Calculates vs. analyzed composition of four modified fat diets. Formulated to study effects in human subjects of kind and amount of dietary fat.
Four diets, varying in kind and amount of fat, were calculated to meet the needs of adult men. Commonly available U.S.A. food were used. Fourteen days of menus, each with five caloric levels varying from 2,400 to 4,000 kcal, were calculated. Chemical analyses of composites were carried out to determine proximate composition, food energy, selected vitamins and minerals, sugars, fatty acids, and sterols. The diets were used in a controlled study of the effects of fat level and P:S on blood pressure, blood lipids, platelet aggregation, and other variables. In general, good agreement was found between calculated and analyzed nutrient contents. However, analyzed values for fiber, iron, cholesterol, and vitamin C showed larger than desirable differences from calculated values.


CD34+ VEGFR-3+ progenitor cells have a potential to differentiate towards lymphatic endothelial cells.
Endothelial progenitor cells (EPCs) play an important role in postnatal neovascularization. However, it is poorly understood whether EPCs contribute to lymphangiogenesis. Here, we assessed differentiation of a novel population of EPCs towards lymphatic endothelial cells and their lymphatic formation. CD34(+) VEGFR-3(+) EPCs were isolated from mononuclear cells of human cord blood by fluorescence-activated cell sorting. These cells expressed CD133 and displayed the phenotype of the endothelial cells. Cell colonies appeared at 7-10 days after incubation. The cells of the colonies grew rapidly and could be repeatedly subcultured. After induction with VEGF-C for 2 weeks, CD34(+) VEGFR-3(+) EPCs could differentiate into lymphatic endothelial cells expressing specific markers 5'-nucleotidase, LYVE-1 and Prox-1. The cells also expressed hyaluronan receptor CD44. The differentiated cells had properties of proliferation, migration and formation of lymphatic capillary-like structures in three-dimensional collagen gel and Matrigel. VEGF-C enhanced VEGFR-3 mRNA expression. After interfering with VEGFR-3 siRNA, the effects of VEGF-C were diminished. These results demonstrate that there is a population of CD34(+) VEGFR-3(+) EPCs with lymphatic potential in human cord blood. VEGF-C/VEGFR-3 signalling pathway mediates differentiation of CD34(+) VEGFR-3(+) EPCs towards lymphatic endothelial cells and lymphangiogenesis. Cord blood-derived CD34(+) VEGFR-3(+) EPCs may be a reliable source in transplantation therapy for lymphatic regenerative diseases.


Factors Influencing Male Involvement in Family Planning in Ntchisi District, Malawi - A Qualitative Study.
Malawi is among countries with the highest maternal mortality ratio (MMR) and fertility rate (FR) in Africa, among others caused by an unmet need for family planning (FP). In Malawi, FP is seen as a women's domain and because of this, male involvement in FP remains lower than wanted. This study aimed to explore influencing factors of male involvement in FP. In this qualitative study, 23 semi-structured interviews were held with 14 men, 5 women and 4 health surveillance assistants (HSAs) in Ntchisi District, Malawi. Transcribed data was analyzed through inductive content-analysis and generated five domains influencing male involvement: health behaviour motivation, gender relations, health behavioural skills, health behaviour information, socio-economic factors. Male involvement in FP could assist in reducing shame about going to the FP clinic, ignorance among men and in increasing understanding of the importance of shared decision-making and responsibilities in FP. This could eventually improve maternal and reproductive health within Ntchisi district.


Feasibility of complex coronary and peripheral interventions by trans-radial approach using large sheaths.
Trans-radial approach (TRA) reduces vascular access-site complications but has some technical limitations. Usually, TRA procedures are performed using 5 Fr or 6 Fr sheaths, whereas complex interventions requiring larger sheaths are approached by trans-femoral access. During 4 years, at two Institutions with high TRA use, we have attempted to perform selected complex coronary or peripheral interventions by TRA using sheaths larger than 6 Fr. Clinical and procedural data were prospectively collected. Attempt to place a 7 Fr or 8 Fr sheath (according to the planned strategy of the procedure) was performed after 5-6 Fr sheath insertion, administration of intra-arterial nitrates and radial artery angiography. Late (>3 months) patency of the radial artery was checked (by angiography in the case of repeated procedures or by palpation + reverse Allen test). We collected 60 patients in which TRA large sheath insertion was attempted. The large sheath (87% 7 Fr, 13% 8 Fr) was successfully placed in all cases. Most of the procedures were complex coronary interventions (bifurcated or highly thrombotic or calcific chronic total occlusive lesions), whereas 8.3% were carotid interventions. Procedural success rate was 98.3% (1 failure to reopen a chronic total occlusion). No access-site related complication occurred. In 57 (95%) patients, late radial artery patency was assessed and showed patency in 90% of the cases, the remaining patients having asymptomatic collateralized occlusion. In selected patients, complex percutaneous interventions requiring 7-8 Fr sheaths can be successfully performed by RA approach without access-site clinical consequences.


Recognizing medicalization and demedicalization: discourses, practices, and identities.
Scholars of the medicalization of social problems have paid inadequate attention to medicalization's multiple dimensions - discourses, practices and identities - and to the multiple levels of analysis at which it occurs - macro, meso and micro. As a result, scholars of a given social problem typically examine only a few aspects of its medicalization, fail to recognize changes in medicalization, and miss occasions where medicalization and demedicalization occur simultaneously. Moreover, by conceptualizing medicalization as a category or state rather than a continuous value, and failing to specify the threshold at which a phenomenon becomes 'medicalized' or 'demedicalized', scholars have discouraged attention to demedicalization. The article provides a new typology of medicalization and illustrates its utility through an analysis of two episodes in American abortion history. Previous analysts of these episodes miss many aspects of medicalization and disagree about whether these episodes involve medicalization or demedicalization. The typology helps resolve these differences.


Feasibility and effectiveness of postoperative adjuvant concurrent chemoradiation therapy in Japanese patients with high-risk early-stage cancer of the uterine cervix.
This study was undertaken to evaluate the feasibility and effectiveness of postoperative concurrent chemoradiation (CCRT) in patients with high-risk early-stage cervical cancer who were treated by radical hysterectomy and pelvic lymphadenectomy. From July 2001 to September 2005, CCRT was performed in 37 patients who had undergone radical hysterectomy with pelvic lymph node dissection at Nagoya University Hospital. Adjuvant chemotherapy consisted of cisplatin (70 mg/m(2) on day 1) and 5-fluorouracil (5-FU; 700 mg/m(2) per day on days 1-4) every 4 weeks for a total of three cycles. Pelvic radiotherapy was started concurrently with the first cycle of chemotherapy. The radiation dose was 45 Gy in 25 fractions. A nonrandomized control group of 52 patients who had undergone radiation therapy alone after radical hysterectomy between 1991 and 2000 served for historical comparison. In the CCRT group, the incidences of grade 3/4 toxicities were 24.3% for neutropenia, 8.1% for nausea and vomiting, and 18.9% for diarrhea. The 5-year progression-free survival (PFS) rates in the CCRT group and control group were 89.2% and 69.2%, respectively (P = 0.0392). This study showed that adjuvant CCRT with cisplatin and 5-FU could be safely performed and improved the prognosis in Japanese patients with high-risk early-stage cervical cancer after radical hysterectomy.


Time trends in obesity among adults with asthma in the United States: findings from three national surveys.
Obesity may affect the respiratory health of people with asthma. Because the temporal trends in the prevalence of obesity among people with asthma have not been described in the United States, our objective was to describe these trends. Using data from National Health and Nutrition Examination Survey (NHANES) I (1971-1975), II (1976-1980), and III (1988-1994), the authors examined changes in the prevalence of obesity during the period covered by these surveys. The age-adjusted prevalence of current asthma was 3.5% for NHANES I, 3.1% for NHANES II, and 5.2% in NHANES III. Among people with current asthma, age-adjusted mean body mass index increased from 26.1 kg/m2 in the NHANES I to 28.0 kg/m2 in NHANES III, and the age-adjusted prevalence of obesity increased from 21.3 to 32.8%. Among people without asthma, age-adjusted mean body mass index increased from 25.4 kg/m2 in NHANES I to 26.6 kg/m2 in NHANES III, and the prevalence of obesity increased from 14.6 to 22.8%. These results show that people with asthma are far more likely to be obese than people who do not have asthma. Because excess weight may adversely affect the respiratory health of people with asthma, weight management for overweight and obese patients with asthma may be an important component in the medical care of these patients.


Analysis of human skin mast cell proteins by two-dimensional gel electrophoresis. Identification of tryptase as a sialylated glycoprotein.
Proteins of mast cells purified from human foreskin were separated by 2-D polyacrylamide gel electrophoresis using either nonequilibrium pH gradient electrophoresis or isoelectric focusing in the first dimension and SDS-PAGE in the second dimension. Silver staining showed that a major feature of skin mast cell 2-D protein maps was a variety of relatively abundant proteins in the m.w. range of 29 to 37 kDa and covering a broad pH range from 5.0 to 8.5. Tryptase was identified on Western blots of 2-D-separated proteins by its binding of mAb and of 3H-diisopropylfluorophosphate. The precise distribution of tryptase varied among individuals but this protein generally occupied a continuum of molecular weights between 28 and 37 kDa and ranged in isoelectric point between 5.0 and 6.5. Tryptase was one of a number of mast cell proteins that bound the lectin concanavalin A as well as lectins specific for sialic acid, demonstrating that this enzyme is a sialylated glycoprotein. The diffuse m.w. distribution of skin mast cell tryptase (31 to 36 kDa) observed after SDS-PAGE was reduced to a single band of 30 kDa after treatment with protein-N-glycosidase F to remove asparagine-linked oligosaccharides. This finding suggests that intrinsic m.w. heterogeneity of tryptase in skin mast cells is largely a result of the addition of variable amounts of oligosaccharide to the tryptase polypeptide.


Idiopathic systemic capillary leak syndrome in children.
Adult subjects with systemic capillary leak syndrome (SCLS) present with acute and recurrent episodes of vascular leak manifesting as severe hypotension, hypoalbuminemia, hemoconcentration, and generalized edema. We studied clinical disease characteristics, serum cytokine profiles, and treatment modalities in a cohort of children with documented SCLS. Six children with SCLS were recruited from the United States, Australia, Canada, and Italy. Serum cytokines from SCLS subjects and a group of 10 healthy children were analyzed. Children with SCLS (aged 5-11 years old) presented with at least 1 acute, severe episode of hypotension, hypoalbuminemia, and hemoconcentration in the absence of underlying causes for these abnormalities. In contrast to what is observed in adult SCLS, identifiable infectious triggers precipitated most episodes in these children, and none of them had a monoclonal gammopathy. We found elevated levels of chemokine (C-C motif) ligand 2 (CCL2), interleukin-8, and tumor necrosis factor α in baseline SCLS sera compared with the control group. All patients are alive and well on prophylactic therapy, with 4 patients receiving intravenous or subcutaneous immunoglobulins at regular intervals. The clinical manifestations of pediatric and adult SCLS are similar, with the notable exceptions of frequent association with infections and the lack of monoclonal gammopathy. Prophylactic medication, including high dose immunoglobulins or theophylline plus verapamil, appears to be safe and efficacious therapy for SCLS in children.


Preservation of Mitochondrial Coupling and Renal Function by Controlled Oxygenated Rewarming of Porcine Kidney Grafts.
Warm reperfusion after previous cold storage has been shown to have a negative impact on mitochondrial function of organ grafts. Here, we wanted to investigate whether a more controlled warming up of the cold graft by ex vivo machine perfusion with gradually elevated temperature from cold to normothermia (including comparison of two warming up protocols) prior to implantation would be effective in preventing mitochondrial dysfunction upon reperfusion. All experiments were conducted on porcine kidneys retrieved 15 min after cardiac arrest. After 18 h of cold storage in HTK solution (CS, n = 6), kidneys (n = 6) were subjected to 2 h of reconditioning machine perfusion starting with a hypothermic period followed by a gradual increase in perfusion temperature up to 35 °C (controlled oxygenated rewarming-COR). For a second group (n = 6), the slow warming up was begun instantly after connecting the graft onto the machine (iCOR). Functional recovery of all grafts was then observed upon normothermic reperfusion in vitro. At the conclusion of the experiments, tissue specimens were taken for immediate isolation and analysis of renal mitochondria. COR resulted in a significantly and more than 3-fold increased glomerular filtration rate upon reperfusion, along with a significant higher tubular sodium reabsorption and lesser loss of glucose in comparison to the controls. Enzyme release (AST) was also massively reduced during the reperfusion period. Specific analysis at the mitochondrial level revealed significantly better coupling efficiency and spare respiratory capacity in the COR group compared to the cold storage group. Interestingly, additional experiments revealed that the omission of a hypothermic perfusion period did not deteriorate any of the results after COR, provided that the instant temperature increase from 10 to 35 °C was effectuated in the same controlled manner. Controlled rewarming after extended cold preservation effectively improves mitochondrial recovery upon reperfusion and early functional outcome of kidney grafts.


Survival of a Salmonella typhimurium poultry isolate in the presence of propionic acid under aerobic and anaerobic conditions.
Propionic acid is commonly found as a fermentation product in the gastrointestinal tracts of food animals and has also been used to limit the microbial contaminants in animal feeds. Because propionic acid is known to have antibacterial activity, the propionic acid encountered by foodborne pathogens during their life cycles may play an important role in inhibiting the survival of the pathogens. The survival patterns of Salmonella typhimurium poultry isolate were determined both in aerobic and anaerobic tryptic soy broth (TSB; pH 5.0 or 7.0) containing various concentrations of propionic acid (0-200 mM). The levels of recovered cells were consistently greater at pH 7.0 compared to those at pH 5.0. For the first 4 days, the levels were significantly decreased by incubation under anaerobic conditions as compared to aerobic condition at pH 7.0 (P<0.05). However, there were fluctuations of cell populations with different patterns depending on both concentrations and growth conditions. To characterize the nature of the capability which allowed the cell multiplication following decreases in cell population during incubation at pH 7.0, the cells isolated from the outgrowth cultures were tested for survival in aerobic or anaerobic TSB (pH 5.0 or pH 7.0) containing propionic acid (50 mM). The outgrowth isolates did not show significant differences in the level of recovered cells in the presence of propionic acid when compared to the wild type strain (P>0.05), suggesting that the cells in the outgrowth cultures did not harbour mutation(s) conferring increased resistance to propionic acid. In addition, the level of recovered cells of isogenic rpoS mutant strain of S. typhimurium was not significantly different from that of the wild type strain in the same assay conditions (P<0.05). The results of this study show that the bactericidal activity of propionic acid on S. typhimurium can be affected by environmental conditions such as acidic pH levels and anaerobiosis in food materials and gastrointestinal tracts. However, S. typhimurium is also able to multiply in the presence of sublethal concentrations of propionic acid at neutral pH during prolonged incubation under both aerobic and anaerobic conditions.


A clinic for the prevention of osteoporosis in general practice.
A clinic for women aged 40-60 years, offering screening and education about diet and hormone use and other measures for the prevention of osteoporosis, was organized in a group practice. Out of 582 eligible women contacted from the age-sex register, 252 (43%) attended the clinic. A year after the start of the clinic postal questionnaires were sent to all attenders and non-attenders to ascertain smoking habit, hormone use, calcium intake and social class. The use of hormone replacement therapy by the clinic attenders increased from a baseline of 15% to 45% but this had decreased to 38% one year later. Attending women were of higher social class and had slightly higher calcium intake than non-attenders. Although the use of hormone replacement therapy for prevention of osteoporosis is controversial, the risks and benefits were explained carefully to the women and the clinic provided a valuable opportunity for screening for weight problems, high blood pressure, menstrual problems and for health education about diet for the woman and her family.


Cognitive processing of cluster headache patients: evidence from event-related potentials.
The peripheral and central origins of pain in cluster headache (CH) have been a matter of much debate. The development and application of functional imaging techniques have provided more evidence supporting the hypothesis that CH is not a disorder exclusively peripheral in origin, and in fact central regions might be more important. Event-related potentials confer advantages in the functional evaluation of the cortex, but few studies thus far have employed this method in cluster headache. Seventeen cluster patients (15 males; mean age = 35.4 years) and 15 age-matched healthy participants (13 males; mean age = 34.6 years) were recruited. A visual oddball paradigm was employed to analyze target processing using event-related potentials. We investigated the P3/P3d components in the experiment. P3/P3d amplitudes were decreased in CH patients (P3, 3.82 μV; P3d, 5.8 μV) compared with controls (P3, 7.28 μV; P3d, 8.95 μV), F(1,30) = 4.919, p < 0.05, η2 = 0.141 for P3 and F(1,30) = 8.514, p < 0.05, η2 = 0.221 for P3d, respectively). Moreover, the amplitudes of P3/P3d were no significantl difference in the side of pain as compared to contralateral one (p > 0.05). These results provide evidence of dysfunction in the cognitive processing of CH patients, which may also contribute to the pathophysiology of CH.


The Gastroprotective Effect of Naringenin against Ethanol-Induced Gastric Ulcers in Mice through Inhibiting Oxidative and Inflammatory Responses.
Naringenin is a major flavanone found in grapes, tangelos, blood oranges, lemons, pummelo, and tangerines. It is known to have anti-inflammatory, antioxidant, anticancer, antimutagenic, antifibrogenic, and antiatherogenic pharmacological properties. This study aims to investigate the anti-inflammatory effects of naringenin in ethanol-induced gastric damage in vivo and ethanol-stimulated KATO III cells in vitro. Our results showed that pretreatment with naringenin significantly protected mice from ethanol-induced hemorrhagic damage, epithelial cell loss, and edema with leucocytes. It reduced gastric ulcers (GU) by suppressing ethanol-induced nuclear factor-κB (NF-κB) activity and decreasing the levels of nitric oxide (NO), malondialdehyde (MDA), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-8 (IL-8), and myeloperoxidase (MPO). In addition, pretreatment with naringenin might inhibit the secretion of TNF-α, IL-6, and IL-8, as well as the proteins cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) via the suppression of NF-κB and mitogen-activated protein kinase (MAPK) signaling in ethanol-stimulated stomach epithelial KATO III cells. Together, the results of this study highlight the gastroprotective effect of naringenin in GU of mice by inhibiting gastric secretion and acidity, reducing inflammation and oxidative stress, suppressing NF-κB activity, and restoring the histological architecture. These findings suggested that naringenin has therapeutic potential in the alleviation of ethanol-induced GU.


Minituriazed percutaneous nephrolithotomy: what does it mean?
A lot of interest has been recently attracted to miniaturized Percutaneous Nephrolithotomy (PCNL). Smaller diameter tracts and instruments, in comparison to standard PCNL are utilized to decrease the morbidity of PCNL. However, a debate is ongoing regarding the safety and efficacy of these methods. The growing enthusiasm toward miniaturized PCNL led to different techniques and instruments, and eventually generated confusion in the terminology of PCNL. In this review, we highlight the different modalities of miniaturized PCNL, their indication, their safety and efficacy, and the appropriate terminology is suggested. A comprehensive review of current literature was performed using PubMed(®). Publications relevant to the subject were retrieved and critically appraised. Miniaturized PCNL was introduced with the desire to reduce access-related complications and bleeding. Miniaturized PCNL has yet to prove clear advantage over the standard PCNL. Nevertheless, the current experience proves the safety of the miniaturized techniques. Advantages of the miniaturized PCNL suggested in the literature are the lower bleeding rate and decreased hospital stay. In addition, the miniaturized PCNL has been proven a safe and effective modality of renal stone treatment in pediatric population.


The Emergence of Carbapenem- and Colistin-Resistant Enterobacteria in Senegal.
Antibiotic resistance is a public health problem. The emergence of carbapenemase-producing Enterobacterales (CPE) infections is a concern, particularly in Senegal. (1) Methods: Between January 2019 and July 2022, 240 isolates of enterobacteria resistant to third-generation cephalosporins and imipenem from biological samples from Fann Hospital (Dakar) and Hôpital Paix (Ziguinchor) were selected. The isolates were identified by MALDI-TOF mass spectrometry, and susceptibility tests were performed by the disk diffusion method. Antibiotic-resistance genes for class A beta-lactamases, carbapenemases, and plasmid resistance to colistin resistance (mcr-1-8) were screened by RT-PCR. (2) Results: The 240 enterobacteria were composed of: Escherichia coli (60.83%), Klebsiella pneumoniae (21.67%), Enterobacter cloacae (13.75%), Citrobacter freundii (2.08%), Serratia marcescens (0.83%), Klebsiella aerogenes (0.42%), and Proteus mirabilis (0.42%). Class A beta-lactamase genes were found in 229 isolates (70.41% blaTEM, 37.5% blaSHV, 83.75% blaCTX-A, and 0.42% blaCTX-B). The carbapenemase genes blaOXA-48 and blaNDM were found in 25 isolates, including 14 isolates with blaOXA-48, 13 isolates with blaNDM, and 2 isolates with both genes simultaneously. The mcr-8 gene was found in one isolate of E. cloacae. (3) Conclusions: The epidemiology of antibiotic-resistance genes in enterobacteria in Senegal shows the emergence of CPEs. This phenomenon is worrying, and rigorous surveillance is necessary to avoid further spread.


Tear meniscus analysis with Fourier-domain optical coherence tomography in keratoconus.
To measure the lower tear meniscus dynamics with Fourier domain-optical coherence tomography (FD-OCT) in keratoconus patients without dry eye findings to evaluate the effects of the corneal ectasia on lower tear meniscus parameters, and to determine the most affected meniscus variable from the corneal ectasia in keratoconus. Prospective, clinical study. Forty-one eyes of 25 keratoconus patients without dry eye and 40 eyes of 20 healthy subjects were included. The lower tear meniscus analysis with FD-OCT, and corneal topography, keratometry, and pachymetry measurements were performed in all eyes. The main outcomes, including the lower tear meniscus height (TMH), depth (TMD), area (TMA), and angle between cornea and the tear meniscus (α-angle), were assessed. The results were compared between the patients and the control subjects. The average keratometric power was 53.94 ± 5.76 D (between 44.46 to 63.75 D) in keratoconic eyes. It was 43 ± 0.8 D (between 40.50 to 45.94 D) in the controls. The average TMH, TMD, and TMA values did not show any statistically significant difference between the patients and the controls (p = 0.39, p = 0.824, p = 0.516, respectively). However, the average value of the α-angle was significantly higher in keratoconic eyes when compared to controls (p = 0.031). It was positively correlated with the keratometric power (r = 0.577, p = 0.001). The TMH, TMD, and TMA did not show any change with the corneal protrusion; however, the α-angle had positive correlation with the keratometric power in keratoconic eyes.


Holographic thermalization, stability of anti-de sitter space, and the Fermi-Pasta-Ulam paradox.
For a real massless scalar field in general relativity with a negative cosmological constant, we uncover a large class of spherically symmetric initial conditions that are close to anti-de Sitter space (AdS) but whose numerical evolution does not result in black hole formation. According to the AdS/conformal field theory (CFT) dictionary, these bulk solutions are dual to states of a strongly interacting boundary CFT that fail to thermalize at late times. Furthermore, as these states are not stationary, they define dynamical CFT configurations that do not equilibrate. We develop a two-time-scale perturbative formalism that captures both direct and inverse cascades of energy and agrees with our fully nonlinear evolutions in the appropriate regime. We also show that this formalism admits a large class of quasiperiodic solutions. Finally, we demonstrate a striking parallel between the dynamics of AdS and the classic Fermi-Pasta-Ulam-Tsingou problem.


COVID-19 and diabetes: Is there enough evidence?
The pandemic of COVID-19, a disease caused by a novel coronavirus SARS-CoV-2, is associated with significant morbidity and mortality. Recent data showed that hypertension, diabetes mellitus, cardiovascular diseases, and chronic obstructive pulmonary disease were the most prevalent comorbidities in COVID-19 patients. Additionally, data indicate that hypertension, diabetes, and cardiovascular diseases are important risk factors for progression and unfavorable outcome in COVID-19 patients. There is only limited amount of data regarding follow-up of these patients, and they provided conflicting results. The main limitation is a small number of participants and particularly those who experienced primary composite outcome (admission in intensive care unit, use of mechanical ventilation, or death). Additionally, the limited number of patients was essential obstacle for performing analysis that would include many confounding factors such as advanced age, smoking status, and obesity and potentially change conclusion. So far, there is no study that demonstrated independent predictive value of diabetes on mortality in COVID-19 patients, but there are many speculations about the association between diabetes and susceptibility to novel coronavirus, as well as its impact on progression and prognosis of COVID-19. The aim of this review article was to summarize the current knowledge about the relationship between diabetes and COVID-19 and its role in outcome in these patients.


Motivations, barriers, and communication recommendations for promoting face coverings during the COVID-19 pandemic: Survey findings from a diverse sample.
State and local health departments have been tasked with promoting the use of face coverings to decrease the spread of COVID-19 in their respective communities. However, little is known about motivations and barriers to wearing face coverings in the context of COVID-19 prevention, particularly among communities of color who are at an increased risk of serious illness from the disease. The purpose of this study was to identify common motivations and barriers to face covering use, as well as explore perceptions of messages encouraging the use of face coverings among a racially and ethnically diverse sample. A survey was distributed electronically to North Carolina (NC) residents through NC Department of Health and Human Services listservs in July 2020. Participants self-categorized as Latino/a (33.5%), Black (39.1%), or white or another race (27.5%). The most commonly endorsed motivations for wearing face coverings were to avoid spreading COVID-19 (77%), as well as to protect people who are vulnerable (76%) and one's community (72%). Being uncomfortable (40%) was the most commonly endorsed barrier. Messages that included a clear request (ex. please wear a face covering) and a direct benefit (ex. keep community safe) were more commonly endorsed than those that did not. Commonly endorsed motivations, behaviors, and messages differed by race and ethnicity. Increased attention to message content, message structure, and access to information and resources may aid local officials in increasing consistent use of face coverings.


Intracerebral rhabdoid and papillary meningioma with leptomeningeal spread and rapid clinical progression.
Rhabdoid meningioma (RM) is a relatively new, Grade III tumor entity according to the latest WHO classification. We report rhabdoid and partly papillary, highly anaplastic, intracerebral meningioma with diffuse leptomeningeal spread and distant SCF metastasis to the cervical cord. This 27-year-old female was admitted to the hospital with radiological findings suggestive of a primary brain tumor or a metastasis. After subtotal resection and during radiotherapy, follow-up MRI revealed recurrence, metastasis to meninges at the high cervical level, and diffuse basal leptomeningeal enhancement indicating infiltrating tumor. She died approximately 3 months after onset of symptoms. Histological examination revealed rhabdoid and papillary meningioma with high proliferation rate (80% of MIB1-positive cells), necrosis and extensive brain invasion. It was positive for vimentin and S-100 protein, showed focal epithelial membrane antigen expression and accumulation of intermediate filaments on ultrastructural examination. The recurrent tumor diffusely infiltrated leptomeninges and subarachnoid space. This is a rare example of mixed, rhabdoid and papillary variant of meningioma, located entirely within the brain parenchyma and accompanied by a fulminant clinical course. The combination of the histological anaplasia with the highest reported proliferation rate, and loss of the cohesion of neoplastic cells led to diffused infiltration of the leptomeninges and metastasis to the spinal cord.


Atrial septal defect in cyanotic CL/Fr mice.
It is widely known that some newborn CL/Fr mice with cleft lip and palate (CLP) also have cyanotic symptoms, which have been thought to depend on an atrial septal defect (ASD). In a previous study, we found that cyanotic mice tended to have more severe types of CLP. We hypothesize that the mechanical airway obstruction due to a poorly developed palatal shelf and unmoved tongue in CLP(+) mice might be related to the occurrence of cyanosis. The purpose of this study was to examine the relationships between ASD and cyanosis in CLP(+) newborns. The newborn hearts from CLP(-), noncyanotic CLP(+), cyanotic CLP(+), CL/Fr mice and ICR mice were examined histologically, and the incidence and size of ASD was determined on neonatal day (ND) 0. In CLP(-) newborns, similar procedures were performed from ND 1 to ND 4. Furthermore, in CLP(+) newborns, development of the palatal shelf was examined. While all the ICR mice had a well-developed atrial septum, and the incidence of ASD was 0%, about 80% of CL/Fr mice had ASD, irrespective of the presence or absence of CLP and cyanosis. On ND 0, the septum primum was significantly shorter in cyanotic CLP(+) mice than in CLP(-) mice. It also tended to be shorter in CLP(+) mice than in CLP(-) mice. Between the cyanotics and noncyanotics, there were no significant differences in the incidences of ASD and the rate of septal development. In CLP(-) mice, the septum primum developed well later and no ASD was observed on ND 4. Cyanotic newborns had significantly less developed palatal shelves than did noncyanotics. Cyanosis may not be related to ASD and the rate of septal development, but may be related to the occurrence of CLP in this strain. Furthermore, we confirmed that some relationship exists between the development of the palatal shelf and cyanosis. The present study supports our hypothesis concerning the cause of cyanosis in CL/Fr mice.


Improvement in symptoms and signs in the forefoot of patients with rheumatoid arthritis treated with anti-TNF therapy.
Inhibition of tumour necrosis factor (TNF) is an effective way of reducing synovitis and preventing joint damage in rheumatoid arthritis (RA), yet very little is known about its specific effect on foot pain and disability. The aim of this study was to evaluate whether anti-TNF therapy alters the presence of forefoot pathology and/or reduces foot pain and disability. Consecutive RA patients starting anti-TNF therapy (infliximab, etanercept, adalimumab) were assessed for presence of synovial hypertrophy and synovitis in the 2nd and 5th metatarso-phalangeal (MTP) joints and plantar forefoot bursal hypertrophy before and 12 weeks after therapy. Tender MTP joints and swollen bursae were established clinically by an experienced podiatrist and ultrasound (US) images were acquired and interpreted by a radiologist. Assessment of patient reported disease impact on the foot was performed using the Manchester Foot Pain and Disability Index (MFPDI). 31 patients (24 female, 7 male) with RA (12 seronegative, 19 seropositive) completed the study: mean age 59.6 (SD 10.1) years, disease duration 11.1 (SD 10.5) years, and previous number of Disease Modifying Anti Rheumatic Drugs 3.0 (1.6). Significant differences after therapy were found for Erythrocyte Sedimentation Rate (t = 4.014, p < 0.001), C-reactive protein (t = 3.889, p = 0.001), 28 joint Disease Activity Score (t = 3.712, p = 0.0001), Visual Analog Scale (t = 2.735, p = 0.011) and Manchester Foot Pain and Disability Index (t = 3.712, p = 0.001).Presence of MTP joint synovial hypertrophy on US was noted in 67.5% of joints at baseline and 54.8% of joints at twelve weeks. Presence of plantar forefoot bursal hypertrophy on US was noted in 83.3% of feet at baseline and 75% at twelve weeks. Although there was a trend for reduction in observed presence of person specific forefoot pathology, when the frequencies were analysed (McNemar) this was not significant. Significant improvements were seen in patient reported foot pain and disability 12 weeks after commencing TNF inhibition in RA, but this may not be enough time to detect changes in forefoot pathology.


The Friday afternoon pulmonary angiogram: temporal relationship between onset of symptoms and requests for angiography.
To determine if pulmonary embolism symptoms and pulmonary angiography have a proclivity for a particular day of the week, month or season (Part I) and to assess the length of time elapsing between the appearance of symptoms and requests for pulmonary angiography (Part II). Prospective (in part) collection of data and retrospective review of clinical records. Large metropolitan, university affiliated hospital. Part I: 2,969 consecutive pulmonary angiograms performed over 17 years, were collected according to the day of the week, month and season of their performance. Relevant rates were calculated. Part II: A study of the time interval between the onset of pulmonary embolism symptoms and requests for and performance of angiography was conducted in 128 patients. Results. Part 1. In the course of 17 years, more pulmonary angiograms were performed on Fridays (mean 37.2, SE 1.8), than on any other day of the week (p <.001). No proclivity for a particular month or season was observed. Part II. The mean time elapsed between the onset of symptoms and requests for angiography was 24 hours (range 0.2-162, SE 4.3) for inpatients, and 45 hours (range 3-358, SE 7.8) for outpatients. The angiogram was completed urgently, within two hours of the onset of symptoms, only in 2.4%. Pulmonary angiography has a proclivity for Fridays. Pulmonary embolism symptoms and consequent angiograms do not favour a specific day, month or season. In most cases the time elapsing between the onset of symptoms and requests for angiography is too long to be consistent with urgency. The frequent Friday pulmonary angiogram reflects a tendency to "mop up" unfinished business prior to the week's end.


Sex and gender in psychopathology: DSM-5 and beyond.
Sex and gender differences in psychopathology have been understudied, yet identifying and understanding variability by sex and gender is important for the development of comprehensive etiological models as well as effective assessment and treatment of psychopathology in all persons. In the current article, we discuss the importance of sex and gender in psychopathology research, review terminology used when examining these constructs, and present multiple explanations for differential prevalence rates. Next, we review articles from psychopathology journals and conclude that researchers more often include both males and females than they did two decades ago, but still do not consistently analyze by sex or gender. We also provide an update of male-to-female ratios as presented in the DSM-5 and conduct a systematic review of the literature for selected disorders. We conclude that the DSM-5 presentation of sex or gender ratios is not systematic. Finally, we provide suggestions for the next DSM task force, researchers, journal editors, and funding agencies. These recommendations focus on more consistently and systematically considering sex and gender in all aspects of psychopathology research. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Comparative analysis of complete plastid genomes from wild soybean (Glycine soja) and nine other Glycine species.
The plastid genomes of different plant species exhibit significant variation, thereby providing valuable markers for exploring evolutionary relationships and population genetics. Glycine soja (wild soybean) is recognized as the wild ancestor of cultivated soybean (G. max), representing a valuable genetic resource for soybean breeding programmes. In the present study, the complete plastid genome of G. soja was sequenced using Illumina paired-end sequencing and then compared it for the first time with previously reported plastid genome sequences from nine other Glycine species. The G. soja plastid genome was 152,224 bp in length and possessed a typical quadripartite structure, consisting of a pair of inverted repeats (IRa/IRb; 25,574 bp) separated by small (178,963 bp) and large (83,181 bp) single-copy regions, with a 51-kb inversion in the large single-copy region. The genome encoded 134 genes, including 87 protein-coding genes, eight ribosomal RNA genes, and 39 transfer RNA genes, and possessed 204 randomly distributed microsatellites, including 15 forward, 25 tandem, and 34 palindromic repeats. Whole-plastid genome comparisons revealed an overall high degree of sequence similarity between G. max and G. gracilis and some divergence in the intergenic spacers of other species. Greater numbers of indels and SNP substitutions were observed compared with G. cyrtoloba. The sequence of the accD gene from G. soja was highly divergent from those of the other species except for G. max and G. gracilis. Phylogenomic analyses of the complete plastid genomes and 76 shared genes yielded an identical topology and indicated that G. soja is closely related to G. max and G. gracilis. The complete G. soja genome sequenced in the present study is a valuable resource for investigating the population and evolutionary genetics of Glycine species and can be used to identify related species.


GDF15: A Hormone Conveying Somatic Distress to the Brain.
GDF15 has recently gained scientific and translational prominence with the discovery that its receptor is a GFRAL-RET heterodimer of which GFRAL is expressed solely in the hindbrain. Activation of this receptor results in reduced food intake and loss of body weight and is perceived and recalled by animals as aversive. This information encourages a revised interpretation of the large body of previous research on the protein. GDF15 can be secreted by a wide variety of cell types in response to a broad range of stressors. We propose that central sensing of GDF15 via GFRAL-RET activation results in behaviors that facilitate the reduction of exposure to a noxious stimulus. The human trophoblast appears to have hijacked this signal, producing large amounts of GDF15 from early pregnancy. We speculate that this encourages avoidance of potential teratogens in pregnancy. Circulating GDF15 levels are elevated in a range of human disease states, including various forms of cachexia, and GDF15-GFRAL antagonism is emerging as a therapeutic strategy for anorexia/cachexia syndromes. Metformin elevates circulating GDF15 chronically in humans and the weight loss caused by this drug appears to be dependent on the rise in GDF15. This supports the concept that chronic activation of the GDF15-GFRAL axis has efficacy as an antiobesity agent. In this review, we examine the science of GDF15 since its identification in 1997 with our interpretation of this body of work now being assisted by a clear understanding of its highly selective central site of action.


Extracorporeal carbon dioxyde removal for additional pulmonary resection after pneumonectomy.
Additional pulmonary surgery in a previously pneumonectomized patient requires apnea during surgical manipulation of the surviving lung. We report on a novel approach to manage the intraoperative apnea period, combining apneic oxygenation and minimally invasive, low flow extracorporeal CO2 removal. A 69-year-old man previously submitted to left pneumonectomy was scheduled for wedge resection of a single right upper lobe lesion. During the intraoperative apnea period, oxygenation was maintained through apneic oxygenation with continuous positive airway pressure (CPAP) of 5 cmH2O and inspiratory oxygen fraction (FiO2) of 1 and respiratory acidosis was prevented through extracorporeal CO2 removal, performed with the Decap® system (Hemodec, Salerno, Italy), a veno¬venous pump-driven extracorporeal circuit including a neonatal membrane lung. The extracorporeal circuit was connected to the right femoral vein, accessed via a 14 Fr double lumen catheter. The blood flow through the circuit was 350 mL/min and the sweep flow of oxygen through the membrane lung was 8 L/min. The intraoperative apnea period lasted 13 minutes. Our approach allowed maintaining normocapnia (PaCO2 38,5 and 40 mmHg before and at the end of the apnea period, respectively), preserving oxygenation (P/F ratio 378, 191, 198 and 200 after 3, 6, 9 and 12 min of apnea, respectively). Our report suggests that the minimally invasive CO2 removal associated with apneic oxygenation is an useful technique for managing anesthesiological situations requiring moderate apnea periods.


Grain Yield and Water Use Efficiency in Extremely-Late Sown Winter Wheat Cultivars under Two Irrigation Regimes in the North China Plain.
Wheat production is threatened by water shortages and groundwater over-draft in the North China Plain (NCP). In recent years, winter wheat has been increasingly sown extremely late in early to mid-November after harvesting cotton or pepper. To improve water use efficiency (WUE) and guide the extremely late sowing practices, a 3-year field experiment was conducted under two irrigation regimes (W1, one-irrigation, 75 mm at jointing; W2, two-irrigation, 75 mm at jointing and 75 mm at anthesis) in 3 cultivars differing in spike size (HS4399, small spike; JM22, medium spike; WM8, large spike). Wheat was sown in early to mid-November at a high seeding rate of 800-850 seeds m(-2). Average yields of 7.42 t ha(-1) and WUE of 1.84 kg m(-3) were achieved with an average seasonal evapotranspiration (ET) of 404 mm. Compared with W2, wheat under W1 did not have yield penalty in 2 of 3 years, and had 7.9% lower seasonal ET and 7.5% higher WUE. The higher WUE and stable yield under W1 was associated with higher 1000-grain weight (TGW) and harvest index (HI). Among the 3 cultivars, JM22 had 5.9%-8.9% higher yield and 4.2%-9.3% higher WUE than WM8 and HS4399. The higher yield in JM22 was attributed mainly to higher HI and TGW due to increased post-anthesis biomass and deeper seasonal soil water extraction. In conclusion, one-irrigation with a medium-sized spike cultivar JM22 could be a useful strategy to maintain yield and high WUE in extremely late-sown winter wheat at a high seeding rate in the NCP.


Dynamic contrast enhanced magnetic resonance imaging in chronic Achilles tendinosis.
Chronic Achilles tendinosis is a common problem. When evaluating and comparing different therapies there is a need for reliable imaging methods. Our aim was to evaluate if chronic Achilles tendinosis affects the dynamic contrast-enhancement in the tendon and its surroundings and if short-term eccentric calf-muscle training normalizes the dynamic contrast-enhancement. 20 patients with chronic Achilles tendinopathy were included. Median duration of symptoms was 31 months (range 6 to 120 months). Both Achilles tendons were examined with dynamic contrast enhanced MRI before and after a 12- week exercise programme of eccentric calf-muscle training. The dynamic MRI was evaluated in tendon, vessel and in fat ventrally of tendon. Area under the curve (AUC), time to peak of signal, signal increase per second (SI/s) and increase in signal between start and peak as a percentage (SI%) was calculated. Pain and performance were evaluated using a questionnaire. In the fat ventrally of the tendon, dynamic contrast enhancement was significantly higher in the symptomatic leg compared to the contralateral non-symptomatic leg before but not after treatment. Despite decreased pain and improved performance there was no significant change of dynamic contrast enhancement in symptomatic tendons after treatment. In Achilles tendinosis there is an increased contrast enhancement in the fat ventrally of the tendon. The lack of correlation with symptoms and the lack of significant changes in tendon contrast enhancement parameters do however indicate that dynamic enhanced MRI is currently not a useful method to evaluate chronic Achilles tendinosis.


Molecular markers of radiation effectiveness in head and neck squamous cell carcinoma.
The response of cancer to ionizing radiation treatment varies in a manner not fully explained by standard clinical, demographic, or histologic factors. Response may be related to intrinsic biologic capability of the tumor cells and/or the host immune or stromal support tissues. The availability of molecular biological methods to detect specific tumor-related genetic alterations and altered protein expression has prompted a search for molecular markers that accurately predict tumor response to therapy. Tumor suppressor genes and oncogenes such as p53 and Cyclin D1, key components of pathways that control tumor behavior, such as epidermal growth factor receptor and apoptotic factors including bcl-2, markers of proliferation (Ki-67), and markers of angiogenesis such as vascular endothelial growth factor have been examined. To date, results for each of these are mixed. This is not surprising given the complexity of the biologic system of tumor response to damage and the multitude of factors that contribute to the diversity of clinical presentation of disease. This manuscript reviews the literature to date in an effort to summarize results and suggest the direction for further study.


[Effect of partial hepatectomy on the state of liver chromatin in adult and old rats].
Partial hepatectomy in rats of two age groups--adult (6-8 months) and old (24-26 months)--is found to increase the intensity of [2-14C] orotic acid incorporation into RNA of the liver chromatin which reaches the maximum values 15 h after the operation simultaneously in animals of both groups. In the age groups under study the transcription activation is accompanied by an increase in the relative quantity of the active chromatin fraction. The study of the process of thermodenaturation of inactive and active chromatin fractions in the liver of adult rats after the partial hepatectomy has revealed no considerable shifts in the melting point and in distribution of the hyperchromism percentage within different temperature ranges as compared to the intact liver. Parameters characterizing the melting process of chromatin fractions in the regenerating liver of old animals differ from the analysis of the intact liver: the melting point decreases and hyperchromism percentage distribution varies. The chromatin activation with the liver regeneration leads to more pronounced changes of its properties in old animals as a result of which age differences observed in the intact liver are levelled.


Lymph node imaging for thyroid cancer.
Cervical lymph nodes (LNs) in the central (level VI) and lateral (levels II-V) compartments of the neck are the most common sites of locoregional metastases associated with thyroid cancer. Prophylactic nodal dissections are uncommon in modern thyroid surgery and are not routinely performed due to concern for increased morbidity and do not offer improved survival. Therefore, a selective approach for LN dissections is increasingly important. Preoperatively, this is most frequently assessed with cervical ultrasound (US). Contrast-enhanced computed tomography (CT) of the neck can also be used for preoperative assessment. Both US and CT imaging can be used to characterise LNs in levels II-VI and their risk of malignancy based on size, morphology, and growth. US-guided fine-needle aspiration of equivocal LN with thyroglobulin (Tg) washout can also determine if a LN harbours malignancy. For postoperative surveillance after total thyroidectomy, both US and CT continue to play an important role at 6-12 months intervals. These patients may also benefit from additional biochemical data such as Tg levels in addition to LN and thyroid bed imaging. Thyroid uptake scans may also play a role in LN surveillance postoperatively for well-differentiated thyroid carcinoma in certain clinical contexts. Less commonly, positron emitted tomography may play a role, but is typically reserved for patients with aggressive or radioactive iodine refractory disease.


Provider and Caregiver Perspectives on Telehealth Assessments for Autism Spectrum Disorder in Young Children: A Multimethod DBPNet Study Exploring Equity.
Telehealth uptake increased dramatically during the COVID-19 pandemic, including for autism spectrum disorder (ASD) assessment by developmental-behavioral pediatric (DBP) clinicians. However, little is known about the acceptability of telehealth or its impact on equity in DBP care. Engage providers and caregivers to glean their perspectives on the use of telehealth for ASD assessment in young children, exploring acceptability, benefits, concerns, and its potential role in ameliorating or exacerbating disparities in access to and quality of DBP care. This multimethod study used surveys and semistructured interviews to describe provider and family perspectives around the use of telehealth in DBP evaluation of children younger than 5 years with possible ASD between 3/2020 and 12/2021. Surveys were completed by 13 DBP clinicians and 22 caregivers. Semistructured interviews with 12 DBP clinicians and 14 caregivers were conducted, transcribed, coded, and analyzed thematically. Acceptance of and satisfaction with telehealth for ASD assessments in DBP were high for clinicians and most caregivers. Pros and cons concerning assessment quality and access to care were noted. Providers raised concerns about equity of telehealth access, particularly for families with a preferred language other than English. This study's results can inform the adoption of telehealth in DBP in an equitable manner beyond the pandemic. DBP providers and families desire the ability to choose telehealth care for different assessment components. Unique factors related to performing observational assessments of young children with developmental and behavioral concerns make telehealth particularly well-suited for DBP care.


Effects of Transportation and Relocation on Immunologic Measures in Cynomolgus Macaques (Macaca fascicularis).
NHP are a small, but critical, portion of the animals studied in research laboratories. Many NHP are imported or raised at one facility and subsequently moved to another facility for research purposes. To improve our understanding of the effects of transportation and relocation on the NHP immune system, to minimize potential confounds associated with relocation, and to maximize study validity, we examined the phenotype and function of PBMC in cynomolgus macaques (Macaca fascicularis) that were transported approximately 200 miles by road from one facility to another. We evaluated the phenotype of lymphocyte subsets through flow cytometry, mitogen-specific immune responses of PBMC in vitro, and plasma levels of circulating cytokines before transportation, at approximately 24 h after arrival (day 2), and after 30 d of acclimation. Analyses of blood samples revealed that the CD3+ and CD4+ T-cell counts increased significantly, whereas NK+, NKT, and CD14+ CD16+ nonclassical monocyte subsets were decreased significantly on day 2 after relocation compared with baseline. We also noted significantly increased immune cell function as indicated by mitogen-specific proliferative responses and by IFNγ levels on day 2 compared with baseline. After 30 d of acclimation, peripheral blood CD4+ T-cells and monocyte counts were higher than baseline, whereas B-cell numbers were lower. The mitogen-induced responses to LPS and IFNγ production after stimulation with pokeweed mitogen or phytohemagglutinin remained significantly different from baseline. In conclusion, the effects of transportation and relocation on immune parameters in cynomolgus monkeys are significant and do not fully return to baseline values even after 30 d of acclimation.


Effects of Spray Surfactant and Particle Charge on Respirable Coal Dust Capture.
Surfactant-containing water sprays are commonly used in coal mines to collect dust. This study investigates the dust collection performance of different surfactant types for a range of coal dust particle sizes and charges. Bituminous coal dust aerosol was generated in a wind tunnel. The charge of the aerosol was either left unaltered, charge-neutralized with a neutralizer, or positively- or negatively-charged using a diffusion charger after the particles were neutralized. An anionic, cationic, or nonionic surfactant spray or a plain water spray was used to remove the particles from the air flow. Some particles were captured while passing through spray section, whereas remaining particles were charge-separated using an electrostatic classifier. Particle size and concentration of the charge-separated particles were measured using an aerodynamic particle sizer. Measurements were made with the spray on and off to calculate overall collection efficiencies (integrated across all charge levels) and efficiencies of particles with specific charge levels. The diameter of the tested coal dust aerosol was 0.89 μm ± 1.45 [geometric mean ± geometric standard deviations (SD)]. Respirable particle mass was collected with 75.5 ± 5.9% (mean ± SD) efficiency overall. Collection efficiency was correlated with particle size. Surfactant type significantly impacted collection efficiency: charged particle collection by nonionic surfactant sprays was greater than or equal to collection by other sprays, especially for weakly-charged aerosols. Particle charge strength was significantly correlated with collection efficiency. Surfactant type affects charged particle spray collection efficiency. Nonionic surfactant sprays performed well in coal dust capture in many of the tested conditions.


Biological and pathological studies of rosmarinic acid as an inhibitor of hemorrhagic Trimeresurus flavoviridis (habu) venom.
In our previous report, rosmarinic acid (RA) was revealed to be an antidote active compound in Argusia argentea (family: Boraginaceae). The plant is locally used in Okinawa in Japan as an antidote for poisoning from snake venom, Trimeresurus flavoviridis (habu). This article presents mechanistic evidence of RA's neutralization of the hemorrhagic effects of snake venom. Anti-hemorrhagic activity was assayed by using several kinds of snake venom. Inhibition against fibrinogen hydrolytic and collagen hydrolytic activities of T. flavoviridis venom were examined by SDS-PAGE. A histopathological study was done by microscopy after administration of venom in the presence or absence of RA. RA was found to markedly neutralize venom-induced hemorrhage, fibrinogenolysis, cytotoxicity and digestion of type IV collagen activity. Moreover, RA inhibited both hemorrhage and neutrophil infiltrations caused by T. flavoviridis venom in pathology sections. These results demonstrate that RA inhibited most of the hemorrhage effects of venom. These findings indicate that rosmarinic acid can be expected to provide therapeutic benefits in neutralization of snake venom accompanied by heat stability.


Doppler assessment of pulmonary artery pressure in neonates at risk of chronic lung disease.
To evaluate the pulmonary artery pressure (PAP) change in very low birth-weight (VLBW) infants at risk of chronic lung disease (CLD). The time to peak velocity:right ventricular ejection time (TPV:RVET) ratio calculated from the pulmonary artery Doppler waveform, which is inversely related to PAP, was used. The TPV:RVET ratio was corrected for different heart rate (TPV:RVET(c)). Seventy three VLBW infants studied on days 1, 2, 3, 7, 14, 21 and 28 were enrolled for the analysis. Twenty two infants developed CLD with a characteristic chest radiograph at day 28. Fifty one did not, of whom 17 were oxygen dependent on account of apnoea rather than respiratory disease, and 34 were non-oxygen dependent. The TPV:RVET(c) ratio rose progressively in all three groups over the first three days of life, suggesting a fall in PAP. In the oxygen and non-oxygen dependent groups, the mean (SD) ratio rose to 0.53 (0.09) and 0.57 (0.09), respectively, on day 7, then remained relatively constant thereafter. The CLD group rose more slowly after day 3 and had a significantly lower mean ratio from day 7 onwards compared with the other two groups (day 7: P < 0.001, days 14-28: P < 0.0001), and fell significantly from 0.47 (0.11) on day 7 to 0.41 (0.07) on day 28 (P = 0.01), suggesting a progressive rise in PAP. The mean (SD) ratios at day 28 of all infants were: CLD group 0.41 (0.07); oxygen dependent group 0.66 (0.15); and the non-oxygen group 0.67 (0.11). The CLD group had a significantly lower ratio than the oxygen dependent group and the non-oxygen group (P < 0.0001). Using the TPV:RVET(c) ratio of < 0.46, infants at risk of developing CLD could be predicted on day 7 (predictive value 82.8%, sensitivity 54.5%, specificity 94.1%). The non-invasive assessment of PAP using the TPV:RVET(c) ratio may be useful in the longitudinal monitoring of PAP change in VLBW infants, and for prediction of chronic lung disease.


Quantification of functional near infrared spectroscopy to assess cortical reorganization in children with cerebral palsy.
Cerebral palsy (CP) is the most common motor disorder in children. Currently available neuroimaging techniques require complete body confinement and steadiness and thus are extremely difficult for pediatric patients. Here, we report the use and quantification of functional near infrared spectroscopy (fNIRS) to investigate the functional reorganization of the sensorimotor cortex in children with hemiparetic CP. Ten of sixteen children with congenital hemiparesis were measured during finger tapping tasks and compared with eight of sixteen age-matched healthy children, with an overall measurement success rate of 60%. Spatiotemporal analysis was introduced to quantify the motor activation and brain laterality. Such a quantitative approach reveals a consistent, contralateral motor activation in healthy children at 7 years of age or older. In sharp contrast, children with congenital hemiparesis exhibit all three of contralateral, bilateral and ipsilateral motor activations, depending on specific ages of the pediatric subjects. This study clearly demonstrates the feasibility of fNIRS to be utilized for investigating cortical reorganization in children with CP or other cortical disorders.


Structural mechanism of DNA interstrand cross-link unhooking by the bacterial FAN1 nuclease.
DNA interstrand cross-links (ICLs) block the progress of the replication and transcription machineries and can weaken chromosomal stability, resulting in various diseases. FANCD2-FANCI-associated nuclease (FAN1) is a conserved structure-specific nuclease that unhooks DNA ICLs independently of the Fanconi anemia pathway. Recent structural studies have proposed two different mechanistic features for ICL unhooking by human FAN1: a specific basic pocket that recognizes the terminal phosphate of a 1-nucleotide (nt) 5' flap or FAN1 dimerization. Herein, we show that despite lacking these features, Pseudomonas aeruginosa FAN1 (PaFAN1) cleaves substrates at ∼3-nt intervals and resolves ICLs. Crystal structures of PaFAN1 bound to various DNA substrates revealed that its conserved basic Arg/Lys patch comprising Arg-228 and Lys-260 recognizes phosphate groups near the 5' terminus of a DNA substrate with a 1-nt flap or a nick. Substitution of Lys-260 did not affect PaFAN1's initial endonuclease activity but significantly decreased its subsequent exonuclease activity and ICL unhooking. The Arg/Lys patch also interacted with phosphates at a 3-nt gap, and this interaction could drive movement of the scissile phosphates into the PaFAN1-active site. In human FAN1, the ICL-resolving activity was not affected by individual disruption of the Arg/Lys patch or basic pocket. However, simultaneous substitution of both FAN1 regions significantly reduced its ICL-resolving activity, suggesting that these two basic regions play a complementary role in ICL repair. On the basis of these findings, we propose a conserved role for two basic regions in FAN1 to guide ICL unhooking and to maintain genomic stability.


BioID: A Screen for Protein-Protein Interactions.
BioID is a unique method to screen for physiologically relevant protein interactions that occur in living cells. This technique harnesses a promiscuous biotin ligase to biotinylate proteins based on proximity. The ligase is fused to a protein of interest and expressed in cells, where it biotinylates proximal endogenous proteins. Because it is a rare protein modification in nature, biotinylation of these endogenous proteins by BioID fusion proteins enables their selective isolation and identification with standard biotin-affinity capture. Proteins identified by BioID are candidate interactors for the protein of interest. BioID can be applied to insoluble proteins, can identify weak and/or transient interactions, and is amenable to temporal regulation. Initially applied to mammalian cells, BioID has potential application in a variety of cell types from diverse species. © 2018 by John Wiley & Sons, Inc.


Interleukin 4 potentiates the antiproliferative effects of tumor necrosis factor on various tumor cell lines.
In response to a given stimulus, usually a number of cytokines are secreted simultaneously by the immune system. Whether these cytokines are meant to function as a single agent or in combination with others is not understood. Tumor necrosis factor (TNF) has been shown to exhibit antiproliferative effects against a wide variety of tumor cell lines in vitro. In the present report, we investigated the effects of a T-cell-derived cytokine, interleukin 4 (IL-4), on the antiproliferative effects of TNF against different tumor cell lines. The growth characteristics of human breast cancer cells (MDA-MB-330) were minimally affected when the cells were exposed to either TNF or IL-4 alone. However, together these 2 cytokines inhibited cell growth in a dose-dependent manner. The enhancement of the cytotoxic effects of TNF by IL-4 were not just limited to breast tumor cells, but were also observed with human epidermoid carcinoma cells (A-431) and human histiocytic lymphoma cells (U-937). The enhancement of the cytotoxic effect of TNF by IL-4 against various tumor cell lines was found comparable with that by gamma-interferon (IFN-gamma). Interestingly, for certain tumor cell types, IL-4 alone was found to enhance cell proliferation. IL-4 had no effect on the growth-stimulatory activity of TNF on normal human foreskin fibroblasts. Pre-exposure of U-937 cells to IFN-gamma led to a greater than 2-fold induction in TNF receptors, but no modulation of TNF receptors by IL-4 was observed. Moreover, the presence of IFN-gamma was found to further potentiate the antiproliferative effects of TNF and IL-4. These results clearly suggest that IL-4 potentiates the antiproliferative responses of TNF by a mechanism different from that of IFN-gamma. Although it is well known that IL-4 can modulate the production of TNF from macrophages, this is the first report to suggest that IL-4 can also modulate TNF-dependent antiproliferative responses.


Regulation of MET receptor tyrosine kinase signaling by suppressor of cytokine signaling 1 in hepatocellular carcinoma.
Suppressor of cytokine signaling 1 (SOCS1) is considered as a tumor suppressor protein in hepatocellular carcinoma (HCC), but the underlying mechanisms remain unclear. Previously, we have shown that SOCS1-deficient hepatocytes displayed increased responsiveness to hepatocyte growth factor (HGF) due to enhanced signaling via the MET receptor tyrosine kinase. As aberrant MET activation occurs in many tumors including HCC, here we elucidated the mechanisms of SOCS1-mediated regulation. SOCS1 attenuated HGF-induced proliferation of human and mouse HCC cell lines and their growth as tumors in NOD.scid.gamma mice. Tumors formed by SOCS1 expressing HCC cells showed significantly reduced MET expression, indicating that SOCS1 not only attenuates MET signaling but also regulates MET expression. Mechanistically, SOCS1 interacted with MET via the Src homology 2 domain and this interaction was promoted by MET tyrosine kinase activity. The SOCS1-mediated reduction in MET expression does not require the juxtamembrane Y1003 residue implicated in Cbl-mediated downmodulation. Moreover, the proteasome inhibitor MG-132, but not the inhibitors of lysosomal degradation bafilomycin and chloroquine, reversed the SOCS1-mediated reduction in MET expression, indicating that this process is distinct from Cbl-mediated downmodulation. Accordingly, SOCS1 promoted polyubiquitination of MET via K48-dependent but not K63-mediated ubiquitin chain elongation. Furthermore, siRNA-mediated downmodulation of Cbl did not abolish SOCS1-mediated reduction in MET expression in HCC cells. SOCS1-dependent ubiquitination of endogenous MET receptor occurred rapidly following HGF stimulation in HCC cells, leading to proteasomal degradation of phosphorylated MET receptor. These findings indicate that SOCS1 mediates its tumor suppressor functions, at least partly, by binding to MET and interfering with downstream signaling pathways as well as by promoting the turnover of the activated MET receptor. We propose that loss of this control mechanism due to epigenetic repression of SOCS1 could contribute to oncogenic MET signaling in HCC and other cancers, and that MET inhibitors might be useful in treating these patients.


Promoting seismic retrofit implementation through "nudge": using warranty as a driver.
This article proposes a new type of warranty policy that applies the "nudge" concept developed by Thaler and Sunstein to encourage homeowners in Japan to implement seismic retrofitting. Homeowner adaptation to natural disasters through loss reduction measures is known to be inadequate. To encourage proactive risk management, the "nudge" approach capitalizes on how choice architecture can influence human decision-making tendencies. For example, people tend to place more value on a warranty for consumer goods than on actuarial value. This article proposes a "warranty for seismic retrofitting" as a "nudge" policy that gives homeowners the incentive to adopt loss reduction measures. Under such a contract, the government guarantees all repair costs in the event of earthquake damage to the house if the homeowner implements seismic retrofitting. To estimate the degree to which a warranty will increase the perceived value of seismic retrofitting, we use field survey data from 1,200 homeowners. Our results show that a warranty increases the perceived value of seismic retrofitting by an average of 33%, and an approximate cost-benefit analysis indicates that such a warranty can be more economically efficient than an ex ante subsidy. Furthermore, we address the failure of the standard expected utility model to explain homeowners' decisions based on warranty evaluation, and explore the significant influence of ambiguity aversion on the efficacy of seismic retrofitting and nonanalytical factors such as feelings or trust.


Gender disparities in health and healthcare use among older adults.
Gender differences in health and the use of health services are a long-standing concern for the U.S. medical system. Our purpose was to examine if there are patterns of gender differences in the type of medical service used among older Americans. We conducted a prospective study of 9164 Americans aged >or=65 followed through the Health and Retirement Study (HRS), a national probability sample of community dwelling adults. Self-reported medical utilization between 2002 and 2004 was modeled as a function of 2002 baseline characteristics of the sample. Health needs were substantially greater among older women compared with men, but women had fewer economic resources. Controlling for health needs did little to explain gender differences in preventive care and increased gender differences in the use of hospital services. Women were less likely to have hospital stays (adjusted odds ratio [OR] = 0.79) and had fewer physician visits (3.07 vs. 3.30 median visits within 2 years) than men with similar demographic and health profiles. In contrast, the greater use of home healthcare among women was almost entirely explained by their greater health needs. These national data show that simple evaluations of age-adjusted gender differences in the use of hospital and physician services that do not account for underlying health needs are in danger of understating these disparities.


Face and brow presentation: independent risk factors.
The objectives of this study were to determine clinical characteristics including pregnancy and delivery outcome, among patients with face/brow presentation, and to investigate independent risk factors for these malpresentations. This was a retrospective cohort study comparing all singleton pregnancies of patients with and without face/brow presentation. Deliveries occurred during the years 1988-2002 at the Soroka University Medical Center. Stratified analyses using a multiple logistic regression model were performed to control for confounders. Two hundred and nineteen cases were included in the study out of 130,247 deliveries with vertex presentation, giving a prevalence for face/brow presentation of 0.17%. No significant difference was found with regard to maternal age and gravidity between the control and study groups, but the primiparity rate was lower in the study group (20.4% vs.14.6%, p = 0.034). There was a significantly higher rate of previous history of cesarean delivery (CD), polyhydramnios, non-progressive labor, and non-reassuring fetal heart rate in the study group, but the rate of hypertensive disorders was lower. The prevalence of congenital anomalies was higher in the study group than in the control group, 7.3% vs. 3.6%, respectively. Also the CD rate in the study group was 67.1% as compared to 8.6% in the control group (p < 0.001). In contrast, neonatal outcome was not different between groups, including Apgar scores and perinatal mortality (0.5% vs. 1.2%, p = NS). In a logistic regression analysis model for face/brow presentation, the independent risk factors were fetal malformations (OR = 2.0), polyhydramnios (OR = 2.77) and primiparity (OR = 0.65). Face/brow presentation was associated with several adverse pregnancy outcomes, although there was a favorable neonatal outcome. Independent risk factors for face/brow presentation were fetal malformations and polyhydramnios, but primiparity had a protective effect.


Clotting of mammalian fibrinogens by papain: a re-examination.
Papain has long been known to cause the gelation of mammalian fibrinogens. It has also been reported that papain-fibrin is insoluble in dispersing solvents like strong urea or sodium bromide solutions, similar to what is observed with thrombin-generated clots in the presence of factor XIIIa and calcium. In those old studies, both the gelation and subsequent clot stabilization were attributed to papain, although the possibility that the second step might be due to contaminating factor XIII in fibrinogen preparations was considered. I have revisited this problem in light of knowledge acquired over the past half-century about thiol proteases like papain, which mostly cleave peptide bonds, and transglutaminases like factor XIIIa that catalyze the formation of ε-lysyl-γ-glutamyl cross-links. Recombinant fibrinogen, inherently free of factor XIII and other plasma proteins, formed a stable gel when treated with papain alone. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that the intermolecular cross-linking in papain-fibrin leads to γ-chain dimers, trimers, and tetramers, just as is the case with thrombin-factor XIIIa-stabilized fibrin. Mass spectrometry of bands excised from gels showed that the cross-linked material is quite different from what occurs with factor XIIIa, however. With papain, the cross-linking occurs between γ chains in neighboring protofibrils becoming covalently linked in a "head-to-tail" fashion by a transpeptidation reaction involving the α-amino group of γ-Tyr1 and a papain cleavage site at γ-Gly403 near the carboxy terminus, rather than by the (reciprocal) "tail-to-tail" manner that occurs with factor XIIIa and that depends on cross-links between γ-Lys406 and γ-Gln398.


Outpatient CPOE orders discontinued due to 'erroneous entry': prospective survey of prescribers' explanations for errors.
Computerised prescriber order entry (CPOE) systems users often discontinue medications because the initial order was erroneous. To elucidate error types by querying prescribers about their reasons for discontinuing outpatient medication orders that they had self-identified as erroneous. During a nearly 3 year retrospective data collection period, we identified 57 972 drugs discontinued with the reason 'Error (erroneous entry)." Because chart reviews revealed limited information about these errors, we prospectively studied consecutive, discontinued erroneous orders by querying prescribers in near-real-time to learn more about the erroneous orders. From January 2014 to April 2014, we prospectively emailed prescribers about outpatient drug orders that they had discontinued due to erroneous initial order entry. Of 2 50 806 medication orders in these 4 months, 1133 (0.45%) of these were discontinued due to error. From these 1133, we emailed 542 unique prescribers to ask about their reason(s) for discontinuing these mediation orders in error. We received 312 responses (58% response rate). We categorised these responses using a previously published taxonomy. The top reasons for these discontinued erroneous orders included: medication ordered for wrong patient (27.8%, n=60); wrong drug ordered (18.5%, n=40); and duplicate order placed (14.4%, n=31). Other common discontinued erroneous orders related to drug dosage and formulation (eg, extended release versus not). Oxycodone (3%) was the most frequent drug discontinued error. Drugs are not infrequently discontinued 'in error.' Wrong patient and wrong drug errors constitute the leading types of erroneous prescriptions recognised and discontinued by prescribers. Data regarding erroneous medication entries represent an important source of intelligence about how CPOE systems are functioning and malfunctioning, providing important insights regarding areas for designing CPOE more safely in the future.


Cardiovascular Disease in Antiphospholipid Syndrome.
Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by venous, arterial or microvascular thrombosis or obstetric events in the presence of persistently positive antiphospholipid antibodies and constitutes a major cause of cardiovascular events in young people. Τhis review highlights the pathophysiology of cardiovascular complications in patients with APS and possible treatment options. Patients with APS have endothelial dysfunction, accelerated endothelial proliferation and intimal hyperplasia, atherogenesis, platelet activation, inflammatory products secretion and coagulation-fibrinolytic dysregulation. Cardiovascular complications include accelerated atherosclerosis, acute coronary syndrome, Libman-Sacks endocarditis, cardiomyopathy and venous, arterial or intracardiac thrombi. Moreover, pulmonary hypertension and peripheral microvascular dysfunction are common findings. Management of these patients is not well documented. The role of primary thrombosis prevention remains controversial in individuals with positive antiphospholipid antibodies. Treatment of traditional cardiovascular risk factors according to current guidelines for the prevention of cardiovascular disease in the general population is recommended for primary prevention of APS. Anticoagulation therapy with unfractionated or low-molecular-weight heparin overlapped with a vitamin K antagonist remains the mainstay of the treatment for APS patients with venous thrombosis, whereas direct oral anticoagulants are not yet recommended. Data are scarce regarding the secondary arterial thrombosis prevention and it is not clear whether dual or triple antithrombotic therapy is necessary. To date, it is recommended to follow current guidelines for the management of acute coronary syndrome in the general population. New treatment targets are promising options for patients with catastrophic APS.


Liposomal bleomycin: increased therapeutic activity and decreased pulmonary toxicity in mice.
Conventional and sterically stabilized liposomes derived from phosphatidylcholine or the antitumor agents, hexadecylphosphocholine and octadecyl-(1,1-dimethyl-4-piperidino-4-yl)-phosphate, as bilayer forming constituents, containing bleomycin, were developed and tested. Liposomal encapsulation of bleomycin enhanced strongly the antitumor activity against P388 leukemia and the Lewis lung carcinoma. This effect was clearly dependent on the size and lipid composition of the bleomycin-containing liposomes. The therapeutic effects were nearly equal for liposomal and free bleomycin in the B16 melanoma. The partial replacement of phosphatidylcholine by alkylphospholipids and the inclusion of polyethylene glycol modified lipids for sterical stabilization did not further improve the therapeutic efficacy but increased, in some cases, the toxicity of liposomes. Bleomycin-induced lung injury was not observed if liposomal bleomycin was administered.


A novel Staphylococcus aureus vaccine: iron surface determinant B induces rapid antibody responses in rhesus macaques and specific increased survival in a murine S. aureus sepsis model.
Staphylococcus aureus is a major cause of nosocomial infections worldwide, and the rate of resistance to clinically relevant antibiotics, such as methicillin, is increasing; furthermore, there has been an increase in the number of methicillin-resistant S. aureus community-acquired infections. Effective treatment and prevention strategies are urgently needed. We investigated the potential of the S. aureus surface protein iron surface determinant B (IsdB) as a prophylactic vaccine against S. aureus infection. IsdB is an iron-sequestering protein that is conserved in diverse S. aureus clinical isolates, both methicillin resistant and methicillin sensitive, and it is expressed on the surface of all isolates tested. The vaccine was highly immunogenic in mice when it was formulated with amorphous aluminum hydroxyphosphate sulfate adjuvant, and the resulting antibody responses were associated with reproducible and significant protection in animal models of infection. The specificity of the protective immune responses in mice was demonstrated by using an S. aureus strain deficient for IsdB and HarA, a protein with a high level of identity to IsdB. We also demonstrated that IsdB is highly immunogenic in rhesus macaques, inducing a more-than-fivefold increase in antibody titers after a single immunization. Based on the data presented here, IsdB has excellent prospects for use as a vaccine against S. aureus disease in humans.


Semantic generality, input frequency and the acquisition of syntax.
In many areas of language acquisition, researchers have suggested that semantic generality plays an important role in determining the order of acquisition of particular lexical forms. However, generality is typically confounded with the effects of input frequency and it is therefore unclear to what extent semantic generality or input frequency determines the early acquisition of particular lexical items. The present study evaluates the relative influence of semantic status and properties of the input on the acquisition of verbs and their argument structures in the early speech of 9 English-speaking children from 2;0 to 3;0. The children's early verb utterances are examined with respect to (1) the order of acquisition of particular verbs in three different constructions, (2) the syntactic diversity of use of individual verbs, (3) the relative proportional use of semantically general verbs as a function of total verb use, and (4) their grammatical accuracy. The data suggest that although measures of semantic generality correlate with various measures of early verb use, once the effects of verb use in the input are removed, semantic generality is not a significant predictor of early verb use. The implications of these results for semantic-based theories of verb argument structure acquisition are discussed.


[The etiology of urinary tract infections and the antimicrobial susceptibility of urinary pathogens].
Antibiotic treatment of urinary tract infections in adults is usually empirical, and use of urine culture is an exception. The choice of antibiotic is normally made based on the results of published case studies (positive urine cultures), which are used to determine the most probable etiology and likely antimicrobial susceptibility. The results of studies published in recent years were reviewed, detailing the differences in relation to the place of residence and characteristics of the patients, and any temporary trends. In lower urinary tract infections in patients without risk factors, treatment must mainly cover Escherichia coli. Nevertheless, in complicated urinary tract infections or in patients with risk factors, the available clinical epidemiological data do not provide for safe empirical choice of antibiotic without the use of urine culture. There has been a reduction in the susceptibility of E. coli to various antibiotics, and this shows wide geographic variations; the reduction in the activity of fluoroquinolones could limit its empirical use in the future.


Origin, genetic diversity and evolution of Andaman local duck, a native duck germplasm of an insular region of India.
Domestic ducks are of paramount importance as a cheap source of protein in rural India. Andaman local duck (ALD) is an indigenous avian genetic resource of Andaman and Nicobar islands (ANI) and is mainly distributed in Middle and Northern parts of these islands. Negligence has brought this breed on the edge of extinction necessitating immediate conservation efforts. Here, we report the genetic diversity, population structure and matrilineal genetic root of ALD. Partial mtDNA D-loop sequences were analyzed in 71 ALD samples and analysis revealed 19 polymorphic sites and 13 haplotypes. Estimated haplotype (Hd ± SD) and nucleotide diversity (π ± SD) were 0.881 ± 0.017 and 0.00897 ± 0.00078 respectively. The high genetic diversity of ALD indicates introgression of genetic material from other local duck breeds. In addition, it can be postulated that ALD bearing high genetic diversity has strong ability to adapt to environmental changes and can withstand impending climate change. Phylogenetic and network analysis indicate that ALD falls under Eurasian clade of mallard and ALD forms three clusters; one cluster is phylogenetically close to Southeast Asian countries, one close to Southern part of mainland India and the third one forms an independent cluster. Therefore, ALD might have migrated either from Southeast Asian countries which enjoy a close cultural bondage with ANI from time immemorial or from Southern part of India. The independent cluster may have evolved locally in these islands and natural selection pressure imposed by environmental conditions might be the driving force for evaluation of these duck haplotypes; which mimics Darwin's theory of natural selection. The results of the study will be beneficial for formulating future breeding programme and conservation strategy towards sustainable development of the duck breed.


INTRAARTERIAL INJECTION OF IODINATED CONTRAST MEDIUM FOR CONTRAST ENHANCED COMPUTED TOMOGRAPHY OF THE EQUINE HEAD.
Minimizing the volume of contrast administered for contrast-enhanced computed tomography (CT) of the equine head is desirable for reducing costs and risks of adverse reactions, however evidence-based studies on the effects of varying volumes on image quality are currently lacking. The objective of the current study was to determine whether low-volume intraarterial administration of contrast medium would result in an equivalent image quality and tissue attenuation vs. high-volume intravenous bolus administration. A prospective cross-over experimental design was used in a sample of six horses. After anesthetic induction, the right carotid artery was exposed surgically and catheterized. Four CT scans of the cranium were performed for each horse: baseline, immediately following intraarterial contrast injection, five-min postinjection (return to baseline) and a final scan after intravenous contrast administration. Soft tissue attenuation in predetermined regions of interest (ROI); and length, width, and height measurements of the pituitary gland were recorded at each time point. Horses were euthanized and measurements of the pituitary gland were repeated postmortem. No adverse reactions to contrast administration were observed. Intraarterial and intravenous administration of contrast medium resulted in significantly greater soft tissue enhancement of some brain ROI's and the pituitary gland vs. baseline values. Pituitary gland measurements made on postcontrast CT images did not differ from those obtained during postmortem examination. Findings indicated that low-dose intraarterial administration of contrast material in the equine head resulted in comparable soft tissue enhancement vs. high volume intravenous administration.


Differences in stress response after UVC or UVA irradiation in Vibrio parahaemolyticus.
The SOS response is a global regulatory network for repairing DNA damage induced by various environmental stresses such as UV irradiation. The Escherichia coli SOS response has been extensively studied. However, there are no reports on the SOS response in Vibrio parahaemolyticus. In this study, we examined the SOS response in V. parahaemolyticus and compared the differential expression of genes induced by UVC and UVA irradiation. In UVC-exposed wild-type cells, expression of several DNA repair genes was increased. However, expression of these genes was not increased in ΔrecA or lexA mutants. Cell filamentation was observed in wild-type cells, but not in ΔrecA and lexA mutant cells. Sensitivity to UVC was significantly increased in ΔrecA, lexA mutant and Δlon strains compared with wild type. In the case of UVA irradiation, LexA-controlled DNA repair genes were minimally induced and cell filamentation was not observed. Sensitivity to UVA was the same in the mutant and wild-type strains. These findings suggest that there is a RecA-LexA-mediated SOS response in V. parahaemolyticus, and that this response is important to UVC tolerance but does not contribute to UVA tolerance.


Tumor microenvironment responsive FePt/MoS2 nanocomposites with chemotherapy and photothermal therapy for enhancing cancer immunotherapy.
The metastasis and recurrence of tumors are the main reasons for cancer death. In this work, a promising therapy for tumor treatment that can eliminate primary tumors and prevent tumor relapses is introduced by combining chemotherapy, photothermal therapy (PTT) and immunotherapy. Multifunctional FePt/MoS2-FA nanocomposites (FPMF NCs) were obtained via anchoring FePt nanoparticles and folic acid (FA) on MoS2 nanosheets. As an efficient ferroptosis agent, FePt nanoparticles could catalyze the Fenton reaction to produce the reactive oxygen species (ROS). Through the highly effective photothermal conversion of MoS2 nanosheets, the primary tumor cells could be ablated by photothermal therapy (PTT). Moreover, the metastatic tumors were eliminated effectively with the help of oligodeoxynucleotides containing cytosine-guanine (CpG ODNs) combined with systemic checkpoint blockade therapy using an anti-CTLA4 antibody. Even more intriguingly, a strong immunological memory effect was obtained by this synergistic therapy. Taking all these results into consideration, we anticipate that the photo-chemo-immunotherapy strategies show great promise toward the development of a multifunctional platform for anticancer therapeutic applications.


Health related quality of life and pain characteristics among Iranian patients suffering non-malignant chronic pain.
Chronic pain is a frequent disability that negatively affects patient's quality of life. Understanding of the possible relation between sociodemographic and medical variables with Health Related Quality of Life (HRQL) may help identifying the multidimensionality of pain and risk factors that limit physical and psychological adjustment of the patients. The present study was done to find these possible relationships, based on using Medical Outcomes Survey-Short Form (SF-36). Among the patients who were referred to pain clinic of Iranian Pain Society, 101 consecutive outpatients were select based on the defined inclusion and exclusion criteria. All the participants in this study orally satisfied and were fully informed by a check list and SF-36 questionnaire. The possible impact of demographic variables, characteristics, diagnosis, analgesic use, smoking and opium addiction were collected as the first part of a routine pretreatment evaluation. Our findings showed significant relation between HRQL and gender (P < 0.05), the rate of chronic pain in female was higher than male, and same results found for elderly patients compared to younger ones. Our findings also showed significant relation between employment and intensity of pain (p = 0.001) as, employed patients showed less physical and psychotic problems than unemployed ones. The mean average of intensity of pain in these patients was 7.5±2.2; few patients used alcohol (4%), opium (1%) and cigarette (10%). Large number of participants used analgesic (%78.2). No significant difference between sociodemographic features with pain duration and quality of life was found. In contrast our data showed significant difference between pain intensity and quality of life (p < 0.001). Based on our findings it could be concluded that chronic pain in Iranian patients certainly leads to poor HRQL, the state is more serious in the elderly and female patients. Thus, in order to re-socialize the patients suffering chronic pain and decrease the impact of their pain on their life, these findings should be considered in any kind of pain relief therapy.


Scaffold-hopping as a strategy to address metabolic liabilities of aromatic compounds.
Understanding and minimizing oxidative metabolism of aromatic compounds is a key hurdle in lead optimization. Metabolic processes not only clear compounds from the body, but they can also transform parent compounds into reactive metabolites. One particularly useful strategy when addressing metabolically labile or oxidation-prone structures is scaffold-hopping. Replacement of an aromatic system with a more electron-deficient ring system can often increase robustness towards cytochrome P450-mediated oxidation while conserving the structural requirements of the pharmacophore. The most common example of this substitution strategy, replacement of a phenyl ring with a pyridyl substituent, is prevalent throughout the literature; however scaffold-hopping encompasses a much wider scope of heterocycle replacement. This review will showcase recent examples where different scaffold-hopping approaches were used to reduce metabolic clearance or block the formation of reactive metabolites. Additionally, we will highlight considerations that should be made to garner the most benefit from a scaffold-hopping strategy for lead optimization.


Molecular diagnosis of T cell-mediated rejection in human kidney transplant biopsies.
Histologic diagnosis of T cell-mediated rejection is flawed by subjective assessments, nonspecific lesions and arbitrary rules. This study developed a molecular test for T cell-mediated rejection. We used microarray results from 403 kidney transplant biopsies to derive a classifier assigning T cell-mediated rejection scores to all biopsies, and compared these with histologic assessments. The score correlated with histologic lesions of T cell-mediated rejection (infiltrate, tubulitis). The accuracy of the classifier for the histology diagnoses was 89%. Very high and low molecular scores corresponded with unanimity among three pathologists on the presence or absence of T cell-mediated rejection, respectively. The molecular score had low sensitivity (50%) and positive predictive value (62%) for the histology diagnoses. However, histology showed similar disagreement between pathologists--only 45-56% sensitivity of one pathologist with diagnoses of T cell-mediated rejection by another. Discrepancies between molecular scores and histology were mostly when histology was ambiguous ("borderline") or unreliable, e.g. in cases with scarring or inflammation induced by tissue injury. Vasculitis (isolated v-lesion TCMR) was particularly discrepant, with most cases exhibiting low TCMR scores. We propose new rules to integrate molecular tests and histology into a precision diagnostic system that can reduce errors, ambiguity and interpathologist disagreement.


Preclinical and clinical studies of bone marrow uptake of fluorine-1-fluorodeoxyglucose with or without granulocyte colony-stimulating factor during chemotherapy.
To evaluate the effect of granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on bone marrow glucose metabolism in rodents and in patients, as assessed by 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (FDG) uptake measured directly or by positron-emission tomography (PET) scanning. Groups of three rats received either daily saline, G-CSF, or GM-CSF injections for 7 days. After treatment, FDG was injected and F-18 activities in tissues measured 1 hour later. Twenty-two breast cancer patients treated with multiagent chemotherapy were sequentially studied with PET. Eleven patients received G-CSF therapy as an adjunct to chemotherapy, while 11 received chemotherapy only. The standardized uptake value-lean (SUL) of bone marrow FDG uptake was measured and compared. In rats, bone marrow F-18 activity was significantly higher in both CSF groups than in the saline group (G-CSF, 0.44 +/- 0.08; GM-CSF, 0.33 +/- 0.02; saline, 0.18 +/- 0.02% injected dose [ID]/g x kg; P < .05), but the other normal tissues had comparable biodistributions to controls. In breast cancer patients, the FDG uptake of bone marrow did not change with chemotherapy alone; however, marrow uptake was increased after treatment with G-CSF. The dose of G-CSF and duration of treatment were correlated with the extent of increase in FDG uptake. The SUL of bone marrow was as follows: baseline, 1.56 +/- 0.23; after one cycle, 3.13 +/- 1.40 (P < .01); after two cycles, 2.22 +/- 0.85 (P < .05); and after three cycles, 2.14 +/- 0.79 (P < .05), respectively. Although the FDG uptake of bone marrow declined after G-CSF treatment was completed, it was higher than the baseline level for up to 4 weeks postcompletion of G-CSF and the elevated marrow FDG uptake was sustained longer than the period of blood neutrophil count elevation. Substantial increases in bone marrow FDG uptake are rapidly induced by CSF treatments and should not be misinterpreted as diffuse bone marrow metastases.