responses. In humans, at least two distinct DC subsets have been characterized based on phenotypic markers: the myeloid DC (MDC) and the plasmacytoid DC (PDC). Both subsets are critical producers of cytokines (IL-12 for MDC and type I/II IFNs for PDC) and are functionally different. We show in this study that HIV(+) individuals have a significant decrease in the number of the Lin(-)HLA-DR(+)CD123(+) and BDCA-2(+) PDC compared with uninfected donors (p = 0.0001). HIV(+) individuals also have a sustained impairment in viral-induced IFN-alpha production (p < 0.0001). The decrease of the PDC subsets did not correlate with CD4 count or viral load and was not reversed in subjects under virally suppressive treatment, suggesting an irreversible change after infection. By contrast, the absolute number and median frequency of MDC in HIV-infected individuals were similar to those observed in uninfected controls, while a significant decrease was present in subjects with >5000 HIV-1 copies/ml. The inverse association with viral load of the MDC number, but not of IFN-alpha secretion or the number of PDC, suggests a role for MDC in viral control. Our data suggest that DC subsets are differentially reconstituted during the immune recovery associated with antiviral therapy. The persistent impairment of certain DC subsets may result in a sustained defect in DC-mediated innate immune functions despite an effective treatment regimen.


Assessing the activity of rheumatoid arthritis.
Disease activity in rheumatoid arthritis is not easily measured. The validity of current measures has been reviewed. Recent international efforts have resulted in consensus over a minimum (WHO/ILAR) core set of endpoints in RA trials: pain, patient and physician (assessor) global assessment, physical disability, swollen joint count, tender joint count, acute phase reactants; and for studies of one or more years' duration: radiographs of joints. The near future will hopefully see validation of new measures, also in terrains not currently covered by the core set.


Corneal graft curvature change after relaxing incisions for post-penetrating keratoplasty astigmatism.
To evaluate change in graft steepness after graft refractive surgery (GRS) consisting of relaxing incisions with or without counterquadrant compression sutures and discover the existing influential factors. In this retrospective study, 78 eyes of 76 patients who had received penetrating keratoplasty for keratoconus underwent GRS because of high post-penetrating keratoplasty astigmatism. Any shift in graft curvature was calculated using the keratometric coupling ratio (CR; the ratio of flattening of the incised meridian to steepening of the opposite meridian). Multiple regression analysis was used to investigate the possible effect of age, graft curvature, number of incisions, use of compression sutures, achieved vector astigmatic correction, and total arc length on CR. Mean patient age was 30.1 ± 10.3 years and mean follow-up period after GRS was 40.1 ± 29.0 months. There was a significant increase in average keratometry from 44.79 ± 2.08 diopters (D) preoperatively to 45.65 ± 1.86 D postoperatively (P < 0.001). Mean keratometric CR was 0.62 ± 1.09. Keratometric CR was significantly associated with patient age (R = 0.53, P = 0.04) and preoperative average keratometry (R = 0.61, P = 0.02). However, keratometric CR failed to show any significant correlation with other variables. A significant increase in graft steepening occurred after GRS, averaging 0.86 D. When both GRS and cataract extraction or phakic intraocular lens implantation are indicated, a staged approach (first GRS followed by phacoemulsification, for example) is advocated to calculate intraocular lens power with accuracy.


Thrombolytic therapy during acute myocardial infarction due to sudden occlusion of the left main coronary artery.
Two patients who suffered from sudden occlusion of the left main coronary artery were successfully treated with intracoronary infusion of streptokinase. One of them underwent successful coronary bypass surgery and the other was treated with medical therapy only. The outcome of this highly lethal condition is discussed.


CD38 is associated with communal behavior, partner perceptions, affect and relationship adjustment in romantic relationships.
Given the significance of close relationships for human survival, it is thought that biological mechanisms evolved to support their initiation and maintenance. The neuropeptide oxytocin is one such candidate identified in non-human animal research. We investigated whether variation in CD38, a gene involved in oxytocin secretion and attachment behavior in rodents, predicts romantic relationship dynamics in daily life. Community couples participated in an event-contingent recording (ECR) study in which they reported their social behavior, perception of their partner's behavior, and affect during their interactions with one another over a 20-day period; couples also completed various measures of relationship adjustment. Out of the 111 couples (N = 222 individuals) who provided either ECR and/or relationship adjustment information, we had information on CD38 for 118 individuals. As hypothesized, variation in rs3796863, a single nucleotide polymorphism (SNP) identified in prior work, predicted communal behaviors (e.g., the expression of affection), as well as overall relationship adjustment, such that individuals with the CC (vs. AC/AA) allele reported higher levels of communal behavior across their daily interactions with their romantic partner, as well as higher levels of relationship adjustment. Individuals with the CC (vs. AC/AA) allele of rs3796863 also reported less negative affect and felt insecurity in their interactions with their romantic partner. Notably, we found that variation in the romantic partner's rs3796863 SNP was related to the person's outcomes, independent of the person's rs3796863 genotype. These findings support the role of oxytocin in the interpersonal processes implicated in the maintenance of close relationships.


Effect of 100% oxygen on E-selectin expression, recruitment of neutrophils and enterocyte apoptosis following intestinal ischemia-reperfusion in a rat.
Recent evidence suggests that neutrophil recruitment may initiate cell apoptosis in ischemic tissues. We have recently shown that enterocyte apoptosis is increased following intestinal ischemia-reperfusion (IR) injury. The purpose of the present study was to examine the effect of hyperoxia on E-selectin expression, neutrophil recruitment and enterocyte apoptosis following intestinal IR in a rat. Male Sprague-Dawley rats were divided into three experimental groups: (1) sham rats underwent laparotomy without vascular occlusion and were ventilated with air (Sham) (2) IR rats underwent occlusion of both the superior mesenteric artery and portal vein for 30 min and were ventilated with air (IR), and (3) IR-O2 rats underwent IR and were ventilated with 100% started 10 min before reperfusion and continued for 6 h (IR-O2). Intestinal structural changes were determined 24 h following IR. Immunohistochemistry for E-selectin (using E-selectin cleaved concentrated polyclonal antibody) was performed to identify E-selectin immunoreactivity localized to the endothelium of venules. The recruitment of neutrophils was calculated per 100 venules. Immunohistochemistry for Caspase-3 was performed for identification of apoptotic cells. Non-parametric one-way ANOVA test was used for statistical analysis with p less than 0.05 considered statistically significant. A significant increase in E-selectin expression in the jejunum (6.1 +/- 2.2 vs. 2.5 +/- 1.0 E-selectin positive vessels/100 vessels, p < 0.05) and ileum (12.1 +/- 2.7 vs. 3.3 +/- 1.2 E-selectin positive vessels/100 vessels, p < 0.05) and a concomitant increase in neutrophil recruitment in the ileum (5.5 +/- 1.6 vs. 1.3 +/- 0.6 adhered PMN's per 100 venules) were observed in IR rats compared to sham animals and were accompanied by increased cell apoptosis (p < 0.05). Treatment with 100% oxygen resulted in a significant attenuation in E-selectin expression in the ileum (2.7 +/- 1.1 vs. 12.1 +/- 2.7 E-selectin positive vessels/100 vessels, p < 0.05), and neutrophil recruitment in the jejunum (2.5 +/- 1.4 vs. 7.7 +/- 1.9 adhered PMN's per 100 venules, p < 0.05) and ileum (1.5 +/- 0.7 vs. 5.5 +/- 1.6 adhered PMN's per 100 venules, p < 0.05) compared to IR animals, and was accompanied by decreased cell apoptosis (p < 0.05). Hyperoxia inhibits enterocyte apoptosis following intestinal ischemia-reperfusion. Down-regulation of E-selectin expression with subsequent decrease in neutrophil recruitment may be responsible for this effect.


Assessment of brazilian mangroves hydrocarbon contamination from a latitudinal perspective.
The present study investigated the contamination of Brazilian mangroves sediments by aliphatic hydrocarbons (AHs) and polycyclic aromatic hydrocarbons (PAHs). Samples were obtained from mangroves located along the brazilian coast, between the northern coast and the austral limit of the occurrence of this ecosystem. Total AH ranged from 1.9 to 311.3 μg g-1 and compound distribution pointed to biogenic sources, mainly from mangrove forests, and petrogenic sources, with a significant presence of an unresolved complex mixture in some areas. PAH values (34.4-977.3 ng g-1) indicated low to moderate contamination levels in mangrove sediments, reflecting the socioeconomic diversity observed along the Brazilian coast. The predominant PAH sources ranged from pyrolytic to petrogenic. According to sediment quality reference values, the evaluated sediments are not likely to cause biological effects, but deserve attention due to the current expansion scenario of oil prospecting activities off the Brazilian coast.


Successive Nucleophilic and Electrophilic Allylation for the Catalytic Enantioselective Synthesis of 2,4-Disubstituted Pyrrolidines.
Successive nucleophilic and electrophilic allylation mediated by the bis-Boc-carbonate derived from 2-methylene-1,3-propane diol enables formation of enantiomerically enriched 2,4-disubstituted pyrrolidines. An initial enantioselective iridium-catalyzed transfer hydrogenative carbonyl C-allylation is followed by Tsuji-Trost N-allylation using 2-nitrobenzenesulfonamide. Subsequent Mitsunobu cyclization provides the N-protected 2,4-disubstituted pyrrolidines.


Osteochondral Allograft Transplantation of the Knee in Adolescent Patients and the Effect of Physeal Closure.
The primary aim was to compare osteochondral allograft (OCA) transplantation outcomes between adolescent patients aged 16 years or younger and those older than 16 years. A secondary aim was to analyze the association between physeal closure status and outcomes. Consecutive patients aged 18 years or younger who underwent OCA transplantation with a minimum 2-year follow-up were identified from a prospectively collected database. Patients were divided into 2 groups: those aged 16 years or younger (group 1) and those aged 17 to 18 years (group 2). Outcomes included patient-reported outcomes (PROs), complications, reoperations, and cartilage revision surgery. Outcomes were compared between groups, and physeal status was analyzed as a prognostic indicator. A total of 36 patients met the inclusion criteria: 18 in group 1 and 18 in group 2. There were no significant differences between the groups in terms of demographic characteristics, prior surgical procedures, and surgical details, including concomitant procedures. The mean overall follow-up period was 4.6 ± 2.5 years (range, 2-10.3 years), with no significant difference between the groups (P = .21). There were 10 reoperations (28.8%), 4 in group 1 and 6 in group 2 (P = .47). The overall time to reoperation was 2.8 years and did not significantly differ between groups (P = .75). The failure rate was 5.6%, with 1 patient in each group undergoing either graft debridement or revision OCA transplantation. All PROs were significantly improved postoperatively (P < .05), except for the Western Ontario and McMaster Universities Arthritis Index stiffness score (P = .28) and the Short Form 12 mental score (P = .19). There were no significant between-group differences in terms of PROs. Patients with closed physes had a significantly greater increase in most PROs compared with patients with open physes (P < .05). OCA transplantation in adolescents results in significant PRO score improvement and a low failure rate, albeit reoperations are not uncommon. Patients with closed physes show greater PRO score improvement than those with open physes. Level III, retrospective comparative study.


A cell culture platform for quantifying metabolic substrate oxidation in bicarbonate-buffered medium.
Complex diseases such as cancer and diabetes are underpinned by changes in metabolism, specifically by which and how nutrients are catabolized. Substrate utilization can be directly examined by measuring a metabolic endpoint rather than an intermediate (such as a metabolite in the tricarboxylic acid cycle). For instance, oxidation of specific substrates can be measured in vitro by incubation of live cultures with substrates containing radiolabeled carbon and measuring radiolabeled carbon dioxide. To increase throughput, we previously developed a miniaturized platform to measure substrate oxidation of both adherent and suspension cells using multiwell plates rather than flasks. This enabled multiple conditions to be examined simultaneously, ideal for drug screens and mechanistic studies. However, like many metabolic assays, this was not compatible with bicarbonate-buffered media, which is susceptible to alkalinization upon exposure to gas containing little carbon dioxide such as air. While other buffers such as HEPES can overcome this problem, bicarbonate has additional biological roles as a metabolic substrate and in modulating hormone signaling. Here, we create a bicarbonate-buffered well-plate platform to measure substrate oxidation. This was achieved by introducing a sealed environment within each well that was equilibrated with carbon dioxide, enabling bicarbonate buffering. As proof of principle, we assessed metabolic flux in cultured adipocytes, demonstrating that bicarbonate-buffered medium increased lipogenesis, glucose oxidation, and sensitivity to insulin in comparison to HEPES-buffered medium. This convenient and high-throughput method facilitates the study and screening of metabolic activity under more physiological conditions to aid biomedical research.


NMDA receptor activation modulates evoked release of substance P from rat spinal cord.
The possible modulation exerted by glutamate on substance P (SP) release from the rat spinal cord has been investigated. The N-methyl-D-aspartate (NMDA) receptor agonist, NMDA (1 microM), increased SP basal outflow by 46.5+/-10.9% (n = 3, P<0.01) without changing the evoked release of the peptide. Conversely, NMDA antagonists but not 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) inhibited both electrically-evoked and capsaicin-induced release of SP. In particular, D-2-amino-5-phosphonopentanoate (D-AP5; 50 microM) inhibited electrically-evoked and capsaicin-induced release of SP by 93+/-2.4% and 93.2+/-3.8% (n = 12, P<0.01), respectively. Functional pharmacological evidence is provided for glutamate exerting a positive feedback on SP release evoked by C fibre stimulation via NMDA receptor activation.


Internal mass transfer effect on biodegradation of phenol by Ca-alginate immobilized Ralstonia eutropha.
Phenol biodegradation by free and Ca-alginate immobilized Ralstonia eutropha was performed in batch system. Optimum initial pH and temperature were determined as 7 and 30 degrees C, respectively for free cells, while a wide pH and temperature range were obtained for immobilized cells. Phenol had a strong inhibitory effect on the microbial growth and Haldane model was used to describe the substrate inhibition. Model parameters were determined as mumax=0.89 h(-1), KS=55.11 mg dm(-3) and KI=257.94 mg dm(-3) by non-linear regression analysis. The effective diffusion coefficient of phenol in immobilized particles was calculated. For this purpose, using biodegradation rates experimental effectiveness factors were determined for different sized immobilized particles. The Thiele modulus was evaluated from experimental effectiveness factors. Then the average effective diffusion coefficient was calculated as 1.21 x 10(-7)cm2 s(-1). These results showed that intraparticle diffusion resistance was important for this system and could not be ignored.


Trifluoroacetate is an allosteric modulator with selective actions at the glycine receptor.
Trifluoroacetic acid is a metabolite of the inhaled anesthetics halothane, desflurane and isoflurane as well as a major contaminant in HPLC-purified peptides. Ligand-gated ion channels, including cys-loop receptors such as the glycine receptor, have been the targets of peptide-based drug design and are considered to be likely candidates for mediating the effects of anesthetics in vivo, but the possible secondary contributions of contaminants and metabolites to these effects have not been studied. We used two-electrode voltage-clamp electrophysiology to test glycine, GABA(A) and 5-HT3 receptors expressed in Xenopus oocytes for their sensitivities to sodium trifluoroacetate. Trifluoroacetate (100 μM-3mM) enhanced the currents elicited by low concentrations of glycine applied to α1 homomeric and α1β heteromeric glycine receptors, but it had no effects when co-applied with a maximally-effective glycine concentration. Trifluoroacetate had no effects on α1β2γ2S GABA(A) or 5-HT3A receptors at any GABA or serotonin concentration tested. The results demonstrate that trifluoroacetate acts as an allosteric modulator at the glycine receptor with greater specificity than other known modulators. These results have important implications for both the secondary effects of volatile anesthetics and the presence of contaminating trifluoroacetate in HPLC-purified peptides, which is potentially an important source of experimental variability or error that requires control.


When independent healthcare behaviors develop in adolescents with inflammatory bowel disease.
Patients with chronic health needs are expected to gradually assume responsibility for health maintenance behavior as they move toward adulthood. We sought to evaluate the influence of factors such as age, duration of disease, and gender by examining the self-reported health behaviors of adolescents with inflammatory bowel disease (IBD). Confidential voluntary surveys were administered to all IBD outpatients over age 10 during a 4-month period. Questions addressed responsibility for health behaviors such as medication, provider visits, and communication. Likert scales measured the degree of independence: 1 (my parents only) through 3 (parents share equally with me) to 5 (I do it myself). Patient participation during doctor visits was also assessed. Of 358 patients approached, 294 (82%) returned completed surveys. Respondents were 51% male and 69% had Crohn's disease. Patients took increasingly active roles, but by ages 19-21 only 45% ordered medication refills, and 50% picked up medication from pharmacy. Only 35% of 19-21-year-olds scheduled appointments and 30% contacted providers between visits if problems arose. Most patients could answer provider questions (55% at age 16-18) but fewer asked questions of the provider (15% at the same age). Males were less likely to order their own prescription refills (P = 0.017) or prepare questions (P = 0.009). Duration of disease did not change skill acquisition. Adolescents develop independence in managing their IBD slowly and many patients ≥ 18 years are still assisted by parents. Focus on specific skill acquisition may help patients with self-management skills expected in adult healthcare.


Phylodynamic of SARS-CoV-2 during the second wave of COVID-19 in Peru.
At over 0.6% of the population, Peru has one of the highest SARS-CoV-2 mortality rate in the world. Much effort to sequence genomes has been done in this country since mid-2020. However, an adequate analysis of the dynamics of the variants of concern and interest (VOCIs) is missing. We investigated the dynamics of the COVID-19 pandemic in Peru with a focus on the second wave, which had the greatest case fatality rate. The second wave in Peru was dominated by Lambda and Gamma. Analysis of the origin of Lambda shows that it most likely emerged in Peru before the second wave (June-November, 2020). After its emergence it reached Argentina and Chile from Peru where it was locally transmitted. During the second wave in Peru, we identify the coexistence of two Lambda and three Gamma sublineages. Lambda sublineages emerged in the center of Peru whereas the Gamma sublineages more likely originated in the north-east and mid-east. Importantly, it is observed that the center of Peru played a prominent role in transmitting SARS-CoV-2 to other regions within Peru.


Gas chromatographic determination of mefloquine in human and dog plasma using electron-capture detection.
A sensitive and selective gas-liquid chromatographic method for the determination of plasma levels of mefloquine in human and dog plasma is described. The drug and internal standard were extracted from plasma at pH 9.0 into isopropyl acetate. After evaporation of the solvent, the residue was taken up in toluene and derivatised with heptafluorobutyrylimidazole. The derivative was quantified by gas-liquid chromatography on a 3% GC GE-SE30 column with electron-capture detection. The limit of detection for mefloquine in plasma was 10 ng/ml. The mean overall recovery from plasma was 102.7 +/- 3.3%. The method was shown to be specific for mefloquine without any interference from endogenous compounds in plasma or from the drugs pyrimethamine and sulfadoxine (compounds often administered in combination with mefloquine). The assay described was successfully applied to the determination of plasma levels of mefloquine in man and dog following oral and intravenous administration, respectively.


Determination of cholesterol and phospholipid concentrations in high-density lipoproteins by heparin-manganese chloride precipitation.
Cholesterol as well as phospholipids in high-density lipoproteins (HDL) have been measured in 60 serum samples after heparin-manganese chloride precipitation of the apolipoprotein B containing lipoproteins. The values obtained correlated well with values from ultracentrifugal separation (slope 1.11 for cholesterol, 0.92 for phospholipids). Furthermore, there was a significant correlation between the low-density lipoprotein (LDL) cholesterol estimated by the formula of Friedewald et al. and the ultracentrifugally separated LDL cholesterol (slope 1.02). By the additional determination of HDL phospholipids with a precipitation procedure, further information about the "antiatherogenic" is easily available.


Primary progressive cerebellar ataxia.
Thirty-two patients with primary progressive cerebellar ataxia were studied using MRI. This technique is better than CT in demonstrating atrophy of cerebellar structures as well as of brainstem and spinal cord. The differential diagnosis from other diseases particularly with multiple sclerosis is easier. The degree of ataxia correlated well with the degree of atrophy of cerebellum. However we could not see any correlation between the degree of atrophy and the onset and duration of the disease and no certain specific aspects could be demonstrated in the different groups examined.


Acute alterations of pre- and afterload: are Doppler-derived diastolic filling patterns able to differentiate the loading condition?
The net effects of acute changes in pre- and afterload on left ventricular filling, were examined by altering loading conditions in normal subjects. The specific purpose of this study was to investigate whether Doppler-derived transmitral flow patterns are able to differentiate the type of loading conditions. In 24 normal subjects (13 females, 11 males, mean age 44.1 +/- 11.5 years), the following Doppler variables were determined at baseline, after rapid volume infusion (preload increase), after nitroglycerin administration (preload decrease), during isometric exercise (afterload increase), and after application of a converting enzyme inhibitor (afterload decrease): the peak and integrated early (E, Ei) and late (A, Ai) diastolic flow velocities, their ratios (E/A, Ei/Ai), the percentage of atrial contribution (ACON), and the acceleration and deceleration times (Ac, Dc) of early filling. Reduced preload and increased afterload led to similar filling patterns characterized by a significant E and Ei decrease (p < 0.05, compared to baseline) accompanied by an A and Ai increase with a resultant reduction of E/A and Ei/Ai. Both changes increased the atrial contribution to filling and reduced Ac and Dc. Increased preload only significantly increased E and Ei, while reduced afterload did not induce any significant changes. Different loading conditions alter Doppler-derived diastolic filling patterns. However, the transmitral flow profile is not specific enough to distinguish the manner in which loading conditions have been altered.


MID-FTIR-PLS Chemometric Analysis of Cr(VI) from Aqueous Solutions Using a Polymer Inclusion Membrane-Based Sensor.
A partial least squares (PLS) quantitative chemometric method based on the analysis of the mid-Fourier transform infrared spectroscopy (MID-FTIR) spectrum of polymer inclusion membranes (PIMs) used for the extraction of Cr(VI) from aqueous media is developed. The system previously optimized considering the variables membrane composition, extraction time, and pH, is characterized in terms of its adsorption isotherm, distribution coefficient, extraction percent, and enrichment factor. A Langmuir-type adsorption behavior with KL = 2199 cm3/mmol, qmax = 0.188 mmol/g, and 0 < RL < 1 indicates that metal adsorption is favorable. The characterization of the extraction reaction is performed as well, showing a 1:1 Cr(VI):Aliquat 336 ratio, in agreement with solvent extraction data. The principal component analysis (PCA) of the PIMs reveals a complex pattern, which is satisfactorily simplified and related to Cr(VI) concentrations through the use of a variable selection method (iPLS) in which the bands in the ranges 3451-3500 cm-1 and 3751-3800 cm-1 are chosen. The final PLS model, including the 100 wavelengths selected by iPLS and 10 latent variables, shows excellent parameter values with root mean square error of calibration (RMSEC) of 3.73115, root mean square error of cross-validation (RMSECV) of 6.82685, bias of -1.91847 × 10-13, cross-validation (CV) bias of 0.185947, R2 Cal of 0.98145, R2 CV of 0.940902, recovery% of 104.02 ± 4.12 (α = 0.05), sensitivity% of 0.001547 ppb, analytical sensitivity (γ) of 3.8 ppb, γ-1: 0.6 ppb-1, selectivity of 0.0155, linear range of 5.8-100 ppb, limit of detection (LD) of 1.9 ppb, and limit of quantitation (LQ) of 5.8 ppb. The developed PIM sensor is easy to implement as it requires few manipulations and a reduced number of chemical compounds in comparison to other similar reported systems.


Imipramine in the treatment of panic disorder and its complications.
The recognition of the efficacy of imipramine for treating panic disorder and its complications has had major implications for clinical practice, diagnostic classification, theoretic understanding, and research strategies in the anxiety disorders. It has also resulted in benefit for a great number of affected individuals and promises to yield even greater relief of suffering as the findings become more widely disseminated.


[Cervical spondylotic myelopathy: early diagnosis and timing of operation].
To study early clinical characteristics and diagnosis of cervical spondylotic myelopathy and to search the timing of surgery. Seventy-four cases of early diagnosed cervical spondylotic myelopathy (CSM) were treated with anterior cervical decompression and autologous ilium graft fusion. The early stage of CSM was indistinct, and symptoms were mild. Neck pain, abnormality of motion and sensation of limbs, and hand and arm symptoms were shown frequently. Changes in neurological function could found during physical examination. Characteristic changes in imaging were helpful in early diagnosis of the disease. Early diagnosis and surgery of CSM are important in improving the therapeutic results.


Influence of the Ionic Liquid Type on the Gel Polymer Electrolytes Properties.
Gel Polymer Electrolytes (GPEs) composed by ZnTf₂ salt, poly(vinylidene fluoride-co-hexafluoropropylene) (PVdF-HFP), and different ionic liquids are synthesized using n-methyl-2-pyrrolidone (NMP) as solvent. Three different imidazolium-based ionic liquids containing diverse cations and anions have been explored. Structural and electrical properties of the GPEs varying the ZnTf₂ concentration are analyzed by ATR-FTIR, DSC, TG, and cyclic voltammetry. Free salt IL-GPEs present distinct behavior because they are influenced by the different IL cations and anions composition. However, inclusion of ZnTf₂ salt inside the polymers provide GPEs with very similar characteristics, pointing out that ionic transport properties are principally caused by Zn(2+) and triflate movement. Whatever the IL used, the presence of NMP solvent inside the polymer's matrix turns out to be a key factor for improving the Zn(2+) transport inside the GPE due to the interaction between Zn(2+) cations and carbonyl groups of the NMP. High values of ionic conductivity, low activation energy values, and good voltammetric reversibility obtained regardless of the ionic liquid used enable these GPEs to be applied in Zn batteries. Capacities of 110-120 mAh·g(-1) have been obtained for Zn/IL-GPE/MnO₂ batteries discharged at -1 mA·cm(-2).


New delivery approaches for pediatric brain tumors.
For many types of childhood brain tumors, including malignant gliomas, disease progression at the primary site is the predominant mode of treatment failure. Accordingly, interest has been directed during the last decade on exploring strategies to enhance the delivery of therapeutically active agents into the tumor microenvironment. Two approaches that have been the focus of considerable attention in the treatment of adult malignant brain tumors include interstitial administration of chemotherapeutic agents using time-release polymers and convection-enhanced delivery of immunotoxin conjugates targeted to receptors overexpressed in brain tumors relative to normal brain cells. Although it remains to be determined whether these approaches will lead to meaningful improvements in disease control and long-term prognosis in children with brain tumors, the encouraging results from studies in adults support the rationale for further exploring these strategies in the pediatric setting.


Technique to prevent fracture of a partial auricular prosthesis mold.
One of the difficulties faced during the essential and demanding step of fabricating a mold for a partial auricular prosthesis is the fracture of its most elevated part, which engages the remnant concha and triangular fossa region, because of the presence of excessive convolutions and undercuts. This technique describes a 4-part mold for a partial auricular prosthesis in which the most elevated portion is poured separately, thereby preventing mold fracture.


Bis(μ-benzoato-κ2O:O')bis-(benzoato-κO)octabutyldi-μ3-oxido-tetra-tin(IV).
The asymmetric unit of the title compound, [{Sn(C4H9)2(C6H5COO)}2O]2, consists of two half molecules, completed by application of inversion symmetry. Both mol-ecules adopt a ladder structure typical for this class of dimeric tetra-organodistannoxane di-carboxyl-ates characterized by a centrosymmetric four-membered (Sn-O)2 ring of rhomboidal shape that is extended on both sides by folded six-membered Sn-O-C rings. To a first approximation, both kinds of Sn atoms (Sn i and Sn o ) are trigonal-bipyramidally coordinated. The bond angles between the n-butyl groups are widened [135.64 (7)-146.20 (7)°] in comparison with an ideal trigonal bipyramid. Sn-O bond lengths within the {R2SnO3} coordination sphere depend strongly on the position of the corresponding O atom - axial (ax) or equatorial (eq) - as well as on the functionality of the carboxyl-ate groups which exhibit μ2 (-COO i ) and μ1 (-COO o ) coordination modes, respectively. In summary, the following sequence of distances [mean values] is found: d(Sn o -Oμ3) eq [2.024 (2) Å] < d(Sn i -Oμ3) eq [2.044 (2) Å] < d(Sn i -Oμ3) ax [2.158 (6) Å] < d(Sn o -Oμ1-carb) ax [2.182 (6) Å] < d(Sn i -Oμ2-carb) ax [2.250 (2) Å] ≃ d(Sn o -Oμ2-carb) ax [2.247 (12) Å]. The n-butyl groups adopt an anti-anti conformation with exception of two disordered outer n-butyl groups of the second mol-ecule which exhibit gauche-anti and anti-gauche conformations. Weak intra-molecular Sn⋯O inter-actions between the different O atoms of the outer carboxyl groups with the inner, as well as outer, Sn atoms give rise to a strongly distorted octa-hedral coordination at these Sn atoms. Inter-molecular inter-actions between the individual mol-ecules are restricted to van der Waals and O⋯H-C inter-actions of which a nearly linear very short C-H⋯O contact between the H atom of the phenyl group of one of the mol-ecules with the outer non-coordinating C=O group of the other molecule is the most prominent. It gives rise to a chain-like arrangement of the mol-ecules along [111]. The two n-butyl groups attached to the outer Sn atom of one mol-ecule are disordered over two sets of sites with occupancies of 0.806 (3)/0.194 (3) and 0.702 (3)/0.298 (3).


Gingerol ameliorates neuronal damage induced by hypoxia-reoxygenation via the miR-210/brain-derived neurotrophic factor axis.
The specific mechanism of gingerol in cerebral ischemia remains unknown. A neuroprotective function for miR-210 in cerebral ischemia has been identified. The brain-derived neurotrophic factor (BDNF)-mediated signaling pathway protects against cerebral ischemic injury. This investigation aimed to determine whether gingerol plays a neuroprotective role in cerebral ischemia via the miR-210/BDNF axis. N2a cells subjected to 10 h of hypoxia and 4 h of reoxygenation were treated with 5, 10, or 20 μmol/L gingerol. The levels of viability, apoptosis, and proteins in N2a cells were determined using MTT assays, flow cytometry, and western blotting, respectively. The binding relationship between BDNF and miR-210 was studied using a dual luciferase reporter assay. The expression levels of miR-210 and BDNF were determined using qPCR. Gingerol repressed the increase in apoptosis and decrease in viability observed in response to hypoxia/reoxygenation. Gingerol increased Bcl-2, BDNF, and TrkB levels and reduced Bax and cleaved caspase 3 levels after hypoxia/reoxygenation. Gingerol evoked decreased expression of miR-210. Inhibition of miR-210 resulted in increased viability and reduced apoptosis along with increased levels of Bcl-2, BDNF, and TrkB and reduced levels of Bax and cleaved caspase 3 after hypoxia/reoxygenation. Additionally, the miR-210 mimic reversed changes induced by gingerol. The cotransfection of the miR-210 mimic and wild type BDNF led to decreased luciferase activity. BDNF was negatively regulated by miR-210. BDNF siRNA reversed these changes evoked by miR-210 inhibition. Gingerol ameliorated hypoxia/reoxygenation-stimulated neuronal damage by regulating the miR-210/BDNF axis, indicating that gingerol is worthy of further application in cerebral ischemia therapy.


The p53 codon 72 single nucleotide polymorphism lacks a significant effect on implantation rate in fresh in vitro fertilization cycles: an analysis of 1,056 patients.
To determine whether the p53 codon 72 single nucleotide polymorphism, a change of the amino acid arginine (Arg) to proline (Pro) resulting from a single nucleotide mutation of guanine (G) to cytosine (C), has a clinically significant effect on implantation rate in fresh IVF cycles. Prospective cohort analysis. University-affiliated private IVF center. One thousand fifty-six female patients undergoing fresh nondonor IVF cycles. Embryo implantation rate. Of the 1,056 patients (2,600 total embryos transferred) undergoing their first IVF cycle, 289 had no implantation events and attempted a second cycle. Of the 289 patients in their second cycle, 72 had no implantation events and attempted a third cycle. The p53 codon 72 single nucleotide polymorphism frequencies in the first cycle (homozygous major allele Arg/Arg [G_G] = 45%, heterozygous allele Arg/Pro [G_C] = 44%, and homozygous minor allele Pro/Pro [C_C] = 11%) did not differ significantly across subsequent IVF cycles. There was no statistically significant difference in embryo implantation rate with respect to the single nucleotide polymorphism. The p53 codon 72 single nucleotide polymorphism lacks a clinically significant effect on embryo implantation rate in patients undergoing fresh nondonor IVF cycles.


Environmental assessment of energy production based on long term commercial willow plantations in Sweden.
The present paper analyzed the environmental assessment of short rotation willow plantations in Sweden based on the standard framework of Life Cycle Assessment (LCA) from the International Standards Organisation. The analysis is focused on two alternative management regimes for willow plantations dedicated to biomass production for energy purposes. The data used included the averages of a large sample of commercial plantations. One of the scenarios is carried out under nitrogen based fertilized conditions and the other under non-fertilized management with total biomass yields (dry weight) of 140t/ha and 86t/ha over a 21 and 22-year life time respectively. The environmental profile was analyzed in terms of the potentials for abiotic depletion, acidification, eutrophication, global warming, ozone layer depletion, photochemical oxidant formation, human toxicity, fresh water aquatic ecotoxicity, marine aquatic ecotoxicity and terrestrial ecotoxicity. In addition, an energy analysis was performed using the cumulative energy demand method (CED). The application of nitrogen based fertilizers allows an increase in the biomass yield per ha of up to 40% although the contributions to almost all impact categories, particularly the eutrophication potential and toxicity potential impact categories are also considerably higher. Conversely, due to the higher biomass yields achieved with fertilization of these willow plantations, that regime presents a better overall environmental profile in terms of energy yield and global warming potential.


Premalignant Disorders of the Breast in Pregnancy and Lactation.
Papillomas, atypical hyperplasias, and lobular carcinoma in situ of the breast are not malignant tumors, but present serious management challenges when they are diagnosed in a breast biopsy . Upgrading after excision and increased possibility of future cancer are risks that accompany these lesions. While some features have been defined as high-risk for upgrading, many practitioners now recommend conservative non-surgical treatment and vacuum-assisted biopsy . However, the challenge gets worse when the patient is pregnant or breastfeeding because of the limitations in imaging and treatment in relation to the fetus. This chapter deals with these problems, although the best management strategy cannot be defined because of lack of evidence at present.


Amide-sialoside protein conjugates as neomucin bioshields prevent influenza virus infection.
We report the preparation of multivalent amide-sialoside-decorated human serum albumin (HSA) and bovine serum albumin (BSA) as mimics of natural mucin and bioshields against influenza virus infection. Free sialic acid with an amine on C-2 was covalently attached to the protein scaffolds using di-(N-succinimidyl) adipate. Dynamic light scattering (DLS) showed that the synthetic neomucins were able to act as bioshields and aggregate the influenza virion particles. The dissociation constants (KD) of the interactions between the prepared glycoconjugates and three different viral strains were measured by isothermal titration calorimetry (ITC) indicating the multivalent presentation of sialyl ligands on the HSA and BSA backbones can dramatically enhance the adsorbent capability compared to the corresponding monomeric sialoside. Hemagglutinin inhibition (HAI) and neuraminidase inhibition (NAI) assays showed that the glycoconjugates acted as moderate HA and NA inhibitors, thus impeding viral infection. Moreover, the different binding affinities of the glycoproteins to HA and NA proteins from different influenza viruses demonstrated the importance of HA/NA balance in viral replication and evolution. These findings provide a foundation for the development of antiviral drugs and viral adsorbent materials based on mimicking the structure of mucin.


Virtual Surgical Planning in Craniosynostosis Reduces Operative Time and Length of Stay for Cranial Vault Remodeling.
Cranial vault remodeling (CVR) with and without frontal orbital advancement remodels the skull in craniosynostosis. Virtual surgical planning (VSP) for preoperative planning has been previously shown to be effective in CVR. In this study, the authors aimed to evaluate the impact of VSP on operative and perioperative efficiency for craniosynostosis surgery. A retrospective chart review was conducted of patients with craniosynostosis who underwent CVR. Patient demographics, perioperative variables, use of VSP, and complications were obtained. Perioperative variables collected include operative time and length of stay. An independent t test was used to compare variables from patients who had surgery with VSP and patients who did not. Records were available for 126 patients with craniosynostosis who underwent CVR of whom 79 (62.7%) utilized VSP. There was no difference in average age at surgery (9.3±5.7 mo versus 13.2±31.1 mo, P =0.39). Surgeries planned using VSP demonstrated a decreased operative time of 1.3 hours (3.7±1.1 versus 5.0±1.1 h, P <0.001) and a shorter length of stay (3.9±1.3 versus 4.6±1.7 d, P =0.01). There were no differences in complication rates of dehiscence, infection, returns to the operating room, or 30-day readmission. These trends were similar among patients who underwent fronto-orbital advancement in addition to CVR. Virtual surgical planning was associated with decreased operative time and length of stay for patients with craniosynostosis and comparable complication rates. Virtual surgical planning is an effective tool for reducing anesthetic exposure time.


FISH scoring on paraffin sections versus single-cell suspension for chromophobe renal carcinoma and renal oncocytoma.
Sectioning of the nuclei on tissue sections may give an overestimate of monosomy, a feature diagnostic of chromophobe renal cell carcinoma versus renal oncocytoma. The aim of the study was to assess whether or not nuclear sectioning may distort the results obtained from interphase fluorescence in situ hybridization (FISH) comparing the data obtained from analysis of isolated nuclei derived from formalin-fixed, paraffin-embedded sections with histological sections from the adjacent sections from the same tumors. Five chromophobe renal cell carcinomas and five renal oncocytomas were recruited. Sections of 5 μm and 30 μm were cut for FISH to investigate chromosomes 1, 2, 6 10 and 17. FISH of isolated nuclei from renal oncocytomas showed a mean increase of 3.0% for nuclei with two signals when compared to tissue sections. For chromosomes 2, 6, 10 and 17, isolated nuclei showed a mean increase of 4.9% of fluorescent signals over nuclei from tissue sections. FISH analysis of isolated nuclei from chromophobe renal cell carcinoma showed a similar counts. When a tumor section exhibits a borderline percentage of nuclei with single signals around the cut-off level on tissue sections, the test should be repeated on isolated nuclei to confirm chromosomal loss, diagnostic of chromophobe renal carcinoma.


Influence of Light, Relative Humidity, and Maturity of Populations on Discharge of Ascospores of Venturia inaequalis.
ABSTRACT Ascospore release in 20 populations of Venturia inaequalis was generally suppressed in wind tunnel tests during darkness and simulated rain, but the following relieved this suppression: (i) exposure to low relative humidity during simulated rain and (ii) protracted incubation of leaf samples and the consequent senescence of the pathogen population. No counterpart to (i) was observed under orchard conditions. Although V. inaequalis also released a high percentage of ascospores during darkness in field studies under simulated rain late in the season of ascospore release, this phenomenon has not been reported for natural rain events. A threshold value of 0.5 muW/cm(2) at 725 nm was identified as the minimum stimulatory light intensity. Ascospore release increased with increasing light intensity from 0.5 to 5.2 muW/cm(2) at 725 nm. There was also an intrinsic increase in ascospore release as duration of rain increased. In orchards, the combined impact of both processes is probably responsible for a delay in reaching peak ascospore release at several hours after sunrise. Ascospore release during darkness will generally constitute a small proportion of the total available supply of primary inoculum. Significant ascospore release, and therefore infection periods, can be assumed to begin shortly after sunrise, when rain begins at night in orchards with low potential ascospore dose (PAD). A PAD level of 1,000 ascospores per m(2) of orchard floor per season is suggested as a threshold, above which the night-released ascospores should not be ignored.


Palliative right ventricular outflow tract construction for patients with pulmonary atresia, ventricular septal defect, and hypoplastic pulmonary arteries.
From December, 1977, through June, 1981, 15 patients with pulmonary atresia, ventricular septal defect, and hypoplastic pulmonary arteries underwent a palliative right ventricular outflow tract construction. In seven (Group A) this was the first surgical procedure, whereas in the remaining eight (Group B) previous systemic-pulmonary artery anastomoses had been performed. A high morbidity of the pulmonary arteries was present in Group B, resulting in part from the previous shunting procedures. The left pulmonary artery was severely hypoplastic in five patients; the right was hypoplastic in seven of the eight patients and was severely stenotic or atretic in three. All the patients in Group A survived the palliative right ventricular outflow tract reconstruction, and only one in Group B died. Almost all patients had an increase in the aortic PO2 and oxygen saturations after palliative right ventricular outflow tract construction, with a concomitant fall in hemoglobin concentration. Three of the five patients in Group A who underwent postoperative angiography were found to have proximal left pulmonary artery stenosis, and three had lesser involvement of the proximal right pulmonary artery as well. Three of the six patients in Group B who were studied postoperatively also had severe stenosis or proximal atresia of the right pulmonary artery, and three patients had stenosis and hypoplasia of the left pulmonary artery as well, two severe. Thus in no patient in this series were normal pulmonary arteries achieved by palliative right ventricular outflow tract construction will provide the potential for ultimate complete repair. The rather constant finding of severe proximal left pulmonary artery stenosis and hypoplasia in Group A is disappointing.


Thermal latency adds to lesion depth after application of high-power short-duration radiofrequency energy: Results of a computer-modeling study.
The use of ultra-short RF pulses could achieve greater lesion depth immediately after the application of the pulse due to thermal latency. A computer model of irrigated-catheter RF ablation was built to study the impact of thermal latency on the lesion depth. The results showed that the shorter the RF pulse duration (keeping energy constant), the greater the lesion depth during the cooling phase. For instance, after a 10-second pulse, lesion depth grew from 2.05 mm at the end of the pulse to 2.39 mm (17%), while after an ultra-short RF pulse of only 1 second the extra growth was 37% (from 2.22 to 3.05 mm). Importantly, short applications resulted in deeper lesions than long applications (3.05 mm vs. 2.39 mm, for 1- and 10-second pulse, respectively). While shortening the pulse duration produced deeper lesions, the associated increase in applied voltage caused overheating in the tissue: temperatures around 100 °C were reached at a depth of 1 mm in the case of 1- and 5-second pulses. However, since the lesion depth increased during the cooling period, lower values of applied voltage could be applied in short durations in order to obtain lesion depths similar to those in longer durations while avoiding overheating. The thermal latency phenomenon seems to be the cause of significantly greater lesion depth after short-duration high-power RF pulses. Balancing the applied total energy when the voltage and duration are changed is not the optimal strategy since short pulses can also cause overheating.


Recurrent DNA copy number changes revealed by comparative genomic hybridization in primary Merkel cell carcinomas.
Comparative genomic hybridization (CGH) was used to search for gains, high-level amplifications and losses of DNA sequences along all chromosome arms in 19 primary Merkel cell carcinomas (MCC). Extensive genetic aberrations, with a mean value of 5.5+/-1.1 changes per tumor were detected in 13 out of the 19 samples analyzed. Our CGH results reveal several new and other previously known chromosomal regions that are involved in the pathogenesis of MCC. The majority of the alterations were gains of whole chromosomes or whole chromosome arms. Compared to losses, the frequency of DNA copy number gains was two-fold. DNA sequence copy number gains were most common in chromosomes 6 (42%), 1 (37%), and 5 (32%). The most frequent minimal common regions of gains were 6pterqter (42%), 1q11q31 (32%), and 5p (32%). No recurrent high-level amplifications were observed. High-level amplifications of small chromosomal regions were found in four samples out of the 19 tumors analyzed (21%). Amplifications affected 1q22q24 (5%), 4p (5%), and 5p (5%). Losses most frequently affected chromosomes 13 (21%) and 4 (16%). Minimal common regions with the most frequent losses were 13q13q31 (21%), 4q (16%), and 16q (11%). No significant statistical correlation between genomic aberrations and clinicopathological factors was revealed, despite the fact that there was an obvious tendency towards it. Primary MCC expressing DNA alterations were predominantly distinguished in large tumors, and risk of metastatic dissemination was three-fold compared to tumors with no DNA alterations.


Relative resistance to 1,25-dihydroxyvitamin D3 in a keratinocyte model of tumor progression.
We have examined the effect of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on mitogen-stimulated growth and on c-myc proto-oncogene expression in a keratinocyte model of tumor progression. A dose-dependent inhibition of cell growth by 1,25-(OH)2D3 was demonstrated in both established (HPK1A) and malignant (HPK1A-ras) cells. However, this inhibition was observed with the addition of 1,25-(OH)2D3 at a higher concentration in HPK1A-ras cells than in HPK1A cells. Cell cycle analysis revealed a blockage of the normal progression of the cell cycle from G0 to S phase in the presence of 1,25-(OH)2D3. A higher concentration of 1,25-(OH)2D3 was required in HPK1A-ras cells to overcome the mitogen-stimulated progression into S phase, when compared with HPK1A cells. Analysis of c-myc messenger RNA revealed a strong inhibition of its expression at early time points with higher concentrations of 1,25-(OH)2D3 being required to obtain an inhibition in HPK1A-ras cells similar to that obtained in HPK1A cells. 1,25-(OH)2D3 receptor characterization by sucrose gradient analysis and equilibrium binding demonstrated the presence of a single 3.7 S protein with similar receptor numbers and affinity in both cell lines. These observations therefore demonstrate that an alteration of the growth inhibitory response to 1,25-(OH)2D3 occurs when keratinocytes acquire the malignant phenotype and suggest that the alteration lies beyond the interaction of the ligand with its receptor. In addition, relative resistance to 1,25-(OH)2D3 was also observed in the expression of the cell-cycle associated oncogene c-myc. These studies may therefore have important implications in vivo in the development and growth of epithelial cell cancers.


Identification of alpha-fetoprotein polymers. Artifacts of the isolation procedure.
By combining polyacrylamide gel electrophoresis and radioimmunoassay, a method has been developed to detect polymeric forms of alpha-fetoprotein (AFP) during the isolation procedure. The method is capable of detecting AFP polymers in the presence of other serum proteins in serum samples that contain as little as 100 ng of AFP. Using this method, we have found that AFP polymers do not exist in cord serum; if encountered, we feel they should be considered to be artifacts of the isolation procedure AFP polymers appear in 7.5% polyacrylamide gel as multiple bands. We believe the multiple bands to be AFP polymers and not serum protein contaminants for the following reasons: (1) the electrophoretic pattern is very similar to that of serum albumin; (2) the polymers do exhibit AFP activity, although less than the monomeric form does; (3) the molecular weight of the dimer is exactly twice that of the monomer; (4) in the presence of sodium dodecyl sulfate and mercaptoethanol, the polymers move to the same position as do the monomers in polyacrylamide gel electrophoresis; (5) the polymers cannot be removed by repeated use of an immunoadsorbent affinity column designed to remove contaminant serum proteins.


Murine trophoblast cells are not killed by tumor necrosis factor-alpha.
Purified midgestation murine trophoblast cannot be killed by a variety of cell-mediated effector mechanisms, with the exception of highly lytic effectors such as lymphokine-activated killer cells. We now report that this trophoblast population is also resistant to tumor necrosis factor (TNF)-alpha.


Effect of cholecystokinin receptor antagonist on pancreatic responses to exogenous gastrin and cholecystokinin and to meal stimuli.
Exocrine pancreatic response to food is believed to result from the interaction of neural and hormonal factors, but their contribution in the net postprandial secretion is unknown. Recent description of a highly specific and potent cholecystokinin (CCK)-receptor antagonist permitted the evaluation of the physiologic role of CCK in postprandial pancreatic secretion. In dogs with chronic pancreatic fistula, CCK antagonism caused little alteration in sham feeding- or urecholine-induced pancreatic protein secretion, but reduced by approximately 60% the pancreatic protein response to a gastrointestinal meal and virtually abolished the pancreatic responses to duodenal perfusion with amino acids or oleate and to exogenous CCK, but not to secretin or neurotensin. The pancreatic protein responses, particularly to lower doses of gastrin, were also reduced by CCK-receptor antagonist, but no changes in the responses to secretin or neurotensin were detected. Cholecystokinin antagonism also significantly reduced the pancreatic polypeptide responses to CCK, gastrin, and the gastrointestinal meal, possibly due to removal of the CCK-mediated release of pancreatic polypeptide. We conclude that CCK plays a crucial role in the mediation of the gastrointestinal phase, but not the cephalic phase, of pancreatic secretion.


A review of newborn outcomes during the COVID-19 pandemic.
As the COVID-19 pandemic continues to spread worldwide, it is crucial that we determine populations that are at-risk and develop appropriate clinical care policies to protect them. While several respiratory illnesses are known to seriously impact pregnant women and newborns, preliminary data on the novel SARS-CoV-2 Coronavirus suggest that these groups are no more at-risk than the general population. Here, we review the available literature on newborns born to infected mothers and show that newborns of mothers with positive/suspected SARS-CoV-2 infection rarely acquire the disease or show adverse clinical outcomes. With this evidence in mind, it appears that strict postnatal care policies, including separating mothers and newborns, discouraging breastfeeding, and performing early bathing, may be more likely to adversely impact newborns than they are to reduce the low risk of maternal transmission of SARS-CoV-2 or the even lower risk of severe COVID-19 disease in otherwise healthy newborns.


Age and sex dependency of thoracic aortopathy in a mouse model of Marfan syndrome.
Thoracic aortic aneurysm is one of the manifestations of Marfan syndrome (MFS) that is known to affect men more severely than women. However, the incidence of MFS is similar between men and women. The aim of this study is to show that during pathological aortic dilation, sex-dependent severity of thoracic aortopathy in a mouse model of MFS translates into sex-dependent alterations in cells and matrix of the ascending aorta, consequently affecting aortic biomechanics. Fibrillin-1 C1041G/+ (Het) mice were used as a mouse model of MFS. Ultrasound measurements from 3 to 12 mo showed increased aortic diameter in Het aorta, with larger percentage increase in diameter for males compared with females. Immunohistochemistry showed decreased contractile smooth muscle cells in Het aortic wall compared with healthy aorta, which was accompanied by decreased contractility measured by wire myography. Elastin autofluorescence, second-harmonic generation microscopy of collagen fibers, and passive biomechanical assessments using myography showed more severe damage to elastin fibers, increased medial fibrosis, and increased stiffness of the aortic wall in MFS males but not females. Male and female Het mice showed increased expression of Sca-1-positive adventitial progenitor cells versus controls at young ages. In agreement with clinical data, Het mice demonstrate sex-dependent severity of thoracic aortopathy. It was also shown that aging exacerbates the disease state especially for males. Our findings suggest that female mice are protected from progression of aortic dilation at early ages, leading to a lag in aneurysm growth.NEW & NOTEWORTHY Male Fbn1C1041G/+ mice show more severe thoracic aortic changes compared with females, especially at 12 mo of age. Up to 6 mo of age, Sca-1+ smooth muscle progenitor cells are more abundant in the adventitia of both male and female Fbn1 Het mice compared with wild types (WTs). Male and female Het mice show similar patterns of expression of Sca-1+ cells at early ages.


Comparison of selectivity of LDL removal by double filtration and dextran-sulfate cellulose column plasmapheresis, and changes of subfractionated plasma lipoproteins after plasmapheresis in heterozygous familial hypercholesterolemia.
The possibility of selective removal of low density lipoprotein (LDL) by double filtration (DF) and dextran-sulfate cellulose (DSC) column plasmapheresis in hypercholesterolemia and the acute recovery process of the subfractionated plasma lipoproteins after plasmapheresis in heterozygous familial hypercholesterolemia were investigated. Sixty-six percent of the LDL cholesterol and 42% of the HDL cholesterol were removed by 2.5 L DF plasmapheresis with the second filters having average pore diameters of 30 nm and 40 nm. Fifty-nine percent of the LDL cholesterol was removed by 2.5 L DSC column plasmapheresis, while HDL cholesterol did not change. Therefore, DSC column plasmapheresis could remove LDL much more specifically than DF plasmapheresis. VLDL increased rapidly and reached the preplasmapheresis level within four days after plasmapheresis. IDL returned to the preplasmapheresis level in 2 weeks. The LDL1 level was approximately 80% of the preplasmapheresis level on the 14th day. LDL2 reached the peak at the seventh day. HDL2 and HDL3 moved in the same manner and reached the peak on the seventh day after DF plasmapheresis.


Starch turnover: pathways, regulation and role in growth.
Many plants store part of their photosynthate as starch during the day and remobilise it to support metabolism and growth at night. Mutants unable to synthesize or degrade starch show strongly impaired growth except in long day conditions. In rapidly growing plants, starch turnover is regulated such that it is almost, but not completely, exhausted at dawn. There is increasing evidence that premature or incomplete exhaustion of starch turnover results in lower rates of plant growth. This review provides an update on the pathways for starch synthesis and degradation. We discuss recent advances in understanding how starch turnover and the use of carbon for growth is regulated during diurnal cycles, with special emphasis on the role of the biological clock. Much of the molecular and genetic research on starch turnover has been performed in the reference system Arabidopsis. This review considers to what extent information gained in this weed species maybe applicable to annual crops and perennial species.


Association between number of pairs of opposing posterior teeth, metabolic syndrome, and obesity.
We investigated the relationship between the number of pairs of posterior teeth and metabolic syndrome (MetS), abdominal obesity (AO), and obesity, among Japanese adults. In 2005, 2,807 Japanese adults aged 25-74 years participated in the Survey of Dental Diseases and the National Health and Nutrition Survey. Based on the survey data, BMI, AO (JAS) determined by the Japan Atherosclerosis Society, AO (IDF) by the International Diabetes Federation, and MetS were assessed. Total functional tooth units (t-FTUs) were scored with pairs of opposing posterior teeth, including artificial teeth. Subjects were divided into three categories of chewing ability based on the score of t-FTUs: Poor (if score ≤ 9), Good (if score = 10-11), and Complete (if score = 12). The relationships between chewing ability and BMI ≥ 25, BMI ≥ 30, AO (JAS), AO (IDF), and MetS were tested using univariate and multivariate logistic regression analysis. The chewing ability was significantly associated with MetS, AO, and obesity in the univariate and multivariate logistic regression analysis. Adjusted OR of "Poor" compared to "Complete" were 1.51 (95% confidence interval (CI), 1.24-1.84) for BMI ≥ 25, 2.10 (95% CI 1.40-3.14) for BMI ≥ 30, 1.31 (95% CI 1.07-1.61) for AO (JAS), 1.40 (95% CI 1.15-1.70) for AO (IDF), and 1.34 (95% CI 1.04-1.72) for MetS. All were statistically significant. Preventing tooth loss and maintaining pairs of good chewing ability may be important factors in preventing MetS, AO, and obesity.


Low back pain in schoolchildren. A study of familial and psychological factors.
The results of a survey organized in the school system of the Swiss canton of Fribourg. An original questionnaire was developed for this study are reported. The goal of this study was to evaluate the possible role of familial or psychological factors in schoolchildren reporting nonspecific low back pain. Previous surveys have shown a high prevalence of nonspecific low back. pain among schoolchildren, particularly teen-agers. The reported familial incidence raises, among others, the question of a possible role of psychological or behavioral factors. This survey was performed with a validated 43-item self-administered questionnaire eliciting information about back pain history, family characteristics, children's activities, and psychological parameters. All schoolchildren (n = 615), ages 12-17 years, in two secondary schools (Fribourg, Switzerland) were surveyed. The response rate was 98%. Reported lifetime prevalence of back pain was 74%. Lumbar pain was the most frequent localization of pain (69% of back pain). The measured psychological factors were significantly associated with reported nonspecific low back pain and its consequences as well as with sibling history of low back pain. The study suggests that psychological factors play a role in children's reporting of nonspecific low back pain.


Low density lipoprotein receptors and catabolism in primary cultures of rabbit hepatocytes.
Rabbit 125I-labelled low density lipoproteins (LDL) were incubated with primary monolayer cultures of rabbit hepatocytes in studies designed to assess the role of liver in LDL catabolism at the cellular level. After hepatocytes were preincubated for 20 h in lipoprotein-free medium, they exhibited time- and concentration-dependent interaction with 125I-labelled DLD at concentrations to 1 mg LDL protein/ml and times to 24 h. After a 3 h (37 degrees C) incubation with 50 microgram LDL protein/ml, hepatocytes bound 400 ng (LDL protein)/mg (cell protein), internalized 280 ng/mg, and degraded 660 ng/mg. Internalization and degradation may be greater than indicated by these values since pulse studies suggested the presence of a deiodinase which attacks cell associated 125I-labelled LDL. The amounts of LDL bound to hepatocytes after 3 h (37 degrees C) were similar to amounts for fibroblasts, but DLD internalization and degradation were considerably less. Rabbit hyperlipidemic 125I-labelled DLD showed the same amount of binding but 1.39 times more internalization and degradation than normolipidemic 125I-labelled LDL. Binding of both control and hyperlipidemic LDL was 3-fold greater at 24 and 42 h than at O or 3 h but addition of a 50-fold molar excess of high density lipoproteins (HDL) prevented increased LDL binding with time. Induction of specific high affinity receptors for binding LDL was shown to occur by preincubation of hepatocytes for increasing periods in lipoprotein-free medium and then measuring 125I-labelled LDL binding at 4 degrees C in the presence and absence of excess unlabelled LDL. Finally, hepatocytes took up 40 times more LDL than sucrose or dextran over a 24-h period, an indication that the uptake of LDL occurs via some mechanism other than simple bulk fluid endocytosis.


Liners for waste containment constructed with class F and C fly ashes.
Hydraulic conductivity of a Class F fly ash containing residual organic carbon was evaluated in this study using laboratory and field tests. Compacted specimens of the Class F fly ash mixed with various materials (sand, Class C fly ash, and bottom ash) were prepared in the laboratory at various water contents and different compactive efforts. Hydraulic conductivity of the compacted specimens was measured using flexible-wall permeameters. A test pad was constructed to determine whether a low hydraulic conductivity liner could be constructed with Class F fly ash mixtures. Sealed double-ring infiltrometers and two-stage borehole permeameters were used to measure the field hydraulic conductivity of the test pad. Specimens were also removed from the test pad for hydraulic conductivity testing in the laboratory. Results of the study showed that mixtures of Class F and Class C fly ashes along with coarse aggregate can be compacted to hydraulic conductivities needed for landfill liners provided compaction is wet of optimum water content. The field tests showed that constructing a fly ash liner with hydraulic conductivities similar to those found in the laboratory is challenging, and requires careful attention to factors that result in cracks and permeable interlift regions that result in high field hydraulic conductivity. Leachate collected from the base of the test pad also showed that metal leaching must be considered when designing a liner with fly ash.


High tumor necrosis factor-α/interleukin-10 ratio is associated with hepatocellular carcinoma in patients with chronic hepatitis C.
Hepatitis C virus (HCV) is the main cause of chronic liver disease, cirrhosis and hepatocellular carcinoma (HCC) worldwide. The risk for the development of HCC increases with the severity of liver inflammation and fibrosis. The hepatic inflammation caused by HCV involves host regulatory immune response, which is mediated by cytokines with anti-viral role upon the interaction of viral polypeptides with innate and adaptive immunity. Two cytokines; tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) play key roles in the regulation of cellular immune response in HCV infection. The aim of the present study was to determine the levels of IL-10 and TNF-α, as well as the ratio of TNF-α and IL-10 serum levels in patients with HCV and HCC caused by HCV (HCC-HCV). The study included 173 patients with chronic HCV. TNF-α and IL-10 serum levels were measured by ELISA (R&D Systems, Inc.). In the present study, 54 patients presented liver mild fibrosis, 68 had severe fibrosis and 51 patients had HCC. After adjustment in the multivariate regression analysis, the following variables remained significantly associated with HCC-HCV occurrence: diabetes (p=0.012 OR 10.44 CI 1.66-65.60), IL-10 lower levels (p<0.0001 OR 0.83 CI 0.78-0.89) and TNF-α higher levels (p<0.0001 OR 1.19 CI 1.11-1.28). Individuals with HCC presented higher TNF-α/IL-10 ratio than those with fibrosis grade F4, F3 or F0+F1+F2 (p=0.0003, p<0.0001, p<0.0001, respectively). Patients with HCC were associated to higher index TNF-α/IL-10 ratio, suggesting that the unbalanced production of these cytokines may represent progression to the liver disease severity in HCV infected patients.


Clinical trial data sharing: a cross-sectional study of outcomes associated with two U.S. National Institutes of Health models.
The impact and effectiveness of clinical trial data sharing initiatives may differ depending on the data sharing model used. We characterized outcomes associated with models previously used by the U.S. National Institutes of Health (NIH): National Heart, Lung, and Blood Institute's (NHLBI) centralized model and National Cancer Institute's (NCI) decentralized model. We identified trials completed in 2010-2013 that met NIH data sharing criteria and matched studies based on cost and/or size, determining whether trial data were shared, and for those that were, the frequency of secondary internal publications (authored by at least one author from the original research team) and shared data publications (authored by a team external to the original research team). We matched 77 NHLBI-funded trials to 77 NCI-funded trials; among these, 20 NHLBI-sponsored trials (26%) and 4 NCI-sponsored trials (5%) shared data (OR 6.4, 95% CI: 2.1, 19.8). From the 4 NCI-sponsored trials sharing data, we identified 65 secondary internal and 2 shared data publications. From the 20 NHLBI-sponsored trials sharing data, we identified 188 secondary internal and 53 shared data publications. The NHLBI's centralized data sharing model was associated with more trials sharing data and more shared data publications when compared with the NCI's decentralized model.


Seasonal Variation and Association of Heavy Metals in the Vital Organs of Edible Fishes from the River Jhelum in Punjab, Pakistan.
The toxic effects of heavy metals are drastic, including accumulation. Fish species are important bio-indicators of heavy metal pollution in aquatic bodies. The current study aimed to assess the seasonal variation of heavy metals in the vital organs of mostly consumed fishes in River Jhelum, Pakistan. Samples of fish, including Wallago attu (Malhi), Rita rita (Khagga), and Mystus seenghala (Singhari), were collected from four different sites, i.e., Khushab, Muhammad Wala (M. Wala), 8.R.D and Rasool barrage during summer and winter seasons. Heavy metals such as iron (Fe), lead (Pb), chromium (Cr), cobalt (Co) and Cadmium (Cd) were estimated through acid digestion and spectrometric analysis. Results showed a significantly higher (P < 0.05) amount of these metals in the liver, followed by the kidneys of fish species. There were seasonal variations in the absorption of these metals as well. Cr (11.71) and Fe (58.66) were detected in higher amounts in Khagga which showed the greatest affinity for certain metals in some cases. In contrast, Singhari showed the greatest affinity to other metals in other cases. Comparative analysis revealed that there was a highly significant (P < 0.05) difference for the accumulation of almost all metals in both seasons and summer had the highest concentration of Cd, Pb, Co, Cr and Fe as compared to winter in all four sampling stations in the case of kidney and liver of all the three fishes. Elevated levels of heavy metals were detected in the summer due to increased temperature. Heavy metals found in the River Jhelum may demonstrate that metals can significantly affect the fish species.


Chitosan/carboxymethylcellulose-stabilized poly(lactide-co-glycolide) particles as bio-based drug delivery carriers.
Poly(lactide-co-glycolide) (PLGA) colloidal particles stabilized by complexes of two oppositely charged polysaccharides, chitosan (cationic, CS) and sodium carboxymethylcellulose (anionic, NaCMC), were fabricated. Dichloromethane containing dissolved PLGA was first emulsified in an aqueous phase containing mixtures of CS and NaCMC. Evaporation of dichloromethane from the resulting emulsion led to CS/NaCMC-covered-PLGA particles. CS and NaCMC contents affected the short-term stability of PLGA particles and also their intrinsic characteristics. The particles displayed pH-dependent characteristic. Zeta potential varied from +54 to -50 mV when pH was varied from 3 to 10. CS/NaCMC-covered-PLGA particles showed colloidal stability, over a wider pH range as compared to CS-covered-PLGA particles. Curcumin, a model hydrophobic drug, was encapsulated into the particles up to 10 wt% of PLGA. The CS/NaCMC-covered-PLGA particles loaded with curcumin showed delayed release in mildly acidic conditions and faster release in neutral and basic conditions. Cytotoxicity experiments were carried out with human colorectal carcinoma cells.


Risk factors and outcomes associated with unplanned intraoperative extubation of the pediatric surgical patient: An analysis of the NSQIP-P database.
Unplanned intraoperative extubation is a rare but potentially catastrophic safety event. Inadvertent extubation in the neonatal and pediatric critical care setting is a recognized quality improvement metric whereas literature for intraoperative extubation is scarce. The aim of this study was to identify risk factors and outcomes associated with unplanned intraoperative extubation. We queried the National Surgical Quality Improvement Program-Pediatric database from 2019 to 2020 for patients <18 years of age. A total of 253 673 patients were included in the analysis. Associations between demographics, clinical variables, and unplanned intraoperative extubation were evaluated with univariable and multivariable logistic regression models. The primary outcome was unplanned intraoperative extubation. Secondary outcomes were postoperative pulmonary complication, unplanned reintubation within 24 h, cardiac arrest on day of surgery, and surgical site infection. Unplanned intraoperative extubation occurred in 163 (0.06%) patients. Specific procedures experienced unplanned intraoperative extubation at a higher rate such as bilateral cleft lip repair (1.31% of procedure type) and thoracic repair of tracheoesophageal fistula (1.11% of procedure type). Age, operative time (z-score), American Society of Anesthesiologists Classification 3 and 4, neurosurgery, plastic surgery, thoracic surgery, otolaryngology, and structural pulmonary/airway abnormalities were independent risk factors. Unplanned intraoperative extubation was associated with an increased unadjusted risk for postoperative pulmonary complication (p < .005; OR, 6.05; 95% confidence interval [CI]: 1.93-14.44), unplanned reintubation within 24 h (p < .005; OR, 8.41; 95% CI: 2.08-34.03), cardiac arrest on day of surgery (p < .05; OR, 22.67; 95% CI: 0.56-132.35), and surgical site infection (p < .0005; OR, 3.27; 95% CI 1.74-5.67). Unplanned intraoperative extubation occurs at a higher frequency in a subset of procedures and patient types. Identifying and targeting at-risk patients with preventative measures may decrease the incidence of unplanned intraoperative extubation and its associated outcomes.


The effect of food on the bioavailability of temafloxacin. A review of 3 studies.
Temafloxacin is a new fluoroquinolone antibacterial agent. Previous pharmacokinetic studies have shown that the extent of absorption of temafloxacin is independent of dose and that the dispositional pharmacokinetics are linear. The pharmacokinetics of 3 tablet formulations of temafloxacin were investigated in phase I studies in healthy adult volunteers, to determine whether the bioavailability is altered by the presence of food. Results of these studies indicate that the absorption of temafloxacin is slightly enhanced by concomitant administration of food. Thus, special coordination of temafloxacin administration and meals appears to be unnecessary.